CN103275030A - Synthesis method of fenpropimorph - Google Patents
Synthesis method of fenpropimorph Download PDFInfo
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- CN103275030A CN103275030A CN2013102181543A CN201310218154A CN103275030A CN 103275030 A CN103275030 A CN 103275030A CN 2013102181543 A CN2013102181543 A CN 2013102181543A CN 201310218154 A CN201310218154 A CN 201310218154A CN 103275030 A CN103275030 A CN 103275030A
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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, the 6-thebaine, pure product are oily liquids colourless, that have aromatic odour, boiling point is a kind of interior absorption morpholine series bactericidal agent and ergosterol reduction inhibitor agent with preventive and therapeutic action at 392 ℃ (101.3kPa).
Chemical structural formula is:
The synthesis technique of domestic existing fenpropimorph is as shown below: be starting raw material with the p-t-Butylbenzaldehyde, under alkaline condition with after the propionic aldehyde condensation, obtain the tert-butyl-phenyl propenal of 2-methyl-4-, obtain the tert-butyl-phenyl propionic aldehyde of 2-methyl-4-through the selective hydrogenation reduction again, last with 2, the reaction of 6-thebaine obtains product.Its reaction equation is as follows:
The fenpropimorph synthesis technique of foreign patent report is as shown below: be raw material with the tert.-butylbenzene; at first pass through after F-C reaction acidylate makes 4 tert.-butylbenzene acetone; in dimethyl formamide with phosphorus oxychloride, alkali take place Vilsmeier react 4-tert-butyl-phenyl-1-chloro-2 Methylacrylaldehyde more than 95%; olefine aldehydr through the Pd/C hydrogenating reduction to 4-tert-butyl-phenyl isobutyric aldehyde; saturated aldehyde can make fenpropimorph with the reaction of 2,6-thebaine again.Its reaction equation is as follows:
More than two kinds of methods all use the dangerous technology of high-pressure hydrogenation, working load catalyzer in the one-step synthesis process in the end in addition, with to the tertiary butyl-methylbenzene propionic aldehyde or to the tertiary butyl-methylbenzene propyl alcohol and 2, the reaction of 6-thebaine, finally synthesize fenpropimorph, reaction yield is lower, generally all is no more than 80%.No industrial production is worth.
Summary of the invention
The object of the present invention is to provide a kind of reaction yield height, non-environmental-pollution, finished product content height, technology is simple, has the synthetic method of the fenpropimorph of industrial production value.
Technical solution of the present invention is:
A kind of synthetic method of fenpropimorph, it is characterized in that: being starting raw material to the tertiary butyl-Beta-methyl phenylpropyl alcohol, after carrying out esterification or carry out the chlorination synthetic intermediate with sulfur oxychloride with Methanesulfonyl chloride, intermediate is again with 2, the 6-thebaine is synthetic, generates fenpropimorph.
The synthetic method of described fenpropimorph is characterized in that: to be starting raw material to the tertiary butyl-Beta-methyl phenylpropyl alcohol, carry out esterification synthetic intermediate sulphonate with Methanesulfonyl chloride after, synthetic with 2,6-thebaine again, generate fenpropimorph; Chemical equation is as follows:
The synthetic method of described fenpropimorph comprises the following steps:
(1) esterification: add Methanesulfonyl chloride in to the tertiary butyl-Beta-methyl phenylpropyl alcohol, 0-10 ℃ drips down triethylamine, after dropwising, remove 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%, reacts and finishes; Add water the salt that dissolving generates then, standing demix, lower floor is reaction rear center body sulphonate;
(2) condensation: in the first step esterification synthetic product sulphonate, add 2, the 6-thebaine, temperature rising reflux is incubated 4 hours, sampling analysis after being warming up to 140 ℃, until intermediate to the tertiary butyl-Beta-methyl phenyl-chloride propane GC normalization method content≤0.5%, reaction finishes, and is neutralized to PH=14 with liquid caustic soda then, standing demix, upper strata oil reservoir vacuum distillation is collected the finished product fenpropimorph behind the removal front-end volatiles.
The synthetic method of described fenpropimorph, to be starting raw material to the tertiary butyl-Beta-methyl phenylpropyl alcohol, carry out chlorination with sulfur oxychloride after, synthetic with 2,6-thebaine again, generate fenpropimorph; Chemical equation is as follows:
The synthetic method of described fenpropimorph comprises the following steps:
(1) halo: in to the tertiary butyl-Beta-methyl phenylpropyl alcohol, add 0.5% weight percent catalyzer, be warming up to 40 ℃, the beginning dripping thionyl chloride after dropwising, is warming up to 90 ℃ of insulations 1 hour; Sampling analysis until to the tertiary butyl-Beta-methyl phenylpropyl alcohol GC normalization method content≤0.5%, reacts and finishes; The HCl that reaction process produces, SO
2Gas water and the classification of the 30%NaOH aqueous solution absorb; Reaction finishes the back and is neutralized to PH=8 with liquid caustic soda, standing demix, and the upper strata is for reacting rear center body to the tertiary butyl-Beta-methyl phenyl-chloride propane;
(2) condensation: add 2 in to the tertiary butyl-Beta-methyl phenyl-chloride propane at the first step halo synthetic product, the 6-thebaine, temperature rising reflux is after being warming up to 160 ℃, be incubated 6 hours, sampling analysis, to the tertiary butyl-Beta-methyl phenyl-chloride propane GC normalization method content≤0.5%, reaction finishes until intermediate; Be neutralized to PH=14 with liquid caustic soda then, standing demix, upper strata oil reservoir vacuum distillation is collected the finished product fenpropimorph behind the removal front-end volatiles.
Methanesulfonyl chloride can be used replacements such as benzene sulfonyl chloride, p-methyl benzene sulfonic chloride in the middle esterification of the present invention.Sulfur oxychloride can be used replacements such as phosphorus oxychloride, phosphorus trichloride, solid phosgene, tribromo oxygen phosphorus, phosphorus tribromide in the middle halogenating reaction of the present invention.
Reaction yield height of the present invention, non-environmental-pollution, finished product content height, technology is simple, has industrial production and is worth, and has processing ease, equipment is simple, the three wastes are few, low cost and other advantages.
The invention will be further described below in conjunction with embodiment.
Embodiment
Embodiment 1:
Add the tertiary butyl of 206g-Beta-methyl phenylpropyl alcohol and 120g Methanesulfonyl chloride in the 500ml round-bottomed flask, be cooled under 0 ℃, drip the triethylamine of 111g, after dropwising, be incubated 1 hour.Sampling analysis is until qualified.Insulation finishes the back and adds 200g water, standing demix.Lower floor is reaction rear center body sulphonate.Weigh intermediate 282.6g, analyze content (GC normalization method) 99.0%.Yield 99.5%.
The first step esterification synthetic product sulphonate is dropped in the 1000ml four-hole boiling flask, add 345g2, the 6-thebaine, temperature rising reflux is after being warming up to 140 ℃, be incubated 4 hours, be neutralized to PH=14 with the 30%NaOH aqueous solution then, standing demix, upper strata oil reservoir vacuum distillation is collected the finished product fenpropimorph behind the excision front-end volatiles.Weigh fenpropimorph 299.3g.Analyze content 98.1%.Total recovery 98.2%.
Embodiment 2:
Add the tertiary butyl of 103g-Beta-methyl phenylpropyl alcohol and 60g Methanesulfonyl chloride in the 500ml round-bottomed flask, be cooled under 0 ℃, the triethylamine of Dropwise 5 6g after dropwising, is incubated 1 hour.Sampling analysis is until qualified.Insulation finishes the back and adds 100g water, standing demix.Lower floor is reaction rear center body sulphonate.Weigh intermediate 141.4g, analyze content (GC normalization method) 98.9%.Yield 99.5%.
The first step esterification synthetic product sulphonate is dropped in the 500ml four-hole boiling flask, add 173g2, the 6-thebaine, temperature rising reflux is after being warming up to 140 ℃, be incubated 4 hours, be neutralized to PH=14 with the 30%NaOH aqueous solution then, standing demix, upper strata oil reservoir vacuum distillation is collected the finished product fenpropimorph behind the excision front-end volatiles.Weigh fenpropimorph 149.7g.Analyze content 98.3%.Total recovery 98.5%
Embodiment 3:
Add the tertiary butyl of 412g-Beta-methyl phenylpropyl alcohol and 240g Methanesulfonyl chloride in the 1000ml round-bottomed flask, be cooled under 0 ℃, drip the triethylamine of 222g, after dropwising, be incubated 1 hour.Sampling analysis is until qualified.Insulation finishes the back and adds 400g water, standing demix.Lower floor is reaction rear center body sulphonate.Weigh intermediate 567.4g, analyze content (GC normalization method) 98.5%.Yield 99.4%.
The first step esterification synthetic product sulphonate is dropped in the 2000ml four-hole boiling flask, add 690g2, the 6-thebaine, temperature rising reflux is after being warming up to 140 ℃, be incubated 4 hours, be neutralized to PH=14 with the 30%NaOH aqueous solution then, standing demix, upper strata oil reservoir vacuum distillation is collected the finished product fenpropimorph behind the excision front-end volatiles.Weigh fenpropimorph 598.4g.Analyze content 98.2%.Total recovery 98.4%.
Embodiment 4:
Add the tertiary butyl of 206g-Beta-methyl phenylpropyl alcohol in the 500ml round-bottomed flask, add again 1g catalyzer, be warming up to 40 ℃, 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 finishes the back and is neutralized to PH=8 with liquid caustic soda, standing demix.The upper strata is for reacting rear center body to the tertiary butyl-Beta-methyl phenyl-chloride propane.Weigh intermediate 225g, analyze content (GC normalization method) 98.0%.Yield 99.2%.
The first step halo synthetic product is dropped in the 1000ml four-hole boiling flask the tertiary butyl-Beta-methyl phenyl-chloride propane, add 345g2, the 6-thebaine, temperature rising reflux is after being warming up to specified temperature, be incubated 6 hours, be neutralized to PH=14 with the 30%NaOH aqueous solution then, standing demix, upper strata oil reservoir vacuum distillation is collected the finished product fenpropimorph behind the excision front-end volatiles.Weigh fenpropimorph 297.2g.Analyze content 97.5%.Total recovery 97.2%.
Embodiment 5:
Add the tertiary butyl of 103g-Beta-methyl phenylpropyl alcohol in the 500ml round-bottomed flask, add again 0.5g catalyzer, heat up 40 ℃, 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 finishes the back and is neutralized to PH=8 with liquid caustic soda, standing demix.The upper strata is for reacting rear center body to the tertiary butyl-Beta-methyl phenyl-chloride propane.Weigh intermediate 113g, analyze content (GC normalization method) 98.2%.Yield 99.4%.
The first step halo synthetic product is dropped in the 500ml four-hole boiling flask the tertiary butyl-Beta-methyl phenyl-chloride propane, add 173g2, the 6-thebaine, temperature rising reflux is after being warming up to specified temperature, be incubated 6 hours, be neutralized to PH=14 with the 30%NaOH aqueous solution then, standing demix, upper strata oil reservoir vacuum distillation is collected the finished product fenpropimorph behind the excision front-end volatiles.Weigh fenpropimorph 150.1g.Analyze content 97.3%.Total recovery 97.8%.
Embodiment 6:
Add the tertiary butyl of 412g-Beta-methyl phenylpropyl alcohol in the 1000ml round-bottomed flask, add again 2g catalyzer, be warming up to 40 ℃, 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 finishes the back and is neutralized to PH=8 with liquid caustic soda, standing demix.The upper strata is for reacting rear center body to the tertiary butyl-Beta-methyl phenyl-chloride propane.Weigh intermediate 451g, analyze content (GC normalization method) 97.9%.Yield 99.3%.
The first step halo synthetic product is dropped in the 2000ml four-hole boiling flask the tertiary butyl-Beta-methyl phenyl-chloride propane, add 690g2, the 6-thebaine, temperature rising reflux is after being warming up to specified temperature, be incubated 6 hours, be neutralized to PH=14 with the 30%NaOH aqueous solution then, standing demix, upper strata oil reservoir vacuum distillation is collected the finished product fenpropimorph behind the excision front-end volatiles.Weigh fenpropimorph 603g.Analyze content 97.1%.Total recovery 98.0%.
Claims (5)
1. the synthetic method of a fenpropimorph, it is characterized in that: being starting raw material to the tertiary butyl-Beta-methyl phenylpropyl alcohol, after carrying out esterification or carry out the chlorination synthetic intermediate with sulfur oxychloride with Methanesulfonyl chloride, intermediate is again with 2, the 6-thebaine is synthetic, generates fenpropimorph.
2. the synthetic method of fenpropimorph according to claim 1, it is characterized in that: to be starting raw material to the tertiary butyl-Beta-methyl phenylpropyl alcohol, carry out esterification synthetic intermediate sulphonate with Methanesulfonyl chloride after, again with 2, the 6-thebaine is synthetic, generates fenpropimorph; Chemical equation is as follows:
3. the synthetic method of fenpropimorph according to claim 2 is characterized in that: comprise the following steps:
(1) esterification: add Methanesulfonyl chloride in to the tertiary butyl-Beta-methyl phenylpropyl alcohol, 0-10 ℃ drips down triethylamine, after dropwising, remove 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%, reacts and finishes; Add water the salt that dissolving generates then, standing demix, lower floor is reaction rear center body sulphonate;
(2) condensation: in the first step esterification synthetic product sulphonate, add 2, the 6-thebaine, temperature rising reflux is incubated 4 hours, sampling analysis after being warming up to 140 ℃, until intermediate to the tertiary butyl-Beta-methyl phenyl-chloride propane GC normalization method content≤0.5%, reaction finishes, and is neutralized to PH=14 with liquid caustic soda then, standing demix, upper strata oil reservoir vacuum distillation is collected the finished product fenpropimorph behind the removal front-end volatiles.
4. the synthetic method of fenpropimorph according to claim 1 is characterized in that: to be starting raw material to the tertiary butyl-Beta-methyl phenylpropyl alcohol, carry out chlorination with sulfur oxychloride after, synthetic with 2,6-thebaine again, generate fenpropimorph; Chemical equation is as follows:
5. the synthetic method of fenpropimorph according to claim 4 is characterized in that: comprise the following steps:
(1) halo: in to the tertiary butyl-Beta-methyl phenylpropyl alcohol, add 0.5% weight percent catalyzer, be warming up to 40 ℃, the beginning dripping thionyl chloride after dropwising, is warming up to 90 ℃ of insulations 1 hour; Sampling analysis until to the tertiary butyl-Beta-methyl phenylpropyl alcohol GC normalization method content≤0.5%, reacts and finishes; The HCl that reaction process produces, SO
2Gas water and the classification of the 30%NaOH aqueous solution absorb; Reaction finishes the back and is neutralized to PH=8 with liquid caustic soda, standing demix, and the upper strata is for reacting rear center body to the tertiary butyl-Beta-methyl phenyl-chloride propane;
(2) condensation: add 2 in to the tertiary butyl-Beta-methyl phenyl-chloride propane at the first step halo synthetic product, the 6-thebaine, temperature rising reflux is after being warming up to 160 ℃, be incubated 6 hours, sampling analysis, to the tertiary butyl-Beta-methyl phenyl-chloride propane GC normalization method content≤0.5%, reaction finishes until intermediate; Be neutralized to PH=14 with liquid caustic soda then, standing demix, upper strata oil reservoir vacuum distillation is collected the finished product fenpropimorph behind the removal front-end volatiles.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US4863917A (en) * | 1986-07-22 | 1989-09-05 | Bayer Aktiengesellschaft | Decahydronaphth-2-al-alkylamines |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4863917A (en) * | 1986-07-22 | 1989-09-05 | Bayer Aktiengesellschaft | Decahydronaphth-2-al-alkylamines |
Non-Patent Citations (1)
| Title |
|---|
| AMIR AVDAGIC等: "Enantioselective Chemoenzymatic Synthesis of the S-Enantiomer of the Systemic Fungicide Fenpropimorph", 《SYNTHESIS》 * |
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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. |
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