Page 669 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

5
−1
aqueous solution. For example, the values for acetone (4 7 × 10 M ), 3-pentanone 651
−1
−1
4
5
(7 7 × 10 M ), and cyclopentanone (4 0 × 10 M ) have been measured. 24 Tradi-
tionally, the additional stability was attributed to the participation of the atom adjacent SECTION 7.3
to the nitrogen in delocalized bonding. Condensation Reactions
of Aldehydes and
Ketones with Nitrogen
: – + : – + Nucleophiles
R C N OH R C N OH R C N NH 2 R C N NH 2
2
2
2
2
:
∗
However, analysis based on HF/6-31G computations suggests that reduction of the
lone pair repulsions that are present in hydroxylamine and hydrazine reactants may be
more important. 25
The formation of oximes and hydrazones is usually catalyzed by both general
acids and general bases. The acid-catalyzed addition step can be depicted as concerted
proton transfer and nucleophilic addition. 26
H R H R
X N: C O H A X N + C O H + A –
R
H X = OH, NH , NHR' H R
2
General base catalysis of dehydration of the tetrahedral intermediate involves nitrogen
deprotonation concerted with elimination of hydroxide ion. 27
OH
fast
R C O + H NX R CHNHX
2
2
2
OH
slow
+
R CHNHX + B: R C NX + B H + – OH
2
2
X = OH, NH , NHR'
2
General acid catalysis of the breakdown of the carbinolamine intermediate occurs by
assistance of the expulsion of water.
H
+
R C O R C NR' + H O + A –
2
2
2
H A
:N H
H R'
As with imines, the identity of the rate-limiting step changes with solution pH.
As the pH decreases, the rate of addition decreases because protonation of the amino
compound reduces the concentration of the nucleophilic unprotonated form. Thus,
while the dehydration step is normally rate determining in neutral and basic solutions,
addition becomes rate determining in acidic solutions. Figure 7.8 shows the pH-rate
profiles for oximation of benzaldeyhyde and acetone. The acetone profile shows a
region from pH 8 to 10 that is pH independent and corresponds to catalysis by
water. The profile for benzaldehyde shows only a very slight contribution from a
pH-independent reaction.
24
J. Hine, J. P. Zeigler, and M. Johnston, J. Org. Chem., 44, 3540 (1979).
25 K. B. Wiberg and R. Glaser, J. Am. Chem. Soc., 114, 841 (1992).
26 C. G. Swain and J. C. Worosz, Tetrahedron Lett., 3199 (1965).
27
W. P. Jencks, Prog. Phys. Org. Chem., 2, 63 (1964); J. M. Sayer, M. Peskin, and W. P. Jencks, J. Am.
Chem. Soc., 95, 4277 (1973).