Synthesis 2009(11): 1935-1940  
DOI: 10.1055/s-0029-1216795
PSP
© Georg Thieme Verlag Stuttgart ˙ New York

One-Pot Curtius Rearrangement Processes from Carboxylic Acids

Olivier Leogane, Hélène Lebel*
Département de chimie, Université de Montréal, Montréal H3C 3J7, Québec, Canada
Fax: +1(514)3437586; e-Mail: [email protected];
Further Information

Publication History

Received 8 January 2009
Publication Date:
12 May 2009 (online)

Abstract

An efficient and practical synthesis of amine derivatives from carboxylic acids is described using new one-pot Curtius rearrangement processes. The preparation of carbamate-protected amines and anilines, as well as ureas was achieved in good to excellent yields on a multigram scale.

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8

When the reaction was run at 66 ˚C, the yields for compounds 9 and 13 decreased to 48% and 40%, respectively. The remaining product was the corresponding tert-butyl ester.

9

Lower yields (15-40%) were obtained with other solvents, such as Et2O, dioxane, DMSO, and CH2Cl2. This process is not compatible with protic solvents.

11

79% of unsubstituted Boc-aniline was obtained under these reaction conditions. However, functional groups such as methyl ether, thiomethyl ether, nitro, and halides were not tolerated, and the corresponding anilines were isolated in less than 25% yield.

12

A control experiment was run with chloroformate, NaN3, and carboxylic acid at r.t., which showed the formation of acyl azide, suggesting that the base is not essential for the formation of this intermediate. The base is probably involved in the formation of the carbamate from the isocyanate, by trapping the proton of the nucleophile.

15

The chloroformate reagent must be stored in a refrigerator prior to use.