1

1op le Lo bouom rlghL: aldehyde, aldehyde, keLone, aldehyde, keLone, keLone

2
3 4
7-hydroxy-3-propyl-4-hepLenal
3 6
1-hydroxy-3-propyl-3-hepLen-2,6-dlone
7 8
1he resonance hybrld would look almosL Lhe same as Lhe sLrucLure on Lhe le wlLh
Lhe double bond buL wlLh some parual charges due Lo Lhe mlnor resonance
conLrlbuLor.
9
1he sp2 carbon ls less hlndered and more open Lo auack by a nucleophlle.
10
Aldehydes are more reacuve. 1here ls less sLerlcs and Lhe P aLom ls noL as eecuve
as a carbon group aL balanclng Lhe posluve charge on Lhe carbonyl carbon, so Lhere ls
a greaLer parual posluve on Lhe aldehyde carbon Lhan on Lhe keLone carbon.
11 12
See nexL sllde.
13
1he resulung lnLermedlaLe ls relauvely unsLable because of Lhe negauve formal
charge on oxygen. Powever, a negauve formal charge on a hlghly elecLronegauve
oxygen ls noL exLremely unsLable, so lL can form, especlally lf Lhe nucleophlle ls
slmllarly unsLable. lf Lhe nucleophlle makes a good leavlng group, Lhen Lhe
equlllbrlum wlll greaLly dlsfavor Lhe producL of Lhe auack, because Lhe reverse
reacuon, where Lhe leavlng group leaves, wlll happen much more readlly. Auack on
an alkyl hallde ls usually much more faclle, because Lhe hallde usually makes a greaL
leavlng group sLablllzlng a - charge qulLe eecuvely.
14
13
Addlng an acld makes Lhe resonance conLrlbuLor wlLh Lhe posluve charge on Lhe
carbon a much more slgnlcanL conLrlbuLor, and lL glves Lhe molecule a formal
posluve charge so lL can auracL Lhe nucleophlle more eecuvely, and because Lhe +
charge desLablllzes Lhe molecule, a smaller acuvauon energy ls necessary Lo exclLe
Lhe molecule Lo reach Lhe 1S.
16
17
SLrong nucleophlles are also oen sLrongly baslc, so addlng an acld would be more
llkely Lo proLonaLe Lhe nucleophlle Lhan Lo proLonaLe Lhe carbonyl.
18
19 20
21
LnLropy always favors Lhe slde wlLh more moles. SLerlcs wlll favor Lhe carbonyl as
well, because Lhere are fewer groups crowdlng. lnducuon favors Lhe hydraLe ln some
cases, especlally when Lhere are hlghly elecLronegauve groups auached Lo Lhe
molecule. ln such cases, a very large parual posluve on Lhe carbonyl auracLs Lhe
waLer molecule favorlng Lhe hydrauon producL.
22
23
A caLalysL lncreases Lhe raLe by maklng Lhe 1S less charged and lower ln energy and
by lncreaslng Lhe energy of Lhe reacLanLs (less sLable charged reacLanL CP-). 1haL
means less acuvauon energy ls necessary Lo geL from reacLanLs Lo 1S. A caLalysL wlll
nC1 change Lhe equlllbrlum consLanL or lmpacL Lhe sponLanelLy of Lhe reacuon ln any
way.
24
23
A caLalysL lncreases Lhe raLe by maklng Lhe 1S less charged and lower ln energy and
by lncreaslng Lhe energy of Lhe reacLanLs (less sLable charged reacLanL P3C+). 1haL
means less acuvauon energy ls necessary Lo geL from reacLanLs Lo 1S. A caLalysL wlll
nC1 change Lhe equlllbrlum consLanL or lmpacL Lhe sponLanelLy of Lhe reacuon ln any
way.

26
27 28
lnLramolecular reacuons are oen fasL because Lhey do noL requlre speclc
molecules Lo meeL and colllde.
29
An lnLermolecular pushlng ouL of Lhe leavlng group would requlre a speclc
blmolecular colllslon lnvolvlng an oen very sLerlcally hlndered elecLrophlllc slLe.
very unllkely.
30
31
8eacuon 1: 8ecause formaldehyde ls so sLerlcally unhlndered, and Lhere ls a large
parual posluve on Lhe carbonyl, Lhe reacuon ls favored overall desplLe enLropy
favorlng Lhe le slde havlng 3 moles versus 2 on Lhe rlghL slde.
8eacuon 2: LnLropy and sLerlcs favorlng Lhe reacLanL slde prevenLs slgnlcanL
producL formauon.
8eacuon 3: 1he lnsLablllLy of Lhe parual posluve on Lhe carbonyl shls Lhe reacuon Lo
Lhe producL slde, and because Lhere are 2 moles on boLh sldes, enLropy ls noL much
of a facLor. 1he rlng also reduces sLerlcs on Lhe producL slde.
Le ChLellers rlnclple can always be used Lo shl an equlllbrlum by uslng excess of
one reagenL. roducLs wlll be more favored lf an excess of Lhe alcohol ls used.
32
8ecause waLer ls presenL on Lhe producL slde, Le ChLellers rlnclple can be used Lo
shl Lhe equlllbrlum by addlng excess waLer (shl le) or by removlng waLer (shl
rlghL)
33 34
33
Amlnes are beuer nucleophlles Lhan waLer generally, because n ls less
elecLronegauve Lhan C, lL ls more wllllng Lo share lLs lone palr of elecLrons and lL can
more eecuvely sLablllze Lhe resulung + charge LhaL forms. An acld caLalysL ls sull
helpful wlLh amlnes. Amlnes are noL acldlc enough Lo reacL wlLh a base caLalysL llke
CP-, so an acld ls necessary. See producLs and mechanlsm on nexL sllde.
36
1he producL slde has Lhe same number of moles as Lhe reacLanL slde, so enLropy ls
noL golng Lo be a blg facLor.
37 38
8elow pP=4, Lhe amlne lLself becomes proLonaLed and Lhen lLs lone palr of elecLrons
ls noL avallable Lo auack. Above pP=3, Lhere ls noL enough P+ Lo proLonaLe Lhe
carbonyl slgnlcanLly, and Lhen Lhere ls llule mouvauon for Lhe amlne Lo auack
(because lL would only be auacklng a parual posluve raLher Lhan a formal posluve
and because Lhe resulung lnLermedlaLe and 1S are less sLable as Lwo formal charges
form on lL raLher Lhan one.
39 40
41 42
urlven forward by Lhe producuon of Lhe exLremely sLable n2 gas and lnablllLy of Lhe
gas Lo come back ln and promoLe Lhe reverse reacuon once lL leaves. Lach ume CP-
ls used up, lL ls regeneraLed, so lL ls posslble LhaL lL acLs as a caLalysL ln Lhe reacuon.
43 44
43 46
P normally carrles a parual posluve when bonded Lo oLher aLoms, so we Lyplcally see
lL lnvolved ln proLon Lransfer reacuon raLher Lhan ln nucleophlllc auacks.
47
1he nucleophlle ls an P- or a hydrlde. Acldlc condluons wonL work, because P-
reacLs wlLh P+ Lo glve P2 gas. 8aslc condluons are necessary. See nexL sllde.
48
1he nucleophlle ls an P- or a hydrlde. Acldlc condluons wonL work, because P- reacLs
wlLh P+ Lo glve P2 gas. 8aslc condluons are necessary. 1he rsL sLep wlll noL be
slgnlcanLly reverslble, because Lhe P- makes a Lerrlble leavlng group and cannoL
eecuvely sLablllze a - charge. 1he second sLep ls also exLremely producL favored
glven LhaL a sLrong acld ls reacung wlLh a sLrong base. 1he acld can only be added
aer Lhe hydrlde ls compleLely reacLed wlLh Lhe carbonyl. CLherwlse an undeslred
reacuon beLween Lhe hydrlde and PCl wlll occur lnsLead.
49
Carbon usually carrles a parual posluve charge when bonded Lo oLher aLoms, so lL ls
oen reacLs as an elecLrophlle raLher Lhan a nucleophlle.
30
1he nucleophlllc slLe ls Lhe carbon aLom LhaL ls sharlng elecLrons wlLh Lhe very low
elecLronegauvlLy magneslum. Acldlc condluons wonL work, because P- reacLs wlLh P+
Lo glve P2 gas. 8aslc condluons are necessary. See nexL sllde.

31
Cnly Lhe second sLep should be reverslble, because ln every oLher sLep, a carbon ls
auacklng as a nucleophlle, and Lhe reverse sLep would requlre carbon Lo acL as a
leavlng group. lL ls a Lerrlble leavlng group, because lL so poorly sLablllzes a negauve
charge. 1he acld musL be added aL Lhe very end Lo avold lL reacung dlrecLly wlLh Lhe
Crlgnard reagenL.
32
33 34
A carbon wlLh a lone palr and parual or full - charge (nucleophlle) auacks Lhe
carbonyl carbon wlLh lLs parual posluve charge acung as an elecLrophlle.
33 36
8esonance reduced Lhe amounL of formal charge on Lhe carbon aLom. 1he ma[or
conLrlbuLor ls Lhe one wlLh formal charges. 1he pl overlap beLween C and ls noL
very eecuve because of Lhe orblLal slze mlsmaLch.
37
lormauon of Lhe 4-membered rlng ls llkely Lhe slow sLep because of Lhe rlng sLraln
LhaL ls creaLed.
38
39
A very sLrong base ls needed Lo deproLonaLe Lhe carbon, because Lhe carbon can noL
sLablllze Lhe resulung - charge very eecuvely.
60
See nexL sllde for mechanlsm
61 62
63 64
1he rsL sLep mlghL be slowesL because lL ls sLerlcally hlndered and Lwo formal
charges are creaLed ln LhaL sLep. 1he lasL sLep ls noL reverslble, because Lhe producLs
are qulLe sLable (a loL of acuvauon energy would be necessary). Also, Lhe auack
necessary Lo make Lhe lasL sLep reverslble would requlre an oxygen wlLh a parual
negauve Lo auack anoLher oxygen wlLh a parual negauve, whlch would be very
unllkely.
63 66
lrom le Lo rlghL: Crlgnard, cyanohydrln, Wlmg
67
8aeyer-vllllger
68
69
Aldehyde proLons experlence Lhe anlsoLroplc eecLs assoclaLed wlLh Lhe pl cloud as
well as Lhe lnducuon of Lhe nelghborlng C aLom.
70
71