Yoshio Sumida

Intramolecular 1,5-cyclization of ylides : Synthesis of pyrazolo-[1,5-a]pyridines and indolizines

Abstract N-(β-Acylvinyl)iminopyridinium betaines have been shown to cyclize in refluxing toluene to produce pyrazolo[1,5-a]pyridines. This intramolecular 1,5-cyclization reaction of ylides was extended to the synthesis of indolizine derivatives.

Effects of 3-substituents upon orientation in the 1,3-dipolar cyclo-addition reaction between 3-substituted pyridine N-imides and ethyl propiolate: syntheses of ethyl 4- and 6-substituted pyrazolo[1,5-a]-pyridine-3-carboxylates

Quantitative data are presented relating to the effects of a series of 3-substituents upon orientation in the formation of ethyl pyrazolo[1,5-a]pyridine-3-carboxylates by a 1,3-dipolar cycloaddition reaction between 3-substituted pyridine N-imides and ethyl propiolate. The observed regioselectivity is discussed in terms of electronic and steric factors as well as hydrogen-bond formation.

Synthesis and thermal reaction of pyridinium 3,3-diacyl-1-benzoylallylides [3,3-diacyl-1-benzoyl-1-(1-pyridinio)prop-2-enides]: formation of indolizine derivatives

Pyridinium 3,3-diacyl-1-benzoylallylides [(IIIa–e), (IV), and (V)] are prepared by the reaction of pyridinium phenacylides with 2,2-diacyl-1-ethoxyethylenes. Refluxing compounds (IIIa), (IIIb), and (IV) in xylene provides 1-acyl-3-benzoylindolizines [(VI), (VII), and (IX)] in poor yields; similar treatment of the 2-methyl-pyridinium congeners (IIIc–e) affords 1,3-diacetyl-2-phenylindolizines [(X)–(XII)], accompanied by small amounts of 1-acetyl-3-benzoylindolizines [(VI)–(VIII)].

Synthesis of indolizines by intramolecular cyclisation of pyridinium allylides [1-(1-pyridinio)prop-2-enides]

Pyridinium ethoxycarbonyl-(3-oxocyclohexen-1-yl)methylides (VII)–(IX) and 3,3-diacyl-1-ethoxycarbonylallylides (X)–(XIII) are prepared by the reaction of 1-ethoxycarbonylmethylpyridinium bromides (III) and (IV) with 3-chlorocyclohex-2-enones and 3-ethoxymethylenepentane-2,4-dione or diethyl ethoxymethylenemalonate, respectively. Refluxing the ylides (VII)–(IX) in xylene affords the ethyl 10-oxo-7,8,9,10-tetrahydropyrido[2,1-a]isoindole-6-carboxylates (XVI)–(XVIII), and the ylides (X) and (XII) give diethyl indolizine-1,3-dicarboxylate (XIX) and ethyl 1-acetylindolizine-3-carboxylate (XX), respectively. However, similar treatment of the ylides (XI) and (XIII) affords ethyl indolizine-3-carboxylate (XXVII) and the keto-ester (XX), respectively. The mechanisms for the formation of the indolizine derivatives are discussed.

Synthesis and some properties of a new class of six membered heteroaromatic betaines, 3H-pyrido[3,2,1-ij][1,2,4]benzotriazin-4-ylium-3-ides

A series of 3H-pyrido[3,2,1-ij][1,2,4]benzotriazin-4-ylium-3-ides has been synthesised by reaction of 8-acylaminoquinolines with O-mesitylenesulphonylhydroxylamine followed by treatment with aqueous alkali. The spectral (u.v., 1H n.m.r., and 13C n.m.r. spectra) and chemical properties (bromination and 1,3-dipolar cycloaddition) of the new mesomeric betaines have been investigated.

Synthesis and thermal reaction of 2,2-diacyl-N-(1-pyridinio)vinylaminides: formation of pyrazolo[1,5-a]pyridines and isoxazoles

2,2-Diacyl-N-(1-pyridinio)vinylaminides have been prepared by the reaction of pyridine N-imides with 1,1-diacyl-2-ethoxyethylenes. Refluxing the bisethoxycarbonylvinylaminides (VIa, b, and d–f) in xylene afforded the ethyl pyrazolo[1,5-a]pyridine-3-carboxylates (Xa, b, and d–f); however the diacetylvinylaminides (IVa–c) and the acetyl(ethoxycarbonyl)vinylaminides (Va–c) are thermally labile and, upon heating in benzene, undergo N–N bond cleavage to give isoxazole derivatives [(XV) and (XVI)] in high yields.