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Reaction of gamma-Hydroxy-N-[1-(dimethylcarbamoyl)ethyl]butanamides under the ‘Direct Amide Cyclization’ Conditions


Iliev, Boyan; Linden, Anthony; Heimgartner, Heinz (2006). Reaction of gamma-Hydroxy-N-[1-(dimethylcarbamoyl)ethyl]butanamides under the ‘Direct Amide Cyclization’ Conditions. Helvetica Chimica Acta, 89(1):153-175.

Abstract

The preparation of the title compounds was achieved via the ‘azirine/oxazolone method’ starting from the corresponding gamma-hydroxy acids. Upon subjecting the gamma-hydroxy-N-[1-(dimethylcarbamoyl)-
ethyl]butanamides 4 to the so-called ‘direct amide cyclization’ (DAC) conditions, chlorinated acids 11 or imino lactones 12 were obtained as the sole products instead of the expected cyclodepsipeptides A or their cyclodimers (Scheme 4). Variation of the substituents in 4 did not affect the outcome of the reaction and a mechanism for the formation of both products from the intermediate oxazolone 13 has been proposed. Under the acidic conditions of the DAC, the imino lactones are formed as their HCl salts 12,
which, in polar solvents or on silica gel, reacted further to give the chlorinated acids 11. Stabilization of the imino lactones was achieved by increasing the substitution in the five-membered ring, and their structure, in the form of the hydrochlorides, was established independently by X-ray crystallography (Fig. 4). A derivative 15 of the imino lactone 12a was prepared by the reaction with the 2H-azirin-3-amine 10a; its structure was also established by an X-ray crystal-structure determination (Fig. 3). Furthermore, the structures of the omega-chloro acids 11a and 11b were determined by X-ray crystallography (Fig. 2).

Abstract

The preparation of the title compounds was achieved via the ‘azirine/oxazolone method’ starting from the corresponding gamma-hydroxy acids. Upon subjecting the gamma-hydroxy-N-[1-(dimethylcarbamoyl)-
ethyl]butanamides 4 to the so-called ‘direct amide cyclization’ (DAC) conditions, chlorinated acids 11 or imino lactones 12 were obtained as the sole products instead of the expected cyclodepsipeptides A or their cyclodimers (Scheme 4). Variation of the substituents in 4 did not affect the outcome of the reaction and a mechanism for the formation of both products from the intermediate oxazolone 13 has been proposed. Under the acidic conditions of the DAC, the imino lactones are formed as their HCl salts 12,
which, in polar solvents or on silica gel, reacted further to give the chlorinated acids 11. Stabilization of the imino lactones was achieved by increasing the substitution in the five-membered ring, and their structure, in the form of the hydrochlorides, was established independently by X-ray crystallography (Fig. 4). A derivative 15 of the imino lactone 12a was prepared by the reaction with the 2H-azirin-3-amine 10a; its structure was also established by an X-ray crystal-structure determination (Fig. 3). Furthermore, the structures of the omega-chloro acids 11a and 11b were determined by X-ray crystallography (Fig. 2).

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Language:English
Date:2006
Deposited On:22 May 2012 07:13
Last Modified:05 Apr 2016 15:47
Publisher:Verlag Helvetica Chimica Acta
ISSN:0018-019X
Funders:Swiss National Science Foundation , F. Hoffmann-La Roche AG, Basel
Publisher DOI:https://doi.org/10.1002/hlca.200690008

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