[21749-63-3]  · C7H9NS  · 2-(Methylamino)thiophenol  · (MW 139.24)

(template for assisting ring closure of cyclic ketones;1 protecting group for ketones and aldehydes2)

Physical Data: mp 65 °C; bp 126 °C/18 mmHg.

Solubility: sol ethanol, chloroform.

Form Supplied in: solid; commercially available.

Preparative Methods: reduction of 2-Methylbenzothiazole with Lithium Aluminum Hydride,3 hydrolysis of N-methylbenzothiazolone,4 or reduction of the disulfide with Sodium Borohydride.1

Purification: vacuum distillation.

Handling, Storage, and Precautions: store away from air to avoid dimerization.

Template for Ketone Synthesis.

2-(Methylamino)thiophenol (1) has been used to assist in the formation of bonds to carbonyl carbons, leading to cyclic1,5-7 and acyclic ketones,5 as well as to b,g-unsaturated esters and ketones.7 Amido sulfides can be formed by treatment of (1) with an alkyl bromide followed by an acid chloride. Deprotonation with Lithium Diisopropylamide leads to acyl transfer (eq 1). Reductive desulfurization then liberates the new ketone. Enolizable amides will undergo acyl transfer only after oxidation of the thioether to a sulfoxide or sulfone.1

Benzothiazine and Benzothiazoline Synthesis.

A variety of heterocycles have been prepared starting from (1). Treatment of (1) with bromo esters leads to the formation of 2-substituted 2H-1,4-benzothiazin-3-ones (eq 2).8 Alkylation of (1) with dibromopyridazine-3,6-dione provides access to 10-methyl-2,3-dihydropyridazino[4,5-b][1,4]benzothiazine-1,4-diones.9

Condensation of (1) with aldehydes or ketones results in benzothiazolines, which can be used as protecting groups for aldehyde and ketone carbonyl groups.2 The benzothiazoline moiety is highly resistant to attack by acids, bases, and reducing agents. The reaction is selective for aldehydes over ketones (eq 3), conjugated ketones over nonconjugated ketones, and ketones over acids and esters. The selectivity for conjugated over nonconjugated ketones is superior to that of acetalization or thioacetalization. Hydrolysis to regenerate the aldehyde proceeds in good yield with mild oxidants (AgNO3, NCS, HgCl2, others) or with FSO3Me.

1. Ohtsuka, Y.; Oishi, T. TL 1979, 4487.
2. Chikashita, H.; Komazawa, S.; Ishimoto, N.; Inoue, K.; Itoh, K. BCJ 1989, 1215.
3. Hünig, S.; Scheutzow, D.; Schlaf, H.; Quast, H. LA 1972, 110.
4. Fenner, H.; Grauert, R. W.; Hemmerich, P. LA 1978, 193.
5. Ohtsuka, Y.; Oishi, T. CPB 1983, 443.
6. Ohtsuka, Y.; Oishi, T. CPB 1983, 454.
7. Ohtsuka, Y.; Sasahara, T.; Oishi, T. CPB 1982, 1106.
8. Kajino, M.; Mizuno, K.; Tawada, H.; Shibouta, Y.; Nishikawa, K.; Meguro, K. CPB 1991, 2888.
9. Duro, F.; Condorelli, P.; Pappalardo, G. FES 1977, 173.

Mark S. Meier

University of Kentucky, Lexington, KY, USA

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