SU474149A3 - Method for preparing 2,3,5,6-tetrahydroimidazo (2,1-b) thiazole derivatives - Google Patents

Description

isolation of the target product in free form, or in the form of a salt, or a mixture of salts.

Process expedient to a irisutstvii ospoviyh compounds such as ammonium hydroxide, alkali metal hydroxides (nanrnmer, caustic Calne or sodium hydroxide), alkali metal carbonates (ianrimer, sodium carbonate or potassium carbonate), bnkarboiaty alkali metals (nanrimer, bicarbonate iatry or hydrogencarbonate : Aliy.) The reaction is desirable to lead in the aquatic environment, and this cyclization usually takes place at room temperature.

Compounds of the formula PA or PV, in which D is a halogen atom, rarely chlorine or bromine, can be obtained from the corresponding hydroxy derivatives by reacting with a halogenating compound. From the number of halogenating compounds, the reading is given to hydrogen bromide, phosphorus tribromide, thioiyl chloride, phosphoric acid chlorohydride, and phosphorus trichloride. The hydroxy derivatives of the formula PA or PW and the rotation are converted to the corresponding bromo derivatives by reaction with hydrogen bromide, and this process is carried out in an aqueous medium. Chloroethyl derivatives of the formula PA nli PV can be obtained but the reactions of the corresponding hydroxyethyl derivatives with thionyl chloride or phosphoric acid chlorohydride. Chlorination, achieved with thionyl chloride, is advisable to keep at lower temperatures, approximately 5-10 ° С, while using phosphoric acid chloride it is desirable to keep the process temperature in the range of 80-100 ° С.

The compounds of formula I can be converted to salts by known methods, not infrequently by reacting the base of formula I with an equivalent amount of the corresponding acid in the presence of an organic solvent.

As an acid, non-orthotic, for example, hydrochloric, hydrobromic, serine, or organic, for example, citrus, tartaric, and hydrochloric acids are used.

The compounds of formula I are isolated from their salts, treated and subsequently grounds.

Example 1. In 3.6 ml of water is dissolved 0.5 g of 2- (2-bromoethnl) -imiotiazolidine and 2 mg of concentrated ammonium hydroxide is added to the solution. The precipitated crystals are filtered and washed with water. As a result, 0.12 g of 2,3,5,6-tetrahydroimidazo- (2,1-b) -thiazole hydrobromide is obtained, t. Il. 179-190 ° C. The product crystallizes from acetone.

The starting material is obtained as follows. To 104.4 g of 2-methylmercantothiazoline iodohydrate is added a solution of 24.4 g of primary ethanolamine in 200 ml of methyl alcohol. The reaction mixture is refluxed for 20 hours. The solution is evaporated and the oily residue crystallizes on aging. As a result, 88 g of 2- (2-hydroxyethyl) -iminothiazolndium iodohydrate with t. NL are obtained. 132-135 ° C.

The resulting product is dissolved in water,

5, alkalinized with concentrated ammonium hydroxide and extracted with chloroform. After the solution, the solution in chloroform is evaporated and the residue is crystallized in benzene, t.nl. 2- (2-hydroxyethpl) -mino-nazo-lndia-bases 97-UGS.

Calculated,%: C 41.06; P 6,89; N 19.16 S 21.93.

Paydeno,%: C 41.15; H 7.47; N 19.07S 21.96.

15 8.11 g of 2- (2-hydroxyethyl) -iminothiazolidine-base is added to the concentrated hydrogen bromide, while the reaction mixture is cooled. Hydrogen bromide is then slowly, over 8 hours, distilled from

0 specified mixture. The mixture is evaporated to dryness, the residue is crystallized from acetone and acetonitrile. As a result, 5 g of 2- (2-bromoethyl) -imiotnazolidine bromohydrate with t il is added. 151 -152 ° C.

5 Calculated,%: C, 20.70; H 3.48; N 9.66; S 1.05: Vgosch 55,10.

Found

C 21.22; And 3.11; N 9.92;

S 11.18; 55.46.

Example 2. Dissolve in 15 ml of water

0 3.0 g of a mixture of 2- (2-bromoethyl) -iminothiazolidine iodohydrate and 2- (2-bromoethyl) -imothiazolidine bromohydrate, after which 120 ml of 10% sodium carbonate are added to the solution. The precipitated iro5 Duct is filtered and the nescrystallized is taken up in acetonitrile. The result is 0.25 g of a mixture of hydrobromide and 2,3,5,6-tetrahydroimidazo- (2,1-b) thiazole iodohydrate with t. Nl. 142-143 ° C.

0 The starting reagent was prepared as follows. 13.70 g of 2- (2-hydroxyethyl) -nminothiazolidine iodohydrate is mixed with 100 ml of concentrated hydrogen bromide, after which the last medleppo is distilled from the mixture for 7 hours. The reaction mixture is arnive dry. The residue is a gummy product (15.98 g), which crystallizes first in acetone and then ji ethyl acetate. A mixture of bromo hydrate and iodgndrata 2 - (2-bromoethyl) -imiotiothiazolide 1a is obtained with m. Pl. 132-135 ° C.

Example 3. To 23 ml of thionyl chloride was added 6.3 g of 2- (p-hydroxyethyl-a-phenylimino) -thiazolidine, while the temperature

Support the rabbi at 5-10 ° C with ice cooling. After dissolution, the mixture is stirred at room temperature for 2 hours. 105 ml of acetic anhydride is added dropwise to the reaction mixture and then acetic acid chlorohydride is distilled off for 1 hour. The solution is then shed for 2 hours and vaporized to dryness. The residue is dissolved in 100 ml of dilute hydrochloric acid (10: 1), defend

5 is alkalinized with ammonium hydroxide and extracted with toluene. The solution in toluene is dehydrated and evaporated. The oily residue is dissolved in acetone. The hydrochloride is precipitated and the addition of an isoiron sodium salt containing hydrochloric acid.

The result is 1.33 g of hydrochloride of 2,3,5,6-ststrahydro-6-feiylimndazo-2,1-b) -thiazole with m. Pl. 245-25GS. When non-recrystallization of the product in anhydrous ethanol t. Pl. rises to 261-263 ° C.

P1 SIMPLE reagent is prepared as follows. In 60 ml of anhydrous ethyl alcohol, 14.4 g of isothiociaic acid 2-bromoethyl ester is dissolved, after which a solution of 12.03 g of 2-feiyl-2-amio ethai-thiol in 25 ml is added to the resulting mass in 2 hours. 100 ml of anhydrous ethyl alcohol. The reaction mixture is moved at room temperature for 1 h and boiled for 2 h, evaporated, the residue is suspended in water, alkalinized 2 and. sodium hydroxide solution. The precipitated product is filtered and washed with gasoline. The result is 13 g of 2- (p-hydroxyethyl-a-phenylimino) -thiazolidine with so pl. 154 ° C. The product is crystallized in ethyl alcohol.

Calculated,%: C 59.42; H 6.35; N 12.60; S 14.42.

Paydeno,%: C 59.37; H 6.56; N 12.65; S 13.96.

Example 4. A mixture of 1.5 g of 2- (p-hydroxyethl-cs-fennlimino) -thiazolidine and 20 ml of phosphoric acid chloride is kept at 100 ° C for 2 hours. After 2 hours the mixture is poured onto ice, alkalified with ammonium hydroxide and extracted toluene After removing the solvent, the precipitate is dissolved in acetone. When hydrochloric acid-containing isoironyl alcohol is added to the solution, hydrochloride precipitates. Obtain 0.2 g of 2,3,5,6-tetrahydro-6-phenylimidazo-2, -b) -thiazole hydrochloride with m.p. 2b- After recrystallization in anhydrous acetone, the product melts at 261 - 263 ° C.

Subject and title of li

The method obtained derivatives of 2,3,5,6-tetrahydroimidazo- (2,1-b) -thiazole of the general formulu I

-N-

Hi C

.. And R-HC

where R is a hydrogen atom or a phenyl group which may be substituted by one or more halogen atoms, an alkyl, alkoxy, trihalomethyl group,

or a salt thereof, a mixture of salts, characterized in that, in order to simplify the process and expand the range of imidazothiazole derivatives, the compound of the general formula HA

D N W-CH. III i

H c-HG- c;: n,

m

30 or its tautomeric derivative, obi1, her formula PV

N-Cll,

R

i

-N-ON „

ns

 S n

where R 1meet specified s: 1ache 1 1, and D is a halogen atom,

subjected to cyclization followed by isolation of the target androdhkta in free form, or ideally salt, or a mixture of salt.