CN103275030B - Synthesis method of fenpropimorph - Google Patents
Synthesis method of fenpropimorph Download PDFInfo
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- CN103275030B CN103275030B CN201310218154.3A CN201310218154A CN103275030B CN 103275030 B CN103275030 B CN 103275030B CN 201310218154 A CN201310218154 A CN 201310218154A CN 103275030 B CN103275030 B CN 103275030B
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Abstract
The invention discloses a synthesis method of fenpropimorph. The method adopts p-tert-butyl-beta-methylphenylpropanol as a start raw material and comprises the following steps of: performing esterification by use of methylsufonyl chloride or performing chlorination by use of thionyl chloride to synthesize an intermediate; and synthesizing by use of the intermediate and 2,6-dimethylmorpholine to generate fenpropimorph. The method disclosed by the invention has the advantages of high reaction yield, no environmental pollution, high finished product content, simple process, industrial production value, easiness in operation, simple equipment, few three wastes, low cost and the like.
Description
Technical field
The present invention relates to a kind of synthetic method of fenpropimorph.
Background technology
Fenpropimorph (Fenpropimorph), have another name called Fen Pufu, the third bacterium spirit, chemistry (±) by name is along 4-[3-(4 tert-butyl-phenyl)-2-methyl-propyl]-2,6-thebaine, sterling is oily liquids that is colourless, that have aromatic odour, boiling point, at 392 DEG C (101.3kPa), is a kind of interior absorption morpholine bactericide and ergosterol reduction inhibitor agent with preventive and therapeutic action.
Chemical structural formula is:
The synthesis technique of domestic existing fenpropimorph is as shown below: take p-t-Butylbenzaldehyde as starting raw material, obtain 2-methyl-4-to tert-butyl-phenyl propenal in the basic conditions with after propionic aldehyde condensation, 2-methyl-4-is obtained to tert-butyl-phenyl propionic aldehyde again through selective hydrogenation reduction, last and 2,6-thebaines are obtained by reacting product.Its reaction equation is as follows:
The fenpropimorph synthesis technique of foreign patent report is as shown below: take tert.-butylbenzene as raw material; first react after the obtained 4 tert.-butylbenzene acetone of acidylate through F-C; occur with phosphorus oxychloride, alkali in dimethyl formamide Vilsmeier react more than 95% 4-tert-butyl-phenyl-1-chloro-2 Methylacrylaldehyde; olefine aldehydr through Pd/C hydrogenating reduction to 4-tert-butyl-phenyl isobutyric aldehyde; saturated aldehyde reacts can obtain fenpropimorph with 2,6-thebaine again.Its reaction equation is as follows:
Above two kinds of methods all use the dangerous technique of high-pressure hydrogenation, in the end working load catalyzer in one-step synthesis process in addition, with to t-butyl-methyl phenylpropyl aldehyde or to t-butyl-methyl phenylpropyl alcohol and 2,6-thebaine reacts, finally synthesize fenpropimorph, reaction yield is lower, is generally all no more than 80%.Be worth without industrial production.
Summary of the invention
The object of the present invention is to provide a kind of reaction yield high, non-environmental-pollution, finished product content is high, and technique is simple, has the synthetic method of the fenpropimorph that industrial production is worth.
Technical solution of the present invention is:
A kind of synthetic method of fenpropimorph, it is characterized in that: with to the tertiary butyl-Beta-methyl phenylpropyl alcohol for starting raw material, carry out esterification with Methanesulfonyl chloride or after carrying out chlorination synthetic intermediate with sulfur oxychloride, intermediate is again with 2,6-thebaine synthesizes, and generates fenpropimorph.
The synthetic method of described fenpropimorph, is characterized in that: with to the tertiary butyl-Beta-methyl phenylpropyl alcohol for starting raw material, after carrying out lactate synthesis intermediate sulfonic acid ester with Methanesulfonyl chloride, then synthesize with 2,6-thebaine, generate fenpropimorph; Chemical equation is as follows:
The synthetic method of described fenpropimorph, comprises the following steps:
(1) esterification: add Methanesulfonyl chloride in the tertiary butyl-Beta-methyl phenylpropyl alcohol, drip triethylamine at 0-10 DEG C, after dropwising, removes freezing, natural heating and heat preservation 1 hour; Sampling analysis, until to the tertiary butyl-Beta-methyl phenylpropyl alcohol GC normalization method content≤0.5%, reaction terminates; Then add the salt that water dissolution generates, stratification, lower floor is reaction rear center body sulphonate;
(2) condensation: add 2 in the first step lactate synthesis product sulphonate, 6-thebaine, temperature rising reflux, until after being warming up to 140 DEG C, is incubated 4 hours, sampling analysis, until intermediate is to the tertiary butyl-Beta-methyl phenyl-chloride propane GC normalization method content≤0.5%, reaction terminates, and is then neutralized to PH=14 with liquid caustic soda, stratification, upper strata oil reservoir vacuum distillation, collects finished product fenpropimorph after removing front-end volatiles.
The synthetic method of described fenpropimorph, with to the tertiary butyl-Beta-methyl phenylpropyl alcohol for starting raw material, after carrying out chlorination with sulfur oxychloride, then synthesize with 2,6-thebaine, generate fenpropimorph; Chemical equation is as follows:
The synthetic method of described fenpropimorph, comprises the following steps:
(1) halo: add the catalyzer of 0.5% weight percent in the tertiary butyl-Beta-methyl phenylpropyl alcohol, be warming up to 40 DEG C, start to drip sulfur oxychloride, after dropwising, is warming up to 90 DEG C of insulations 1 hour; Sampling analysis, until to the tertiary butyl-Beta-methyl phenylpropyl alcohol GC normalization method content≤0.5%, reaction terminates; The HCl that reaction process produces, SO
2gas water and the classification of the 30%NaOH aqueous solution absorb; Reaction terminates rear liquid caustic soda and is neutralized to PH=8, stratification, and upper strata is for reaction rear center body is to the tertiary butyl-Beta-methyl phenyl-chloride propane;
(2) condensation: add 2 in the first step halo synthetic product is to the tertiary butyl-Beta-methyl phenyl-chloride propane, 6-thebaine, temperature rising reflux is until after being warming up to 160 DEG C, be incubated 6 hours, sampling analysis, until intermediate is to the tertiary butyl-Beta-methyl phenyl-chloride propane GC normalization method content≤0.5%, reaction terminates; Then be neutralized to PH=14 with liquid caustic soda, stratification, upper strata oil reservoir vacuum distillation, after removing front-end volatiles, collect finished product fenpropimorph.
In middle esterification of the present invention, Methanesulfonyl chloride can use the replacement such as benzene sulfonyl chloride, p-methyl benzene sulfonic chloride.In middle halogenating reaction of the present invention, sulfur oxychloride can use the replacements such as phosphorus oxychloride, phosphorus trichloride, solid phosgene, tribromo oxygen phosphorus, phosphorus tribromide.
Reaction yield of the present invention is high, non-environmental-pollution, and finished product content is high, and technique is simple, has industrial production and is worth, have processing ease, equipment is simple, the three wastes are few, low cost and other advantages.
Below in conjunction with embodiment, the invention will be further described.
Embodiment
Embodiment 1:
206g is added to the tertiary butyl-Beta-methyl phenylpropyl alcohol in 500ml round-bottomed flask, and 120g Methanesulfonyl chloride, at being cooled to 0 DEG C, dripping the triethylamine of 111g, after dropwising, be incubated 1 hour.Sampling analysis is until qualified.200g water is added, stratification after insulation terminates.Lower floor is reaction rear center body sulphonate.Weigh to obtain intermediate 282.6g, analyzes content (GC normalization method) 99.0%.Yield 99.5%.
The first step lactate synthesis product sulphonate is dropped in 1000ml four-hole boiling flask, add 345g2,6-thebaine, temperature rising reflux is until after being warming up to 140 DEG C, be incubated 4 hours, be then neutralized to PH=14, stratification with the 30%NaOH aqueous solution, upper strata oil reservoir vacuum distillation, collects finished product fenpropimorph after excision front-end volatiles.Weigh to obtain fenpropimorph 299.3g.Analyze content 98.1%.Total recovery 98.2%.
Embodiment 2:
103g is added to the tertiary butyl-Beta-methyl phenylpropyl alcohol in 500ml round-bottomed flask, and 60g Methanesulfonyl chloride, at being cooled to 0 DEG C, dripping the triethylamine of 56g, after dropwising, be incubated 1 hour.Sampling analysis is until qualified.100g water is added, stratification after insulation terminates.Lower floor is reaction rear center body sulphonate.Weigh to obtain intermediate 141.4g, analyzes content (GC normalization method) 98.9%.Yield 99.5%.
The first step lactate synthesis product sulphonate is dropped in 500ml four-hole boiling flask, add 173g2,6-thebaine, temperature rising reflux is until after being warming up to 140 DEG C, be incubated 4 hours, be then neutralized to PH=14, stratification with the 30%NaOH aqueous solution, upper strata oil reservoir vacuum distillation, collects finished product fenpropimorph after excision front-end volatiles.Weigh to obtain fenpropimorph 149.7g.Analyze content 98.3%.Total recovery 98.5%
Embodiment 3:
412g is added to the tertiary butyl-Beta-methyl phenylpropyl alcohol in 1000ml round-bottomed flask, and 240g Methanesulfonyl chloride, at being cooled to 0 DEG C, dripping the triethylamine of 222g, after dropwising, be incubated 1 hour.Sampling analysis is until qualified.400g water is added, stratification after insulation terminates.Lower floor is reaction rear center body sulphonate.Weigh to obtain intermediate 567.4g, analyzes content (GC normalization method) 98.5%.Yield 99.4%.
The first step lactate synthesis product sulphonate is dropped in 2000ml four-hole boiling flask, add 690g2,6-thebaine, temperature rising reflux is until after being warming up to 140 DEG C, be incubated 4 hours, be then neutralized to PH=14, stratification with the 30%NaOH aqueous solution, upper strata oil reservoir vacuum distillation, collects finished product fenpropimorph after excision front-end volatiles.Weigh to obtain fenpropimorph 598.4g.Analyze content 98.2%.Total recovery 98.4%.
Embodiment 4:
Add 206g in 500ml round-bottomed flask to the tertiary butyl-Beta-methyl phenylpropyl alcohol, then add 1g catalyzer, be warming up to 40 DEG C, drip the sulfur oxychloride of 125g, after dropwising, be incubated 1 hour.The HCl that reaction process produces, SO
2gas water and the classification of the 30%NaOH aqueous solution absorb.Insulation terminates rear liquid caustic soda and is neutralized to PH=8, stratification.Upper strata is for reaction rear center body is to the tertiary butyl-Beta-methyl phenyl-chloride propane.Weigh to obtain intermediate 225g, analyzes content (GC normalization method) 98.0%.Yield 99.2%.
The first step halo synthetic product is dropped in 1000ml four-hole boiling flask to the tertiary butyl-Beta-methyl phenyl-chloride propane, add 345g2,6-thebaine, temperature rising reflux is until after being warming up to specified temperature, be incubated 6 hours, be then neutralized to PH=14, stratification with the 30%NaOH aqueous solution, upper strata oil reservoir vacuum distillation, collects finished product fenpropimorph after excision front-end volatiles.Weigh to obtain fenpropimorph 297.2g.Analyze content 97.5%.Total recovery 97.2%.
Embodiment 5:
Add 103g in 500ml round-bottomed flask to the tertiary butyl-Beta-methyl phenylpropyl alcohol, then add catalyzer, the intensification 40 DEG C of 0.5g, drip the sulfur oxychloride of 62.5g, after dropwising, be incubated 1 hour.The HCl that reaction process produces, SO
2gas water and the classification of the 30%NaOH aqueous solution absorb.Insulation terminates rear liquid caustic soda and is neutralized to PH=8, stratification.Upper strata is for reaction rear center body is to the tertiary butyl-Beta-methyl phenyl-chloride propane.Weigh to obtain intermediate 113g, analyzes content (GC normalization method) 98.2%.Yield 99.4%.
The first step halo synthetic product is dropped in 500ml four-hole boiling flask to the tertiary butyl-Beta-methyl phenyl-chloride propane, add 173g2,6-thebaine, temperature rising reflux is until after being warming up to specified temperature, be incubated 6 hours, be then neutralized to PH=14, stratification with the 30%NaOH aqueous solution, upper strata oil reservoir vacuum distillation, collects finished product fenpropimorph after excision front-end volatiles.Weigh to obtain fenpropimorph 150.1g.Analyze content 97.3%.Total recovery 97.8%.
Embodiment 6:
Add 412g in 1000ml round-bottomed flask to the tertiary butyl-Beta-methyl phenylpropyl alcohol, then add 2g catalyzer, be warming up to 40 DEG C, drip the sulfur oxychloride of 250g, after dropwising, be incubated 1 hour.The HCl that reaction process produces, SO
2gas water and the classification of the 30%NaOH aqueous solution absorb.Insulation terminates rear liquid caustic soda and is neutralized to PH=8, stratification.Upper strata is for reaction rear center body is to the tertiary butyl-Beta-methyl phenyl-chloride propane.Weigh to obtain intermediate 451g, analyzes content (GC normalization method) 97.9%.Yield 99.3%.
The first step halo synthetic product is dropped in 2000ml four-hole boiling flask to the tertiary butyl-Beta-methyl phenyl-chloride propane, add 690g2,6-thebaine, temperature rising reflux is until after being warming up to specified temperature, be incubated 6 hours, be then neutralized to PH=14, stratification with the 30%NaOH aqueous solution, upper strata oil reservoir vacuum distillation, collects finished product fenpropimorph after excision front-end volatiles.Weigh to obtain fenpropimorph 603g.Analyze content 97.1%.Total recovery 98.0%.
Claims (1)
1. a synthetic method for fenpropimorph, is characterized in that: comprise the following steps:
(1) esterification: add Methanesulfonyl chloride in the tertiary butyl-Beta-methyl phenylpropyl alcohol, drip triethylamine at 0-10 DEG C, after dropwising, removes freezing, natural heating and heat preservation 1 hour; Sampling analysis, until to the tertiary butyl-Beta-methyl phenylpropyl alcohol GC normalization method content≤0.5%, reaction terminates; Then add the salt that water dissolution generates, stratification, lower floor is reaction rear center body sulphonate;
(2) condensation: add 2 in the first step lactate synthesis product sulphonate, 6-thebaine, temperature rising reflux, until after being warming up to 140 DEG C, is incubated 4 hours, sampling analysis, until intermediate is to the tertiary butyl-Beta-methyl phenyl-chloride propane GC normalization method content≤0.5%, reaction terminates, and is then neutralized to PH=14 with liquid caustic soda, stratification, upper strata oil reservoir vacuum distillation, collects finished product fenpropimorph after removing front-end volatiles.
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Address after: 226407 Yang Kou Chemical Industrial Park, Rudong County, Nantong, Jiangsu Patentee after: Jiangsu Rico crop protection Co., Ltd. Address before: 226407 Yang Kou Chemical Industrial Park, Rudong County, Nantong, Jiangsu Patentee before: Nantong WEILIKE Chemical Co., Ltd. |