Carbamate groups

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]. 

Up to this point we have discussed only carbamates la-4a with a single carbamate group on the phenyl ring as model systems for aromatic polyurethane photodecomposition. In polyurethane coatings based on the aromatic diisocyanate TDI two carbamate groups are attached to the phenyl ring. Furthermore commercially available TDI is actually a mixture of 2,4-toluene diisocyanate (2,4-TDI) and 2,6-toluene diisocyanate (2,6-TDI) which when formulated give 2,4- and 2,6-biscarbamates. Model systems for these species would then be biscarbamates of 2,4-TDI and 2,6-TDI (as shown below) and not carbamates such as la-4a. 

The use of ( )-enolcarbamates of type 1-56 allowed the generation of tetrahy-dropyrans 1-58 with complementary orientation of the carbamate functionality (Scheme 1.15). In all cases, the carbamate group adopts an axial orientation in the chairlike transition state 1-57. 

The imidazole carbamate group is more stable to hydrolysis in aqueous buffer than the NHS-carbonate group, which is similar in reactivity to an NHS ester. However, this means that the imidazole carbamate also is slower to react and couple with amines. NHS-carbonate reactions usually go to completion within 1-2 hours at room temperature, whereas imidazole carbamates typically require higher pH conditions and overnight incubations to get maximal yield of ligand coupling. 

To remove excess CDI and reaction by-products, Beauchamp et al. (1983) dialyzed against water at 4°C. However, the imidazole carbamate groups on mPEG formed during the activation process are subject to hydrolysis in aqueous environments. A better method may be to precipitate the activated mPEG with diethyl ether as in the protocol described previously for SC activation (Section 1.2, this chapter). 

Removal of the carbamate group of thiadiazolidine 65 was achieved with conventional procedures and the resulting deprotected thiadiazolidine 66 can be iV-alkylated (Scheme 6) <2004CEJ5581>. 

The phenylcarbamates of polysaccharides also separate several nonpolar aromatic compounds,141 which cannot interact with the carbamate group through polar interaction. This indicates that, besides the polar interactions,... 

The stability of Molsidomine 84 and SIN-1 85 in aqueous systems under acidic, basic, thermic and photolytic conditions was investigated by Asahi et al. [92] (Scheme 6.17). In alkaline solutions the carbamate group is hydrolysed and decarboxylated to 85. This product immediately opens to SIN-1 A 105 that, in turn, is transformed into SIN-1C 106. The authors postulated that elimination of HNO underlies this last transformation. 

Among the strategies used for the development of GST Pl-1 inhibitors is the modification of the GSH backbone to leverage its inherent affinity for GST Pl-1. One approach centered on the incorporation of a carbamate group as an isosteric replacement of the y-carboxylic Glu linkage in GSH. Synthesis and in vitro testing of 42 and 43 showed that this carbamate-replacement approach was not well tolerated [67]. 

Tsukamoto, H., Yoshimura, H. and Tatsumi, K. (1963) Metabolism of drugs. XXXV. Metabolic fate of meprobamate. (3). A new metabolic pathway of carbamate group - the formation of meprobamate N-glucuronide in animal body. Chemical S[ Pharmaceutical Bulletin, 11, 421. 

Our study has clearly shown that carbamate groups can be attached to the poly(vinyl alcohol) backbone. Further studies are in progress to ascertain whether the N-phenylcarbamoyl modified poly(vinyl alcohol) samples will show any utility as a herbicide or a drug. These modified polymers would, of course, have potential use as a new plastics or fibers but we would not expect great thermal stability from this system (63). 

N-(2-Hydroxypropyl)carbamates (8.139, Fig. 8.13,b) are prodrugs that resemble the A-(2-hydroxyphenyl)carbamates discussed above. Here, activation yielded the tranquilizer mephenoxalone (8.140, Fig. 8.13,b) and an alcohol or a phenol such as paracetamol. Other active oxazolidinones could be obtained by replacing the MeO group in 8.139 (Fig. 8.13, b) with another substituent. For this series, the mechanism of activation is not an intramolecular nucleophilic attack, but, rather, decomposition of the deprotonated carbamate group as shown in Fig. 8.7,b, Reaction b, with the intermediate isocyanate being trapped to form the oxazolidinone ring. 

Replacement of the carbamate group with isosteric functionalities such as an IV-methyl carbamate, urea, or amide group clearly confirmed the favorable qualities of the carbamate group [57], While the introduction of a urea group, as in case of iV-9-(tert-butylcarbamoyl)-9-desoxy-9-aminoquinine selector, instead of carbamate functionality turned out to be virtually equivalent in terms of enantiorecognition capabilities [57,58], the enantiomer separation potential was severely lost on iV-methylation of the carbamate group, like in 0-9-(N-me hy -N-tert-butylcarbamoyl)quinine [32,58], or its replacement by an amide, such as in case of Af-9-(pivaloyl)-9-desoxy-9-aminoquinine selector [57,58], For example, enantioselectivities dropped for DNB-alanine from 8.1 for the carbamate-type CSP, over 6.6 for thein-ea-type CSP, to 1.7 for the amide-type CSP, and 1.3 for the A -methyl... 

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