S-Ethyl Chlorothioformate

[2941-64-2]  · C3H5ClOS  · S-Ethyl Chlorothioformate  · (MW 124.585)

(used in synthesis of carbothioate S-esters)

Physical Data: mp -60 °C; bp 132 °C; bp 39 °C/20 mmHg; n20D 1.4820; d 1.195 g cm-3; fp 30 °C.

Solubility: sol DMF (17.9 g 100 mL-1).

Form Supplied in: liquid; 95-98%, dependent on supplier.

Purification: two short-path distillations.

Handling, Storage, and Precautions: the liquid is flammable, moisture sensitive, harmful if swallowed and causes burns. It is also a lachrymator. Use in a fume hood.

Carbothioate S-Esters.

This reagent provides a superior procedure for the preparation of carbothioate S-esters. These are interesting synthetic intermediates, due to their activated carbonyl group,1 and have, amongst other things, been used as a complexing reagent in some organometallic systems.4 The previous method of Schotten-Baumann involves the reaction of a carboxylic acid with either Thionyl Chloride or Oxalyl Chloride followed by a thiol and base.2 This has the disadvantage of introducing an acid chloride moiety into the substrate during the first step of the sequence with the consequent possibility of side reactions. The modified procedure involves the reaction of the sodium salt of the carboxylic acid with the reagent in DMF and pyridine, firstly at 0 °C and then at room temperature (eq 1).3

This reaction works considerably better if the S-phenyl ester is used instead (64%); with the same derivative, use of the lithium salt gave an improved yield over the sodium salt although no reaction of the S-ethyl ester with this cation was attempted.

Fungicidal carbanilates have have also been prepared using this method. Electron-donating meta-substituted phenyl(ethylthio-N-substituted amide)s were prepared, using a dichloromethane-pyridine solvent mixture.5

Tarbell et al. have studied the reaction of aromatic carboxylic acids with chlorothioformate S-esters to yield the corresponding mixed anhydrides.6 Thermal decomposition of this gives the arenecarbothioate S-ester.

An alternative to forming carbothioate esters uses the O-ester isomer of ethyl chlorothioformate.7 Treatment of dibutylethoxyphosphine in toluene with ethoxythiocarbonyl chloride gave 70-80% of the S-ethylcarboxydibutylphosphine oxide. This could then be reacted with benzylamine in isopropyl alcohol to give the benzylaminocarboxydibutylphosphine oxide.

a-Fluoro-b-thioester Esters.

An a-fluoro-b-thioester ester has been prepared in 57% yield using this reagent and some phosphorus chemistry.8 Tri-n-butylphosphine and ethyl bromofluoroacetate were initially reacted in THF at rt; deprotonation with n-Butyllithium at -78 °C was followed by addition of the acid chloride; workup was with mild aqueous base to give EtSC(O)CFHCO2Et.

a,b-Unsaturated Thiocarboxylates.9

Synthesis of a,b-unsaturated thiocarboxylates by Schaumann has been achieved by two different methods: ipso substitution of the silyl group in vinylsilanes or cyclopropylsilane by Lewis acid-activated S-ethyl chlorothiocarbonate;10 and standard Horner-Emmons type alkenation.11 With the former the best results were obtained with Aluminum Chloride, rather than Titanium(IV) Chloride or Magnesium Bromide as catalysts, in dichloromethane at -60 °C and yields varied between 25% and 66% depending on the substrate. It is thus assumed that the reactive intermediate is the hard S-ethylcarbonyl cation; S-t-butyl, -hexyl, and -cyclohexyl chlorothiocarbonates gave no substitution, due to cation breakdown, even with AlCl3 at -78 °C, yielding instead the alkyl halide and carbonyl sulfide.12 The workup was with saturated NH4Cl (aq) followed by saturated NaHCO3 (aq), brine, water, drying with MgSO4 and distillation in vacuo, with added hydroquinone. More vigorous conditions were required with the cyclopropylsilane but no ring opening was observed. It appears that edge coordination of the cyclopropane to the electrophile is involved.13

The Horner-Emmons type reaction is a more general procedure and allows the use of the S-t-butyl, -hexyl, and -cyclohexyl chlorothiocarbonates, unlike the previously mentioned method. Yields for this one-pot reaction scheme were quite variable (21-81%). However, usually only the (E)isomer product was formed.

Other Reactions of S-Ethyl Chlorothioformate.

Bis(tributyltin) sulfide has been used as a sulfur transfer reagent under neutral and mild conditions with S-ethyl chlorothioformate; using 1 mol equiv in CHCl3 at 110 °C for 12 h gave 97%, via GLC, of bis(S-ethylcarboxy) thioanhydride.14

A facile Rosenmund type reduction of acid chlorides, including the S-ethyl ester, with hypervalent silicon hydrides has been demonstrated.15 Ethyl chlorothioformate was unreactive compared to most acid chlorides with this reaction, so a more efficient silane (1) had to be used; the yield of ethylthioformaldehyde was greater than 95% via NMR integration. In a continuation of this work, Corriu has also shown that reaction of the standard silane (2) with Phenyl Isocyanate yielded an adduct which, on addition of the reagent, gave the N-acylthioformamide EtSC(O)NPhCHO in 80% yield.16 In addition the chlorosilane produced was readily recycled by reduction with Lithium Aluminum Hydride. Only one paper previously existed on the preparation of N-acylthioformamides.17

1. Nicolau, K. C.; Barnette, W. E.; Gasic, G. P.; Magolda, R. L. JACS 1977, 99, 7736. Gennari, C.; Beretta, M. G.; Bernardi, A.; Moro, G.; Scolastico, C.; Todeschini, R. TL 1986, 27, 893.
2. Bruce, T. C. In The Chemistry of Organic Sulfur Compounds; Pergamon: New York, 1961; Vol. 1, p 421. Speziale, A. J.; Frazier, H. W. JOC 1961, 26, 3176.
3. Gorski, R. A.; Dineshkumar; Dagli, J.; Patronik, V. A.; Wemple, J. S 1974, 811.
4. Lagadec, A.; Dabard, R.; Misterkiewicz, B.; Le Rouzic, A.; Patin, H. JOM 1987, 326, 381.
5. Baker, D. R.; Brownell, K. H.; Kezerian, C. CA 1988, 109, 165 714t.
6. Tarbell, D. S. ACR 1969, 2, 296; Wei, L.; Tarbell, D. S. JOC 1968, 33, 1884; Tarbell, D. S.; Parasaran, T. JOC 1964, 29, 2471.
7. Buvashkina, N. I.; Kovalenko, L. V.; Virin, L. I.; Popova, I. Yu. ZOR 1988, 58, 31 (CA 1988, 110, 23 990b).
8. Thenappan, A.; Burton, D. J. TL 1989, 30, 6113. Thenappan, A.; Burton, D. J. JOC 1991, 56, 273.
9. Fehr, C.; Galindo, J. JOC 1988, 53, 1828. Kobayashi, S.; Tamura, M.; Mukaiyama, T. CL 1988, 91.
10. Schaumann, E.; Mergadt, B. JCS(P1) 1989, 7, 1361.
11. Schaumann, E.; Mergadt, B.; Fittkau, S. S 1990, 1, 47.
12. Olah, G. A.; Schilling, P. LA 1972, 761, 77.
13. Paquette, L. A. CR 1986, 86, 733.
14. Harpp, D. N.; Gingras, M.; Aida, T.; Cahn, T. H. S 1987, 1122.
15. Corriu, R. J. P.; Lanneau, G. F.; Perrot, M. TL 1988, 29, 1271.
16. Corriu, R. J. P.; Lanneau, G. F.; Perrot-Petta, M.; Mehta, V. D. TL 1990, 31, 2585.
17. Chupp, J. P.; Leschinsky, K. L. JOC 1975, 40, 66.

Greg J. Sarnecki

University of Cambridge, UK

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