Carbamic acid anhydrides

According to this picture, the first step in the reaction between the isocyanate and water is indeed the formation of the carbamic acid which, however, has the choice of three reaction paths. It can either decompose to the amine and CO2, react with isocyanate to form the carbamic acid anhydride or combine with the amine to form a carbamate salt. In subsequent reaction steps, then, the anhydride and salt are converted to the urea by loss of CO2 and water respectively. 

A more detailed quantitative study of the water-o-tolyl isocyanate reaction by Shkapenko et al. 51) showed that at 80° in dioxane solution and in the presence of triethylamine or other catalysts the consumption of the isocyanate was complete within a short period when only approximately half of the theoretical amount of carbon dioxide was released. The evolution of carbon dioxide proceeded from this point on at a slow rate. It was also demonstrated that by heating the reaction mixture to 100°, 30-35% of theoretical CO2 was released, and that this portion of the CO2 was given off by the decomposition of the carbamic acid anhydride formed from the acid and a second molecule of isocyanate. Additional tests showed that 4-5% of the isocyanate formed o-tolyl ammonium-W-o-tolyl carbamate, 18.7% of the water added remained unreacted, and that a trace of the free o-tolyl amine was also present. In addition, the presence of di-o-tolyl urea was proven. 

Carbamic acid anhydrides from carbamyl chlorides... 

Carbalkoxyhydrazonoesters Carbamic acid anhydrides 0-Carbamylhydroxamates 1 -Hydroxylamino-1 -carbalkoxyamines Oxamhydroxamic acids Pseudonitrosites... 

N-Acyl-N -carbalkoxy-hydrazines N-Acoxyureas Allophanates (Carbalkoxyureas) Carbamic acid anhydrides... 

Carbalkoxyhydrazonoesters Carbamic acid anhydrides Carbamylhydroxamates 1-Hydroxylamino-l-carbalk-oxyamines Pseudonitrosites... 

The most important group of derivatives for the amino function (Fig. 7-4) is the carbamate group, which can be formed by reactions with acids, acid chlorides or acid anhydrides. A series of chlorides as 2-chloroisovalerylchloride [1], chrysanthe-moylchloride [2] and especially chloride compounds of terpene derivatives (cam-phanic acid chloride [3], camphor-10-sulfonyl chloride [4]) are used. The a-methoxy-a-trifluoromethylphenylacetic acid or the corresponding acid chloride introduced by Mosher in the 1970s are very useful reagents for the derivatization of amines and alcohols [5]. 

Methods of acylating pyrrole similar to the present one have been reported using oxalyl chloride,5 trifluoroacetic anhydride,6 carbamic acid chloride,7 and trichloroacetyl chloride.8 In the last preparation, it was necessary to separate the product from highly colored by-products by alumina chromatography. Pyrrol-2-yl trichloromethyl ketone has also been prepared by the interaction of pyrrolylmagnesium halide and trichloroacetyl chloride.9... 

A series of solid-state reactions has been explored by Kaupp et al., in which gaseous amines were reacted with aldehydes to give imines. Analogous reactions with solid anhydrides, imides, lactones or carbonates, and isothiocyanates were used to give, respectively, diamides or amidic carboxylic salts or imides, diamides, carbamic acids, and thioureas [24]. In general the yields were found to be quantitative. Ammonia and other gaseous amines, in particular methyl-amine, have also been shown to aminolyse thermoplastic polycarbonates [25]. 

Initially, water can cause the hydrolysis of the anhydride or the isocyanate, Scheme 28 (reaction 1 and 2), although the isocyanate hydrolysis has been reported to occur much more rapidly [99]. The hydrolyzed isocyanate (car-bamic acid) may then react further with another isocyanate to yield a urea derivative, see Scheme 28 (reaction 3). Either hydrolysis product, carbamic acid or diacid, can then react with isocyanate to form a mixed carbamic carboxylic anhydride, see Scheme 28 (reactions 4 and 5, respectively). The mixed anhydride is believed to represent the major reaction intermediate in addition to the seven-mem bered cyclic intermediate, which upon heating lose C02 to form the desired imide. The formation of the urea derivative, Scheme 28 (reaction 3), does not constitute a molecular weight limiting side-reaction, since it too has been reported to react with anhydride to form imide [100], These reactions, as a whole, would explain the reported reactivity of isocyanates with diesters of tetracarboxylic acids and with mixtures of anhydride as well as tetracarboxylic acid and tetracarboxylic acid diesters [101, 102]. In these cases, tertiary amines are also utilized to catalyze the reaction. Based on these reports, the overall reaction schematic of diisocyanates with tetracarboxylic acid derivatives can thus be illustrated in an idealized fashion as shown in Scheme 29. 

This chapter deals with the kinetics and mechanisms of the hydrolysis of carboxylic acid derivatives of general formula RCOX. These include carboxylic acid halides, amides, and anhydrides with small sections on carboxylic acid cyanides etc. Many recent developments in this field have been made with acid derivatives in which R is not an aliphatic or aromatic group, for example, carbamic acid derivatives, and these are reported where relevant, as are reactions such as ethanolysis, aminolysis, etc. where they throw light on the mechanisms of hydrolysis. 

Volume 10 is devoted to formation and solvolysis of esters and related reactions, with discussion of the effect of neighbouring groups and biological implications, e.g. enzyme action, where appropriate. The first chapter deals mainly with esters of the inorganic acids of phosphorus and sulphur, Chapter 2 with the formation and solvolysis of esters of organic acids and the final chapter with the solvolysis of related derivatives of carboxylic acids, e.g. halides, amides, anhydrides, cyanides, carbamic acid derivatives. 

If benzyl carbamate is used as the amide component in the reaction with a-oxo acids 23 then the Na-benzyloxycarbonyl-DHA 24 is obtained directly (Scheme 8). Shin and et al.[77 84l widely exploited the above method in the synthesis of various a, 3-didehydropeptides (Table 3). In presence of 3 M thionyl chloride and acetyl chloride, 24 gave the A-carboxy-DHA anhydride ANCA 25, which could be conveniently converted into dehydropeptides.[77 84 Compared with the common saturated A-carboxy-a-amino acid anhydrides (NCAs), ANCAs were found to be stable at room temperature for several months. 

As discussed in Section 11.1.1.2.3 most of the aliphatic DHAs such as AAla, AVal, ALeu, Alle, AAsp, AGlu, and AOrn have been prepared either by (3-elimination, N-chlorination/ dehydrochlorination, or from Af-carboxy a, 3-didehydroamino acid anhydrides which, in turn, are prepared by condensation of an a-oxo acid with benzyl carbamate. 

Studies of the polymerisation of alanine A-carboxylic acid anhydride with diethylzinc or triisobutylaluminium as the catalyst have revealed the relatively fast deprotonation of the monomer NH group by the metal alkyl as the first reaction step. This reaction (easily detectable by evolution of the ethane or isobutane) produces A-metallated initiating species (substituted metal carbamates) which, however, are not monomeric but undergo association via metal-heteroatom coordination bonds [75,175]. 

Another protecting group often employed for amines is the benzyloxycarbonyl group. The chemistry here is reminiscent of that of the BOC group in that the amine is protected by conversion to a carbamate. This time an acyl chloride derivative, car-bobenzoxy chloride, rather than an acid anhydride derivative, is reacted with the amine. 

As shown in Figure 5, the coupling reaction between an amino acid and an N-carboxy-a-amino acid anhydride is performed at alkaline pH but the resulting carbamate intermediate is decomposed at acidic pH in order to give the dipeptide and allow further reaction leading to polyamino acids. Polymer formation is performed most frequently at neutral pH since the half-life of the intermediate carbamate is very short (see Figure 6). 

Another way of making urethanes is to treat an alcohol or a phenol with an isocyanate, which is an anhydride of a carbamic acid. Although the carbamic acid is unstable, the... 

Acylation of triazolates is expected to occur at N-1 but transacylation by displacement of an electrophilic substituent from N-1 might be predicted to proceed by attack of the electrophile on N-4. The actual course of the reaction may be explained on the analogy of isotopic studies on imidazole (66CB2955) applied to triazole (Scheme 28) the first product of the sequence is the mixed anhydride (84) that reacts with the liberated triazole at N-1 to afford benzoyltriazole (85) and the unstable carbamic acid (86). 

Meprobamate is very stable as a solid. Meprobamate is stable in dilute acid and dilute alkali and is not broken down in gastric or intestinal fluid. It is recognized that heating solutions of meprobamate in strong acid will cause hydrolysis of the material26. it has been proposed that during treatment of meprobamate with alkaline alcohol the sodium salt of carbamic acid 7 is formed, which may undergo a dehydration to form a cyanate o. The amino moieties of the carbamate can form its diacetyl derivative with acetic anhydride, 27, and will condense with aldehydes. ... 

The compound reacts with alcohols, phenols and amines to form products similar to those obtained from the corresponding reaction with COCI [1358]. Depending upon the conditions and stoicheiometry, carbonates and chloroformates [612,1380], carbamates [1380], isocyanates [1184] and ureas [938] can be obtained with diphosgene, in addition to more complicated products such as carbamoyl chlorides, imidic chlorides, carboxylic acid chlorides, isonitriles and IV-carboxy-Q-amino acid anhydrides [1358]. 

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