DE1645985C - Process for the preparation of dl 6 phenyl 2,3,5,6 tetrahydroimidazo square bracket to 2,1 square bracket to thiazole - Google Patents

Description

the clear supernatant liquid has a measured value of + 31 ° in a 2-dm polarimeter tube. The reaction mixture is heated in an oil bath for 6 hours at 108 ⁰ C. At this time, the measured optical rotation of + 13.5 °. The reaction mixture is heated to the same temperature for a further 6 hours. A rotation value of + 8 ° is now measured. The reaction mixture is poured into water and the product is recovered by extraction with methylene chloride. The methylene chloride is evaporated and the residue is converted into the hydrochloride with acetone and isopropanolic hydrogen chloride. The yield of dl-ö-PhenyW.SSo-tetrahydroimidazo- [2.1b] thiazole hydrochloride, mp = 259 to 263 ° C., is 0.46 g. A determination of the specific rotation value shows that the product is practically 100% racemized.

Example

From 4 ml of dimethyl sulfoxide and 100 mg of sodium methylate a suspension is made. Then 1 g of d (+) - 6-phenyl-2,3,5,6-tetrahydroimidazo [2, l-b] -thiazole dissolved in the mixture. For the clear liquid above the relatively insoluble sodium methylate a rotation value of + 34 ° is measured when determined in a 2 dm tube. The mixture is heated to 108 ° C. in an oil bath for 6 hours. At this point in time the rotation value has decreased by + 8 ° 40 '. After heating for a further 6 hours, the rotation value is + 5 ° 30 '. The The hydrochloride is prepared as in Example 4. The yield of product, mp = 259 to 261 ° C, is 0.42 g. Determination of the specific rotation value shows that the product racemizes practically completely is.

Example 6

A solution of 2 g (9.8MoI) d (+> 6-phenyl-2,3,5,6-tetrahydroimidazo [2,1-b] thiazole in 20 ml of benzene is mixed with 2 ml (3.2 mmol) of Butylliüiium-Hexenlösung treated. After standing for two days, the benzene is decanted from a dark solid and evaporated, 1 / g of one sticky solid remains. The solid

ίο is washed with triethylamine and dissolved in acetone. By adding a small amount of isopropanolic hydrogen chloride, the hydrochloride, F. = 257 to 260 ° C, deposited. The yield is 200 mg. It becomes a specific rotation value

measured from + 6.3 °, which indicates that the product is almost completely racemized.

Example 7

By dissolving about 0.5 g of sodium amide in

A solution is prepared ao 25 ml of dimethyl sulfoxide. 1 ml of this solution becomes a solution of 1 g d (+) - 6-Phenyl-2,3,5,6-tetrahydroimidazo [2, l-b] thiazole in 8 ml of dimethyl sulfoxide was added. Nai.h few Minutes, the rotation value of the solution is 0 °. The reaction mixture is poured into water, and that Product is extracted with methyl chloride. The methylene chloride extract is washed with water and dried over anhydrous potassium carbonate. Remain after evaporation of the solvent

0.6 g dl-6-phenyl-2,3,5,6-tetrahydroimidazo [2, l-b] -thiazole, F. = 87 to 89 ° C. The product is dissolved in acetone and mixed with a little isopropanol Hydrogen chloride added. The deposited hydrochloride is filtered off and washed with acetone.

The dl-6-phenyl-2,3,5,6-tetrahydroimidazo [2, lb] thiazole hydrochloride melts at 264-265 ⁰ C.

Claims (1)

0.5 g of a 50 percent dispersion of sodium patent claim: hydride in mineral oil, a mixture is produced. After standing overnight at room temperature it becomes Process for the preparation of dl-6-phenyl- the suspension poured into water, and the dl-6-Phe-2,3,5,6-tetrahydroimidazo [2, lb] thiazole and sein- 5 nyl-2,3,5 , 6-tetrahydroimidazo [2, lb] thiazole is a hydrochloride, characterized by extracting the water mixture with methylene acetate, which is obtained on d (+) - 6-phenyl-2,3,5,6-tetrachloride. The methylene chloride extract is hydroimidazo [2, lb] thiazole in the absence of dried over anhydrous potassium carbonate and water an alkali metal alkoxide, alkali metal evaporated. The residue is dissolved in ether Hydrochloride transferred. - at 260 to 263 ° C. The product has a specific rotation value of + 10.5 °, which indicates- ______ 15 that it consists of about 95% racemic dl-6-Phe- nyl - 2,3,5,6 - tetrahydroimidazo [2,1 - b] thiuene hydrochloride consists. The invention relates to a method for Her- _R ■; _e 1 9 position of di-o-phenyl ^^. ö-tetrahydroimid- ^p azo [2, l-b] thiazole and its hydrochloride. ao A mixture of 200 mg d (+) -6-phenyl- d (+) -6-phenyl-2,3,5,6-tetrahydroimidazo [2.1b] - 2,3,5,6-tet.rahydroimidazo [2.1b] thiazole and 50 mg thiazole is difficult to racemize. It is racemized potassium tert-butoxide is heated in an oil bath for 2 hours is not in acidic solutions in which salt formation ER- to 100 C ^c. The product is between follows. It is distributed by heating to high temperatures methylene chloride and water. The methylene tures, or by heating them in solutions of a chloride layer, are separated off and dried over water bases in solvents containing hydroxyl groups, free of potassium carbonate. Replaced in a Polari-E. meter the rotation value is measured. The rotation value Surprisingly, however, a process is 0 °, which indicates complete racemization, for the production of dl-6-phenyl-2,3,5,6-tetrahydro- The methylene chloride is evaporated, and the Rückimidazol2, Ib] thiazole and its hydrochloride are 30 stand is dissolved in acetone. The hydrochloride is found, which consists in reacting to d (+) -6-Phe- by adding some isopropanolic chloromyl-2,3,5,6-tetrahydroimidazo [2.1b] thiazole in waste hydrogen to the solution manufactured. The absence of water, an alkali metal alkoxide, harmful hydrochloride is filtered off. The aus-alkali metal amide, alkali metal hydride or an al- beute is 145 mg (62%) dl-6-phenyl-2,3,5, organo-potassium compound and 35 6-tetrahydroimidazo [2, ib] thiazole hydrochloride; F. = then optionally the dl-base obtained 262 ° C.
converted into their hydrochloride. B ice T he 1 3 The reaction can be with or without a solvent be performed. If a solvent dissolves 200 mg potassium tert-butyiate is used, it must neither destroy the activity of the base to be used in about 8 ml of dimethylformamide, nor produce solvolysis of the ring. Then 2 gd (+) -6-phenyl-2,3, systems will cause. The preferred solvents are 5,6-tetrahydroimidazo [2.1b] thiazole. They are dimethylformamide and dimethylsulfoxide, since the reaction mixture cools down when the amine goes into them, good solvents for the said bases and solutions. After dissolution of the solid matter are easily accessible. Other solvents can be used. 45 (about 10 minutes) the rotation value of the solution can be used, but they do seem to work. It is only 2 °. Dtr rotation value one nend no advantages. The preferred bases are non-racemized solution de. The same concentration of potassium tert-butoxide, sodium amide and sodium trate ion would be about 30 °. After 30 minutes hydride. Also other alkali metal alkoxides, alkali, the reaction mixture is poured into water. The metal amides and alkali metal hydrides are suitable, 50 deposited free base is filtered off and they are, however, less advantageous. Washed butyllithium and water. This product weighs 0.52 g and phenyllithiuir. can also be used. Melts at 88 to 89 ° C. Further product is The contact time can be from a few minutes to several hours, depending on the amount of the material in the polarimeter tube and the base used and the solvent used to extract the filtrates with methylene chloride. 55 wins. All fractions of the free base The temperatures at which combines the racemization and is carried out by treating an acetone solution, are preferably between 20 with isopropanolic hydrogen chloride in the ⁰ and 120 C. Higher and lower temperatures hydrochloride transferred. Although the yield of oil can be used, it does not appear to offer any advantage to 6-phenyl-2,3,5,6-tetrahydroimidazo [2.1b] thiazole-hynend. 60 hydrochloride, m.p. = 264 to 266 ° C, is 1.67 g The dI-6-pheny) -2,3,5,6-tetrahydroimidazo [2, I-b] - (68%). thiazole is used as an intermediate in the manufacture of example 4 the anti-helmintic l (-! compound. The following examples illustrate the invention. From 4 ml of dimethylformamide and 100 mg of sodium 65 methylate a suspension is made. Then it will be ^Beis P ' ^el ' · 1 gd (+) -6-phenyl-2,3.5 / letrahyclroimidazo [2, lb] - Dissolved from 300 mg of d (() - fi-PhcnyI-2,3,5,6-tetrahydrothiazole in the mixture imidazo [2, l-b] thiazole, 20 ml of dimethyl sulfoxide and almost insoluble sodium methylate has deposited