CN105152886A - Synthetic method of 1-(4-chlorophenyl)-2-cyclopropyl-1-propanone - Google Patents
Synthetic method of 1-(4-chlorophenyl)-2-cyclopropyl-1-propanone Download PDFInfo
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- CN105152886A CN105152886A CN201510521752.7A CN201510521752A CN105152886A CN 105152886 A CN105152886 A CN 105152886A CN 201510521752 A CN201510521752 A CN 201510521752A CN 105152886 A CN105152886 A CN 105152886A
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- cyclopropyl
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
- C07C45/516—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of nitrogen-containing compounds to >C = O groups
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- C—CHEMISTRY; METALLURGY
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C249/04—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes
- C07C249/08—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes by reaction of hydroxylamines with carbonyl compounds
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Abstract
The invention relates to a synthetic method of 1-(4-chlorophenyl)-2-cyclopropyl-1-propanone. The synthetic method comprises steps as follows: (1), hydroxy lamine hydrochloride is dissolved in a solvent, alkali is added, the pH (potential of hydrogen) value is adjusted, a raw material of cyclopropyl propionaldehyde is added at the appropriate temperature for a reaction, and cyclopropyl acetaldoxime is obtained through extraction, concentration and drying after the reaction ends; (2), newly prepared p-chlorophenyl diazonium salt and a catalyst are added to cyclopropyl acetaldoxime at the lower temperature, acid is added, the mixture is heated to have a reaction, and 1-(4-chlorophenyl)-2-cyclopropyl-1-propanone is obtained through aftertreatment after the reaction ends. The synthetic route is shown in the specification. The synthetic method has the advantages as follows: the cost of raw materials is low, the overall yield of the reaction is high, the technological operation is safe, aftertreatment is simple and convenient, and the synthetic method has industrial application value.
Description
Technical field
The present invention relates to the synthetic method of the key intermediate of SN-108266, particularly the synthetic method of a kind of 1-(4-chloro-phenyl-)-2-cyclopropyl-1-acetone.
Background technology
SN-108266 is the triazole bactericidal agent developed by mountain pass scholar company of Switzerland (being now Syngenta Co., Ltd), and fungicidal spectrum is wide, residual few, is sterol demethylation inhibitors, has preventive and therapeutic action.All effective to the Erysiphales on cereal crop, coffee, beet, fruit tree and grape, Uredinales, the mould genus of genus spore, Rhynchosporium spp．, Septoria, Venturia bacterium.Mixed with other sterilant, cereal eye spot disease, leaf spot and net blotch can be prevented and treated very well.Sales volume is in the market increasing, purposes is more and more extensive, so how at low cost volume production SN-108266 has become the task of top priority, and the key that it is controlled cost depends on the technological breakthrough of its intermediate 1-(4-chloro-phenyl-)-2-cyclopropyl-1-acetone.
About 1-(4-chloro-phenyl-)-2-cyclopropyl-1-acetone, its chemical formula is: C12H13ClO; CAS accession number: 123989-29-7; Chemical name is: 1-(4-chloro-phenyl-)-2-cyclopropyl-1-acetone; English name is: 1-(4-Chlorophenyl)-2-cyclopropylpropan-1-one; Structural formula is:
To the synthesis of SN-108266 key intermediate, industrially mainly contain following three kinds of routes:
(1) p-chlorobenzyl cyanide method:
This synthetic route is longer, and atom utilization is low, and total yield of products is low, and produces a large amount of three wastes, is not suitable for industrial mass production.
(2) 4-chloro-benzaldehyde method:
This route technical process is long, uses the costlinesses such as methyl iodide and the reagent of high poison, is difficult to industrial applications.
(3) 4-chlorobenzyl chloride method:
this synthetic method uses the reagent such as boron trifluoride, sodium borohydride, expensive, has certain operational danger; Overall yield of reaction is low, and product content is not high.
Summary of the invention
The technical problem to be solved in the present invention is to provide that a kind of raw materials cost is low, and overall yield of reaction is high, technological operation safety, and aftertreatment is easy, has the synthetic method of 1-(4-the chloro-phenyl-)-2-cyclopropyl-1-acetone of industrial application value.
For solving the problems of the technologies described above, technical scheme of the present invention is: the synthetic method of a kind of 1-(4-chloro-phenyl-)-2-cyclopropyl-1-acetone, its innovative point is, described synthetic method comprises the steps:
(1) oxammonium hydrochloride is dissolved in solvent, adds adjusting PH with base value, add raw material at appropriate temperatures
Cyclopropylpropanal reacts, and after reaction terminates, through extraction concentrate drying, obtains cyclopropyl ethylidenehydroxylamine; Synthetic route is as follows:
;
(2) at a lower temperature, freshly prepd rubigan diazonium salt and catalyzer are joined
In cyclopropyl ethylidenehydroxylamine, add concentrated acid, temperature reaction, after reaction terminates, through concentrated rectifying
Obtain 1-(4-chloro-phenyl-)-2-cyclopropyl-1-acetone; Synthetic route is as follows:
.
Further, the solvent in described step (1) is one or more in protic solvent methyl alcohol, ethanol, propyl alcohol, Virahol, water, formic acid and acetic acid; Or one or more in non-protonic solvent DMF, acetone, ethyl acetate, methylene dichloride, ether, tetracol phenixin, toluene, benzene, normal hexane, hexanaphthene, tetrahydrofuran (THF) and chloroform.
Further, the alkali in described step (1) is one or more in sodium carbonate, sodium bicarbonate, salt of wormwood, saleratus, sodium hydroxide, potassium hydroxide, triethylamine and pyridine.
Further, the pH value in described step (1) controls 4.0 ~ 7.0, and certain temperature is 0 ~ 80 DEG C, and the reaction times is 1 ~ 5h.
Further, the X in the rubigan diazonium salt in described step (2) is any one in F, Cl, Br, I; Catalyzer is one or more in ammonium sulfate, ammonium acetate, copper sulfate and manganous sulfate; Concentrated acid is one or more of hydrochloric acid and sulfuric acid.
Further, the lesser temps in described step (2) is-20 ~ 20 DEG C, rises to 60 ~ 150 DEG C.
The invention has the advantages that: oxammonium hydrochloride is dissolved in solvent, add adjusting PH with base value, add raw material cyclopropylpropanal at appropriate temperatures, after reaction terminates, through extraction concentrate drying, obtain cyclopropyl ethylidenehydroxylamine; At a lower temperature, freshly prepd rubigan diazonium salt and catalyzer are joined in cyclopropyl ethylidenehydroxylamine, adds concentrated acid, temperature reaction, after reaction terminates, obtain 1-(4-chloro-phenyl-)-2-cyclopropyl-1-acetone through concentrated rectifying; This synthetic method is relative in traditional synthetic method, and raw materials cost is low, and overall yield of reaction is high, technological operation safety, and aftertreatment is easy, has industrial application value.
Embodiment
The following examples can make the present invention of professional and technical personnel's comprehend, but therefore do not limit the present invention among described scope of embodiments.
Embodiment
one, pH value screening
1, synthetic route:
2, synthetic method:
Step 1: oxammonium hydrochloride is dissolved in etoh solvent, adds sodium bicarbonate adjust pH to 6.0; (offer four parallel condition, in the test-results of table 1, the preferred of pH value can be found out
Be 6.0.）
The test-results of table 1:pH value screening
| Numbering | PH value | Solvent | Temperature (DEG C) | Yield |
| 1 | 7.0 | Ethanol | 35 | 92% |
| 2 | 6.0 | Ethanol | 35 | 96% |
| 3 | 5.0 | Ethanol | 35 | 88% |
| 4 | 4.0 | Ethanol | 35 | 83% |
Step 2: 35
odrip raw material cyclopropylpropanal under C, insulation reaction 1.5h, follow the tracks of through liquid phase and confirm that raw material consumption is complete, stopped reaction;
Step 3: after reaction terminates, decompression and solvent recovery, crude product obtains organic phase through extraction;
Step 4: concentrate drying, obtains cyclopropyl ethylidenehydroxylamine (content is 97%).
two, the screening of halogen X and the screening of temperature of reaction in rubigan diazonium salt
1, synthetic route:
(offer 3 parallel condition, in the test-results of table 2, the preferred Cl of halogen X in rubigan diazonium salt can be found out.）
Table 2: the screening of halogen X in rubigan diazonium salt
| Numbering | Halogen X | Catalyzer | Temperature (DEG C) | Yield |
| 1 | Cl | Ammonium acetate, copper sulfate | 80 | 83% |
| 2 | Br | Ammonium acetate, copper sulfate | 80 | 79% |
| 3 | I | Ammonium acetate, copper sulfate | 80 | 75% |
2, synthetic method:
Step 1 :-10
ounder C, the rubigan diazonium salt just prepared and appropriate ammonium acetate, copper sulfate are dropped in cyclopropyl ethylidenehydroxylamine, stirs 30min;
Step 2: add 48% vitriol oil, be warming up to 90
oc, reaction 2h, after liquid phase tracking raw material consumption is complete, stopped reaction; (offer 4 parallel condition, in the test-results of table 3, temperature of reaction preferably 90 DEG C can be found out.）
Table 3: the screening of temperature of reaction
| Numbering | Temperature (DEG C) | Halogen X | Catalyzer | Yield |
| 1 | 60 | Cl | Ammonium acetate, copper sulfate | 73% |
| 2 | 90 | Cl | Ammonium acetate, copper sulfate | 86% |
| 3 | 120 | Cl | Ammonium acetate, copper sulfate | 78% |
| 4 | 150 | Cl | Ammonium acetate, copper sulfate | 55% |
Step 3: after reaction terminates, obtains organic phase through extraction;
Step 4: after concentrated rectifying, obtain 1-(4-chloro-phenyl-)-2-cyclopropyl-1-acetone.
Conclusion: by the synthetic method of the present embodiment 1-(4-chloro-phenyl-)-2-cyclopropyl-1-acetone, the method, raw materials cost is low, and overall yield of reaction is high, technological operation safety, and aftertreatment is easy, has industrial application value.
More than show and describe ultimate principle of the present invention and principal character and advantage of the present invention.The technician of the industry should understand; the present invention is not restricted to the described embodiments; what describe in above-described embodiment and specification sheets just illustrates principle of the present invention; without departing from the spirit and scope of the present invention; the present invention also has various changes and modifications, and these changes and improvements all fall in the claimed scope of the invention.Application claims protection domain is defined by appending claims and equivalent thereof.
Claims (6)
1. a synthetic method for 1-(4-chloro-phenyl-)-2-cyclopropyl-1-acetone, it is characterized in that, described synthetic method comprises the steps:
(1) oxammonium hydrochloride is dissolved in solvent, adds adjusting PH with base value, add raw material at a certain temperature
Cyclopropylpropanal reacts, and after reaction terminates, through extraction concentrate drying, obtains cyclopropyl second
Aldoxime; Synthetic route is as follows:
;
(2) at a lower temperature, freshly prepd rubigan diazonium salt and catalyzer are joined
In cyclopropyl ethylidenehydroxylamine, add concentrated acid, temperature reaction, after reaction terminates, through concentrated essence
1-(4-chloro-phenyl-)-2-cyclopropyl-1-acetone is obtained after heating up in a steamer; Synthetic route is as follows:
.
2. the synthesis side of 1-according to claim 1 (4-chloro-phenyl-)-2-cyclopropyl-1-acetone
Method, is characterized in that: the solvent in described step (1) is protic solvent methyl alcohol, second
One or more in alcohol, propyl alcohol, Virahol, water, formic acid and acetic acid; Or it is non-proton
Property solvent DMF, acetone, ethyl acetate, methylene dichloride, ether,
In tetracol phenixin, toluene, benzene, normal hexane, hexanaphthene, tetrahydrofuran (THF) and chloroform one
Kind or several.
3. the synthesis side of 1-according to claim 1 (4-chloro-phenyl-)-2-cyclopropyl-1-acetone
Method, is characterized in that: the alkali in described step (1) is sodium carbonate, sodium bicarbonate, carbon
One in acid potassium, saleratus, sodium hydroxide, potassium hydroxide, triethylamine and pyridine
Or it is several.
4. the synthesis side of 1-according to claim 1 (4-chloro-phenyl-)-2-cyclopropyl-1-acetone
Method, is characterized in that: the pH value in described step (1) controls 4.0 ~ 7.0, one
Fixed temperature is 0 ~ 80 DEG C, and the reaction times is 1 ~ 5h.
5. the synthesis side of 1-according to claim 1 (4-chloro-phenyl-)-2-cyclopropyl-1-acetone
Method, is characterized in that: the X in the rubigan diazonium salt in described step (2) be F,
Any one in Cl, Br, I; Catalyzer be ammonium sulfate, ammonium acetate, copper sulfate and
One or more in manganous sulfate; Concentrated acid is one or more of hydrochloric acid and sulfuric acid.
6. the synthesis side of 1-according to claim 1 (4-chloro-phenyl-)-2-cyclopropyl-1-acetone
Method, is characterized in that: the lesser temps in described step (2) is-20 ~ 20 DEG C, rises
Temperature rise to 60 ~ 150 DEG C.
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| CN201510521752.7A CN105152886B (en) | 2015-08-24 | 2015-08-24 | A kind of synthetic method of 1 (4 chlorphenyl) 2 cyclopropyl, 1 acetone |
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| CN201510521752.7A CN105152886B (en) | 2015-08-24 | 2015-08-24 | A kind of synthetic method of 1 (4 chlorphenyl) 2 cyclopropyl, 1 acetone |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012059441A2 (en) * | 2010-11-03 | 2012-05-10 | Basf Se | Method for preparing substituted isoxazoline compounds and their precursors 4-chloro, 4-bromo- or 4-iodobenzaldehyde oximes |
| CN102584558A (en) * | 2011-12-21 | 2012-07-18 | 湖南化工研究院 | Preparation method of 1-(4-chlorphenyl)-2-cyclopropyl-1-acetone |
| CN102603508A (en) * | 2012-04-17 | 2012-07-25 | 江苏澄扬作物科技有限公司 | Preparation method of 1-(4-chlorophenyl)-2-cyclopropyl-1-acetone and intermediate thereof as well as preparation method of intermediate |
| CN102675074A (en) * | 2012-05-25 | 2012-09-19 | 江西华士药业有限公司 | Preparation method of cyproconazole key intermediate 1-(4-chlorphenyl)-2-cyclopropyl-1-acetone |
-
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- 2015-08-24 CN CN201510521752.7A patent/CN105152886B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012059441A2 (en) * | 2010-11-03 | 2012-05-10 | Basf Se | Method for preparing substituted isoxazoline compounds and their precursors 4-chloro, 4-bromo- or 4-iodobenzaldehyde oximes |
| CN102584558A (en) * | 2011-12-21 | 2012-07-18 | 湖南化工研究院 | Preparation method of 1-(4-chlorphenyl)-2-cyclopropyl-1-acetone |
| CN102603508A (en) * | 2012-04-17 | 2012-07-25 | 江苏澄扬作物科技有限公司 | Preparation method of 1-(4-chlorophenyl)-2-cyclopropyl-1-acetone and intermediate thereof as well as preparation method of intermediate |
| CN102675074A (en) * | 2012-05-25 | 2012-09-19 | 江西华士药业有限公司 | Preparation method of cyproconazole key intermediate 1-(4-chlorphenyl)-2-cyclopropyl-1-acetone |
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