CN102993013B - Synthesis method of tetraconazole intermediate - Google Patents
Synthesis method of tetraconazole intermediate Download PDFInfo
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- CN102993013B CN102993013B CN201210580331.8A CN201210580331A CN102993013B CN 102993013 B CN102993013 B CN 102993013B CN 201210580331 A CN201210580331 A CN 201210580331A CN 102993013 B CN102993013 B CN 102993013B
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- KTHIYWSQQVYFII-UHFFFAOYSA-N COC(C(c(c(Cl)c1)ccc1Cl)=C)=O Chemical compound COC(C(c(c(Cl)c1)ccc1Cl)=C)=O KTHIYWSQQVYFII-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention relates to a synthesis method of a tetraconazole intermediate, which solves the problems of many synthesis steps, complicated operation, lower efficiency and higher cost of the prior art. The method provided by the invention takes 2,4-dichlorophenylacetic acid as a raw material and comprises the following steps of: (1) adding the raw material into a single-mouth bottle, and adding methanol and concentrated sulfuric acid for reflux reaction, wherein the reaction time is 0.5-1 hour; and spin-drying, adding ethyl acrylate, dissolving, cleaning, drying and spin-drying to obtain a compound 1; and (2) mixing the compound 1, paraformaldehyde, potassium carbonate and dimethyl sulfoxide, and reacting at 65 DEG C, wherein the reaction time is 1-1.5 hours; cooling and pouring the product into water; and performing PE (polyethylene) extraction, strong brine washing, drying and spin-drying to obtain a compound 2. According to the synthesis method provided by the invention, the intermediate product can be used for preparing the next intermediate without any treatment, thus the process is simplified, and the method is suitable for industrial production.
Description
Technical field
The present invention relates to a kind of synthetic method of tetraconazole intermediate.
Background technology
Tertraconazole belongs to s-generation triazole bactericidal agent, fluorine-containing in molecular structure, fungicidal activity is than being 2 ~ 3 times of the first-generation, fungicidal spectrum is wide, efficiently, lasting period reaches 4 ~ 6 weeks, there is protection and therapeutic action, and have good Uptake and translocation performance, suitable for crop cereal crop is as wheat, barley, oat, rye etc., fruit tree is as banana, grape, pears, apple etc., vegetables are as melon, beet, ornamental plant etc., Erysiphe can be prevented and treated, sick Rust, Rhynchosporium spp．, nuclear cavity Pseudomonas and the microbial disease of Septoria are as wheat powdery mildew, loose smut of wheat, the blessing of wheat grain husk is sick, jowar head smut and uncinula necator etc.
But existing tertraconazole is raw material mainly with 2,4 dichloro benzene acetonitrile greatly, by steps such as addition, the esterification of first sulphur, condensation, hydrolysis, esterification, reduction, obtains tertraconazole key intermediate, then obtains tertraconazole through tetrafluoroethylene etherificate.Its step is more, troublesome poeration, and efficiency is lower, and cost is higher, can not meet the demand of people.
Summary of the invention
The present invention relates to a kind of synthetic method of tetraconazole intermediate, solve prior art synthesis step more, troublesome poeration, efficiency is lower, the problem that cost is higher.
The present invention is achieved through the following technical solutions:
The synthetic method of tetraconazole intermediate, with 2,4 dichloro benzene acetic acid for raw material, comprises the following steps:
(1) compound 1:
Joined by raw material in single port bottle, then add methyl alcohol and the vitriol oil carries out back flow reaction, the reaction times is 0.5 ~ 1h, be then spin-dried for, add that ethyl propenoate dissolves, cleaning, dry, be spin-dried for obtain compound 1, its structural formula is as follows:
；
(2) react under the condition of 65 DEG C after compound 1, paraformaldehyde, salt of wormwood and dimethyl sulfoxide (DMSO) being mixed, reaction times 1 ~ 1.5h, cooling, is poured into water, then through PE extraction, strong brine washes, dry, be spin-dried for obtain compound 2, its structural formula is as follows:
。
Further, in described step (1), cleaning specifically adopts washing successively, saturated sodium bicarbonate is washed, strong brine is washed.
Again further, the mol ratio of described step (1) Raw and the vitriol oil is 1:1.
Further, in described step (2), compound 1 is 1:2 with the mol ratio of paraformaldehyde, and compound 1 is 1:2 with the mol ratio of salt of wormwood.
The present invention compared with prior art has the following advantages and beneficial effect:
(1) synthetic method of the present invention, intermediate product does not need to do any process can prepare next step intermediate, thus simplifies operation, adapts to industrialization and produces.
(2) present invention substantially reduces synthesis step, operation is succinct, convenient, and compared with prior art, in its reaction process, by product is less, and yield also increases to some extent.
(3) the present invention due to synthesis step less, thus improve reaction efficiency, cost is also lower simultaneously, is suitable for promoting.
Embodiment
Below in conjunction with embodiment, the invention will be further described, and embodiments of the present invention include but not limited to the following example.
Embodiment 1
The synthetic method of tetraconazole intermediate, with 2,4 dichloro benzene acetic acid for raw material, comprises the following steps:
(1) in 500ml single port bottle, 50g raw material is added, methyl alcohol 200ml, vitriol oil 1eq, carry out back flow reaction, the reaction times is 0.5 hour, is spin-dried for solvent, add 300ml ethyl propenoate dissolve, then adopt washing successively, saturated sodium bicarbonate washed, strong brine is washed, drying, be spin-dried for obtain compound
50g, purity 100%, yield 94%.
(2) by 10g compound
2eq paraformaldehyde (2.8g), the salt of wormwood (12.5g) of 2eq, 50ml dimethyl sulfoxide (DMSO) joins in container, reacts under the condition of 65 DEG C, and the reaction times is 1h, then cool, pour in 150ml water, then through PE extraction (300ml/3 time), finally adopt strong brine wash, drying, be spin-dried for obtain compound
7.8g, purity is 100%, yield 75%.
Embodiment 2
The synthetic method of tetraconazole intermediate, with 2,4 dichloro benzene acetic acid for raw material, comprises the following steps:
(1) in 500ml single port bottle, 50g raw material is added, methyl alcohol 200ml, vitriol oil 1eq, carry out back flow reaction, the reaction times is 1 hour, is spin-dried for solvent, add 300ml ethyl propenoate dissolve, then adopt washing successively, saturated sodium bicarbonate washed, strong brine is washed, drying, be spin-dried for obtain compound
50g, purity 100%, yield 94%.
(2) by 10g compound
2eq paraformaldehyde (2.8g), the salt of wormwood (12.5g) of 2eq, 50ml dimethyl sulfoxide (DMSO) joins in container, reacts under the condition of 65 DEG C, and the reaction times is 1.5h, then cool, pour in 150ml water, then through PE extraction (300ml/3 time), finally adopt strong brine wash, drying, be spin-dried for obtain compound
7.8g, purity is 100%, yield 75%.
Embodiment 3
The synthetic method of tetraconazole intermediate, with 2,4 dichloro benzene acetic acid for raw material, comprises the following steps:
(1) in 500ml single port bottle, 50g raw material is added, methyl alcohol 200ml, vitriol oil 1eq, carry out back flow reaction, the reaction times is 0.8 hour, is spin-dried for solvent, add 300ml ethyl propenoate dissolve, then adopt washing successively, saturated sodium bicarbonate washed, strong brine is washed, drying, be spin-dried for obtain compound
50g, purity 100%, yield 94%.
(2) by 10g compound
2eq paraformaldehyde (2.8g), the salt of wormwood (12.5g) of 2eq, 50ml dimethyl sulfoxide (DMSO) joins in container, reacts under the condition of 65 DEG C, and the reaction times is 1.3h, then cool, pour in 150ml water, then through PE extraction (300ml/3 time), finally adopt strong brine wash, drying, be spin-dried for obtain compound
7.8g, purity is 100%, yield 75%.
According to above-described embodiment, just the present invention can be realized well.
Claims (1)
1. the synthetic method of tetraconazole intermediate, is characterized in that, with 2,4 dichloro benzene acetic acid for raw material, comprises the following steps:
(1) compound 1 is prepared:
Joined by raw material in single port bottle, then add methyl alcohol and the vitriol oil carries out back flow reaction, the reaction times is 0.5 ~ 1h, be then spin-dried for, add that ethyl propenoate dissolves, cleaning, dry, be spin-dried for obtain compound 1, its structural formula is as follows:
；
(2) react under the condition of 65 DEG C after compound 1, paraformaldehyde, salt of wormwood and dimethyl sulfoxide (DMSO) being mixed, reaction times 1 ~ 1.5h, cooling, is poured into water, then through PE extraction, strong brine washes, dry, be spin-dried for obtain compound 2, its structural formula is as follows:
；
In described step (1), cleaning specifically adopts washing successively, saturated sodium bicarbonate is washed, strong brine is washed;
The mol ratio of described step (1) Raw and the vitriol oil is 1:1;
In described step (2), compound 1 is 1:2 with the mol ratio of paraformaldehyde, and compound 1 is 1:2 with the mol ratio of salt of wormwood.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201210580331.8A CN102993013B (en) | 2012-12-28 | 2012-12-28 | Synthesis method of tetraconazole intermediate |
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| CN201210580331.8A CN102993013B (en) | 2012-12-28 | 2012-12-28 | Synthesis method of tetraconazole intermediate |
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| CN102993013A CN102993013A (en) | 2013-03-27 |
| CN102993013B true CN102993013B (en) | 2015-03-18 |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3317356A1 (en) * | 1982-05-14 | 1983-11-17 | Basf Ag, 6700 Ludwigshafen | Process for the preparation of substituted alpha- phenylacrylates |
| CN1312791A (en) * | 1998-08-11 | 2001-09-12 | 克诺尔有限公司 | Method for producing atropic acid ethyl ester |
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2012
- 2012-12-28 CN CN201210580331.8A patent/CN102993013B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3317356A1 (en) * | 1982-05-14 | 1983-11-17 | Basf Ag, 6700 Ludwigshafen | Process for the preparation of substituted alpha- phenylacrylates |
| CN1312791A (en) * | 1998-08-11 | 2001-09-12 | 克诺尔有限公司 | Method for producing atropic acid ethyl ester |
Non-Patent Citations (1)
| Title |
|---|
| Min Wang,et al..The first synthesis of [11C]SB-216763, a new potential PET agent for imaging of glycogen synthase kinase-3 (GSK-3).《Bioorganic & Medicinal Chemistry Letters》.2010,第21卷245-249. * |
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