CN103242190A - Synthetic method of propyzamide - Google Patents
Synthetic method of propyzamide Download PDFInfo
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- CN103242190A CN103242190A CN2013101844313A CN201310184431A CN103242190A CN 103242190 A CN103242190 A CN 103242190A CN 2013101844313 A CN2013101844313 A CN 2013101844313A CN 201310184431 A CN201310184431 A CN 201310184431A CN 103242190 A CN103242190 A CN 103242190A
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Abstract
The invention discloses a synthetic method of propyzamide. The method comprises the following steps: by taking 3, 5-dichlorobenzoic acid as a raw material, chlorinating 3, 5-dichlorobenzoic acid to generate 3, 5-dichlorobenzoyl chloride; further performing reaction between generated 3, 5-dichlorobenzoyl chloride and 3-amino-3-methyl butyne in the presence of alkaline matters and solvents; and filtering, drying and recrystallizing the reaction solution to obtain propyzamide. The material in the process is easy to obtain and low in cost, the production cost of products is low, and the safety coefficient of the process is high. The method is simple to operate, short in process flow and beneficial for industrialized production, and is a novel process for synthesizing propyzamide.
Description
Technical field
The present invention relates to a kind of novel method of synthetic pentyne grass amine, being specifically related to a kind of is the synthetic method of the pentyne grass amine of starting raw material with 3,5-dichlorobenzoic acid.
Background technology
Pentyne grass amine, commodity are called the alkynes Stam F-34, are a kind of widely used acetamide-group herbicides, are usually used in the control of broadleaf weeds.At present, have only The Dow Agrosciences, LLC. to produce 98% pentyne grass amine, other countries produce the pentyne grass amine of 94-95%, and the former medicine of pentyne grass amine is sold over past ten years very steady always, good market prospects.
The present pentyne of report grass amine synthetic method, mainly be 3,5-dichlorobenzoic acid through acidylate, get 3,5-dichlorobenzoyl chloride, 3,5-dichlorobenzoyl chloride is produced with 3-amino-3-methyl butine reaction again.
Wherein 3,5-dichlorobenzoic acid synthetic method has following two kinds by the raw material classification:
The one,, be raw material with 3,5-diaminotoluene, first diazotization generates 3,5-toluene dichloride, is solvent again with acetic acid, and acetic acid bores and is catalyzer, and oxidation produces 3, the 5-dichlorobenzoic acid;
The 2nd,, be raw material with the anthranilic acid, it is raw material synthetic 3 with the anthranilic acid, the 5-dichlorobenzoic acid has following several operational path: (1) is raw material with the anthranilic acid, is solvent with ethylene dichloride, DMF, uses the SULPHURYL CHLORIDE chlorination, obtain 2-amino-3, the 5-dichlorobenzoic acid, diazotization and getting again, yield is 60%.(2) with the anthranilic acid be raw material, hydrochloric acid is solvent, and iron trichloride is catalyzer, about 10 ℃, directly logical chlorine obtains 2-amino-3, the 5-dichlorobenzoic acid, carry out diazotization reaction again, adding copper sulfate, isopropanol reaction get crude product, get product with the toluene recrystallization again.(3) with the anthranilic acid be raw material, acetic acid and aqueous solution liquid directly lead to Cl down as solvent about 40 ℃
2, obtain 3,5-, two chloro-o-amino benzoic acids, carry out diazotization reaction again, add Virahol, hydrochloric acid and Catalysts Cu SO
4Reaction obtains crude product, and the toluene recrystallization gets product.(4) anthranilic acid has been to expect, and 10% hydrochloric acid is solvent, and logical chlorine is 4 hours under 28-30 ℃, adds Virahol under above-mentioned reaction conditions, drips NaNO down at 80-85 ℃
2The aqueous solution dripped off in 2 hours, reacted half an hour again under this temperature, and reaction solution carries out simple distillation again, collected 80-90 ℃ of Virahol and water, and the distillation residuum is cooled to 20-25 ℃ and placed 2 hours, carries out suction filtration.Filter cake is 3,5-dichlorobenzoic acid, and drying gets 3,5-dichlorobenzoic acid dry product.(5) anthranilic acid is raw material, and hydrochloric acid is solvent, adds hydrogen peroxide and carries out chlorination, sulfuric acid system dropping NaNO
2Solution, ethanol is made reductive agent, carries out diazotization reaction and obtains target product.
Adopt the technology of synthetic 3, the 5-dichlorobenzoic acid of other technologies not appear in the newspapers as yet at present.
In above-mentioned two kinds of methods, be raw material with 3,5-diaminotoluene, this method raw materials cost height, yield is low, pollutes greatlyyer, and production environment is abominable.Anthranilic acid has been that the method for expecting is comparatively economical, but this method ubiquity, long reaction time is operated loaded down with trivial details shortcoming, and in especially synthetic 3, the 5-dichlorobenzoic acid process, the diazotization operation is dangerous high.Therefore seeking new synthetic route for pentyne grass amine is problem demanding prompt solution.
Summary of the invention
Purpose of the present invention provides a kind of synthetic method of pentyne grass amine, and this method provides a kind of new thinking for pentyne grass amine is synthetic, and process safety, good product quality overcome the shortcoming that exists in the prior art.
Technical solution of the present invention is as follows:
The synthetic method of a kind of pentyne grass amine is characterized in that: earlier the chlorination of 3,5-dichlorobenzoic acid is generated 3,5-dichlorobenzoyl chloride, will generate then 3,5-dichlorobenzoyl chloride and 3-amino-careless amine of 3-methyl butine reaction generation pentyne; Used 3, the synthetic method of 5-dichlorobenzoic acid may further comprise the steps: be raw material with the cyanophenyl, in the presence of solvent and chlorizating agent, chlorination generates 3,5-dichlorobenzonitrile in sour environment; 3,5-dichlorobenzonitrile earlier is hydrolyzed to 3,5-dichlorobenzoic acid salt under alkaline environment, acidifying gets 3,5-dichlorobenzoic acid under sour environment again, and perhaps 3, the 5-dichlorobenzonitrile is hydrolysis under sour environment directly, gets 3,5-dichlorobenzoic acid.
In the aforesaid method, when synthesizing 3,5-dichlorobenzoic acid, step comprises: be raw material with the cyanophenyl, cyanophenyl is dissolved in solvent and the acidic medium, drip chlorizating agent at a certain temperature, and the suitable pH value of control, reaction obtains 3,5-dichlorobenzonitrile; Under normal pressure, in 3,5-dichlorobenzonitrile, add alkaline matter then, pH value of reaction system is kept within the specific limits, insulation reaction, hydrolysis gets 3,5-dichlorobenzoic acid salt, and 3,5-dichlorobenzoic acid salt filters, dries through acidifying, namely gets 3,5-dichlorobenzoic acid; Or in 3,5-dichlorobenzonitrile, directly add acid, and pH value of reaction system is kept within the specific limits, insulation reaction directly obtains 3,5-dichlorobenzoic acid.
In the aforesaid method, when synthesizing 3,5-dichlorobenzoic acid, described solvent is one or more of methyl alcohol, Virahol, second cyanogen, ethyl acetate, chloroform, methylene dichloride, ether, toluene, trichloromethane and ethanol.Be preferably the mixture of trichloromethane and ethanol, most preferably trichloromethane and ethanol mass ratio are 3: 1.
In the aforesaid method, when synthesizing 3,5-dichlorobenzoic acid, described solvent and cyanophenyl mass ratio are 1-80: 1.
In the aforesaid method, when synthesizing 3,5-dichlorobenzoic acid, described chlorizating agent is clorox, or the mixture of hydrogen peroxide and hydrochloric acid.Cyanophenyl and clorox mol ratio are 1: 2.0-2.4; Cyanophenyl, HCl and hydrogen peroxide (refer to H
2O
2) mol ratio be 1: 2.0-2.5: 2.1-2.6, HCl provides with the form of aqueous hydrochloric acid, concentration of hydrochloric acid solution has no special requirements.
In the aforesaid method, when synthesizing 3,5-dichlorobenzoic acid, during the cyanophenyl chlorination, keeping the pH value is 0-6.0, and temperature of reaction is 50-70 ℃, and used acid is monobasic or polynary mineral acid, and described acid includes but not limited to hydrochloric acid, sulfuric acid, phosphoric acid or nitric acid; Wherein concentration of hydrochloric acid is more than 25%, and sulfuric acid concentration is more than 30%, and phosphoric acid concentration is more than 85%, concentration of nitric acid is more than 65%, consider the operating equipment utilization ratio and simplify last handling process, the concentrated acid that preferred water content is less, for example concentrated hydrochloric acid, the vitriol oil, strong phosphoric acid or concentrated nitric acid.
In the aforesaid method, when synthesizing 3,5-dichlorobenzoic acid, during 3,5-dichlorobenzonitrile alkaline hydrolysis (i.e. hydrolysis under alkaline environment), keeping the pH value is 11-14, and temperature of reaction is 50-90 ℃, and preferred 80-90 ℃, the general reaction times is 2-3h.When being hydrolyzed under 3, the 5-dichlorobenzonitrile normal pressure alkaline environment, keep alkaline environment with sodium hydroxide, potassium hydroxide or their aqueous solution, used sodium hydroxide solution or potassium hydroxide solution concentration generally between 10wt%-30wt%, are preferably sheet alkali.
In the aforesaid method, synthetic 3, during the 5-dichlorobenzoic acid, during the acidifying of 3,5-dichlorobenzoic acid salt, maintenance pH is 0-3, keeping temperature is 50-90 ℃, and preferred 50-60 ℃, the general reaction times is 0.5-1h, used acid is monobasic or polynary mineral acid, and described acid includes but not limited to hydrochloric acid, sulfuric acid, phosphoric acid or nitric acid; Wherein concentration of hydrochloric acid is more than 25%, and sulfuric acid concentration is more than 30%, and phosphoric acid concentration is more than 85%, concentration of nitric acid is more than 65%, consider the operating equipment utilization ratio and simplify last handling process, the concentrated acid that preferred water content is less, for example concentrated hydrochloric acid, the vitriol oil, strong phosphoric acid or concentrated nitric acid.
In the aforesaid method, when synthesizing 3,5-dichlorobenzoic acid, during the direct acidic hydrolysis of 3,5-dichlorobenzonitrile (i.e. directly hydrolysis under sour environment), keeping the pH value is 1-4, and temperature is 50-90 ℃, and preferred 80-90 ℃, the general reaction times is 2-3h.Used acid is monobasic or polynary mineral acid, and described acid includes but not limited to hydrochloric acid, sulfuric acid, phosphoric acid or nitric acid; Wherein concentration of hydrochloric acid is more than 25%, and sulfuric acid concentration is more than 30%, and phosphoric acid concentration is more than 85%, concentration of nitric acid is more than 65%, consider the operating equipment utilization ratio and simplify last handling process, the concentrated acid that preferred water content is less, for example concentrated hydrochloric acid, the vitriol oil, strong phosphoric acid or concentrated nitric acid.
In the aforesaid method, synthetic 3,5-may further comprise the steps during dichlorobenzoyl chloride: with 3,5-dichlorobenzoic acid and sulfur oxychloride mix, at 70-80 ℃ of following back flow reaction 2-4h, first at normal pressure, the 75-82 ℃ following sulfur oxychloride that reclaims, again at 185-195 ℃ then,-0.5～-steam 3,5-dichlorobenzoyl chloride under the 0.01MPa; 3,5-dichlorobenzoic acid and sulfur oxychloride mol ratio are 1: 1.0-1.5.
In the aforesaid method, specifically may further comprise the steps when synthesizing pentyne grass amine: 3,5-dichlorobenzoyl chloride and 3-amino-3-methyl butine is reaction 2-4h in the presence of solvent, under pH8-10, temperature 15-25 ℃, reaction after-filtration reaction solution, get crude product, the crude product recrystallization gets pentyne grass amine; 3,5-dichlorobenzoic acid and 3-amino-3-methyl butine mol ratio is 1: 1.0-1.4.
In the aforesaid method, when synthesizing pentyne grass amine, control pH with alkaline matter, alkaline matter is sodium hydroxide, potassium hydroxide or their aqueous solution.Used sodium hydroxide solution or potassium hydroxide solution concentration generally between 10wt%-30wt%, are preferably sheet alkali.
In the aforesaid method, when synthesizing pentyne grass amine, solvent is one or more in methyl alcohol, Virahol, second cyanogen, ethyl acetate, chloroform, methylene dichloride, ether, toluene, trichloromethane and the ethanol, the mixture of preferred trichloromethane and ethanol, most preferably trichloromethane and ethanol mass ratio are 3: 1.
In the aforesaid method, when synthesizing pentyne grass amine, the mass ratio of solvent and 3,5-dichlorobenzoic acid is 1-80: 1.
In the aforesaid method, when synthesizing pentyne grass amine, the crude product of filtering reacting liquid gained need wash, and drying is recrystallization again, and drying temperature is 100-105 ℃, and drying time is 4-6h; The recrystallization solvent for use is methyl alcohol.
The invention has the beneficial effects as follows:
1, proposing first with the cyanophenyl is raw material, elder generation's chlorination generates 3, the 5-dichlorobenzonitrile, hydrolysis then, acidification reaction get 3,5-dichlorobenzoic acid, traditional chlorinated with chlorine has been abandoned in chlorination, make chlorination safe, gained 3,5-dichlorobenzonitrile purity height, need not the diazotization operation, improved process safety.
2, by 3, the 5-dichlorobenzoic acid is raw material synthetic 3, the 5-dichlorobenzoyl chloride has adopted sulfur oxychloride to cook chlorizating agent, and easy ease is gone because its by product is gas, be conducive to separate, this reaction conditions is relatively gentleer, reaction back noresidue by product, and productive rate height, and sulfur oxychloride can recycling, has reduced cost.
3, generate pentyne grass amine by 3,5-dichlorobenzoyl chloride and 3-amino-3-methyl butine reaction, simple to operate, products obtained therefrom is handled purity through recrystallization and can be reached more than 99%.
4, this raw materials technology be easy to get, cheapness, the products production cost is low, process safety coefficient height, simple to operate, technical process is brief, more is conducive to suitability for industrialized production, is the novel process of synthetic pentyne grass amine.
Description of drawings
Fig. 1 is the liquid phase spectrogram of the pentyne grass amine of the present invention's preparation.
Among the figure:
Embodiment
The invention will be further described below in conjunction with specific embodiment, should be understood that, following explanation only is in order to explain the present invention, its content not to be limited.
100.0g in the cyanophenyl (content 99%), add the 300g trichloromethane respectively, 100g ethanol, drop into 1209.4g clorox (content 13%) again, it is 3.0-4.0 that hydrochloric acid with 37% keeps system pH, and under 55-60 ℃, reaction is to 3, control content is 99.5% in the 5-dichlorobenzonitrile, under normal pressure, add 30% sodium hydroxide then, make pH value of reaction system remain on 12-13, behind the 80-90 ℃ of insulation reaction 2.5h, be 1.0 with 37% hcl acidifying to system pH again, under 50-60 ℃, reaction 1.0h, refilter, 90-110 ℃ of down oven dry, namely get 182.5g content and be 99.0% 3, the 5-dichlorobenzoic acid.
Get 3 of gained, 5-dichlorobenzoic acid 100g mixes with 74.7g sulfur oxychloride (content 99%), at 70-80 ℃ of following back flow reaction 2.0h, first at normal pressure, the 75-82 ℃ following sulfur oxychloride that reclaims then, again at 185-195 ℃, steam 3 under the-0.01MPa, the 5-dichlorobenzoyl chloride is got single step reaction ready and is used.
Get 52.8g3-amino-3-methyl butine (content 98%), 6000g trichloromethane and 2000g ethanol, under 15-25 ℃ of stirring, add 3,5-dichlorobenzoyl chloride, keep reaction pH8.0 with 30%NaOH, and under this temperature, react 4.0h, filtering reacting liquid, filter cake is at 100-105 ℃ of oven dry 2.0h, and crude product is in methyl alcohol behind the recrystallization, get 132.4g pentyne grass amine, analyzing pentyne grass amine purity through HPLC is 99.8%.
Embodiment 2
100.0g in the cyanophenyl (content 99%), add the 1500g trichloromethane respectively, 500g ethanol, drop into 1209.4g clorox (content 13%) again, it is 5.0-6.0 that sulfuric acid with 98% keeps system pH, and under 60-70 ℃, reaction is to 3, control content is 99.4% in the 5-dichlorobenzonitrile, under normal pressure, add 20% sodium hydroxide then, make pH value of reaction system remain on 11-12, behind the 80-90 ℃ of insulation reaction 3.0h, be 0 with 37% hcl acidifying to system pH again, under 50-60 ℃, reaction 0.5h, refilter, 90-110 ℃ of down oven dry, namely get 182.5g content and be 99.0% 3, the 5-dichlorobenzoic acid.
Get 3 of gained, 5-dichlorobenzoic acid 100g mixes with g74.7 sulfur oxychloride (content 99%), at 70-80 ℃ of following back flow reaction 2.5h, first at normal pressure, the 75-82 ℃ following sulfur oxychloride that reclaims then, again at 185-195 ℃, steam 3 under the-0.05MPa, the 5-dichlorobenzoyl chloride is got single step reaction ready and is used.
Get 52.8g3-amino-3-methyl butine (content 98%), 3000g trichloromethane and 1000g ethanol, under 15-25 ℃ of stirring, add 3,5-dichlorobenzoyl chloride, keep reaction pH8.5 with 20%NaOH, and under this temperature, react 3.5h, filtering reacting liquid, filter cake is at 100-105 ℃ of oven dry 3.0h, and crude product is in methyl alcohol behind the recrystallization, get 132.4g pentyne grass amine, analyzing pentyne grass amine purity through HPLC is 99.8%.
100.0g in the cyanophenyl (content 99%), add the 75g trichloromethane respectively, 25g ethanol, drop into 1209.4g clorox (content 13%) again, it is 0-1.0 that hydrochloric acid with 25% keeps system pH, and under 55-70 ℃, reaction is to 3, control content is 99.5% in the 5-dichlorobenzonitrile, under normal pressure, add 10% sodium hydroxide then, make pH value of reaction system remain on 13-14, behind the 80-90 ℃ of insulation reaction 2.7h, be 1.5 with 37% hcl acidifying to system pH again, under 50-60 ℃, reaction 0.6h, refilter, 90-110 ℃ of down oven dry, namely get 182.3g content and be 99.0% 3, the 5-dichlorobenzoic acid.
Get 3 of gained, 5-dichlorobenzoic acid 100g mixes with 74.7g sulfur oxychloride (content 99%), at 70-80 ℃ of following back flow reaction 3.0h, first at normal pressure, the 75-82 ℃ following sulfur oxychloride that reclaims then, again at 185-195 ℃, steam 3 under the-0.15MPa, the 5-dichlorobenzoyl chloride is got single step reaction ready and is used.
Get 52.8g3-amino-3-methyl butine (content 98%), 2000g Virahol, under 15-25 ℃ of stirring, add 3,5-dichlorobenzoyl chloride, keep reaction pH9.0 with 10%NaOH, and under this temperature, react 3.0h, filtering reacting liquid, filter cake is at 100-105 ℃ of oven dry 4.0h, and crude product is in methyl alcohol behind the recrystallization, get 132.5g pentyne grass amine, analyzing pentyne grass amine purity through HPLC is 99.6%.
Embodiment 4
100.0g in the cyanophenyl (content 99%), add 75g trichloromethane, 25g ethanol respectively, drop into 1209.4g clorox (content 13%) again, it is 0-1.0 that hydrochloric acid with 25% keeps system pH, and under 55-70 ℃, reaction is to 3, control content is 99.5% in the 5-dichlorobenzonitrile, under normal pressure, adds 25% hydrochloric acid then, make pH value of reaction system remain on 1.0-2.5, behind the 80-90 ℃ of insulation reaction 2.7h, refilter 90-110 ℃ of oven dry down, namely get 182.3g content and be 99.0% 3, the 5-dichlorobenzoic acid.
Get 3 of gained, 5-dichlorobenzoic acid 100g mixes with 74.7g sulfur oxychloride (content 99%), at 70-80 ℃ of following back flow reaction 3.5h, first at normal pressure, the 75-82 ℃ following sulfur oxychloride that reclaims then, again at 185-195 ℃, steam 3 under the-0.3MPa, the 5-dichlorobenzoyl chloride is got single step reaction ready and is used.
Get 52.8g3-amino-3-methyl butine (content 98%), 1000g methyl alcohol, under 15-25 ℃ of stirring, add 3,5-dichlorobenzoyl chloride, keep reaction pH9.5 with 30%KOH, and under this temperature, react 2.5h, filtering reacting liquid, filter cake is at 100-105 ℃ of oven dry 5.0h, and crude product is in methyl alcohol behind the recrystallization, get 132.6g pentyne grass amine, analyzing pentyne grass amine purity through HPLC is 99.5%.
Embodiment 5
100.0g in the cyanophenyl (content 99%), add 75g trichloromethane, 25g ethanol respectively, drop into 1209.4g clorox (content 13%) again, it is 0-1.0 that hydrochloric acid with 25% keeps system pH, and under 55-70 ℃, reaction is to 3, control content is 99.5% in the 5-dichlorobenzonitrile, under normal pressure, adds 37% hydrochloric acid then, make pH value of reaction system remain on 2.0-4.0, behind the 80-90 ℃ of insulation reaction 2.7h, refilter 90-110 ℃ of oven dry down, namely get 182.3g content and be 99.0% 3, the 5-dichlorobenzoic acid.
Get 3 of gained, 5-dichlorobenzoic acid 100g mixes with 74.7g sulfur oxychloride (content 99%), at 70-80 ℃ of following back flow reaction 4h, first at normal pressure, the 75-82 ℃ following sulfur oxychloride that reclaims then, again at 185-195 ℃, steam 3 under the-0.5MPa, the 5-dichlorobenzoyl chloride is got single step reaction ready and is used.
Get 52.8g3-amino-3-methyl butine (content 98%), 20g trichloromethane and 80g ethanol, under 15-25 ℃ of stirring, add 3,5-dichlorobenzoyl chloride, keep reaction pH10.0 with sheet alkali, and under this temperature, react 2.0h, filtering reacting liquid, filter cake is at 100-105 ℃ of oven dry 6.0h, and crude product is in methyl alcohol behind the recrystallization, get 132.5g pentyne grass amine, analyzing pentyne grass amine purity through HPLC is 99.7%.
100.0g in the cyanophenyl (content 99%), add 3000g methyl alcohol respectively, 5000g ethanol, drop into 1099.5g clorox (content 13%) again, it is 2.0-3.2 that phosphoric acid with 85% keeps system pH, and under 55-65 ℃, reaction is to 3, control content is 99.4% in the 5-dichlorobenzonitrile, under normal pressure, add 30% potassium hydroxide then, make pH value of reaction system remain on 11-13, behind the 80-90 ℃ of insulation reaction 2.6h, be 3.0 with 37% hcl acidifying to system pH again, under 50-60 ℃, reaction 0.8h, refilter, 90-110 ℃ of down oven dry, namely get 181.3g content and be 98.1% 3, the 5-dichlorobenzoic acid.
Get 3 of gained, 5-dichlorobenzoic acid 100g mixes with 61.7g sulfur oxychloride (content 99%), at 70-80 ℃ of following back flow reaction 2.5h, first at normal pressure, the 75-82 ℃ following sulfur oxychloride that reclaims then, again at 185-195 ℃, steam 3 under the-0.2MPa, the 5-dichlorobenzoyl chloride is got single step reaction ready and is used.
Get 43.6g3-amino-3-methyl butine (content 98%), 1000g second cyanogen, under 15-25 ℃ of stirring, add gained 3, the 5-dichlorobenzoyl chloride keeps reaction pH9.0 with sheet alkali, and under this temperature, react 3.0h, filtering reacting liquid, filter cake is at 100-105 ℃ of oven dry 5.0h, and crude product is in methyl alcohol behind the recrystallization, get 130.1g pentyne grass amine, analyzing pentyne grass amine purity through HPLC is 99.1%.
100.0g in the cyanophenyl (content 99%), add the 6000g Virahol respectively, drop into 1154.4g clorox (content 13%) again, it is 4.0-5.0 that nitric acid with 65% keeps system pH, and under 50-65 ℃, reaction is to 3, control content is 99.1% in the 5-dichlorobenzonitrile, under normal pressure, add sheet alkali then, make pH value of reaction system remain on 12-14, behind the 80-90 ℃ of insulation reaction 2.0h, be 2.0 with 37% hcl acidifying to system pH again, under 50-60 ℃, reaction 0.9h, refilter, 90-110 ℃ of down oven dry, namely get 181.5g content and be 98.0% 3, the 5-dichlorobenzoic acid.
Get 3 of gained, 5-dichlorobenzoic acid 100g mixes with 67.8g sulfur oxychloride (content 99%), at 70-80 ℃ of following back flow reaction 2.5h, first at normal pressure, the 75-82 ℃ following sulfur oxychloride that reclaims then, again at 185-195 ℃, steam 3 under the-0.2MPa, the 5-dichlorobenzoyl chloride is got single step reaction ready and is used.
Get 47.9g3-amino-3-methyl butine (content 98%), 1000g toluene, under 15-25 ℃ of stirring, add gained 3, the 5-dichlorobenzoyl chloride keeps reaction pH9.0 with sheet alkali, and under this temperature, react 3.0h, filtering reacting liquid, filter cake is at 100-105 ℃ of oven dry 5.0h, and crude product is in methyl alcohol behind the recrystallization, get 130.2g pentyne grass amine, analyzing pentyne grass amine purity through HPLC is 99.0%.
100.0g in the cyanophenyl (content 99%), add 4000g second cyanogen respectively, drop into 1264.4g clorox (content 13%) again, it is 5.0-6.0 that sulfuric acid with 30% keeps system pH, and under 50-68 ℃, reaction is to 3, control content is 99.3% in the 5-dichlorobenzonitrile, under normal pressure, add sheet alkali then, make pH value of reaction system remain on 12-13, behind the 80-90 ℃ of insulation reaction 2.2h, be 2.5 with 37% hcl acidifying to system pH again, under 50-60 ℃, reaction 0.7h, refilter, 90-110 ℃ of down oven dry, namely get 181.2g content and be 98.4% 3, the 5-dichlorobenzoic acid.
Get 3 of gained, 5-dichlorobenzoic acid 100g mixes with 80.5g sulfur oxychloride (content 99%), at 70-80 ℃ of following back flow reaction 2.5h, first at normal pressure, the 75-82 ℃ following sulfur oxychloride that reclaims then, again at 185-195 ℃, steam 3 under the-0.2MPa, the 5-dichlorobenzoyl chloride is got single step reaction ready and is used.
Get 56.8g3-amino-3-methyl butine (content 98%), 1000g ethyl acetate, chloroform, under 15-25 ℃ of stirring, add gained 3, the 5-dichlorobenzoyl chloride keeps reaction pH9.0 with sheet alkali, and under this temperature, react 3.0h, filtering reacting liquid, filter cake is at 100-105 ℃ of oven dry 5.0h, and crude product is in methyl alcohol behind the recrystallization, get 130.9g pentyne grass amine, analyzing pentyne grass amine purity through HPLC is 99.2%.
100.0g in the cyanophenyl (content 99%), add 3000g toluene respectively, drop into 1319.4g clorox (content 13%) again, it is 1.0-3.0 that sulfuric acid with 80% keeps system pH, and under 53-65 ℃, reaction is to 3, control content is 99.0% in the 5-dichlorobenzonitrile, under normal pressure, add sheet alkali then, make pH value of reaction system remain on 12-13, behind the 80-90 ℃ of insulation reaction 3.0h, be 1.5 with 37% hcl acidifying to system pH again, under 50-60 ℃, reaction 0.5h, refilter, 90-110 ℃ of down oven dry, namely get 181.0g content and be 98.4% 3, the 5-dichlorobenzoic acid.
Get 3 of gained, 5-dichlorobenzoic acid 100g mixes with 86.7g sulfur oxychloride (content 99%), at 70-80 ℃ of following back flow reaction 2.5h, first at normal pressure, the 75-82 ℃ following sulfur oxychloride that reclaims then, again at 185-195 ℃, steam 3 under the-0.2MPa, the 5-dichlorobenzoyl chloride is got single step reaction ready and is used.
Get 61.2g3-amino-3-methyl butine (content 98%), 1000g methylene dichloride, under 15-25 ℃ of stirring, add gained 3, the 5-dichlorobenzoyl chloride keeps reaction pH9.0 with sheet alkali, and under this temperature, react 3.0h, filtering reacting liquid, filter cake is at 100-105 ℃ of oven dry 5.0h, and crude product is in methyl alcohol behind the recrystallization, get 130.9g pentyne grass amine, analyzing pentyne grass amine purity through HPLC is 99.4%.
100.0g in the cyanophenyl (content 99%), add the 6000g ethyl acetate respectively, the 1000g chloroform, drop into 266.0g hydrogen peroxide (content 27%) again, 227.3g hydrochloric acid (content 37%), keeping system pH with 65% nitric acid again is 1.0-4.0, under 60-70 ℃, reaction to 3, control content is 99.0% in the 5-dichlorobenzonitrile, then under normal pressure, add sheet alkali, making pH value of reaction system remain on 12-13, behind the 80-90 ℃ of insulation reaction 2.5h, is 1.0 with 37% hcl acidifying to system pH again, under 50-60 ℃, reaction 1.0h refilters, 90-110 ℃ of oven dry down, namely get 181.9g content and be 98.3% 3, the 5-dichlorobenzoic acid.
Get 3 of gained, 5-dichlorobenzoic acid 100g mixes with 92.8g sulfur oxychloride (content 99%), at 70-80 ℃ of following back flow reaction 2.5h, first at normal pressure, the 75-82 ℃ following sulfur oxychloride that reclaims then, again at 185-195 ℃, steam 3 under the-0.2MPa, the 5-dichlorobenzoyl chloride is got single step reaction ready and is used.
Get 65.5g3-amino-3-methyl butine (content 98%), 1000g ether, under 15-25 ℃ of stirring, add gained 3, the 5-dichlorobenzoyl chloride keeps reaction pH9.0 with sheet alkali, and under this temperature, react 3.0h, filtering reacting liquid, filter cake is at 100-105 ℃ of oven dry 5.0h, and crude product is in methyl alcohol behind the recrystallization, get 131.3g pentyne grass amine, analyzing pentyne grass amine purity through HPLC is 99.2%.
Embodiment 11
100.0g in the cyanophenyl (content 99%), add the 1000g methylene dichloride respectively, drop into 241.9g hydrogen peroxide (content 27%) again, 294.4g hydrochloric acid (content 25%), keeping system pH with 80% sulfuric acid again is 1.0-4.0, under 60-65 ℃, reaction to 3, control content is 99.0% in the 5-dichlorobenzonitrile, then under normal pressure, add sheet alkali, making pH value of reaction system remain on 12-13, behind the 80-90 ℃ of insulation reaction 2.5h, is 2.0 with 37% hcl acidifying to system pH again, under 50-60 ℃, reaction 0.9h refilters, 90-110 ℃ of oven dry down, namely get 181.3g content and be 98.4% 3, the 5-dichlorobenzoic acid.
With gained 3, the 5-dichlorobenzoic acid according to the method for embodiment 1 and sulfur oxychloride (content 99%) react 3, the 5-dichlorobenzoyl chloride is again with 3-amino-3-methyl butine (content 98%) reaction, recrystallization, get pentyne grass amine, analyzing pentyne grass amine purity through HPLC is 99.1%.
Embodiment 12
100.0g in the cyanophenyl (content 99%), add the 500g ether respectively, drop into 302.3g hydrogen peroxide (content 27%) again, 246.2g hydrochloric acid (content 37%), keeping system pH with 30% sulfuric acid again is 1.0-4.0, under 60-65 ℃, reaction to 3, control content is 99.0% in the 5-dichlorobenzonitrile, then under normal pressure, add sheet alkali, making pH value of reaction system remain on 12-13, behind the 80-90 ℃ of insulation reaction 2.5h, is 1.0 with 37% hcl acidifying to system pH again, under 50-60 ℃, reaction 1.0h refilters, 90-110 ℃ of oven dry down, namely get 181.2g content and be 98.3% 3, the 5-dichlorobenzoic acid.
With gained 3, the 5-dichlorobenzoic acid according to the method for embodiment 1 and sulfur oxychloride (content 99%) react 3, the 5-dichlorobenzoyl chloride is again with 3-amino-3-methyl butine (content 98%) reaction, recrystallization, get pentyne grass amine, analyzing pentyne grass amine purity through HPLC is 99.2%.
Claims (10)
1. the synthetic method of pentyne grass amine is characterized in that: earlier the chlorination of 3,5-dichlorobenzoic acid is generated 3,5-dichlorobenzoyl chloride, will generate then 3,5-dichlorobenzoyl chloride and 3-amino-careless amine of 3-methyl butine reaction generation pentyne; Used 3, the synthetic method of 5-dichlorobenzoic acid may further comprise the steps: be raw material with the cyanophenyl, in the presence of solvent and chlorizating agent, chlorination generates 3,5-dichlorobenzonitrile in sour environment; 3,5-dichlorobenzonitrile earlier is hydrolyzed to 3,5-dichlorobenzoic acid salt under alkaline environment, acidifying gets 3,5-dichlorobenzoic acid under sour environment again, and perhaps 3, the 5-dichlorobenzonitrile is hydrolysis under sour environment directly, gets 3,5-dichlorobenzoic acid.
2. synthetic method according to claim 1, it is characterized in that: synthetic 3, during the 5-dichlorobenzoic acid, described solvent is one or more of methyl alcohol, Virahol, second cyanogen, ethyl acetate, chloroform, methylene dichloride, ether, toluene, trichloromethane and ethanol, and being preferably mass ratio is 3: 1 trichloromethane and the mixture of ethanol.
3. synthetic method according to claim 1 is characterized in that: during synthetic 3,5-dichlorobenzoic acid, the mass ratio of solvent and cyanophenyl is 1-80: 1.
4. synthetic method according to claim 1 is characterized in that: during synthetic 3,5-dichlorobenzoic acid, described chlorizating agent is clorox, or the mixture of hydrogen peroxide and hydrochloric acid.
5. synthetic method according to claim 4 is characterized in that: during synthetic 3,5-dichlorobenzoic acid, during the cyanophenyl chlorination, the mol ratio of cyanophenyl and clorox is 1: 2.0-2.4; The mol ratio of cyanophenyl, HCl and hydrogen peroxide is 1: 2.0-2.5: 2.1-2.6.
6. synthetic method according to claim 1 is characterized in that: during synthetic 3,5-dichlorobenzoic acid, during the cyanophenyl chlorination, keeping the pH value is 0-6.0, and temperature of reaction is 50-70 ℃; During the alkaline hydrolysis of 3,5-dichlorobenzonitrile, keeping temperature is 50-90 ℃, and the pH value is 11-14; During the acidifying of 3,5-dichlorobenzoic acid salt, maintenance pH is 0-3, and souring temperature is 50-90 ℃; During 3,5-dichlorobenzonitrile acidic hydrolysis, keeping temperature is 50-90 ℃, and the pH value is 1-4.
7. synthetic method according to claim 1 is characterized in that: during synthetic 3,5-dichlorobenzoic acid, when 3,5-dichlorobenzonitrile alkalescence or acidic hydrolysis, temperature is 80-90 ℃, and the time is 2-3h; During the acidifying of 3,5-dichlorobenzoic acid salt, temperature is 50-60 ℃, and the time is 0.5-1h.
8. synthetic method according to claim 7 is characterized in that: when synthesizing 3,5-dichlorobenzoic acid, keep sour environment with monobasic or polynary mineral acid, keep alkaline environment with sodium hydroxide, potassium hydroxide or their aqueous solution.
9. according to each described synthetic method among the claim 1-8, it is characterized in that: synthetic 3,5-may further comprise the steps during dichlorobenzoyl chloride: with 3,5-dichlorobenzoic acid and sulfur oxychloride mix, at 70-80 ℃ of following back flow reaction 2-4h, first at normal pressure, the 75-82 ℃ following sulfur oxychloride that reclaims, again at 185-195 ℃ then,-0.5～-steam 3,5-dichlorobenzoyl chloride under the 0.01MPa; 3,5-dichlorobenzoic acid and sulfur oxychloride mol ratio are 1: 1.0-1.5;
Specifically may further comprise the steps when synthesizing pentyne grass amine: 3,5-dichlorobenzoyl chloride and 3-amino-3-methyl butine is reaction 2-4h in the presence of solvent, under pH8-10, temperature 15-25 ℃, and reaction after-filtration reaction solution gets crude product, and the crude product recrystallization gets the careless amine of pentyne; 3,5-dichlorobenzoic acid and 3-amino-3-methyl butine mol ratio is 1: 1.0-1.4.
10. synthetic method according to claim 9 is characterized in that: purity 〉=99% of recrystallization gained pentyne grass amine.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105669483A (en) * | 2016-03-01 | 2016-06-15 | 滨海新东方医化有限公司 | Preparation method of propyzamide |
| CN107540566A (en) * | 2017-08-28 | 2018-01-05 | 江苏绿叶农化有限公司 | A kind of preparation method of propyzamide |
| CN107903181A (en) * | 2017-10-18 | 2018-04-13 | 江苏绿叶农化有限公司 | A kind of preparation method of propyzamide |
| CN114181139A (en) * | 2021-12-27 | 2022-03-15 | 四川仁安药业有限责任公司 | Synthetic method of 5-halogenated nicotinic acid |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102093149A (en) * | 2010-12-08 | 2011-06-15 | 天津理工大学 | Method for preparing carboxylic acid compound by promoting rapid hydrolysis of cyan |
| CN102320960A (en) * | 2011-08-02 | 2012-01-18 | 安徽东健化工科技有限公司 | Preparation method of 6-fluoro salicylic acid |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU177428B (en) * | 1977-05-31 | 1981-10-28 | Egyt Gyogyszervegyeszeti Gyar | Process for preparing 3,5-dichloro-benzoic acid /1,1-dimethyl-propin-2-yl/-amide |
-
2013
- 2013-05-20 CN CN201310184431.3A patent/CN103242190B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102093149A (en) * | 2010-12-08 | 2011-06-15 | 天津理工大学 | Method for preparing carboxylic acid compound by promoting rapid hydrolysis of cyan |
| CN102320960A (en) * | 2011-08-02 | 2012-01-18 | 安徽东健化工科技有限公司 | Preparation method of 6-fluoro salicylic acid |
Non-Patent Citations (4)
| Title |
|---|
| JEAN ROUCHAUD等: "Metabolism of 14C-Pronamide in the Soil and in Lettuce (Lactuca sativa) under Field Conditions", 《WEED SCIENCE》, vol. 35, 31 December 1987 (1987-12-31), pages 470 - 2 * |
| 刘洁: "除草剂戊炔草胺的合成研究", 《中国优秀博硕士学位论文全文数据库》, no. 5, 15 September 2005 (2005-09-15) * |
| 孙旭军等: "2,4-二氯苯甲酸的合成研究", 《应用化工》, vol. 30, no. 1, 28 February 2001 (2001-02-28) * |
| 陈玉琴等: "3,5-二溴-4-羟基苯甲腈的合成", 《青岛科技大学学报》, vol. 24, no. 4, 31 August 2003 (2003-08-31) * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105669483A (en) * | 2016-03-01 | 2016-06-15 | 滨海新东方医化有限公司 | Preparation method of propyzamide |
| CN105669483B (en) * | 2016-03-01 | 2018-02-23 | 滨海新东方医化有限公司 | A kind of preparation method of pentyl xanthate |
| CN107540566A (en) * | 2017-08-28 | 2018-01-05 | 江苏绿叶农化有限公司 | A kind of preparation method of propyzamide |
| CN107903181A (en) * | 2017-10-18 | 2018-04-13 | 江苏绿叶农化有限公司 | A kind of preparation method of propyzamide |
| CN107903181B (en) * | 2017-10-18 | 2020-11-06 | 江苏绿叶农化有限公司 | Preparation method of propyzamide |
| CN114181139A (en) * | 2021-12-27 | 2022-03-15 | 四川仁安药业有限责任公司 | Synthetic method of 5-halogenated nicotinic acid |
| CN114181139B (en) * | 2021-12-27 | 2023-12-08 | 四川仁安药业有限责任公司 | Synthesis method of 5-halogenated nicotinic acid |
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