Roger L. Snowden

Esters of furan-, thiophen-, and N-methylpyrrole-2-carboxylic acids. Bromination of methyl furan-2-carboxylate, furan-2-carbaldehyde, and thiophen-2-carbaldehyde in the presence of aluminium chloride

Convenient routes from readily available starting materials to furan- and thiophen-2-carboxylic acids with substituents (mainly halogen atoms) at various positions are described. A series of esters (methyl, ethyl, t-butyl, and 17-oxo-5α-androstan-3β-yl) have been prepared from these acids and from the unsubstituted heterocyclic 2-carb-oxylic acids.Methyl furan-2-carboxylate reacts with bromine in the presence of aluminium chloride to give the 4,5-dibromo-ester. The presence of 1,2-dichloroethane changes the course of the reaction, the product then being the 4-bromo-5-chloro-ester. Furan-2-carbaldehyde shows the opposite behaviour, giving as the main products the 4-bromo-5-chloro-aldehyde in the absence of a solvent and the 4,5-dibromoaldehyde when 1,2-dichloroethane is present. Careful control of conditions is necessary in the preparation of 4-bromothiophen-2-carbaldehyde from thiophen-2-carbaldehyde, bromine, and aluminium chloride.

Preparation of thiophen esters by the Hinsberg reaction

The Hinsberg reaction (interaction between an α-diketone and a dialkyl thiodiacetate) has been used to prepare a series of 3,4-disubstituted thiophen-2-carboxylates and -2,5-dicarboxylates.

Preparation of deuteriated furan- and thiophen-2-carbaldehydes and -2-carboxylic esters

Methods have been developed for introducing deuterium at some or all of the furan and thiophen ring positions. The compounds prepared include all the mono-, di-, and tri-deuteriofuran-2-carbaldehydes and -2-carboxylic acids, 5-deuteriofuran-2-[2H]carbaldehyde, and the monodeuteriothiophen-2-carbaldehydes. Furyl- and thienyl-lithium compounds are the key intermediates for replacing hydrogen or halogen atoms by deuterium, and for carrying out selective reactions at the α- or β-positions of the heterocyclic rings.

Preparation of the ‘fixed conformation esters’ 4,5-dihydrofuro- and 4,5-dihydrothieno-[2,3-c]pyran-7-one

The title compounds, required as models in spectrometric work, have been synthesised by a six-stage route from 3-bromofuran-2-carbaldehyde diethyl acetal and the corresponding thiophen acetal.

The infrared bands of thiophen-2-carbaldehydes in the carbonyl region : multiple absorption caused by Fermi resonance

Thiophen-2-carbaldehyde and 19 related aldehydes have been examined under high resolution in the i.r. CO region. It has been established that the multiple absorptions shown by many of the aldehydes are caused by Fermi resonance. Deuteriation of an aldehyde may lead to an increase in the complexity of its spectrum; bromination is also often effective in diagnosing the occurence of Fermi resonance.

Infrared carbonyl absorptions of 2-oxofurans: fermi resonance versus rotational isomerism as the cause of carbonyl band doubling in furan-2-carbaldehyde and related aldehydes

43 2-Oxofurans have been examined at high resoultion in the i.r. CO region. The CO doublets observed for furan-2-carbaldehyde (and six related aldehydes) originate in Fermi resonance and not rotational isomerism: the CO stretching bands of the two rotational isomers in these systems must have almost exactly equal wave-numbers.

Convenient preparations of deuterium-substituted furan-, thiophen-, and N-methylpyrrole-2-carboxylic acids, and of tetradeuteriofuran

Deuterium-substituted furan-, thiophen-, and N-methylpyrrole-2-carboxylic acids are conveniently prepared by heating the corresponding protio-acids with sodium deuterioxide in deuterium oxide; the 3,4,5-trideuteriofuran-2-carboxylic acid so obtained is readily converted into tetradeuteriofuran.

Preparation of substituted furan- and thiophen-2-carbaldehydes and -2-[2H]carbaldehydes, and of 2-furyl ketones

A series of heterocyclic 2-carbaldehydes and 2-[2H]carbaldehydes have been prepared, most of them by Vilsmeier formylation of mono- and di-substituted furans and thiophens. Isopropylation of methyl furan-2-carboxylate was used to obtain the 4- and 5-monoisopropyl- and 4,5-di-isopropyl-furan-2-carboxylic acids. With different aryl 2-furyl ketones bromine may attack either the benzenoid ring or the heterocyclic ring preferentially.

Regioselectivity and control in alkene formation from a carbonium ion after diphenylphosphinoyl migration

Conversion of 2-hydroxyalkyldiphenylphosphine oxides into allylphosphine oxides by acid-catalysed diphenyl-phosphinoyl migration shows complete regioselectivity in favour of the more substituted olefin when the migration origin is unsymmetrical. The other, less substituted olefin is formed exclusively when a trimethylsilyl group is present on the appropriate carbon atom as it both increases the rate of the rearrangement and is lost in preference to a proton. The allylphosphine oxides are used in diene synthesis.

Investigation of rotational isomerism in thiophen- and furan-2-carbonyl halides by nuclear magnetic resonance and infrared spectrometry

The possible occurrence of rotational isomerism in 35 thiophen- and furan-2-carbonyl fluorides and chlorides has been investigated by n.m.r. and i.r. spectrometry. At room temperature, solutions of the fluorides in trichlorofluoromethane, carbon tetrachloride, and acetonitrile contain appreciable amounts of the syn- and anti-rotamers. With furan-2-carbonyl fluoride, the compound investigated in most detail, the rotamer giving the higher field 19F signal in non-polar solvents at low temperature corresponds to the rotamer of the 5-deuterio-analogue which has the higher wavenumber CO band; these are the predominant forms (ca. 70% in trichiorofluoromethane) and are thought to be the syn-rotamers. It is probable that the chlorides also exhibit rotational isomerism, but the absence of halogen n.m.r. evidence makes the interpretation less certain.