Secondary interactions arrest the hemiaminal intermediate to invert the modus operandi of schiff base reaction: a route to benzoxazinones

TitleSecondary interactions arrest the hemiaminal intermediate to invert the modus operandi of schiff base reaction: a route to benzoxazinones
Publication TypeJournal Article
Year of Publication2017
AuthorsPatel, K, Deshmukh, SS, Bodkhe, D, Mane, M, Vanka, K, Shinde, D, Rajamohanan, PR, Nandi, S, Vaidhyanathan, R, Chikkali, SH
JournalJournal of Organic Chemistry
Volume82
Issue8
Pagination4342-4351
Date PublishedAPR
Type of ArticleArticle
Abstract

Discovered by Hugo Schiff, condensation between amine and aldehyde represents one of the most ubiquitous reactions in chemistry. This classical reaction is widely used to manufacture pharmaceuticals and fine chemicals. However, the rapid and reversible formation of Schiff base prohibits formation of alternative products, of which benzoxazinones are an important class. Therefore, manipulating the reactivity of two partners to invert the course of this reaction is an elusive target. Presented here is a synthetic strategy that regulates the sequence of Schiff base reaction via weak secondary interactions. Guided by the computational models, reaction between 2,3,4,5,6-pentafluoro-benzaldehyde with 2-amino-6methylbenzoic acid revealed quantitative (99%) formation of 5-methyl-2-(perfluoropheny01,2-dihydro-4H-benzo[d][1,3]oxazin-4-one (15). Electron donating and electron withdrawing ortho-substituents on 2-aminobenzoic acid resulted in the production of benzoxazinones 936. The mode of action was tracked using low temperature NMR, IN vis spectroscopy, and isotopic (O-18) labeling experiments. These spectroscopic mechanistic investigations revealed that the hemiaminal intermediate is arrested by the hydrogen-bonding motif to yield benzoxazinone. Thus, the mechanistic investigations and DFT calculations categorically rule out the possibility of in situ imine formation followed by ring-closing, but support instead hydrogen-bond assisted ring-closing to prodrugs. This unprecedented reaction represents an interesting and competitive alternative to metal catalyzed and classical methods of preparing benzoxazinone.

DOI10.1021/acs.joc.7b00352
Type of Journal (Indian or Foreign)

Foreign

Impact Factor (IF)

4.785

Divison category: 
Central NMR Facility
Physical and Materials Chemistry
Polymer Science & Engineering