• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
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    • 专利摘要:
    2-Mercaptoethylamine hydrohalides of the formula …<CHEM>… wherin R1, R2, R3 and R4 are identical or different, and each represents a hydrogen atom, a lower alkyl group, a hydroxy-substituted lower alkyl group or a phenyl group, and X represents a halogen atom.… are produced by reacting …<CHEM>… in the presence of water. The process may proceed via the intermediate …<CHEM>… which is hydrolysed to give compound III.
    公开号:SU1072800A3
    申请号:SU813310052
    申请日:1981-07-14
    公开日:1984-02-07
    发明作者:Накаяма Сигенобу；Нода Ейити；Ногути Есиаки；Ямамото Исаму；Кавасаки Набору
    申请人:Мицуи Тоацу Кемикалз,Инк (Фирма)；
    IPC主号:
    专利说明:

    water S, (2-aminoethyl) -dithiocarbonate General formula
    / m
    JHXK2lf- J-C- t 3 0 1U.
    where R-H and X are indicated otherwise, at 50-150 ° g,
    4. The way pop. 3, I distinguish: u and so that the process is carried out in the presence of an inert organic solvent,
    The invention relates to methods for the production of 2-mercaptoethylamine hydrohalogen species, which are used in the manufacture of various drugs. The literature describes various methods for the preparation of 2-mercaptoethylamine hydrohalides, for example, by hydrolytic cleavage of 2,2-dialkylthiazolidines with solutions of halide acids at boiling ij. The disadvantage of this method is that in its implementation, poisonous gaseous hydrogen sulfide is used as one of the starting products. Closest to the present invention is a method for producing one of the representatives of 2-me captoethylamine hydrohalides, in particular 2-mercaptoethylamine hydrochloride, concluded that 2-mercaptothiazoline is subjected to acid cleavage by long-term boiling with hydrogen chloride f2J. The disadvantage of this method is the formation in the process of poisoned gaseous hydrogen sulfide as a by-product in an amount equivalent to the amount of reacted starting product, which generally complicates the process. The purpose of the invention is to simplify the process. This goal is achieved in that according to the method for producing 2-mercaptoethylamine hydrohalides of the form RI R, Hg-CC-lTHg-HX where R is the same or different, hydrogen, lower alkyl, lower oxyalkyl or phenyl, X is halogen, based on 2- mercaptothiazoline of the general formula t, i В 2-е-Their БЗ-СR, where they have the indicated values, when heated the interaction with 2 mercaptothiazoline is subjected to the 2-halogeno tylamine hydrohalide of the general formula B. Кз Х-- (5-С-7 "Н, -НХ II 2 4 where and X has the indicated meanings, in the presence of at least 20 mol of water per 1 mol of the compound of the formula with SO-I SO C. Preferably, the process is carried out in the presence of an inert organic solvent. A fixed goal is also achieved by the fact that according to the method for producing 2-mercaptoethylamine hydrohalides of the formula I, 2-mercaptothiazoline of the formula I, is reacted with a 2-haloethylamine hydrohalide of the formula (in the presence of less 20 mol of water per 1 mol of the compound of the formula (M followed by hydrolysis of the obtained derivative of s, 8-bis (2-aminoethyl) -di. Thiocarbonate of the formula / / 1 I 1 HX-H2H-CC-S4C 0 Of 1. 1 I / 2 where R is K. and X have the indicated values, at 50-150 ° C. Preferably, the process is carried out in the presence of an inert organic solvent. The methods according to the invention make it possible to obtain 2-mercaptoethylamines safely, since the starting products have low toxicity and the reactions taking place do not lead to the release of poisonous gases. Moreover, since the reactions in the proyess according to the invention proceed in acidic conditions, no formation of by-products such as bis (2-aminoethyl) sulfides and bis (2-aminoethyl) disulfides occurs, and very pure 2-mercaptoethylamines can be obtained. 2-mercaptothiazolines of the general formula And can be easily obtained by known methods, for example, by the method that is contained in. reacting the sulfuric acid ester of monoethanolamine with a relatively more convenient carbon disulfide in the presence of alkali (l.Chem.Soc. 1976,1367), according to the method, which consists in reacting monoethanolamine with twice the amount of carbon disulfide in the presence of alkali (Chemical Agustrate, 53, 90 4. (1959), or according to the method, which consists in reacting 2-halogenethylamine with carbon disulfide in the presence of alkali (US Patent No. 225145 2-mercaptothiazoline, 4-phenyl-2-mercaptothiazoline, 4,5-diphenyl 2 are used as compounds of formula II - mercaptothiazole n, 4-methyl-2-mercap totazolin, 4,4-dimethyl-2-mercaptotoiazolin, 4,4-bis- (hydroxymethyl) -2-mercaptothiazoline, 4-butyl-5-phenyl-2-mercaptothiazoline, 5,5-dimethyl-2 -mercaptothia & oline, 5-ethyl-2-mercaptothiazoline, 4,5-dimethyl-2-mercaptothiazoline, 4,4,5-trimethyl-2-mercaptothiazo LINT, 4,4,5,5-tetramethyl-2-mercaptote Azoline, 4,5-bis- (hydroxymethyl) -2-mercaptothiazoline, 4-phenyl-5-butyl-2-mercaptothiazoline, 4-propyl-2-mercapt thiazoline, 4-ethyl-2-mercapto-thiazoline, 5-propyl-2-mercaptothiazoline, 4 -methyl 5-phenyl-2-mercaptothiazoline or 5-methyl-2-mercaptothiazoline. As compounds of the general formula (5, hydrohalides of 2-halogenthylamines, 1-phenyl-2-GH, S-Genethylamines, 1,2-diphenyl-2-halogen-ethylamines, 1-methyl-2-halogenethylamines, 1,1-dimethyl-2-halogenethylamines, 1,1-bis- (hydroxymethyl) -2halogenethylamines, 1-butyl-2-phenyl2-yrshogenethylamines, 2,2-dimethyl-2haloethylamines, 2-ethyl-2-haloethylamines, 1,2-dimethyl-2-haloethylamines, 1, 1,2-trimethyl-2-halogen-ethylamines, 1,1,2,2-tetramethyl-2 galgenethylamines, 1,2-bis- (hydroxy methyl) -2-halogenethylamines, 1-phenyl2-butylg2-GSSOgenethylamine, 1-pro - drank-2-halogenate lamins, 1-ethyl 2halogenethylamines, 2-propyl-2-haloethylamines, 1-methyl-2-phenyl-2-galgene ethyl amines, 2-propyl 2-halo.genetilg1minov, 1-methyl-2-phenyl-2-halogenoethylamines and 2-methyl-2-haloethyl amines. In these compounds halogen is preferably chlorine, bromine or iodine. These compounds of formula III can be easily obtained by known methods .. When implementing the methods according to the invention, amounts of 2-mercaptothiazoline and 2-halogenethylamine hydrohalide can to be theoretically equimolar, but quantities outside this range pazona not "have an adverse effect on the reaction. However, to suppress side effects. It is especially preferable to use 1.02-1.20 mol of 2-mercaptothiazoline per 1 mol of 2-halogenethylamine hydrohalide. The amount of water used determines the type of reaction. If the amount of water is large, one-step reactions take place according to the basic method, and if it is small, the reaction optionally becomes very slow, and therefore the process is two-step. The process according to the invention is carried out in aqueous solution. It can also be carried out in an aqueous solution of halide acid to increase the reaction rate. The process does not require a solvent other than vrda. However, depending on the starting material used, an organic solvent inert to the reaction may be used as needed to increase the solubility of the starting product. The presence of such a solvent in the reaction system does not at all have an adverse effect on the reaction. Both miscible and water-miscible inert organic solvents can be used, for example aliphatic hydrocarbons, such as cyclohexane, and aliphatic ethers, such as butyl ether and di glyme, alicyclic ethers, such as tetrahydrofuran and dioxane, sulfur-containing compounds, such as dimethyl sulfoxide and sulfolane, and aeo-containing compounds such as dimethylformamide. Hexane, heptane, toluene, xylene, propachol butanol and dimethylformamide are preferred. . After completion of the reaction, water and an organic solvent (when used) are distilled ω-g under reduced pressure and the residue is concentrated to this state. So, hydrohalide. 2-mercaptoethylamine can be obtained in almost quantitative yield in the form of high-purity crystals. . The 2-mercaptoethylamine hydrohalides obtained according to the invention are generally of high purity. The products resulting from the two-stage process have higher purity. The even higher purity hydrohalo enid of 2mercaptoethylamine can be obtained by separating the compound of general Formula ij and purifying it. Example 1i A 100 ml four-necked flask equipped with a stirrer, thermometer and reflux condenser is charged with 2.98 g (0.025 mol) of 2-mercaptothiazoline , 2.90 g (0.025 mol) of 2-chloroethylamine hydrochloride and 50 g (2.78 mol) of water, all this is heated at the right temperature, boiling with a reflux condenser (9810 C) for 50 hours with stirring. After completion of the reaction, water is distilled off under reduced pressure, and the residue is concentrated to a dry state to obtain white crystals. Recrystallization from ethanol gives 5.12 g of 2-mercaptoethylamine hydrochloride / having a mp of 70 ,. Example 2. In the reactor, as in example 1, load 18.7 g (0.157 mol) of 2-mercapto.thiazoline, 17.4 g (0.150 mol) of 2-chloroethylamine hydrochloride and 15 g (0.83 mol) of water, all it is heated to 95-100 ° C. After 20.h., the reaction mixture is analyzed by means of those. It has been found to consist of S, S -bis- (2-aminostil) -dithiocarbonate as the main component, with 2-chloro-thylamine hydrochloride almost completely disappearing. Water (40 g, -2.22 mol) is added to the reaction mixture and, after this, the mixture is heated under reflux (98-100 ° C) for 30 hours while stirring. After completion of the reaction, the reaction mixture was concentrated to a dry residue under reduced pressure to obtain 34.5 g of white crystals. According to the iodometric analysis, these crystals (2-mercaptoethylamine hydrochloride) have a purity of 98.2%. TLC of these crystals practically does not give the spot attributable to monoethanolamine or the original products. Example Z. In the same reactor as in Example 1, 3.10 g (0.026 mol) of 2-mercaptothiazoline, 2.90 g (0.025 mol) of 2-chloroethylamine hydrochloride and 50 ml (60 g; 2.1 mol of water) concentrated hydrochloric acid, the whole is heated at reflux temperature (105-108 ° C / for s; for 20 hours with stirring. After the reaction is complete, hydrochloric acid is distilled off under reduced pressure and the residue is concentrated to dryness obtaining white crystals. Recrystallization from ethanol gives 5.23 g of 2gmerctoethylamine hydro chloride, i.e., mp 71 ,. The reagent after recrystallization of the mother liquor is concentrated to dry residue and the concentrated product is subjected to H-NMR. The product is identified as 2-mercaptoethylamine hydrochloride containing small amounts of starting materials Example 4. in the same reactor as in Example 1, 18.7 g (0.157 mol) of 2-mercaptothiazoline, 17.4 g (0.150 mol) of 2-chlorostilamine hydrochloride, and 15 g (0.67 mol in water) of 20% hydrochloride chloride are charged, all this is heated at 105110 s for 10 h. Analysis of the reaction mixture using TC X indicates that 2-chloroethylamine hydrochloride disappears almost completely and s, s-bis (2-aminoethyl) -dithiocarbonate is formed as the main product. Then, 60 g (2.67 mol in water) of 20% hydrochloric acid are added to the reaction mixture, and the mixture is heated for 20 hours at reflux. After completion of the reaction, the reaction mixture was treated in the same manner as in Example 3 to obtain 31.4 g of 2-mercaptoethylamine hydrochloride having mp. 71-72c. Example 5. In the same reactor as in Example 1, 12.2 g (0.102 mol) of 2-mercaptothiazoline, 20.5 g (0.100 mol) of 2-bromo ethylamine hydrobromide and 80 g (4.44 mol) of water were charged. this is heated under reflux (98-100 ° C) for 20 hours. After completion of the reaction, the reaction mixture is concentrated to a dry residue under reduced pressure to obtain 32.8 g of white crude crystals. Iodometric analysis shows that the crude crystals have a purity of 95.8% 2mercaptoethylamine hydrobromide. Recrystallization: from ethanol gives 27.8 g of 2-mercaptoethylamine hydrochloride having a purity of 99.4%. M.p. product 159160 with. Obtained after recrystall-. The mother liquor is concentrated to dryness and the concentrated product is subjected to H-NMR. It is identified as 2-mercaptoethylamine hydrobromide, containing not large amounts of the starting products. Analysis by TLC gives a spot of monoethanolamine. Example 6. In the same reactor as in Example 1, 18.7 g (0.157 mol) of 2-mercaptothiaeoline, 30.8 g (0.150 mol) of 2-bromo ethylamine hydrobbromide and 35 g (1.9 mol) of water were charged, all this is reacted at 95-100 ° C for 10 hours. The reaction mixture is analyzed by TLC. It is determined that 2-bromoethylamine hydrobromide disappears almost completely and S, s-bis- (2-aminoethyl) -dithiocarbonate is formed as the main product. water (60 g, 3.33 mol) is added to the reaction mixture and the reaction is continued at reflux (.98-100 s) for 20 h. After completion of the reaction, the reaction mixture is concentrated to dryness under reduced pressure to obtain 48 , 8 g of white crude crystals. According to iodometric analysis, the crude crystals have a purity of 97.6% 2-mercaptoethylamine hydrobromide. Crude crystals have a mp of 1557159 ° C.
    Example 7. 7.3 g (0.055 mol) of 5-methyl-2-mercaptothiazoline, 6.5 g (0.050 mol of 2-chloropropylamine hydrochloride and 60, 50 mol. In water) of 25% strength are loaded into a glass reactor for pressure operation. hydrochloric acid, all this is heated at a pressure of 5 kgf / s for 20 hours with stirring. After completion of the reaction, the hydrochloric acid is removed to give 15.9 g of a pale yellow wet cake. Recrystallization from isopropanol gives 10.8 g of white crystals having a mp of 90-92c. Iodometric analysis indicates that the crystals have a purity of 98.8% 2-mercaptopropylimine hydrochloride.
    Example 8. 14.6 g (0.110 mol) of 5-methyl 2-mercaptothiazoline, 13.0 g ((O, 10 mol) of 2-chloropropylamine hydrochloride and 4. g (mol in water) are loaded into a glass reactor for pressure operation. 15% hydrochloric acid, all this is heated at 100-110 L. After 15 hours, the reaction mixture is analyzed with the help of those. It was found that 2-chloropropylamine hydrochloride disappears almost completely, and S, S-bis (1 -methyl-2-amino-ethyl -dithiocarbonate. To the reaction mixture are then added 40 g (1.67 mol in water) of 25% hydrochloric acid, and the mixture reacts at and at a pressure of 5 kgf / cm for 20 hours: after completion of the reaction, the reaction mixture is treated in the same way as in Example 7 to obtain 22.1 g of white crystals. An iodometer shows that the crystals are 99% pure. , 1% 2-mercaptopropyllamine hydrochloride, mp.91-92 C.
    Example -9. According to the procedure of Example 5, the reaction was carried out at 60-70 seconds for 50 hours using 80 g (4.00 mol. In water) of a 10% aqueous solution of hydrobromic acid instead of water. After completion of the reactions, the reaction mixture was worked up in the same manner as in Example 3, with the receipt of 27.2 g of white purified crystals. Iodometry indicates that the crystals are 99.5% pure 2-mercaptoethylamine hydrochloride; t, pl. 159-161 S. ...
    Example 10. According to the method of Example 6 25 g (1.11 mol in water) of a 20% aqueous solution of hydrobromic acid are used instead of water in the first stage reaction and 60 g (3.00 mol in water) of a 10% aqueous solution of hydrobromic acid instead of water in the second stage reaction. At 60-70® C, first stage reaction
    carried out for 15 hours, and the reaction of the second stage is carried out for 40 hours. After completion of the reaction, the product is treated in the same way as in Example 4 to obtain 48.5 g of white crude crystals. According to iodometric analysis, the crystals have a purity of 97.3% 2-mercaptoethylamine hydrobromide; m.p. 159-160.5 ° C
    Example 11. In the same reactor as in example 1, load 6,78 g (0,025 mol) of 3,5-diphenyl-2-mercaptothiazoline, 6,70 g (0,025 mol) of 1,2-diphenyl-2-chloro hydrochloride -ethylamine, 10 g (0.56 mol) of water and 40 ml of dimethylformamide. All this is heated at 130-135 seconds for 30 hours. After completion of the reaction, water and dimethylformamide are distilled off under reduced pressure to obtain 13.6 g of a viscous pale yellow liquid. According to n-NMR and IR spectrometry, this product was identified as 1,2-diphenyl-2-mercaptoethylamine hydrochloride, containing small amounts of starting materials and dimethylformamide.
    Example 12. In the same reactor as in example 1, 15.0 g (0.055 mol) of 4,5-diphenyl-2-mercaptothiazoline, 13.4 g (0.05 mol) of 1,2-diphenyl- 2-chloroethylamine hydrochloride, 1.8 g (0.10 mol) of water and 40 ppm of dimethylformamide, the whole is heated at 130-135 ° C for 10 hours. After this, 22.5 g (1.25 mol) of water are added and the mixture is heated at reflux for 25 hours. After completion of the reaction, the mixture is treated according to the procedure of Example 9 to obtain 29.2 viscous pale yellow liquid. According to the data and IR spectrometry, this product was identified as 1,2-diphenyl-2mercaptoethylamine hydrichloride containing small amounts of starting materials and dimethylformamide.
    PRI me R 13. In the same reactor as in Example 1, load 3.68 g (0.025 mol) of 4,4-dimethyl-2-mercaptothiazoline, 3.6 g (0.025 mol) of 1,1-di-methyl- 2-chloroethylamine hydrochloride, 10 g (0.56 mol) of water and 40 ml of 1-butanol are heated at 105110 s for 50 hours. After completion of the reaction, the mixture is worked up. to the procedure of Example 11 to obtain 7.4 g of a viscous pale yellow liquid. By H-NMR and IR spectrometry, this product was identified as 1,1-dimethyl-2-mercapt-ethylamine hydrochloride, containing small amounts of starting materials and 1-butanol. Recrystallization from isopropanol gave 5.1 g of 1,1-dimethyl-2-mercaptoethylamine hydrochloride in the form of white crystals having a mp of 180-182 s.
    Example 14. In the same reactor as in example 1, load 17.6 g
    (0.120 mol) 4,4-dimethyl-2-mercaptothiaeoline, 14.4 g (0.100 mol) 1,1-dimethyl-2.-Chloroethylamine hydrochloride 5.4 g (0.30 mol) of water and 50 ml of 1-butaiol, all it is heated at 105110 C for 15 h.
    Then 40 (2.22 mol) of water is further added and the mixture is heated at the boil under reflux for 40 hours. After completion of the reaction, the mixture is treated according to the procedure of Example 11 to obtain 32.9 g of a viscous pale yellow liquid. By n-NMR and IR spectrometry, this product was identified as 1,1-dimethyl-2-mercaptoethyllamine hydrochloride containing small amounts of starting materials and 1-butanol. Recrystallization from isopropanol afforded 22.8 g of 1,1-dimethyl-2-mercaptoethy. Pamine hydrochloride as white crystals, mp 181-182 ° C.
    Example 15. In the same reactor as in Example 1, 4.7 g (0.026 mol) of 4y4-bis- (hydroxymethyl) -2-mercaptothiazoline, 4.4 g (0.025 mol) of 1,1-bis- ( hydroxymethyl) 2-chloroethylamine hydrochloride, 10 g (0.56 mol) of water and 40 ml of dimethylformamide, all this is heated at 105 OI C for 50 h. After the end of the reaction, the mixture is treated according to the method of example 11 to obtain 9j3 viscous pale yellow liquid . According to NgNMR and IR spectrometry, this product was identified as 1,1-bis- (hydroxymethyl) 2-mercaptozythylamine hydrochloride containing a small amount of starting materials and dimethylformamide.
    Example 16. In the same reactor as in Example 1, 18.6 g (0.105 mol) of 4, 4-bis- (hydroxymethyl) 2-mercaptothiazlina, 17.6 (0.100 mole of 1.1-bis- (hydroxymethyl)) were charged. -2-chloroethylamine hydrochloride, 9 g (0.50 mol) of water and 30 ml of dimethylformamide are heated at lOS-llO C for 15 hours. Then 70 g (3.89 mol) of water are added and the mixture is heated in reverse refrigerator for 30 hours. After the end of the reaction, the mixture is treated according to the procedure described above, to obtain 37.1 g of a viscous pale yellow liquid, P6 according to H-NMR and IR spectrometry, this product is identified as hydrochloride ID 1,1-bis- (hydroxymethyl) -2-mercaptoethylamine, containing non-E 1 S1e quantities of raw materials and dimethylformamide.
    Example 17. In the same reactor as in Example 1, 7.0 g (0.028 mol) of 4-c-butyl-5-phenyl-2-mercaptothiazoline, 6.2 g (O, 025 mol) of 1-l-butyl hydrrichloride are loaded. -2-phenyl-2-chloroethylamine, 10 g (0.56 mol) howls 10 g (0.36 mol by water) concentrate
    Hydrated hydrochloric acid and 30 ml of dimethylformamide are heated at 105-110 ° C for 50 hours. The reaction mixture is worked up as in Example 11 to obtain 13.7 g of a viscous pale yellow liquid. According to n-NMR and IR spectrometry, this product is identified as 1-n-butyl-2-phenyl-2-mercapto-ethylamine hydrochloride, containing non-small amounts of starting materials and dimethylformamide.
    Example 18. In the same reactor as in example 1, load of 13.8 g (0,055 mol) 4-n-butyl-5-phenyl-2-mercaptothiazoline, 12.4 g (0.05 mol) of hydrochloride 1-H -butyl-2-phenyl-2chloroethylamine, 5 g (0.21 mol in water) of 25% hydrochloric acid and 30 ml of dimethylformamide, all this is heated. at 105-110 ° C for 15 hours. Then 50 g (2.08 mol in water) of 25% hydrochloric acid are added and the mixture is heated under reflux for 25 hours. After completion of the reaction, the mixture is treated in the same way as and in Example 11, to obtain 26.9 g of a viscous pale yellow liquid. According to H-NMR and IR spectrometry, this product was identified as 1-n-butyl-2-phenyl-2-mercaptoethyllamine hydrochloride containing small amounts of starting materials and dimethylformamide.
    PRI me R 19. In the same reactor as in Example 1, 4.0 g (0.027 mol) of 5-ethyl-2-mercaptothiazoline, 3.6 g (0.0025 mol) of 2-chloro- butylamine hydrochloride, 10 g (0.56 mol) water, 10 g (0.36 mol water) concentrated hydrochloric acid and 30 ml 1-butanol, all this is heated at 105-110 ° C for 40 hours the mixture is concentrated to give 7.7 g of a viscous pale yellow liquid. According to H-NMR and IR spectrometry, this product was identified as 2-mercaptobutylamine hydrochloride containing small amounts of starting materials and 1-butanlar.
    PRI im p 20. In the same reactor as in example 1, load 16.2 g (0.11 mol) of 5-ethyl-2-mercaptothiazole Ha, 14.3 g (0.10 mol) of 2-chlorobutylamine hydrochloride, 20. G ( 0.78 mol of water) of 30% hydrochloric acid and 20 ml of 1-butanol, the whole is heated at 105-110 seconds for 15 hours. Then 50 g (1.94 mol of water) of 30% is added hydrochloric acid and the mixture is heated at boiling under reflux for 30 hours. After completion of the reaction, the mixture is concentrated to obtain 30.6 g of a viscous pale yellow liquid. According to x-NMR and IR spectrometry, this product is identified as g drohlorid 2-merkaptobutilamina, zhaschy contain small amounts of the starting materials and 1-butanol. Example .21, In the same reactor as in example 1, load 28 g (0.21 mol) of 5-methyl-2-mercaptothiazoline, 26 g (0.20 mol) of 2-chloropropylamine hydrochloride and 56 g (2, 8 mol of water) of 10% hydrochloric acid, all this is heated at 100105 C for 15 hours. TLC analysis shows that 2-chloropropylamine hydrochloride disappears almost completely and S, s-bis- is formed as the main product (1 -methyl-2-aminoethyl) dithiocarbonate. Heating is continued and the reaction is continued for another 40 hours. After the end of the reaction, the mixture is treated according to an approximate procedure to obtain 42.9 g of white crystals. According to the iodometric analysis, these crystals are 99.0% pure 2-mercaptopropylamine hydrochloride, mp 91- 92s. Example 22. In the same reactor as in example 1, load 19.6 g (0.165 mol) of 2-mercaptothiazoline, 17.4 g (0.150 mol) of 2-chloroetclamine hydrochloride and 15 g (0.67 mol in water) 20 % hydrochloric acid, all this is heated at for 10 hours. TLC analysis shows that 2-chloroethylamine hydrochloride disappears almost completely. The reaction mixture is cooled to room temperature and 80 ml of chloroform is added to remove the unreacted 2-mercaptothiazoline by extraction. The residue is concentrated to a dry residue and 34.1 g of white crystals are obtained by recrystallization from isopropanol. According to H-NMR and IR-spectrometry, the crystals are identified as S, S of bis- (2-aminoethyl) -dithiocarbonate hydrochloride. 30 g (0.119 mol) of the obtained white crystals and 60 g (2.67 mol in water) of 20% hydrochloric acid are loaded into a glass reactor for working under pressure and heated at a pressure of 5-8 kgf / cm for 15 h After the reaction, the mixture is concentrated to a dry residue under reduced pressure to obtain 26.9 g of white crystals. According to iodometric analysis, the crystals are 99.1% pure 2-mercaptoethylamine hydrochloride.
    权利要求:
    Claims (4)
    [1]
    1. The method of producing 2-mercaptoethylamine hydrohalides of the general formula
    B 1 K 5
    I I ’
    Н§-С-С-1ГН 2 'НХ 1
    in 2 in 4
    where ', in - in * - identical or different / hydrogen, lower alkyl, lower oxyalkyl or phenyl;
    X - halogen,
    based on 2 - ** ercaptothiazoline with the general formula
    B X K 5
    HGC-S-VN-’NHH 5 '
    II 2 V 2 K 4
    where in -e, and X have the indicated otherwise,
    in the presence of at least 20 mol of water per 1 mol of the compound of the formula f at 50-150 ° C.
    [2]
    2. The method according to claim 1, which is based on the fact that the process is carried out in the presence of an inert organic solvent.

    [3]
    .3. The method of producing hydrohalides of 2-mercaptoethylamine of general formula 1c in 5
    H $ -C-C-CH 2 -HX ι II.
    • ^ .2 B 4
    : Nz- "in
    S-VN
    where K 1 ~ B 4 ~ same or different,
    hydrogen, lower alkyl, lower oxyalkyl or phenyl,
    X - halogen,
    on the basis of 2-mercaptothiazoline general Formula 1
    In years C- _
    2 C- $ N I /
    At 4
    where in 1 _ c. they have the indicated values, when heated, which differs with me in that in order to simplify the process, the interaction with 2-mercaptothiazoline of formula II is subjected to the guide * · halogenethylamine halogenide of the general formula
    5TS 1072800
    where B ^ -B ^ have the indicated values, 'when heated, which differs: in order to simplify the process, the 2-halogenethylamine hydrohalide is subjected to the interaction with 2-Mercaptotiazole of formula 1Ϊ formulas
    Х-С --С-ЯНа-НХ II ί . to 2 to 4
    and and X have the indicated values
    in the presence of less than 20 mol of water per 1 mol of the compound of the formula $ followed by hydrolysis of the resulting prod
    aqueous Z'Z'-bisC 2-aminoethyl) -dithiocarbonate of General formula
    ΗΧΉ 2 Ή - <! - (! - £ -} - <Μ>'
    1 · to 4 Kg
    where is H. and X are as defined enache Nia April 1, at 50-150 ° c.
    [4]
    4. Method pop.s, characterized in that the process is carried out in the presence of an inert organic solvent.
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    同族专利:
    公开号 | 公开日
    KR830006196A|1983-09-20|
    HU186897B|1985-10-28|
    DE3164300D1|1984-07-26|
    EP0044203B1|1984-06-20|
    JPS5721366A|1982-02-04|
    YU114286A|1987-04-30|
    KR840001923B1|1984-10-25|
    KR840001922B1|1984-10-25|
    EP0044203A1|1982-01-20|
    YU42694B|1988-10-31|
    BR8104513A|1982-03-30|
    JPS6050186B2|1985-11-07|
    YU169681A|1983-12-31|
    CA1173461A|1984-08-28|
    ES8300695A1|1982-11-01|
    US4507500A|1985-03-26|
    YU43996B|1990-02-28|
    ES503944A0|1982-11-01|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US3213091A|1961-04-26|1965-10-19|Eastman Kodak Co|Mercaptoethylation of amines with ethylene monothiolcarbonate|
    US3280162A|1963-07-08|1966-10-18|American Cyanamid Co|Bisdithiolcarbonate salts and process|
    US4086274A|1975-06-23|1978-04-25|The Dow Chemical Company|N-alkanamides from H2 S and 2-H-2-oxazolines or 2-alkyl-2-oxazolines|DE3742265A1|1987-12-12|1989-06-22|Basf Ag|METHOD FOR PRODUCING CYSTEAMINE ACID ADDITION SALTS|
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    AT172711T|1992-10-21|1998-11-15|Yoshitomi Pharmaceutical|2-AMINO-1, 3-PROPANEDIOL COMPOUND AND IMMUNOSUPPRESSIUM|
    TWI659209B|2013-06-17|2019-05-11|地平線罕見醫學製藥有限責任公司|Methods for analyzing cysteamine compositions|
    IT201600106709A1|2016-10-24|2018-04-24|Chemelectiva S R L|Process for the preparation of a sulphurated amine|
    EP3842418A1|2019-12-23|2021-06-30|Farmabios S.p.A.|Method for the purification of cysteamine|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    JP55095642A|JPS6050186B2|1980-07-15|1980-07-15|
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