Hydrolysis of benzamide

Hydrolysis of Benzamide. When acid amides are hydrolysed, the corresponding acid and ammonia are formed. Consequently the hydrolysis, which is extremely slow with water alone, is hastened con-... 

Scheme 1.1 Hydrolysis of benzamide. The first published example (1986) of microwave-assisted organic synthesis.

Further evidence for this mechanism is that a small but detectable amount of 180 exchange (see p. 332) has been found in the acid-catalyzed hydrolysis of benzamide.551 (180 exchange has also been detected for the base-catalyzed process,562 in accord with the Bac2 mechanism). Kinetic data have shown that three molecules of water are involved in the ratedetermining step,563 suggesting that, as in the Aac2 mechanism for ester hydrolysis (0-10), additional water molecules take part in a process such as... 

Results of Kappe el al. were consistent with these findings for scale-up of the hydrolysis of benzamide by 100-fold from 50 mg (Scheme 9.5). 

Acid hydrolysis of benzamides in water at 100° 36. Tetraphenylcyclopentadiene with methyl propiolates in phenyl- 0.12 -0.219 -0.074 0.018 p... 

A vast amount of research has shown that the Hammett relationship holds for hundreds of sets of reactions. (Ionization of 40-odd p-substituted benzoic acids, for example, is one set.) By use of just two tables—one of a constants and one of p constants— we can calculate the relative Keq s or relative rates for thousands of individual reactions. For example, from the a value for W-NO2 ( + 0.710) and the p value for ionization of benzoic acids in water at 25" (+1.000), we can calculate that Ka for m-nitrobenzoic acid is 5.13 times as big as the Ka for benzoic acid. Using the same acid-catalyzed hydrolysis of benzamides in 60% ethanol at 80° (-0.298), we can calculate that m-nitrobenzamide will be hydrolyzed only 0.615 as fast as benzamide. 

Sotomatsu, T. and Fujita, T. (1989). The Steric Effect of Ortho Substituents on the Acidic Hydrolysis of Benzamides. J. Org. Chem., 54,4443-4448. 

Independent support for this suggestion has been obtained by Swain (1961) who found a kinetic isotope effect (N14)/ (N15)< 1 in the acid hydrolysis of benzamide. This is considered to be evidence that the C—N bond is shorter in the transition state than in the ground state and rules out a direct bimolecular displacement mechanism on carbonyl carbon. 

The formation of the tetracovalent intermediate appears to be the rate-determining step. On the other hand the hydroxide ion-catalysed hydrolysis of benzamide (Bender and Ginger, 1955) is accompanied by oxygen exchange with solvent (see Table 6). In basic solution, the reaction proceeds via the symmetrical intermediate. 

The scheme is given in detail for the alkaline hydrolysis of benzamide and ethyl benzoate where Ea was found to be independent of temperature (15). The reaction may be written schematically as... 

The usual hydrolysis of benzamide takes 1 hr. However, under microwave conditions, the hydrolysis is completed in 7 min giving 99% yield of benzoic... 

Since it is known that the hydrolysis of benzamides is facilitated by sub-... 

TABLE 10.4 Comparisonofenergy consumed by microwave and oil-bath heating for the hydrolysis of benzamide in 5% sulfuric acid. 

It is now evident that the acmal rate enhancement due to intramolecular carboxylic-acid-assisted hydrolysis of phthalamic acid is °o, because for the hydrolysis of benzamide under identical experimental conditions is nearly zero. However, if one compares the for the hydrolysis of phthalamic acid... 

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