Carbamate and ring

Cleavage of the carbamate and ring closure are also achieved in a single step... 

Formulae (1.6) and (1.7) show other functions which present problems of classification. The former has a group which may be regarded as either a ureide or a carboxamide, and is classified as a carboxamide in this book. Since it is the ester group of (1.7) that reacts in the second example, the conversion is classified under carbamate and ring-nitrogen (Chapter 61). 

Carbamate and ring-nitrogen Torm a fused triazole ring when an ethoxycarbonyihydrazinoazine is heated in diphenyl ether. 

Five approaches to the synthesis of 5-amino-4-unsubstituted imidazoles (96) have been described and are summarized in Scheme 9. These are (a) reduction of 5-nitroimidazoles (97), (b) hydrolysis of carbamates and amides (98), (c) decarboxylation of imidazole carboxylic acids (99), (,d) ring transformations of 5-aminothiazoles (100), and (e) cyclisation of nitrile derivatives (101). 

The reaction of azetidines with dinitrogen pentoxide is found to reflect the reduced ring strain in this system compared to aziridines.Accordingly, while the carbamate and V-alkyl... 

BuLi-TMEDA , are similarly powerful directors (Scheme 54). By contrast, the related amides, carbamates and ureas (125, R = COAr, CONR2, CO2R) usually undergo ben-zylic a-lithiation (see Section II.B). The bias can be shifted towards ortholithiation by additional electron-withdrawing substituents on the ring . 

Carboxy substituted diazepines 226 and 229 react with phenyl isocyanate to afford pyrimido diones 227 and 230, correspondingly (Scheme 48, Section 3.1.1.3 (1993JHC897)). N-Hydroxymethylation on an indole ring annulated to benzaze-pinone, as well as formation of the corresponding carbamate and urea, has been described (2004MI1076). 

The nature of the aromatic substituents is apparently not critical for SSRI activity, as indicated by the structure of duloxetine (23-5), where one ring is replaced by thiophene and the other by naphthalene. The synthesis starts as above by the formation of the Mannich base (23-1) from 1-acetyl thiophene with formaldehyde and dimethyl-amine. Treatment of that intermediate with the complex from lithium aluminum hydride and the 2R,3S entantiomer of dimethylamino-l,2-diphenyl-3-methyl-butane-2-ol gives the S isomer (23-2) in high enantiomeric excess. Treatment of the aUcoxide from (23-2) and sodium hydride with 1-fluoronaphthalene leads to the displacement of halogen and thus the formation of ether (23-2). The surplus methyl group is then removed by yet another variant of the von Braun reaction that avoids the use of a base for saponifying the intermediate urethane. Thus, reaction of (23-3) with trichloroethyl formate leads to the A -demethylated chlorinated urethane (23-4). Treatment of that intermediate with zinc leads to a loss of the carbamate and the formation of the free secondary amine duloxetine (23-5) [23]. 

A variety of alkaloid skeletons can be prepared from 5-exo cyclizations of aminium cation radicals derived from PTOC carbamates, and some are listed in Table VI (90T2329). Perhydroindoles (entry 1), 1-, 2-, and 3-substituted pyrrolizidines (entry 2-4), tropanes (entry 5), and other pyrrolidine containing ring systems were obtained in 50-96% yields. Direct com-... 

Generally, hydrocarbons tethered with sulfamate esters or carbamates are suitable substrates and afford five- or six-membered ring products through intramolecular C-H amidation. For reasons not yet understood, carbamates and sulfamate esters prefer to form five- and six-membered rings, respectively. In general, this important and useful selectivity can avoid formation of product mixtures, a major drawback for similar organic transformations. 

The important commercial compound (/ )-pantolactone is formed in high yield and ee from the bis-carbamate 417 after carboxylation and lactonisation.178 Attempts to quench the organolithium with Me3SiCl failed instead the silyl chloride acted as a Lewis acid, promoting displacement of the second carbamate and leading to the cyclopropane 420.162>179 Further functionalisation of the cyclopropane was possible by stereospecific alkylation of the ring. 

Toxicity has been demonstrated in analogues of pyrrolizidine alkaloids with a pyrrole or dihydropyrrole ring. The vascular changes in the lungs of rats after intravenous injection of pyrrole carbamates have been reported.60 The distribution of radioactivity in rats given tritium-labelled synthanecine A (16) bis-N-ethyl-carbamate and bis-hydroxymethyl-l-methylpyrrole has been studied.61 Biliary excretion is important for the disposal of pyrrolic metabolites from retrorsine and synthanecine A bis-N-ethylcarbamate, but not for the parent compounds.62... 

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