CN105152886B - A kind of synthetic method of 1 (4 chlorphenyl) 2 cyclopropyl, 1 acetone - Google Patents
A kind of synthetic method of 1 (4 chlorphenyl) 2 cyclopropyl, 1 acetone Download PDFInfo
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- CN105152886B CN105152886B CN201510521752.7A CN201510521752A CN105152886B CN 105152886 B CN105152886 B CN 105152886B CN 201510521752 A CN201510521752 A CN 201510521752A CN 105152886 B CN105152886 B CN 105152886B
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- GGGINUGSQIXGCL-DAXSKMNVSA-N CC(C1CC1)/C=N\O Chemical compound CC(C1CC1)/C=N\O GGGINUGSQIXGCL-DAXSKMNVSA-N 0.000 description 1
- ZQCOZVCLROSHBR-UHFFFAOYSA-N CC(C1CC1)C1OC1c1ccc(C)cc1 Chemical compound CC(C1CC1)C1OC1c1ccc(C)cc1 ZQCOZVCLROSHBR-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- 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
- C07—ORGANIC CHEMISTRY
- 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 present invention relates to a kind of synthetic method of 1 (4 chlorphenyl) 2 cyclopropyl, 1 acetone, the synthetic method comprises the steps：（1）Oxammonium hydrochloride is dissolved in solvent, plus adjusting PH with base value, the reaction of raw material cyclopropylpropanal is added at appropriate temperatures, after reaction terminates, through extracting concentrate drying, cyclopropyl aldoxime is obtained；（2）At a lower temperature, freshly prepd rubigan diazol and catalyst are added in cyclopropyl aldoxime, add acid, temperature reaction to react after terminating, post processing obtains 1 (4 chlorphenyl) 2 cyclopropyl, 1 acetone；Synthetic route：It is an advantage of the current invention that：The synthetic method, cost of material are low, and overall yield of reaction is high, technological operation safety, and post processing is easy, has industrial application value.
Description
Technical field
The present invention relates to the synthetic method of the key intermediate of SAN-619F, more particularly to a kind of 1- (4- chlorphenyls) -2-
The synthetic method of cyclopropyl -1- acetone.
Background technology
SAN-619F is the triazole bactericidal agent that is developed by mountain pass scholar company of Switzerland (being now Syngenta Co., Ltd), fungicidal spectrum
Extensively, remain less, be sterol demethylation inhibitors, with preventive and therapeutic action.To cereal crop, coffee, Radix Betae, fruit tree
Effective with the Erysiphales on Fructus Vitis viniferae, Uredinales, the mould category of category spore, beak genuss, Septoria, Venturia bacterium.Kill with other
Microbial inoculum is used with, can prevent and treat frumentum eye spot disease, leaf spot and net blotch very well.Sales volume in the market is increasing, purposes
More and more extensively, thus how at low cost volume production SAN-619F into the task of top priority, and which controls being critically depend on for cost
The technological break-through of its intermediate 1- (4- chlorphenyls) -2- cyclopropyl -1- acetone.
With regard to 1- (4- chlorphenyls) -2- cyclopropyl -1- acetone, its chemical formula is：C12H13ClO；CAS accession number：
123989-29-7；Chemical name is：1- (4- chlorphenyls) -2- cyclopropyl -1- acetone；English name is：1-(4-
Chlorophenyl)-2-cyclopropylpropan-1-one；Structural formula is：
Synthesis to SAN-619F key intermediate, industrial mainly have following three kinds of routes：
（1）P-chlorobenzyl cyanide method：
The 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 industry
Large-scale production.
（2）4-chloro-benzaldehyde method：
The route technological process is long, uses the reagent of the costliness such as iodomethane and high poison, it is difficult to industrial applications.
（3）P-chlorobenzylchloride method：
The synthetic method uses the reagents such as boron trifluoride, sodium borohydride, expensive, has certain operational danger；Reaction is total
Yield is low, and product content is not high.
Content of the invention
It is low that the technical problem to be solved in the present invention is to provide a kind of cost of material, and overall yield of reaction is high, technological operation safety,
Post processing is easy, has the synthetic method of 1- (4- the chlorphenyls) -2- cyclopropyl -1- acetone of industrial application value.
For solving above-mentioned technical problem, the technical scheme is that：A kind of 1- (4- chlorphenyls) -2- cyclopropyl -1- third
The synthetic method of ketone, its innovative point are that the synthetic method comprises the steps：
（1）Oxammonium hydrochloride is dissolved in solvent, plus adjusting PH with base value, raw material is added at appropriate temperatures
Cyclopropylpropanal reacts, and after reaction terminates, through extracting concentrate drying, obtains cyclopropyl aldoxime；Synthetic route is such as
Under：
；
（2）At a lower temperature, freshly prepd rubigan diazol and catalyst are added to
In cyclopropyl aldoxime, concentrated acid, temperature reaction is added to react after terminating, concentrated rectification
Obtain 1- (4- chlorphenyls) -2- cyclopropyl -1- acetone；Synthetic route is as follows：
.
Further, the step（1）In solvent be protonic solvent methanol, ethanol, propanol, isopropanol, water, formic acid
With one or more in acetic acid；Or non-protonic solvent DMF, acetone, ethyl acetate, dichloromethane, second
One or more in ether, carbon tetrachloride, toluene, benzene, normal hexane, hexamethylene, tetrahydrofuran and chloroform.
Further, the step（1）In alkali be sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, sodium hydroxide,
One or more in potassium hydroxide, triethylamine and pyridine.
Further, the step（1）In pH value control 4.0～7.0, uniform temperature is 0～80 DEG C, the response time
For 1～5h.
Further, the step（2）In rubigan diazol in X be F, Cl, Br, I in any one；Urge
Agent is one or more in ammonium sulfate, ammonium acetate, copper sulfate and manganese sulfate；Concentrated acid is one kind or several of hydrochloric acid and sulphuric acid
Kind.
Further, the step（2）In lower temperature be -20～20 DEG C, rise to 60～150 DEG C.
It is an advantage of the current invention that：Oxammonium hydrochloride is dissolved in solvent, plus adjusting PH with base value, raw material ring is added at appropriate temperatures
Propyl group propionic aldehyde, after reaction terminates, through extracting concentrate drying, obtains cyclopropyl aldoxime；At a lower temperature, will be freshly prepd right
Chlorobenzene aryldiazonium salt and catalyst are added in cyclopropyl aldoxime, add concentrated acid, and temperature reaction is after reaction terminates, concentrated
Rectification obtains 1- (4- chlorphenyls) -2- cyclopropyl -1- acetone；The synthetic method relative in traditional synthetic method, raw material into
This is low, and overall yield of reaction is high, technological operation safety, and post processing is easy, has industrial application value.
Specific embodiment
The following examples can make professional and technical personnel that the present invention is more fully understood, but not therefore by this
Bright it is limited among described scope of embodiments.
Embodiment
First, pH value screening
1st, synthetic route：
2nd, synthetic method：
Step 1：Oxammonium hydrochloride is dissolved in etoh solvent, plus sodium bicarbonate adjusts pH value to 6.0；（Four parallel conditions are opened up,
Be shown in Table 1 result of the test, it can be seen that pH value preferred
For 6.0.）
Table 1：The result of the test of pH value screening
| Numbering | PH value | Solvent | Temperature（℃） | 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 2:35oDeca raw material cyclopropylpropanal under C, insulation reaction 1.5h confirm consumption of raw materials through liquid phase tracking
Complete, stopped reaction；
Step 3:After reaction terminates, decompression and solvent recovery, crude product is through being obtained by extraction organic faciess；
Step 4：Concentrate drying, obtains cyclopropyl aldoxime（Content is 97%）.
2nd, in rubigan diazol halogen X screening and the screening of reaction temperature
1st, synthetic route：（Open up 3 to put down
Row condition, is shown in Table 2 result of the test, it can be seen that the preferred Cl of halogen X in rubigan diazol.）
Table 2：The screening of halogen X in rubigan diazol
| Numbering | Halogen X | Catalyst | Temperature（℃） | 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% |
2nd, synthetic method：
Step 1：- 10oUnder C, by the rubigan diazol for just having prepared and appropriate ammonium acetate, copper sulfate input
In cyclopropyl aldoxime, 30min is stirred；
Step 2：48% concentrated sulphuric acid is added, 90 are warming up tooC, reacts 2h, after liquid phase tracking consumption of raw materials is complete, stopped reaction；
（4 parallel conditions are opened up, 3 result of the test is shown in Table, it can be seen that preferably 90 DEG C of reaction temperature.）
Table 3：The screening of reaction temperature
| Numbering | Temperature（℃） | Halogen X | Catalyst | 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, through organic faciess are obtained by extraction；
Step 4：After concentrated rectification, 1- (4- chlorphenyls) -2- cyclopropyl -1- acetone is obtained.
Conclusion：By the synthetic method of the present embodiment 1- (4- chlorphenyls) -2- cyclopropyl -1- acetone, the method, raw material into
This is low, and overall yield of reaction is high, technological operation safety, and post processing is easy, has industrial application value.
The ultimate principle and principal character and advantages of the present invention of the present invention has been shown and described above.The skill of the industry
Simply explanation of the art personnel it should be appreciated that the present invention is not restricted to the described embodiments, described in above-described embodiment and description
The 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, these
Changes and improvements are both fallen within scope of the claimed invention.The claimed scope of the invention by appending claims and
Its equivalent thereof.
Claims (5)
1. a kind of synthetic method of 1- (4- chlorphenyls) -2- cyclopropyl -1- acetone, it is characterised in that the synthetic method includes
Following steps：
(1) oxammonium hydrochloride is dissolved in solvent, plus adjusting PH with base value is to 4.0～7.0, is that raw material ring third is added at 0～80 DEG C in temperature
Base propionic aldehyde reacts, and after reaction terminates, through extracting concentrate drying, obtains cyclopropylpropanal oxime, and synthetic route is as follows：
(2) at a temperature of -20～20 DEG C, freshly prepd rubigan diazol and catalyst are added to cyclopropylpropanal oxime
In, concentrated acid is added, 60～150 DEG C of reactions is warming up to, after reaction terminates, after concentrated rectification, is obtained 1- (4- chlorphenyls) -2- rings
Propyl group -1- acetone, synthetic route are as follows：
X in rubigan diazol be F,
Any one in Cl, Br, I, concentrated acid are one or more of hydrochloric acid and sulphuric acid.
2. the synthetic method of 1- (4- chlorphenyls) -2- cyclopropyl -1- acetone according to claim 1, it is characterised in that：Institute
It is the one kind or several in protonic solvent methanol, ethanol, propanol, isopropanol, water, formic acid and acetic acid to state the solvent in step (1)
Kind；Or non-protonic solvent DMF, acetone, ethyl acetate, dichloromethane, ether, carbon tetrachloride, toluene,
One or more in benzene, normal hexane, hexamethylene, tetrahydrofuran and chloroform.
3. the synthetic method of 1- (4- chlorphenyls) -2- cyclopropyl -1- acetone according to claim 1, it is characterised in that：Institute
It is sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, triethylamine and pyrrole to state the alkali in step (1)
One or more in pyridine.
4. the synthetic method of 1- (4- chlorphenyls) -2- cyclopropyl -1- acetone according to claim 1, it is characterised in that：Institute
It is 1～5h to state in step (1) response time.
5. the synthetic method of 1- (4- chlorphenyls) -2- cyclopropyl -1- acetone according to claim 1, it is characterised in that：Institute
It is one or more in ammonium sulfate, ammonium acetate, copper sulfate and manganese sulfate to state the catalyst in step (2).
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| CN105152886B true CN105152886B (en) | 2017-03-15 |
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| US9006447B2 (en) * | 2010-11-03 | 2015-04-14 | Basf Se | Method for preparing substituted isoxazoline compounds and their precursors 4-chloro, 4-bromo- or 4-iodobenzaldehyde oximes |
| CN102584558B (en) * | 2011-12-21 | 2013-10-30 | 湖南化工研究院 | Preparation method of 1-(4-chlorphenyl)-2-cyclopropyl-1-acetone |
| CN102603508B (en) * | 2012-04-17 | 2014-03-12 | 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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