Advances in Organic Synthesis: Volume 13

Atta-ur-Rahman

• Publisher: Bentham Science Publishers
• Year: 2020
• ISBN:
  9789811405099
• Topic: Naturwissenschaften
• Subtopic: Organische Chemie

Advances in Organic Synthesis is abook series devoted to the latest advances in synthetic approaches towardschallenging structures. The series presents comprehensive reviews written byeminent authorities on different synthetic approaches to selected targetmolecules and new methods developed to achieve specific synthetictransformations or optimal product yields. Advances in Organic Synthesisis essential for all organic chemists in academia and the industry who wish tokeep abreast of rapid and important developments in the field. This volume presents the following reviews: Electroluminescent polymers - a review on synthesis from organic compoundsRemarkable advances in the asymmetric synthesis of biologically active natural compounds from the advent of chiral auxiliariesThe chemistry of ynamides and their application in organic synthesisCarbon-heteroatom bond formation for medium ring heterocyclesTin(ii) salts: versatile and efficient lewis acid catalysts in reactions to add value to the glycerol and terpenic alcohols(E)-n-methyl-1-(methylthio)-2-nitroethenamine (nmsm) as a versatile ambiphilic synthon in organic synthesis

(E)-N-Methyl-1-(Methylthio)-2-Nitroethenamine (Nmsm) as a Versatile Ambiphilic Synthon in Organic Synthesis

Pedavenkatagari Narayana Reddy^{1, *}, Pannala Padmaja^{2, *}

¹ Department of Chemistry, School of Science, Gitam University, Hyderabad, India

² Centre for Semio Chemicals, CSIR-Indian Institute of Chemical Technology, Hyderabad, India

Abstract

(E)-N-methyl-1-(methylthio)-2-nitroethenamine (NMSM) 1 is a versatile molecule that contains four active sites with three functional groups on an ethane motif. NMSM as a precursor reactant has been widely applied in the diversity-oriented synthesis of various heterocyclic motifs, bis-heterocyclic, fused heterocyclic and spirocyclic scaffolds. These privileged scaffolds were synthesized via numerous types of reactions, such as Michael addition, 1,3-dipolar cycloaddition, heteroannulation reaction and also many cascade reactions via multi-component reactions. Moreover, the flexibility and high reactivity of NMSM as a versatile ambiphilic synthon signify it as a suitable building block in medicinal chemistry and bulk drug synthesis. In the present book chapter, we focused on the advances in the chemistry of NMSM as an effective reagent in organic synthesis.

Keywords: Ambiphilic synthon, Bulk drugs, Bis-heterocyclic compounds, (E)-N-methyl-1-(methylthio)-2-nitroethenamine, Fused heterocyclic compounds, Multi-component reactions, Nitroketene N,S-acetal, One-pot reactions, Spirocyclic compounds.

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^* Corresponding author Pedavenkatagari Narayana Reddy: Department of Chemistry, School of Science, Gitam University, Hyderabad, India; Tel: [phone]; E-mail: [email protected]

INTRODUCTION

Ambiphilic synthons, which bear both nucleophilic and electrophilic sites, have great potential in developing new synthetic routes in organic synthesis. Ketene acetals are versatile ambiphilic synthons, which bear electron-withdrawing and electron-releasing substituents, lead to inimitable structural features and earned great interest to synthetic chemists due to their significance as useful starting materials in organic chemistry [1^-5].

Among them, nitroketene N, S-acetal, (E)-N-methyl-1-(methylthio)-2-nitroethena-mine (1N-methyl-1S-methyl-2-nitroethylene) (NMSM) 1 is a two-carbon synthon that contains four active sites with three functional groups on an ethane motif (Fig. 1) [6^-8].

The three functional groups on the ethylene moiety include nitro, methylsfulfany and methylamino, each one of which is suitable for synthetic utility and functional group manipulation. With a strong electron-withdrawing nitro group, the nitroethylene substructure in NMSM is a good Michael acceptor. The methylsulfanyl group is a good leaving group and also an electron donor. It can be substituted with a range of nucleophiles following the nucleophilic vinylic substitution (S_NV) mechanism. The methylamino group in NMSM acts as an electron donor and thus is a good Michael donor. The ethylene moiety is a polarized push–pull alkene and due to polarization, C2 exhibits nucleophilic characteristics and C1 exhibits electrophilic characteristics. These features of NMSM make it highly adaptable and simple to use in the Michael addition, annulations, cyclization and multicomponent reactions.

Fig.(1))
The reaction profile of NMSM.

NMSM is a synthetic equivalent of nitroacetic acid and glycine. It is also used in industrial scale for the synthesis of anti-ulcer bulk drugs ranitidine [9, 10] and nizatidine [11]. NMSM participates in several commonly known reactions, such as heteroannulation reaction, 1,3-dipolar cycloaddition, Michael addition, and also several cascade reactions, to afford novel N-, O- and S-containing heterocycles with high regio- and stereoselectivities [12]. These qualities make NMSM a multi-faceted building block and utilized as a starting material for the construction of a variety of heterocycles. In the present book chapter, we demonstrate the chemistry of NMSM in terms of reactivity pattern, and applications in the synthesis of a range of heterocycles.

Preparation of NMSM

The key starting material in the preparation of NMSM is 1,1-bis(methylthio)-2-nitroethylene 2. This can be synthesized by the addition of the nitromethane anion to CS₂ and methylation to give 1,1-bis(methylthio)-2-nitroethylene 2 [13^-15]. The preparation of NMSM involves an amination of 1,1-bis(methylthio)-2-nitroethylene 2 or of the correspo...