Isobutyraldehyde, enamines hydrolysis

FIGURE 1. pH-rate profile for the hydrolysis of three isobutyraldehyde enamines at 24.84 °C O, morpholine (1) A, piperidine (2) , pyrrolidine (3). Reprinted with permission from Maas et al., J. Org. Chem., 32, 111. Copyright (1967) American Chemical Society1 ld... 

Recently Stamhuis et al. (33) have determined the base strengths of morpholine, piperidine, and pyrrolidine enamines of isobutyraldehyde in aqueous solutions by kinetic, potentiometric, and spectroscopic methods at 25° and found that these enamines are 200-1000 times weaker bases than the secondary amines from which they are formed and 30-200 times less basic than the corresponding saturated tertiary enamines. The baseweakening effect has been attributed to the electron-withdrawing inductive effect of the double bond and the overlap of the electron pair on the nitrogen atom with the tt electrons of the double bond. It was pointed out that the kinetic protonation in the hydrolysis of these enamines occurs at the nitrogen atom, whereas the protonation under thermodynamic control takes place at the -carbon atom, which is, however, dependent upon the pH of the solution (84,85). The measurement of base strengths of enamines in chloroform solution show that they are 10-30 times weaker bases than the secondary amines from which they are derived (4,86). 

The differenee in reaction rates of the amino alcohols to isobutyraldehyde and the secondary amine in strong acidic solutions is determined by the reactivity as well as the concentration of the intermediate zwitterions [Fig. 2, Eq. (10)]. Since several of the equilibrium constants of the foregoing reactions are unknown, an estimate of the relative concentrations of these dipolar species is difficult. As far as the reactivity is concerned, the rate of decomposition is expected to be higher, according as the basicity of the secondary amines is lower, since the necessary driving force to expel the amine will increase with increasing basicity of the secondary amine. The kinetics and mechanism of the hydrolysis of enamines demonstrate that not only resonance in the starting material is an important factor [e.g., if... 

More recently the acylation of aldehyde enamines has been reinvestigated (75) and shown to proceed normally when the enamine is added to the acid chloride. The morpholine enamine of isobutyraldehyde (98), on being added to an ether solution of acetyl chloride, afforded the iminium salt (99), from which the ketoaldehyde (100) was obtained in 66% yield by hydrolysis (75). 

Recently, Capon and Wu49 have reported the generation of secondary enamines from their TV-trimethylsilyl derivatives through hydrolysis. In DMSO-d6 (99% v/v)-D20 (1% v/v) solution, enamine 40 is converted to the TV-deuteriated enamine 41 quantitatively in 5-10 min at room temperature. The solution obtained is stable for several hours, but over a period of 2-3 days 41 is oxidized to acetone and iV-deuterio-TV-phenylforma-mide. On adding 15% (v/v) D20/DC1 (0.1 M) to the solution, enamine 41 is completely hydrolyzed to 2-[2//]isobutyraldehyde and aniline without detection of any intermediates. Enamine 42 is formed by the acid-catalyzed hydrolysis of 40 (Scheme 3). Similar results are obtained with other iV-aryl enamines. 

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