Thioanisole

[100-68-5]  · C7H8S  · Thioanisole  · (MW 124.22)

(preparation of phenylthiomethyllithium1-3 and (2-lithiophenylthio)methyllithium;2 deprotection of aromatic methyl ethers;9 deprotection of N-benzyloxycarbonyl groups;10 cleavage of epoxides;11 oxidation of diols to hydroxy ketones12)

Physical Data: bp 188 °C.

Form Supplied in: colorless liquid; commercially available.

Handling, Storage, and Precautions: stench; handle in a fume hood.

Phenylthiomethyllithium.

Thioanisole (1) can be efficiently monometalated by treatment with Phenyllithium,1 n-Butyllithium and DABCO,1 n-butyllithium and TMEDA,2 or t-Butyllithium and HMPA3 to afford phenylthiomethyllithium (2) which reacts smoothly with primary and secondary alkyl halides, leading to alkylaryl sulfides (eq 1).1,2

Treatment of phenylthiomethyllithium (2) with ketones produces (phenylthiomethyl)carbinols (eq 2), which can be dehydrated to vinyl sulfides1 or converted to alkenes, either directly4 or via the corresponding benzoate esters.5

In the case of cyclic a,b-unsaturated ketones, exclusive 1,2-addition of phenylthiomethyllithium (2) occurs to provide tertiary allylic alcohols which can undergo oxidative allylic transposition to afford 3-(phenylthio)methyl a,b-unsaturated ketones (eq 3).6

A one-pot synthesis of substituted cyclopent-2-en-1-ones relies on the addition of phenylthiomethyllithium (2) to ethyl 2-chloro-2,3-dialkylbut-3-enoate esters, followed by sulfur-assisted SN2 displacement of chloride ion and [1,2]-sigmatropic rearrangement of the resultant ylide (eq 4).7 This procedure has been applied to the synthesis of cis-jasmone and dihydrojasmone.7

(2-Lithiophenylthio)methyllithium.

When thioanisole (1) is treated with 2.2 equiv of n-butyllithium and TMEDA, dimetalation occurs to give (2-lithiophenylthio)methyllithium.2,8 The latter compound can be dialkylated, diacylated, dicarboxylated, or disilylated (eq 5).2 Monoacylation of (2-lithiophenylthio)methyllithium is followed by intramolecular cyclization, leading to benzothiophenes after dehydration (eq 6).8

Deprotection of Aromatic Methyl Ethers and N-Benzyloxycarbonyl Groups.

In combination with Trifluoromethanesulfonic Acid, thioanisole (1) effects the demethylation of O-methyltyrosine (eq 7).9 Similarly, Trifluoroacetic Acid and thioanisole (1) remove the N-benzyloxycarbonyl (N-Cbz) group from the amino terminus of peptides (eq 8).10

Epoxide Cleavage and Oxidation of Diols.

The chlorosulfonium salt, formed when thioanisole (1) is reacted with Chlorine, causes ring opening of epoxides to give a-chloro sulfoxonium salts which can be converted to a-chloro alcohols or a-chloro ketones (eq 9).11 When 1,2-diols are treated with the thioanisole (1)-chlorine complex, oxidation to a-hydroxy ketones takes place (eq 10).12


1. Corey, E. J; Seebach, D. JOC 1966, 31, 4097.
2. Cabiddu, S; Fattuoni, C; Floris, C; Gelli, G; Melis, S; Sotgiu, F. T 1990, 46, 861.
3. Dolak, T. M; Bryson, T. A. TL 1977, 23, 1961.
4. Watanabe, Y; Shiono, M; Mukaiyama, T. CL 1973, 871.
5. Welch, S. C; Loh, J-P. JOC 1981, 46, 4072.
6. Luzzio, F. A; Moore, W. J. JOC 1993, 58, 2966.
7. Mathew, J; Alink, B. CC 1990, 684.
8. Cabiddu, S; Cancellu, D; Floris, C; Gelli, G; Melis, S. S 1988, 888.
9. Kiso, Y; Nakamura, K; Ito, K; Ukawa, K; Kitagawa, K; Akita, T; Morioki, H. CC 1979, 971.
10. Kiso, Y; Ukawa, K; Akita, T. CC 1980, 101.
11. Nakai, H; Kurono, M. CL 1977, 995.
12. Corey, E. J; Kim, C. U. TL 1974, 297.

Simon Bailey

The Ohio State University, Columbus, OH, USA



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