Friedel-Crafts Acylation of 2(3H)-Benzoxazolone: Investigation of the Role of the Catalyst and Microwave Activation

Abstract

To study the scope and limitations of the use of complexed species of AlCl 3 in FriedelCrafts reactions, we investigated the acetylation and benzoylation of 2(3H)-benzoxazolone and 3-methyl-2(3H)-benzoxazolone varying the amide complexing agent. We replaced dimethylformamide by N-methylformamide, dimethylacetamide, pyrrolidone, N-methylpyrrolidone, tetramethylurea, and dimethylsulfoxide. However, there was no particular advantage of substituting dimethylformamide by another amide ligand. This can probably be ascribed to the fact that the complex formed between AlCl 3 and the complexing agent becomes too stable. Alternatively, a route using polyphosphoric acid and microwave activation was explored. The major advantage of running the reaction in a microwave oven was that a good yield was reached in a rather short period of time.

2(3H)-Benzoxazolone and Bioisosters as “Privileged Scaffold” in the Design of Pharmacological Probes

“…. DMF complex [21][22][23][24][25][26][27][28][29], to give 6-acyl derivatives of type 14 (Scheme 1). As a most fruitful alternative, N-acyl derivatives of type 10 can be rearranged at high temperature (160°C) in a Fries-like reaction promoted by AlCl 3 , to 6-acyl derivatives of type 15 [27] (Scheme 1).…”

Synthesis of Some Novel Benzoxazolinonylcarboxamides as Potential Anti-Inflammatory Agents

“…6-Acetyl-2(3H)-benzoxazolone derivatives were obtained as previously reported by taking advantage of the AlCl 3 -DMF complex used as a Friedel-Crafts catalyst. [18][19][20] The product of the haloform reaction was hydrolysed in basic medium to give the corresponding acid (3a). Treatment of these acids with thionyl chloride gave the intermediate acid chloride which was coupled with 2-amino-4,6-dimethylpyridine to provide the target amide (4a).…”

“…17,20 Synthesis of the 2(3H)-(benzoxazolinon-6-yl) carboxylic acid derivatives (3a, 3b); general procedure Method B: Anhydrous AlCl 3 (13.334 g, 0.10 mol), and under stirring, over 15 min dropwise anhydrous DMF (1.5 mL, 0.02 mol) were added to a 250 mL three-necked flask. When HCl evolution had subsided 2(3H)-benzoxazolone (1.351 g, 0.01 mol) was added in one portion.…”

“…benzoxazolone; general procedure 6-Acetylbenzoxazolinones (2a, 2b) and acid (3a, Method A) were prepared according to the reported method and the physical properties (m.p., IR, 1 H NMR) are in accordance with published data. 17,20 Synthesis of the 2(3H)-(benzoxazolinon-6-yl) carboxylic acid derivatives (3a, 3b); general procedure Method B: Anhydrous AlCl 3 (13.334 g, 0.10 mol), and under stirring, over 15 min dropwise anhydrous DMF (1.5 mL, 0.02 mol) were added to a 250 mL three-necked flask. When HCl evolution had subsided 2(3H)-benzoxazolone (1.351 g, 0.01 mol) was added in one portion.…”

Synthesis and Antiepileptic Activity Assessment of 5-Benzoyloxindole, a Novel Phenytoinergic Template

“…The target compound was incidentally synthesized in 1976 and its synthesis was reproduced in 2003 using a somewhat improved method. Various efforts were made to further improve access to this compound using a straightforward Friedel-Crafts benzoylation process of oxindole along with some known classical Friedel-Crafts catalysts [16,17].…”