C‐Acylierung von 5 gliedrigen N‐Heterocyclen, II. Acylierung von 1‐Acylimidazolen, Thiazolen und Oxazolen sowie Darstellung N‐unsubstituierter C‐Acylazole

Abstract

Imidazol (1) reagiert mit Säurechloriden in Gegenwart von Triethylamin zu Triacylimidazol‐inylimidazolen 5. Analog erhält man aus Benzimidazol (7) die Triacylverbindungen 8. — In 1‐Stellung unsubstituierte 2‐Acylimidazole 4 und C‐Acyl‐1,2,4‐triazole 13 werden durch Acylierung der 1‐Methoxymethylverbindungen 10 und nachträgliche Abspaltung der Methoxymethylschutzgruppe hergestellt. — Andere Azole wie Benzoxazol (14b), Benzothiazol (14c) und 2‐Phenyl‐1,3,4‐oxadiazol (14d) bilden mit Säurechloriden C‐Acylazole 15 und Carbonsäure‐diazolylmethylester 16.

Regioselectivity in the Addition of Grignard Reagents to Bis(2‐benzothiazolyl) Ketone: C‐ vs. O‐Alkylation Using Aryl Grignard Reagents

“…In light of the present findings, both the tars recovered in the reaction between 1 and phenylmagnesium halide [12] and the fact that the reaction between ptolylmagnesium bromide (4d) and ketone 1 gave carbinol 5d in only 5 % yield [15] after 36 h at 50°C could now be explained by the formation of the poorly stable O-alkylation products in high yields.…”

“…This might also explain the reported [12] recovery of a mixture of unidentified products and tars from the reaction between 1 and phenyl Grignard reagents and the isolation of the expected carbinol in only 5 % yield in the reaction between 1 and para-tolylmagnesium bromide. [15] With these considerations in mind, we decided to reinvestigate and to deepen the reaction between compound 1 and a series of ring-substituted phenyl Grignard reagents. Herein we report the results obtained, together with an efficient methodology that permits the limit imposed by O-vs. Calkylation competition to be overcome, and to obtain aryl 2-benzothiazolyl carbinols through a simple and clean procedure.…”

Current methods for the synthesis of 2-substituted azoles

“…19 1,3-Azoles readily undergo electrophilic substitution reactions. In fact, halogenation reactions are difficult to control and often result in di-or tri-halogenation.…”

“…In general, the reactions are run with an amine base for acid chlorides and are proposed to proceed via an intermediate carbene/ylide species (25). 19 Imidazoles are sufficiently nucleophilic to condense with aldehydes under thermal conditions in the presence of acid to give 2-hydroxymethylimidazoles. The reaction, however, is highly variable and substrate dependent.…”

Acetic Anhydride Generated Imidazolium Ylide in Ring Closures onto Carboxylic Acids; Part of the Synthesis of New Potential Bioreductive Antitumor Agents

“…3,4 In 1977, seminal work by Regel and Büchel established substitution of ketone and ester functionality onto the 2-position of imidazole (and benzimidazole) using imidazolium ylide species. 5,6 These reactions used various acid chlorides or chloroformic esters in the presence of triethylamine in polar solvents. Some years later, the protocol was used in the regioselective acylation of the electron-deficient position of imidazopyridines using benzoyl chloride under thermal or triethylaminemediated conditions.…”