Esters carbamic

Rea.ctlons, As with other tertiary alcohols, esterification with carboxyUc acids is difficult and esters are prepared with anhydrides (181), acid chlorides (182), or ketene (183). Carbamic esters may be prepared by treatment with an isocyanate (184) or with phosgene followed by ammonia or an amine (185). 

The reaction of a vinyl ether with carbon dioxide and a secondary amine gives a carbamic ester (246). 

Urea and poly(vinyl alcohol) form a polymeric carbamate ester (123—126) ... 

Reaction between poly(vinyl alcohol) and isocyanates yields substituted carbamate esters (127—134) ... 

MejSil, CHCI3 or CH3CN, 25°, 6 min, 100% yield. Me3SiI also cleaves carbamates, esters, ethers, and ketals under neutral, nonhydrolytic conditions. Some selectivity can be achieved by control of reaction conditions. 

A further development of this subject is due to Aeschlimann and Reinert, who found that in the series represented by (XLI) thedimethyl-carbamic ester (XLI R = Me) and the methylphenylcarbamic ester (XLI R = Ph) were at least as active as physostigmine in stimulating peristalsis. The miotic activity of the dimethylcarbamic ester (prostig-mine, neostigmine) is similar to that of physostigmine, that of the methylphenylcarbamic ester being weak. 

OPs or carbamate esters are potent inhibitors of both AChE and BChE. These include drugs (e.g. for AD or myasthenia gravis, MG), pesticides, insecticides and... 

Cholinesterase inhibitor (anti-cholinesterase, ChEI) is a chemical that prevents cholinesterases (ChEs) from breaking down. ACh, which consequently increases the level and duration of action of this neurotransmitter. ChEIs such as organophosphates (esters of phosphoric acid) and carbamates (esters of carbamic acid) - serve as insecticides, pesticides, warfare agents and drugs. 

Kostic et al. reported the use of various palladium(II) aqua complexes as catalysts for the hydration and alcoholysis of nitriles,435,456 decomposition of urea to carbon dioxide and ammonia, and alcoholysis of urea to ammonia and various carbamate esters.457 Labile aqua or other solvent ligands can be displaced by a substrate. In many cases, the coordinated substrate thus becomes activated toward nucleophilic addition of water or alcohols. 

Kostic et al. recently reported the use of various palladium(II) aqua complexes as catalysts for the hydration of nitriles.456 crossrefil. 34 Reactivity of coordination These complexes, some of which are shown in Figure 36, also catalyze hydrolytic cleavage of peptides, decomposition of urea to carbon dioxide and ammonia, and alcoholysis of urea to ammonia and various carbamate esters.420-424, 427,429,456,457 Qggj-jy palladium(II) aqua complexes are versatile catalysts for hydrolytic reactions. Their catalytic properties arise from the presence of labile water or other solvent ligands which can be displaced by a substrate. In many cases the coordinated substrate becomes activated toward nucleophilic additions of water/hydroxide or alcohols. New palladium(II) complexes cis-[Pd(dtod)Cl2] and c - Pd(dtod)(sol)2]2+ contain the bidentate ligand 3,6-dithiaoctane-l,8-diol (dtod) and unidentate ligands, chloride anions, or the solvent (sol) molecules. The latter complex is an efficient catalyst for the hydration and methanolysis of nitriles, reactions shown in Equation (3) 435... 

V-Ethyl carbamate esters of fenoldopam, used for treatment of acute circulatory failure, provide another example of a carbamate ester prodrug. The intrinsically short half-life and extensive first-pass metabolism of fenoldopam limit its oral administration. /V-Ethyl carbamate esters of fenoldopam provide elevated plasma fenoldopam levels and increases in the renal blood flow of significantly greater duration than when the parent compound is administered orally [30],... 

Terbutaline ethoxycarbonyloxyethyl ester, and phatalidyl ester Carbamate ester, e.g., bambuterol, a mono carbamate es- 16,17... 

Fenoldopam ter of terbutaline bis-A,A-dimcthyl carbamate Carbamate ester, e.g., A-ethyl carbamate ester 18... 

T Anders, LA Svensson. Bambuterol, a carbamate ester prodrug of terbutaline, as inhibitor of cholinesterases in human blood. Drug Metabol Dispos 16(5) 759-763,... 

Rhodium compounds have also been used as catalysts since the late 1960s and mechanistic studies date from the 1970s.534,578-582 The binuclear rhodium complex [(Ph3P)4Rh2(//-OH)2] was found to be an effective catalyst for the reductive carbonylation of nitrobenzenes to carbamate esters. Electron-withdrawing groups at the para-position enhance the reactivity of the substrate.583... 

Carbamate esters of zinc, zineb, and ziram are carcinogenic and teratogenic in animals, but this is attributed to the action of the carbamate esters and not to zinc (Elinder 1986). Results of studies with small mammals showed zinc to be cocarcinogenic with 4-nitroquinoline-N-oxide on oral cancer, and with N-ethyl-N-nitrosourea on brain cancer (Leonard and Gerber 1989). 

A more recent application of this chemistry was reported by Oestreich and Hoppe [74] and involved the enantioselective deprotonation of the enyne carbamate ester 125 with sec-butyllithium in the presence of (-)-sparteine (Scheme 2.41). Removal of the pro-S hydrogen atom led to the corresponding organolithium intermediate, which then underwent a highly enantioselective intramolecular 1,4-addition to the enyne. Protonation of the resulting allenyllithium species 126 provided a 70 30 mixture of the two diastereomeric allenes 127. 

Scheme 2.41 Enantioselective intramolecular 1,4-addition ofenyne carbamate ester 125. Bn = benzyl.

The direct conversion of alcohols and amines into carbamate esters by oxidative carbonylation is also an attractive process from an industrial point of view, since carbamates are useful intermediates for the production of polyurethanes. Many efforts have, therefore, been devoted to the development of efficient catalysts able to operate under relatively mild conditions. The reaction, when applied to amino alcohols, allows a convenient synthesis of cyclic urethanes. Several transition metal complexes, based on Pd [218— 239], Cu [240-242], Au [243,244], Os [245], Rh [237,238,246,247], Co [248], Mn [249], Ru [224,250-252], Pt [238] are able to promote the process. The formation of ureas, oxamates, or oxamides as byproducts can in some cases lower the selectivity towards carbamates. 

Primary aliphatic or aromatic amines RNH2 are converted into carbamates RNHCC Et on treatment with carbon monoxide and di-t-butyl peroxide in the presence of palladium(II) chloride and copper(II) chloride357. Carbamic esters 304 and 305 are also obtained from aliphatic amines and ortho carbonates (R30)4C358. Vinyl carbamates R12NC02CH=CHR2 are produced from secondary aliphatic amines, acetylenes R2C=CH (R2 = Bu or Ph) and carbon dioxide in the presence of ruthenium(III) chloride359. 

The analogous reaction of benzyl and butyl naphthylcarbamates and of benzyl phenylcarbamates has been carried out in good yield under both liquiddiquid and solidrliquid two-phase conditions, using benzyltriethylammonium chloride as the catalyst [16, 17]. A similarly catalysed /V-alkylation of the ethyl carbamic esters derived from 1,2-diaminobenzene is reported [17] to lead to the formation of 1,3-dialkylbenzimidazol-3-ones (Scheme 5.7). 

Fig. 7.3. Hydrolysis of carbamate esters (7.2) to carbamic acid (7.3), and spontaneous breakdown of the latter...

H. Bundgaard, A. Buur, V. H. L. Lee, Timolol Prodrugs Preparation and Hydrolysis Kinetics of A-Benzoyl Carbamate Esters of Timolol and Related Compounds , Acta Pharm. Suec. 1988, 25, 293 - 306. 

K. T. Hansen, P. Faarup, H. Bundgaard, Carbamate Ester Prodrugs of Dopaminergic Compounds Synthesis, Stability, and Bioconversion ,. /. Pharm. Sci. 1991, 80, 793-798. 

S. O. Thorberg, S. Berg, J. Lundstrom, B. Pettersson, A. Wijkstrom, D. Sanchez, P. Lind-berg, J. L. G. Nilsson, Carbamate Ester Derivatives as Potential Prodrugs of the Pre-synaptic Dopamine Autoreceptor Agonist (-)-3-(3-Hydroxyphenyl)-A-propylpiperidine J. Med. Chem. 1987, 30, 2008-2012. 

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