Some chemistry of chromenes and chromanones

Brogden, Peter John (1986) Some chemistry of chromenes and chromanones. Doctoral thesis, Lancashire Polytechnic.

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A range of 2-substituted, symmetrically and unsymmetrically 2,2- disubstituted and 2-spiro-annulated chroman-4-ones has been synthesised by the pyrrolidine catalysed condensation of 2-hydroxyacetophenones with aldehydes and ketones. The synthesis has been extended to yield 5-, 6, 7- and 8- substituted chromanones and the 5,6- and 7,8-benzologues.
Additional chroman-4-ones have been prepared by the Fries rearrangement of aryl 3-methylbut-2-enoates.
An n.m.r. analysis of chroman-4-ones has revealed that unsymmetrical substitution at C-2 leads to a preference for one conformer, whereas symmetrically substituted chromanones rapidly interchange between energetically equivalent conformers. Similar effects were observed with chroman-4-oximes, although some anomalous results were noted.
Reduction and dehydration of the resulting chroman-4-ols yielded the corresponding chromenes. The established synthesis of chromenes involving the rearrangement of aryl propargyl ethers has been modified such that the chromene can be prepared directly by reaction of an alkynol with a suitably activated phenol at an alumina surface, without the need to prepare the intermediate ether.
The addition of halogens and of hypobromous acid to chromenes has been examined. Increasing the size of the spiro-substituent at C-2 caused a change in the dihedral angle between 11-3 and 11-4 which was reflected in the n.m.r. spectra. Unsymmetrically 2-substituted chromenes yielded a diastereoisomeric mixture, the composition and configuration of which
were dependent on the nature of the 2-substituents.
The base catalysed dehydrobromination of 3-bromochroman-4-ols gave the 3,4-epoxychromans which were ring opened by lithium aluminium hydride and hydrogen chloride to yield the chroman-3-ols and their 4-chloro derivatives, respectively. Addition of water to the epoxides on activated alumina yielded the trans-chroman-3,4-diols; the isomeric &iadiols resulted from the permanganate oxidation of chromenes.
The reaction of halogens with chroman-4-ones has been studied. The influence of the substituents at the 2-position was again observed. Unsymmetrical 2-substitution led to the formation of separable mixtures of diastereoisomers, the composition of which was dependent on the size of the 2-substituents.
Metal hydride reduction of 3-bromochroman-4-ones gave complex mixtures of products, the major component being the -bromochromanol. Debromination was observed at higher temperatures. Dehydrobromination of the j-bromohydrins gave chroman-4-ones in contrast to the epoxides which resulted from the trans-bromohydrins.
The generation of metal enolates from chroman-4-ones has been achieved by reaction with lithium diisopropylamide. The lithium enolates have been trapped as their silyl enol ethers by reaction with trimethylstlyl chloride. Alkylation at C-3 occurred on reaction with iodomethane and whilst the reaction with acetyl chloride resulted in 0-acylation, Cacylation
occurred with benzoyl chloride. Formylation at C-3 resulted on treatment of a chroman-4-one with ethyl formate and sodium ethoxide, although the product exists exclusively as the 3-hydroxymethylene tautomer.

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