Amide hydrolysis during

Reaction of 5-trichloromethyl-1,2,4-thiadiazoles with secondary amines leads to amides. For example, treatment of (84) with piperidine gives (86) which presumably arises by nucleophilic displacement of chloride ion from the trichloromethyl group, followed by hydrolysis during work up of the resulting dichloro compound (85) (Scheme 21) <86PS(26)151>. 

When k lk is larger than unity, the rate-determining step is the breakdown of the tetrahedral intermediate and the corresponding kinetic expression is k k jk. It is only in this case that an accumulation of tetrahedral intermediates would be expected to be observed experimentally. The breakdown of the tetrahedral intermediate is rate-determining in alkaline amide hydrolysis however, no reports of the detection of an addition intermediate during hydrolysis have yet appeared in the literature for this or any other system. Figure 8 illustrates the energy-reaction co-ordinate profile for various values of k jk. ... 

The process of xenobiotic metabolism contains two phases commonly known as Phase I and Phase II. The major reactions included in Phase I are oxidation, reduction, and hydrolysis, as shown in Figure 10.1. Among the representative oxidation reactions are hydroxylation, dealkylation, deamination, and sulfoxide formation, whereas reduction reactions include azo reduction and addition of hydrogen. Such reactions as splitting of ester and amide bonds are common in hydrolysis. During Phase I, a chemical may acquire a reaction group such as OH, NH2, COOH, or SH. 

Fig. 4.74. Nucleophilic catalysis during amide hydrolysis by papain.

Among substitution reactions, ester and amide hydrolysis are common, and often operate during detoxification processes. Both specific enzymatic and chemical hydrolysis may occur. Acid-catalyzed reactions may occur in the stomach and the kidney, whereas base-catalyzed reactions may be assisted by the alkaline pH of the intestine. 

The use of the transition-state analogue concept is an effective approach in the design of potent enzyme inhibitors. For the aspartyl proteases, structures that mimic the tetrahedral hydrated amide formed during the peptidic bond hydrolysis led to the preparation of compounds with very high binding affinity to the enzymes. In the... 

As an unexpected result of our investigations on the arylation of amines, a new catalysis with nickel complexes was pointed out for the aminolysis of nitriles indeed, in the reaction of the p-bromobenzonitrile with the 4-phenylpyridine in the presence of catalytic amounts of NiBr2, in addition to the expected arylamine, the amide resulting from the aminolysis of the cyano group (and subsequent hydrolysis during the work-up) was isolated (eqn. 8). 

Because bleaching compositions are usually formulated between pH 9 and 11, the hydrolysis of peptide and amide bonds and the formation of lan-thionyl residues in hair are possible side reactions during bleaching. The hydrolysis of amide groups of the residues of aspartic and glutamic acids, in addition to the formation of cysteic acid residues, will increase the ratio of acidic to basic groups in the fibers (i.e., amide hydrolysis will decrease the isoelectric and isoionic points of the fibers). 

The structure of the amine acrylates used in this study after curing is likely to be very complex and this makes it difficult, if not impossible, to evaluate clearly the nature and mechanism of the photooxidation and photoyellowing observed in these systems. The infra-red data clearly indicates the loss of amine alkyl functionality resulting in amine or amide formation. The carbonyl absorption reported previously (14,15) at 1680 cm indicates the latter. The band situated at 1612 cm l, also reported previously (14,15), may be due to imine, enamine, vinyl ether, amine or an, -unsaturated carbonyl species. If it was due to imine or enamine it would be easy to explain its loss due to hydrolysis during irradiation. 

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