Current Organic Chemistry - Volume 22, Issue 26, 2018

Although, numerous antimicrobial agents have been reported by the scientists to control fungal and bacterial diseases, but due to less cost effectiveness, non-availability and environmental hazardous of existing antimicrobial agents, there is still a need to synthesize new class of antimicrobial agents to control microbes effectively. Coumarin, a heterocyclic compound containing oxygen in its scaffold, acts as a building block for large number of biologically active compounds and is known to possess variety of biological activities viz. antiviral, antimicrobial, anticonvulsant, anticancer analgesic and antiinflammatory. This review mainly focuses on various methods related to synthesis of coumarin derivatives and its biological activity as antimicrobial.

Biaryls are a key structural motif in compounds with various applications, ranging from pharmaceuticals to material science, including ligands for organic synthesis. Given the growing concern about the use of transition metals in organic synthesis in terms of reaction condition mildness, substituents tolerance, reagents costs and toxicity, and purification of the products from metal traces, several alternatives have been developed to overcome the limitations of metal-catalyzed biaryls synthesis. Herein, we review the transition metal-free approaches to biaryls, which can be divided into metal-free crosscoupling of aromatics and metal-free benzannulation of aryl-substituted chains, as both fields have shown an impressive growth in recent years.

Heterocycles are cyclic compounds with one or more heteroatom in their structures. They have various pharmaceutical applications. Incorporation of ferrocene scaffold into heterocyclic compounds can change the chemical and physiochemical properties of compounds. Ferrocene derivatives have a significant importance in pharmaceutical sciences like antibacterial, anticancer, antifungal, antiparasitic drug candidates, etc. Multicomponent reactions lead to simple and rapid procedures for the synthesis of organic compounds with molecular diversity. Multicomponent reactions have been used widely in heterocyclic synthesis, pharmaceutical chemistry, natural product synthesis, combinatorial chemistry, and polymer chemistry in the past two decades. This review deals with the synthesis of ferrocene-based heterocycles by multicomponent reactions.

Background and Objective: Continuing our research in the field of heterocyclic compounds and exploiting our experience in the synthesis of pyridothieno(furo)[3,2- d]pyrimidine derivatives decorated by suitable reactive groups (in turn able to give rise to the formation of new heterocyclic rings), we now carried out a research with the aim of building in different position of the pyrimidine some new hetero-rings: the 1,3,4-triazole, thiazole and thiazine. Moreover their possible antimicrobial activity against some grampositive and gram-negative bacilli strains has been evaluated. Methods: Starting from the hydrazino derivative of pyrido[3',2':4,5]thieno(furo)[3,2- d]pyrimidines 2 (7) by reflux with triethyl orthoformate or formic acid, some substituted isomeric pyrido[3',2':4,5]thieno(furo)[2,3-e][1,2,4]triazolopyrimidines 3 and 4 (10) have been synthesized. By alkylation of compounds 8 with alkyl dichlorides, the cyclization to a thiazoline or to a thiazine ring on the [a] side of the pyrimidine ring occurs, with the formation of the new pentacyclic systems: pyrido[3',2':4,5]thieno[ 3,2-d][1,3]thiazolo[3,2-a]pyrimidin-7(8)-one 15 and pyrido[3'',2'':4',5']furo(thieno)[3',2':4,5]pyrimido[2,1- b][1,3]thiazin-7(8)-ones 16. Results: 11-Alkyl(aryl)-8,8-dimethyl-7,10-dihydro-8H-pyrano[4'',3'':4',5']pyrido[3',2':4,5]thieno[2,3-e][1,2,4] triazolo[4,3-c]pyrimidines 3 gave a Dimroth rearrangement in acidic media. It was observed that the cyclization of compounds 7 and 8 occurred linearly with the expected formation of pyrido[3',2':4,5]thieno(furo)[3,2- d][1,2,4]triazolo[4,3-a]pyrimidin-7(8)-ones 10 and pyrido[3',2':4,5]thieno[3,2-d][1,3]thiazolo[3,2-a]pyrimidin- 7(8)-one 15 and pyrido[3'',2'':4',5']furo(thieno)[3',2':4,5]pyrimido[2,1-b][1,3]thiazin-7(8)-ones 16: that is triazole, thiazole and thiazine ring condensation occurs at the [b] side of the pyrimidine ring. During the alkylation of compounds 7, the unusual cleavage of the hydrazino group took place with the formation of 8(9)- methylpyrido[3',2':4,5]thieno(furo)[3,2-d]pyrimidin-7(8)-ones 12. Conclusion: The synthesis of some new ‘complex’ pentaheterocyclic systems containing triazolopyrimidine, thiazolo[3,2-a]pyrimidine and pyrimido[2,1-b]thiazine moiety based on the pyrido[3',2':4,5]thieno(furo)[3,2- d]pyrimidines is described. During the alkylation of 9(10)-hydrazinopyrido[3',2':4,5]thieno(furo)[3,2- d]pyrimidin-7(8)-ones 7 an unexpected cleavage of the hydrazino group has been observed with the formation of 8(9)-methylpyrido[3',2':4,5]thieno(furo)[3,2-d]pyrimidin-7(8)-ones 12. Biological tests on the newly synthesized compounds evidenced that some of them showed promising antimicrobial activity.

A series of chiral imidazolium salts derived from natural amino acids has been obtained. The synthetic route involves a multicomponent condensation reaction between the corresponding amino acid {(S)-methionine, (S)-threonine, (S)-phenylalanine, (S)- valine and (S)-alanine} in acidic medium and ammonium acetate, glyoxal and formaldehyde in aqueous solution at 95°C to form an imidazole ring in one pot. The imidazole carboxylic acids [{R1-CH-CO2H}Im] (R1 = CH2CH2SCH3, CH(OH)CH3, CH2Ph, CH(CH3)2, CH3) (1a-e) were converted into sodium carboxylate compounds to carry out the esterification and N-alkylation of imidazole with an excess of the suitable alkyl halide in acetonitrile to give rise to a series of chiral imidazolium salts [{R1-CH-CO2R2}ImR2][X] (R1 = CH2CH2SCH3, CH(OH)CH3, CH2Ph, CH(CH3)2, and CH3; R2 = CH3, CH2CH3, X = I, Br) (2a-e and 3a-e). Characterization of all of compounds by IR, HR-MS, 1H and 13C{1H} NMR confirmed the proposed structures. The molecular structure of the imidazole carboxylic acid 1c (spatial group P21) as a zwitterion, was obtained by single-crystal X-ray diffraction study, showing that the chiral center is preserved.