CN100447135C - 2-chloro-4,6-dimethoxy pyrimidine preparing method - Google Patents
2-chloro-4,6-dimethoxy pyrimidine preparing method Download PDFInfo
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- CN100447135C CN100447135C CNB2005100772417A CN200510077241A CN100447135C CN 100447135 C CN100447135 C CN 100447135C CN B2005100772417 A CNB2005100772417 A CN B2005100772417A CN 200510077241 A CN200510077241 A CN 200510077241A CN 100447135 C CN100447135 C CN 100447135C
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Abstract
The present invention relates to a method for preparing 2-chlorine-4, 6-dimethoxypyrimidine through a cyclization reaction with the existence of hydrogen chloride by cyan esteramide in binary double solvent. The present invention is characterized in that the binary double solvent is composed of toluene and amide solvent or cyclic ether solvent. The purpose of the present invention is to provide a method for preparing 2-chlorine-4, 6-dimethoxypyrimidine which has high yield rate and is suitable for industrialization.
Description
Technical field
The present invention relates to a kind of 2-chloro-4, the preparation method of 6-dimethoxypyridin
Background technology
2-chloro-4,6-dimethoxypyridin are the valuable intermediates of agricultural chemicals and pharmaceutical prod, for example can be used as to produce pyrimidine salicylic acid weedicide.European patent 0547411A1 has disclosed and has carried out ring-closure reaction by the inferior carboxylic acid amide esters of cyano group in the presence of hydrogenchloride and prepare 2-chloro-4, the synthesis technique of 6-dimethoxypyridin, this technology is to adopt single solvent, for example tetrahydrofuran (THF), toluene, acetonitrile, methylene dichloride or lower boiling alcohols, and point out to be the best to use toluene especially.The yield of its ring-closure reaction is 73.9% (in the inferior carboxylic acid amide esters of cyano group).
Summary of the invention
The object of the present invention is to provide a kind of high yield to be suitable for industrialized 2-chloro-4,6-dimethoxypyridin preparation method.
2-chloro-4 of the present invention, 6-dimethoxypyridin preparation method, logical hydrogen chloride gas carries out ring-closure reaction in binary complex solution by 3-amino-3-methoxyl group-N-cyano group-2-propionyl imines methyl esters (being called for short the inferior carboxylic acid amide esters of cyano group), reaction finishes to add certain water gaging, layer is isolated organic layer, and the distillation desolventizing gets 2-chloro-4,6-dimethoxypyridin crude product, get high purity 2-chloro-4 with recrystallizing methanol again, 6-dimethoxypyridin finished product.Its productive rate generally can reach (in the inferior carboxylic acid amide esters of cyano group) more than 85%, if the control reaction conditions is proper, best productive rate can reach (in the inferior carboxylic acid amide esters of cyano group) more than 90%.Crude product purity is higher than 97%, and refining back purity surpasses 99%.
The present invention compares with European patent 0547411A1, mainly is to have selected suitable binary complex solution for use, thereby makes ring-closure reaction carry out well having improved productive rate.Binary complex solution of the present invention is based on toluene, the binary complex solution that is mixed with amides or cyclic ethers kind solvent.Wherein amide solvent is for being selected from N, any in dinethylformamide, the N,N-dimethylacetamide; The cyclic ethers kind solvent is to be selected from any in the tetrahydrofuran (THF), diox.The weight proportion of toluene and amides or cyclic ethers kind solvent is 1: 1 to 10: 1 in the binary complex solution of the present invention, preferred 4: 1 to 7: 1.The consumption of binary complex solution is 5～10 times of the inferior carboxylic acid amide esters weight of cyano group, preferred 6～8 times amount.
After ring-closure reaction finishes, need add the aftertreatment that water carries out eccysis ammonium chloride by product in the reaction system, like this in the binary complex solution the miscible component of these and water of amides or cyclic ethers class also by eccysis.Toluene is recovered out in the desolventizing process, and the toluene that reclaims out through washing, can be used further to prepare new double solvents again behind the azeotropic water removing.
In a word, technological method of the present invention is as follows:
2-chloro-4, the preparation method of 6-dimethoxypyridin, with the inferior carboxylic acid amide esters of cyano group is that raw material carries out ring-closure reaction and prepares 2-chloro-4 in the presence of hydrogenchloride, and the 6-dimethoxypyridin is characterized in that selecting for use the binary complex solution of being made up of toluene and amides or cyclic ethers kind solvent; Its proportion of composing is a toluene: amides or cyclic ethers kind solvent=1: 1 to 10: 1 (weight ratio); Binary complex solution is a binary complex solution in the employed amount of ring-closure reaction: the amount (weight ratio) of the inferior carboxylic acid amide esters of cyano group=5～10 times.
Above-mentioned 2-chloro-4, the preparation method of 6-dimethoxypyridin is characterized in that above-mentioned amide solvent is to be selected from N, any in dinethylformamide, the N,N-dimethylacetamide; The cyclic ethers kind solvent is to be selected from any in the tetrahydrofuran (THF), diox.
Above-mentioned 2-chloro-4, the preparation method of 6-dimethoxypyridin, the proportion of composing that it is characterized in that above-mentioned binary complex solution is a toluene: amides or cyclic ethers kind solvent=4: 1 to 7: 1 (weight ratio).
Above-mentioned 2-chloro-4, the preparation method of 6-dimethoxypyridin is characterized in that above-mentioned binary complex solution is a binary complex solution in the employed amount of ring-closure reaction: the amount (weight ratio) of the inferior carboxylic acid amide esters of cyano group=6～8 times.
Above-mentioned 2-chloro-4, the preparation method of 6-dimethoxypyridin is characterized in that reacted binary complex solution through handling the recyclable toluene that goes out, participates in the new double solvents of preparation.
Reaction formula is:
Embodiment:
The invention will be further described below in conjunction with embodiment, but be not limited to this.
Embodiment 1
The inferior carboxylic acid amide esters of 100 parts of cyano group are suspended in 700 parts by toluene and N, in the binary complex solution (weight ratio is 5: 1) that dinethylformamide is formed, are cooled to-15 ℃, logical HCL gas is to saturated, temperature control-10～-15 ℃, common 3 hours.Reaction adds 1000 parts of water after finishing, and layer separates.Water layer more once with the extraction of 200 parts of toluene, combining methylbenzene, underpressure distillation concentrates, dry 106.5 parts of 2-chloro-4,6-dimethoxypyridin crude product (content 97%), yield are 91.7% (in the inferior carboxylic acid amide esters of cyano group).Once obtain 103 parts of white 2-chloro-4 with recrystallizing methanol, 6-dimethoxypyridin finished product (content 99.3%, 104～105 ℃ of fusing points).The toluene that distills out washes twice again with water, is used to prepare new binary complex solution behind the azeotropic water removing.
Embodiment 2
The inferior carboxylic acid amide esters of 100 parts of cyano group is suspended in 600 parts by toluene and N, in the binary complex solution (weight ratio is 7: 1) that the N-N,N-DIMETHYLACETAMIDE is formed, other are with embodiment 1, get 102 parts of 2-chloro-4,6-dimethoxypyridin crude product (content 97%), yield are 87.9% (in the inferior carboxylic acid amide esters of cyano group).
Embodiment 3
The inferior carboxylic acid amide esters of 100 parts of cyano group is suspended in 700 parts of binary complex solution of being made up of toluene and tetrahydrofuran (THF) (weight ratio is 5: 1), other are with embodiment 1, get 105 parts of 2-chloro-4,6-dimethoxypyridin crude product (content 97.7%), yield are 91.1% (in the inferior carboxylic acid amide esters of cyano group).
Embodiment 4
With the inferior carboxylic acid amide esters of 100 parts of cyano group be suspended in 500 parts by toluene Yu in the binary complex solution that diox is formed (weight ratio is 5: 1), other are with embodiment 1, get 103.5 parts of 2-chloro-4,6-dimethoxypyridin crude product (content 97.9%), yield are 90% (in the inferior carboxylic acid amide esters of cyano group).
Claims (4)
1.2-chloro-4, the preparation method of 6-dimethoxypyridin, with the inferior carboxylic acid amide esters of cyano group is that raw material carries out ring-closure reaction and prepares 2-chloro-4 in the presence of hydrogenchloride, and the 6-dimethoxypyridin is characterized in that selecting for use the binary complex solution of being made up of toluene and amides or cyclic ethers kind solvent; Its proportion of composing is a toluene: amides or cyclic ethers kind solvent=4: 1 to 7: 1 (weight ratio); Binary complex solution is a binary complex solution in the employed amount of ring-closure reaction: the amount (weight ratio) of the inferior carboxylic acid amide esters of cyano group=5～10 times.
2. 2-chloro-4 according to claim 1, the preparation method of 6-dimethoxypyridin is characterized in that above-mentioned amide solvent is to be selected from N, any in dinethylformamide, the N,N-dimethylacetamide; The cyclic ethers kind solvent is to be selected from any in the tetrahydrofuran (THF), diox.
3. 2-chlorine 4 according to claim 1, the preparation method of 6-dimethoxypyridin is characterized in that above-mentioned binary complex solution is a binary complex solution in the employed amount of ring-closure reaction: the amount (weight ratio) of the inferior carboxylic acid amide esters of cyano group=6～8 times.
4. 2-chloro-4 according to claim 1, the preparation method of 6-dimethoxypyridin is characterized in that reacted binary complex solution through handling the recyclable toluene that goes out, participates in the new double solvents of preparation.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100772417A CN100447135C (en) | 2005-06-20 | 2005-06-20 | 2-chloro-4,6-dimethoxy pyrimidine preparing method |
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| CNB2005100772417A CN100447135C (en) | 2005-06-20 | 2005-06-20 | 2-chloro-4,6-dimethoxy pyrimidine preparing method |
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| CN100447135C true CN100447135C (en) | 2008-12-31 |
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| CN107759528B (en) * | 2017-11-08 | 2020-05-19 | 营口营新化工科技有限公司 | Synthesis method of 2-chloro-4, 6-dimethoxypyrimidine |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5266697A (en) * | 1991-11-26 | 1993-11-30 | Lonza Ltd. | Process for the production of 2-substituted 4,6-dialkoxypyrimidines |
| US5378845A (en) * | 1992-08-05 | 1995-01-03 | Lonza, Ltd. | Process for the production of 2-halo-4,6-dialkoxy pyrimidines |
| CN1467206A (en) * | 2002-07-09 | 2004-01-14 | 金坛希望化工有限公司 | Preparation method of 2-chloro-4, 6-dimethoxypyrimidine |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5266697A (en) * | 1991-11-26 | 1993-11-30 | Lonza Ltd. | Process for the production of 2-substituted 4,6-dialkoxypyrimidines |
| US5378845A (en) * | 1992-08-05 | 1995-01-03 | Lonza, Ltd. | Process for the production of 2-halo-4,6-dialkoxy pyrimidines |
| CN1467206A (en) * | 2002-07-09 | 2004-01-14 | 金坛希望化工有限公司 | Preparation method of 2-chloro-4, 6-dimethoxypyrimidine |
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Address after: 213200 No. 95 Park North Road, Jintan Economic Development Zone, Jiangsu, China Patentee after: Jiangsu Institute of Ecomones Co.,Ltd. Address before: 213022 No. 98 Minjiang Road, Changzhou New District, Jiangsu, Changzhou Patentee before: Jiangsu Prov. Hormone Inst., Co., Ltd. |