Organic Chemistry

Compared with other carbon nucleophiles, cyanide ion is a relatively weak base

(the of is 9.14, the of is 25, the of is 50),

which means that the cyano group is the most easily eliminated of the carbon nucleo-

philes from the addition product. Cyanohydrins, however, are stable because the OH

group will not eliminate the cyano group; the transition state for the elimination reac-

tion would be relatively unstable since the oxygen atom would bear a partial positive

charge. If the OH group loses its proton, however, the cyano group will be eliminated

because the oxygen atom would have a partial negative charge instead of a partial pos-

itive charge in the transition state of the elimination reaction. Therefore, in basic solu-

tions, a cyanohydrin is converted back to the carbonyl compound.

Cyanide ion does not react with esters because the cyanide ion is a weaker base

than an alkoxide ion, so the cyanide ion would be eliminated from the tetrahedral

intermediate.

The addition of hydrogen cyanide to aldehydes and ketones is a synthetically useful

reaction because of the subsequent reactions that can be carried out on the cyanohydrin.

For example, the acid-catalyzed hydrolysis of a cyanohydrin forms an -hydroxycar-

boxylic acid (Section 17.18).

The catalytic addition of hydrogen to a cyanohydrin produces a primary amine with an

OH group on the -carbon.

PROBLEM 11

Can a cyanohydrin be prepared by treating a ketone with sodium cyanide?

PROBLEM 12

Explain why aldehydes and ketones react with a weak acid such as hydrogen cyanide in the

presence of but do not react with strong acids such as HCl or in the pres-

ence of or

PROBLEM 13 SOLVED

How can the following compounds be prepared, starting with a carbonyl compound with

one fewer carbon atoms than the desired product?

a. b.

O

CH 3 CHCOH

OH

HOCH 2 CH 2 NH 2

Cl- HSO 4 -.

• C‚N, H 2 SO 4

H 2

OH

CH 3 CH 2 CH 2 CHC

OH

N Pt CH 3 CH 2 CH 2 CHCH 2 NH 2

b

a cyanohydrin an α-hydroxy carboxylic acid

HCl, H 2 O

OH OH

CH 2 CH 3

CH 3 CH 2 CCN

O

CH 2 CH 3

∆ CH^3 CH^2 C COH

a

H 2 O

HO

HO−

CN O CN

+ −CN

− O

cyclohexanone

cyanohydrin

pKa HC‚N pKa HC‚CH pKa CH 3 CH 3

742 CHAPTER 18 Carbonyl Compounds II