DE1113695B - Process for the preparation of pure 2-sulfanilamido-4-methylpyrimidine - Google Patents

Description

GERMAN

PATENT OFFICE

V16962IVd / 12p

REGISTRATION DATE: JULY 25, 1959

NOTICE THE REGISTRATION AND ISSUE OF EDITORIAL: SEPTEMBER 14, 1961

2-sulfanilamido-4-methylpyrimidine can be omitted p-aminobenzenesulfonylguanidine and butinone or Represent dichlorobutanone- (2). If you start from the reaction with butynone, you work in an alkaline way Solution in a mono- or polyhydric alcohol, preferably methanol. The products available in this way occur with a melting point of 234 ° C. The main disadvantage of this method is the strong explosiveness of the starting product butinone.

It is also known by the action of dichlorobutanone- (2) on p-aminobenzenesulfonylguanidine to prepare 2-sulfanilamido-4-methylpyrimidine in the presence of sodium methylate and methanol. That required dichlorobutanone- (2) is obtained by introducing vinyl chloride into a suspension of the Complex compound of acetyl chloride and aluminum chloride in carbon tetrachloride. Here falls the dichlorobutanone (2) also as a complex compound with aluminum chloride in solid form, the is separated from the mother liquor containing carbon tetrachloride by suction filtration. The complex compound of dichlorobutanone contains considerable amounts due to its physical nature of carbon tetrachloride, which after the decomposition of the complex compound with ice water the Contains dichlorobutanone (2) in solution. For further processing it is necessary to go through this solution Treatment with a desiccant, such as anhydrous sodium sulfate, to dry.

However, the described method has various disadvantages. For example, the dichlorobutanone (2) aluminum chloride complex and the free dichlorobutanone- (2) or its solutions are very uncomfortable to handle substances because they are pungent smelling products with physiological effects on human skin and respiratory organs. In addition, the dichlorobutanone decomposes even when stored at room temperature with elimination of hydrogen chloride and is consequently not distillable. This results in the work-up of the carbon tetrachloride mother liquor the need to first treat the dissolved hydrogen chloride by an aqueous alkaline treatment tie. This is followed by the separation of the carbon tetrachloride, its drying and distillation before it can be used again. on the other hand the carbon tetrachloride content of dichlorobutanone causes it to accumulate in the methanolic Mother liquor of the resulting, insoluble in methanol 2-sulfanilamido-4-methylpyrimidine sodium, so that, as has been found by the inventor, at one Method of manufacture

of pure 2-sulfanilamido-4-methyl-

pyrimidine

Applicant:

VEB paint factory Wolfen,
Wolfen (district of Bitterfeld)

Dr. Hans Wesche and Dr. Günther Peümann,

Wolfen (district of Bitterfeld),
have been named as inventors

Reuse of this mother liquor, which has been purified by simple distillation, results in a rapid lowering of the 2-sulfanilamido-4-methylpyrimidine yield occurs. In this way of working, you are forced to go ahead to make a clean separation of the carbon tetrachloride when reusing the methanol, which is cumbersome and associated with great costs, since a simple fractional distillation fails here. The complete removal of the carbon tetrachloride is necessary for another reason. Because the recovered methanol is used to react with sodium to produce the sodium methylate solution is used, it is necessary for safety reasons that carbon tetrachloride is absolutely necessary is absent.

The disadvantages of the known method are avoided if one follows according to the invention is working:

The dichlorobutanone (2) aluminum chloride complex prepared in a known manner is not separated from the mother liquor containing carbon tetrachloride, but the suspension is left of the said complex in carbon tetrachloride run directly into ice water and separates the lower Layer from which contains the dichlorobutanone- (2) dissolved in the carbon tetrachloride used. In In this way, handling these dangerous substances is completely eliminated.

The moist carbon tetrachloride solution is continuously fed to a thin-film evaporator, see above that this continuous operation achieves a momentary separation of the two components becomes and the dichlorobutanone- (2) without decomposition

109 688/212

3 4

accrues. In contrast, a separation would flow into the evaporator chamber 1. With help of a

Carbon tetrachloride through a discontinuous regulating valve 6 is the feed rate

Distillation with unacceptable decomposition of dichloro-regulated. The evaporator chamber 1 is heated by

butanones connected. the boiler room 2, the heating means through the

Advantageously, the thin-film 5 line 3 enters and the heating evaporator through the line 4 in the implementation of the invention space 2 leaves again. The one in the evaporator compartment 1 Carbon tetrachloride evaporated under reduced pressure according to the process is transferred to the body. A device 7 is supplied to a cooler 8 in this simple manner. Then runs Dichlorobutanone- (2) which is free from water and tetra; the carbon tetrachloride by having a carbon base is and continuously see the p-amino io layer, e.g. B. quicklime, charged absorber 11 benzenesulfonylguanidinsuspension in methanolic and is free of water and from line 12 Sodium methylate solution can be supplied, the hydrochloric acid removed. The one in the evaporator chamber 1 in a downstream apparatus under the remaining dichlorobutanone- (2) is also same reduced pressure is located. In addition, it is passed through a cooler 8 'into which the cooling water but then there is a substantial recovery of the incoming 15 through line 9 'and which it enters through line 10' set carbon tetrachloride leaving again after that. From the line 13 one receives a Passing one with a basic layer of z. B. dichlorobutanone- (2), which is free of water and tetra quicklime The absorber charged is free of water and chlorocarbon and continuously contains 2-p-amino hydrochloric acid accrues and readily used again benzenesulfonylguanidinsuspension in methanolic can be. 2 ° sodium methylate solution is supplied. In advantageous

The absence of water and tetrachlorous manner is the method according to the invention in

carbon in dichlorobutanone (2) causes a thin film evaporator under reduced

Reaction with p-aminobenzenesulfonylguanidine carried out a print. For this purpose the appa-

Excellent yield of 2-sulfanilamido-4-methyl- temperature provided with vacuum connections 14.
pyrimidine sodium or after working up in 25

known way on 2-sulfanilamido-4-methylpyrimi- example

din. Furthermore, the work-up of the methano- In a suspension of 65.5 parts by weight of aluminum

mother liquor, which is now free of tetrachlorine chloride in 655 parts by weight of carbon tetrachloride

carbon is very simplified, so that 38.5 parts by weight of acetyl

Distillation will regain the methanol and flow 30 chloride at room temperature. Be on it

can be used again without further ado. 31 parts by weight of vinyl chloride with ordinary or

It was by no means to be foreseen that one would initiate with the increased pressure. The resulting suspension

described thin film evaporator a tetrachloride sion of dichlorobutanone (2) aluminum chloride com-

carbon-free product that allows plexes in carbon tetrachloride is then left

very pure 2-sulfanilamido-4-methylpyrimidine to syn- 35 flow into a mixture of water and ice and stir

thetize (m.p. 236 to 237 ° C). until the complex decomposes. Then the

Of course, instead of the tetra-carbon tetrachloride layer, you can use the dichlorobuta-

chlorocarbon also other suitable, preferably non- (2) separated. This runs within about

Use halogenated hydrocarbons. Requires the thin film evaporator at about 50 ⁰ C for 1 hour

The only thing borrowed is that they don't work with acetyl chloride, vinyl 40 and 300 mm vacuum too. The yield of dichloro

chloride or dichlorobutanone (2) react, the latter butanone (2) is 55 parts by weight or 80% of the

however dissolve, hardly soluble in water and good theory of it. The distilled off carbon tetrachloride runs

are separable, e.g. B. methylene chloride, trichloroethane, through the absorber charged with quick lime and falls

Tetrachloroethane or chlorobenzene. in an amount of 550 parts by weight or 84%,

The method according to the invention must be applied in a 45 to the amount used. The dichloro apparatus, from a butanone (2) resistant to hydrochloric acid flows continuously with stirring into a Material such as glass, enamel, the suspension under the goods - under the same vacuum sign Igurit known graphite-containing synthetic resin by adding 64 parts by weight of p-aminobenzolod. Like. Is to be carried out. The sulfonylguanidine in 668 parts by weight of sodium methy separation des dichlorobutanone (2) carbon tetrachloride solution (= 29 parts sodium) was obtained. Sostorf mixture used thin-film evaporator soon the inflow of dichlorobutanone (2) has ended, can be with an internal heater (Fig. 1) or with a condensation after breaking the vacuum External heating (Fig. 2). In the case of apparatus, it is completed by stirring at the boiling point, with a higher output, it is advantageous if the 2-sulfanilamido-4-methylpyrimidine thin-film evaporator produced an inner and an outer 55 sodium is separated on a pressure filter and has heating. It is also useful if covered with 400 parts by weight of methanol. By a the upper heating jacket for the external heating a simple distillation of the mother liquor will be 830 higher Temperature than the lower one. Also recovered by weight of methanol. Corresponding similar constructions using a bundle - 80 percent by weight of the amount used. the pipe system as a heat source can be used. 60 sodium compound of 2-sulfanilamido-4-methyl-

The pyrimidines shown schematically in the figures are mixed with salt after dissolving in water Apparatus is thin-layer acid set to a pH of about 7. Purpose vaporizer, as it is moderate, for example, to carry out the aqueous solution before the addition of acid of the method according to the invention are subjected to a treatment with activated carbon. the can. To separate the dichlorobutanone (2) - 65 extracted free compound of the 2-sulfanilamido-carbon tetrachloride mixture with one of the two 4-methylpyrimidines it is sucked off, with To achieve illustrated thin film evaporator, leaves water covered and dried. There are 67.5 gems the mixture to be separated via the feed vessel 5 parts by weight of pure product. The melting point is

at 236 to 237 ° C. The yield is 85% of theory, based on the p-aminobenzenesulfonylguanidine used. If one takes into account that part of the p-aminobenzenesulfonylguanidine used is recoverable is, the yield is 95%> based on consumed p-aminobenzenesulfonylguanidine.

Claims (2)

PATENT CLAIMS: 1. A process for the preparation of pure 2-SuIfanilamido-4-methylpyrimidine by decomposition of dichlorobutanone (2) aluminum chloride with ice water and condensation of the dichlorobutanone obtained with p-aminobenzenesulfonylguanidine in the presence of alcoholic solutions of alkali metal alcoholates, characterized in that the at the Decomposition of the dichlorobutanone (2) aluminum chloride complex compound which is suspended in carbon tetrachloride and which is formed and separated from the aqueous layer, is continuously separated into carbon tetrachloride and dichlorobutanone (2) on a thin-film evaporator and continues as stated above. 2. The method according to claim 1, characterized in that instead of carbon tetrachloride other suitable suspending agents are used which do not react with the reaction components, are sparingly soluble in water and dissolve the dichlorobutanone. Considered publications:
German Auslegeschrift No. 1 033 666;
U.S. Patent No. 2,690,439;
"Chemical Abstracts", Vol. 51 (1957), Col. 15449; Houben-Weyl, "Methods of Organic Chemistry", Vol. 1/1 (1958), pp. 815 to 818. 1 sheet of drawings © 109 688/212 9.61