Methylthiomaleic Anhydride

[64810-01-1]  · C5H4O3S  · Methylthiomaleic Anhydride  · (MW 144.16)

(2p partner in [4 + 2] cycloaddition reactions;1 synthon for methoxycarbonylketene or methyleneketene5)

Alternate Name: 3-(methylthio)-2,5-furandione.

Physical Data: mp 36-37 °C (ether); bp 123-125 °C/0.5 mmHg.

Analysis of Reagent Purity: IR 1845, 1745, 1566 cm-1; 1H NMR (CDCl3) d 6.28, 2.56; 13C NMR (CDCl3) d 162.4, 162.1, 155.5, 118.5, 15.2.

Preparative Method: prepared by the addition of Methyl Isothiocyanate to acetylenedicarboxylic acid (ethanol, 25 °C) to afford a 6:1 mixture of 2-(methylthio)fumaric and -maleic acids, which are dehydrated by dissolution in Thionyl Chloride for 1 h at 25 °C, then 7 h at 60 °C. Excess SOCl2 is removed at 120 °C at aspirator pressure, followed by distillation of the residue to afford the crystalline anhydride in 68-77% yield.1

Reactivity.

Methylthiomaleic anhydride (1) has been reported to react as a regioselective, endo-selective, electron-deficient 2p partner in [p4s + p2s] cycloaddition reactions.1

Cycloaddition Reactions.1

Cycloadditions were carried out by mixing the neat dieneophile (1) with the appropriate diene at 0-80 °C in the presence of 2,6-di-t-butyl-4-methylphenol (BHT) or hydroquinone as a stabilizer. Exclusive endo selectivity was observed in the cycloaddition of cyclopentadiene with dienophile (1) to afford the bicyclo[2.2.1]heptene adduct (eq 1). Reaction of (1) with Isoprene afforded the cyclohexene adduct as a single regioisomer (eq 2). Similarly, a single regioisomeric cycloadduct was observed with (1) and 1-vinyl-6-methoxy-3,4-dihydronaphthalene (eq 3). The thiomethyl group2 was postulated to be responsible for the excellent regiocontrol observed in cycloadditions of (1), since comparable cycloadditions with methylmaleic anhydride exhibited poor regioselectivity.3

Oxidative decarboxylation4 of cycloadducts of (1) affords access to b-keto ester functionality. Treatment of the isoprene-(1) cycloadduct with methanol followed by N-Chlorosuccinimide afforded the corresponding dimethyl acetal, which could be hydrolyzed to afford the b-keto ester (eq 4).1

In bicyclic adducts (eq 1), thiol enol ethers are the direct products of oxidative decarboxylation; reduction of the ester and subsequent hydrolysis of the thiol enol ethers affords a-methylene ketones (eq 5).5 Thus eqs (4) and (5) demonstrate the utility of (1) as a methoxycarbonylketene (2) or methyleneketene (3) synthon in [4 + 2] cycloaddition reactions.


1. Trost, B. M.; Lunn, G. JACS 1977, 99, 7079.
2. (a) Trost, B. M.; Bridges, A. J. JACS 1976, 98, 5017. (b) Cohen, T.; Mura, A. J., Jr.; Shull, D. W.; Fogel, R. J.; Ruffner, R. J.; Fabek, J. R. JOC 1976, 41, 3218. (c) Evans, D. A.; Bryan, C. A.; Sims, C. L. JACS 1972, 94, 2891.
3. Bachman, W. E.; Chemerda, J. M. JACS 1948, 70, 1468.
4. (a) Trost, B. M.; Tamaru, Y. JACS 1977, 99, 3101. (b) Trost, B. M.; Tamaru, Y. TL 1975, 3797. (c) Trost, B. M.; Tamaru, Y. JACS 1975, 97, 3528.
5. Trost, B. M. ACR 1978, 11, 453.

John C. Arthur & Robert S. Coleman

University of South Carolina, Columbia, SC, USA



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