Arylglyoxals in synthesis of heterocyclic compounds.

Recent progress in synthesis and bioactivity studies of indolizines.

Structurally diverse pyridinium salts are quite familiar structures in many natural products and bioactive pharmaceuticals. Over the centuries, these privileged scaffolds have played an intriguing role in a wide range of research topics and, thus, this review aims at highlighting the pyridinium salts in terms of their synthetic routes, reactivity and their importance as pyridinium ionic liquids, as pyridinium ylides, as anti-microbial, anti-cancer, anti-malarial and anti-cholinesterase inhibitors, as well as their applications in materials science and biological issues related to gene delivery.

Pyridinium salts: from synthesis to reactivity and applications

Indolizine (pyrrolo[1,2-a]pyridine) is one of the five isomers of indole and it serves as a precursor for widespread indolizidine alkaloids. The straightforward synthesis of indolizines based on classical methodologies such as Scholtz or Chichibabin reactions has overshadowed numerous new strategies that have been revealed especially within the last ten years. The desire to achieve substitution patterns which were hard to build sparked the discovery of completely new pathways, e.g. transition metal-catalyzed reactions and approaches based on oxidative coupling. In this review, selected strategies toward indolizines published since 2005 are briefly summarized, commented upon, compared, and illustrated. The literature discussed here involves reactions based on either pyridine or pyrrole scaffolds, as well as selected methodologies leading to π-expanded indolizines.

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Recent advances in the synthesis of indolizines and their π-expanded analogues.

Palladium-Catalyzed Annulation of Aryl Heterocycles with Strained Alkenes

Publisher Summary This chapter discusses the synthetic routes, physical properties, and reactions of indolizines. One of the synthetic routes presented is Tschitschibabin reaction involving the quaternization of a 2-substituted pyridine, normally using an α -halo carbonyl compound, followed by intramolecular cyclization of the quaternary salt with a mild base, usually aqueous sodium bicarbonate. Another route is ring closure reactions providing indolizines unsubstituted in the five-membered ring. Several physical properties including electronic spectra, acid–base properties, mass spectra, infrared spectra, nuclear magnetic resonance (NMR) spectra and X-ray diffraction are described. The most widely investigated reaction of the indolizine nucleus is electrophilic substitution. The other reactions of indolizines discussed are cyclizations, reduction, oxidation, and polymerization. Cyclization is concerned with reactions that result in the fusion of one or more additional rings to the indolizine system. Various indolizines containing vinyl groups in the pyridine ring are synthesized by polymerization reactions.

Advances in Indolizine Chemistry

Chalcone and 4-methoxychalcone react with chlorosulfonic acid to give chalcone-p-sulfonyl chloride and 4-methoxchalcone-3-sulfonyl chloride respectively. The sulfonyl chlorides were converted into 13 sulfonyl derivatives by reaction with nucleophiles. With hydrazine and phenylhydrazine the chalconesulfonyl chlorides were cyclised to the corresponding hydrazinopyrazolines. In contrast, with N,N-dimethyl-hydrazine only the dimethylsulfonohydmides were obtained, and no attack on the carbonyl group was observed. Possible reasons for this difference in behaviour are discussed, together with spectroscopic evidence for the structures proposed.

Some Reactions of Chalcone‐4‐Sulfonyl Chloride and 4‐Methoxychalcone‐3‐Sulfonyl Chloride

Cyclisation of benzils

The 13C NMR spectra of a series of 2,3-diaryl-1,3-thiazolidin-4-ones were measured and the resonance signals produced by the methylene, methine and carbonyl groups of the heterocyclic ring assigned. The variations in their chemical shifts were examined and the influence of S-oxidation was investigated. 3-Benzyl-2-phenyl-1,3-thiazolidin-4-one, 3-butyl-2-phenyl-1,3-thiazolidin-4-one and 2,3-diphenyl-5-methyl-1,3-thiazolidin-4-one were also examined, the last compound being shown to exist as a mixture of isomers. T1 relaxation times were determined for three thiazolidinones and related to structural effects.

Proton NMR investigation of some substituted 1,3‐thiazolidin‐4‐ones

Benzalacetone 1 with an excess of chlorosulfonic acid did not give the expected 4, ω-disulfonyl dichloride 2, but 4,β-dichlorosulfonylstyrene 3, which was identified by microanalytical and spectral data, and characterised as the bis-N,N-dimethylsulfonamide 4 and the bis-acetone hydrazone 5. A mechanism for the conversion of 1 into 3 is proposed.

F. J. Swinbourne

Papers

Advances in Indolizine Chemistry

Some Reactions of Chalcone‐4‐Sulfonyl Chloride and 4‐Methoxychalcone‐3‐Sulfonyl Chloride

Cyclisation of benzils

Proton NMR investigation of some substituted 1,3‐thiazolidin‐4‐ones

A novel reaction of benzalacetone with chlorosulfonic acid