Reaction Gives Heterocyclics, Carbocyclics Compounds made so far by general route include 3,4-chromene, 2,5-dihydro-2,3-dimethylfuran, and nitrogen heterocyclics A general reaction for synthesizing heterocyclic and carbocyclic ring compounds has been developed by a team of chemists at the University of Delaware. According to Dr. Edward E. Schweizer, Robert D. Bach, Kenneth K. Light, and George J. O'Neill, the reaction is not a specific route to a specific compound. Instead, it opens up a whole area of heterocyclic and carbocyclic ring syntheses [J. Am. Chem. Soc, 86, 2744 (1964)]. Some compounds already prepared include 3,4-chromene and 2,5-dihydro-2,3-dimethylfuran. Nitrogen heterocyclic and carbocyclic compounds have also been synthesized by the Delaware group. Work is under way
to prepare a series of sulfur, oxygen, and phosphorus heterocyclics. The pharmaceutical industry will ^probably show the most interest in the reaction for tailormaking various ring systems, Dr. Schweizer says. The synthesis is, to a degree, a combination of both the standard Michael and Wittig reactions. Key to the reaction is a vinyltriphenylphosphonium salt. Dr. Schweizer and Mr. Bach have developed a ready route to the phosphonium salt by first allowing triphenylphosphorene and 2-phenoxyethyl bromide to react (using phenol as the solvent) to produce 2 - phenoxyethyltriphenylphosphonium bromide. This bromide is then decomposed by heating in ethyl acetate
to give vinyltriphenylphosphonium bromide (yield above 9 0 % ) . Functional groups such as —OH, —NH, and —SH undergo nucleophilic conjugate addition reactionssimilar to the Michael reaction—with vinyltriphenylphosphonium bromide. By reacting anions of these groups with the vinylphosphonium salt, the Delaware chemists produce phosphorus ylids. (In the standard Michael reaction, an anion derived from a component that is an active hydrogen donor attacks the relatively positive carbon atom of acceptors such as unsaturated esters, aldehydes, or ketones.) The reaction used by Dr. Schweizer and his co-workers is similar to one reported earlier this year by Dr. Martin Grayson and Patricia T. Keough of American Cyanamid [/. Org. Chem., 29, 631 (1964)]. In their study, the Cyanamid scientists found that a base-catalyzed reaction (which they call phosphonioethylation) of vinylphosphonium salts with compounds having replaceable hydrogens gives 2-substituted ethylphosphonium salts. The study involved addition of compounds containing —CH, —NH, —PH, —OH, and —SH to tributyl vinylphosphonium bromide. The ylids then attack a carbonyl group by a Wittig reaction. The Wittig reaction involves the reaction of a carbonyl with a phosphorus ylid,
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GENERAL. Robert D. Bach and Dr. Edward E. Schweizer plan their next application of the general route to heterocyclic and carbocyclic compounds 68
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(C 6 H r ) ) 3 P—CR 2 , to form a carbonto-carbon double bond. This final step is irreversible, producing either heterocyclic or carbocyclic compounds and triphenylphosphine oxide. Dr. Schweizer synthesized 3,4-chromene by reacting vinyltriphenylphosphonium bromide with the sodium salt of salicylaldehyde. Yields as high as 7 1 % of 3,4-chromene and 5 1 % triphenylphosphine oxide were obtained, using acetonitrile as a solvent. The carbocyclic compound, 2,5-dihydro-2,3-dimethylfuran, was synthesized by reacting acetoin vinyltriphenylphosphonium bromide in the presence of sodium hydride. A 39% yield of the dihydrofuran and 49% triphenylphosphine oxide were obtained.
