Facilitator: Chris Lovero Task

Symmetrical ethers through dehydration of 1o alcohols Cleavage of ethers byvstrong acids

Organic Chemistry II Reactions Reaction Notes

R OH
x2
O CH3
HBr

H2SO4 140oC

R
Br

O R

*cannot be unsymetrical (you will get mixtures!)

*can also use HI, HCl,

H3C

Br

etc * vinyl or aryl do not get cleaved (NO SN2 ON

HBr

SP2)

O
Autoxidation

Br R R R O R O OH

HO
*basically forms

R O R

O2 (xs) slow

R R O O R H

peroxides.... which EXPLODE!

MCPBA

CH3 CH3

MCPBA

CH3 O CH3

*epoxide will form along the more substituted alkene

Intramolecular Williamson

Br OH H3C

OH

NaOH

*SN2 like *forms O- that attacks halogenated C

NaOH

H3C

Cl
Opening of Epoxides
*activate the O first *weak Nu are good *more substituted side attacked

CH3
H3O+

CH3 OH OH D OH
1)-OH H2O

O D CH3 O D

*SN2 like (least subs) so strong Nu and base

CH3 D OH

*Grignard reagent and acetylide anion can work tooo

2)H3O+

Facilitator: Chris Lovero Task

Free Radical Halogenation Expanded

Organic Chemistry II Reactions Reaction

CH3 CH3
NBS 60oC NBS hv 0oC

Notes
*Low T: more stable TS

CH3 Br CH3

*High T: more stable compound

transition state
CH3 CH3
CH3

CH3 CH3

CH3

Br
Conjugated Systems
*in this example we will examine the case of HBr *Low T: more stable TS *High T: more stable

H2C
HBr Br2

CH2
H3O+

compound *NOTE: If more than one conjugated system possibly exists, examine the transition states of

HBr / 0oC

HBr / 40oC

each one and do the reactions with the more stable transtion states!

H H2C Br Br

transition state
+ +
*1,2 or 1,4 adduct

Diels-Alder Reaction

D = donating group

W = withdraw group

+
W D

heat

D W D

*know endo rule *Diene and Dienophile *Know Stereochem *PRACTICE THIS!!!

+
W

heat

Facilitator: Chris Lovero Task

Halogenation of Benzene

Organic Chemistry II Reactions Reaction

X2, FeX3 or (I2 / CuCl2)

NOTE: FROM HERE, YOU HAVE TO KNOW YOUR META, ORTHO, AND PARA DIRECTORS Notes
X
*X = Cl or Br

Nitration of Benzene

HNO3 H2SO4 heat

NO2

*H2SO4 acts as a catalyst

Sulfonation (fuming sulfuric)

SO3 / H2SO4 heat

SO 3H

*REVERSIBLE DUE TO ENTROPY

SO 3H

+
Friedel-Crafts Alkylation

H2SO 4

H2O

*watch rearrangement!

RCl AlCl3

*no strong deactivators (no strong W grps) *no amino groups *watch for polyalkylation

Friedel-Crafts Acetylation
Cl

O R

O R

*no strong deactivators (no strong W grps) *no amino groups

AlCl3

Gatterman-Koch Formation (forming benzaldehyde)

O
CO / HCl AlCl3 / CuCl

*no strong deactivators (no strong W grps)

*no amino groups

Clemmensen Reduction

O
Zn(Hg)

*avoid using this reactant in the presence

HCl

of alkenes, alkynes, alcohols and amines.

Facilitator: Chris Lovero Task

Reduction of Nitro group into Amino Group

Organic Chemistry II Reactions Reaction

Zn, Sn, or Fe

Notes
*Do not confuse with Clemmenson Red.

NO2
W = withdraw group X = leaving grp (halide) Nu = nucleophile

HCl

NH2
*need Strong W groups

Nucleophilic Aromatic Substitution of Aryl Halides: Addition / Elimination

X W W

Nu (2eq) heat, pressure

Nu W W

ortho and/or para to leaving group. *Nu can be OH-, RO-, NH3.

W
Nucleophilic Aromatic Substitution of Aryl Halides: Elimination / Addition

W X
1) NaOH (2eq) / 340oC / 2500 psi 2) H3O+

*NOTE: If - OCH3 is the Nu, only need 1 eq

OH

*occurs when Strong W group is not O/P *formation of benzyne in mechanism

X
NaNH2 / NH3 (l)

NH2

* Nu can be OH-, RO-,

+
CH3 Cl
3 Cl2 / heat pressure

NH2

NH2.

*will get a mixture (like second example)

CH3
Chlorination of Benzene

CH3
*8 different stereochems actually occur

Cl Cl Cl

Cl Cl

*this particular molecule is the commercial compound Rid (lice killer)

Catalytic Hydrogenation

3 H2 / 1000 psi / 100oC Ru or Rh (Pt,Pd,Ni also)

Birch Reduction

W
Na or Li
0 0

*withdraw groups -> sp3 *donating groups ->

NH3(l) / ROH

sp2

Facilitator: Chris Lovero Task

Side Chain Rxn: Oxidation
(CH2)n

Organic Chemistry II Reactions Reaction

CO2H

Notes
*Can use either reagent *Does not work for bulky

KMnO4/H2O
O

groups.

OH-/100oC

HO2 C

CO2 H CO2 H

Na2Cr2O7 / H2SO4 heat

(no rxn)

Halogenation of side chains

Cl CH2CH3

*If aromatic ring is

Cl2 / light

+
Cl

activated, use NBS instead of Br2 *Pay attention to Temp (if it's low or high) *WILL EXPLAIN THIS BETTER IN CLASS

54% Br2 (or NBS) / light

Br

44%

Nucleophilic Subs of Benzylic Halides

*SN1

major! CH2 Br CH3OH heat

+ +
CH2 OCH3

*SN1 or SN2 or E2? Depends on conditions! *Resonance form that does not disrupt the aromaticity is more stable

NaI
Br

*SN2

acetone CH3CH2ONa+

*E2
NaOH
O
-

Rxns of phenols similar to alochols

*2nd rxn is Fischer Estherification *3rd rxn is only one that

OH

RCO2H or RCOCl PBr3

O O

is different!

OH

(no rxn)

Facilitator: Chris Lovero

Task
Oxidation of Phenols to Quinones
HO OH

Organic Chemistry II Reactions

Reaction
Na2Cr2O7 H2SO4 1) NaOH 2) CO2 3) H3O
+

Notes
*This reaction forms a

D-A dienophile!

Formation of Salycilic Acid

OH

*Phenoxide anion can

OH

O OH

react with the weak electrophile because it is so strongly activated.

REVIEW: Oxidation of alcohols

2o alcohols

Na2CrO7 H2SO4 / H2O

*any [ox] can be used *KMnO4 and NO3 can be used but they are

OH

CrO3 / H2SO4 / H2O acetone / 0oC (Jones reagent)

harsh.

PCC CH2Cl2
1o alcohols

H OH
PCC CH2Cl2

*Only use PCC because

Jones reagent will yield carboxyllic acid

REVIEW: Cleavage of Alkenes by Ozonolysis

H3C H

CH3 CH3

1) O3 2) (CH3)2S

H3C O H

CH3 O CH3

REVIEW: Hydration of Alkynes

H2O / H2SO4

R HO R H

H H H

R CH3 O H RCH2 O

*Really know the mechanism now and how the enols tautomerize.

HgSO4 1) Sia2BH 2) H2O2 / OH-

OH

either reagent

mixture of ketones

Facilitator: Chris Lovero

Task
Dithiane Synthesis of Aldehydes and Ketones

Organic Chemistry II Reactions

Reaction
O
1) BuLi

Notes
*Dithiane will be given *BuLi =

S H

S H

2) R - X

S R

S H
1) BuLi 2) R1 - X

H3O+ HgCl2

CH3(CH2)2CH2-Li *Halide must be methyl or 1o

S R
Ketones from Carboxylic Acids

S R
1

H3O+ HgCl2

O R R
1

O R OH

1) R1 - Li (2eq) 2) H3O
+

O R R
1

*2 eq because first is used to make salt

Ketones from Nitriles

1) R1-MgX

O R R
1

R C N

2) H3O+

Aldehydes from Acid Chlorides

*lithium aluminum tri(t-butoxy)hydride

O R Cl

LiAlH(OtBu)3
*Rosenmund Reduction

O R H

H2 / Pd / BaSO4 / S

Ketones from Acid Chlorides

*Make sure you know

O R Cl

(R1)2CuLi

O R R
1

how to form Gilman Reagent (refer to CoreyHouse in previous rxn sheet)

Wittig Reaction: Ald and Ketones ONLY

H (Ph)3 P C

*Know how to prep the phosphorous ylide!

O H

*trans is more stable because you want

+
H H

bulky groups to be furthest away from each other.

maj

Facilitator: Chris Lovero

Task
Aldehydes and Ketones: Formation of Cyanohydrins

Organic Chemistry II Reactions

Reaction
O R O H
-

Notes
OH R C CN H OH
*Aldehydes or unhindered ketones *will use this as a reagent in the future.

CN

HCN

NaCN

H3CH2C
Aldehydes and Ketones: Addition of 1o Amines

H+

H3CH2C C CN H
*non AQ favors reactant

O C

RNH2 H+

C N R

*AQ favors product

Wolf-Kishner Reaction

*avoid halogens and

NH2NH2 KOH/DMSO

other good LGs. (Use Clemmensen instead)

Aldehydes and Ketones: Addition of 2o Amines

(CH3)2NH H3O+

(H3C)2N

Acetal Formations "protected carbonyls"

CH3 O

2(CH3CH2OH) H+

OEt CH3 EtO

*aldehyde protected *easier to just use OH OH

1) OH
H O

OH /H

HO

CH 3

before ketone because it is more reactive

2) CH3MgBr 3) H3O+
O

CH 3

H O O O

H O