Page 651 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

solvents are fast, irreversible reactions that provide a convenient basis for comparing 633
the reactivity of different carbonyl compounds. 1
SECTION 7.1
Reactivity of Carbonyl
OBH – OH Compounds toward
O 3 Addition
H 2 O
+ BH – R C R' RCHR'
R R' 4
H
The reaction is second-order overall, with the rate equal to k[R C=O][NaBH . The
2 4
interpretation of the rates is complicated somewhat by the fact that the alkoxyborohy-
drides produced by the first addition can also function as reducing agents by successive
hydride transfers, but this has little apparent effect on the relative reactivity of the
carbonyl compounds. Table 7.1 presents some of the rate data obtained from these
studies.
Reductions by NaBH are characterized by low enthalpies of activation (8 to
4
13 kcal/mol) and large negative entropies of activation (−28 to −40 eu). These data
suggest an early TS with considerable organization. Aldehydes are substantially more
reactive than ketones, as can be seen by comparing benzaldehyde and acetophenone.
This relative reactivity is characteristic of nearly all carbonyl addition reactions. The
lower reactivity of ketones is due primarily to steric effects. Not only does the additional
substituent increase the steric restrictions to approach of the nucleophile, but it also
causes greater steric interaction in the tetrahedral adduct as the hybridization changes
from trigonal to tetrahedral. Alkyl substituents also act as electron donors toward
carbonyl groups by hyperconjugation (see Section 2.2.1).
Among the cyclic ketones shown in Table 7.1, the reactivity of cyclobutanone
is enhanced because of the strain of the four-membered ring, which is decreased
3
2
on going from sp to sp hybridization. The higher reactivity of cyclohexanone
compared to cyclopentanone is quite general for carbonyl addition reactions. The
major factor responsible for the difference in this case is the change in torsional
3
2
strain as addition occurs. As the hybridization goes from sp to sp , the torsional
strain is increased in cyclopentanone. The opposite is true for cyclohexanone. The

Table 7.1. Rates of Reduction of Aldehydes
and Ketones by Sodium Borohydride
4
s
Carbonyl compound k×10 M −1 −1a
Benzaldehyde 12,400 b
Benzophenone 1.9
Acetophenone 2.0
Acetone 15.1
Cyclobutanone 264
Cyclopentanone 7
Cyclohexanone 161

a. In isopropanol at 0 C.
b. Extrapolated from data at lower temperatures.
1
H. C. Brown, O. H. Wheeler, and K. Ichikawa, Tetrahedron, 1, 214 (1957); H. C. Brown and K. Ichikawa,
Tetrahedron, 1, 221 (1957).