Page 347 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

328 wide range and it is not easy to make direct experimental comparisons. In Scheme 3.2
some available kinetic data are provided that allow at least a qualitative comparison of
CHAPTER 3 the reactivity of the most common derivatives. The ratio of reaction toward hydroxide
Structural Effects on is anhydride > ester > amide, reflecting the expected trend and is dominated by the
Stability and Reactivity
resonance effect. Acyl chlorides are even more reactive, judging by a comparison
of methanolysis and hydrolysis. The data for esters give the nucleophilicity order as
− OH > NH > H O, as expected.
3
2
A more extensive and precise set of data has been developed that includes
aldehydes and ketones (but not acyl halides), which pertains to the equilibrium constant
for hydration. 119
O OH
RC X + H O R C X
2
OH

Table 3.24 shows the values for equilibrium constants for nucleophilic addition of
both water and hydroxide ion. We can see the following trends in these data: For
aldehydes and ketones, the addition is disfavored in the order Ph > alkyl > H. The order
NH < OR < CH < H is indicated by the K hydr values of 10 −13 8 ,10 −6 6 ,10 0 03 , and
2
3
10 3 36 for N,N-dimethylformamide, methyl formate, acetaldehyde, and formaldehyde,
Scheme 3.2. Relative Reactivity Data for Some Carboxylic Acid Derivatives

O O O O
CH 3 C Cl (CH 3 C) O CH 3 C OR′ CH 3 C N(CH )
2
3 2
–1 –1 1.8x10 M s
–2
–1 –1
2
8.9 x 10 M s 2.2 x 10 M s –5 –1 –1
–
Hydrolysis ( OH) at 25° C (a) at 0° C E a = 24.1 (c)
E = 18.5 (b)
a
–3 –1
s
O) 2.4 x 10 s 3 x 10 –10 –1
Hydrolysis (H 2
at 25° C (a) at 0° C
E = 30.2 kcal(b)
a
–1 –1
OH) 1 x 10 s
Methanolysis (CH 3
at 0° C (d)
–1
–7
2.8 x 10 M s –1
Aminolysis (NH )
3
in 10 M H O in dioxane (e)
2
–1
–7
3.7 x 10 M s –1
in 5 M HOCH CH OH in dioxane (f)
2
2
a. C. Castro and E. A. Castro, J. Org. Chem., 46, 2939 (1981); J. F. Kirsch and W. P. Jencks, J. Am. Chem. Soc., 86,
837 (1964).
b. J. P. Guthrie, J. Am. Chem. Soc., 95, 6999 (1973).
c. J. P. Guthrie, J. Am. Chem. Soc., 96, 3608 (1974).
d. T. W. Bentley, G. Llewelyn, and J. A. McAlister, J. Org. Chem., 61, 7927 (1996).
e. F. H. Wetzel, J. G. Miller, and A. R. Day, J. Am. Chem. Soc., 75, 1150 (1953).
f. E. M. Arnett, J. G. Miller, and A. R. Day, J. Am. Chem. Soc., 72, 5635 (1950).
119
J. P. Guthrie, J. Am. Chem. Soc., 122, 5529 (2000).