1,2-Ethanedithiol1

[540-63-6]  · C2H6S2  · 1,2-Ethanedithiol  · (MW 94.20)

(1,3-dithiolane formation; ether cleavage; reduction (carbonyl to methylene; sulfoxide to thioether); gem-difluoride formation; dithiolenium ion formation)

Physical Data: d 1.123 g cm-3 (23.5 °C); bp 146 °C/760 mmHg; 63 °C/46 mmHg.

Solubility: slightly sol water; miscible with many organic solvents.

Form Supplied in: widely available.

Handling, Storage, and Precautions: stench! Inhalation can cause chest pain, headache, nausea, pulmonary edema; LD50 (oral, mouse) 342 mg kg-1; see 1,3-Propanedithiol. Use in a fume hood.

1,3-Dithiolane Formation.

1,2-Ethanedithiol (1) condenses with aldehydes, ketones, and acetals to afford 1,3-dithiolanes,1,2 useful for carbonyl protection (eqs 1 and 2).3a,b Stability, condensation selectivity, and conditions for carbonyl regeneration parallel those discussed for 1,3-Propanedithiol.4 Esters and lactones can be protected as ketene dithioacetals and/or dithioortholactones, resistant to nucleophilic attack, using the bis(dimethylalanyl) derivative of (1).5

Ether Cleavage.

An acetonide can be cleaved in the presence of a nearby t-butyldiphenylsilyl ether with (1).6a Under more vigorous conditions, aliphatic methyl ethers are cleaved (eq 3).6b

Reduction.

Raney Nickel desulfurization of 1,3-dithiolanes effects overall reduction of C=O to CH2, as does Sodium-Ammonia in THF (eqs 4 and 5).7a,b Na/hydrazine is an alternative reagent (eq 6).10a Peptidic sulfoxides are reduced to thioethers with (1) and an electrophilic catalyst.11a

gem-Difluoride Formation.

1,3-Dithiolanes yield geminal difluorides on treatment with Pyridinium Poly(hydrogen fluoride) and a mild oxidant (eq 7).8a,b 1,3-Dithianes react more slowly and give lower yields.8a

Dithiolenium Ion Formation.

Acid chlorides, anhydrides, esters, and orthoesters, upon treatment with (1) and a Lewis acid, can produce electrophilic 1,3-dithiolenium cations which react with a variety of carbon nucleophiles.9 Selective indole formylation in the presence of a primary carboxamide could thus be achieved (eq 8).9a

Miscellaneous.

Racemic ketones have been resolved by condensation with (R,R)- or (S,S)-2,3-butanedithiol, then reduced as above to give resolved deoxy compounds (eq 6).10a,b Oxidation of prochiral 1,3-dithiolanes under modified Katsuki-Sharpless conditions yields monosulfoxides of high ee.10c In peptide synthesis, (1) is frequently used as a cation scavenger during deprotection.11a,b Transition metal cations are strongly chelated by (1), as exemplified by demetalation of CuII and NiII metalloporphyrins.11c


1. (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991; p 201. (b) Page, P. C. B.; van Niel, M. B.; Prodger, J. C. T 1989, 45, 7643; see pp 7647-7651.
2. 1,3-Dithiolanes are not generally useful as acyl anion equivalents: (a) Oida, T.; Tanimoto, S.; Terao, H.; Okano, M. JCS(P1) 1986, 1715. (b) An exception: Barton, D. H. R.; Bielska, M. T.; Cardoso, J. M.; Cussans, N. J.; Ley, S. V. JCS(P1) 1981, 1840.
3. (a) Liu, H.-J.; Yeh, W.-L.; Chew, S. Y. TL 1993, 34, 4435. (b) Wolf, G.; Seligman, A. M. JACS 1951, 73, 2082.
4. (a) Sato, T.; Otera, J.; Nozaki, H. JOC 1993, 58, 4971. (b) Stahl, I.; Schramm, B.; Manske, R.; Gosselck, J. LA 1982, 1158. (c) Nakata, T.; Nagao, S.; Takao, S.; Tanaka, T.; Oishi, T. TL 1985, 26, 73. (d) Cardani, S.; Bernardi, A.; Colombo, L.; Gennari, C.; Scolastico, C.; Venturini, I. T 1988, 44, 5563. (e) Ni, Z.-J.; Luh, T.-Y. OS 1992, 70, 240. (f) Bellesia, F.; Boni, M.; Ghelfi, F.; Pagnoni, U. M. T 1993, 49, 199.
5. Corey, E. J.; Beames, D. J. JACS 1973, 95, 5829.
6. (a) Williams, D. R.; Sit, S.-Y. JACS 1984, 106, 2949. (b) Vidari, G.; Ferriño, S.; Grieco, P. A. JACS 1984, 106, 3539.
7. (a) Maurer, P. J.; Takahata, H.; Rapoport, H. JACS 1984, 106, 1095. (b) Numazawa, M.; Mutsumi, A. Biochem. Biophys. Res. Commun. 1991, 177, 401.
8. (a) Sondej, S. C.; Katzenellenbogen, J. A. JOC 1986, 51, 3508. (b) Jekö, J.; Timár, T.; Jaszberenyi, J. C. JOC 1991, 56, 6748.
9. (a) Benes, J.; Semonský, M. CCC 1982, 47, 1235. (b) Stahl, I. CB 1987, 120, 135. (c) Okuyama, T.; Fujiwara, W.; Fueno, T. BCJ 1986, 59, 453. (d) Houghton, R. P.; Dunlop, J. E. SC 1990, 20, 1.
10. (a) Corey, E. J.; Ohno, M.; Mitra, R. B.: Vatakencherry, P. A. JACS 1964, 86, 478. (b) Buding, H.; Deppisch, B.; Musso, H.; Snatzke, G. CB 1985, 118, 4597. (c) Bortolini, O.; Di Furia, F.; Licini, G.; Modena, G.; Rossi, M. TL 1986, 27, 6257.
11. (a) Futaki, S.; Taike, T.; Akita, T.; Kitagawa, K. CC 1990, 523. (b) Fields, C. G.; Fields, G. B. TL 1993, 34, 6661. (c) Battersby, A. R.; Jones, K.; Snow, R. J. AG(E) 1983, 22, 734.

Raymond E. Conrow

Alcon Laboratories, Fort Worth, TX, USA



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