Morpholine-polysulfide

Sulfur Donors. MBSS, DPTH, and the thiuram disulfides (see Table 2) ate examples. The morpholine disulfide and caprolactam disulfide examples in Table 4 can also donate one atom of sulfur from their molecular stmcture for cross-linking purposes. Monosulfide cross-links provide better thermal stabiUty than the sulfur—sulfur bonds in di- and polysulfide cross-links, which predominate when elemental sulfur is used. 

The Kindler modification dodges heating in closed vessels under pressure by using, instead of aqueous ammonium polysulfide, a mixture of sulfur and morpholine. After being refluxed for 6-12 h, the ketone is converted into the thiomorpholide of the carboxylic acid. Subsequent alkaline hydrolysis yields the carboxylic acid as the final product [501, 503, 504, 1170]. 

The original Willgerodt Reaction conditions required high temperature and pressure, with use of ammonium polysulfide (NH4)2S and H2O to give either an amide or the ammonium salt of the corresponding acid. Kindler s modification, shown above, eliminated these problems and substituted Sg and a dry amine, most commonly morpholine. 

Side chains may be degraded, as in the example already cited in which 5,6,7,8-tetrahydro-2-naphthoic acid appears as a by-product in the reaction of ethyl 6-tetralyl ketone with morpholine and sulfur. Ammonimn polysulfide and long-chain alkyl phenyl ketones give some benzoic acid. Ethyl 9-anthryl ketone, on the other hand, produces anthracene in 85% yield, possibly owing to the great lability of a substituent in the 9-position of anthracene. 

The Willgerodt reaction is useful in the preparation of arylacetic acids and amides from substituted methyl aryl ketones or vinyl aromatic compounds. The aliphatics and acetylenes give lower yields. The conversion is effected by heating aromatic compounds at 160°-200°C in an aqueous solution under pressure using ammonium polysulfide. In the Kindler modification, the ketone or styrene is refluxed with a mixture of sulfur and an amine, usually morpholine, to give a thioamide, ArCHjCSNRj. 

Schwenk and Block [23] also suggested the use of morpholine as an amine, which permits operations in ordinary laboratory equipment. The reaction appears to be quite general for aromatic monomethyl ketones. Substitutions such as nitro, amino, hydroxy, or second ace-toxy groups interfere with the standard reaction, probably because these functional groups are capable of reacting with sulfur, polysulfides, or other components of the reaction mixture. 

Treatment of [ C]methyl aryl ketones with thaUium(lll) nitrate in acidic methanol (McKillop rearrangement) or with ammonium polysulfide or sulfur and morpholine at elevated temperatures (Willgerodt-Kindler reaction) provides labeled arylacetic acid derivatives. In the first case the aryl group migrates from the carbonyl position into the former methyl position, so that the label is shifted by one position. For example (Figure 6.12), in the synthesis of [6- / C]porphobilinogen the pyrrole 22 was acetylated with... 

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