Synthesis of Carbamate Esters

The most common industrial syntheses of carbamate esters are based on either the alcoholysis of phosgene, followed by aminolysis of the intermediate chlorofor-mate, or the reaction of an alcohol with an isocyanate, usually prepared from COCl2 [6, 7]. The development of phosgene-free routes to carbamates represents an important synthetic challenge, and several synthetic strategies are currently under investigation in this area. 

A few of these imply the carbonylation of nitroaromahc substrates [41], or the oxidative carbonylation of amines [42], or the reaction of amines with carbonic acid diesters [11] that are currently available, even on an industrial scale, through phosgene-free routes [43]. 

To date, several organic substrates have been investigated an overview of this research is presented, and its recent advances reviewed in the following sections. 

Alkyl halides have been extensively investigated as electrophilic substrates in carbamahon reactions of amines with C02. 

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Yoshida et al. were the first to report the synthesis of carbamate esters by the direct reaction of aliphatic amines, C02 and alkyl halides [47]. The process involved the O-alkylation of intermediate alkylammonium carbamate salt, and required relatively, severe conditions (333-393 K 4MPa C02), long reaction times (1-2 days) and an excess of amine (2.5 equiv.) with respect to the alkylating agent. The method was shown to be effective only with secondary aliphatic amines which, however, were converted into organic carbamates in low to moderate yield and with modest selectivity because of significant side-formation of N-alkylation products. 

Aresta and Quaranta focused on the direct synthesis of carbamate esters by the reaction of aliphatic primary amines with alkyl halides in the presence of C02. Under the conditions used (293-353 K 0.1 MPa C02 solvent = tetrahydrofuran (THF), MeOH, PhCH3/CH2Cl2 mixtures), the formation of carbamate ester was... 

Scheme 6.5 Direct synthesis of carbamate esters from primary amines, C02, and alkyl halides in the presence of 18-crown-6-ether.

One transformation that is closely related to the synthesis of carbamate esters from alcohols, amines and C02, is the formation of cyclic urethanes, such as oxazolidin-2-ones, by reaction of C02 with 1,2-amino alcohols or their formally dehydrated derivatives, aziridines. 

The synthesis of carbamic esters of 1,2-diols has been achieved by reacting oxiranes and amines in an atmosphere of carbon dioxide under various experimental conditions. ... 

The interest in the synthesis of carbamate esters [12] remains very high owing to their wide utilization [13]. The synthesis of these compounds generally uses phosgene [14] or isocyanates [15] as starting material. These are toxic, harmful compounds and, therefore, it is of interest to discover new synthetic routes to carbamate esters involving the use of less noxious starting materials. 

H. Al-Rawi and A. Williams, Elimination-Addition Mechanisms of Acyl Group Transfer the Hydrolysis and Synthesis of Carbamate Esters, J. Am. Chem. Soc., 1977, 99, 2671. 

Carbon dioxide can also form carbamates by reaction with amides of non-metallic elements [78-84, 136-144]. Most examples reported in the literature deal with amides of silicon, germanium, and phosphorus. Among these, the insertion of the heterocumulene into the P-N bond of hexaalkylphosphorus triamides P(NR2)3, which affords phosphocarbamates species of formula P(NR2)3 (02CNR2) t, has received particular attention for its potential in chemical synthesis, because this reaction opens a route to the phosgeneless synthesis of carbamate esters [138,139] and ureas [140]. 

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