Lithium 2-Lithiobenzenethiolate

[117526-82-6]  · C6H4Li2S  · Lithium 2-Lithiobenzenethiolate  · (MW 122.05)

(reagent for preparation of ortho-substituted thiophenols1)

Preparative Methods: easily prepared in the form of a white viscous slurry by stirring Thiophenol with 2 equiv n-Butyllithium and 2 equiv N,N,N,N-Tetramethylethylenediamine in dry cyclohexane in a nitrogen atmosphere for 20 h.1 No purification of the crude product is generally required. It is stable in the absence of air and moisture.

Handling, Storage, and Precautions: the title reagent (1) is best made as needed and should be handled and stored under nitrogen in a fume hood. Both preparation and decomposition of (1) on exposure to moisture release the foul smelling, toxic thiophenol. Great care should be taken in disposing of (1) and cleaning apparatus exposed to (1). Excess thiophenol or reagent (1) should be destroyed in a good fume hood using an oxidizing agent such as sodium hypochlorite solution (see Thiophenol).

Reaction with Electrophiles.

Diverse thiophenols can be prepared by trapping 2-LiC6H4SLi (1) with various electrophiles, as illustrated in eq 1 and Table 1.

If 2-LiC6H4SLi is treated with elemental sulfur1b followed by acid,5 1,2-benzenedithiol is formed in 96% yield. 1,2,3-Benzenetrithiol can be prepared in 35% yield by extension of this procedure.1b This reaction represents the method of choice to prepare 1,2-benzenedithiol. If 2-LiC6H4SLi is coupled with chlorophosphines or phosphonic chlorides, a variety of 2-phosphino- or 2-phosphinylbenzenethiols results.6 These two classes of compounds have utility as multidentate ligands for metals such as Ni,7a Os,7b and Tc7c and have been used in the synthesis of a cyclophane phosphine.7 With Chlorotrimethylsilane, chlorotriethylsilane, chlorotriphenylsilane, and chloro(t-butyl)dimethylsilane, the products were the corresponding 2-[tris(organosilyl)]benzenethiols in 92, 79, 43, and 28% yields, respectively.1b Multiple silylation could be used to prepare 2,6-bis(trimethylsilyl)benzenethiol in 55% overall yield from 2-LiC6H4SLi. With dichlorosilanes or dichlorodisilanes, various bis(thiophenols) could be prepared.1b These thiophenols are useful as hindered ligands.2,3 Through reaction of 2-LiC6H4SLi with Trichlorosilane, a novel cyclophane silane was prepared.4

This procedure can be used with substituted thiophenols,1b with 2-naphthalenethiol,1b and with 2-mercaptopyridine.8 2-Acetylbenzo[b]thiophene, a key intermediate in the synthesis of the 5-lipoxygenase inhibitor zileuton, has been prepared in 75% overall yield from thiophenol via condensation of lithium 2-lithiobenzenethiolate with DMF followed by chloroacetone (eq 2).9 If 0.5 equiv of iodine is used instead of chloroacetone, the product is 2,2-dithiobisbenzaldehyde, a stable precursor to 2-mercaptobenzaldehyde.9


1. (a) Figuly, G. D.; Loop, C. K.; Martin, J. C. JACS 1989, 111, 654. (b) Block, E.; Eswarakrishnan, V.; Gernon, M.; Ofori-Okai, G.; Saha, C.; Tang, K.; Zubieta, J. JACS 1989, 111, 658. (c) Smith, K.; Lindsay, C. M.; Pritchard, G. J. JACS 1989, 111, 665.
2. (a) Block, E.; Kang, H.; Ofori-Okai, G.; Zubieta, J. ICA 1989, 156, 27. (b) Block, E.; Kang, H.; Ofori-Okai, G.; Zubieta, J. ICA 1990, 167, 147.
3. (a) Block, E.; Gernon, M.; Kang, H.; Ofori-Okai, G.; Zubieta, J. IC 1989, 28, 1263. (b) Block, E.; Brito, M.; Gernon, M.; McGowty, D.; Kang, H.; Zubieta, J. IC 1990, 29, 3172.
4. L'Esperance, R. P.; West, A. P., Jr.; Van Engen, D.; Pascal, R. A., Jr. JACS 1991, 113, 2672.
5. Giolando, D. M.; Kirschbaum, K. S 1992, 451.
6. Block, E.; Ofori-Okai, G.; Zubieta, J. JACS 1989, 111, 2327.
7. (a) Franolic, J. D.; Wang, W. Y.; Millar, M. JACS 1992, 114, 6587. (b) Dilworth, J. R.; Zheng, Y.; Miller, J. R. JCS(D) 1992, 1757. (c) de Vries, N.; Cook, J.; Jones, A. G.; Davison, A. IC 1991, 30, 2662.
8. Block, E.; Gernon, M.; Kang, H.; Zubieta, J. AG(E) 1988, 27, 1342.
9. Basha, A.; Brooks, D. W. JOC 1993, 58, 1293.

Eric Block

SUNY-Albany, NY, USA



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