Method of obtaining threo-2-oxy-(4-methoxyphenyl)-3-(2-nitrophenylthio) propione ester and its versi

专利摘要:
1. Method for producing threo 2-hydroxy-3
公开号:SU1149873A3
申请号:SU823396151
申请日:1982-02-25
公开日:1985-04-07
发明作者:Иноуе Хирозуми；Хасияма Томики
申请人:Танабе Сейяку Ко,Лтд (Фирма)；
IPC主号:

专利说明:

In order to intensify the process, a compound of the formula:
G -®
O, 1 or 2;
R
2 or 4;
 X
halogen or alkanoyloxy,
in equimolar amount at room temperature.
Recognized priority:
The method according to claim 1 - in the presence of a Lewis acid;
The method according to claim 1, in the presence of a catalytic amount of a compound of formula (III), and the method according to claim 2,
The invention relates to an improved method for producing a threo-2-hydroxy-3- (A-methoxyphenyl) -3 (2-nitrophenylthio) propionic ester of the general formula: (O where R is alkyl with 1-4 carbon atoms, and its variant Which is used as an intermediate in the synthesis of biologically active compounds. A known method for the preparation of compounds of formula (1) is that trans-3- (4-methoxyphenyl) glycidyl ester of the general formula) -Hng where R is alkyl with 1 -4 carbon atoms are reacted with 2-nitrothiophenol an organic solvent such as acetonitrile, under a nitrogen atmosphere at LP-Bo for 68-120 hours yield the desired products 38-56% D. disadvantage of the method -. the processing time. The aim of the invention is to intensify the process. This goal is achieved in that according to the method for producing compounds of general formula (1), the compound of general formula (p) is reacted with 2-nitrothiophenol in an organic solvent, for example, ether, toluene, dioxane, dimethoxyethane or acetone, in the presence of a catalytic amount of a Lewis acid at a temperature of (-3) -50 ° C or a catalytic amount of a compound of the general formula: where p is O, 1 or 2; (- 2 or 4; X is a halogen and an alkanoyloxy group, at room temperature. In addition, according to the method of the second embodiment, the compound of general formula (p) is reacted with a catalytic amount of the compound of formula (III) in an ooganic solvent , dioxane, dimethoxyethane or acetone, at room temperature. The yield of the target products according to the proposed method is 38-74%, the duration of the processes of 5 minutes is 22.5 hours.
Example 1: Dissolve 2 g of 2-nitrothiophenol in anhydrous ether and argon atmosphere. Add 0.1 ml of boron trifluoride etherate. The resulting solution is cooled to 10 ° C and 3.2 g of methyltran s-3- (4-methoxyphenyl) glygidate are added dropwise at this temperature over T5 min. Then the resulting mixture was stirred at 16-20 ° C for 20 minutes. After the reaction, the mixture is evaporated under reduced pressure to remove the solvent. 20 ml of ethanol-isopropyl ether (1: 1) are added to the crystalline residue and the mixture is thoroughly mixed. This mixture is then cooled for 20 minutes. The resulting crystals are collected by filtration, washed with 10 ml of a mixture of ethanol-isopropyl ether (1: 1) and ether, and then dried. 2.39 g of methyl-threo-2-hydroxy-3- (4-methoxyphenyl) 3- (2-nitrophenylthio) propionate is obtained. Yield 51.3%. Melting point 154156 °.
Example 2: Dissolve 2 g of 2-nitrbphenol and 3.2 g of methyl trans-3- (4-methoxyphenyl) -glycidate in 10 ml of anhydrous ether and in a nitrogen atmosphere over a period of about 10 minutes dropwise A solution of O, 1 ml of boron trifluoride ethorate in 10 MP of anhydrous ether is added. The resulting mixture was stirred at the same temperature as in Example 1 for about 10 minutes. After the reaction, the mixture obtained is processed analogously to Example 1. 2.435 g of methyl-threo-2-hydroxy-3- (4-methoxyphenyl) 3- (2-nitrophenylthio) propionate are obtained. The yield is 52.2%.
Physico-chemical characteristics of the obtained product are identical to the characteristics of the product obtained in example 1.
Examples 3-21. 2-nitrothiophenol is reacted with methyl trans-3- (4-methoxy-phenesh1) glycidate in the presence of one of the Lewis acids listed in the table. The reaction is carried out according to the same method as in Examples 1 or 2. The yields of methyltreo-2-hydroxy-3- (4-methoxyphenyl) -3 (2-nitrophenyl-tir) propionate obtained in this way are listed in the table.
Example 22. 14 g of 2-nitrothiophenol is dissolved in 70 ml of toluene.
and 0.05 t of zinc acetate dihydrate is added to them. The resulting mixture was stirred at room temperature for 5 minutes. Then, 19.7 g of methyl trans-3- (4-methoxyphenyl) -glycidate was added to the mixture and the mixture was stirred at room temperature for 6-7 hours. After the reaction, the crystals were collected by filtration. The crystals thus obtained are treated in the same manner as in Example 1. 24.3 g of methyltreo-2-hydroxy-3- (4-methoxyphenyl) -3 (2-nitrophenylthio) propionate is obtained. The yield is 74.1%.
The physicochemical characteristics of this product are identical to those obtained for the sample of Example 1.
EXAMPLE 23 1. Dissolve 33.05 g (0.213 mol) of 2-nitrothiophenol in 30 ml of anhydrous benzene and cool the resulting solution to 10 C. To this solution add solution 25 dropwise to this solution in 30 minutes 0 g (0.0968 mol) of tin chloride (4) in 50 ml of anhydrous benzene and the resulting mixture is stirred at 10 ° C for one hour. The insolubles were removed by filtration and washed with anhydrous benzene. The filtrate and the washings were combined, evaporated under reduced pressure to remove the solvent, 100 ml of anhydrous benzene and H-hexane (3: 1) was added to the residue, and the crystalline precipitate was collected by filtration. Then 15.6 g of yellow crystals crystallize from anhydrous benzene (melting point 138-143 ° C with decomposition). 8.8 g of tin chloride adduct (4) and 2-nitrothiophenol are obtained.
Elemental analysis.
Found,%: C 27.13; H 1.71; N 5.32; S 12.06.
C, 2 H ,,, S, S4C1,
Calculated,%: C 26.98; H 1.70; N 5.24; S 12.00.
Mass Spectrum (t / e):
WOJ
, OS ;; „,
J79
NMR (5, SDSe): 4.05 (C, 18); 7.268, 35 (m, 8H); IR spectrum (, сe,): 2600, 1585, 1570, 1510, 1460, 1340, 1305, 1260, 1140, 1115, 1010, 855. Physicochemical data allow us to propose the following structural formula for the adduct: 2. 1.5 g 0.0028 mol of tin chloride adduct (4) and 2-nitrothiophenol obtained in production (1), dissolved in to ml of anhydrous benzene and 0.584 g of 0.0028 mol of methyl trans-3 added to it at room temperature 4-methoxyphenyl) -glycidate. The resulting mixture was stirred at room temperature for 10 minutes. After the reaction, the resulting mixture was evaporated under reduced pressure to remove the solvent. The residue thus obtained was adsorbed on a column of 60 g of silica gel, after which the column was eluted with a mixture of benzene and ethyl acetate (t5: 1). The eluates are combined and evaporated to remove the solvent. Then the crystals thus obtained (0.69 g) are washed with benzene. As a result, 0.48 g of methoxy-threo-2-hydroxy-3- (4-labels, syphenyl) -3- (2-nitrophenylthio) propionate is obtained. Yield 47.1%. The temperature melts at t54-156 ° С. Example 24: Dissolve 2 g (0.013 mol) of 2-nitrothiophenol in 20 ml of anhydrous toluene. At the room temperature, 0.06 g of tin chloride adduct (4), 2-nitrothiophenol, obtained in Example 23 (1), and 3.2 g (0.01555 mol) of MeTyl Trane-3- (4- methoxyphenyl) glycidate at room temperature. The resulting mixture is stirred at room temperature for 17 hours. After the reaction, the crystalline precipitate is collected by filtration, filtered with anhydrous benzene, and then dried. Thus, 3.18 g of methyl-threo 2-hydroxy-3- (4-methoxyphenyl) -3- (2-nitro-fekylthio) propionate is obtained. Yield 67.9%. Melting point 154-156 ° C. Example 25. 1. 2-Nitrothiophenol and tin chloride (2) are treated in the same manner as in Example 23 (1) and an adduct of x. Porous tin (2) and 2-nitrothiophenol is obtained. 2. The 2-nitrothiophenol is reacted with methyl trans-3 .- 4-methoxyphenyl) glucidate in the presence of tin chloride adduct (2) and 2-nitrothiophenol, as obtained in paragraph (1). The above reaction is carried out analogously to Example 24. Thus, methyl-threo-2-hydroxy-3- (4-methoxyphenyl) -3- (2-nitrophenylthio) propionate is obtained. Exit 63%. Example 26. 1. 2-Nitrothiophenol and tin octylate (2) are treated analogously to example 23 (1), resulting in the formation of an adduct of tin octylate (2) and 2-nitrothiophenol. 2. The 2-nitrothiophenol is reacted with methyl trans-3 (4-methoxyphenyl) glycidate in the presence of tin (2) octylate adduct and 2-nitrothiophenol, as obtained in (t). The above reaction is carried out analogously to example 24. Thus. Methyl-threo-2-oxy-3- (4-methoxyphenyl) -3- (2-nitrophenylthio) propionate is obtained. Yield 68%. PRI me R 27. Dissolve 2.0 g of 2-nitrothiophenap in anhydrous ether and cool the solution to -3 to 0 ° C. 0.1 ml of boron trifluoroether was added to the solution and g of methyltrans-3- (4-methoxyphenyl) glycidate was added to the mixture. The mixture was stirred at the same temperature for 30 minutes. After the reaction, the mixture is worked up as in Example 1. 2.35 g of threo-2-hydroxy-3- (4-methoxyphenyl) 3- (2-nitrophenylthio) pro-pionic acid methyl ester are obtained. Exit 50.4X. The physicochemical properties of the product are similar to the properties of the product of example 1. Thus, the proposed method and its variant allow to intensify the process several times.

权利要求:
Claims (2)
[1]
1. The method of producing threo-2-hydroxy3- (4-methoxyphenyl) -3- (2-nitre ofenylthio) propionic ester is that, in order to intensify the process, the latter is carried out in the presence of a catalytic amount of Lewis acid at a temperature (- 3) - 50 ° C or a catalytic amount of a compound of the general formula:
where p is 0.1 or 2;
- 2 or 4;
X is halogen or alkanoyloxy, § at room temperature.
where R is alkyl 1-4 carbon atoms2. The method of obtaining threo-2-hydroxy-3 (4-toxiphenyl) -3- (2-nitrophenylthio) propionic ester of a common and
alkyl with 1 to 4 carbon atoms (1)
-C — COOR. I
OH tbttp'tg ^ of the genus, by the reaction of a trans-3- (4-methoxyphenyl) glycidyl ester where R has the indicated meaning, £ 2-nitrothiophenol in an organic solvent, based on yes, based on trans-3- (4-methoxyphenyl) glycidyl ester total>
where R has the indicated meaning, in an organic solvent, characterized in that.
in order to intensify the process, a compound of the general formula is subjected to interaction with a compound of the general formula (P)
- where p is 0.1 or 2;
[2]
(| - 2 or 4;
X is a halogen or alkanoyloxy group, in an equimolar amount at room temperature.
Priority by signs:
A method according to claim Lewis acid;
- in the presence
The method of claim 1, in the presence of a catalytic amount of a compound of formula (III), and the method of claim 2.

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法律状态:

优先权:

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JP56028779A|JPS6118549B2|1981-02-27|1981-02-27|

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JP56078317A|JPS6351148B2|1981-05-22|1981-05-22|

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