20 Chapter 18

18
! The Chemistry of
Aryl Halides, Vinylic
Halides, and Phenols.
Transition-Meta I Cata lysis
An aryl halide is a compound in which a halogen is bound to the carbon of a benzene ring (or
another aromatic ring).
cH2cH3
O,CH2CH2I
not an uryl halide;
I - ethyl-2 -iodobenzene halogen not attached directly
(an aryl iodide) to benzene ring
In a vinylic halide, a halogen is bound to a carbon of a double bond.
H CH2CHzCH:
\/\--U /-
HzC:CH-Cl r'\
/\ -
vinyl chloride BrH
(chloroethylene)
(E) - 1-bromo- 1 -pentene
(a vinylic bromide)
Be sure to differentiate carefully between vinylic and allylic halides (p. 788). Allylic groups
are on a carbon adjacent to the double bond. Likewise, be sure that the distinction between
aryt andbenzylic halides is clear. Benzylic grotps are on a carbon adjacentto an aromatic ring.
822
,18.1
LACK OF REACTIVITY OF VINYLIC AND ARYL HALIDES UNDER SN2 CONDITIONS 823
The reactivity of aryl and vinylic halides is quite different from that of ordinary alkyl
halides. In fact, one ofthe major points ofthis chapter is that aryl halides do nol undergo nu-
cleophilic substitution reactions by the S*2 or S*1 mechanisms.
In a phenol, a hydroxy (-OH) group is bound to an aromatic ring. As the following struc-
tures illustrate, phenol is also the name given to the parent compouhd, and a number of phe-
nols have traditional names.
OH OH OH OH OH OH
r'\ oH
d* +
I
tll
\--'
phenol catechol resorcinol OH
d-cH:
o-cresol
+ CH:
hydroquinone p-cresol
Although phenols and alcohols have some reactions in common, there are also important
differences in the chemical behavior of these two functional groups.
A relatively recent field of organic chemistry involves the use of transition-metal catalysts in
organic reactions, particularly in reactions that involve formation ofcarbon-carbon bonds. The
reactivity of aryl and vinylic halides in substitution reactions is dramatically increasedby cer-
tain catalysts of this type, and this heightened reactivity will be the vehicle through which we
can learn some of the basic principles involved in transition-metal catalysis.
The nomenclature and spectroscopy of aryl halides and phenols were discussed in
Secs. 16. I
and 16.3, respectively. The nomenclature of vinylic halides follows the principles
of alkeni: nomenclature (Sec. 4.2A), and the spectroscopy of vinylic halides, exceptlor minor
differences due to the halogen, is also similar to that of alkenes.
LACK OF REACTIVITY OF VINYLIC AND ARYL HALIDES

18.1 UNDER SN2 CONDTTTONS
One of the most important differences between vinylic or aryl halides and alkyl halides is their
reactivity in nucleophilic substitution reactions. The two most important mechanisms for nu-
cleophilic substitution reactions of alkyl halides are the S*2 (bimolecular backside substitu-
tion) mechanism, and the S*1 (unimolecular carbocation) mechanism (Secs. 9.4 and 9.6).
What happens to vinylic and aryl halides under the conditions used for Sr1 or S*2 reactions
of alkyl halides?
Consider first the S*2 reaction. One of the most dramatic contrasts between vinylic or aryl
halides and alkyl halides is that simple vinylic and aryl halides are inert under S"2 conditions.
For example, when ethyl bromide is allowed to react with Na+ C2H'O- in CTHTOH solvent at
55'C, the following S*2 reaction proceeds to completion in about an hour with excellent
yield:
cH3cH2-Br * Na+ ctt.t;tl,-ci:- cHicH2-o-cH2cH.r * Na+ Br-

-*=#E* (18.1)
Yet when vinyl bromide or bromobenzene is subjected to the same conditions, nothing happens!
HBr
\/
C:C and are inert to lr{a+ CrHsO- in CTH.OH at 55 "C
/\
HH
824 CHAPTER 18 . THE CHEMISTRY OF ARYL HALIDES, VINYLIC HALIDES, AND PHENOLS. TRANSITION-METAL CATALYSIS
Why don't vinylic halides undergo S"2 reactions? In Sec. 9.4C (Fig. 9.2, p. 390), we
learned that, in the transition state of an S"2 reaction of an alkyl halide, the carbon undergo-
ing substitution has a2p orbital to which the nucleophile and the leaving group are partially
bound, and is therefore sp2-hybridized. In other words, this carbon rehybridizes from sp3 in the
alkyl halide to sp2 in the transition state. The carbon undergoing substitution in a vinylic
halide is sp2-hybridized in the starting material; it contains aZp orbital involved in the double
bond. If the S"2 reaction results in the development of a second 2p orbital at this carbon, then
this carbon must become sp-hybridized. Therefore, an S"2 reaction at a vinylic carbon in-
volves rehybridization from sp2 in the vinylic halide to sp in the transition state.
sp -hr-br
Rl Gxt R1 RIH
\t/r--/- \/
\- \-, C C-C + ( 18.2)
/ -/ \ /\
R2 IH R2 R2 Nuc
Nuc:-
I
Nuc: r
transrtron state
The sp hybridization state has such high energy (Sec. 14.2) that conversion of an sp'-hy-
1 I
bridized carbon into an sp-hybridized carbon requires about 21 kJ mol- (5 kcal mol- ) more
energy than is required for an sp3 to sp2 hybridization change. The relatively high energy of
the transition state caused by sp hybridization reduces the rate of Sr2 reactions of vinylic
halides by almost four orders of magnitude (by Eq. 9.22a, p. 385). This means that, under the
conditions in which the S"2 reaction of ethyl bromide takes an hour, transition-state hybridiza-
tion alone would cause the same reaction of vinyl bromide to take almost 200 days.
Rehybridization, however, is not the only reason that vinylic halides are unreactive in the
S"2 reaction. A second reason is that the nucleophile (Nuc:- in Eq. 18.2) would have to ap-
proach the vinylic halide at the back side of the halogen-bearing carbon and in the plane of the
alkene. This arrangement results in significant van der Waals repulsions (a steric effect) of
both the nucleophile and the leaving group with the groups on the other vinylic carbon. This
is shown for the S*2 reaction of vinyl bromide in Fig. 18.1. When the groups on the other
vinylic carbon are larger than hydrogen, the repulsions are even greater. These repulsions raise
the energy ofthe transition state and decrease the reaction rate even further.
In summary, both hybridization and van der Waals repulsions (steric effects) within the
transition state retard the S*2 reactions of vinylic halides to such an extent that they do not
occur.
S*2 reactions of aryl halides have the same problems as those of vinylic halides and two
others as well. First, backside approach to the carbon ofthe carbon-halogen bond would place
the nucleophile on a path that goes through the plane of the benzene ring-an obvious
impossibility. Furthermore, because the carbon at which substitution occurs would have to un-
dergo stereochemical inversion, the reaction would necessarily yield a benzene derivative con-
taining a twisted and highly strained double bond.
twisted double bond
(18.3)
If the impossibility of this result is unclear, try to build a model of the product-but don't
break your models!
18.2 ELIM INATION REACTIONS OF VINYLIC HALIDES 82 5
rran der \\Iilals

reprulsion
van der Wtrals
"6-
I :Br: retrrulsion
t\i
C-C-H
H
/i .1.*
\\t/ :o:
r.an der \\Iaals
|
vrln rfer \\Ia;rls CH: replrlsion

repr-rlsior-r
(a) (b)
FiSure 18.1 Van derWaals repulsions in the transition state of the S"2 reaction of vinyl bromide with methox-
ide, illustrated with (a) Lewis structures and (b) space-filling models.These van der Waals repulsions raise the en-
ergy ofthe transition state and decrease the rate ofthe reaction.
18.1 Within each set, rank the compounds inixder of increasing rates of their S*2 reactions. Ex-
plain your reasdning.
ia) benzyf UromlOe](l-Uromopropyl)benzene, p-bromotoluene
(b) 1-bromocyclohexene, bromoeyclohexane, l-(bromomethyl)cyclohexene
18.2 ETIMINATION REACTIONS OF VINYLIC HALIDES

Although Sr2 reactions of vinylic halides are unknown, base-promoted B-elimination reac-
tions of vinylic halides do occur and can be useful in the synthesis of alkynes.
200oc> + K+ Br- * H2o
Ph-CH:CH-Br + KoH Ph-c:c-H (18.4)
(E orZ) (distills from
reaction mixture;
67o/a vield)
Br Br
tl
Ph-CH-CH-Ph + 2 KOH-
CTHcOH
-y'^^r-^' r> Ph-Q-C-Ph + 2K+ Br- + 2H2O (18.s)
(67o/o yield)
In Eq. 18.5, two successive eliminations take place. The first gives a vinylic halide and the sec-
ond gives the alkyne.
Many vinylic eliminations require rather harsh conditions (heat or very strong bases), and
some of the more useful examples of this reaction involve elimination of B-hydrogens with en-
hanced acidity. Notice, for example, that the hydrogens which are eliminated in Eqs. 18.4 and
18.5 are benzylic (Sec. 17.38).
Can aryl halides undergo B-elimination? Try to answer this question by constructing a
model of the alkyne that would be formed in such an elimination. We'll return to this issue in
Sec. 18.4B.
826 cHAprER 18 . THE cHEMtsrRy oF ARyL HALIDES. vtNylrc HALTDES. AND pHENoLs. TRANsrloN-METAL cATALysrs
@18.2ArrangethefollowingcompoundsaccordingtoincreasingrateofeliminationwithNaoC,H,
in CrHrOH. What is the product in each case?
Ph Ph Ph Br Ph Ph HBr
\/C:C \/C:C \/C:C \/c-?
U-U
/\/\/\
HBTHPhHCI
/\
HPh
LACK OF REACTIVITY OF VINYTIC AND

18.3 ARYL HALIDES UNDER S"1 CONDITIONS
Recall that tertiary and some secondary alkyl halides undergo nucleophilic substitution and
elimination reactions by the S*l and El mechanisms (Sec. 9.6). For example, tert-butylbro-
mide undergoes a rapid solvolysis in ethanol to give both substitution and elimination products.
CHt
I CrHsOHll..
[ 9"' ]
lr-.H-nlrl\
9n, u:c,
H,C-C , Br: H3C-C+ :Br:- ..1
lv' ssoc l"
====--> l
|cu, |cH, ' /
|
CH: L I (72o/o\
H:c
(28o/o) (18.6)
Vinylic and aryl halides, however, are virtually inert to the conditions that promote S*1 or El
reactions of alkyl halides. Certain vinylic halides can be forced to react by the S*1-81 mech-
anism under extreme conditions, but such reactions are relatively uncommon.
CH:
ss "c >
H2C:C-Br * C2H5OH no reaction (1g.7)
/a
(f ,/YBr + C2H5OH
55 0C
( 1 8.8)
\_7
To understand why vinylic and aryl halides are inert under S*l conditions, consider what
would happen if they were to undergo the S*1 reaction. If a vinylic halide undergoes an S*1
reaction, it must ionize to form a vinvlic cation.
qI
R
+
v
Further Exploration 18.1 /x
c-cH, ------+ R-C-CHz
..
:Br:- ( 18.e)
a vinylic cation
Vinylic Cation s tWt)
A vinylic cation is a carbocation in which the electron-deficient carbon is also part of a dou-
ble bond. An orbital diagram of a vinylic cation is shown in Fig. 18.2a. The electron-deficient
carbon is connected to two groups, the R group and the other carbon of the double bond.
Hence, the geometry at this carbon is linear (Sec. 1.3B) and the electron-deficient carbon is
therefore sp-hybridized. Notice that the vacant 2p orbitalis nol conjugated with the n'-electron
system of the double bond; in order to be conjugated, it would have to be coplanar with the
double-bond z,'system. Vinylic cations are considerably less stable than alkyl carbocations be-
cause their sp hybridization has a higher energy than the sp2 hybridization of alkyl cations (the
18.3 LACK OF REACTTVTTY OF VINYL|C AND ARYL HALTDES UNDER SN't CONDTTTONS 827
+
HzC-C-R
2p orbitals of the
double bond these three carbons
cannot become co-linear
H_c Wâ Cllllltlr

17* lp orbitirl
-rre
\Jj<F r-mpt\. sp- ctrbitir|
r\n
sp-hybridized carbon
(a) vinylic cation (b) aryl cation
Fitufe 18.2 Lewis structures and corresponding orbital diagrams of vinylic and aryl cations.The thin gray lines
indicate orbital overlap. (a) A vinylic cation. In this cation, the empty 2p orbital of the cation (b/ue) is oriented at
right angles to the 2p orbitals of the zr bond.The carbon with the empty 2p orbital is sp-hybridized. (b) Phenyl
cation, the simplest aryl cation.The electron-deficient carbon and the two adjacent carbons cannot become co-
linear. Consequently, the empty orbital (b/ue) is not a true 2p orbital; it has more s character than the empty orbital
in the vinylic cation.
same reason that alkynes are less stable than isomeric dienes), and because the electron-with-
drawing polar effect of the double bond discourages formation of positive charge at a vinylic
carbon. Hence, one reason that vinylic halides do not undergo the S*1 reaction isthe instabil-
ity of the vinylic cations that would necessarily be involved as reactive intermediates.
The second reason that vinylic halides do not undergo the S*1 reaction is that carbon-halo-
gen bonds are stronger in vinylic halides than they are in alkyl halides. A vinylic
carbon-halogen bond involves an sp2 carbon orbital, whereas an alkyl carbon-halogen bond
involves an sp3 carbon orbital. Hence, a vinylic carbon-halogen bond has more s character.
Recall that bonds with more r character are stronger (Eq. 14.26,p.664). Consequently, it takes
more energy to break the carbon-halogen bond of a vinylic halide. This additional energy is
reflected in a smaller rate of ionization.
S*1 reactigns of aryl halides would involve aryl cations as reactive intermediates.
fr.
I\:,
ttl
\-/
X. O.+,ii; (18.10)
dHl{l::1"31)
An aryl cation is a carbocation in which the electron-deficient carbon is part of an aromatic
ring. An orbital diagram of an aryl cation is shown in Fig. 18.2b. Because the electron-defi-
cient carbon in an aryl cation is bonded to two groups, it prefers a linear geometry; but this
geometry is impossible, because it would introduce too much strain in the six-membered ring.
Consequently, the vacant orbital cannot become a2p orbital, and must remain an sp2 orbital.
828 cHAprER 18 . THE cHEMtsrRy oF ARvL HALIDES, vtNyltc HALIDES, AND pHENoLs. TRANSIIoN-METAL cATALysts
Because an aryl cation is forced to assume a nonoptimal geometry and hybridization, it has a
very high energy. The electron-withdrawing polar effect of the ring double bonds also desta-
bilizes an aryl cation, just as a double bond destabilizes a vinylic cation. Thus, S*1 reactions
of aryl halides do not occur because they would require the formation of carbocation interme-
diates-aryl cations-with very high energy.
Note that an aryl cation is quite different from the cation formed in electrophilic aromatic substitu-
tion (Eq. 16.9a, p. 7 53), in which the carbocation intermediate is stabilized by resonance. In an aryl
cation, the empty orbital is not part of the ring a'-electron system but is orthogonal (at right angles)
to it. Hence, this carbocation is zot resonance-stabilized.
The first direct observation ofan aryl cation (the phenyl cation, Eq. 18.10) was reported in 2000
by chemists at the Ruhr-Universitat in Bochum, Germany, who trapped the cation at 4 K and ob-
served it spectroscopically. Thus, aryl cations are known species. However, they ue far too unstable
to form from aryl halides under typical S*1 conditions.
tr@ ts.: wi&in each saies, a'aage the compourds aceording to increasing rates of their reactions by
the S;l-El mechanism. Explain your reasoning.
(a) Br
,/at',nI \:icH-cH3
\-fc:cHz
Br
/-\
-
\,1/}*cH-cHr
Br,
|
|
(b)
,n, t-_ Ql \
,n_
u/-eH-cH3 \_/ts*
NUCLEOPHITIC AROMATIC SUBSTITUTION

{8;4 REACTIONS OF ARYI HATIDES
Although aryl halides do not undergo nucleophilic substitution reactions by S*1 and S"2
mechanisms, aryl halides that have one or more nitro groups ortho or para to the halogen un-
dergo nucleophilic substitution reactions under relatively mild conditions.
o,*OF + K+ cH3o- i*#=' o,*-$ocH3 + K+ F- (18.r)
p-fluoronitrobenzene p-nitroanisole
(93olo yield)
170'c'6b
ozN cl + :NH: (pressure)
> ozN xu, + HCi (18.12)
I -chloro -2,4-dinitroben zene 2,4-drnitroaniline

(7 \a/o yield)
18.4 NUCLEOPHILIC AROMATIC SUBSTITUTION REACTIONS OF ARYL HALIDES 829
These reactions are examples of nucleophilic aromatic substitution: substitution that occurs
at a carbon of an aromatic ring by a nucleophilic mechanism.
Let's examine some of the characteristics of this mechanism. Like S*2 reactions, nucle-
ophilic aromatic substitution reactions involve nucleophiles and leaving groups, and they also
obey second-order rate laws.
rate: f[arylhalide][nucleophile] (18.13)
However, nucleophilic aromatic substitution reactions do not involve a concerted backside

substitution for the reasons given in Sec. 18. 1 . Two clues about the reaction mechanism come
from the reactivities of different aryl halides. First, the reaction is faster when there are more
nitro groups ortho and para to the halogen leaving group:
relative
/,NO, /,NO, rate
o,*< F.t + -ocH3 orN< )=o.", * .t- 105-106 (r8.14a)

E \-,/
ozN$.t + -ocH3 ----* ozN+ocH3 + cl- ( 18.14b)
( \}- cr + -ocH3 ---+ no reaction =Q (18.14c)

\_/
Second, the effect of the halogen on the rate of this type of reaction is quite different from that
in the S*1 or S*2 reaction of alkyl halides. In nucleophilic aromatic substitution reactions, aryl
fluorides are most reactive.
Reactivities of aryl halides:
Ar-F (18.1s)
In S*2 and S*1 reactions of allql halides, the reactivity order is exactly the reverse: alkyl flu-
orides are the least reactive alkyl halides (Secs. 9.4F and 9.6C).
These data are consistent with a reaction mechanism in which the nucleophile reacts at the
halide-bearing carbop belqw (or above) the plane of the aromatic ring to yield a resonance-
stabilized anion called a Meisenheiiner complei.In this anion, the ndgative charge is delocal-
ized throughout the z'-electron system of the ring. Formation of this anion is the rate-limiting
step in many nucleophilic aromatic substitution reactions.
d [t?''nt
-L J/\J \y-F
rate-rimirineo s-
o.,N
a Meisenheimer complex
830 CHAPTER 18 . THE CHEMISTRY OF ARYL HALIDES. VINYLIC HALIDES. AND PHENOLS. TRANSITION-METAL CATALYSIS
The negative charge in this complex is also delocalized into the nitro group.
ocH3
(18.16b)
F
[,]
The Meisenheimer complex breaks down to products by loss of the halide ion.
(18.16c)
Let's see how this mechanism fits the experimental facts. Ortho and para nitro groups
accelerate the reaction because the ratelimiting transition state resembles the Meisenheimer
complex, and ortho and para nitro groups (but not meta nitro groups) stabilize this complex by
resonance. Fluorine also stabilizes the negative charge by its electron-withdrawing polar ef-
fect, which is greater than the polar effect of the other halogens. Because the /oss of halide is
not rate-limiting, the basicity of the halide, or equivalently, the strength of the carbon-halogen
bond, is not important in determining the reaction rate.
Although we have used aryl halides substituted with ortho- and para-nitro groups to
illustrate nucleophilic aromatic substitution, it stands to reason that other substituents that can
provide resonance stabilization to the Meisenheimer complex can also activate nucleophilic
aromatic substitution. (See, for example, Problem 18.5a.)
Notice how the nucleophilic aromatic substitution reaction differs from the S*2 reaction of
alkyl halides. First, there is an actual intermediate in the nucleophilic aromatic substitution re-
action-the Meisenheimer complex, (In some cases, this is sufficiently stable that it can be di-
rectly observed.) There is no evidence for an intermediate in any S*2 reaction. Second, the nu-
cleophilic aromatic substitution reaction is a frontside substitution; it requires no inversion of
configuration. The S*2 reaction of an alkyl halide, in contrast, is a backside substitution with
SruDY GUIDE LINK 18.1
Contrast of Aromatic
inversion of configuration. Finally, the effect of the halogen on the reaction rate (Eq. 18.15) is
Substitution different in the two reactions. Aryl fluorides react most rapidly in nucleophilic aromatic sub-
Reactions
stitution, whereas alkyl fluorides react most slowly in S"2 reactions.
18.4 Complete the following reactions. (No reaction may be the correct response.)
{a)
ozN cl + crHrNH, -E!
Noz
F + CH3(CHz)rS:- cHbT-
(c)
cH3o +CHIO:- 1frfu
.I8.5 INTRODUCTION TO TRANSITION-METAL CATALYZED REACTIONS 831
18.5 Which of the two compounds in each of the following sets should react more rapidly in a nu-
cleophilic aromatic substitution reaction with CHrO- in CH3OH? Explain yorr answers.
{n} F F(b)F
Noz ..\
or
dNoz \ No,
Noz
ar'c-ocH.
I NTRODUCTION TO TRANSITION.M ETAL

18.5 GATALYZED REACTIONS
ions cannot be carried out on either aryl or vinylic
much like nucleophilic substitutions can be carried
. Here are some examples.
CH CH:
+ H,{l
-cH- CH3C-N (solvent)
+ HBr (18.17)
neutralizedbY
Br 1g h, 125 'c [,H:(,H1
the (CH:CHz):N
o-bromotoluene o-methylstyrene
(86% yield)
This reaction, called the Heck reaction, has become very important in organic synthesis. We'll
revisit this reaction in Sec. I 8.6A. Notice the formation of the carbon--carbon bond and the re-
lease of bromide as HBr. Superficially, it looks as if the conjugate-base anion of ethylene dis-
places brornide ion from the aromatic ring. However, this reaction occurs by a very different
mechanism and does not happen without the palladium catalyst. (Only about 1 mole Vo of the
catalyst is required.)
In the following reaction, we see the substitution of a vinylic bromide by a thiolate anion.
Ph Br Ph SCHTCFI l
\/c'-c + -scHr(-Fr., f1#?'
Pd(PPh3)4
\/C:d + Li+ Br- (18.18)
Li+ Denzene
/\
H H HH
(93o/o yield)
This reaction, too, looks superficially like a nucleophilic substitution reaction. But this reac-
tion also proceeds by a different mechanism and does not take place without the catalyst,
which is present in only I mole 7o. Notice also the retention of alkene stereochemistry, a very
different result from that expected in an S*2 reaction.
These are but two examples of thousands now known in which transition-metal catalysts
bring about seemingly "impossible" reactions. The field of transition-metal catalysis has ex-
ploded in the last four decades, and it has become very important in both laboratory and indus-
trial chemistry, as well as in some areas of biology. This field is part of the larger field of
organometallic chemistry: the chemistry of carbon-metal bonds. (Grignard reagents and

lithium dialkylcuprate reagents are examples of organometallic compounds that you encoun-
tered in Secs. 8.8 and 1 1.4C and will encounter again in subsequent chapters.) Our goal in this
section is to understand some of the basic ideas of transition-metal catalysis. Then, in Sec.
18.6, we'll examine a few important transition-metal catalyzed reactions in the light of these
principles.
A. Transition Metals and Their Gomplexes

Recall from general chemistry that transition metals are the elements in the "d block" or "B"
groups of the periodic table (groups 3-12 in the IUPAC numbering). These elements are
shown in Fig. 18.3. In a given period n, elements are characterizedby the progressive filling
of d orbitals in quantum level n - 1 and the s orbital in quantum level n. Thus, in the fourth
period, the ffansition elements are characterizedby the filling of the one 4s and the five 3d or-
bitals. Because the 4s and 3d orbitals have very similar energies, it is usually convenient to
think of the elecffons in both types of orbitals together as valence electrons. For example, Ni
has the electronic configuration fArl4s23d8,but we classify Ni as a 10-valence electron atqm.
Central to transition-metal chemistry are a wide variety of compounds containing transition
metals surrounded by several groups, called ligands. Such compounds are called coordination
compounds or transition-metal complexes. These can be neuffal molecules, as in the first of
the following examples, or complex ions, as in the second example.
t- NH, 13+
CIr,,... NHI t'n"
-\NH: I Jo'jNH:
r,* z 1-,uu.
p1 ....rrr
^ I
cl/ I
LNHrI
I
cis-diamminedichloroplatinlm(Il) hexamminecobalt(il)ion
(cis-platin, anuantiruTor drug) a complex ion
To deal systematically *itft t unrltion-metal complexes, we/must be aware of, and be able
to apply, certain conventions:
1. how to classify ligands
2. how to specify formal charge on the metal
3. how to calculate the oxidation state of the metal
4. how to count electrons around the metal
In transition-metal chemistry, all ligands arc lzwis bases. That is, ligands interact with tran-
sition metals by donating electron pairs. Therp are two types of ligands. The first we'll call an
Group number 3B 4B 5B 6B 7B 8B 1B 2B
Valence electrons
in the neutral atom 8 9 l0 11 l2
PeriorJ tI -------rr> Sc Ti VCr Mn Fe Co Ni Cu Zn
Pt'riotl 5 --------> Y Zr Nb Mo Tc Ru Rh Pd Ag Cd
Pcriotl 6 --------> La Hf thw Re Os Ir Pt Au Hg
Fiture 18.3 The transition metals.The red numbers indicate the number of valence electrons (outer shell s and
d electrons) in the neutral atoms. (These are the same as the IUPAC group numbers in the periodic table;see the
inside of the rear cover.)
18.5 INTRODUCTION TO TRANSITION-METAL CATALYZED REACTIONS 833
L-type ligand. If you imagine that if a ligand dissociates from the metal with its bonding elec-
tron pair and thus becomes a neutral molecule, the ligand is an L-type ligand. For example, any
one of the NH, ligands in the two preceeding complexes is an L-type ligand because if we re-
move it with its bonding electron pair, we get:NHr, the neutral molecule ammonia.
The second type of ligand is termed an X-type ligand. If you imagine that if a ligand disso-
ciates from the metal with its bonding electron pair and thus becomes a negative ion, the lig-
and is an X-type ligand. Thus, Cl in cls-platin (the first example) is an X-type ligand, because
removing it with its bonding pair of electrons gives the chloride ion, Cl-.
The classification of ligands has implications for computing formal charge. From aformal-
charge perspectiye, the bonding electrons on L-type ligands are consideredto "belong" com-
pletely to the ligand. Let's see how this differs from the way we treat bonds in main-group
chemistry. We know that a nitrogen with four bonds in main-group chemistry, for example, the
ammonium ion, +NHo, has a positive formal charge. If we were to take a similar view with cis-
platin, the nitrogens would each have a positive charge; and, because the complex is neutral, the
Pt would have a charge of -2. A neutral transition-metal complex bearing six L-type ligands
would thus have a charge of -6 on the metal and a positive charge on each ligand. It is incon-
venient to draw out all of these charges; moreover, a formal charge of -6 on a metal is highly
unrealistic. Instead, we adopt the convention that the electron pair in an L-type ligand is as-
signed completely to the ligand. Sometimes this point is emphasized by leaving the bonding
electron pair on the ligand and depicting the ligand-metal bond as an arrow from these elec-
trons to the metal. This is called a dative bond.
tt.t.
/:NHr
Pt clative Lronr1s
c( \:NH:
Because electrons on an L-type ligand belong to the ligand, removal of the ligand does not
change the formal charge on either the ligand or the metal:
cl. NH: cl NH:

\/ --+
\/ +:NHr
Pt Pt (18"1e)
/ \ /
CI NH: CI
In contrast, electrons in the bonds to X-type ligands are assigned in the same way that we
assign electrons in main-group chemistry: one electron is assigned to the ligand and one to the
metal. This means that if we remove an X-type ligand, it takes on an additional negative
charge and the metal takes on a compensating positive charge:
Cl NH: CI NH:
\/ -+ \ +.,,
Pt Pt+ (I 8.20)
\ \
:C1-\ NH:
o r I\-./
NH:
Differentiating between X-type and L-type bonds is a very convenient bookkeeping device,
but we should bear in mind that both types of bonds are covalent bonds, and the degree to
which electrons (and charge) are transferred to the metal varies widely in both types of bonds,
depending on the metal and the ligand.
Table 18.1, on p. 834, lists some of the common ligands used in transition-metal chemistry.
These are classified as L-type or X-type ligands. It is worth noting two things about this table.
First, alkenes or aromatic rings can act as ligands by donating their z'electrons to a metal. Sec-
ond, allyl and cyclopentadienyl (Cp) are classified as both L-type and X-type ligands. Let's
834 cHAprER 't8 . THE cHEMtsrRy oF ARvL HALTDES. vrNyLrc HALIDES. AND pHENoLs. TRANsIIoN-METAL cATALysrs
@ Some Typical Ligands Used in Transition-Metal Chemistry
Ligand Name Abbreviation Type Electron count*
H3N: ammtne
.L
H2o: aquo 2l
RrP: (R - alkyl, aryl) trialkylphosphino,

triarylphosphino
:(-[: carbonyl 2+
*
H,C:CH,$ ethylene
cHrc-N: acetonitrile MeCN 2$$
benzene L3
.L
F-, Cl-, Br-,l- halo (e.g.,chloro) 2l
H_ hydrido
o
tl *
HrC- C-O- acetato AcO 2l
R:- .9.,H3C:- alkyl (e.g.,methyl)
-:(-frl: cyano 2+
+
HzC: CH- CH2 a llyl 4**
o cyclopentadienyl Cp L,X
*The sum of all electrons in the bond(s) between the ligand and the metal.
rOnly one electron pair is involved in the ligand-metal interaction.
+Only the electron pair on carbon is involved in the ligand-metal interaction.
9Ethylene is listed as a prototype for many alkenes.
SSDonation ofthe nitrogen unshared election pair.
**Allyl can also bind to metals as an X-type ligand. In such a situation,the a bond is not involved in coordination and
the electron count is 2 (as with alkyl).
consider the Cp case to understand this. The cyclopentadienyl anion was discussed in Sec.
15.7D as an example of an aromatic ion with six z' electrons. Table 18. 1 indicates that Cp is
an example of an LrX ligand. What this means is that one X-type bond accounts for the fact
that Cp takes on one negative charge when removed with a bonding pair from the metal, and
that the four remaining rr electrons (that is, two double bonds) take part in two L-type bonds.
In other words, we can think of a metal-Cp complex in the following way (M : metal):
( 1 8.21)
M
We know that the n elecftons in Cp are completely delocahzed, and they remain delocalized
in metal complexes.. (See the structure of ferrocene [CprFe] on p. 728, which shows this delo-
calization.) Consequently, a more accurate picture of such a complex would show the "L" and
"X" character ofthe bonds parceled out equally over all five carbons, with each carbon partic-
ipating in 207o of an X-type bond (5 x 0.20 : 1.0 X-type bond) and 40% of an L-type bond
(5 x 0.40 :2.0L-type bonds). But this delocalization can be ignored for the bookkeeping
purposes discussed in this section.
1E.6 Noting the LX character of the allyl ligand in Table 18.1, sketch the allyl-metal interaction,
showing both L-type and X-type bonds. Use M as a general metal.
B. Oxidation State
The oxidation state of the metal is an important concept in organometallic chemistry. Oxida-
tion state can be conceptualized as the charge the metal would have if all covalently bonded
atoms-that is, all X-type ligands-were dissociated with their bonding electron pairs. For ex-
ample, if the oxygens of manganese dioxide, O:Mn:O, were to dissociate from the man-
ganese with their bonding electron pairs, the oxygens would each take on a -2 charge, and the
manganese would take on a 14 charge. Therefore, the manganese has an-oxidation state of
+4. (This process is essentially the same as the one used for assigning oxidation numbers to
carbon atoms in oxidation-reduction reactions [Sec. 10.5A]). Eq. 18.22 formalizes this idea:
Oxidation state of M - number of X-type ligands + Qw (r8.22)
In this equati on, Qu is the actual charge that M has before the fictitious dissociation of the X-
type ligands. To illustrate a situation involving Qr, consider the hexachloroplatinate dianion,
[P(Cl6)]'z-. For this species, Qw: -2.If the six chlorines were to dissociate with their bond-
ing electrons, the charge on Pt would be t4, because Pt starts out with a -2 charge before the
fictitious dissociation. To be sure that the oxidation state and the actual charge Qutre not con-
fused, the oxidation state is sometimes indicated with Roman numerals. Hence, the name of
the ion tP(Cl6)1'z- is hexachloroplatinate(IV).
L-type ligands do not contibute to the oxidation state. You should verify that the oxidation
state of platinum in the neutral complex Cl2Pt(PPh3)2 is +2.
18.7 Calculate the oxidation state of the metal in each of the following complexes.
ta) o (b) Pd(PPhr)4
Pd(PPh3)4 tc) Cp2Fe
tl
O:Mn-O- tetrakis(triphenylphosphine)paltadium ferrocene
o-
ll
permanganate
18.8 What is the oxidation state of the metal in the starting material in the following reaction?
How does it change, if at all, as a result of the reaction?
PPh. PPhr
|
.: " ph3p\ |
ph3P-T-PPh3 + H2 -+ -ffh,
Cl
H/T_.,
H
chlorotris (triphenylphosphine) rhodium
836 CHAPTER 18 . THE cHEMrsrRy oF ARYL HALTDES. vrNyLrc HALTDES. AND pHENoLs. TRANsrroN-Mernl cnrn&sts
c. The da Notation
In understanding the reactions of main-group elements that follow the octet rule, it is impor-
tant in applying acid-base concepts for us to know whether the element undergoing a transfor-
mation has unshared valence electrons. Often these unshared electrons are shown explicitly. In
transition-metal chemistry, it is also important to know whether the metal has unshared va-
lence electrons. In many cases, the metal has so many unshared valence electrons that it would
be impractical or confusing to draw them all. Instead, we use a convenient algcirithm to calcu-
late the number of unshared valence electrons. The number of unshared valence electrons on
the metal is the number n in a notation called d". For example, if the metal in a complex has
eight unshared valence electrons, we say that the complex is a d8 complex.
We calculate n by determining the number of valence electrons.remaining on the metal
after removing all ligands with their electron pairs. We start with the number of valence elec-
trons in the neutral transition element (from Fig. 18.3). We remove an electron for each posi-
tive charge, add an electron for each negative charge, and then subtract one electron for each
bond to an X-type ligand. L{ype ligands have no effect on dn.
n - valence electrons in neutral M - Qn'r - number of X-type ligands ( 18.23)
Introducing the definition of oxidation state in Eq. 18.22, Eq. 18.23 becomes
n - valence electrons in neutral M - oxidation state of M ( 18.24)
SOlUtiOn We'll make this calculation with both Eqs. 18.23 and 18.24. From Fig. 18.3 we see
that neutral Fe has eight valence electrons. The charge of the iron is zero, and Table I 8. I shows
that each Cp ligand has one X-type bond; the iron thus has two bonds to X-type ligands. Hence,
: - :
n 8 2 6, andferrocene is thus a d6 complex.
From Eq. 18.24, we calculate that with two X-type ligands and zero charge, the Fe in fer-
rocene has a 42 oxidation state; hence, Eq. 18.24 gives the value of z as 8 2 6.- :
18.9 What ts dn for each of the following complexes?

ta) [w(co)r]'- (b) Pd(PPhr)n {c} PPh:
Ph3P\_1.
Rh- -PPh,
H,/ H| -ct
D. Electron counting: The 16- and 18-Electron Rules

In main-group chemistry, we use the octet rule as one indicator of reactivity. For example, we
know that if a main-group element in a compound has fewer than an octet of electrons, it can ac-
cept an electron pair from a Lewis base in a Lewis acid-base association reaction. In other
words, main-group elements have a tendency to complete their octets. Recall that counting for
the octet involves adding an element's unshared valence electrons to the number of electrons in
all bonds to the element. The electron count in transition-metal complexes is also important and
is determined in a similar manner.
fb determine the electron count for a transition-metal complex, we start with the n elec-
trons in the d" count-the unshared electrons-and add two electrons for every ligand (both
L-type and X-type). Thus,
electron count - n * 2(number of all ligands) ( 18.2s)
The multiplier 2 is required because there are two electrons per bond. The rationale for
this formula is that the number n is the number of unshared valence electrons on the metal; the
total electron count is the unshared valence electrons plus all electrons in bonds, just as in
counting for the octet rule. Using Eq. 18.24, we can rewrite this formula in terms of the
oxidation state of the metal:
electronbount : valence electrons in neutral M : oxidation state ofM

* 2lnumber of all ligands) (18.26)
By incorporating the definition of oxidation state (Eq. 18.27), we obtain yet another equiva-
lent formula:
electron count : valence electrons in neutral M - Qw

rber of X-type ligands * 2(number of all ligands) ( 18.27 )
Recognizing that all ligands : X-type ligands + L-type ligands, we finally obtain a very use-
ful formula for electron count:
elec-tron.count - valence electrons in neutral V . Ou
* number of- X-type ligands * 2(number of L-type ligands) ( 18.28)
Thus, to obtain the electron count in a complex, we start with the electron count of the neutral
metal from Fig. 1'8.3; we subtract the charge on the metal (taking into account its algebraic
sign); we add the number of X-type ligands; and we add twice the number of L-type ligands.
Don't let the mathematical derivation of Eq. 18.28 obscure its rationale. Remember that the
goal is to count all unshared and bonding electrons about the metal. Because an X-type ligand
by definition has one electron in its M-X bgnd assigned to X, we have to add this electron
back to obtain the total number of electrons in the bond. Because both electrons in the dative
bond to an L-type ligand are assigned to the ligand, we have to multiply each L-type ligand by
2 to count both of these bonding electrons.
Let's use Eq. | 8.28 to calculate some electron counts. For example, the electron count of
Ni(CO)4 is 10 - 0 - 0 + 2(4) : 18. This is an lS-elec,tron complex. (This compound,
tetracarbonylnickel(0), is a very stable complex of Ni.)
The electron count of Cl2Pd(PPh3)2 is 10 - 0 + 2 + 2(2): 16. This is a 16-electron
complex.
In transition-metal chemistry, the most stable complexes in many cases have electron
counts of 18 electrons. This statement is called the 18-electron rule. Ni(CO)4, a very stable
complex of Ni(O), is an example of the 1S-electron rule. Just as the octet represents the num-
ber of valence electrons (8) in the outermost s and p orbitals of the nearest noble gas, I 8 elec-
trons is also the number of total s -l p 4 dvalence electrons in the nearest noble gas.
Exceptions to the 18-electron rule occur, and an important type of exception occurs fre-
quently with transition metals in the 8-1 1 valence-electron group (Fig. 18.3), which includes
Ni and Pd, two metals of prime importance in the transition-metal-catalyzed reactions dis-
cussed in this section. Although a number of stable complexes of these metals have l8 elec-
trons, others contain 16 electrons. The tendency of these metals to surround themselves with
16 electrons can be called the 16-electron rule. The Cl2Pd(PPh3)2 example shows the opera-
tion of the 16-electron rule.
I
838 cHAprER 18 . THE cHEMrsrRy oF ARyL HALTDES, vrNyLrc HALTDES, AND pHENoLs. TRANSIIoN-METAL cATALysrs
1E.10 What is the electron count for tlrc Ri complex shown in Problem 18.9c?
18.11 How many CO ligands would be accommodated by Fe(O) if we assume ttrat ttre resulting
complex follows the l8-electron rule?
18.12 Using the l8-elechon rule, explain why V(CO). can be easily reduced to tY(CO)ul-.
We used hybridization arguments to understand the basis of the octet rule in main-group
chemistry (Sec. 1.9). Thus, the main-group elemeni carbon has four valence orbitals (for ex-
ample, four sp3 hybrid orbitals) that can either form two-electron-ionds or house unshared
electron pairs. We can justify the l8-electron rule in a similar way. Consider, for example, the
complex ion [Co(CN)u]3-. Using Eq. 18.22, we see that the oxidation state of Co is *3, and,
from Eq. 18.24, that this is a d6 complex. This means that Co(IID in this complex has six un-
shared electrons. Let's.imagine building this complex from a "naked" Co3+ ion. Start with the
electronic configuration of this ion, as shown in Fig. 18.4a. Allow all the electrons to pair, as
shown in Fig. 18.4b. Because this electron pating violates Hund's rules, it requires energy. This
electron pairing leaves two 3d,one4s, and tlree4St orbitals unoccupied. These are hybridized,
as shown in Fig.i8.4c, to give six equivalent d2sp3 hybricl orbitats. Six equivalent hybrid or-
bitals are directed to the corners of a regular octahedron in the same sense that sp3 carbon or-
bitals in methane are directed to the corners of a regular tetrahedron. Hybridization also requires
energy. Each of these empty hybrid orbitals can accept an electron pair from a cyanide ion
(-CN). Because these hybrid orbitals are directed in space, they can form sfronger bonds to
Unhybridized Co3+ (d6),
4p
pair the
electrons
4s
, 4s
3d6 J+ tl
,1\
I 3d6
(a)
hl,Lrridize the empt\r orbitals;
dt-rp'
hvbrid -r(x- io+- -x)e -+<x- +<x- -+(x-
orbitals
XX : t-f ilt/ itlt' (lt-t-tt-0tis
3d6 ++ -fF
( unaffected by hybridization)
(c)
Figure 18.4 Development of the hybrid orbital description of [Co(CN)J3-, an I 8-electron complex ion. (a) The
electronic configuration of Co3+. (b)The Co electrons are arranged in pairs;the empty orbitals that remain (red) are
used to form hybrid orbitals. (c) The empty orbitals are hybridized into six equivalent d2sp3 hybrid orbitals. Each of
*CN
these orbitals can accept an electron pair (symbolized by XX) from a ion. (d) The hybrid orbitals and, hence,
the six -CN that bind to them are oriented to the corners of a regular octahedron. (The edges of the octahedron
are indicated with blue dashed lines.)
cyanide than unhybridized orbitals, and the strength of these bonds more than compensates for
the energy cost of electron pairing and hybridization. The result is the octahedral [Co(CN)u]3-
complex shown in Fig. 18.4d. In other words, the l8-electron rule results from the rehybridiza-
tion and maximal occupancy of all valence orbitals of the Co3+ ion.
The 16-electron rule is important in square planar complexes of the lO-electron elements
Ni, Pd, and Pt. For example, consider the antitumor drug cis-platin, Cl2Pt(NH3)2 (p. 832). This
is a 16-electron d8 complex of Pt(D that has square planar geometry. If we start with a Pt2+
ion and rurange its eight electrons in pairs within four 5d orbitals, this leaves a single 5d or-
bital, a 6s orbital, and three 6p orbitals empty. It turns out that hybridization of four of the five
empty orbitals to give four dsp2 hybrid orbitals and one relatively high-energy 6p orbital is a
particularly favorable hybridization:
6p
( empry,r.rn f-,yU.idized )
XX - /i{rrllr/ tr/t:r-tr,r'rrllr,
,J-t?t hrfurid j(X-
orbitarls
-+<X- -J(X- -+(x- (square planar)
5d8 {.F -t+- J+

The four hybrid orbitals are directed to the corners of a square and accept the electron pairs
from the four ligands to give a square planar complex. The element platinum can also adopt 18-
electron configurations, but the point is that the 16-electron conflguration is reasonably stable.
As in main-group chemistry hybridization arguments are useful for visualizing electrons in
bonds, but they are inferior to molecular orbital arguments for detailed understanding of mol-
ecular energies. The branch of molecular orbital theory that deals with transition-metal com-
plexes is called ligand field theory. We need not explore this theory here; but suffice it to say
that this theory provides excellent support for the 16- and 18-electron rules.
@18'13Useahybridizationargumenttopfedictthegeometryofta}the[Zn(CN)o]2-ion;(b)the
neutral compound Pd(PPhr)o
E. Fundamental Reactions of Transition-Metal Complexes

We have now been introduced to the preliminaries that we need to understand the mechanistic
basis of some transition-metal-catalyzed reactions, and we're ready to look at these reactions
in detail. It turns out that transition-metal complexes undergo a relatively small number of fun-
damental reaction types, and many reactions are readily understood simply as combinations of
these fundamental processes. The goal of this section is to introduce a few of these.
Ligand Dissociation-lssociation; Litand Substitution One of the most common re-

actions of transition-metal complexes is ligand dissociation and its reverse, ligand associa-
tion. In ligand dissociation, a ligand simply departs from the metal with its pair of electrons,
leavins a vacant site (orbital) on the metal.
Pd(PPh3)4 Pd(PPh3)3 + :PPh: ( 18.2e)
Pd(o) Pd(o)
an 18e- complex
- a I6e- complex
This process does not change the oxidation state ofthe metal, but it does change the electron
count. A ligand substitution can occur by the dissociation of one ligand and the association of
another, which is somewhat analogous to an S*l reaction in alkyl halides, or by a direct sub-
stitution, in which one ligand displaces another, somewhat analogous to the S*2 reaction.
Ph3P, ,I PhsP\ CH*

\,/
Pd + H:C-Li Pd + Li+ I-
/J
( 18.30)
/\
Ph3P ph -> Ph3P/ Ph
Pd(rr) Pd(rr )
a 16e- complex a l6e- complex
In the most common ligand substitution reactions, ligands of the same type are exchanged: X-
type ligands for X-type ligands and L-type ligands for L-type ligands.
Oxidative Addition In oxidative addition, a metal M reacts with a compound X-Y to

form acompound X-M-E the metal "inserts" into the X-Y bond. We have already stud-
ied an important reaction of this type: the formation of a Grignard reagent from Mg metal and
an alkvl halide (Sec. 8.8A).
R-Br+Nng + R-Mg-Br ( 18.31a)

Ms(0) Mg(II)
As the term "oxidative addition" implies, the Mg is oxidized- An electron count for Mg in this
reaction is 2 for a metal and 4 in the Grignard reagent-(Remember, though, that Mg is a main-
group metal and is not subject to the 16- or l8-electron rules.)
An example of oxidative addition from transition-metal chemistry is the insertion of Pd
into the carbon-halosen bond of iodobenzene:
Ph3P. Ph.P Ph
\ -r\
Pd + Ph-I
/
Pd (18.3rb)
/ /\
Ph3P I
Ph3P
-
Pd(o); Pd(rr):
a l4e- complex a 16e- complex
Both of new bonds are X-type bonds. As a result of this reaction, both the electron count and
the oxidation number of the metal increase by two units.
Oxidative addition is a remarkable reaction that lies at the heart of transition-metal catalysis
with aryl and vinylic halides. Why is it that a metal can break a sigma bond in this way? Mole-
cular orbital theory provides a simple way to understand this process, as shown in Fig. 18.5.
Think of the carbon-halogen bond as a localized bond for simplicity, and imagine a molecular
orbital treatment of this bond much like the molecular orbital treatment of the H-H bond in
H, (Sec. 1.8A). The carbon-halogen bond has an associatedbonding molecular orbital, which
is occupied by the two bonding electrons, and an antibonding molecular orbital, which is un-
occupied. The bonding molecular orbital can serye as a ligand, donating its electrons to one of
the empty hybrid orbitals on the metal. At the same time, one of the filled d orbitals of the metal
overlaps with the antibonding molecular orbital of the carbon-halogen bond. This additional
overlap strengthens the metal-ligand interaction, but weakens-ihe carbon-halogen bond, be-
cause addition of electrons to an antibonding molecular orbital removes the energetic advan-
tage ofbonding. (See Fig. 1.14. p. 35.) The carbon-halogen bond is weakened sufficiently that
it actually breaks. Hence, electrons flow from the aryl halide to the metal and, at the same time,
filled metal d orbital

led mt
F- tcr'
q,.,''.\
\j M
bonding
MO of
antibonding
MO of C-X
//
,/t-'--\,
empty metal
hvbrid orbital
C-X
t/
t/
\=*/
Figure 18.5 An orbital description of concerted oxidative addition.The bonding MO of the C-X bond donates
electrons to an empty hybrid orbital on the metal.(The shape of this hybrid orbital is simplified.)These orbitals are
shown in purple, the thin purple lines indicate the electronic overlap, and the purple arrow shows the direction of
electron flow.At the same time,a filled d orbital on the metal donates electrons to an antibonding MO of the C-X
bond. (A 3d orbital is used for simplicity.) Because the peaks and troughs of the d orbital (shown in blue and green,
respectively) match the peaks and troughs of the antibonding MO of the C-X bond,this is a bonding interaction.
The electronic overlap in this interaction is indicated with thin blue and green lines,and the blue and green ar-
rows show the direction of electron flow. Because this interaction populates the antibonding MO of C-X, this
bond is weakened, and it breaks.
from the metal to the aryl halide. We can approximate the process as follows with the curved-
arrow notation (L : other ligands):
"\ r;l
TAT
\/
Ar
NI:X+ M (r 8.32)
,'/
r)l I L/ \t
I
electron pair
in a d orbital
Oxidative addition can occur by a variety of mechanisms, but a concerted (one-step) process
is fairly common.
Reductive Elimination Reductive elimination is conceptually the reverse of oxidative

addition, and the orbital interactions involved are the same, only in reverse. In reductive elim-
ination, then, two ligands bond to each other and their bonds to the metal are broken;
X-M-Y -------+ X-Y + M. An example of this process is the formation of a carbon-carbon
bond between two ligands within a Ni complex:
H ,cH2cH2cH2cH3
\/
/ !:C \ "\ H
Ph3P\
Ni H+Ni+
Ph3Pr
\.-c /LL
,cH2cH2cH2cH3
(r 8.33)
\ 'cHr ._/ H:C H
Ph3P/ Ph3P
Ni(rr) Ni(o)
a l6e- complex a L4e- comPlex
842 cHAprER '18 . THE cHEMtsrRy oF ARyL HALTDEs, vrNylrc HALTDEs, AND pHENoLs. TRANSIIoN-METAL cATALysts
Because two X-type ligands are lost, the metal is reduced, and its electron count is decreased.
Notice in this particular example that the alkene stereochemistry is retained. Reductive elimi-
nation in general occurs with retention of stereochemisl4y. Because this process is the reverse
of oxidative addition, it follows that concerted oxidative addition also occurs with retention of
stereochemistry.TlteelectronflowinFig. 18.5orEq. l8.32isconsistentwiththisobservation.
Ligand Insertion In this process, a ligand inserts into a metal-ligand bond; that is,
L-M-R ------> M-L-R. Notice the difference between oxidative addition and ligand in-
sertion. Both are insertion processes. In an oxidative addition, the metal inserts into a chemi-
cal bond within a compound not initially associated with the metal. In a ligand insertion, a lig-
and L inserts into the bond between the metal and a different ligand R, and the inserting ligand
gains a bond.
Two types of ligand insertion are most frequently observed in transition-metal chemistry.
In a I ,I -insertion, the new bond is formed at the same atom that was bound to the metal. In-
sertions ofCO ligands are frequently observed examples ofthis type. The first reaction below
is an example.
(lH.
_\ CHI co cH,
\u\,,
\
rI'
r\tvnrT.\-:\r
/r (CO)nMr-C-O
I
CC_) ll c: o
(co)4M (18.34)
l:l /l.grtilr/ ngilfld
'rrist'rf
/orl associatiott
Mn(I) Mn(I) Mn(I)
an 18e- complex a I6e- complex an 18e- complex
- -
In this reaction, the methyl group migrates,with its bonding electrons, to the carbon of the car-
bonyl ligand, which in turn forms an X-type bond to the metal. This migration is possible be-
cause the carbon ofthe carbon monoxide ligand is electron-deficient. Hence, the carbonyl car-
bon inserts into the Mn-CH, bond. Notice that this insertion leaves a vacant site (that is, an
empty orbital) on the metal, as we can see from the reduction in the electron count. In the sec-
ond reaction, this empty metal orbital is filled by another molecule of the ligand from solution.
Another type of ligand insertion is 1,2-insertion. In this process, the migrating group
moves to an atom adjacent to the one bound to the metal. A common example of this process
is the following, in which an ethylene ligand inserts into a Pd-aryl bond.
Ar (.H' PPh3
i
Br-Pd+ + J,J-/isaridi Br Pd -llH -CH ,,Ar : PPhr-\- Br
I
Pd- CHrtlH,Ar (18.35)

l- - - Itgand -
' (.H, Illsilrfl{rI/ I
associatian I
PPh3 PPh3 PPh3

Pd(rr) Pd(rr) Pd(rr)
a l6e- complex a l4e- complex a I6e- complex
Again, notice that the electron count is reduced by two; that is, the process results in an empty
orbital on the metal. This orbital can then gain another electron pair by ligand association, as
shown by the second step in Eq. 18.35, thus fulfilling the l6-electron rule.
We can approximate the ligand insertion process in the curved-ilrow notation as follows:
+'^cH,
Br-n'o-il| Br-Pd-CH''lH'-Ar
I^, J.,.,
--+ t-
I
( 18.36a)
PPh3 PPh3
As Eq. 18.36a illustrates, 1,2-ligand insertion is essentially a concerted addition of the metal
(Pd in this case) and the migrating ligand (Ar in this case) to the alkene zrbond. Because 1,2-
ligand insertion is a concerted intramolecular addition reaction, the two new bonds must be
formed at the same face of the a'bond. Hence, ligand insertion is a syn-addition. This be-
comes evident when the carbons ofthe alkene double bond are stereocenters, as they are in cy-
clohexene. In this case, syn-addition requires that the Pd and the aryl group have a cis relation-
ship in the insertion product.
Br
lo:n
I
Ar
Br-J.*f 7ll
r(, @ PPh3
insertion
( 18.36b)
Pd and aryl are cis
p-Efimination In B-elimination, a group B to the metal migrates with its bonding electron
pairto the metal. This process is conceptually the reverse of ligand insertion. (Run Eq. 18.36a
backward mentally and you will see the B-elimination of ethylene by migration of aryl.)
It often happens that B-elimination involves a hydride migration. For example, the product of
:
Eq. 18.36a (with Ar phenyl) can undergo B-elimination with hydride migration as follows:
-\cH/
Ht- Ph Ph
Hl
---*
lcH
Br-Pd-CHz
I
Br-Pd<-+f ( 18.37)
I I cH,
PPh3
PPh3
Pd(rr) Pd(rr)
a l4e- complex a l6e- complex
Notice that B-elimination requires an empty orbital on the metal, because, as a result of this
process, the electron count is increased by two units.
We studied another type of B-elimination, the E2 reaction, in Sec. 9.5. The elimination re-
action in Eq. 18.37 looks superficially similar, but it is quite different. In the E2 reaction, a
protonis eliminated. In the B-elimination of Eq. 18.37, ahydride-ahydrogen with its bond-
ing electrons-is eliminated by migration to the metal. We can stress this point with the
curved-arrow notation:
H. -Ph Ph Ph
Hl Hl
lrl
Br-PdlCHz
ICH
Br-Pd^ll Br
ICH
Pd<-11 (18.38)
I I cH, ligand
assocnnon
- I CH,
PPh3 PPh3 PPh3
Pd(rr) Pd(II) Pd(rr)

I6e- complex
a L4e- complex a I4e- complex - a
Because this p-elimination is intramolecular-within the same molecule-it must occur as

a syn-elimination. This makes sense because this reaction is conceptually the reverse of 1,2-
844 cHAprER 18 . THE cHEMtsrRy oF ARvL HALTDES, vrNyLrc HALTDEs, AND pHENoLs. TRANstloN-METAL cATALysts
ligand insertion, which is a syn-addition (Eq. 18.36b). Contrast the stereochemistry of this B-
elimination with that of the E2 elimination, which is a bimolecular reaction and occurs with
anti stereochemistrv (Sec. 9.5E).
Consider the following mechanism for Eq. 18.18 on p. 83 L Identify the process associated with
each step. Counting electrons at each stage may help you.
Pd(PPh3)4 ( --> Pd(PPh3)3

F+ ( 1 8.39a)
PPh3 PPh3
H
HH \H
Ph3P\
\/C:C --* ,rc:e/
Pd(PPh3)2 + Pd\ (18.3eb)
/\
Br _/ \
Ph3P Br
Ph
Ph
H H
\H \H
Ph3P.
"\ ,/,b: C/ Ph3P\
/C:q/
Pd \ + Li+ cH3cH2s- -4 Pd \ +Li+Br- ( 1 8.39c)
_/ \
PhrP Ph / \ \SCHTCH,
Ph
Br Ph3P-
H
\H HH
Ph3P\
/C:q/
Pd
\/C:C
\ ------> + Pd(PPh3)2 ( 18.39d)
PhjP \ 'SCHTCH,
_/ Ph /\
cH3cH2s Ph
SofutiOn Step 18.39a consists of two successive ligand dissociations that reduce the electron
count around the Pd from 18e- to l4e-. This "makes room" for the vinylic halide, which under-
goes an oxidative addition with retention ofconfiguration in Step 18.39b. This step takes the
electron count to l6e- , and oxidizes the Pd(0) to Pd(II). Step I 8.39c is a ligand substitution of a
bromo ligand with an ethylthio ligand. It might occur by a prior dissociation of the Br ligand, by
association of the CH.CHTS- with the Pd to give an 18e- complex followed by dissociation of
Br-, or by a concerted mechanism reminiscent of the Sr2 reaction. Finally, Step I 8.39d is a re-
ductive eliminntion, which forms the product with retention of stereochemislry and regenerates
the catalytic Pd(0) species Pd(PPh3)2.
Let's use the example in Study Problem 18.2 to take stock of what the Pd is actually
doing-why it makes a vinylic or aryl substitution possible. Ligation to the Pd brings two
groups-the vinylic group and the nucleophile-into proximity. The oxidative addition step is
the key step that makes this possible, and, as we have seen (Fig. 18.5), it is driven by the si-
multaneous presence of filled and empty metal orbitals that can interact with the vinylic halide
so that the carbon-halogen bond is broken. The nucleophile CH.CHTS- and the vinylic group
are then connected by reductive elimination. The orbital interactions are essentially the same
as in oxidative addition. The role of the metal finds analogy in the slider of a zipper: it brings
two groups together, causes them to join and lock, and then moves on to do the same thing
over again.
18.6 EXAMPLESOFTRANSITION-METAL-CATALYZEDREACTIONS 845
18.14 A student has written the following ligand substitution reaction, claiming that it changes the
oxidation state of the metal by one unit. What is wrong with this reasoning?
Cl- + Pd(PPhz)t + ClPd(PPh3)3 a :PPh3
18.15 The Wkinson catalyst chlorotis(triphenylphosphine)rhodium(I), ClRh(PPh3)3, brings about

the catalytic hydrogenation of an alkene in homogeneous solution:
R
\/C:C + H, ClRh(PPh3)3
> RCHTCHTR ( 1 8.40)
H
/\ H
(a) Using the following mechanistic steps a$ your guide, draw structures of the transition-
metal complexes involved in each step. Give the electron count and the metal oxidation
state at each step.
1. oxidative addition of H, to the catalyst
2. ligand substitution of one PPh, by the alkene
3. l,2-insertion of the alkene into a Rh-H bond and readdition of the previously ex-
pelled PPh, ligand
4. reductive elimination of the alkane product to regenerate the catalyst
(b) According to the known stereochemistry of the 1,2-ligand insertion and reductive elim-
ination steps, what would be the stereochemistry of the product if Dr were substituted
for H. in the reaction?
18.6 EXAMPLES OF TRANSITION.METAL.CATALYZED REACTIONS

A. The Heck Reaction
In the Heck reaction, an alkene is coupled to an aryl bromide or aryl iodide under the
influence of a Pd(O) catfllyst.
H=rC
[ ,]_.',,'-l
od+P-J(, ))
L ' \---7 /..i.r
|
CH: (catalyst) CH-t

(cH3cH:):N
+ H.C-(lHl + HBr ( 18.41)
CH-rC N (soh,ent)
Br 1g
-h, 125 "C (_"I I: r'H, neutralized bv
the (CH3CHz)rN
(s6% yielcl)
(The aryl substituents of the phosphine ligands used in the catalyst in this case are o-tolyl (that
is, o-methylphenyl) groups rather than phenyl groups, but phenyl groups are also sometimes
used.) The reaction is named for Richard F. Heck (b. 1931), who discovered the reaction in the
early 1970s while a professor of chemistry at the University of Delaware. (A Japanese
chemist, T. Mizoroki, simultaneously discovered the reaction, but it is generally known as the
Heck reaction.) The Heck reaction has proven to be one of the most useful processes for form-
ing carbon--carbon bonds to aromatic rings and even, occasionally, to vinylic grcups.
The mechanism of the Heck reaction is outlined in the following equations. You should
identify the process or processes involved in each step (L : tri-o-tolylphosphine ligands; the
steps in Eq. 18.42b are numbered for reference).
846 CH ER
.I8 T THE CHEMISTRY OF ARYI HALIDES. VINYLIC HALIDES, AND PHENOLS. TRANSINON.METAL
CATALYSIS
The acfiral catalytiea[y active species is believed to be PdI2r which is formed by two lig-
and dissociations:
LL LL L
\,/ \/
Pd <+ <+- Pd+L (18.42a)
(\, ( "d {
+L
The PdLz thus generated enters into the catalytic cycle"
L LAr
"\ -/* ,f,H, Ar
(1),> H,C\
' Pd/ G)>
Pd + fu-Br Pd + HzclScHr
L/ LBr
.r/ \
L/ \;
+ L-'
ATCHCH-' -t oCH, H H
-l-
H o u) >,
/c+{ #2+ P{
Ar L/ tu, tu,
+*
LBr\
-/ L/ G)
+ ArCH-CHz
LH
tr/ 4e+
L
Pd + HBr (18.42b)
{\, { reacts with
(CHsCHe)sNr
Another erample of the }Iock teaction illustates nvo imporantaspcctr of the rEaction.
Pd(OAc)2 catalpt
O+Cr'
(CHrCHz)gl'I
dimethylformamide
+ HI (19.43)
ts h, 100 oc reacts with
(CHrCHz)rN
cyclohexerre iodobenrane (2.cyclohexenyl)benzene
(exce$s) (72o/o yield)
Firsg the catalyst is not Pd(0), but rather a Pd@) species. (Pd(OAc), is used because it is a con-
vmient and easity handled Pd derivative.)In samecases (typicallywith iodobmzenesasthearyl
halidcs), the reaction can be nrn wi0r Pd@, but it is beliwed thatthe Pd(tr) is rc&rced to Pd(0),
pohaps by a few molecules of alkenethat are convertedinto vinylic acetafe*; Pd(0) is the actual
catalyst" Addition of an oxidizable ligand such as PPh, can also serve to rpduce ths Pd(tr). Be-
cause a very small amount of Pdis useq the by-products of these reactions arealss fornred in
very small amounts. Second, thealkene doublebondintheproduct is noratthe siteof coupling
but rather one carbon removed" What has hap'pened hers?
18.6 EXAMPLESOFTRANSITION-METAL.CATALYZEDREACTIONS 847
This sort of product, which occurs commonly with cyclic alkenes in the Heck reaction, is a
direct consequence of the stereochemistry of certain steps in the mechanism. The insertion
step (step 3 in Eq. 18.42b) must occl'r in a syn manner because the reaction is inffamolecular.
Hence, in the initially formed insertion complex, the Pd and the phenyl group become cis sub-
stituents on a cvclohexane ring.
the only p-hyclricle available

fctr syn-elirnination
I
Y
I
H L-Pd
L-Pd I
( 1 8.44)
I
Pd and phenyl are cis
The subsequent B-elimination is also a syn process. Hence, only a hydride cis to the Pd is "el-
igible" for elimination. When a noncyclic alkene is used in the Heck reaction, internal rotation
is possible so that the hydride on the carbon at which insertion occurs can be eliminated.
-Pd
I
, Ph ,l 'Ph
\\
H,,,. \ I..,, H
syn. -Pd\n / ittlt'rttul
' I
H/c=c- H+
,nsertlon
H-f+.{'," rolttt itttt
--+
HH
_ I
Pd-----____.- H
I
\-, v Y sYn
F-elimination a H
-Pd-H
,,,.
H','..',p C.,...,,ph
'c .....ph (18.45)
/\ -c
HH ,r/"-v\t,
la Il
When the starting material is a cyclic alkene, as in Eq. 18.43, an analogous internal rotation is
prevented by the ring. The only cis B-hydride available for elimination is the one (shown in
red in Eq. 18.44) on the other B-carbon. Elimination of this hydride yields an alkene in which
the carbon at the insertion point-the one attached to the phenyl-is not part of the double
bond, but is one carbon removed. We can summarize this in the following way, with the inser-
tion point marked with an asterisk (*):
tl
ll
f(""T-I \,4\,,,H
. syn. DL
rr
SYN Ph
'r
L-Pd-Ph + msernon L-Pd -+
B-elimination -
L-Pd-H (18.46)
I I I
I I I
When the Heck reaction is applied to unsymmetrically substituted alkenes, such as an

R-CH:CHz, two products are in principle possible, because insertion
alkene of the form
848 cHAprER 18 . THE cHEMtsrRy oF ARyL HALTDES, vrNylrc HALTDEs, AND pHENoLS. TRANSIIoN-METAL cATALysrs
might occur at either of the alkene carbons. It is found that when the R group is phenyl, CO'R
(ester), CN, or another relatively electronegative group, the aryl halide tends to react at the un-
substituted carbon; that is, the product is R-CH:CH-Ar, usually the E (or trans)
stereoisomer. When R : alkyl, mixtures of products are often observed (Problem 18.17).
18.17 Whcn iodobenzene and propene are subjected to the conditions of the Heck reaction, two
constitutionally isomeric products are formed. What arc they? Why are two products
formd? l
18.18 lilhatrwo sets of gry1 bromide and alkene starting materials would give the following com-
pound as th pr .oduct of A:it{cck reaction?
.H
I
ocH3
a*c
'l
H,
1&19 The profuct of a lleck reaction is, like the starting materid, an alkene. Why doesn't a Heck
reaction of the @uct compte with the reaction of the starting alkene?
18.20 What product is epectod whe, cyclopentene reacts with iodobenzene in the presence of bi-
e'thYlamine and a Pd(o): catalYst?
B. The Suzukl Coupllng

The Suzuki-Miayura coupling reaction (usually referred to as the Suzuki reaction or the
Suzuki coupling) is a Pd(0)-catalyzed process in which an aryl or vinylic boronic acid (a
compound of the form RB(OH)2, where R : an aryl or vinylic group) is coupled to an aryl or
vinylic iodide or bromide in the presence of a base, which is in many cases aqueous sodium
hydroxide or sodium carbonate. The reaction can be used to prepare three types of com-
pounds: biaryls---compounds in which two aryl rings are connected by a o bond; aryl-substi
tuted alkenes; and conjugated alkenes. Eq. 18.47 illustrates the preparation of a biphenyl.
Pd(OAc)z (0.3 mole %)

PPh3
NaoH + +r,GcH-o Na2CO3
GB(.H)2 propanol-water
phenylboronic acid p-bromobenzaldehyde
(,, /> cH-o + Na* Br * B(oH)3 ( rs.47)

\J \-/ boricacid
4-phenylbenzaldehyde
(a biphenyl; 860lo yield)
The Pd(O) catalyst can be Pd(PPh3)4, the same catalyst used in the Heck reaction, or the Pd(0)
can be formed in the reaction flask from Pd(OAc)2, a strategy that is also used in the Heck re-
action, as in the preceding example.
Eq. 18.48 shows the preparation of an aryl-substituted alkene.
18.6 EXAMPLES OF TRANSITION.METAL-CATALYZED REACTIONS 849
H H
HH Pd(PPh3)4
(\-
4/B(oH)2 \/ (4.5 mol e a/o) U- C
t) + C:C
/\
KOH
H,O/THF
>
CHr
( 1 8.48)
cH30 Br CH:
4-methoxybenzene- (Z) -1 -bromo- I -propene
boronic acid cH3o
(Z) - l-methory- 1 -propenylb enzene
(cis-anethole; 620/o yield)
As this example illustrates, the coupling occurs with retention of alkene stereochemistry. You
may have noticed that this is the type of compound that can be prepared by the Heck reaction.
However, the Suzuki coupling avoids issues of regiochemistry that can sometimes occur with
the Heck reaction. (See Problem 18.17, p. 848.)
The importance of the Suzuki reaction has resulted in the commercial availability of many
boronic acids and their derivatives. Two ways of preparing the required boron derivatives are,
first, the reaction of Grignard or organolithium reagent with trimethyl borate:
+
e(ocHr), MgBr B(OH)2
+ B(OCH3)3 # ltl
\/
I
I
#H.O
Hzo
+
n
Y
+ 3 CH3OH
+ Mg'* + Br-
(18.49)
ocH3 ocH3 ocH3
In this reaction, the Grignard reagent, a strong Lewis base, donates electrons to the boron in a
Lewis acid-base association. A reaction with aqueous acid results in formation of the boronic
acid product. (See Problem 18.24,p.851.) The analogous reaction can be used to form vinylic
boronic acids from vinylic Grignard reagents. A second preparation of vinylic boronic acid
derivatives is the hydroboration of l-alkynes with catecholborane:
/o
H
/o \/\/ B
CH3CH2CH.CHzC-CH + H-B + THF r\

U-U r'-t o (I 8.s0)
o /\ -
l-hexFne cH3cH2cH2cHz H
catecholborane
This is essentially the same reaction discussed in Sec. 14.58, in which hydroboration is car-
ried out with disiamylborane. Recall that hydroboration occurs as a syn-addition. Both the cat-
echolborane adducts and the disiamylborane adducts can be used in the Suzuki coupling. The
following reaction illustrates both the use of vinylic catecholboranes and the formation of a
conjugated alkene.
HH
/o \/
H B H
\/f'-r-'
H Pd(PPh3)a catalyst H C:C
\/ o rI Na+ CH3CH2O- \/\
F-C
/\
U-\J
C:C Ph
/ benzene
/\
cH3cH2cH2cH2 H Br Ph cH3cH2cHzcH2 H
(7 60/o yield) (18.51)
850 cHAprER 18 . THE cHEMtsrRy oF ARvL HALIDES. vtNyltc HALIDES. AND pHENoLs. TRANSIIoN-METAL cATALysts
The mechanism of the Suzuki coupling begins exactly like that of the Heck reaction (Eq.
18.42b, p. 846) with ligand dissociation to give a l4e- complex, followed by oxidative addi-
tion of the arvl halide.
PPh3 PPh3 PPh3
v
I I I
Y Y
PPhr-> Pd +-PPh3 + PPh3+Pd +Ar-Br PPhr--+ Pd-Br
t
I
I4e,Pd(O)
oxidative
addition I
Ar
PPh3
+ 2 PPh3 L6e , Pd(II) (18.52a)
18r, Pd(O)
From this point on, the mechanism is not definitively established, but a reasonable sequence
involves another ligand substitution in which the base displaces the halide ion:
PPh3 PPh3
*
I
v
I
PPhr--+ Pd-Br + -t-,H

ttgana
PPhr+Pd-OH + Br-
I
substitution I
Ar Ar ( 18.52b)
A Lewis acid-base association brings the

- boron into the coordination sphere of the metal:
PPh3 PPh3
IH
PPhr---+Pd-OH
*.-
I
+ */^
PPhr+Pd-O\
- ..
||
B(OH)'ta
l'|
2#
LeW$AC.ld-0ASe " \B(OH)2
assocntnn |
ArR Arl
R ( 18.52c)
This association results in a formal negative charge on boron. Remember, though, that carbon
is more electronegative than boron; this means that carbon bears a significant amount of the
negative charge in this complex. In other words, the Lewis acid-base association of the oxy-
gen with boron endows the carbon in the carbon-boron bond with significant carbanion char-
acter. An intramolecular substitution of this "carbon anion," a strong base, for the weaker base
HO- results in transfer of the R group to the metal. Reductive elimination then gives the cou-
pling product and provides the catalyst for another cycle.
PPh3 PPh3 PPh3
I t\i v
I I
Y
PPh3--+ Pd:O-_
l\__B(oH)z
ts ffi PPhr--> Pd-R reductwe
elimination
PPh3+Pd + Ar-R
Ar -l Iigand
substitution
I
Ar regenerated coupling
catalyst product
+ B(OH)3 -
( 18.52d)
,I8.6 EXAMPLES OFTRANSITION-METAL-CATALYZED
REACTIONS 851
The Suzuki coupling is named for Akira Suzuki (b. 1930), who is on the faculty of the Kirashiki Uni-
versity of Science and the Arts in Khashiki, Japan. Prof. Suzuki had spent two years as a postdoctoral
fellow with Herbert C. Brown (the discoverer of hydroboration), where he was immersed in the or-
ganic chemistry of boron. His intellectual synthesis of transition-metal organometallic chemistry and
organoboron chemistry led to the discovery in the mid-1970s of the reaction that bears his name, in
collaboration with his student Norio Miyaura, while the two were at Hokkaido University in Japan.
The Suzuki coupling has become a very important reaction in both academic and industrial settings.
@l8.2l,CompletethefollowingPd(0)-catalyzedSuzukireactionsbygivingthecouplingproduct.
For parts (b) and (c), include the stereochemistry of the pioducts.
(a)ffi'(oH)2+
2 -naphthaleneboronic acid
ryt'*
\u''
(b) H CHg
(\B(oH)z* \/
C:C --->
cH3o-
r'\,,/ / ,\L:,,
BrH
(c) Hre ,cH, Br
\/ \/
C*=rC + C:C ------>
"/H \B(OH)2 /\
H CH2CH2CHzOH
1E.22 Provide nro different reaction sequences tlrat coiild be used to synthesize 4-methoxy-
3'-methylbiphenyl. Both sequences, however, should start with both p-bromoanisole and
n-bromotoluene.
HnC HsC
OCH3 from Br and CH3O
&methoxry- 3'-methylb iphenyl rn.bromotoluene p-bromoanisole
18.23 Give two different pairs of starting materials that could be used to prcpare the following
compoundbyaSualkicoupling. ' :, :ii. , '',..
FH'
fr1
Ph
1/\
\_/
\tC:C
/\
HH
18.24 Draw a curved-arrow mechanism for the last (acid hydrolysis) step of Eq. 18.49.
852 CHAPTER 18 . THE CHEMISTRY OF ARYL HALIDES, VlNYtlC HALIDES, AND PHENOLS. TRANSITION-METAL CATALYSIS
c. Alkene Metathesis
Certain ruthenium(tV) catalysts bring about a reaction in which two alkenes are "sliced apart"
at their double bonds, and the parts reassembled, to give new alkenes.
HOCH, CH,OH G2 ruthenium catalyst

\- /
cH3o cH2cH-cH, + c:c (2 mole o/o)
/\ cH2clZ
HH
eugenol
cis-2-buten-1,4-diol
HO
\,-
*3oOT, i
C:C + HO-CHzCH:CHz
H
/\ ullyl alcohol
CHzOH
(E) - 4- (4- hydrory- 3- methoqryh enyl )-2- b uten - I - ol
80olo yield ( 18.53)
This remarkable reaction is an example of alkene metathesis, also called olefin metathesis.
A metathesis reaction (pronounced me-ti'-the-sls, from the Greek, meta change, thesis : :
place) can be represented in general as follows:
,t}
A-B+C-DA-C+B-D ( 18.54)
\/
You are probably familiar with some inorganic examples of metathesis reactions, such as the
reaction of silver nitrate with sodium chloride:
+++
Ag NO3 + Na Cl AgCll + Na NO: ( 18.55)
silver(I) sodium silver(I) sodium
nitrate chloride chloride nitrate
In an alkene metathesis, the groups at each end of the double bonds are interchanged. For ex-
ample, the reaction in Eq. 18.53 has the following form:
R'HRRR'R RH
\/\/\/ \/
C:C+C:C-C:C + C: C (18.56)
/\/\ /\ /\
HHHH HH HH
For a metathesis reaction of two unsymmetrical alkenes, ten alkenes (not counting stereoiso-
mers) can be formed. (See Problem 18.25.) However, the.usual applications of this reaction
are typically not this complex.
A number of transition-metal catalysts have been developed for alkene metathesis. These
catalysts are base on tungsten, molybdenum, and especially ruthenium. The two most widely
used laboratory catalysts are the ruthenium-based catalysts Gl, which stands for the Grubbs
first-generation catalyst, and G2, the Grubbs second-generation catalyst. The structures of
1 8.6 EXAMPLES OF TRANSITION-METAL.CATALYZED REACTIONS 8 53
P(Cv).
t'
P(Cy), = 3 ia
{ Cl,,,,... +
cl/ Ru- -ilH-Ph
I Uenzr4idene grollfr
P(cy):
\
Grubbs Gl catalvst
(a)
Mes
- -
mesifyl group =
Y.r- *,V,* - IIes
I{HC
Cl,,,....
I
,-.Y CI,,,,... J
I
HrC ir2T-cH-Ph ir21u-cH-Ph

I I
ij(cy), P(Cy)r
abbreviated structure
Grubbs G2 catalyst for the G2 catalyst
(b)
Fiture 1 8.6 The structures of wvo ruthenium catalysts for alkene metathesis and their abbreviated structures. Cy
isthe abbreviation for the cyclohexyl group. and Mes is the abbreviation for the mesityl, or 2,4,6-trimethylphenyl,
group.The unusual ligand in G2 is a stabilized carbene (see Eq. t 8.57), and it is abbreviated NHC (for"Nitrogen Hete-
rocycle-stabilized Carbene"). Formal charges in the NHC ligand are conventionally not shown. A key aspect of these
catalysts is the ruthenium-carbon double bond.
these catalysts are shown in Fig. 18.6. Although we need not go into detail here, the design of
these catalysts was an evolutionary process that involved a consideration of steric and elec-
tronic effects of the ligands in light of the reaction mechanism (which we'Il discuss below), as
well as some outright fortuitous discoveries! Ruthenium catalysts can be easily handled in the
laboratory, and, as Eq. 18.53 illustrates, they can be used in the presence of alcohols, phenols,
and other functional groups. The molybdenum and tungsten catalysts are much more air-sen-
sitive and less tolerant of other functional groups.
The ruthenium-+arbon double bond plays an important role in the operation of these cata-
lysts. The rather unusual NHC ligand in the G2 catalyst, when "dissociated" from the metal,
is actually a carbene (a molecule containing divalent carbon; Sec. 9.8). Most carbenes are very
unstable, but this carbene is highly stabilized by resonance.
t I
N:r +.+ Mes-T\9'N-NIes <+lvles-Nv{-Mes
LY-
I Mes :N Mes
- I
::.J
uctures for the I{HC ligand
Mes-Nr..V N-Mes
hybrid structur. fo, the NHC ligand ( 18.57)

For elecffon-counting pulposes, the NHC and PCy, ligands are L-type ligands, the chlorines
are X-type ligands, and the benzylidene group is a 2X ligand because it has two bonds to the
ruthenium. You should verify that both catalysts are 16-electron complexes (Eq. 18.28) and
that the oxidation state of ruthenium (Eq. 18.22) is formally Ru(IV).
In many cases, the catalysts bring some or all of the possible alkenes into equilibrium. In
such cases, the practical use of alkene metathesis requires the application of Le Chdtelier's
principle. For example, in Eq. 18.53, one of the starting materials, cis-2-buten-1,4-diol, is used
in excess. Use of an excess of this diol is practical because it is cheap, and because both it and
the by-product allyl alcohol are readily separated from the desired product.
One of the most important applications of alkene metathesis is for closing rings, and it can
be used to close medium- and larse-sized rinss.
Gl catalyst
H,C4r'o\
(2 mole %)
+ H.'t_l ( 18.s8)
j=Ph -cH,,
r
Denzene Ph
(7 2 0/o yield)
HrC
-
In this and many other ring-closing applications, the by-product is ethylene, which bubbles
out of the reaction mixture, thus driving the equilibrium towards the product-Le Chdtelier's
principle in operation again.
The mechanism of alkene metathesis, which we'Il illustrate for Eq. 18.56 using the G2 cat-
alyst, starts with loss of the PCy. ligand by ligand dissociation. Because ruthenium in the re-
sulting complex has l4 electrons, it can accept two electrons from another ligand, in this case
one of the alkenes. Let the alkene RCH:CHR be present in large excess; because of its con-
centration, it is more likely to interact with the catalyst.
NHC NHC NHC

I I RCH:CHR, *
I
Cl2Ru CHPh < --> cl 2Ru CHPh Cl2Ru CHPh ( 18.5ea)

- -
t -
tP(cy): a L4e- complex
RCH+CHR
+ :P(Cy): a l6e- complex
Then follows a key step in alkene metathesis, a cycloaddition to form a metallacycle (a cyclic
compound in which the metal occupies a ring position). This reaction is essentially a ligand
insertion (p.8aD.
NHC I{HC ll NHC I{HC

Y
I
Cl2Ru \ CHPh +
I V I cHPh +
cl2Ru r cHPh +cl2Ru*+ Cl2Ru
v
I
+ RCH-CHPh (18.5eb)
\\ ll-lSC
]H'CHR
RCH'
ll cun
RCH RCH
il
very minor
RCH-CHR by-product
a metallacycle
As shown in this equation, the metallacycle then breaks down in the opposite sense by acyclore-
version (the reverse of a cycloaddition) to give a new alkene, which contains the benzylidene
group. This becomes a very minor by-product, because the catalyst (and thus the benzylidene
group) is fypically present in I or 2 mole percent ofthe reactants. This process leaves the cata-
lyst "primed" with the p611: group.
18.6 EXAMPLESOFTRANSITION-METAL-CATALYZED REACTIONS 855
The cycloaddition--cycloreversion process is now repeated. It is most probable that the

process will occur with the alkene used in Eq. 18.59b, because this alkene is in excess; but the
reaction with this alkene results in no change. (Be sure to demonstrate this point to yourself.)
However, occasionally a molecule of the other alkene R'CH:CHz will bind to the catalyst,
and this produces a metathesis product.
NHC NHC NHC

I
I
+ v
I
Cl2Ru I CHz -------> Cl2Ru

" , CH: Cl2Ru: CHz + RCH:CHR' (18.59c)
RCH
lll *rll
CHR'
lrrl
RCHJ-CHR'
first
metathesis product
This leaves the catalyst with a:CHz group. This catalyst molecule is most likely to react
with the alkene in excess, and when that happens, the second metathesis product (which is
allyl alcohol in Eq. 18.53) is formed, and the catalyst is again primed with a:CHR group.
NHC I{HC NHC

I
v
I I
Y +
Cl2Ru=CHz ------> Cl2RurCH2 + Cl2Ru + RCH:CHz (18.59d)
\\ ll-l
RCHICHR
tl
RCH
second
RCH-CHR metathesis product
I
v
catalyst enters
another cycle
(Eq. l8.5ec)
The sequence in Eqs. 18.59c-d continues repeatedly until the limiting reactant is exhausted.
It is conceivable that, as the product builds up, it might undergo metathesis with itself.
However, self-metathesis is largely avoided in this example because one of the starting mate-
rials is used in excess, and it intercepts the catalyst almost every time. In other words, if the
product enters into the metathesis sequence and is split by the catalyst, the fragments are most
likely intercepted by the alkene present in excess; and such a reaction either gives back that
same alkene or the desired product.
When it is impractical to use one alkene in excess or to exploit Le Chdtelier's principle in
some other way, self-metathesis of the product can be a problem. However, this potential com-
plexity of alkene metathesis is mitigated by the fact that different alkenes undergo metathesis
at greatly different rates. Alkene metathesis is very sensitive to the steric environment of the
alkene double bonds. For example, 2-methylpropene (isobutylene) does not undergo self-
metathesis, presumably because the interaction of two (CHr)rC: fragments with the catalyst
results in severe van der Waals repulsions (that is, steric congestion) with the bulky catalyst
lisands.
HrC
/9H,
H.C
:\ CH.
\ I
/
C- CHz + H,C-C C:C + HzC:CHz
f
(19.60)
/ \ /'\
L
H:C CH: H:C CH:

two molecules of isobutylene not formed
(Isobutylene can be used as a metathesis partner with less crowded alkenes, however.) In fact,
the metathesis catalysts were designed to emphasize such differences in alkene reactivity.
856 cHAprER 18 . THE cHEMrsrRy oF ARyL HALIDES, vlNylrc HALTDES, AND pHENoLs. TRANSIIoN-METAL cATALysts
Alkene metathesis plays a major role in the synthesis of complex organic molecules, and it
is used industrially with increasing frequency in such diverse applications as alkene synthesis,
polymer synthesis, and pheromone synthesis. Because ruthenium catalysts can be used in
aqueous solution, they are providing options for "green chemistry"-chemistry that is envi-
ronmentally friendly. The importance of alkene metathesis was recognized with the 2005
Nobel Prize in Chemistry, which was shared by three chemists: Robert H. Grubbs (b.1942) ot
the California Institute of Technology, who developed the ruthenium catalysts; Richard R.
Schrock (b. 1945) of the Massachusetts Institute of Technology, who developed molybdenum-
based metathesis catalysts; and Yves Chauvin (b. 1930) of the Petroleum Institute of France,
who first proposed the reaction mechanism.
1E.25 Show that the equilibrium mixture produced by alkene metathesis of two completely different
alkenes with the following general struchues contains ten different alkenes. (Assume that all
alkenes have trans stereochemistry.)
RIH R3H
\/C:C +
\/
C-C
\J-\-r
/ \. /\
HR' HR4
18.26 Give the structure of the major product formed in each case when the reactant(s) shown un-
dergo alkene metathesis in the presence of an appropriate ruthenium catalyst.
(a) cH2oH
(R)-HzC : CHCH2CHCH2CH2CH : CH2 -------* acompound with 7 carbons
(b)H.C.
# -------> a compound with r 1 carbons
"rau
(c),a
I l+ "oT,
C:C
fH2oH
-----+
\__/ /\
HH
(large excess)
I 8.27 Suggest an alkene metatheeis reaction that would yield each of the following compounds as a
major product.
citronellol
(oil of roses)
(c) p H
I
(-
Cr' CH,OH
I
18.28 Draw structures analogous to those in Eqs. 18.59a-d for the catalytic intermediates formed in
the conversion of l,7-octadiene to cyclohexene and ethylene catalyzdby the G2 catalyst.
18.6 EXAMPLESOFTRANSITION.METAL-CATALYZEDREACTIONS 857
The three coupling reactions presented in this section are additional examples ofreactions
that can be used to form carbon-<arbon bonds. Here is a list of such reactions that we have en-
countered up to this point:
l. the addition of carbenes and carbenoids to alkenes (Sec. 9.8)

2. the reaction of Grignard reagents with ethylene oxide and lithium organocuprate reagents
with epoxides (Sec. 1 l.4C)
3. the reaction of acetylenic anions with alkyl halides or sulfonate esters (Sec. 14.78)
4. the Diels-Alder reaction (Sec. 15.3)
5. Friedel-Crafts alkylation and acylation reactions (Secs. 16.4E-F)
6. the Heck and Suzuki coupling reactions (Secs. 18.6-4-8)
7. alkene metathesis (this section)
D. Other Examples of Transition-Metal-catalyzed Reactions

One of the most important transition-metal catalysts in commerce is a catalyst formed from
TiCl, and (CH3CH2)2AIC1, called the Ziegler-Natta catalltst. This catalyst brings about the
polymerization of ethylene and other alkenes at25 "C and I atm pressure. Although free-radi-
cal polymerization of ethylene (Sec. 5.7) is very important, the Ziegler-Natta polymerization
of ethylene accounts for most of the polyethylene produced; the resultinghigh-density polyeth'
ylene has different properties from the low-density* polyethylene produced by free-radical
processes. The discoverers of this catalyst, the German chemist KarlZiegler (1898-1973) and
the Italian chemist Giulio Natta (1903-1979) shared the 1963 Nobel Prize in Chemistry for
their work. Although the mechanism of the polymerization has been hotly debated, the follow-
ing sequence is one possibility:
C1 CI
H:[":(,H:>'
cl-Ti-cHrcH3
I I
liganrl
Cl_ Ti-cH2cH3 l,2-Iigancl insertion
forrned from associrttictn +
(CH-rCHz)zAlCl HrC 4c;u,
and Ticl:
CI CI
HrC:CH: ,
cl-Ti-
I I
cHrcHrcH2cH3 Iigct!d.
cl-Ti-cH1cH:cH2cH3
ass0crcltnn t
HzC+CHz (18.61)
Continuation of the insertion-ligand-association sequence gives the polymer. It is believed

that titanium brings about this reaction because a dl metal cannot undergo B-elimination. (B-
Elimination requires some filled metal d orbitals for reasons that we haven't discussed.) The
tendency toward B-elimination of other metals would terminate the reaction.
Hydroformylation is another commercially important process that involves a transition-
metal catalyst, in this case a tetracarbonylhydridocobalt(I) catalyst. Propionaldehyde, for ex-
ample, is produced by the hydroformylation of ethylene. (This is sometimes called the oxo
process.)
o
tl
HzC-CH2+ H2 + t.() # cH3cH2CH ( 18.62)
ethylene propionaldehyde
This process involves, among other things, a I ,2-insertion reaction of ethylene and a 1,1 -inser-
tion reaction of carbon monoxide (Problem 18.29).
858 cHAprER 18 . THE cHEMrsrRy oF ARyL HALTDEs, vrNylrc HALTDEs, AND pHENoLs. TRANstloN-METAL cATALysts
Yet another important transition-metal-catalyzedreaction isthe homogeneous catalytichy-

drogenation of alkenes using a soluble rhodium(I) catalyst called the Wilkinson catalyst,
ClRh(PPh3)3. This reaction was explored in Problem 18.15 (p. 845).
And let's not forget catalytic hydrogenation (Secs.4.9A and 14.6A), an extremely impor-
[*rnm*hlrliinm*m*:""y.*
place on the Wilkinson catalyst.
l!
Many aspects of transition-metal chemistry are beyond the scope of an introduction. How
Itf #:,1#:tr+fiT#ril:lr:,T",,'"",rfi l:;t'*:h"**ff#*.::#

@l8.29Suggestamechanismfortheoxoreaction(Eq.l8.62)involvingintermediatesthatarecon-
sistent with the 16- and l8-electron rules.
18.7 AGIDITY OF PHENOLS

A. Resonance and Folar Effects on the Acidity of phenols
Phenols, like alcohols. can ionize.
..
+ H,Q <
.e
+ ,,,,R ... .o
+ u,o*
\_ro-rl \_fo;- ( 18.63)
phenol phenoxide ion

(phenolate ion)
The conjugate base of a phenol is named, using common nomenclaturc, as a phenoxide ion or,
using substitutive nomenclature, as a phenolate ion. Thus, the sodium salt of phenol is called
sodium phenoxide or sodium phenolate; the potassium salt ofp-chlorophenol is called potas-
sium p-chlorophenoxide or potassium 4-chlorophenolate.
Phenols are considerably more acidic than alcohols. For example, the pK" of phenol is 9.95,
but that of cyclohexanol is about 17. Thus, phenol is approximately 107 times more acidic than
an alcohol of similar size and shape.
PK.
cro'ryoH
= 10 =17
I
vn
II
Recall from Fig. 3 .2, p. 1 13, that the pK" of an acid is decreased by stabilizingits conjugate
Further Exploration 18.2
base. The enhanced acidity of phenol is due to stabilization of its conjugate-baie anion.
Resonance Effects What is the source of this enhanced stability? First, the phenolate anion is stabilized by
on Phenol Activity
resonance:
r
l.Ato:-
llll<+ e
lv resonance structures for the phenoxide anion
18.7 ACIDITY OF PHENOLS 859
Second, the polar effect ofthe benzene ring stabilizes the negative charge. Both resonance sta-
bilization and polar effects are the same effects that stabilize benzylic carbanions (Sec. 17.3).
Actually, a phenoxide anion is abenzylic anion in which the benzylic group is an oxygen in-
stead of a carbon!
Alkoxides are stabilized neither by resonance nor by the polar effect of benzene rings or
double bonds.
cyclohexanolate anion
""il;:'."f.Tl?'iililxTl"o,
Because phenoxide ions are stabilized by both resonance and polar effects, less energy is re-
quired to form phenoxides from phenols than is required to form alkoxides from alcohols. Be-
cause pKîs directly proportional to the standardfree energy of ionization (Eq. 3.38, p. 112),
phenols have lower pK" values, and are thus more acidic, than alcohols.
Substituent groups can also affect phenol acidity by both polar and resonance effects. For
example, the relative acidities of phenol, m-nitrophenol, and p-nitrophenol reflect the opera-
tion of both effects.
A
OH OH OH
A
I
(/
Noz
Y Noz
phenol rn-nitrophenol p-nitrophenol
PKt 9.9s 8.35 7 .2r
m-Nitrophenol is more acidic than phenol because the nitro group is very electronegative. The
polar effect ofthe nitro substituent stabilizes the conjugate-base anion for the same reason that
it would stabilize fhe conjugate base of an alcohol (Sec. 8.6B). Yet p-nitrophenol is more
acidic than n-nitrophenol by more than one pK" unit, even though the p-nitro group is farther
from the phenol oxygen. This cannot be entirely the result of a polar effect, for polar effects on
acidity decrease as the distance between the substituent and the acidic group increases. The
reason for the increased acidity ofp-nitrophenol is that thep-nitro group stabilizes the conju-
gate-base anion by resonance (red structure).
:O:i :o: :o: :o:

'l' lJll \{* C ,\lll++ tl tl
ltll li {*
-a
{-* t))
NT+
:OZ^'-tj,
I
:o
T'
zN\o, :
Y
grN\ rr
O: -
JL)-
-.'
lttl
\."
.\1+
lp
\
-O:
rr
-
chirrge is dekrcalizecl
ir-rto the nitro grollll ( 1 8.6s)
860 cHAprER 18 . THE cHEMrsrRy oF ARvL HALTDEs, vrNylrc HALTDES. AND pHENoLs. TRANSTToN-METAL cATALysts
Ihe structure shown in red is especially important because it places charge on the electroneg-
ative oxygen atom. In rz-nitrophenol, however, it is not possible to draw a resonance structure
that delocalizes the negative charge into the nitro group.
:o: :o:
A
.: O: :o:
\l
I\- ll .o,- <+cd. .Q:-$(ft,o,- ll\'t |
7\,
.o,-
ri
tl
b-rt'
\-/ ll ll tl
:o: :o: :o: :o:
fewer important structures than the para-isomer ( 18.66)
Because p-nitrophenoxide has more resonance structures, it is more stable relative to its cor-
responding phenol than is n-nitrophenoxide. Hence p-nitrophenol is the more acidic of the
two nitrophenols. The acid-strengthening resonance effect of ortho and para nitro groups is so
large that 2,4,6-tinitrophenol (picric acid) is actually a strong acid.
OH
ozN Noz
NOz
2,4,6-trinitrophenol
(Picric acid)
PKa = 0'96
Let's summarize the factors that govern acidity as we've seen them in operation so far:
7. Element effecfs.' Other things being equal, compounds are more acidic when the element
to which the acidic hydrogen is bound has a higher atomic number within either a row
or group of the periodic table.
a. The effect within a row (period) of the periodic table is dominated by relative elec-
tronegativities (or electron affinities). Thus, water is much more acidic than methane,
and phenol is much more acidic than toluene, because oxygen (higher atomic num-
ber) is more elecffonegative than carbon (lower atomic number).
b. The effect within a column of the periodic table is dominated by relative bond
energies. Thus, thiols are more acidic than alcohols because the S-H bond is weaker
than the O-H bond.
2. Charge effects: A positive charge on the atom to which the acidic proton is attached en-
hances acidity. For example, HrO+ is more acidic than HrO.
3. Resonance effects: Enhanced delocalization ofelectrons in the conjugate base enhances
acidity.
4. Polar effects: Stabilization ofcharge in the conjugate base enhances acidity.
@l8.30Whichofthe,twophsnolsineachsetismoreacidic?Explain.
(a) 2,5-dinitrophenol. or Z,4-dinitrophenol
(b) phenol or ru,chloiophenol
18.7 ACIDITY OF PHENOLS 861
OH
)-
(A CH:O
B' Formation and use of Phenoxides

Alcohols are not converted completely into alkoxides by aqueous NaOH solution because the
pK" values of water and alcohols are similar (Sec. 8.64,). In contrast, the equilibrium for the
reaction of phenol and NaOH lies almost completely to the right:
/,/...:_'\ .. ..
( ''
( 1 8.67)
\_7 \_/
-(" pK, - 15.7
phenol phenoxide
pK. - 9.95 1()n
Because the difference in pK" values of water and phenol is about 6, the equilibrium constant
for this reaction is about 106 1Sec. 3.4E). Thus, for all practical purposes, phenols are con-
verted completely into their conjugate-base anions by NaOH solution. Although the stronger
bases used to ionize alcohols (Sec. 8.64) can also be used for phenols, hydroxide ion or alkox-
ide bases such as ethoxide ion are often perfectly adequate for the purpose. Thus, when phe-
nol is treated with a solution containing one equivalent of NaOH or NaOCrHr, the phenol
O-H proton is titrated completely to give a solution of sodium phenoxide.
The acidities of phenols can sometimes be used to separate them from mixtures with other
organic compounds. For example, suppose that we wish to separate the water-insoluble phe-
nol, 4-chlorophenol, from the water-insoluble alcohol, 4-chlorocyclohexanol. Although the
phenol itself is water-insoluble, its sodium or potassium salt, like many other alkali metal
salts, has considerable solubility in water because it is an ionic compound. (Recall from Sec.
8.4B that water is one of the best solvents for ionic compounds.)
4-chlorophenol sodium 4-chlorophenolate 4-chlorocyclohexanol

soluble in ether insoluble in ether soluble in ether
insoluble in water soluble in water insoluble in water
(an ionic compound)
Thus, when a mixture of the phenol and the alcohol in ether solution is shaken with aqueous
NaOH, the phenol is selectively extracted into the aqueous solution as its sodium salt, sodium
4-chlorophenolate, while the alcohol, which is not significantly ionized by NaOH, remains in
the ether. (Although alcohols of low molecular mass are soluble in water, the chlorine and hy-
drocarbon parts of 4-chlorocyclohexanol dominate its solubility properties.) Acidification of
the aqueous solution gives the phenol, which separates from solution because, after acidifica-
tion, it is no longer ionized.
It is usually said that phenols are "soluble in sodium hydroxide solution." What is really
meant by this statement is that if sodium hydroxide solution is added to a phenol, the phenol
862 cHAprER 18 . THE cHEMtsrRy oF ARvL HALIDEs, vtNyLtc HALIDEs, AND pHENoLs. TRANSInoN-METAL cATALysrs
is converted into its conjugate-base phenoxide ion, which, because it is ionic, is the species
that actually dissolves in the aqueous solution. Solubility in 57o NaOH solution is a qualitative
test for phenols (and other compounds of equal or greater acidity).
Phenoxides, like alkoxides, can be used as nucleophiles. For example, aryl ethers can be
prepared by the reaction of a phenoxide anion and an alkyl halide.
..n t :B..r:- (rs.68)

\_lh9'--i[>cH2cH2cH3
l-bromopropane
\_1f9-cH2cH2cH3
phenoxide proporybenzene
ron (630/o yield)
This is another example of the Williamson ether synthesis (Sec. 11.1A). Note that the reaction
of sodium propoxide, the sodium salt of l-propanol, with bromobenzene, would notbe asat-
isfactory synthesis of this ether. (Why? See Sec. 18.1.)
@ I 8.3 I CIrrlino a prry*im of eeh of tu fo[ffi,ing compq,ods from dre irdicared sarting marc-
dcl ad'eyo{ihr ' .:'r r '
14lp4iqoqen$ $$ry@ot Oft@nosa.efrauot_{pom phenol

fE'32 Tbe fd@ingrso+ip4$d; Wlite most pbcnols, is sofuIe in neutral aqgeous solutio6 but
insalfilc in aqucous bosa Explain this unusual behavior.
+
N(CH3)3 Cl-
lt I
-1,
tg.g oxrDATroN oF PHENOTS TO QUTNONES :
Even though phenols do not have hydrogen at their a-carbon atoms, they do undergo oxida-
tion. The most common oxidation products of phenols are quinones.
OH
( 18.6e)
OH o
hydroquinone p-benzoquinone
(8G92o/o yield)
OH o
Hgc"A"cH, HrC CHr
J] )
NarCrrOz
18.70)
, L
(
HzSOa
HsC HzO H:C
2,3, 6 -trimethylph enol o
2, 3,5 - trimethyl - l, 4-benzoquinone
(50a/o yield)
18.8 OXIDAT|ON OF PHENOLS TO QUTNONES 863
OH
HrC oH o?_'*".
Agzu H.C
J
( 18.71)
4-methylcatechol 4-methyl- l, 2 -benzoquinone

(unstable red crystals)
(680lo yield)
As Eqs. 18.69-18.71 illustrate, p-hydroxyphenols (hydroquinones), o-hydroxyphenols (cate-

chols), and phenols with an unsubstituted position para to the hydroxy group are oxidized to
quinones. A quinone is any compound containing either of the following structural units.
o o
tl
./vo
tl
ilt
lltl v
tl
o an ortho-quinone
a para-quinone
If the quinone oxygens have a 1,4 (para) relationship, the quinone is called a para-quinone; if
the oxygens are in a 1,2 (ortho) arrangement, the quinone is called an ortho-quinone. The fol-
lowing compounds are typical quinones.
o
//vo
@
tl
.4,'r./\
ltl
\/
derived from
o-benzoquinone o naphthalene
( 1,2-benzoquinone)
p-benzoquinone 1,4-naphthoquinone
( I,4-benzoquinone)
derived from
l0
anthracene
9,10-anthraquinone
As illustrated by the preceding structures, the names of quinones are derived from the names
of the corresponding aromatic hydrocarbons: benzoquinone is derived from benzene, naph-
thoqainone from naphthalene, and so on.
Ortho-quinones, particularly ortho-benzoquinones, are typically considerably less stable
thmtheir para-quinone isomers. One reason for this difference is that in ortho-quinones, the
ends of the C:O bond dipoles with like charges are close together and therefore have a
854 CHAPTER '18 . THE CHEMISTRY OF ARYL HALIDES. VINYLIC HALIDES. AND PHENOLS. TRANSITION-METAL CATALYSIS
repulsive, destabilizing interaction. Inpara-qtinones these dipoles are pointed in opposite di-
rections and are farther apart.
e
o-benzoquinone
like charges in the bond dipoles
are close together
p-benzoquinone
bond dipoles have opposite directions
and are farther apart
A number of quinones occur in nature. Coenzyme Q, shown in the following structures in

its oxidized form ubiquinone, is an important factor in the respiratory chain localized in the
mitochondrion that converts oxygen ultimately into water and harnesses the energy thus re-
leased to synthesize adenosine triphosphate (ATP), an important "biochemical fuell' Doxoru-
bicin (adiamycin), isolated from a microorganism, is an important antitumor drug.
o
ooH \ CCH,OH
cH3o CH:
CH. 2\ ./\ ,/\ ,/\ 'rOH
cH3o cH2cH-c-cHz
I
\-. \-/
I
\t
I
\-./
o cH3o ooH O
-
sugar
coenzFme Q doxorubicin
(ubiquinone) (adriamycin)
The oxidation of phenols by air (Or) to colored, quinone-containing products is the reac-
tion responsible for the darkening that is observed when some phenols are stored for a long
time. The oxidation of hydroquinone and its derivatives to the corresponding p-benzoquinones
can also be carried out reversibly in an electrochemical cell. Oxidation potentials of a number
of phenols with respect to standard electrodes are well known.
1E.33 Postulate a structure for the compound formed when ubiquinone undergoes a two-elecEon
reduction.
Practical Applicatlons of Phenol Oxidatlon The oxidation of phenols has several im-
portant practical applications. For example, phenols are sometimes used to inhibit free-radical
reactions that result in the oxidation of other compounds (Sec. 5.6C). The basis of this effect
is that many free radicals (R' in Eq. 18.72a) abstract a hydrogen from hydroquinone to form a
very stable radical called a semiquinone.
.R
(t8.t2a)
a semlqurnone
18.8 OXIDATION OF PHENOLS TO QUINONES 865
(The semiquinone radical, like the benzyl radical (Eq. 17. 10, p.793), is resonance-stabilized, as
shown in Eq. 18.72b.) A second free radical can react with the semiquinone to complete its ox-
idation to quinone.
Alo' Ot
^d'
,ON;
ttJ
Icf G-'
.5
ll
. -y'
-* + R-H (18.72b)
H
K
H)
R.'
\
Hydroquinone thus terminates free-radical chain reactions by intercepting free-radical

intermediates R'and reducing them to RH.
The effectiveness of several widely used food preservatives is based on reactions such as
these. Examples of such preservatives are "butylated hydroxytoluene" (BHT) and "butylated
hydroxyanisole" (BHA).
OH OH OH
(cH3)3c c(cH3)3 c(cH3)3
c(cH3)3
CHr ocH3 ocH3
BHT BHA
Oxidation involving free-radical processes is one way that foods discolor and spoil. A preser-
vative such as BHT inhibits these processes by donating its OH hydrogen atom to free radicals
in the food (as in Bq. 18.72a). The BHT is thus transformed into a phenoxy radical, which is
too stable and unreactive to propagate radical chain reactions. Although the use of BHT and
BHA as food additives has generated some controversy because oftheir potential side effects,
without such additives foods could not be stored for any appreciable length of time or trans-
ported over long distances.
Vitamin E, a phenol, is the major compound in the blood responsible for preventing oxida-
tive damage by free radicals. Vitamin E acts by terminating radical chains in the manner
shown in E,q.I8.72a.
CHr
HO
CH:
H:C CH:
t\
Ii' CH: |.I CH: CH:

CH:
a-tocopherol
a major form of vitamin E
Poison lvy and ltchy Quinones

Over half of the people in the United States suffer from allergy to poison ivy, poison oa(and poison
sumac.The active principle in these plants is a family of catechol derivatives known collectively as
urushiol.
urushiol (one of several components)

(The various urushiol components differ in the number, positions, and possibly the stereochemisfiy
of the side-chain double bonds.) The allergic reaction is not caused by the catechol itselt but rather
by its oxidation product, an o-quinone:
OH o
ll
tol
enzyme /v,a
biological oxidation | | | 118.73)
\.4R
The long hydrocarbon side chain of urushiol probably imbeds itself into the lipid bilayer (Sec.8.5A)
of a skin-cell membrang thus immobilizing it near membrane-localized oxidizing enzymes. Ortho-
quinones are examples of a, punsaturated ketones, which are compounds in which a ketone car-
bonyl group (C:O) is conjugated with a carbon-carbon double bond. As we'll explore in Sec. 22.8,
these compounds undergo rapid conjugate addition with nucleophiles, including nucleophiles
available in the cell, such as the thiol and amino groups of proteins. Using the thiol group of a pro-
tein as an example, a typical addition reaction occurs as follows:
OH
?
/v,o /Y'o
I
H- J"
sH + !! ____>
F sA,z\n | | (18.74a)
protein \z\* ':y;,?,:':
H
A subsequent rapid reaction with Bronsted acids and bases forms a substituted catechol.
OH
ln OH
/*e'
.. +
-
Q:-H,
..v_> B
sA4a
r\ t
R
H -
Ar) OH
OH
+
R (18.74b)
modified protein
18.9 ELECTROPHILIC AROMATIC SUBSTITUTION REACTIONS OF PHENOLS 857
''l:1"':l''
i r"
Ortho-quinones are not aromitii but the catechol addition products are; the artlmatic stabilizationa
of the product makes the reaction irreversible.These reactions result in an irrerrersibly modified pro-
tein,which is now sensed as"foreign"bythe immune q/stem.The resulting bidogical response is the
all-toqfamiliar allergic reaction-the skin eruptions and the intense itch.
18.34 Given the structure of phenanthrene, draw sffuctures of

(a) 9,I0-phenanthraquinone (h) l,4-phenanthraquinone
phenanthrene
Indicate whether each is an o- or a p-quinone.

18.35 Complete the following reactions.
(a) oH (b)
/
Noz ',-./a-oH cr(vl).
..1!T). Ho-{
\_/ h\-^r
Hzso+
HzSO+
18.36 Drawtheimportantresonancestructuresoftheradioalgrfutmedwheneae!:ofthefollowing
reacts wittr R., a general free radieal. t :,,,,"'
(a) vitamin E O) BtfI
1E.37 (a) Give the structure of the @uct formed in the reaction of urushiol with K2CO, and a,
large excess of methyl iodide.
O) Would this compound be likely to provoke the .same allergrc skin response as urushiol?
ETECTROPHITIC AROMATIC SUBSTITUTION

18.9 REACTIONS OF PHENOTS
Phenols are aromatic compounds, and they undergo electrophilic aromatic substitution
reactions such as those described in Sec. 16.4. In some of these reactions, the group has
special effects that are not common to other substituent groups.
-OH
Because the group is a sffongly activating substituent, phenol can be halogenated
-OH
once under mild conditions that are totallv ineffective for benzene itself.
* Br2 ccr,"-- t.OoH * HBr (18.7s)

"+oH
phenol p-bromophenol
(82o/o yield)
Notice the mild conditions of this reaction. A Lewis acid such as FeBr, is not required. (A so-
lution of Br, in CCl. is the reagent usually used for adding bromine to alkenes.) But when phe-
868 cHAPTER 18 . THE cHEMrsrRy oF ARvL HALTDEs, vrNylrc HALTDEs, AND pHENoLs. TRANsIIoN-METAL cATALysts
nol reacts with Br, in HrO (bromine water), more extensive bromination occurs and2,4,6-ti-
bromophenol is obtained.
OH OH
),
[- |J+3P,12 -]rr.* + 3HBr (18.76)
\,/
phenol Br
21416-tnbromophenol
= 100o/o yield
(precipitates)
This more extensive bromination occurs for two reasons. First, bromine reacts with water to
give protonated hypobromous acid, a more potent elechophile than bromine itself.
+
Br2 * HrCi: + Br- + nr-OU, HBr + Sr-OFl (18.i7)
protonated -* hypobromous
hypobromous acid acid
Second, in aqueous solutions near neuffality, phenol partially ionizes to its conjugate-base
phenoxide anion. Although only a small amount of this anion is present, it is very reactive and
brominates instantly, thereby pulling the phenollhenolate equilibrium to the right.
OH o- o- OH
o + H3O+ Br Br
lu.,rt,o
| (t*o rlactions)
I
OH o-
Br- -( -Br
ff ( 1 8.78)
Br Br
(very insoluble;
precipitates)
Phenoxide ion is much more reactive than phenol because the reactive intermediate is not a
carbocation, but is instead a more stable neutral molecule (red structure).
:o:-
( 18.7e)
BrH BrH
+H2O
18.9 ELECTROPHILIC AROMATIC SUBSTITUTION REACTIONS OF PHENOLS 869
p-Bromophenol is also in equilibrium with its conjugate basep-bromophenoxide anion, which

brominates again until all ortho and para positions have been substituted. Notice in Eq. 18.78
that in the second and third substitutions the powerful ortho, para-directing and activating ef-
fects of the group override the weaker deactivating and directing effects of the bromine
-O:-
substituents. In strongly acidic solution, in which formation of the phenolate anion is sup-
pressed, bromination can be stopped at the 2,4-dibromophenol stage.
Br
+ 2Br2 FIB'+
CV'H
\-/ ' Hzo ,rdoH
\J
+ 2HBr ( 1 8.80)
phenol 2,4-dibromophenol
(87o/o yield)
Phenol is also very reactive in other electrophilic substitution reactions, such as nitration.
Phenol can be nitrated once under mild conditions. (Notice that HrSOo is not present as it is in
the nitration of benzene; Eq. 16.10, p.754.)
phenol o-nitrophenol p-nitrophenol

(260/o yield) (61,a/o yield)
Because phenol is activated towarci electrophilic substitution, it is also possible to nitrate phe-
nol two and three times. However, direct nitration is not the preferred method for synthesis of
di- and trinitrophenol, because the concentrated HNO, required for multiple nitrations is also
an oxidizing agent, and phenols are easily oxidized (Sec. 18.8). Instead, 2,4-dinitrophenol is
synthesized by the nucleophilic aromatic substitution reaction of l-chloro-2,4-dinitrobenzene
with -OH (Sec. 18.4A).
HNor r) -oH J*o'

( V.r zjuro*
' o,N-{ ' orN-(
H'so'
\J \-/V.t \J\-o*r (18.82)
chlorobenzene I - chlor o -2,4- dinitrobenzene 2,4-dinitrophenol
The basic conditions of this reaction result in formation of the conjugate-base anion of the
product; the H,O+ is added following the reaction to give the neutral phenol.
The great reactivity of phenol in electrophilic aromatic substitution does not extend to the
Friedel-Crafts acylation reaction, because phenol reacts rapidly with the AlCl, catalyst.
2,,-,.Q,
+Arcr3 ----+
| **^rr,
{-----}
z-ra.t.:,ucr,l + Hcr (1883)
U LU U I
The adduct of phenol and AlCl, is much less reactive than phenol itself in electrophilic aro-
matic substitution reactions because, as shown in Eq. 18.83, the oxygen electrons are delocal-
ized onto the elecffon-deficient aluminum. Because of their delocalization away from the ben-
zene ring, these electrons are less available for resonance stabilization of the carbocation
intermediate formed within the ring during Friedel-Crafts acylation (Eq. 16.24, p. 760).
Thus, Friedel-Crafts acylation ofphenol occurs slowly, but can be carried out successfully at
elevated temperatures. Because it is not highly activated, the ring is acylated only once.
</ \FoH + Alcl3 + Hzot

il
cH:(cHz)s-C-ct
\_/ #
(as a complex) o
\c-(cHz)scH:
o
+ cH:(cHz)s-A+oH (1884)
Further Exploratlon 1 8.3
Fries Rearrangement (34alo yield) (47o/o yield)
Friedel-Crafts alkylation of phenol is also possible.
CH.
HrC-C-OH 70olo HzSO+

H:C-f
I
GoH+ I
CH:
g0 "c -
CHi
oH + HzO (18.8s)
p-tert-butylphenol
(80% yield)
trE@ 18.38 Give the principal organic product(s) formed in each of the following reacrions.
(a) o-cresol * Br2 in CCla ------>
(b) n-chlorophenol + HNO3, lowtemperature ------>
(c) O
p"bromophenol + H3c-8-cl
tl
dcl't H:o+
t
18.39 Give a curved-arrow mechanism for the reaction in Eq. 18.85. Be sure to identify the elec-
tophilic species in the reaction and to show how it is formed.
18.10 REACTIVITY OF THE ARYL-OXYGEN BO D
R. tack of Reactivity of the Aryl-oxygen gond in s"1 and sN2 Reactions

Just as the reactions of alcohols that break the carbon-oxygen bond have close analogy to the
reactions of alkyl halides that break the carbon-halogen bond, the carbon-oxygen reactivity
of phenols follows the poor carbon-halogen reactivity of aryl halides. (That is, we can think
of phenols as o'aryl alcohols.") Recall that aryl halides do not undergo S*1 or El reactions
(Sec. I 8.3); for the same reasons, phenols also do not react under conditions used for the S* I
or El reactions of alcohols. Thus, phenols do not form aryl bromides with concentrated HBr;
they do not dehydrate with concentrated HrSOo. flnstead, they undergo sulfonation; see Sec.
18.10 REACTIVITY OF THE ARYL-OXYGEN BOND 871
I6.4D.) The reasons for these observations are exactly the same as those that explain the lack
ofreactivity ofaryl halides (see Secs. 18.1 and 18.3).
More generally, any derivative of the form
A-*
\_/
in which X is a good leaving group, such as tosylate, mesylate, o. has the same
lack of reactivity toward S*1 and S*2 conditions as aryl halides-and
-6H2,
"u"o for the same reasons.
The lack of reactivity of the aryl-oxygen bond can be put to good use in the cleavage of
aryl ethers. Recall that when ethers cleave--depending on the particular ether and the mecha-
nism-products resulting from cleavage at either of the carbon-oxygen bonds are possible
(Sec. 1 1.3). In the case of aryl ethers, cleavage occurs only at the alkyl-oxygen bond; conse-
quently, only one set ofproducts is formed:
here]
@e occurs
,-', lF
vcHr + HBr heat' + cH3Br ( 18.86)
[}o GoH
observed products
Br + CH3OH
(not observed)
In this example, ether cleavage gives phenol and methyl bromide rather than bromobenzene
and methanol because the S*2 reaction of the bromide-ion nucleophile can oriy ocur at the
methyl group of the protonated ether:
( 1 8.87)
@.,,il*.,**eachset,,&"0f,;;tbatwouldrorreadilycloavewithcomemaredin,i*a
heat, and explain. Then give the prcducB of ctrr ctreavago and ttre mochanisms of tbeir for-
mfltiffi for the other ether(s) in the,'set.
(n) CHr
,R, i ,'l
O-CHzGCHT
H3C -l
UfcHzTg-cH, CHg
benz$ me.thyl ether
( 2,2-dimethylpropo:ry) benrrlne
( nmpentyl phenyl ether)
872 cHAprER 18 r THE cHEMrsrRy oF ARyL HALTDES, vrNylrc HALTDEs, AND pHENoLs. TRANSInoN-METAL cATALysts
(b)
,n' i
QHs
,n'
\/iFo_T_cHs \_/h*o
CHs
ferf-butylphend ether
(te*-butoqfuenzene)
B. substltutlon at the Aryl{rrygen eonOjThe stiile Reaction

We learned in Secs. 18.5 and 18.6 that certain transition-metal catalysts, particularly Pd(0),
can catalyze the substitution of aryl halides at aryl carbons. Pd(0) catalysts can also catalyze
substitution at the aryl--oxygen bond. The first requirement for this to occur is conversion of
the phenolic group into a triflate, a very reactive leaving group. (Triflates were intro-
-OH
ducted in Sec. 10.3A, p.M5.)
o o
'
tl
+ F:C-S-O-S-CFr
tl
+ I',4\,ll
\*
o"c-
cH3o ll il
t\t'/
o o
trifl uoromethanesulfonic pyridine
(solvent and base)
anhydride
(triflic anhydride)
o
tl
O-S-CF: o
,4\,
a"rog
tl
o ttl
\fir/
il
-OSCF.
tl
H o
4-metho{ryhenyl trifluoromethanesulfonate
(p-metho4ryhenyl trifl ate )
(93o/o yield) ( 18.88)
Aryl triflates react readily with organotin derivatives in the presence of Pd(0) catalysts to
give coupling products.
triflate
group
Pd(PPh3)4
o
ll /^/\
,F,vn,';il:a"
H:C _C,V\-'rr \-oTi r+ (r />Sn(cHr)s
)rr\u'n3/3 + LiCl ffi
(catalyst)
\-/ /evcecc\
(excess)
trimethylph enyls tan nane
o
ll
H'gc-cVL/ + (cH:)rsncl + Liorf (18.8e)
(8s% yield)
This reaction is called the Stille reaction, after John K. Stille (1930-1989), who was a profes-
sor of chemistry at Colorado State Universify. Stille and his students developed this reaction
18.10 REACTIVITY OF THE ARYL-OXYGEN BOND 873
in the early 1980s. The Stille reaction is another important application of transition-metal
catalysis for the formation of carbon--carbon bonds.
A number of metals can be used to bring about similar transformations, but tin was chosen
because the organotin compounds used in the Stille reaction are relatively insensitive to mois-
ture, tolerant of other functional groups, and very easy to handle. (Some can be distilled or
crystallized.) Many of them are either commercially available, or they are readily prepared
from Grignard reagents and commercially available trialkyltin chlorides. The very basic "car-
banion" of the Grignard reagent displaces chloride, a weak base, from the tin:
Ms,ether, cr-Sn(cH:):, + clMsBr (18.e0)

Gu, Grru, G*(cHr):
In Eq. 18.89, notice that the phenyl group is transferred in preference to the methyl groups
in the Stille reaction. In general, vinylic groups, aryl groups, and other unsaturated groups are
transferred preferentially. However, if a tetraalkylstannane is used, alkyl groups can also be
transferred. This provides an excellent way to prepare alkylbenzenes. In conffast to the
Friedel-Crafts alkylation reaction (Sec. 16.4E), the Stille reaction is nor plagued by rearrange-
ments.
o Pd(PPh3)4
H:C-C{r
ll,n /> OTf + (CH3CH2CH2CH z)ESn + Licl
(catalyst)
t
\__/ (excess)
=?L=!
oloxalle
tetrabutylstannane
o
il
/:\ /FCH2CH2CH2CH3 + (CH3CH2CH2CH2)3SnCI + LiOTf
H3C-C-<r
" \__/
(18.91)
p-butylacetophenone
(82oh yteld)
The mechanism of the Stille reaction (Eq. 18.92) begins with oxidative addition of the aryl
triflate to the 14-electron Pd(PPhr), (the same catalytic species as in the Heck and Suzuki reac-
tions). The resulting complex (1,) is very unstable, and the excess chloride ion (as LiCl) rescues
the complex from decomposition by ligand substitution to form (2).The aryl or alkyl R-groups
on the organotin compounds have carbanion character, and they are nucleophilic enough to
substitute for the chloride on the Pd. A reductive elimination comDletes the mechanism.
(1) (2)
L L OTf L. ,Cl R- sL
\ / \/\
Pd
Ar
-
ofldatlve
OTf
Pd
,/ \
Licr
Iigand
Pd + Iigand
,/ \
{ addition ( Xr substitution ( Xr substitution
(unstable)
+ LioTf
- - ta. L
/ + ./R \
Cl-Sn- Pd
fedVctUe ,/
Pd + Ar-R (18.e2)
\ / \, elimination (
(catalyst
regenerated)
-
87 4 cHAprER 18 . THE cHEMrsrRy oF ARyL HALTDES, vtNylrc HALTDES, AND pHENoLs. TRANsIIoN-METAL cATALysts
Complex (2) inBq. 18.92 is the same complex that would be formed from oxidative addition
of an aryl halide to PdLr. (Compare with the product of Step ( 1) in the Heck mechanism, Eq.
18.42b, p. 846.) Hence, the Stille reaction can be canied out with aryl halides instead of aryl
triflates; and the Heck reaction can be carried out with aryl triflates instead of aryl halides.
The Stille reaction adds another method to our arsenal ofreactions that can be used to form
carbon-carbon bonds:
1. the addition ofcarbenes and carbenoids to alkenes (Sec. 9.8)
2. the reaction of Grignard reagents with ethylene oxide and lithium organocuprate reagents
with epoxides (Sec. 11.4C)
3. the reaction of acetylenic anions with alkyl halides or sulfonates (Sec. 14.78)
4. the Diels-Alder reaction (Sec. 15.3)
5. Friedel-Crafts reactions (Secs. 16.48-F)
6. the Heck and Suzuki coupling reactions (Secs. 18.6,{-8)
7. alkene metathesis (Sec. 18.6C)
8. the Stille reaction (this section)
EE@@ 18.41 predict the product of the stille reaction between ethylnyltrimethylstannane,
HC-C-Sn(CHr)., and phenyl triflate, PhOTf, in the presence of Pd(PPhr)o and excess
Licl.
18.42 What reactants would be required to form the following compound by the Stille reaction?
H
toa 'tH
I
oo'-ocHzcHr
18;11 INDUSTRIAT PREPARATION AND USE OF PHENOL

Historically, phenol has been made in a variety of ways, but the principal method used today
is an elegant example of'a process that gives two industrially important compounds, phenol
and acetone, (CH3)2C:O, from a single starting material. The starting material for the man-
ufacture of phenol is cumene (isopropylbenzene), which comes from benzene and propene,
two compounds obtained from petroleum (Sec. 16.7). The production of phenol and acetone
is a two-stage process. In the first stage, cumene undergoes an autoxidation to form cumene
hydroperoxide. (An autoxidation is an oxidation reaction involving molecular oxygen as the
oxidizing agent).
Autoxidation:
cH. cH.
ll
Ph-C-CH:+02 + P6-C-CH:
ll 8.93a)
(I
o-o-H
.:.". cumene hydroperoxide
In the second stage, cumene hydroperoxide is subjected to an acid-catalyzed rearrangement

that yields both acetone and phenol.
KEY IDEAS IN CHAPTER 1B 87 5
Rearrangement:
CH. ,J
s-2s%
- ph-()H + H:C-C-CH:
STUDY GUIDE LINK 18.2 ll
Ph-C-CH:
I
The cumene 11t.,ln ( 18.93b)

H:r"
Hydroperoxide
Rearrangement o-o-H
I
phenol acetone
Phenol is a very important commercial chemical. It is a starting material for the production
of phenol-formaldehyde resins (Sec. 1 9. l5), which are polymers that have a variety of uses,
including plywood adhesives, glass fiber (Fiberglass) insulation, molded phenolic plastics
used in automobiles and appliances, and many others. Fig. 5.4 (p. 218) shows how the manu-
facture ofphenol and acetone fits into the overall chemical economy.
18.4-t Compound A is a by-product of the autoxidation of cumene, and compound I is a by-prod-

uct of the acid-catalyzed conversion of cumene hydroperoxide to phenol and acetone.
CH, CH:
Ph-c-oH ,n-J-(:)-o"
| | \-_-/
CHI CH:
Give a curved-arrow mechanism that shows how compound A can react with phenol under
the conditions of Eq. 18.93b to give compound B.
I Neither aryl halides, vinylic halides, nor phenols un- t Aryl halides substituted with ortho or para electron-
dergo S*2 reactions because the sp hybridization of attracting groups, particularly nitro groups, undergo
the 5*2 transition state has relatively high energy and nucleophilic aromatic substitution. In this type of re-
because the backside substitution reaction with nu- action, the nucleophile reacts at the ring carbon to
cleophiles is sterically blocked. form a resonance-stabilized anion (Meisenheimer
complex),from which the halide leaving group is then
I Neither aryl halides, vinylic halides, nor phenols un-
expelled.
dergo Sr1 reactions because of the instability of the
carbocation intermediates that would be involved in t The important concepts for electron counting in tran-
such reactions. sition-metal complexes are
r The aryl-oxygen bond is unreactive in both S*1 and 1 . Oxidation state: The number of X-type ligands plus
Sr2 reactions. the charge.
2. The dn configuration;The number of unshared
t Vinylic halides undergo F-elimination reactions in
electrons on a metal within a complex, equal to
base under vigorous conditions to give alkynes.
the electron count of the neutral atom minus the
Strong bases can also promote P-elimination in aryl
oxidation state.
halides to give benzyne intermediates, which are
rapidly consumed by addition reactions with the 3. The electron count:The electron count of the neu-
tral atom plus the number of X-type ligands plus
bases.
twice the number of L-type ligands minus the
cha rge.
876 cHAprER 18 . THE cHEMrsrRy oF ARvL HALTDEs, vrNyllc HALTDEs. AND pHENoLs. TRANsrroN-METAL cATALysrs
I Some fundamental processes in transition-metal group.The Stille reaction can be used to form
catalysis are both alkyl- and aryl-substituted benzenes.
1 . Ligand association and dissociation. A succession The key mechanistic steps in all of these reactions are
of dissociation-association steps gives ligand an oxidative addition of the aryl halide or triflate to
su bstitution. the metal and a reductive elimination of the cou-
2. Oxidative addition. pling product.
3. Reductive elimination (Oxidative addition and re- I In alkene metathesis, two alkenes can be transformed
ductive elimination are conceptually the reverse into other alkenes by breaking the carbon-carbon
of each other.) double bond and scrambling the resulting fragments.
4. Ligand insertion. The ruthenium-based Grubbs catalysts G1 and G2 can
5. p-Elimination. (1,2-Ligand insertion and F-elimina- be used to bring about this transformation. A series of
tion are conceptually the reverse of each other.) ruthenium metallacycles are key intermediates in
alkene metathesis. Formation of cyclic alkenes is one
t Several transition-metal-catalyzed reactions can ef-
of the most important applications of this reaction.
fect the coupling of vinylic and aryl groups.These are
catalyzed by Pd(0), which is typically present as I Phenols are considerably more acidic than alcohols
Pd(PPh3)4 or a related derivative. Pd(OAc), can also be because phenoxide ions, the conjugate bases of phe-
used; it is reduced in the reaction mixture to form nols, are stabilized both by resonance and by the elec-
Pd(0). tron-attracting polar effect of the aromatic ring. Phe-
nols containing substituent groups that stabilize
1 . The Heck reaction brings about the coupling of an
negative charge by resonance or polar effects (or
alkene with an aryl bromide or iodide.The reac-
both) are even more acidic.
tion is typically used to form aryl-substituted
a lkenes. r Phenols can be oxidized to quinones. Two classes of
2. The Suzuki reaction brings about the coupling of quinones are ortho-quinones and para-quinones.
a vinylic or aryl bromide or iodide with an aryl or
Para-quinones are typically more stable.
vinylic boronic acid or borane.The reaction is used I Some electrophilic aromatic substitution reactions of
to form bia ryls, a ryl-su bstituted a lkenes, a nd con- phenols show unusual effects attributable to the
jugated a lkenes. group.Thus, phenol brominates three times in
-OH
bromine water because the group can ionize;
3. The Stille reaction is the coupling of an organic
group derived from an organostannane reagent
-OH
and phenol is rather unreactive in Friedel-Crafts acy-
with the aryl group of a phenol in which the phe- lation reactions because the group reacts with
the AlCl, catalyst.
-OH
nol group has been converted into a triflate
For a summary of reactions discussed in this chapte4 see Section R, Chapter 18, in the Stldy
I
REACTION it r REUIEW
'
trd
Guide and Solutions Manual.
lft."l,l Give the product(s) (if any) expected w'hen (d) Mg in THF
;r-iodotclluene or other cclrnpollnd indicated is sub- (e) product of part (d) + ClSn(CH3)r
jected to each of the following conditic-rns. (f ) Li in hexane
(a) CH.,OH. 25 'C (g) H.C:CH:,, Pcl(PPhr)a catalyst. and (CH.CH.),N
(b) CH.O- in CHTOH. 25 "C in CH.CN
(c) CH,O*. pressllre, heat (h) product of part (e) with phenyl triflate, excess LiCl.
and Pd(PPhr)4 catalyst in dioxane
ADDITIONAL PROBLEMS 877
(i) PhB(OH)2, aqueous NarCO3, itrd Pd(PPhr)a catalyst 18.48 Although enols are unstable compounds (Sec. 14.5A),
fi) product of (d) + B(OCH:):, then H3O+/H'O suppose that the acidity of an enol could be measured.
(k) product of (l) + @)-1-bromopropene, aqueous Which would be more acidic: enol A or alcohol B? i
NarCO,, and Pd(PPh:)+ catalyst whv?

OH OH
18.45 Give the product(s) expected (if any) when ru-cresol or I
H:C-C:CHz
I
other compound indicated is subjected to each of the H:C-CH-CHE

following conditions. A B
(a) concentrated H2SO4
(b) Br, in CCI* (dark)
18.49 Identify compounds A, B, and C from the following in-
(c) Br, (excess) in CCI*, light
formation.
(d) dilute HCI
(a) Compound A, C8H,oO, is insoluble in water but
(e) 0.1 M NaOH solution
soluble in aqueous NaOH solution, and yields 3,5-
(f) HNO., cold
dimethylcyclohexanol when hydrogenated over a
(e) o nickel catalyst at high pressure.
tl
CzHs-C-Cl, AlCl3, heat; then HzO (b) Aromatic compound B, C8Hr.O, is insoluble in
(h) NarCrrO, in HrSOo both water and aqueous NaOH solution. When
(i) triflic anhydride in pyridine, 0 "C treated successively with concentrated HBr, then
Mg in THR then water, it gives p-xylene.
fi) product of part (i) + (CH3)4Sn, excess LiCl, and
(c) Compound C, CeHrrO, is insoluble in water and
Pd(PPh:)q catalyst in dioxane
(k) product of (i) + (tr)-CH3CH-CH-B(OH)2,, in NaOH solution, but reacts with concentrated
HBr and heat to give m-cresol and a volatile alkyl
aqueous NaOH, and Pd(PPh:)q catalyst
bromide.
18.46 Give the products formed in the reaction of

l-hexene with each of the following compounds in the 18.50 Contrast the reactivities of cyclohexanol and phenol
presence of the Grubbs G2 catalyst.
with each of the following reagents, and explain.
(a) aqueous NaOH solution
(a) an excess of allyl alcohol (2-propen- 1-ol)
(b) NaH in THF
(b) an excess of 2-methylpropene (isobutylene)
(c) triflic anhydride in pyridine, 0 "C
(d) concentrated aqueous HBr, H2SO4 catalyst
18.47 Arrange the compounds within each set in order of in-
(e) Br, in CCI*, dark
creasing acidity, and explain your reasoning.
(f ) NarCrzOt in H'SO*
(a) cyclohexyl mercaptan, cyclohexanol, benzenethiol
(g) HrSOu, heat
(b) cyclohexanol, phenol, benzyl alcohol
(c) p -nitrophenol, p-chlorophenol,
lS.sL Choose the one compound within each set (see Fig.
o:
"*/
H_9_*\..
PI8.51 on p. 878) that meets the indicated criterion,
and explain your choice.
O:- (a) The compound that reacts with alcoholic KOH to
liberate fluoride ion.
(d) 4-nitrobenzenethiol, 4-nitrophenol, phenol
(b) The compound that cannot be prepared by a
(e) OH OH OH
d+
OH
Williamson ether synthesis.
-,\ a\ (c) The compound that gives an acidic solution when
V V
allowed to stand in aqueous ethanol.
(d) The ether that cleaves more rapidly in HI.
C
O Q ANO:
A Noz D
B
878 cHAprER 18 . THE cHEMrsrRy oF ARvL HALTDEs, vrNylrc HALTDES. AND pHENoLs. TRANSTToN-METAL cATALysts
18.52 Give the products (if any) when each of the following drops of concentrated NaOH are added, the solution
isomers reacts with HBr and heat. turns yellow and the spectrum changes (spectrum B).
OH
(a OH On addition of a few drops of concentrated acid, the
color disappears and spectrum A is restored. Explain
Y cH2oH
Y ocH3
these observations.
18.57 Vanillin is the active component of natural vanilla

3- ( hydrorrymethyl ) phenol 3-methoxnrhenol flavoring.
18.53 Explain the following observations, which were o

recorded in the chemical literature, concerning the re-
action between tert-butyl bromide and potassium ben-
li ,<
HC</ \FOH
/ocH3
zenethiolate (the potassium salt of benzenethiol): "The

\_/
attempts to prepare phenyl tert-butyl sulfide by this vanillin
route failed. If the reactants were kept at room temper-
ature KBr was formed, but the benzenethiol was re- When a few drops of vanilla extract (an ethanol solu-
covered unchanged." tion of vanillin) are added to an aqueous NaOH solu-
tion, the characteristic vanilla odor is not present.
18.54 What products (if any) are formed when Upon acidification of the solution, a strong vanilla
3,5-dimethylbenzenethiol is treated first with one odor develops. Explain.
equivalent of Na+ C2H5O- in ethanol, and then with
each of the following? 18.58 A mixture of p-cresol (4-methylphenol), pK" - 10.2,
(a) allyl bromide (b) bromobenzene and2,4-dinitrophenol, pK" - 4.1 1, is dissolved in
ether. The ether solution is then vigorously shaken
18.55 Phenols, like alcohols, are Bronsted bases. with one of the following aqueous solutions. Which
(a) Write the reaction in which the oxygen of phenol solution effects the best separation of the two phenols
reacts as a base with the acid H2SO4. by dissolving one in the water layer and leaving
(b) On the basis of resonance and polar effects, decide the other in the ether solution? Explain. (Hinr: Apply
whether phenol or cyclohexanol should be the Eq. 3.21 on p. 101.)
stronger base. (1) a 0.I M aqueous HCI solution
(2) a solution that contains a large excess of pH - 4
18.56 The UV spectrum of p-nitrophenol in aqueous solution buffer
is shown in Fig.Pl8.56 (spectrumA).When a few
ozN
cHz-NOz CH:
0)n
\)
(c)
o
or
Br
Goc2Hs G"C
c-cH.
I
or
I
CH: H:C
(d) phenyl cycloheryl ether or diphenyl ether
Figure P18.51
ADDITIONAL PROBLEMS 87 9
(3) a solution that contains a large excess of pH : 7 cobalt (Co). Characterrze this compound in the follow-
buffer ing ways:
(4) 0.1 M NaOH solution (a) the oxidation state of the cobalt
(b) the dn count (that is, the value of n)
18.59 l-Haloalkynes are known compounds. (c) the total electron count around the metal
(a) Would 1 -bromo-2-phenylacetylene (Br-C:CPh)
be likely to undergo an S*2 reaction? Explain. 18.62 When a suspension of 2,4,6-tribromophenol is treated
(b) Would the same compound be likely to undergo an with an excess of bromine water, the white precipitate
S*l reaction? Explain. of 2,4,6-tribromophenol disappears and is replaced by
a precipitate of a yellow compound that has the fol-
18.60 Ferulic acid is a potent antioxidant found in tomatoes lowing structure. Give a curved-arrow mechanism for
and other vegetables that protects against oxidative the formation of this compound.
stress in neuronal cells, and is thus of some interest in o
research on Alzheimer's disease. (See the sidebar on
Br Br
pp. 519-520.)
HO H
I Br Br
.C. OH
cH3o cr' c/
HO
ttl 18.63 It has been suggested that the solvolysis of 2-(bro-
momethyl)-5-nitrophenol at alkaline pH values in-
4-hydrory- 3 -methorycinnamic acid volves the intermediate shown in brackets (see Fig.
(ferulic acid)
Pl8.63, p. 881). Give a curved-arrow mechanism for
the formation of this intermediate and for its
(a) Show how a free radical R. would react with ferulic
reaction with aqueous hydroxide ion to give the final
acid, and include resonance structures of the prod-
product.
uct radical.
(b) Would the isomer of ferulic acid, 3-hydroxy-4-
18.64 Outline a synthesis for each of the following com-
methoxycinnamic acid, be equally effective as a
pounds from the indicated starting material and any
free-radical inhibitor? Explain.
other reagents.
(a) 1 -chloro -2,,4-dinitrobenzene from benzene
18.6I The structure of cyanocobalamin, one of the forms of
(b) 1 -chloro- 3, 5 -dinitroben zene from benzene
vitamin B,r, is given in Fig. Pl8.61, p. 881. Notice that
cyanocobalamin is a complex of the transition metal ( Problem continues . . . )
0.8
0.7
0.6
q.)
H(g
0.s
bU)
0.4
0.3
0.2
0.1
200 280 360 440 520 600

wavelength (,\), nm
Figure P18.56 UV spectra for Problem 18.56. Spectrum A was taken in the presence of acid; spectrum B was
taken in the presence of NaOH.
880 CHAP TER 18 . THE CHEMISTRY OF ARYL HALIDES, VINYLIC HALIDES, AND PHENOLS. TRANSITION.METAL CATALYSIS
(c) PhH (n) H ocH2cH3

\/C:C
Ph-Q-C-Ph from
/\
I
HPh cH3cH2cH2cHi-\c
I
H ocH2cH3
from l-hexvne and resorcinol
(o)
Ph,',.'{ ) from iodoben zene
(e) 2-chloro-4,6-dinitrophenol from chlorobenzene \/
(f) "butylated hydroxytoluene" (BHT; p. 865) from p- \7
o
cres$l (4-methylphenol)
(e) o
(racemate)
,-(
18.65 Complete each reaction given in Fig. Pl8.65, pp.
(CH3)3C 4 !o from catechol
\J (benzene-1,2-diol) 882-883, by giving the major organic product(s), and
explain your reasoning. "No reaction" may be an ap-
(h) PhqH2CHzOH from bromobenzene propriate response.
(i)
ozN ocHzcr'C) r 8.66 One use of alkene metathesis is to form polymers from
cyclic alkenes ("ROMP," for "ring-opening metathesis
from the product of part (h) and fluorobenzene polymerization"). Give the structure of the polymer
formed when each of the following alkenes is poly-
(j)
merized with an appropriate metathesis catalyst.
,4\, H
f' rl
\-\lrr,y\(Noz
l-
frombenzeneand
(a)
| | ll ethylene as the only

\-/
(k)ln
H ,r.., of carbon cyclooctene
(b) N
to?
-\2 /r /
4/
--/\-
W t! norbornene
18.67 (a) 1,3-Cyclopentadiene undergoes a Diels-Alder re-

action with itself to give a diene known commonly
as endo-dicyclopentadiene. Give the structure of
(l) ozN\z^ f this diene.
llll (b) When endo-dicyclopentadiene is subjected to
\,\ cr'ctcH,oH ROMP (see Problem 18.66), a polymer is formed
that is so strong that a I inch-thick block will stop
,! a 9 mm bullet. Give a structure for this polymer
from bromob enzene, ethylene, and suggest one reason why it is so strong.
and any other reagents
18.68 Explain why, in the reactions given in Fig. Pl8.68,
c-.+ocH3
(m)
p. 883, different stereoisomers of the starting material
give different products.
from PhC-CH and 4-methoxyphenol. (Hint: See

Eqs. 14.23,p.664, and 18.90, p. 873.)
18.69 The reaction given in Fig. P18.69 on p. 884 occurs (IH,t, J : I Hz); 6 8.7 (2H, d, J : lHz). Suggest a
readily at 95 "C (X - halogen). The relative rates of stnicture for this compound.
the reaction for the various halogens are 290 (X : F),
1.4 (X - Cl), and 1.0 (X - Br).When a nitro group is 18.71 Suggest structures for X and Y tn the reaction sequence
in the para position of each benzene ring, the reaction given in Fig. P18.71 (p. 884), including their stereo-
is substantially accelerated. Give a detailed mechanism chemistry. Suggest a mechanism for the formation of
for this reaction, and explain how it is consistent with ). Notice that aluminum (Al) is just below boron (B)
the experimental facts. in the periodic table; to predictX, imagine that the Al
is a B and ask how that compound would react with an
18.70 When 1,3,5-trinitrobenzene [NMR: 6 9.1(s)] is rreared alkene. CrH, r : pertyl and CoHu : butyl . (Hint: See
with Na+ CH3O-, an ionic compound is formed that Secs. 5.48 and 14.58.)
has the following NMR spectrum: 6 3.3 (3H, s); 6 6.3 (Problem texts continue on p. 884) ,
o
il
HzN\6_g
HzN-t-q",
o I CH. I
tl
C-Ht l"HzQ
H2NCCH:- / o
H:C
HsC
.\Jy.-\ "'cH2cHrlNn,
o
N
,/ $r
ll
H2NCCH2 \\ \-N=
\l CHr
CHr
CH:
\ E",.",.n", L
o=a
'tcHt \""A
I
\
NH CN
cHz
I
o-
I
Jo. .]to
N f
''''J'-"?'-? I
N
\)-<>acH:
|
Nr'\,,
ll
CHr
(a) HOCH2 (b) |
FigurePl8.61 Thestructureofcyanocobalamin,thefirstisolatedformofVitaminB,r.(a)ALewisstructure.(b)
A perspective drawing that shows the position of the two ligands that are above and below the plane defined by
the four ring nitrogens.
CH2Br CH,OH
ozN OH
Figure P18.63
i:r;rl.
rlJ
.!r
882 CH PTER 18 . THE CHEMISTRY OF ARYL HALIDES, VINYLIC HALIDES, AND PHENOLS. TRANSITION-METAL CATALYSIS
(a)
orN{r />F + C2H5S- +
\__-7
(b) cl
ozN NOz
I ll +-oH
Y Noz
(c) H2' catalyst
,,R, sorurion
NaoH solution sulfate
dimethvl sulfate
dimethyl high Pressure
CH3CHrful OH , , ,
(d),F, 25
+ cH3cH zcHz-NHz + "C
\__/-.t
(e)AyB(oH)2
4\ ll
+L-
Pd(PPh3)4 catalyst
[-
\N/ U \NAc? -.o
I
CHr
(f) NOr
lll
orf
* (Ho)2BaJ H, Pd(PPh3)4 catalyst
aoueous Na"CO.
\,/
(g) OH
..-/\/oH
I
Ho.
I ll +nr, -+CCI+ (C6HsOrBr)
\-/
pyrogallol
(h) OH triflic Pd(PPh3)4 catalyst

anhydride, (C+Hg):SrrMOH
pyridine,
00c excess LiCl
dioxane
",,.',-
HrC.
"\ /
Br '1O) (excess)
Pd(OAc)2 catalyst, (CH:CHz):N

C:C
O+ -ll
CH3O-C
/\
H
+ K2Cr2O? g
(k)
*-rhlorophenol + Na2Cr2o, -Jz%
Figure P18.65 (continues)
(l)r,n-dinitrophenol
# #'gil
(m) Br
Br Noz
+ (CH3)2CHCH2S-
->
Noz
(n)
cH3o-\_ro\ ocH3 + HBr
heat
t
(o) Give the stereochemistry of the product.

Ti(OiPr)*
Grubbs (+)-diethyl tartrate
"o.{, /rH2oH G2 catalyst - (CH3)3C-O-OH - -OHlH2O
(CH3)3C-CH:CHz + +----+ _
/a:a\
HH
(p) Give the structure and stereochemistry of X, Y, andZ.
Grubbs H2
G2catalyst, Pd/c>
x + y Z
mixture of two a single
optically active optically active
compounds compound
(q) Give the stereochemistry of the product and explain your reasoning. (9-BBN is a sterically hin-
dered hydroboration reagent.)
cHr Br CH.
\lC-CHz
H \/C:C
H
/\
o
/,C-OCH3
Pd(PPh3)4 catalyst
aqueous Na2CO3
9-borabicyclononane
(e-BBN)
Figure P18.65 (continued)
Br .OCzHs
\/C:C -----
KOH s- HrC-C-C-OC2H5
/\
H:C (only elimination product observed)
H
BrH
\/f-c
U-U
KOH
H:C-C-Q-OC2H5 + HzC-C:CH-OC2H5
/\
HrC oc2Hs -->
Figure P18.68
884 cnApTER 18 . THE GHEMISTRY oF ARYL HALIDES, VINYLIC HALIDES, AND PHENOLS. TRANSITION.METAL CATALYSIS
18,72 In somp Pd(0)-catalyzed reactions, a Pd(tr) compound methoxy-4-nitrobenzene, 4.92 D) is greater than that
such a$ PdCIz cffi be used instead of Pd(O), but it is as- of nitrobenzene, even though the electronegativities of
sumed that the Pd(II) is reduced to Pd(0) in the reac- chlorine and oxygen are about the same.
tion. Grue both the product and the curved-arrow
mechafiism for reduction of PdClr to Pd(0) by :PPh:. 18.75 The reaction given in Fig. Pl8.75, used to prepare the
(Hint: If Pd is reduced, something has to be oxidized.) drug Mephenesin (a skeletal muscle relaxant), appears
to be a simple Williamson ether synthesis. During this
18.73 Draw urved-arrow mechanisms for the reactions reaction, a precipitate of NaCl forms after only about
given Fig.P18.73. ten minutes, but a considerably longer reaction time is
required to obtain a good yield of mephenesin. Taking
18.74 Explai why the dipole moment of 4-chloroniffoben- these facts into account, suggest a mechanism for this
zene ( .69 D) is /ess than that of nitrobenzene (3.99 reaction. (Hint: See Sec . ll.7 .)
D), an the dipole moment ofp-nitroanisole (1-
Ph X n\
/
\C C+ C:C
/oc2H5
+x-
/ \
c2Hso- -.ffi> P{\
Ph H
Figufe P18.69
CsHilC-C-H + [(CHr)zCHCHz]eAl-H -* X
diisobutylaluminum hydride
(DrBAr)
I F+Hs
Pd(PPh:)r catalyst
x + \:/ r r
H
/\
H
Figu P18.71
-"+'*r-o,l -!"*Is8n* *-"$- F-
Hzso+t (cH3)3c+oH
oH + (cH3)zc:cHz
P18.73
OH ,cHt oH
2h
ffi
I
O- Naa O-CH2CHCH2OH + Na+ ct-

\J
mephenesin
ô-cnrJHCH2oH
Figufe P18.75
18.76 In 1960, a group of chemists led by Prof. John D. pound A is an example of a rather unstable type of
Roberts at Caltech reported that when chlorobenzene compound called generally a quinone methide.)
containing a r4C isotopic label at carbon-l is treated
with the very strong base potassium amide, a substiru-
H:C CH:
tion product, aniline, is formed in which the isotopic Agro,
label is equally distributed between carbon- 1 and car- A
bon-2 (Fig. P18.76). This result was interpreted as evi-
dence for a very interesting unstable intermediate CH:
called benzyne. Propose a mechanism for this substitu-
tion that accounts for the isotopic labeling result. Proton NMR of A: 6 1.90 (610, 6 5.49 (2II), 6 6.76
(Hint: Think about a B-elimination reaction.) (2H), all broad singlets.
18.77 In the conversion shown in Fig. P18.77, the 18.79 For the reactions given in Fig. P18.79 (p. 886), explain
Diels-Alder reaction is used to trap a very interesting why different products are obtained when different
intermediate by its reaction with anthracene. From the amounts of AlBr, catalyst are used . (Hint: See Eq.
structure of the product, deduce the structure of the in- 18.83, p. 869.)
termediate. Then write a mechanism that shows how
the intermediate is formed from the starting material. 18,80 Give a mechanism for the reaction in Fig. Pl8.80
(p. 886) by showing the catalytic intermediates.
18.78 Propose for the product A obtained in the
a structure
following oxidation of 2,4,6-trimethylphenol. (Com-
*
- carbon-14
CI
+ x*:xu' riq"tdff
potassium
chlorobenzene amide aniline
(about 50o/o of each)
Figure P18.7 5
oC
Mg,60
+ MgBrF
I -bromo-2-fluorobenzene
triptycene
Figure P18.77
18.81 TWo gpneral mechanisms (or various versions of them) (a) The metathesis reaction of cyclopentene and (D-2-
for al$ene metathesis were originally considered. In pentene gives three products (not counting
the firot (pairwise) mechanism, shown in Fig. P18.81, stereoisomers), 2,'l -nonadiene, 2,7 -decadiene, and
the ca$alyst brings about cyclobutane formation be- 3,8-undecadiene, in a ratio of 1:2:1. Show how this
tween two alkenes. The second mechanism involves result can be used to decide between the two mech-
metallpcycle formation, as shown in Eqs. 18.59a{ anisms. (Assume that self-metathesis of (D-Z-pen-
(pp. 8$4-85s). tene does not occur.)
cH3o
cH3o cH3o
cH3o cH3o
cH3o
Figure P18.79
OR
frfr
CC
=", Grubbs Gl
+ catalvst + CH3CH: CHz
))
((
afr
CHI CH
Figure P18.80
P airwise ( cy clob utane) mechanism :

RIH
\/C:C
R'\ R3- -H
-c- /\
HR'
lr" + ll H
H
H
H
-*+
R2H
H/t-*, H.-c- -R4
- 4
\/C:C
cyclobutane
intermediate
/\
HR4
(b)
avcHz .\/CDZ #l CH, CH,

ll +llcHz' + cDz
CD"
l+ I ll- + cDz
ll"
\r"A'CHz \,,4'CDz \./
cyclohexene ethylene ethylene-1,1-d2 ethylene-da
1,7-octadiene lr7-octadiene-
lrlrgrg-d4
figure P18.81
(b) What result is predicted by the two mechanisms for 18.84 Potassium tri(isopropoxy)borohydride sometimes finds
the ratio of the three ethylene products in the reac- use as a source of nucleophilic H:- (hydride ion).
tion shown in Fig. P18.81b? Assume that once an
ethylene molecule is formed, it undergoes no fur-
K+ H-n(o;pt),
ther reaction. potassium tri(isopropoxy) borohydride
OCH(CHr)z
-OiPr
18.82 When vinylic boronic acids are treated with Br, and Suggest a mechanism for the substitution reaction in
then with base, vinylic bromides are formed with in- Fig. Pl8.84 that accounts for the stereochemistry of
version of configuration, as shown in Fig. PI8.82a. the reaction. (Hint: See Sec. I 1.7.)
But when vinylic boronic acids are treated with I, in
the presence of base, vinylic iodides are formed with 18.85 Citaprolam is used as an antidepressant.
retention of configuration, as shown in Fig. P18.82b.
Suggest mechanisms that account for these results.
(Hint: Iodine does not add to double bonds, but it does
form iodohydrins (Sec. 5.28). Remember the stereo- N(CH3)2
chemistry of halogen addition.)
18.83 Bombykol is the mating pheromone of the female silk-

worrn moth.
Citaprolam
HH
\/ A biologist, Heywood U. Clonum, has argued that this
C:C H
/\/ compound could be hazardous because it could release
CH3CHzCHz toxic cyanide (-C-N) and fluoride ions by nucle-
/a:a\ ophilic substitution reactions with biological nucle-
H (CH2)eOH
ophiles such as water. Is this argument chemically rea-
bombykol
sonable? Explain.
Using the result in Problem 18.82, propose a synthes is
of bombykol, using both H-C:C(CH2),OH
(1O-undecyne-1-ol) and 1-hexyne as starting materials.
(a) R H RBr
\ 1) Br2 in CH2CI2
2) NaOH \/ + + e(oH)n
C:C , C:C Ba
/ /\
HH
H B(OH)2
(b)RH RH
\/ \/ - + B(oH)4
C:C
I-,.
o-:
NaOH
C:C + r
H
/\ B(OH)2
/\
HI
Figure P18.82
CH3CH'CH'T' Br CH3CHTCHtC{,
/u(OlPr)z
C:C + K+ H-B(oiPr)3 --+ C:C + K+ Br- + B(OfPr):
H B(OlPr)2
/\
HH
Figure P18.84

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18

In a vinylic halide, a halogen is bound to a carbon of a double bond.

LACK OF REACTIVITY OF VINYLIC AND ARYL HALIDES

cH3cH2-Br * Na+ ctt.t;tl,-ci:- cHicH2-o-cH2cH.r * Na+ Br-

rran der \\Iilals

vrln rfer \\Ia;rls CH: replrlsion

18.2 ETIMINATION REACTIONS OF VINYLIC HALIDES

LACK OF REACTIVITY OF VINYTIC AND

H_c W^a Cllllltlr

(a) vinylic cation (b) aryl cation

NUCLEOPHITIC AROMATIC SUBSTITUTION

o,*OF + K+ cH3o- i*#=' o,*-$ocH3 + K+ F- (18.r)

I -chloro -2,4-dinitroben zene 2,4-drnitroaniline

rate: f[arylhalide][nucleophile] (18.13)

However, nucleophilic aromatic substitution reactions do not involve a concerted backside

o,*< F.t + -ocH3 orN< )=o.", * .t- 105-106 (r8.14a)

ozN$.t + -ocH3 ----* ozN+ocH3 + cl- ( 18.14b)

( \}- cr + -ocH3 ---+ no reaction =Q (18.14c)

Reactivities of aryl halides:

I NTRODUCTION TO TRANSITION.M ETAL

organometallic chemistry: the chemistry of carbon-metal bonds. (Grignard reagents and

A. Transition Metals and Their Gomplexes

PeriorJ tI -------rr> Sc Ti VCr Mn Fe Co Ni Cu Zn

Pcriotl 6 --------> La Hf thw Re Os Ir Pt Au Hg

cl. NH: cl NH:

@ Some Typical Ligands Used in Transition-Metal Chemistry

Ligand Name Abbreviation Type Electron count*

RrP: (R - alkyl, aryl) trialkylphosphino,

cHrc-N: acetonitrile MeCN 2$$

F-, Cl-, Br-,l- halo (e.g.,chloro) 2l

R:- .9.,H3C:- alkyl (e.g.,methyl)

HzC: CH- CH2 a llyl 4**

Oxidation state of M - number of X-type ligands + Qw (r8.22)

n - valence electrons in neutral M - Qn'r - number of X-type ligands ( 18.23)

n - valence electrons in neutral M - oxidation state of M ( 18.24)

18.9 What ts dn for each of the following complexes?

D. Electron counting: The 16- and 18-Electron Rules

electron count - n * 2(number of all ligands) ( 18.2s)

electronbount : valence electrons in neutral M : oxidation state ofM

electron count : valence electrons in neutral M - Qw

Unhybridized Co3+ (d6),

hl,Lrridize the empt\r orbitals;

5d8 {.F -t+- J+

E. Fundamental Reactions of Transition-Metal Complexes

Ligand Dissociation-lssociation; Litand Substitution One of the most common re-

Pd(PPh3)4 Pd(PPh3)3 + :PPh: ( 18.2e)

Ph3P, ,I PhsP\ CH*

Oxidative Addition In oxidative addition, a metal M reacts with a compound X-Y to

R-Br+Nng + R-Mg-Br ( 18.31a)

filled metal d orbital

Reductive Elimination Reductive elimination is conceptually the reverse of oxidative

Pd- CHrtlH,Ar (18.35)

PPh3 PPh3 PPh3

Pd and aryl are cis

Pd(rr) Pd(II) Pd(rr)

Because this p-elimination is intramolecular-within the same molecule-it must occur as

Pd(PPh3)4 ( --> Pd(PPh3)3

Cl- + Pd(PPhz)t + ClPd(PPh3)3 a :PPh3

18.15 The Wkinson catalyst chlorotis(triphenylphosphine)rhodium(I), ClRh(PPh3)3, brings about

18.6 EXAMPLES OF TRANSITION.METAL.CATALYZED REACTIONS

CH: (catalyst) CH-t

the only p-hyclricle available

When the Heck reaction is applied to unsymmetrically substituted alkenes, such as an

B. The Suzukl Coupllng

o,OF + K+ cH3o- i#=' o,*-$ocH3 + K+ F- (18.r)

o,< F.t + -ocH3 orN< )=o.", .t- 105-106 (r8.14a)