Urethans carboxylic acid azide

Peptide synthesis. In the above-mentioned synthesis of urethanes the carboxylic acid azide may be the intermediate, and this possibility prompted the Japanese chemists to investigate the usefulness of diphcnylphosphoryl azide in peptide synthesis. Indeed the reagent allows coupling of acylamino acids or peptides with amino acid esters or peptide esters in the presence of a base in high yield and with practically no racemiza-tion. The new method is compatible with various functional groups. 

Amines from carboxylic acid azides via urethans... 

Urethans from carboxylic acid azides at low temp. 

Without additional reagents Urethans from carboxylic acids via carboxylic acid chlorides, carboxylic acid azides, and isocyanates Shortened Curtins degradation... 

Benzyl urethans from carboxylic acid azides... 

Without additional reagents N-Cyclols from cyclolcarboxylic acid azides Urethans from carboxylic acid azides Retention of configuration in Curtins degradation... 

Early attempts to prepare 5-amino- and 5-acylaminobenzofuroxans by hypochlorite oxidation of the corresponding o-nitroanilines met with failure. Pyrolysis of the appropriate azide, however, gives 5-dimetliylamino- and 5-acetamidobenzofuroxan, whereas urethans of type (33) are produced by Curtius degradation of the 5-carboxylic acid. Controlled hydrolysis of the acetamido compound and the... 

A total synthesis of O-methylarnottianamide (223) was performed by Falck et al. (177) (Scheme 34). The regio- and stereospecific cycloaddition of the 2,4-dinitrophenyl (DNP) salt of 6,7-methylenedioxyisoquinoline (218) with a-methoxystyrene 219 resulted in 220. Compound 220 was hydrolyzed, then aromatized, and the resultant aldehyde was oxidized to carboxylic acid 221. Curtius rearrangement of the appropriate azide yielded urethane 222, which... 

In a direct route from carboxylic acids to acyl azides diphenyl phosphorazidate is used probably the reaction passes through a cyclic transition state (Scheme 41). With aromatic and heteroaromatic educts, yields as high as 75% may be obtained. If aliphatic acids are treated under the same conditions, the corresponding azides are, however, immediately transformed into urethanes via isocyanates. Aroyl azides can also be obtained in excellent yields by reaction of carboxylic acids with NaNa and phenyl di-chlorophosphate in the presence of tetrabutylammonium bromide or pyridine (Scheme 41). ... 

N-1 substituted carboxylic acids 201 (R = Me, = Me, X = O) are transformed into carboxylic azides 203 with 1-methylethyl chloroformate and sodium azide in DMSO (Scheme 77). Curtius rearrangement of 203 at room temperature yields isocyanates 204 that further react with nucleophiles such as ethanol to furnish urethanes 205 (75S405, 92T5473). 

Carboxylic acids are converted to Curtius-rearranged urethanes in one pot using diphenylphosphoryl azide (DPPA, 68), triethylamine, and an alcohol. ... 

Diphenylphosphoryl azide (DPPA) and triethylamine were formerly employed by Yamada and co-workers in a simple one-pot synthesis of urethanes from carboxylic adds [250]. This procedure involved treatment of a carboxylic acid with triethylamine to produce the triethylammonium carboxylate salt, followed by heating in the presence of DPPA to yield the isocyanate via a Curtius-type rearrangement of the acyl azide. An alcohol was then introduced, functionalizing the isocyanate in situ to yield the urethane. 

Diphenyl phosphoryl azide triethylamine Urethans from carboxylic acids Simplified Curtius degradation... 

Diphenyl phosphoryl azide in dimethylformamide followed by triethylamine added at or below 0° to a soln. of N-carbobenzoxy-L-leucyl-L-leucine and L-valyl-L-phenylalanine methyl ester hydrochloride in the same solvent, stirred several hrs. at the above temp, and overnight at room temp. -> product. Y 87%. - Practically no racemization occurred. F. e., also direct prepn. of urethans from carboxylic acids (cf. Synth. Meth. 17, 393) by a simplified Curtius degradation, s. T. Shioiri, K. Ninomiya, and S. Yamada, Am. Soc. 94, 6203 (1972) Tetrah. Let. 1973, 2343 synthesis of N-subst. carboxylic acid amides and peptides with diethyl phosphoryl cyanide s. Tetrah. Let. 1973, 1595 coupling reagents in peptide synthesis, review, s. Y. S. Klausner and M. Bodansky, Synthesis 1972, 453 review of peptide synthesis s. J. Meienhofer, Chem. Technol. 3, 242 (1973). 

The use of azides of carboxylic acids for the preparation of urethanes has practically the same advantages and disadvantages as the use of isocyanates. m-Nitrobenzazide is used mostly, liberating nitrogen on heating at 100 (toluene, xylene, and ligroin are used as solvents), forming m-nitrophenylisocyanate as an intermediary product, which reacts immediately with alcohols, with the formation of urethanes ... 

General. Diphenyl phosphorazidate is a readily available, nonexplosive, and relatively stable azide widely used as a reagent in peptide synthesis, " and as a versatile reagent in a wide array of organic transformations. DPPA has been successfully utilized in the synthesis of a-amino acids and o-aryl carboxylic acids direct preparation of thiol esters from carboxylic acids and thiols the stereospecific preparation of alkyl azides and the phosphorylation of alcohols and amines The application of DPPA in a modified Curtius reaction permits a simple one-step conversion of carboxylic acids to urethanes under mild reaction conditions. DPPA acts as a nitrene source, and can undergo 1,3-dipolar cycloaddition reactions. The Curtius degradation of carboxylic acids in the presence of f-butanol gives the Boc-protected amine directly (eq 1). 

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