Synthesis and Antimicrobial Activity of Some New Pyrimidinone and Oxazinone Derivatives Fused with Thiophene Rings Using 2-Chloro-6-ethoxy-4-acetylpyridine as Starting Material

Aisha Hossan,Mohamed Al-Omar,Abd Amr,Hanaa Abu-Melha

doi:10.3390/molecules171113642

Aisha Hossan, Mohamed Al-Omar + Show 2 more

Open Access

https://doi.org/10.3390/molecules171113642

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Abstract

A series of pyridines, pyrimidinones, oxazinones and their derivatives were synthesized as antimicrobial agents using citrazinic acid (2,6-dihydroxyisonicotinic acid) as a starting material. α,β-Unsaturated ketones 3a–c were condensed with cyanothio-acetamide in the presence of ammonium acetate to give 2-cyanopyridinethiones 4a–c, which were reacted with ethyl chloroacetate to yield the corresponding cyano esters 5a–c. The esters 5a–c were cyclized by action of sodium methoxide to aminoesters 6a–c, which were aminolyzed with ammonia to corresponding aminoamide derivatives 7a-c. Also, the esters 6a–c were hydrolyzed with NaOH to the corresponding sodium salt 8a–c, which were treated with acetic anhydride to afford 2-methyloxazinones 9a–c. The latter compounds were treated with ammonium acetate to afford 2-methylpyrimidinones 10a–c, followed by methylation with methyl iodide to yield 2,3-dimethyl-pyrimidinones 11a–c. The antimicrobial screening showed that many of these compounds have good antibacterial and antifungal activities comparable to streptomycin and fusidic acid used as reference drugs.

Highlights

In previous work, we have found that certain substituted pyridines and their derivatives showed antimicrobial, analgesic, anticonvulsant, antiparkinsonian [1,2,3,4] and antitumor activities [5,6,7].In addition, the biological and analgesic activities of many heterocyclic compounds containing a sulfur atom have been reviewed [8,9,10]
Some new oxazinones, thienopyrimidinones and their derivatives have been synthesized as anti-inflammatory, antimicrobial and anti-HIV agents [14,15,16,17,18]. In view of these observations and in continuation of our previous work in pyridine chemistry, we have synthesized some novel heterocyclic compounds containing the thieno[2,3-b]pyridine moiety fused with a pyridine, oxazinone, or pyrimidinone, nucleus and tested their antimicrobial activities
The IR spectra of 6a–c showed the absence of ν (C N) for 5a–c and the presence of broad band corresponding to ν (NH2)

Summary

Introduction

We have found that certain substituted pyridines and their derivatives showed antimicrobial, analgesic, anticonvulsant, antiparkinsonian [1,2,3,4] and antitumor activities [5,6,7]. Some new oxazinones, thienopyrimidinones and their derivatives have been synthesized as anti-inflammatory, antimicrobial and anti-HIV agents [14,15,16,17,18]. In view of these observations and in continuation of our previous work in pyridine chemistry, we have synthesized some novel heterocyclic compounds containing the thieno[2,3-b]pyridine moiety fused with a pyridine, oxazinone, or pyrimidinone, nucleus and tested their antimicrobial activities

Synthesis

Antimicrobial Activity

Chemistry

Antimicrobial Screening Media

Conclusions