Hydrolysis of carbamates

This method of preparation of 5-aminoimidazoles remains unexplored with only one example reported. Cohen and Kirk applied their successful method of preparing 4-fluoroimidazole (via 4-aminoimidazole (25 R = H)) (73JA4619, 73JOC3647) (Section III,A,2) to 5-aminoimidazoles (96) 

During their studies on the biosynthesis of purines (57JA1511 59JBC1791, 59JBC1799), Lukens and co-workers recognized that AIR 

Attempts to isolate pure C-AIR (107) were unsuccessful due to its instability in acid solution and toward heat resulting in decarboxylation giving AIR (106) (57JA1511). Using UV spectrometry, transformation of C-AIR 

Estimates of the purity of the natural aminoribotide AIR (106) obtained by decarboxylation of C-AIR (107) have been put in the order of 30-60% [57JBC1005 66JCS(C)2270], 

By the same procedure, crystalline picrates of 5-amino- 1-cyclohexyl-2-methylimidazole (112 R = Me) (45%) [71JCS(C)1501] and 5-amino-l-(2-pyridyl) imidazole (96 R1 = pyrid-2-yl, R2 = H) (20%) [80JCS(P1)2316] were obtained from the sodium salts of the corresponding acids. 

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Attempts have been made to apply the structure-activity concept (Hansch and Leo 1995) to environmental problems, and this has been successfully applied to the rates of hydrolysis of carbamate pesticides (Wolfe et al. 1978), and of esters of chlorinated carboxylic acids (Paris et al. 1984). This has been extended to correlating rates of biotransformation with the structure of the substrates and has been illustrated with a number of single-stage reactions. Clearly, this approach can be refined with the increased understanding of the structure and function of the relevant degradative enzymes. Some examples illustrate the application of this procedure ... 

Four approaches to the synthesis of 4(5)-aminoimidazoles (25) have been described and are summarized in Scheme 1. These are (a) reduction of 4(5)-nitroimidazoles (27), (b) hydrolysis of carbamates and amides (28),... 

Fig. 7.3. Hydrolysis of carbamate esters (7.2) to carbamic acid (7.3), and spontaneous breakdown of the latter...

The potential of carbamic acid ester prodrugs (R-O-CO-NR R") is well-established by a number of studies on their stability and metabolism. Upon hydrolysis, they liberate the active agent ROH and the carbamic acid R R"N-COOH, which, being unstable, breaks down to the amine R R"NH and C02 (see also Sect. 8.7). The mechanism of HCT-catalyzed hydrolysis of carbamates, summarized in Fig. 8.7,b, is more complex than that of carbonates [153][158][159]. In the case of N,N-disubstituted carbamates (R-O-CO-NR R"), the only possible mechanism is as for carbonates (Fig. 8.7,b, Reaction a), which is, presumably, also the mechanism of enzyme-catalyzed hydrolysis for all carbamates. 

Figure 13.13 Reaction scheme for the base-catalyzed hydrolysis of carbamates when the mechanism involves a tetrahedral intermediate.

Hudson et a/.156 have shown that N,N-dialkylcarbamates decompose in strongly acidic media to carbon dioxide, olefin, alkyl halide and alcohol, the rate of reaction of the secondary esters closely following h0. This fact, together with the variation in the rate of hydrolysis of carbamates of cyclic alcohols with the ring size154, shows that these reactions involve the intermediate formation of carbonium ions. 

The rates of formation and hydrolysis of carbamates were examined by Faur-holt . A recent, but inconclusive, attempt to confirm the occurrence of ammonium carbamate as an intermediate in the hydrolysis of urea catalysed by urease has been published. Caplow has reported rates of formation and breakdown of a number of carbamates and demonstrated that their formation involves a rate law like... 

Scheme 21 Proposed decarboxylation mechanisms of 49 via oxazolidinone 48 (path A) or via sequential hydrolysis of carbamate and elimination of acetate (path B)...

In the case of hydrolysis of carbamates, the second group of compounds that we want to look at more closely, the base-catalyzed reaction plays the most important role. Regardless of the reaction mechanism, the hydrolysis of carbamates yields the alcohol (R3-OH), the amine (R1R2NH), and C02 ... 

In the case of base-catalyzed hydrolysis of carbamates, the critical question is whether one of the groups bound to the nitrogen (Rl9R2) is a hydrogen atom. This becomes obvious when comparing the kB values at 25°C of the two carbamates I and II (Williams, 1972) ... 

An alternative synthetic approach to Boc-protected l -aminoferrocene-l-carboxylic acid 40 was recently described by Rapic and co-workers, and is shown in Scheme 12.7. Hydrolysis of carbamate-ester by an equimolar amount of sodium hydroxide in aqueous ethanol gave 90% of tert-butyl l -carboxy-l-ferrocenecarbamate.52 During the synthesis the symmetrical ferrocenyl-substituted urea, dimethyl l, l -ureylenedi(l-ferrocenecarboxylate) 39 was formed as a by-product (Scheme 12.7).53 The ferrocenium molecules were conjugated through a urea linker, which upon deprotection may be used in condensation reactions. 

Amides from Esters Hydrolysis of Ureides Hydrolysis of Carbamates Hydrolysis of Carboxamides Decarboxylation ... 

Figure 8.9 Reaction scheme for the hase-catalyzed hydrolysis of carbamates.

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