Imidates, hydrolysis

Another alternative for preparing a primary amine from an alkyl halide is the Gabriel amine synthesis, which uses a phthalimide alkylation. An imide (—CONHCO—) is similar to a /3-keto ester in that the acidic N-H hydrogen is flanked by two carbonyl groups. Thus, imides are deprotonated by such bases as KOH, and the resultant anions are readily alkylated in a reaction similar to the acetoacetic ester synthesis (Section 22.7). Basic hydrolysis of the N-alkylated imide then yields a primary amine product. The imide hydrolysis step is analogous to the hydrolysis of an amide (Section 21.7). 

The hydrolytic stability of water soluble poly[N-(4-sulfo-phenyDdimethacrylamide] (PSPDM) was studied at 90 C in aqueous solutions at pH 7, pH 1.2 (0.1M HC1), and pH 12.3 (0.1M NaOH). PSPDM, which possesses predominantly 5-mem-bered ring imides, was prepared by the cyclopolymerization and subsequent sulfonation of N-phenyldimethacrylamide. No detectable PSPDM imide hydrolysis occurred after 30 days at pH 7 or pH 1.2. Under basic conditions, however, complete hydrolysis to amic acid occurred after one day. The resulting Nsubstituted amide was extremely stable to further basic hydrolysis. 

An example of imide hydrolysis occurs with the cyclic imide-containing API glutethimide (Fig. 14). The mechanism proposed involves direct attack by a hydroxyl ion on the unhindered carbonyl followed by ring cleavage (30). 

Figure 15 Imide hydrolysis of phenobarbital in basic conditions.

A15.1.1.9 Imides. Compounds that have two acyl groups bonded to a single nitrogen are known as imides (R—CO—NH—CO—R ). The most common imides are cyclic ones (maleimide). Maleimide will convert to maleic acid under water and acid/base. Another example of imide hydrolysis is pheno-barbital in which phenobarbital (a cyclic imide) is hydrolyzed to form urea and a-ethylbenzeneacetic acid. 

IR spectroscopy may be used to follow two reactions occurring in polyimides exposed to high temperatures and humidities hydrolysis of the imide linkages and hydrolysis of residual anhydride end groups. The hydrolytic susceptibilities of several polyimides were measured at 90°C/95% R.H. Polymers based on benzophenone tetracarboxylic acid dianhydride (with either oxydianiline or m-phenylene diamine) appeared to undergo rather rapid hydrolysis initially, but the reaction had essentially halted by the time the measured imide content had decreased by 5-6%. Polymers based on 3,3 ,4,4 -biphenyl tetracarboxylic acid dianhydride (with p-phenylene diamine) and pyromellitic dianhydride (with oxydianiline) showed no significant imide hydrolysis. In all the polymers, the anhydride was hydrolyzed quite readily. 

The data for PMDA-ODA shown in Figure 4 indicate a much lower susceptibility to imide hydrolysis. Here, the measured hydrolysis after 400 h is only 1% based on the initial ratios. The sample cured to 4000 C appears to... 

The results given above indicate that, despite some variations in rate, anhydride end groups can all be classed as quite readily hydrolyzed. In contrast, the hydrolytic susceptibility of imide linkages varies much more with the polymer examined. BPDA-PDA showed no measurable imide hydrolysis whatsoever. In PMDA-ODA the amount of hydrolysis observed was small enough that we cannot eliminate the possibility that impurities in the anhydride component, rather than PMDA itself, resulted in the formation of hydrolyzable material. Of the polymers studied here, only those that contained BTDA as the anhydride component showed a marked susceptibility to imide hydrolysis. Even in this case, the data suggest that the reaction is limited in that only about 6-7% of the imide linkages appear to be susceptible to hydrolysis. 

Second, the samples of the BTDA-containing polymers cured to high temperatures appear to undergo imide hydrolysis somewhat more slowly. The differences obtained under the hydrolysis conditions used here are relatively small, but they could translate to significant differences in the time required to reach a given degree of hydrolysis among samples exposed to lower temperatures and/or humidities. 

In their subsequent report, Raymond et al. used the encapsulated gold complex, Au-Ga4L5, in combination with enzymes, esterases, or lipases in a one-pot tandem reaction sequence. Enzymatic ester/imide hydrolysis of allenic ester or amide results in an intermediate [27], which subsequently undergoes... 

Liotta, L.J., Benkovic, P.A., Miller, G.P., Benkovic, S.J. Catalytic antibody for imide hydrolysis featuring a bifimctional transition-state mimic. J. Am. Chem. Soc. 1993, 775(1), 350-351. 

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