Organic Syntheses, Coll. Vol. 2, p.580 (1943); Vol. 12, p.76 (1932).
Caution! Recently it was reported to us that workers, following the procedure in Coll. Vol. II, pg 580 (diazotization of anthranilic acid and its reaction with sodium disulfide) but substituting 2,3-dimethylaniline for anthranilic acid, experienced a serious explosion upon addition of the diazonium salt solution to the disulfide solution. We urge that extreme caution should always be exercised in the handling of diazonium salts even when they are in solution.
In a 4-l. beaker
, 290 cc. of water is heated to boiling, and 260 g. (1.1 moles) of crystallized sodium sulfide (Na2S·9H2O)
and 34 g. of powdered sulfur
are dissolved by heating and stirring. A solution of 40 g. of sodium hydroxide
in 100 cc. of water is then added and the mixture cooled, first in cold water, and finally by a freezing mixture of ice and salt.
In a 2-l. beaker
, set in a freezing mixture and provided with a stirrer
and a thermometer
for reading temperatures to 0°, are placed 500 cc. of water, 137 g. (1 mole) of anthranilic acid
, and 200 cc. of concentrated hydrochloric acid
; the stirrer is started and the mixture cooled to about 6°. Meanwhile 69 g. (1 mole) of sodium nitrite
is dissolved in 280 cc. of hot water and the solution cooled in ice; portions are then placed in a separatory funnel
of convenient size, supported in such a way that the lower end of the stem extends beneath the surface of the anthranilic acid
solution. When the temperature has fallen to 5°, the nitrite solution is run in; about 500 g. of cracked ice is added at such a rate as to keep the temperature below 5°. This takes about ten minutes (Note 1)
. A drop of the solution should give an immediate blue color with starch-iodide paper.
The stirrer and thermometer are now transferred to the alkaline sulfide solution, the temperature of which must be below 5°. The diazo solution is added over a period of twenty to thirty minutes along with 950 g. of ice to prevent the temperature from rising above 5°. When addition is complete, the water bath
is removed and the mixture allowed to warm up to room temperature; after two hours the evolution of nitrogen
ceases (Note 2)
. About 180 cc. of concentrated hydrochloric acid
is added until the solution is acid to Congo red paper, and the precipitate of dithiosalicylic acid
is filtered and washed with water.
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 l. of water, and the mixture is filtered while hot. It is divided into five equal parts (Note 3)
, and the dithiosalicylic acid
is reprecipitated as before with concentrated hydrochloric acid
. The solid is filtered, the cake being sucked as dry as possible.
The moist cake is mixed with 27 g. of zinc dust and 300 cc. of glacial acetic acid
in a 1-l. round-bottomed flask
, and the mixture is refluxed vigorously for about four hours (Note 4)
. When the reduction is complete, the mixture is cooled and filtered with suction. The filter cake is washed once with water and then transferred to a 1-l. beaker
. The cake is suspended in 200 cc. of water, and the suspension is heated to boiling. The hot solution is made strongly alkaline by the addition of about 40 cc. of 33 per cent aqueous sodium hydroxide
solution. The alkaline solution is boiled for about twenty minutes to ensure complete extraction of the product from the filter cake, filtered from the insoluble material (Note 5)
, and the thiosalicylic acid
is then precipitated by the addition of sufficient concentrated hydrochloric acid
to make the solution acid to Congo red paper. The product is filtered with suction, washed once with water, and dried in an oven
at 100–110°. The yield of a product which melts at 162–163°
is 110–130 g.
per cent of the theoretical amount based on the anthranilic acid
This product is sufficiently pure for most purposes (Note 6)
For recrystallization 5 g. of this material
is dissolved in 20 cc. of hot 95 per cent alcohol
, and 40 cc. of water is added. The solution is boiled with a little decolorizing carbon
, filtered hot, and then allowed to cool. The product crystallizes in yellow flakes. The yield of recrystallized material is 4.7 g.
; the melting point of the material is 163–164°
This method is much more rapid than when external cooling alone is used (Org. Syn. Coll. Vol. I, 1941, 374)
. The total volume of the solution is not important since the insoluble dithiosalicylic acid
is readily filtered.
Foaming sometimes becomes very during the evolution of nitrogen
. The addition of a few cubic centimeters of ether
from time to time helps to keep this foaming under control.
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-l. 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.
The reduction does not always run smoothly. If the zinc
lumps and becomes inactive more must be added. To determine whether reduction is complete, a sample is removed, cooled, and filtered. The precipitate is boiled with strong sodium hydroxide
solution, filtered, and then acidified with hydrochloric acid
. If the reduction is complete, the precipitated material will melt at 164° or lower. If the reduction is not complete, the precipitated material will melt above 164°. If the reduction is not complete, the refluxing of the main portion must be continued (and perhaps more zinc
must be added) until a test portion shows that the reaction is complete.
In determining the melting point of the material, the capillary tube containing the test sample should be inserted in a bath previously heated to 163–164°.
When the reduction is carried out in five portions, one extraction with sodium hydroxide
is usually sufficient for each portion. If the reduction is carried out in one operation, several extractions are usually required. When the material is to be extracted more than once, it is best to boil the residue from the first alkaline treatment with hydrochloric acid
, filter, and then treat again with the alkali.
Of the several methods described for the production of thiosalicylic acid
, only the following are of preparative interest: heating o-halogenated benzoic acids
with an alkaline hydrosulfide
at 150–200° in the presence of copper or copper salts
or with sodium sulfide
and reduction of dithiosalicylic acid
in alkaline solution. The dithiosalicylic acid
is prepared by treating diazotized anthranilic acid
with sodium disulfide
in alkaline solution.5
This preparation is referenced from:
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