SU852171A3 - Method of preparing derivatives of 4-oxythiazolidinthioketene-2 and their salts - Google Patents

Description

(54) METHOD FOR OBTAINING DERIVATIVES OF 4-OXYTHIAZOLIDINTHIOKETON-2 OR THEIR SALT

one

This invention relates to a process for the preparation of new derivatives of 4R "s rt

 TinRz4-N-SJ

OH where R is a hydrogen or halogen atom at position -4, -5, or -6 pyridine ring; R, is a hydrogen atom, alkyl, containing from 1 to 8 carbon atoms, an alkyl containing from I to 4 carbon atoms, substitutable from 1 to 3 halogen atoms or phenyl, hydroxy; alkoxy, alkoxy, alkoxy, alkoxy and alkoxy . hydrogen atom, alkyl, acyloxyalkyl alkoxycarbonylalkyl or alkoxycarbonyl or forms alkylene with Rj,

-oxithiazolidinethiketone-2 General formula

Vs

R.f

Cg j N containing 3 or 4 -carbon atoms in the chain of which two adjacent carbon atoms may be part of a benzene radical; K is a hydrogen atom. or lower alkyl (and in all cases alkyl, alkoxy, acyl radicals have from 1 to 4 carbon atoms) or their salts. Compounds of general formula 1 possess antihelminthic activity and can be used in copper. A known method for the preparation of 4-oxythiazolidin-thion-2 derivatives of the general formula He: B-f Y R "YT HF gle R is a mischime alkyl or phenyl; f (- lower alkyl or substituted phenyl; hydrogen atom, methyl or phenyl, zyuchlyuch onys in that the amine of the general formula. where R has the above mentioned eiachenn, is subjected to interaction with the carbon disulfide in the medium of an organic solvent in the presence of potassium acetate and the resulting product cadmiums are reacted with a Qi-halogen ketone of the general formula l-c-en-x where R and R have higher values in the medium of an organic solution in ST. The purpose of the invention is to obtain new derivatives of 4-oxythiazolidin-thioketone-2, possessing anti lamine activity that can be found used in medicine. The goal is achieved by the fact that in the method of producing compounds of the general formula T in which oi is a haloketone of the general formula -o-x where IL, R and Rj have the above values, X is a halogen atom , is reacted with dithiocarbamate of the general formula NHC5S NH (R5), where R has the above values of Rg - lower alkyl in an organic solvent, in water or in an aqueous-organic solution at temperatures from -10. before, and the desired product is available in free or as salt. An example, -To a solution of 65.4 g of tri-thylammonium 2-pyridyl-dithiocarbamate in 30 ml of dimethylformamide was added at 10 ° C 37.7 g of 50 wt. % aqueous solution of chloroacetaldehyde. The reaction is carried out for 16 hours at 20 ° C. After evaporation of the solvents under reduced pressure (0.1 mm Hg) at 50 ° C, the residual oil is treated with 750 ml of chloroform. Chloroform solution. It is circulated twice in total complexity with 200 ml of distilled water, dried over sodium sulfate and evaporated. The oily residue (38 g) is dissolved in 180 ml of boiling ethanol and 180 ml of boiling isopropyl oxide and 1 g of growing saki are added. After filtering the boiling solution, it is cooled to 2 ° C for 2 hours, the crystallized crystals are separated by filtration, washed with a total of 50 ml of ice-cold mixture with 25 ml of ethanol and 25 ml of isopropyl oxide and dried at the same pressure (0.1 mm Hg). ) at. Thus, 17.8 g of 4-hydroxy-3- (pyridyl-2) -2-thiazolidin-thio-ketone, melting at 110 ° C, are obtained. Example 2 To a suspension of 54, 2 g of triethylammonium 2-pyridyl-dithiocarbamate in 300 ml of distilled water, 27.4 g of 2-bromopropanol are added at about 1517 ° C. The reaction is carried out for 35 minutes at 20 ° C. The water is removed by decantation, and the resulting pasty is treated with 250 ml of ethanol. After filtration and evaporation of the solvent at a reduced pressure (20 mm Hg) at 40 ° C, the residual oil (48.3 g) is dissolved in 40 ml of chloroform, the solution is filtered into 350 g of silica (0.2-0.5 mm), which is contained in a 4.5 cm column, diluted with 3.6 liters of chloroform. After evaporation of the solvent at a reduced pressure of 20 mm Hg) while the product obtained (13.3 g, m.p.) is dissolved in a boiling mixture of 200 ml of methylcyclohexane and 55 ml of ethanol. After filtering the boiling solution, and then cooling to 20 ° C, the crystallized crystals are separated by filtration, washed with 50 ml of methylcyclohexane and dried under pressurized pressure (0.1 mm Hg) at. Thus, 10.3 g of 4-hydroxy-5-methyl-3 - (pyridyl-2) -thiazolidine-ketone, melting at 112 s, are obtained. Example 3. To a suspension of 71.2 g of triethylammonium 2-pyridyl-dithiocarbamate in 330 ml of anhydrous acetonitrile, 39.7 g of 2-bromo-2-methylpropanol are added at about 5 ° C. The reaction is carried out for 1 h at. Insoluble bromohydrate triethylamine is removed by filtration. Aceunitrile is evaporated at reduced pressure (20 mm Hg) at. Residual oil is treated with JOO ml of methylene chloride. The organic solution is washed twice with a total of 100 ml of distilled water, dried over sodium sulfate and evaporated. The resulting product (60 g) is dissolved in 30 ml of methylene chloride, the solution is filtered onto 850 g of silica (0.20, 5 mm) contained in a column with a diameter of 5 cm, diluted with 9 liters of methylene chloride. After evaporation of the solvent under reduced pressure (20 mm Hg) at 40 ° C, the product obtained (50 g) is dissolved in 150 ml of boiling methyl cyclohexane. After cooling for 16 hours, the crystals are separated by filtration, expanded into 50 ml of methylcyclohexane and dried, at a reduced pressure (0.1 mm Hg).

at 400C. Thus, 44.1 g of 5.5-methyl-4-hydroxy-3- (pyridyl-2-2-thiaoolidin-thioketone, melting at.

Example 4. The procedure is the same as in Example 2, but starting from 40.6 g of triethylammonium 2-pyridyl dithiocarbamate and 14.0 g of chloroacetone in 250 ml in distilled water. The reaction is continued for 2 hours at 20 ° C. After recrystallization in 40 ml of ethanol, 20.0 g of 4-hydroxy-fd-methyl-3-) pyridyl-21 -2-thiazolidin-thio-ketone, melted at, is obtained.

Example 5 To a suspension of 44.5 g of triethylammonium 5-chloro-2-pyridyl dithiocarbamate in 180 ml of dimethylformamide was added at 13.5 g of chloroacetone. The reaction is carried out for 45 minutes at 2 ° C. The insoluble triethylamine hydrochloride is removed by filtration and washed with 20 ml of dimethylformalvild. Dimethylformamide (filtrate and washing) is evaporated under reduced pressure (0.1 mm Hg) at 45 ° C, the residual oil is treated with 40 ml of ethyl acetate. The organic solution is washed twice with a total of 100 ml of distilled water, dried over sodium sulfate and evaporated. The resulting product (41 g) is dissolved in 100 ml of boiling ethanol. After 4 h of cooling, the crystals are filtered off, washed twice with a total of 15 ml of ice-cold ethanol and dried under reduced pressure (0.1 mm Hg) at 450c. Thus, 16.8 g of 5-chloro-3- (pyridyl-2) -4-hydroxy-4-methyl-2-thiazolidinothioketone are obtained, melting at 95 ° C.

Example 6. The procedure is the same as in Example 5, but starting from 66.0 g of 2-pyridyl-dithiocarbamate of triethylammoni and 26.0 g of 3-chloro-2-tanone-2 in 300 ml of dimethylformamia at 20 s. The reaction is continued for 30 minutes at 20 ° C. After recrystallization in 540 ml of ethanol, 48.5 g of 4,5-dimethyl-4-hydroxy-3- (pyridyl-2) -2-thiazolidinthioketone melting at 159 ° C are obtained.

Example. The procedure is the same as in Example 3, but starting from 27.0 g of triethylammonium 2-pyridyl dithiocarbamate and 16.5 g of 3-bromo-3-methyl-2-butanone in 400 ml of anhydrous acetonitrile at. The reaction lasts 30 minutes at 20 ° C. After recrystallization in 200 ml of ethanol, 15.0 g of 4-hydroxy-3- (pyridyl-2) -4,5,5 trimethyl-2-thiazolidin-thioketone are obtained, melting at 14 bOC.

Example 8. jDienes are the same as in Example 3, but starting from 400.0 g of 2-pyridyl-dithiocarbg # 1 triethylammonium and 22.1 g of 2-chloro-3-oxomethylbutanoate in 270 ml of anhydrous acetonitrile at a maximum temperature of 25 ° C. The reaction lasts 3 hours at 20-25 ° C.

After recrystallization in a mixture of 30 ml of ethanol and 130 ml of isopropyl oxide, 23, 3 g of 4-hydroxy-4-methyl-3- (pyridyl-2) -2-thioxy-5-thiazolidinyl-methylcarboxylate, melted at 95 ° C, are obtained.

Example 9. Act as in Example 3, but starting from 50.0 g of 2-pyridyl-dithiocarbamate triztil1 F1oni and 32.9 g of 3-chloro-4-oxo-amyl acetate in 250 ml of anhydrous acetonitrile at 29c maximum. The reaction lasts 2 hours at 20-29 ° C. After recrystallization in a mixture of 50 MP of ethanol and 210 ml of isopropyl oxide, 46.0 g of 2-C4-hydroxy-4-methyl-3- (pyridyl-2) -2-thioxy-5-thiozolidinyl ethyl acetate are obtained, melting at.

EXAMPLE 10 The procedure is the same as in Example 3, but starting from 21.8 g of tri-ethyl ammonium 2-pyridyl-dithiocarbamate and 17.9 g of methyl 4-bromo-5-oxo-hexanoate in 200 ml of anhydrous acetonitrile at maximum. The reaction was carried out for 2 hours at 20-ZOOs. Recrystallization in a mixture of 10 ml of methylene chloride and 70 ml of ethyl ether gives 20.4 g of 3-f4-hydroxy-4-methyl-3- (pyridyl-2) -2-thioxy-5-thiazolidinyl methyl propionate, melting at 8bc . 23.0 g of 4-bromo-5-oxohexanoate methyl (temp. Bp 94 C) are obtained when exposed to 5.4 g of diazomethane per 26.5 g of 4-bromo-5-oxohexanoic acid in 200 ml of ethyl ether at a temperature of about.

Example 11. The procedure is the same as in Example 5, starting from 64.0 g of triethylammonium 2-pyridyldithiocarbamate and 25.6 g of 1-chloro-2-butanone in 300 ml of dimethylformamide at maximum AOC. The reaction is carried out for 30 minutes at

25-30 s. After recrystallization in a mixture of 75 ml of ethanol and 75 ml of isopropyl oxide, 29.9 g of 4-ethyl-4-hydroxy-3- (pyridyl-2) -2-thiazolidine-thiketone-2, melting at 113 s, are obtained.

Example 12. The same effect is as in Example 5, but the outcome is 5, Og of 2-pyridyl-dithiocarbamate of triethylammonium and 29.0 g of 1-chloro-2-pentanone in 300 ml of dimethylformamide at the maximum. The reaction lasts 2 hours at 20-25 C. After recrystallization in a mixture of 75 ml of ethanol and 75 ml of isopropyl oxide, 41.5 g of 4-hydroxy-4-propyl-3- (pyridyl-2) -2-thiazolidinthiocetone are obtained, melting at .

Example 13. The procedure is the same as in Example 5, but starting from 43.2 g of triethylammonium pyridyl-2-dithiocarbamate and 19.8 g of 1-chloro-3-methylbutanone-2 in 210 ml of dimethylformamide at 20c. The reaction lasts 2 hours at 20 s. After recrystallization in a mixture of 35 ml of ethanol and 75 ml of isopropyl oxide, 33.8 g of 4-hydroxy-4-isopropyl-3- (pyridyl-2) -2-tyazolidintioketone, melting at. Example 14: The procedure is the same as in Example 3, but the outcome is 56.5 g of 2-pyrindyl-dithiocarbamate trnethy ammonium and 28.0 g of 1-chloro-2-hexanone in 250 ml of dimethylformamide at maximum temperature. The reaction continues 2 hours at 20-250 ° C. After a chromato graphite on 600 g of silica (0.2-0.5 mm), distributed in a column with a diameter of 5.5 cm, 46.4 g of oily product are obtained. The product is purified by recrystallization in 250 ml of methylcyclohexane. Thus, 37.4 g of 4-butyl-4-hydroxy-3- (pyridyl-2) -2-thiazolidin-thioketone-2, melting at 5 ° C, are obtained. Observations are made in infrared light, respectively, from 2 to 3% (carbonyl band at 1710 cm) and from 2 to 5% (carbonyl band at 1710 cm; 1-pyridyl-ditioyarbamate 2-rxohexyl in the product in accordance with how examined, between plates in vaseline or in chloroform solution.

Example 15. To a suspension of 46.0 g of diethylammonium 2-pyridyl-dithiocarbamate in 210 ml of dimethylformamide was added at a maximum temperature of 25 ° C 23.0 g of 1-chloro-4-methyl-2-p-entanone. The reaction was carried out 2 hours at 20-25 ° C. The insoluble triethylamine hydrochloride is eliminated by filtration and washed with 50 ml of dimethylformamide, which is evaporated under reduced pressure (0.1 mm Hg) at 50 s, the residual oil is treated with 700 ml of ethyl acetate. The organic solution of ProPF1 is applied 3 times in total using 300 ml of distilled water, dried on sodium sulfate, treated with 3.0 g of vegetable black, filtered and evaporated at reduced pressure (20 mm Hg) at. The resulting product (48 g) is dissolved in 30 ml of boiling ethanol and 60 ml of isopropyl oxide is added to the boiling solution. After 2 hours of cooling to 2 ° C, the crystallized crystals are filtered off, washed three times with 75 ml of isopropyl oxide and dried at a reduced pressure {0, lt / SM Hg) at 40 sec. Thus, 35.0 g of 4-methyl-2-oxoamyl 2-pyrndyldithiocarbamate, melting at 92 ° C, is obtained. When the product is examined in infrared light in a chloroform solution, about 80-90% of 4-scsi-4-isobutyl-3- (pyridyl-2) -thiazolidinthioketone (-OH and H bands, connected from 2700 to 3 OOO CM, decrease the intensity of carbonyl lanes at 1710). This form is not detected when the product is examined between the plates in petroleum jelly.

Example 16. to the suspension of 210 g of 2-pyridyl-dithiocarbamate t | yethyl in them in 1000 ml of anhydrous acetylnite-. within 15 minutes and at a temperature between 18 and 23 ° C, 138 g are added

1-bromo-3, 3-dimethyl-butanone-2. The reaction is continued for 16 hours at. The crystallized crystals are isolated by filtration and washed with 100 ml of acetonitrile, which is evaporated under reduced pressure (20 mm Hg) at 50 ° C. The resulting residual oil is combined with the pre-separated crystalista and treated with 2000 ml of ethyl acetate. The organic solution is washed with 500 ml of distilled water, dried on sodium sulfate, filtered and evaporated under reduced pressure (20 mm Hg) at. The product obtained is dissolved in 1000 ml of boiling acetyl nitrile, 5.8 g of vegetable black is added and the boiling solution is filtered. After 2 hours of cooling to 2 ° C, the crystallized crystals are separated by filtration, washed 2 times in 100 ml of ice-cold adetonitrile, and dried under reduced pressure (0.1 mm Hg) at 5 (Pc. Thus, 137 g of 2-pyridyl dithiocarbamate are obtained 3, 3-dimethyl-2-oxobutyl, melted at.

Example 17. The procedure is the same as in Example 16, but starting from 230 g of triethylammonium 5-chloro-2-pyridyl-dithiocarbamate and 135 g of 1-bromo-3, 3-dimethyl-2-butanone in 2000 ml of anhydrous acetonitrile at 20 ° WITH. The reaction lasts 2 hours at. After recrystallization in 1700 ml of ethanol, 142.1 g of 5-chloro-2-pyridyl-dithiocarbamate 3,3-dimethyl-2-xobutyl are obtained, melting at 139 ° C.

Example 18: The procedure is the same as in example 5, but starting from 27.1 g of 2-pyridyl-dithiocarbamate three, ethylammonium and from 17.6 g of 1-chloro-2-nonanone in 135 ml of dimethylformamide at 2 (PC. Reaction lasts 2 hours at 20 ° C. The product is purified by chromatography on 1 kg of silica (0.20, 5 mg), which is carried out in a column with a diameter of 6.5 cm. Dilute in 5 liters of chloroform, which is eliminated, then in 4 liters of chloroform which is evaporated at reduced pressure (20 NW Hg) at BO – C. The purified oily product is dried for 4 hours at 70 ° C at a pressure of 0.1 mm Hg. In this way 15.0 g of 4-heptyl-4-hydroxy-3- (pyridyl-2) -2-thiazolidinethiketone. When the product is examined by IB infrared radiation between plates in vaseline or in a chloroform solution, 3 to 50% of 5-pyridyl-dithiocarbamate is detected. 2-oxo-nonyl (carbonyl band at 1710 cm).

Claims (1)

Example 19. The procedure is the same as in example 2, but starting from 55.0 g of triethylammonium 2-pyridyl-dithiocarbamate and from 38.7 g of 1-chloro-2-decanone in 280 ml of distilled water at 20 ° C. The reaction is continued at. The product is purified by xp chromatography on 1.5 kg of silica (0.2-0.5 mm) which is carried out in a column with a diameter of 7, Ü cm. Diluted in 2 L of chloroform KOToixdO is removed, then in 1.6 L of chloroform, which is evaporated at reduced pressure (20 mm Hg) at. The oily purified product is dried for 3 hours at 60 ° C at a pressure of 0.1 mm Hg. Thus, 29.0 g of 4-hydroxy-4-octyl-3- (pyridyl-2) -2-thiazoline-thiketone are obtained. When the product is examined in infrared light between plates in petrolatum or in a chloroform solution, from 5 to 10% of 2-pyridyl-dithiocarbamate-2-oxydecyl is found (carbonyl band at 1710 cm). Example 2Q. They act in the same way as in example 3, but starting from 51.5 g of tri-ammonium 2-pyridyldithiocarbamate and from 22.5 g of 2-chloro-1-cyclopropyl-1-ethanone in 500 yl of anhydrous acetylnitrile at. The reaction lasts from 3 h at 20 ° C. After recrystallization in a mixture formed from 230 ml of acetonntril and from 1200 ml of isopropide oxide, 30.8 g of 4-cyclopropi-4-3- (pyridyl-21-2-thiazolidinothioketone melting at 95 ° C) are obtained. in infrared light in a chloroform solution, about 30% pyridyl-2-dithiocarbamate 2-cyclopropyl-2-oxo-ethyl (carbonyl band at 1695 cm) is observed, This form is not detected when examining the product between the plates and vaseline. as in example 3, but starting from 47.4 g of triethylammonium 2-pyridyldithiocarbamate and from 23.2 2-chloro-1-cyclobutyl-1-ethanone in 450 g of anhydrous acetonitrile at 20Q C. The reaction is carried out for 1 h at 20 C. After recrystallization in 100 ml of acetonitrile, 33.1 g of 4-cyclobutyl-4-hydroxy-3- ( pyridyl-2) -2-thiazolidinethioketone melting at 123 ° C. When the product is examined in infrared light in a chloroform solution, a wide band of 1700 cm is observed which can correspond to 2-3% 2-pyridyl dithiocarbamate 2-cyclobutyl-2-oxoethyl . This band does not occur when the product is investigated. blowing between the plates in vazapine. -. Example 22. Act as in example 3, but based on 47.4 g. Triethylammonium 2-pyridyl-dithiocarbamate and from 25.7 g of 2-chloro-1-cyclopentyl-1-tetanerne 1 in 450 ml of anhydrous acetylnitrile at 20c. The reaction is carried out for 1 h at. After recrystallization in 90 ml of acetonitrile, 31.3 g of 4-cyclopentyl-4-hydroxy-3- (pyridyl-2) -2-thiazolidin-thioketoia are obtained, melting at 118 ° C. When the product is studied in infrared light in a chloroform solution, a wide band is observed to 1700 cm. The motor can correspond to 5% 2-pyridyl-dithiocarbamate 2-cyclopentyl-2-oxo-ethyl. This band is not observed when the product is examined between the plates; in petrolatum. The compounds of general formula 1 possess anti-helminth activity. In particular, their activity was observed in your Nematospiroides dubis in doses of 5 to 200 mgg / kg by oral route. In addition, most products are active against phyriosis in rats with Litomosoides carFni i in doses ranging from 25 to 100 mg / kg, orally per day, during treatment, which took place over a period of 5 days. Some products have also shown to be active on the dog at doses ranging from 10 to 58 mg / kg by the oral route, when exposed to Ankylostoma carinum and Uncinaria stenoeephale at doses ranging from 5 to 5U mg / kg by the oral route when exposed to Tochosaga canis or Toxaseag i S 1 eon i pa. The toxicity of the products, expressed in their 50% lethal dose (LDgQ), is from 200 mg / kg by the oral route in a mouse to a value greater than 1000 mg / kg by the oral route. The invention method for producing 4-oxythiazolidinthioketone-2 derivatives of general formula 1 Uf " “-GGUCH,“ i “L where R is hydrogen or halogen at position -4, -5, or -6 of the pyridine ring; R2 is a hydrogen atom containing, from 1 to 8 carbon atoms, alkyl containing from 1 to 4 carbon atoms, substituted with 1 to 3ASH atoms of halogen or phenyl, hydroxy, cycloxy, alkylthio, carboxy, alkoxycarbonyl, alkoxycarbonylalkoxy, alkoxycarbonylalkylthio, acyloxy, acyloxyglykoxy or acyloxycischylthio-radical, cyclohexynyl, phenyl substituted by one halogen atom or by alkyl, alkyloxy, oxy- or nitro-radical, 2-thienyl or alkyloxycarbonyl, alkyloxy, oxy- or nitro-radical, 2-thienyl or alkyloxycarbonyl, alkyloxy, oxy- or nitro-radical, 2-thienyl or alkyloxycarbonyl, alkyloxy, oxy- or nitro-radical Ra is a scar of hydrogen, alkyl, adyloxy-alkyl, alkoxycarbonyl or alkyl. alkoxycarbonyl or K „forms with Rd alkylene containing 3 or 4 carbon atoms, and the chains of which are two adjacent carbon atoms may form part of the benzene ring; Cc is a hydrogen atom or a lower alkyl, (moreover, in all cases alkyl alkoxy, acyl radicals have from 1 to 4 carbon atoms) or their salts, which is different from the fact that f is a halogeno-ketone of the general formula 2 Br-CO-C-X I B4 where K / 2, RO and RI have the above values and X is a halogen atom, which is reacted with dithiocarbamate of the general formula III: -. € LN STiCSSl H (R5) 3 where R has the above values RK is lower alkyl in the organic solvent in water, or in a water-organic solution at a temperature of from -10 to 50 ° C and the target product is recovered in free form or as Is. Priority signs: 17.05.77. when R is a hydrogen atom or halogen and the position is -4, -5 or -6 pyridine ring; RO. - a hydrogen atom or an alkyl containing s from 1 to 4 carbon atoms, benzyl or phenyl; RCs RJ, are the same or different, each of them is a hydrogen atom or an alkyl containing from 1 to 4 carbon atoms. 04/25/78. when R is a hydrogen or halogen atom, at position -4, -6, or -6 of the pyridine ring; R - alkyl containing from 5 to 8 carbon atsmmov, methyl substituted by 1 to 3 halogen atoms or a radical of hydroxy, lower oshkoksi, alkylthio, carboxy, alkyloxycarbonyl, gshkoksikarbonilalkoksi, alkoksikarbonilalkiltio, acyloxy, atsiloksialkoksi or atsiloksialkiltio, alkyl containing from 2 to 4 carbon atoms, hardened with 1 to 3 halogen atoms or a phenyl, hydroxy, alkoxy radical; alkylthio, carboxy, alkoxycarbonyl, gshkoksikarbonilalkoksi, alkoksikarbonilalkiltio, acyloxy, or atsiloksialkoksi atsiloksialkiltio, cycloalkyl having 3 to B carbon ats Job, cyclohexenyl, phenyl substituted with one halogen atom or a radical alkyl, alkyloxy, hydroxy or nitro, 2-thienyl radical or alkoxycarbonyl, and R and R are the same, each of them represents one hydrogen atom or an alkyl containing from 1 to 4 carbon atoms, or Rj has the meaning given in the claims, a hydrogen atom or an alkyl; RI is a lower alkyl group other than R / (, acyloxyalkyl, alkoxycarbonylalkyl or alkoxycarbonyl or forms alkylene with R containing 3 or 4 carbon atoms, in the chain of which two adjacent carbon atoms can form part of the benzene ring. Sources of information taken in consideration in the examination 1. RWLamon et.al. 4-Thiazo1ine-2-thiones III. The the rmody namf with the stabi.Jity of Intermediate Tautomeric thiazo1idines and dithiocarbamates. Het chem, 1967, v.4, p 349.