Page 654 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

636 The high reactivity of the acyl chlorides also reflects the polar electron-withdrawing
effect of the chlorine, which more than outweighs its small -donor effect. Another
CHAPTER 7 factor that strongly affects the reactivity of these carboxylic acid derivatives is the
−
Addition, Condensation leaving-group ability of the substituents. The order is Cl > OAr > OR > NR > O so
and Substitution 2
Reactions of Carbonyl that not only is it easier to form the tetrahedral intermediate in the order Cl > OAr >
−
Compounds OR > NR > O , but the tendency for subsequent elimination to occur is also in the
2
same order. As the two factors work together, there are large differences in reactivity
toward the nucleophiles. (See Scheme 3.3 for some specific data.)
Approximate Relative Reactivity toward
Hydrolysis
RCOCl 10 11
RCO 2 R' 1
10 −3
RCONR' 2
RCO − 2 << 1

Many carbonyl addition and substitution reactions are carried out under acidic
conditions or in the presence of Lewis acids. Qualitatively, protonation or complexation
increases the electrophilicity of the carbonyl group. The structural effects of proton-
ation have been examined for formaldehyde, acetaldehyde, acetone, formamide, and
formyl fluoride. These effects should correspond to those in more complex carbonyl
5
compounds. Protonation results in a substantial lengthening of the C=O bond. The
calculated [B3LYP/ 6-31++G(d p)] gas phase proton affinities reflect the trend of
increasing basicity with donor groups (CH NH ) and decreased basicity for fluorine.
2
3
CH 2 O CH CH O (CH ) C O H NCH O FCH O
3
3 2
2
r C O 1.209 1.214 1.219 1.219 1.186
+
r C OH + CH 2 O H CH CH O H (CH ) C O H H NCH O H FCH O H
+
+
+
+
3
2
3 2
1.252 1.270 1.282 1.294 1.252
PA in
kcal/mol 168.9 184.4 195.7 198.0 156.2
The effect of Lewis acids has also been examined computationally. In agreement
6
with crystal structure determinations, Lewis acids such as BF normally adopt an anti
3
structure for aldehydes. Despite the unfavorable steric effect in acetone, the calculated
(MP2/6-31G) energy of complexation with BF is nearly as high as for acetaldehyde,
3
presumably owing to the additional electron donation by the methyl groups. 7
F B – F B – F B –
3
3
3 + +
O + O O
C C C CH
H CH 3 H Ph CH 3 3
ΔE – 11.9 – 13.0 – 10.3
5
A. K. Chandra, M. T. Nguyen, and T. Zeegers-Huyskens, Chem. Phys., 255, 149 (2000).
6 M. T. Reetz, M. Hullmann, W. Massa, S. Berger, P. Rademacher, and P. Heymanns, J. Am. Chem. Soc.,
108, 2405 (1986).
7
B. W. Gung and M. A. Wolf, J. Org. Chem., 57, 1370 (1992).