CHEM 212 CH 12-16 Review 2014 - Pennsylvania State University

Study Guide for Exam 2-- Aldehydes and Ketones

Oxidation of Alcohols to Carbonyl Compounds

The oxidation of alcohols to carbonyl compounds is the reverse of nucleophilic addition (below).

Most oxidants accept the alcohol oxygen as a nucleophile followed by loss of the acidic hydrogen.

The process is completed by an E2--like elimination of hydrogen from the proto--carbonyl carbon in concert with formation of the C=O --bond and reductive loss of the leaving group.

General

Mechanism

H

O

Ox

H

H O Ox H

B

H

-H+

O Ox

BH O

Ox

Swern

H O H

Cl S Me Me

H

O

Me S

-HCl

H Me

B

H

Me

OS

Me

BH O

Me S

Me

Chromic Acid

H O H

O Cr O O

B

H

O

H+

O Cr O xfer

HO

H

OH

O Cr O

O

BH O

OH Cr O O

Scope and Limitations

1. As a hydrogen atom is needed for the elimination step, 3o alcohols do not oxidize to carbonyl compounds.

2. Normally 1o alcohols are converted to aldehydes and 2o alcohols to ketones.

3. However, in the presence of water, aldehydes form hydrates that undergo more rapid oxidation than the

starting 1o alcohols.

Thus with CrO3/H2SO4, Na2CrO7, K2CrO7, H2CrO4, 1o alcohols are converted to carboxylic

acids.

B

BH

R

O

H2O

H RO

H

HO H

O Cr O O

H

O

H+

R O Cr O xfer

HO H O

H

OH

R O Cr O

HO

O

R O

HO

4. This over--oxidation is avoided with the Swern oxidation or the use of PCC.

OH Cr O O

Nucleophilic Addition

Most of the reactions of aldehydes and ketones in these chapters are nucleophilic addition reactions.

The oxygen in C=O polarizes the bond.

Therefore, while electrophilic addition (electrophile first, followed by nucleophile) was favored for the comparatively non--polar, electron--rich alkene, carbonyls undergo nucleophilic addition (nucleophile first, followed by electrophile).

Note how all the mechanisms begin exactly the same way:

General Mechanism

O

O

E+

OE

Nu

Nu

tetrahderal intermediate

Nu

Hydride

LiAlH4 is similar

O

H

HB

H

H

H3B O H

H OR

OH H

+ H3BOR

Carbanion Grignard/Alkyllithium/Acetylide

O 1)

Br Mg R

BrMg O R

H HOH

2)

OH R

+ BrMgOH2

Ylide

Wittig Reaction

O Ph3P CH2

O Ph3P CH2

O Ph3P CH2

O PPh3 + CH2

The Wittig is unique in that the alkoxide oxygen in the tetrahedral intermediate attacks the phosphonium center forming an oxaphosphetane intermediate.

Thus, the electrophile is not H+ as in the previous examples but the phosphonium center.

The intermediate undergoes a reverse 2+2 process to form triphenylphosphine oxide and an alkene product to complete the process.

If the nucleophile is a weaker base than the alkoxide in the tetrahedral intermediate, an alternative mechanism is proposed.

Here, the electrophile (usually H+) is added first to enhance the polarity of the C=O bond, and reduce the energy of the tetrahedral intermediate (transition state resembles this intermediate; stabilizing it will increase the rate).

The reverse reaction rates are also enhanced, so the mechanisms feature equillibria.

Alcohol as Nucleophile ? Acetal/Ketal Formation

O

H3O+ H O

HO

H+ xfer

HOR H O H -H2O

HOR -H3O+

OR

ROH

ROH

RO

RO

RO

RO

1o Amine as Nucleophile ? Imine Formation

O

H3O+ H O

HO

H+ xfer H O H -H2O

RNH H

RNH H

RN H

2o Amine as Nucleophile ? Enamine Formation

RN

O

H3O+ H O

HO

H+ xfer

H O H -H2O

H

RNH R

RNH R

RN R

Cyanide as Nucleophile ? Cyanohydrin Formation

O

HCN H O

HO

RN R

OH H

RN R

HOH H

NC

N C

Peracid as Nucleophile ? Baeyer--Villager Oxidation

O

H3O+ H O

HO

B:

H+ xfer

HO

BH O

OH OR

O

OH OR

O

O OR

O H

Developmental Problems

1. Complete the following `reactivity tree' for a ketone:

O OR HO

H3O+, H2O

ROH, H3O+

OH, HO

H 3O+ RNH 2, pH 5.5 R 2NH, pH 5.5

O Ph

NH2OH, pH 5.5

PPh 3

HCN, KCN 1) RMgBr

2) dil. H3O+

1) LiAlH4 2) dil H3O+

2. Predict the products:

a.

O

b.

O

c. O

d.

1) LiAlH4

2) dil. H3O+

1) PhMgBr 2) dil. H3O+

H2C PPh3

e.

f.

g.

h.

i.

j.

OH Na2Cr2O7

HO

H 2SO 4/H2O

3. Predict the products ? Part II:

a.

O

mCPBA

CH2Cl2

b. O

PPh 3

c.

O

Ag2O, KOH

H

d.

1) DIBAH, -78 oC

2) H3O+

O

O

e.

O 1) KCN, HCl

2) HCl, H2O

f. 1) DIBAH, -78 oC

2) H3O+

OO

g.

OH

1) (COCl)2, DMSO 2) Et3N

h.

OH

PCC

CH2Cl2

i.

1) Mg, ether

Br

2) O

3) H3O+ j.

O OO

NaBH4 EtOH

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