Amino 6 methylbenzothiazole

Submitted by C. F. H. Allen and James Van Allan. Checked by W. E. Bachmann and N. W. MacNaoghton. 

A solution of 107 g. (1 mole) of -toluidine (Note 1) in 700 cc. of chlorobenzene is prepared in a 3-1. three-necked, round-bottomed flask fitted with a stirrer, reflux condenser, thermometer, and dropping funnel. Over a period of five minutes, 54 g. (29.3 cc., 

55 mole) of concentrated sulfuric acid is added dropwise. To l lie finely divided suspension of / -toluidine sulfate is added 90 g. (1.1 moles) of sodium thiocyanate, and the mixture is heated for lliree hours at 100° (inside temperature) in an oil bath (Note 2). The solution, which now contains the thiourea, is cooled to 30°, and 180 g. (108 cc., 1.34 moles) of sulfuryl chloride is added over. i period of fifteen minutes, with care that the temperature does n ( exceed 50°. The mixture is kept at 50° for two hours (no I m l her evolution of hydrogen chloride), after which the chlorobenzene is removed by filtration (Note 3). 

All lhe chemicals used were from the Eastman Kodak (iimpany. The checkers used the Practical grade of / -toluidine, which was distilled just before use. 

The l tolylthiourca may be isolated at this point, if desired, by hllering and washing the solid residue with ether. The dried solid (172 g.) is a mixture of the urea and sodium sulfate. It is ext rat led willi 250 cc. of warm (50 00 ) water the residual urea, 

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Aminoguanidine sulfate, 26, 12 2-Aminoheptane, 23, 70 df-/3-AMINOHYDROCINNAMIC ACID, 22, 26 ck-Aminoisovaleric ACID, 20, 106 Aminolysis, of phenyl salicylate, 26, 92 2-Amino-6-methylbenzothiazole, 22, 16... 

Amino-6-methylbenzothiazole has been prepared by the action of cupric thiocyanate,1, 2 3 or of chloramine and ammonium thiocyanate,4 on -toluidine by the action of chlorine on di- -tolylthiourea 5 or of bromine on acetyldi- -tolylthiourea 6 by treatment of />-tolylthiourea with halogens7 or acid halides. 8 0110,11 12 2-Aminobenzothiazole has been prepared in... 

For use of the reagent in the synthesis of 2-amino-6-methylbenzothiazole, see Sodium thiocyanate. 

The nmr of the isolated metabolite 5, a glucuronide, suggested that it existed as a mixture of rotational isomers (rotamers), as did the acylat glucuronide 6, due to the hindered rotation about the triazole-phenyl bond. When the structure was confirmed by synthesis from 2-amino-6-methylbenzothiazole, 7, by a series of steps outlined in Scheme 2, the synthesized glucuronides also appeared to exist as a mixture of rotamers. Further, these rotamers were separate as the acylated ucuronides by liquid chromatography and characterized by their nmr spectra which differed in the proton resonances of the peaks assigned to the 2-methyl, the thiomethyl, and the triazole hydrogen. 

Treatment of 2-amino-6-methylbenzothiazole with propargyl bromide yields the imine (787), which cyclises in the presence of acids or bases to the imidazo[2,1 -6]benzothiazole (788). The 2-phenyl derivative of this ring system is obtained from 2-imino-6-methyl-3-phenacyl-benzothiazoIine. ... 

The first thiazoloquinolines, namely angularly annelated 2-methyl-thiazolo [4,5-/]quinoline 19 and linearly annelated 2-methyl-thiazolo[4,5-g]quinoline 20, were prepared in 1937 in poor yield using the Skraup reaction and exploiting the blockage of position 4 in 5-amino-2-methylbenzothiazole with a chlorine atom, as shown in Scheme 10 (37LA60). 

Hmhp = 2-hydroxy-6-methylpyridine. b Hmap = 2-amino-6-methylpyridme. c dmp = 2,6-dimethoxy-phenyl. d Hambt = 2-amino-4-methylbenzothiazole. ° dppe = l,2-bis(diphenylphosphino)cthane. pic = 4-methylpyridine. 

Diazo Components With Amino alkyl Groups. Yellow dyes are prepared by ami-nomethylation of 2-(4 -aminophenyl)-5-methylbenzothiazole followed by diazoti-zation and coupling with acetoacetarylides. Red cationic dyes are obtained with naphthols or hydroxynaphthoic acid arylides. All are suitable for dyeing paper. The bleachability of these dyes is important for the recycling of waste paper [84], The aminomethylation of aromatic amines is carried out by reaction with formal-... 

Indeed, benzoxazoles and benzothiazoles react smoothly with secondary and primary aliphatic amines in acetonitrile in the presence of benzoic acid and silver carbonate, thus giving rise to the corresponding 2-amino derivatives (Scheme 40) [94]. Also the reaction of 6-methylbenzothiazole with morpholine has been carried out in the presence of Zn(OAc)2 as the Lewis acid (catalyst) and Ag20 as oxidant. 

Diazotization. Diazonium salts of benzothiazoles have been useful in interconversions involving amino-derivatives of this ring system. 2-Fluoro-benzothiazoles are accessible by the diazotization of the corresponding 2-amino-compounds, followed by cautious pyrolysis of the isolated diazonium fluoroborate with potassium fluoride and sand under reduced pressure. The four isomeric sulphonic acids of 2-methylbenzothiazoles are obtainable from the amino-compounds by diazotization, followed by treatment with acetic acid saturated with sulphur dioxide in the presence of cupric chloride the resulting sulphonyl chlorides serve as source of the... 

In the course of a wider study of the reaction between active methyl groups and ortho-substituted bifunctional molecules in the presence of sulphur, 2-methylbenzothiazole gave, with phenylenediamine or o-amino-phenol, the 2-substituted benzazoles (92) and (93)."... 

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