Alan O. Fitton

Synthesis of 2-substituted chromones, chromanones, and their thio analogues using organocopper reagents

Improved use of organocopper reagents provides a general route to unsymmetrical 2,2-dialkylchomanones and thiochromanones from chromones and thiochromones via a simple addition - oxidation - addition sequence

Transformation of 3-formylchromones into pyridines and pyrroles

Abstract Interaction of 3-formylchromones with ethyl aminoethanoate provides a novel route to pyridines and pyrroles.

A unique trimolecular Michael reaction and cyclization

Abstract 1,3-Diaryl-2-propene-1-ones react with ethyl cyanoacetate in presence of sodium ethoxide at room temperature to give 2-aroyl-1,3,5-triaryl-4-carbethoxy-4-cyanocyclohexanols. The structure of the reaction products was established by infrared, H-1 and C-13 nuclear magnetic resonance spectral data as well as elemental analysis. X-ray crystallography shows the presence of the cyclohexanol moeity.

A reinvestigation of the Pictet–Gams isoquinoline synthesis. Part 1. The consequences of oxazoline rather than isoquinoline formation

Cyclisation of various 2-acylamino-1-arylalkan-1-ols under typical Pictet–Gams conditions yields Δ2-oxazolines and not isoquinolines as previously reported. Compounds originally formulated as isoquinolines and isoquinoline hydrochlorides are shown to be derivatives of 2-amino-1-phenylalkan-1-ols, and to have arisen through ringcleavage of the Δ2-oxazolines during the isolation procedure. Their mode of formation is fully explained.

Reactions of formylchromone derivatives. Part 1. Cycloadditions to 2- and 3-(aryliminomethyl)chromones

The reactions of several 2- and 3-(aryliminomethyl)chromones with various chloroketens have been investigated. Whereas the 2-substituted chromones gave 2-(4-oxoazetidin-2-yl)chromones, the 3-substituted chromones yielded fused pyridone derivatives.

Reactions of formylchromone derivatives. Part 5. Transformations of 3-formylchromones into pyrroles and pyridines

4-Oxo-4H-1-benzopyran-3-carbaldehyde (3-formylchromone)(1) was treated with various bi-functional nucleophiles. With ethyl aminoethanoate it gave a mixture of ethyl 4-(2-hydroxybenzoyl)-6-(4-oxo-4H-1-benzopyran-3-yl)pyridine-2-carboxylate (2) and ethyl 4-(2-hydroxybenzoyl)pyrrole-2-carboxylate (3) whereas with 2-aminoethanonitrile, only the pyridine, 2-cyano-4-(2-hydroxybenzoyl)-6-(4-oxo-4H-1-benzopyran-3-yl)pyridine (7) was obtained. Ethyl 2-aminopropanoate or ethyl 2-amino-2-phenylethanoate both gave the same pyrrole, 4-(2-hydroxybenzoyl)-2-(4-oxo-4H-l-benzopyran-3-yl)pyrrole (8). and N-methylethanoic acid yielded 3-(2-hydroxybenzoyl)-N-methyl-pyrrole (9). Corresponding products were usually obtained when various substituted 3-formylchromones were used in the reactions. Mechanistic pathways are proposed to account for all the products and the pyridine structure was confirmed by degradation.

Reactions of formylchromone derivatives. Part 2. Addition reactions of 3-(aryliminomethyl)chromones

Whereas chromones are usually cleaved by amines. 3-(aryliminomethyl)chromones undergo nucleophilic addition with aromatic primary amines to give 2-amino-3-(arylaminomethylene)chroman-4-one derivatives. The 3-(aryliminomethyl) group also facilitates addition to the system of a variety of alcohols and thiols, and certain thiol adducts can be cyclised to thiazepine derivatives. The action of manganese dioxide on 3-(aryliminomethyl)chromones leads to 3-(arylaminomethylene)chroman-2,4-diones.

Further observations on the cyclisation of 2-benzamido-1-phenylpropan-1-ol

The formation of threo-2-benzamido-1-phenylpropan-1-ol from attempted cyclisation of its erythro-isomer is explained. In place of the expected 3-methyl-1-phenylisoquinoline, cyclisation yields 4-methyl-2,5-diphenyl-Δ2-oxazoline. Attempted isolation of the product via hydrochloride salt formation results in ring opening and eventual formation of threo-2-benzamido-1-phenylpropan-1-ol via a three-stage process.

Observations on the mechanism of the Pictet-Gams reaction

N-Acyl derivatives of 2-amino-I-phenylpropan-1-ol cyclise either to oxazolines or isoquinolines and since the oxazolines are readily converted into isoquinolines, their intermediacy in the Pictet–Gams reaction is postulated.