Carbamic carboxylic anhydrides

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. 

Carbamic carboxylic anhydrides, such as 3,5-diamino-6-chloro-pyrazine-carboxylic N,N-diphenylcarbamic anhydride, and their viny-... 

Acyl hydroxamates Acylurethans Carbamic carboxylic anhydrides (25)... 

N-(Acoxy)acylamines N-Acylamide acetals 1 -Acylamino-l-peroxides Acyl hydroxamates Acylurethans Carbamic carboxylic anhydrides... 

Carboxyhydroxylamines N-Carbalkoxyiminoesters Carbalkoxyisocyanates N-Carbalkoxylactams Carbamic carboxylic anhydrides Cyanoorthoformic acid esters a-Hydroperoxyoximes N-Hydroxydicarboxylic acid imides... 

Carbamic carboxylic anhydrides from N-carbamylpyridinium salts... 

Carbamic carboxylic anhydrides from carboxylic acids and isocyanates... 

At ambient temperature, the reaction of metal N,N-dialkylcarbamates with acyl halides, R C(0)C1, or acetic anhydride, yields a carbamic-carboxylic mixed anhydride (Equation 6.4) which, on occasion, may undergo decarboxylation and convert into the corresponding amide R2NC(0)R [2]. 

The reaction of metal N-alkylcarbamates M(C)2CN 11 R) (M = Na, Mn(II), Co(II) R = Ph, Pr, Cy) with R C(0)C1 (R = Me, Ph) takes place, at ambient temperature, in a more complex way with the formation of isocyanates (RNCO), carboxylic anhydrides (R C(0)0C(0)CR ), amides (RNHC(O)R ) and C02. Amide formation and the evolution of C02 can be due to (i) the decomposition of mixed anhydride RNHC(0)0C(0)R obtained by addition of the acyl chloride to the oxygen atom of the carbamate group or (ii) the direct reaction of acyl chloride at the carbamic nitrogen atom of M(02CNHR) . The mixed anhydride RNHC(O) 0C(0)R might also decompose via another route so as to afford isocyanate and carboxylic acid. However, a different pathway (Scheme 6.6) has been also envisaged for the formation of RNCO and R C(0)0C(0)CR, which excludes any intermediacy of the mixed anhydride [61a], Two acetic acid molecules, bound to the same metal or to different metal centers, would then be dehydrated and acetic... 

Another method used to remove phosgene substitutes from the desired products is to destroy them with appropriate nucleophiles such as water or alcohols. This method can, of course, only be applied when the product is insensitive to these nucleophiles, as is the case for carbamates, carbonates, ureas, cyanides, isocyanides, and alkyl chlorides. Chloroformates, carbamoyl chlorides, isocyanates, acyl chlorides, N-carboxylic anhydrides, and carbodiimides, on the other hand, cannot be purified by this method. Consequently, a synthesis of these compounds using phosgene is worthy of consideration. 

Acylation. Reaction conditions employed to acylate an aminophenol (using acetic anhydride in alkaU or pyridine, acetyl chloride and pyridine in toluene, or ketene in ethanol) usually lead to involvement of the amino function. If an excess of reagent is used, however, especially with 2-aminophenol, 0,A/-diacylated products are formed. Aminophenol carboxylates (0-acylated aminophenols) normally are prepared by the reduction of the corresponding nitrophenyl carboxylates, which is of particular importance with the 4-aminophenol derivatives. A migration of the acyl group from the O to the N position is known to occur for some 2- and 4-aminophenol acylated products. Whereas ethyl 4-aminophenyl carbonate is relatively stable in dilute acid, the 2-derivative has been shown to rearrange slowly to give ethyl 2-hydroxyphenyl carbamate [35580-89-3] (26). 

A number of nonnatural amino acids were resolved into individual enantiomers on 0-9-(2,6-diisopropylphenylcarbamoyl)quinine-based CSPby Peter and coworkers [48,90,113,114] after derivatization with Sanger s reagent, chloroformates (DNZ-Cl, FMOC-Cl, Z-Cl), Boc-anhydride, or acyl chlorides (DNB-Cl, Ac-Cl, Bz-Cl). For example, the four stereoisomers of P-methylphenylalanine, P-methyltyrosine, P-methyltryptophan, and P-methyl-l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid could be conveniently resolved as various A-derivatives [113]. The applicability spectrum of cinchonan carbamate CSPs comprises also P-amino carboxylic acid derivatives, which were, for example, investigated by Peter et al. [114]. A common trend in terms of elution order of DNP-derivatized P-amino acids was obeyed in the latter study On the utilized quinine carbamate-based CSP, the elution order was S before R for 2-aminobutyric acid, while it was R before S for the 3-amino acids having branched R substituents such as wo-butyl, iec-butyl, tert-butyl, cyclohexyl, or phenyl residues. 

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]. 

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. 

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]. 

TABLE 4.20 Shift Position of the C—O Group and other Carbon Atoms of Carboxylic Acids. Esters, Lactones, Chlorides Anhydrides, Carbamates, and Nitriles (ppm from TMS)... 

The amino group in Z-Ala is protected as the nonnucleophilic amide half of a carbamate ester. The carboxyl group can be activated without reacting with the protected amino group. Treatment with ethyl chloroformate converts the carboxyl group to a mixed anhydride of the amino acid and carbonic acid. It is strongly activated toward nucleophilic attack. 

Table 4.16 Shift Positions for the C=0 group and other carbon atoms of carboxylic acids, esters, Icatones, chlorides, anhydrides, amides, carbamates, and nitriles (ppm from TMS)...

Mixed anhydrides. Mixed carbamic anhydrides can be prepared in aqueous solution by treatment of a carboxylic acid with the reagent and triethylamine ... 

The reaction of a dicarboxylic acid and a diisocyanate (or diisothiocyanate) first produces a mixed carboxylic—carbamic anhydride which decomposes on heating, losing carbon dioxide [115]... 

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]. 

In those Instances where coupling Is observed In basic salt-initiated polymerizations (66) It may be explained by reaction of a portion of the Initiator with the 2-carbonyl of an NCA. This would generate a carboxylic acid salt that can react with an NCA to yield a carbamate Ion that contains a carboxylic acid anhydride function. 

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