Dithiosalicylic acid

Thiosalicylic acid/747-93-3] (0-mercaptobenzoic acid), a sulfur-yellow solid that softens at 158°C, has a melting point of 164°C. It sublimes, is slightly soluble in hot water but freely soluble in glacial acetic acid and alcohol, and yields dithiosalicylic acid [527-89-9] upon exposure to air. 

To remove the excess sulfur, the precipitate is dissolved by boiling with a solution of 60 g. of anhydrous sodium carbonate (soda ash) in 2 1. of water, and the mixture is filtered while hot. It is divided into five equal parts (Note 3) and the dithiosalicylic acid reprecipitated as before with concentrated hydrochloric acid. The solid is filtered, the cake being sucked as dry as possible. 

This method is much more rapid than when external cooling alone is used (Org. Syn. 2, 47). The total volume of the solution is not important since the insoluble dithiosalicylic acid is readily filtered. 

The dithiosalicylic acid may be precipitated all at once if desired and the entire amount reduced in one operation. If this is done, the reduction must be carried out in a 5-I. flask, fitted with a good stirrer. The mixture needs to be refluxed about ten hours over a ring burner. In the laboratory, this is much less convenient than it is to divide the material and reduce in smaller amounts. The yield is not materially lowered by making the reduction in one portion. 

Of the several methods described for the production of thiosalicylic acid, only the following are of preparative interest heating of o-halogenated benzoic acids with an alkaline hydrosulfide at 150-2000 in the presence of copper or copper salts,1 5 or by substitution of sodium sulfide at 2000 2 by reduction of dithiosalicylic acid with glucose,3 or metals 4,5 in alkaline solution. The dithiosalicylic acid is prepared by treating diazo-tized anthranilic acid with sodium disulfide in alkaline solution.4... 

Klyuev and Snegireva41 42 have prepared imino derivatives of 1,2-benzisothiazolines, including 1-imino-1,2-benzisothiazolinone (49) and l,3-diimino-l,2-benzisothiazoline (50). These compounds are formed by treating dithiosalicylic acid (47) with excess chlorine and reacting the product (48) with ammonia or urea. The same workers have also prepared a number of derivatives of these imino compounds.43, 44... 

Benzisothiazolinones (53) are readily prepared by treatment of dithiosalicylic acid (47) with chlorine, followed by an amine.46-55 Variations from this basic reaction include the reaction of dithio-... 

Many diazonium solutions have been reported to react explosively with solutions of metallic polysulfides even at low temperatures.12 A violent reaction with xanthates is mentioned only in one report.3 Neither the authors nor the checkers observed any unusual reactivity during this preparation or with the procedure given for dithiosalicylic acid.4 On a large scale (100 moles of wi-toluidine) flashes of light have been occasionally observed (private communication, L. J. Roll). 

Anthranilic acid is diazotized and the diazonium salt is converted to a mixture of thiosalicyhc acid and dithiosalicylic acid by the action of sodium polysulfide. For these reactions, the following three solutions are prepared ... 

To a solution of 20 g. of anhydrous sodium carbonate in 150 ml. of water are added 10 g. (0.033 mole) of dithiosalicylic acid [Org. Syntheses Coll. Vol. 2, 580 (1943)] and 15 g. of sodium hydrosulfite. The mixture is refluxed for 30 minutes, and then there is added a solution of 15 g. of chloroacetic acid in 200 ml. of water to which sufficient sodium carbonate has been added to neutralize the chloroacetic acid. After being refluxed for 1 hour, the mixture is cooled and acidified to Congo red. The precipitated product is recrystallized from water to give a 70% yield of o-carboxyphenylmercaptoacetic acid melting at 217-218°. 

Sulfur-yellow flakes, plates, needles from glacial acetic acid or alcohol. Softens at 158. mp 164-165. Sublimes. Slightly sol in hot water freely in glacial acetic acid, ale. Exposure to air yields dithiosalicylic acid, which is produced also when an alcoholic soln of thiosalicylic acid comes in contact with FeClj (resulting in a transitory blue color). 

The preparation of 2,2 -dithiodi(benzoic acid) (dithiosalicylic acid)454 may be cited as a further example. 

The antimicrobial thimerosal is used as a preservative in hepatitis vaccines. Two degradation compounds (dithiosalicylic acid, thiosalicylic acid) were separated h om their parent on a C g column (A = 226 nm) using a 65/35/0.9 methanol/water/ H3PO4 mobile phase [559]. Elution was complete in 12 min. A calibration curve from 20 to 80 g/mL was used and a 5 g/mL detection limit (S/N = 3) was rqiorted. 

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