Carbamates production

Attempts have been made to develop methods for the production of aromatic isocyanates without the use of phosgene. None of these processes is currently in commercial use. Processes based on the reaction of carbon monoxide with aromatic nitro compounds have been examined extensively (23,27,76). The reductive carbonylation of 2,4-dinitrotoluene [121 -14-2] to toluene 2,4-diaLkylcarbamates is reported to occur in high yield at reaction temperatures of 140—180°C under 6900 kPa (1000 psi) of carbon monoxide. The resultant carbamate product distribution is noted to be a strong function of the alcohol used. Mitsui-Toatsu and Arco have disclosed a two-step reductive carbonylation process based on a cost effective selenium catalyst (22,23). 

Carbamate, RNHCOOR, produced from carbonylation pathways can be selectively converted to isocyanate (1.4). Carbonylation pathways offer a number of advantages (i) the environmentally benign nature of the reactants, (ii) the high selectivity of the reaction processes, (iii) the stability and low toxicity of carbamate products and (iv) the wide range of applications of carbamate as chemical feedstock. 

Hazardous waste management system carbamate production identification and listing of hazardous waste and CERCLA hazardous substance designation and reportable quantities (proposed rule-40 CFR 261, Appendix VIII) Proposed to include hexane as a hazardous constituent in K156 waste 59 FR 9808 EPA 1994f... 

EPA. 1995e. Hazadous waste management system carbamate production identification and listing quantities. Final Rule. U.S. Environmental Protection Agency. Federal Register. 60 FR 7824. February 9, 1995. 

NMR Carbamate Product (300 MHz, CDCI3 Solvent, Reference SiMe4)... 

Allylic substitution with free carbamate nucleophiles was not accomplished until advanced catalyst precursors were developed. However, products from substitution with carbamate nucleophiles were generated by a decarboxylative allylation. In this process, the imidodicarbonate was shown to undergo decarboxylation to form the carbamate nucleophile, and reaction of the resulting carbamate with the 7i-allyliridium intermediate formed branched allylic carbamate products (Scheme 17) [92, 95]. 

The A -benzyl group of the pyrrolidine 137 is cleaved with ethyl chloroformate to give the carbamate product 138 (Equation 37) <20030BC2111>. 

An interesting variant of cationic-resin capture has recently been reported wherein a strongly acidic cation exchange resin mediated sequential amine deprotection and resin capture (Scheme 6).78 Protected aminoalco-hols were reacted with an excess of isocyanates to form /V-BOC-amine carbamates in solution phase. Methanol was subsequently added to quench excess isocyanates as the neutral methyl carbamate byproducts. Sulfonic acid resin 51 was then used to affect amine-BOC group deprotection and resin capture of the deprotected amines. Washing of the resin bed and release (ammonia/methanol) afforded purified amine carbamate products. 

Scheme 6.2 illustrates the pathway proposed by Danckwerts for the conversion of amines and C02 into alkylammonium carbamates [28a]. The mechanism implies the intermediate formation of a zwitterion species which, by deprotonation, converts into the carbamate product. This reaction pathway has been doubted by Crooks, who proposed a termolecular single-step mechanism [28b], Borowiak and coworkers [28c] have modeled the reaction of dimethylamine with C02 in the presence of a second molecule of amine, obtaining an activation enthalpy (40 kj moT1) which was in good agreement with the experimental value. The reaction product was described as the H-bond-stabilized adduct of dimethylcarbamic acid with dimethylamine. 

The reaction in Equation 6.6 involves, as the key step, the O-methoxycarbonylation of carbamate anion to give a carbamic-carbonic mixed anhydride, RNHC(0)0C(0) OMe (Equation 6.7) [62d], which, under the working conditions, undergoes a very rapid decarboxylation and is converted into the carbamate product (Equation 6.8). 

The synthons of oxiranes have also been used in this respect. For example, the reaction of C02 with a-bromoacylophenones in the presence of aliphatic primary amines, in methanol, afforded 3-alkyl-4-hydroxyoxazolidin-2-one derivatives under mild conditions [83a]. However, neither oc-bromoacetophenone nor a-chloroacetophenone afforded any carbamate product, and no urethanes were obtained with aromatic or aliphatic secondary amines. The proposed mechanism involved, as the first step, the formation of a 3-alkyl-2-methoxy-2-phenyloxirane intermediate, which reacted with alkylammonium carbamate to give the oxazo-lidone product (Scheme 6.16). This synthetic protocol was successfully applied to the synthesis of bis(oxazolidin-2-one) derivatives by reactions of 2-methoxy-3,3-dimethyl-2-phenyloxirane or a-bromoisobutyrophenone with C02 and aliphatic a,G)-diamines [83b],... 

It is clear that BOA detoxification, mainly via glucoside carbamate production of the species tested, is not a feature of certain plant families but is rather combined with their occurrence in defined plant communities where benzoxazinone containing character species exist with high density covers. Plantago major is regarded as an exception. 

The presence and tentative location of these hydrogen atoms was based upon the lack of a terminal vT1 H vibration in the infrared spectrum and also on the reactivity of 37 with CH3I or HC1. Furthermore, when 37 is treated with C02, an intense vN H vibration appears in the IR spectrum of the resulting carbamate product. 

Also, in this case, research results indicate the need for caution in the selection of starter cultures for MLF in wine, since citrulline formation from arginine degradation could result in ethyl carbamate production, even at normal temperatures, during prolonged storage. In addition, spontaneous MLF by undeflned strains should be avoided, as this may lead to formation of ethyl carbamate precursors (Liu etal. 1994). 

In subsequent steps the initial carbamate product is further hydrolyzed to bicarbonate. Jack bean urease is a hexamer containing two nickel ions per monomeric subunit. It is unusually difficult to remove the metal atoms from the protein, requiring low pH and resulting in irreversible inactivation of the enzyme. There are indications that one nickel ion is more tightly bound than the other and, therefore, that the two sites are inequivalent. 

Hazardous Waste Management System Carbamate Production Identification and Listing of Hazardous Waste and CERCLA Hazardous Substance Designation and Reportable Quantities (notice of proposed rulemaking-K157 waste)... 

Carbamate production i denti fi cati on and listing of hazardous waste oral and inhalation toxicity information for waste constituents (Notice of proposed rulemaking)... 

Dimethoxybenzoin (DMB) carbonates (39) were found to be photochemically removable alcohol protecting groups. DMB carbonates can be installedby the carbamate product (38) of DMB-OH (37) and iV,iV -carbonyldiimidazole activated by methylation (eqs 32 and 33). ... 

Figure 9.20 A wine yeast has been genetically engineered to reduce ethyl carbamate production during fermentation. Through increased expression of DUR1/DUR2, this yeast breaks down urea to ammonia and CO2 before it is able to react with ethanol.

Proton shift then gives the benzyloxy carbamate product. 

Synthesis. " (15)-(-i-)-10-Cairphorsulfonyl chloride and its enantiomer continue to serve as building blocks for a number of useful chiral auxiliaries. For exarr5>le, in an effort to develop a chiral version of Lessen reaction as a vehicle to desymmetrize ynesohydroxamic acids, the camphorsulfomyl group was introduced as both an activator and a chiral director. Methanolysis of camphorsulfonate ester 41 derived from the norbomene-fused N-hydroxamic acid 40 led to the formation of the carbamate product in 84% yield and modest ee (33%) (eq 15). ... 

Activation of the carboxylic acid as the acyl chloride permits direct reaction with azide anion to form the acyl azide substrates for Curtius rearrangement. Sodium azide is commonly used, and the reaction has been used on the process chemistry scale for the synthesis of benzyl-A-vinyl carbamate. Acryloyl chloride was combined with sodium azide in a biphasic system with phase-transfer catalysis (PTC), providing acyl azide 25. Upon heating, Curtius rearrangement provided vinyl isocyanate, which was distilled directly into benzyl alcohol containing phenothiazine (27) to inhibit polymerization of 26 and triethylamine to catalyze addition of the alcohol to the isocyanate. The vinyl carbamate product 28 was isolated by crystallization. As the autiior clearly pointed out, preparation and reaction of acyl azides, particularly on large scales, require appropriate safety precautions. 

Interesting studies on carbamate product formation, with a view to enhancing the nucleophilic nature of the oxygen center of the carbanion anion and to ascertain the factors that govern the reactivity of various carbamates in the Sn2 reactions, have been reported [286]. High yield conversion of carbamate anions into the corresponding isocyanates is observed under the extremely mild conditions employed (1 atm CO2, 0-25 °C, <1 h). Symmetric urea formation can be readily inhibited through appropriate manipulation of the reaction conditions. 

---