An efficient general synthesis of 1‐(benzotriazol‐1‐yl)alkyl esters

Abstract

1‐(Benzotriazol‐1‐yl)alkyl esters 2a‐u were obtained in yields averaging 86% by the direct reaction of various aldehydes with the corresponding N‐acylbenzotriazoles in the presence of a catalytic amount of potassium carbonate (10–25 mole %). The procedure was optimized by evaluating the effects of solvent, catalyst, temperature and other parameters.

Unexpected reactions of organozinc reagents with N-acylbenzotriazoles

“…The starting N-acylbenzotriazoles 4a-i (Table 1) were easily prepared by acylation of benzotriazole with acyl chlorides in the presence of a base (method A) 24 or, for acid-sensitive substrates, by the reaction of the corresponding carboxylic acid with readily available 1-benzenesulfonylbenzotriazole (method B). 25 N-Acylbenzotriazoles were unaffected by heating with Grignard reagents or organozinc reagents in the presence of an equivalent of anhydrous zinc bromide (the starting materials were recovered).…”

“…Column chromatography was carried out on silica (200-425 mesh, Fisher). N-Acylbenzotriazoles 4a-e 24 and 4f-h 25 were prepared according to the literature procedures. Benzylzinc bromide 29 and alkylzinc halides 30 were prepared by standard reaction of activated zinc dust with the corresponding halides (for the procedure of the preparation of activated zinc dust see 31).…”

Synthesis of Aliphatic Hydroxyaryl Ketones or (Hetero)aryl Hydroxyaryl Ketones by Acylation of Organometallic Reagents

“…21 N-Acylbenzotriazoles are easily prepared activated derivatives of carboxylic acids. 22 Applications of N-acylbenzotriazoles include: (i) N-acylation of amines, 23 amides, 23, 24 and sulfonamides, 25 (ii) O-acylation of aldehydes, 26 steroids, 27 hydroxyterpenes and alcohols, 28 (iii) many C-acylations of, for example, pyrroles and indoles, 29 ketones and heteroaromatics, 30 alkyl sulfones, 31 alkyl cyanides, 32 alkyl azines, 33 a-nitroalkanes, 34 furan and thiophene; 35 syntheses of (iv) peptides, 36 (v) oxazolines, 37 (vi) esters, 38 (vii) benzodioxin-4-ones, 39 (viii) ketones, 40 (ix) benzodiazepin-2-ones, 41 (x) thiol esters, 42 (xi) alcohols, 43 (xii) acyl azides and hydrazides, 44 (xiii) heteroaromatics, 45 and (xiv) heterocycles. 46 Our approach to a general method for the synthesis of a variety of ketones involved the use of N-acylbenzotriazoles as stable alternatives to the corresponding acid chlorides.…”

Selective Peptide Chain Extension at the C‐terminus of Aspartic and Glutamic Acids Utilizing N‐protected (α‐aminoacyl)benzotriazoles

“…We have applied N-acylbenzotriazoles for N-acylation (30)(31)(32)(33)(34), Cacylation (34)(35)(36)(37)(38)(39), and O-acylation (40)(41). In our previous applications to peptide synthesis, N-(Z-aminoacyl)benzotriazoles prepared from N-protected a-amino acids with unfunctionalized side chains, such as Ala, Val, and Phe; were coupled successfully with unprotected amino acids (Ala, Val, Phe, Ser, Trp) in the presence of Et 3 N in aqueous acetonitrile (42).…”