CN1093533C - Process for preparing N-(2 or 3-M, 5 or 6-M', 4-amino-phenyl)-N',N'-dimethyl acetamidine - Google Patents
Process for preparing N-(2 or 3-M, 5 or 6-M', 4-amino-phenyl)-N',N'-dimethyl acetamidine Download PDFInfo
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- CN1093533C CN1093533C CN95112223A CN95112223A CN1093533C CN 1093533 C CN1093533 C CN 1093533C CN 95112223 A CN95112223 A CN 95112223A CN 95112223 A CN95112223 A CN 95112223A CN 1093533 C CN1093533 C CN 1093533C
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Abstract
The present invention relates to a process for reducing nitryl with unstable guanyl on the para-position of a benzene ring into azyl, which adopts active metal such as Zn or Sn to react with organic acid and proper solvent at a normal temperature and normal pressure so as to reduce N-(2 or 3-M, 5 or 6-M', 4-nitrophenyl)-N', N'-dimethyl acetamidine into N-(2 or 3-M, 5 or 6-M', 4-aminophenyl)-N', N'-dimethyl acetamidine, wherein M is equal to H,-R,-OR and-COOR (R is equal to H and C1 to C6); M' is equal to H,-R,-OR and-COOR (R is equal to H and C1 to C6). Side reactions are reduced to make a reduction yield up to over 80%, and the highest reduction yield can be up to over 95%. The present invention is suitable for industrial production.
Description
The present invention be a kind of with the nitroreduction on the phenyl ring when having unstable amidino groups on the amino method, particularly nitro contraposition, be the method for amino with nitroreduction.
N-(4-aminophenyl)-N ', N '-dimethyl ethanamidine is a kind of intermediate of pharmaceutical prod, especially as the intermediate of some insect repellent, and itself has also found anthelmintic action, begun to come on the scene, as former Deutsches Reichs-Patent Ger.Offen 2,029,299 (1977) have disclosed several preparation methods:
" medicine industry " [1985,16 (3), 101-3] (CA, 103,123115u) middle published article has disclosed a kind of improving one's methods with tin protochloride:
But above several method is because under strong acid or alkali condition, the amidino groups on the phenyl ring is unstable relatively, be easy to generate some side reactions, thereby its highest yield also has only 80%.
The invention provides a kind of under normal temperature, normal pressure, the nitro that contraposition has a unstable amidino groups on the reduction phenyl ring (particularly meets following general formula N-(2 or 3-M, 5 or 6-M ', the 4-nitrophenyl)-N ', N '-dimethyl ethanamidine) is amino method, the reduction yield can reach more than 80%, and cost is low, more is applicable to suitability for industrialized production.
Solution of the present invention is, N-(2 or 3-M, 5 or 6-M ', 4-nitrophenyl)-N ', and N '-dimethyl ethanamidine reacts in the presence of organic acid and appropriate solvent with a kind of active metal, is amino with nitroreduction.
Wherein M, M ' can be H ,-R ,-OR ,-COOR (R=H, C
1-C
6The straight or branched alkyl).
Active metal such as Zn that this reaction is adopted, Sn makes reductive agent, preferably zinc; The organic acid that adopts can be C
1-C
7Organic acid, preferably formic acid or acetate or propionic acid or lactic acid are as acidic medium; Reactant and organic acid mol ratio are 1: 0.3～5.0, and organic acid can be well and the product salify like this, and reduce the destruction that mineral acid causes reactant and product, and reduce side reaction.Therefore, improved the reduction yield.
This reaction also should be carried out in appropriate solvent, and said solvent can be water or alcohols, as ethanol or methyl alcohol; The ester class is as vinyl acetic monomer etc.; It perhaps is the mixture that above-mentioned several solvents are arranged.This reacts under the normal temperature and pressure and carries out, and temperature of reaction is 0～100 ℃, and optimal reaction temperature is 30～40 ℃.
The invention solves the equipment requirements height that exists in the prior art, difficult points such as severe reaction conditions reduce production cost greatly, particularly reduced side reaction, improved reaction yield significantly, yield is generally more than 80%, can reach more than 95%, make it more to be applicable to suitability for industrialized production.The present invention is as N-(4-aminophenyl)-N ', and the preparation method of N '-dimethyl ethanamidine has more high economic benefit, and is suitable equally for other similar compound of the present invention.
Use some examples below again, the invention will be further described, is not confined among these examples certainly.
Example 1
Take by weighing 5.0 gram N-(4-nitrophenyl)-N ', N '-dimethyl ethanamidine mixes with 6.2 gram zinc powders, adds 25ml water, stirs to add 5.0 gram Glacial acetic acid down, and control reaction temperature was reacted 2 hours at 30～40 ℃, finished reaction.
With above reacting liquid filtering, filtrate transfers to strong basicity with sodium hydroxide solution, with ethyl acetate extraction and concentrating under reduced pressure, obtain 4.6 gram products, use the ether recrystallization again, get 4.1 gram N-(4-aminophenyl)-N ', N '-dimethyl ethanamidine, 92～93 ℃ of fusing points, yield are 95.9%.
Example 2
Take by weighing 5.0 gram N-(4-nitrophenyl)-N ', N '-dimethyl ethanamidine mixes with 6.2 gram zinc powders, adds 50ml ethanol, stirs to add 7.0 gram Glacial acetic acid down, and control is reflected at 30～50 ℃, reacts and finishes reaction in 2 hours.
With above reacting liquid filtering, filtrate decompression is distilled to dried, is dissolved in water, and transfers to strong basicity with sodium hydroxide, use the ethyl acetate extraction product, concentrate back ether recrystallization, get 3.9 gram N-(4-aminophenyl)-N ', N '-dimethyl ethanamidine, 92～93 ℃ of fusing points, yield 91.2%.
Example 3
Get 5.0 gram N-(4-nitrophenyl)-N ', N '-dimethyl ethanamidine mixes with 6.2 gram zinc powders, adds the 50ml vinyl acetic monomer, stirs to add 5.0 gram Glacial acetic acid control reaction temperature down at 30～50 ℃, reacts 2 hours, finishes reaction.
Above reaction solution is transferred to strong basicity with 50% sodium hydroxide, tell organic layer, and wash with water, condensing crystal, and use the ether recrystallization, and getting 3.8 gram N-(4-aminophenyl)-N ', N '-dimethyl ethanamidine, fusing point are 92～93 ℃, yield 88.9%.
Example 4
Take by weighing 5.0 gram N-(4-nitrophenyl)-N ', N '-dimethyl ethanamidine mixes with 6.0 gram zinc powders, adds water 25ml, stirs to add 5.0 gram propionic acid down, and control reaction temperature finishes reaction 20～40 ℃ of reactions 2 hours.
Above reaction solution is transferred to strong basicity with sodium hydroxide,, use the ether recrystallization again, get 3.8 gram N-(4-aminophenyl)-N ', N '-dimethyl ethanamidine, 92～93 ℃ of fusing points, yield 88.9% with ethyl acetate extraction and enriched product.
Example 5
Replace propionic acid with 4.0 gram formic acid, other are operated with example 4, obtain 3.9 gram N-(4-aminophenyl)-N ', and N '-dimethyl ethanamidine, fusing point are 92～93 ℃, yield 91.2%.
Example 6
Press example 1 operation, control reaction temperature obtains 3.7 gram products at 90～100 ℃, and fusing point is 91～92 ℃, yield 86.5%.
Example 7
Press example 1 operation, add 7.2 gram Glacial acetic acid, controlled temperature reacted 4 hours at 0～10 ℃, got 3.7 gram products, and fusing point is 92～93 ℃, yield 86.5%.
Example 8
Get 10 gram N-(4-nitrophenyl)-N ', N '-dimethyl ethanamidine replaces propionic acid with 0.8 gram formic acid, and control reaction temperature is at 95～100 ℃, and other are operated with example 4, obtain 3.8 gram products, 91～92 ℃ of fusing points, yield 88.9%.
Example 9
Replace propionic acid with 5 gram lactic acid, control reaction temperature is at 50～70 ℃, and other is operated with example 4, gets product 3.6 grams, 91～92 ℃ of fusing points, yield 84.6%.
Claims (10)
1, a kind of with N-(2 or 3-M, 5 or 6-M ', 4-nitrophenyl)-N ', N '-dimethyl ethanamidine prepares N-(2 or 3-M, 5 or 6-M ', 4-aminophenyl)-N ', the method for N '-dimethyl ethanamidine, M=H wherein ,-R ,-OR ,-COOR (R=H, C
1-C
6The straight or branched hydroxyl), M '=H ,-R ,-OR ,-COOR (R=H, C
1-C
6The straight or branched hydroxyl), it is characterized in that reactant and organic acid react to form in the presence of a kind of active metal and appropriate solvent.
2, method according to claim 1 is characterized in that reaction is at normal temperatures and pressures, and temperature is 0～100 ℃.
3, method according to claim 2 is characterized in that temperature of reaction is 30～40 ℃.
4, method according to claim 1 is characterized in that used organic acid is C
1-C
7Acid.
5, method according to claim 4 is characterized in that used organic acid is acetic acid, propionic acid, formic acid or lactic acid.
6, method according to claim 1, the mol ratio when it is characterized in that reactant and organic acid reaction is: reactant: organic acid=1: 0.3～5.0.
7, method according to claim 1 is characterized in that used active metal is zinc or tin.
8, method according to claim 7 is characterized in that used active metal is a zinc.
9, method according to claim 1 is characterized in that used reaction solvent is water, ethanol, vinyl acetic monomer or its mixture.
10, method according to claim 1 is characterized in that wherein M, M ' respectively are the H atom.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN95112223A CN1093533C (en) | 1995-11-16 | 1995-11-16 | Process for preparing N-(2 or 3-M, 5 or 6-M', 4-amino-phenyl)-N',N'-dimethyl acetamidine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN95112223A CN1093533C (en) | 1995-11-16 | 1995-11-16 | Process for preparing N-(2 or 3-M, 5 or 6-M', 4-amino-phenyl)-N',N'-dimethyl acetamidine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1150147A CN1150147A (en) | 1997-05-21 |
| CN1093533C true CN1093533C (en) | 2002-10-30 |
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ID=5079414
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN95112223A Expired - Lifetime CN1093533C (en) | 1995-11-16 | 1995-11-16 | Process for preparing N-(2 or 3-M, 5 or 6-M', 4-amino-phenyl)-N',N'-dimethyl acetamidine |
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|---|---|
| CN (1) | CN1093533C (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100348577C (en) * | 2004-05-12 | 2007-11-14 | 中国疾病预防控制中心寄生虫病预防控制所 | Medicinal compound and anthelminthic application |
-
1995
- 1995-11-16 CN CN95112223A patent/CN1093533C/en not_active Expired - Lifetime
Non-Patent Citations (1)
| Title |
|---|
| CA:103:123115U * |
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| Publication number | Publication date |
|---|---|
| CN1150147A (en) | 1997-05-21 |
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