Method of preparing thiocarbamide derivatives

专利摘要:
Novel thiocarbamide derivatives of the formula <IMAGE> in which the substituents R1, R2, R3, R4, R5 and R6 have the meaning given in each case in Patent Claim 1, are obtained by reacting an isothiocyanate of the formula <IMAGE> the corresponding dithiocarbamic acid of the formula <IMAGE> its esters or acid halide with an amine of the formula R4NHR5 in the melt or in an inert solvent. The reaction products have favourable diuretic, saluretic, analgesic and/or antidepressive action even at a low dose, combined with low toxicity.
公开号:SU795462A3
申请号:SU752333906
申请日:1975-03-12
公开日:1981-01-07
发明作者:Райтер Йожеф；Толдь Лайош；Борши Йожеф；Шэфер Инге；Секель Йожеф；Кираль Илдико；Элек Шандор；Сондь Элеонора
申请人:Эдьт Дьедьесерведьесети Дьяр (Фирма)；
IPC主号:

专利说明:

(54J METHOD FOR OBTAINING THIOCARBAMIDE DERIVATIVES
Q is a halogen atom, SH or a group, and ft-, is C--C alkyl and X and Q together represent a valence bond,
reacted with an amine
General formula {JII)
/ Rt
K (III) 5
.in which: R and Rg are as defined above,
in the melt or in an inert organic solvent at a temperature of 40-250C.
Example 1. 1- (4-Fluorobenzyl) -3- (2-hydroxyethyl) -thiocarbamide.
a) A solution of 12.6 g (0.0766 mol) of 4-fluorobenzyl isothiocyanate in 100 ml of chloroform is added dropwise with stirring and cooling with ice to a solution of 4.88 g (0.08 mol) of ethanolamine in 50 ml of chloroform. The reaction mixture is refluxed for 1 h, then the solvent is distilled off in vacuo to give 17.45 g (100%) of a yellow, honey-like 1- (4-fluorobenzyl) -3- (2-hydroxyethyl) -thiocarbamide, which crystallizes when standing. After recrystallization of the product from a mixture of 1: 1 ethyl acetate and cyclohexane, its melting point is 58-60 ° C.
.6) A mixture of 21.5 g (0.1 mol) of methyl-N- (4-fluorobenzyl) -dithiocarbamate and 12.2 g (0.2 mol) of ethanolamine is melted at 3 hours. Methyl mercaptan is released from the mixture during the reaction.
An excess of ethanolamine is removed from the reaction mixture by distillation in vacuo, then the remaining honey-like product (22.8 g, 100%) is recrystallized from a mixture of ethyl acetate and cyclohexane 1: 1.
The product melting at 58-60 ° C is identical to that obtained in Example 1a.
c) A solution of 21.5 g (0.1 mol) of methyl M- (4-fluorobenzyl) -dithiocarbamate and 7.32 g (o, 12 mol) of ethanolamine — in 40 ml of isopropyl alcohol is boiled for 3 h. Methyl mercaptan is isolated from the reaction mixture during the reaction.
Isopropanol along with ethanolamine taken in excess was removed from the reaction mixture by vacuum distillation, the remaining honey-like product (22.8 g, 100%) was then recrystallized from a 1: 1 mixture of ethyl acetate and cyclohexane. The product melting at 58-60 ° C is identical to the product obtained in Example 1a.
d) Work according to the procedure of Example 1c with the difference that the mixture is boiled using chloroform instead of isopropyl alcohol.
The resulting honey-like product (22.8 g, 100%) is recrystallized from a 1: 1 mixture of ethyl acetate and cyclohexane to give a compound that melts at 58-60 ° C. The product is identical to that obtained in example 1a.
e) They work according to the procedure of Example 1c, but with the difference that boiling is carried out in dioxane instead of isopropyl alcohol.
The resulting honey-like product
(22.8 g, 100%) is recrystallized from a mixture of 1: 1 ethyl acetate and cyclohexane, it melts at 58-60 C. The resulting product is identical to the product of example 1a.
f) To a solution of 3.13 g (0.025 mol) / 4-fluorobenzylamine in 25 ml of anhydrous ethyl alcohol is added dropwise} l at. and stirring and cooling with ice and salt 3.02 ml (0.05 mol
carbon disulfide. Reaction mixture
stirred for half an hour at a temperature below, then 2.39 ml (p, 025 mol) of ethanolamine was added dropwise at the same temperature and the mixture was stirred for half an hour at. The ethyl alcohol, taken as a solvent, is removed from the reaction mixture, along with the excess carbon disulfide, by distillation, then the remaining honey-like salt is removed.
heated for 1 hour at 140 ° C in an oil bath. During the reaction, methyl mercaptan is released from the reaction mixture. Upon cooling, the resulting honey-like product is dissolved in 50 ml of benzene, shaken with 3 X 50 ml of water, dried and evaporated to dryness under vacuum, yielding 4.85 g (85%) of honey-like 1- (4-fluorobenzyl) -3- (2 -oxyethyl) -thiocarbamide. After recrystallization of the product from
1: 1 mixtures of ethyl acetate and cyclohexane give a product melting at 57-60 ° C. The product is identical to that obtained in Example 1a.
Elementary analysis:
Calculated,%: C 52.61; H 5.71;
N 12.27; S 14.057 F 8.32. CioH jFNjOS.
Found,%: C 52.90; H 6.02; H 12.34; N 14.29; S 8.33.
Example 2. 1- (1-Phenylbutyl) -3-methyl-3- (2-hydroxyethyl) .- iocarbamide.
a) A solution of 43.3 g (0.15 mol) of 1-phenyl butyl isothiocyanate in 100 ml of dichloroethane is added dropwise at
stirring and cooling with ice to
a solution of 12.0 g (0.16 mol) of 2-methylaminoethanol in 50 ml of dichloroethane. The reaction mixture is boiled under reflux for 1 h, then the solvent is distilled off in vacuo to give 39.9 g (100%) of honey-like 1- (1-phenylbutyl) -3-methyl-3- (2-hydroxyethyl ) -thiocarbamide, which crystallizes on standing. Recrystallization from ethyl acetate gives
product melting at 74-75 C.
b) A solution of 14.9 g (0.01 mol) of 1-phenylbutylamine and 17.2 g (0.15 mol) of thiophosgene in 100 ml of anhydrous 1,2-dichloroethane is stirred for 4 hours at room temperature, then the reaction mixture is evaporated to dryness in a vacuum. The resulting N- (1-phenylbutyl) -thiocarbamic acid chloride is dissolved in 50 ml of anhydrous benzene. The solution is filtered, then the filtrate is slowly added dropwise with stirring to a solution of 16.5 g (0.22 mol) of 2-methylaminoethanol in 100 ml of benzene. The reaction mixture was heated under reflux for 4 hours. Then it was allowed to cool and treated with 100 ml of water. Separate the phases. The benzene solution is shaken with 2 x 100 ml of water, dried and evaporated to dryness in vacuo. In this way, 25.5 g (95.7%) of the raw honey-like product is obtained, which crystallizes on standing. By recrystallization from ethyl acetate, a product is obtained which melts at 74-75 ° C and is completely identical to the compound obtained in Example 2a.
Calculated: C 63.11, H 8.32, N 10.52; S 12.04. .M 266.40.
q "H N OS.
Found: C, 63.05; H 8.01, N 10.57; S 12.03.
By using the techniques described in examples 1 and 2, other compounds of general formula (I) given in the tables can also be obtained.
Example 69. 1- (2-Dimethylaminomethyl) -6-methylbenzyl-3- (2-hydroxyethyl) -thiourea.
Honey-like substance: Rf 0.3.
Calculated: C 59.75; H 8, N S 11.39.
 (M. 281.41).
Found: C 59.52; H 8.41; N 14.91; S 11.45.
PRI meme 70. 1 - (. 2-Fluoro-5-sul fonamido) -benzyl-3- (2-hydroxyethyl thiourea.
M.p. 160-170 ° C, Rf 0.4. Calculated: C 39.07; H 4.59; N 13.67} S 20.86; F 6.18.
C.o H, v F.4ap ,, s. (M-M 307.37.
Found 39.12; H 5.71; N 13.48; S21.00; P6,22.
Example 71. 1- (1-Phenylethyl) -3- (3-methyl-3-hydroxyheptyl) -thiourea.
Honey: Rf 0.68
Calculated: C 66.19, H 9.15 / N 9.08; s 10.39;
С, Нг8 «« 05 (М, „308.48).
Found: C, 66.40; H 9.37, N 9.31; S 10.29.
Example 72 1- (1-Phenyl-2-hydroxy) -ethyl; y-3- (2-hydroxyethyl) thiourea.
Honey-like substance 0.4.
Calculated: C 54.97, H 6.71; N 11.66; S 13.34.
C H N O-S Found,: C 55.06 GN 6.89; L11.62; S 13.12.
Example 73. 1- (4-Trichloromethyl) benzyl) -3-methyl-3- (2-hydroxyethyl) -carbamide. M.p. lOS-llO C.
Calculated: C 42.18 ,, H 4.42, N 8.20, S 9.38, C1 31.13.
M. „341,69 C, H, .CUN.OS
,: C 42.05H 4.35; N 8.23; S 9.30; ca 30.98.
Example 74. 1- (l-phenylpropyl) -3- (4-hydroxybutyl) -thiocarbamide. T. pl. 72-74 S.
Calculated: - C 63.11, H 8.32, N 10.52, - 12.04.
CyH NjOS (M. 266.40).
Found: C-62.99; H 8.00 N10.53; 512,10.
Example 75. 1- (2, 4,6-Trimethylbenzyl) -3- (2-hydroxyethyl) -thiocarbamide. M.p. 187-190 C.
Calculated: C 61.86; H 7.98, N 11.10, 5 12.70.
C, 3H5j.oN3, OS (M. 252 (37).

权利要求:
Claims (1)
[1]
Found% j C 61.56, H 7.80, N11.08, .12.71. The claims of the method for producing thiocarbamide derivatives of the general formula (T) / (7 Hcl-CgC, 4. I where R., RJI, RJ may be the same or different and mean hydrogen, halogen, branched or unbranched alkyl, alkoxyl, Su-C dialkylamino group, nitro group, or halogen-substituted alkyl l — hydrogen, alkyl, alkenyl Cj — Cg, cycloalkyl Cg — Cg, each of which may be substituted with hydroxyl; 45 RS hydroxyalkyl, alkenyl (,; Rf, hydrogen, direct or alkyl, cycloalkyl, branched, unsubstituted or substituted by hydroxyl or halogen, from characterized by the fact that h in terms of &amp; 5 rp № C a compound of the general formula (P); H-ir- -r R "X where R has the above-mentioned values, X means a hydrogen atom; GI-atom halogen or SH OR &amp;Y; a group where is alkyl C., a group, and X and Q together represent a valence bond, even interacting with the amine of formula (III) PC. (H} where R and R have The above value is in the melt or in the inertm solvent at a temperature of 40 ° C. Sources of information that are considered in the examination 1. USSR author's certificate 517587, cl. C 07 C 127/19, 07 C 157/09,.

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法律状态:

优先权:

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申请号 | 申请日 | 专利标题

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HU75GO1303A|HU173459B|1975-03-14|1975-03-14|Process for preparing new thiourea derivatives|

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