AU2018100835A4 - Drug intermediates diphenyl acetone synthesis method - Google Patents
Drug intermediates diphenyl acetone synthesis method Download PDFInfo
- Publication number
- AU2018100835A4 AU2018100835A4 AU2018100835A AU2018100835A AU2018100835A4 AU 2018100835 A4 AU2018100835 A4 AU 2018100835A4 AU 2018100835 A AU2018100835 A AU 2018100835A AU 2018100835 A AU2018100835 A AU 2018100835A AU 2018100835 A4 AU2018100835 A4 AU 2018100835A4
- Authority
- AU
- Australia
- Prior art keywords
- solution
- added
- temperature
- diphenyl
- synthesis method
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
Classifications
-
- 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
- C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
- C07C45/28—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation of CHx-moieties
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Drug intermediates diphenyl acetone synthesis method Abstract 5 The present invention discloses drug intermediates diphenyl acetone synthesis method, comprises the following steps: 2-bromo-2'-hydroxy-diphenyl-2-methyl ethyl ketone was added to the reaction vessel, raised the temperature of the solution, then added potassium chloride solution, reacted, increased the temperature gradually, raised the temperature of the solution; controlled the stirring, added isoamyl butyrate 10 solution, added two-methyl-two-methyl titanium in batches, continued to react, then added sodium sulfate solution, stirred, added the potassium carbonate solution to adjust pH, reduced the temperature of the solution, added the sodium chloride solution, precipitated solid, filtered, washed with didecylamine solution for several times, washed with p-cresol solution for several times, re-crystallized in 3-dimethylamine 15 acrylonitrile solution, dehydrated with dehydration, got the finished product diphenyl acetone. Figure 1
Description
The present invention discloses drug intermediates diphenyl acetone synthesis method, comprises the following steps: 2-bromo-2'-hydroxy-diphenyl-2-methyl ethyl ketone was added to the reaction vessel, raised the temperature of the solution, then added potassium chloride solution, reacted, increased the temperature gradually, raised the temperature of the solution; controlled the stirring, added isoamyl butyrate solution, added two-methyl-two-methyl titanium in batches, continued to react, then added sodium sulfate solution, stirred, added the potassium carbonate solution to adjust pH, reduced the temperature of the solution, added the sodium chloride solution, precipitated solid, filtered, washed with didecylamine solution for several times, washed with p-cresol solution for several times, re-crystallized in 3-dimethylamine acrylonitrile solution, dehydrated with dehydration, got the finished product diphenyl acetone.
Figure 1
2018100835 19 Jun 2018
Drug intermediates diphenyl acetone synthesis method
FIELD OF THE INVENTION
The present invention relates to a method for preparing a pharmaceutical 5 intermediate which belongs to the field of organic synthesis, more particularly, relates to drug intermediates diphenyl acetone synthesis method.
GENERAL BACKGROUND
Diphenyl acetone is mainly used as pharmaceutical intermediates, the photo-sensitizer of UV curing resins, pharmaceutical raw materials, organic synthesis intermediates and UV curing agents, as well as insecticides. Most of the existing synthetic methods adopt benzaldehyde and sodium cyanide, which are oxidized by nitric acid. But this synthetic method can produce nitrous acid gas, and pollution caused the harm to the response operation personnel health, the reaction process is intense, the dangerous co-efficient is higher, and the sodium cyanide itself is more toxic, it has a higher environmental pollution, and the later pollution treatment costs are high, which is not conducive to reducing the production cost, so it is necessary to put forward a new synthetic method.
SUMMARY
Based on the technical problems of the background technology, the purpose of the present invention is to provide drug intermediates diphenyl acetone synthesis method, comprises the following steps:
A: 2-bromo-2'-hydroxy-diphenyl-2-methyl ethyl ketone was added to the reaction vessel, raised the temperature of the solution to 50-60 °C,then added potassium chloride solution, reacted for 2-3h, increased the temperature gradually, raised the temperature of the solution to 70-76 °C within 60-80 min;
B: controlled the stirring speed at 150-190 rpm, added isoamyl butyrate solution, added two-methyl-two-methyl titanium in batches within 60-90 min, continued to react for 2-3 h, then added sodium sulfate solution, stirred for 90-110 min, added the potassium carbonate solution to adjust pH to 10-11, reduced the temperature of the solution to 10-16 °C, added the sodium chloride solution, precipitated solid, filtered,
2018100835 19 Jun 2018 washed with didecylamine solution for several times, washed with p-cresol solution for several times, re-crystallized in 3-dimethylamine acrylonitrile solution, dehydrated with dehydration, got the finished product diphenyl acetone.
Preferably, the potassium chloride solution has a mass fraction of 9-15%.
Preferably, the mass fraction of the isoamyl butyrate solution is 30-36%.
Preferably, the sodium sulfate solution has a mass fraction of 10-17%.
Preferably, the potassium carbonate solution has a mass fraction of 15-22%. Preferably, the mass fraction of the sodium chloride solution is 20-26%. Preferably, the didecylamine solution has a mass fraction of 40-45%.
Preferably, the mass fraction of p-cresol solution is 60-66%.
Preferably, the 3-dimethylamine acrylonitrile solution has a mass fraction of
80-87%.
Throughout the reaction process can be the following reaction formula:
Compared with the synthetic method disclosed in the background art, the invention provides drug intermediates diphenyl acetone synthesis method, it is unnecessary to use benzaldehyde and sodium cyanide as reactions and raw materials, avoid the nitrous acid gas caused pollution, and avoid the harm the response operation personnel health, mild reaction process, reduce the risk response co-efficient, avoid to use high toxicity sodium cyanide, reduce the pollution to the environment and the late pollution treatment cost, thus it is beneficial to reduce production cost, reduce intermediate links reaction, decrease the reaction time and improve the reaction yield, at the same time, the present invention provides a new synthetic route which has laid a good foundation for further enhancing the yield of the reaction.
DESCRIPTIONOFTHEDRAWING
Figure 1 is the infrared analysis spectrogram of finished product diphenyl acetone. DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
2018100835 19 Jun 2018
The following examples with reference to specific embodiments of the present invention are further illustrated:
Embodiment 1
Drug intermediates diphenyl acetone synthesis method comprises the following 5 steps:
A: 2 mol 2-bromo-2'-hydroxy-diphenyl-2-methyl ethyl ketone was added to the reaction vessel, raised the temperature of the solution to 50°C,then added 900 ml potassium chloride solution with a mass fraction of 9%, reacted for 2h, increased the temperature gradually, raised the temperature of the solution to 70 °C within 60min;
B: controlled the stirring speed at 150rpm, added 4 mol isoamyl butyrate solution with a mass fraction of 30%, added two-methyl-two-methyl titanium in five times within 60min, continued to react for 2h, then added 1.2 L sodium sulfate solution with a mass fraction of 10%, stirred for 90min, added the potassium carbonate solution with a mass fraction of 15% to adjust pH to 10, reduced the temperature of the solution to 10 °C, added 800ml sodium chloride solution with a mass fraction of 20%, precipitated solid, filtered, washed with didecylamine solution with a mass fraction of 40% for four times, washed with p-cresol solution with a mass fraction of 60% for two times, re-crystallized in 3-dimethylamine acrylonitrile solution with a mass fraction of 80%, dehydrated with anhydrous calcium sulphatedehydration, got the finished product diphenyl acetone
413.7g, yield of 98.5%.
Embodiment 2
Drug intermediates diphenyl acetone synthesis method comprises the following steps:
A: 2 mol 2-bromo-2'-hydroxy-diphenyl-2-methyl ethyl ketone was added to the reaction vessel, raised the temperature of the solution to 58°C,then added 900 ml potassium chloride solution with a mass fraction of 12%, reacted for 2.1h, increased the temperature gradually, raised the temperature of the solution to 75 °C within 65min;
B: controlled the stirring speed at 180rpm, added 5 mol isoamyl butyrate solution with a mass fraction of 32%, added two-methyl-two-methyl titanium in six times within
87min, continued to react for 2.2h, then added 1.2 L sodium sulfate solution with a mass
2018100835 19 Jun 2018 fraction of 16%, stirred for lOOmin, added the potassium carbonate solution with a mass fraction of 17% to adjust pH to 10.5, reduced the temperature of the solution to 12°C, added 800ml sodium chloride solution with a mass fraction of 22%, precipitated solid, filtered, washed with didecylamine solution with a mass fraction of 42% for five times, washed with p-cresol solution with a mass fraction of 62% for three times, re-crystallized in 3-dimethylamine acrylonitrile solution with a mass fraction of 83%, dehydrated with phosphorus pentoxide dehydration, got the finished product diphenyl acetone 415.8g, yield of 99%.
Embodiment 3
Drug intermediates diphenyl acetone synthesis method comprises the following steps:
A: 2 mol 2-bromo-2'-hydroxy-diphenyl-2-methyl ethyl ketone was added to the reaction vessel, raised the temperature of the solution to 60°C,then added 900 ml potassium chloride solution with a mass fraction of 15%, reacted for 3h, increased the temperature gradually, raised the temperature of the solution to 76 °C within 80min;
B: controlled the stirring speed at 190rpm, added 6 mol isoamyl butyrate solution with a mass fraction of 36%, added two-methyl-two-methyl titanium in seven times within 90min, continued to react for 3h, then added 1.2 L sodium sulfate solution with a mass fraction of 17%, stirred for 1 lOmin, added the potassium carbonate solution with a mass fraction of 22% to adjust pH to 11, reduced the temperature of the solution to 16 °C, added 800ml sodium chloride solution with a mass fraction of 26%, precipitated solid, filtered, washed with didecylamine solution with a mass fraction of 45% for six times, washed with p-cresol solution with a mass fraction of 66% for four times, re-crystallized in 3-dimethylamine acrylonitrile solution with a mass fraction of 87%, dehydrated with anhydrous calcium sulphate dehydration, got the finished product diphenyl acetone 417.06g, yield of 99.3%.
The infrared analysis of finished product diphenyl acetone was made by analysis
Infrared spectrogram, as shown in figure 1.
The infrared analysis data is shown in table 1.
2018100835 19 Jun 2018
Table 1 infrared analysis data
| Number | Peak position (cm-1) | Transmittance (%) | Half peak width (cm-1) | Peak difference (%) |
| 1 | 615 | 52 | 16 | 9 |
| 2 | 642 | 9 | 23 | 64 |
| 3 | 675 | 49 | 13 | 29 |
| 4 | 694 | 34 | 13 | 43 |
| 5 | 716 | 22 | 24 | 24 |
| 6 | 793 | 50 | 18 | 45 |
| 7 | 877 | 32 | 17 | 63 |
| 8 | 1000 | 63 | 16 | 31 |
| 9 | 1179 | 42 | 16 | 41 |
| 10 | 1218 | 13 | 18 | 82 |
| 11 | 1331 | 54 | 29 | 35 |
| 12 | 1458 | 34 | 26 | 63 |
| 13 | 1585 | 45 | 13 | 21 |
| 14 | 1600 | 33 | 16 | 42 |
| 15 | 1666 | 15 | 24 | 18 |
| 16 | 1683 | 19 | 21 | 8 |
The embodiments of the present invention are merely preferred embodiments of the present invention, but the range of the present invention is not limited this, and any person who is familiar with those skilled in the arts, within the technical range of the present invention. It is intended that the technical solution and its inventive concept be replaced or modified equivalently with reference to the range of the invention.
2018100835 19 Jun 2018
Claims (4)
- Claims1. Drug intermediates diphenyl acetone synthesis method, comprises the following steps:5 A: 2-bromo-2'-hydroxy-diphenyl-2-methyl ethyl ketone was added to the reaction vessel, raised the temperature of the solution to 50-60°C,then added potassium chloride solution, reacted for 2-3h, increased the temperature gradually, raised the temperature of the solution to 70-76 °C within 60-80 min;B: controlled the stirring speed at 150-190 rpm, added isoamyl butyrate solution, 10 added two-methyl-two-methyl titanium in batches within 60-90 min, continued to react for 2-3 h, then added sodium sulfate solution, stirred for 90-110 min, added the potassium carbonate solution to adjust pH to 10-11, reduced the temperature of the solution to 10-16 °C, added the sodium chloride solution, precipitated solid, filtered, washed with didecylamine solution for several times, washed with p-cresol solution15 for several times, re-crystallized in 3-dimethylamine acrylonitrile solution, dehydrated with dehydration, got the finished product diphenyl acetone.
- 2. Drug intermediates diphenyl acetone synthesis method according to claim 1 wherein the potassium chloride solution has a mass fraction of 9-15%.
- 3. Drug intermediates diphenyl acetone synthesis method according to claim 1 20 wherein the mass fraction of the isoamyl butyrate solution is 30-36%.
- 4. Drug intermediates diphenyl acetone synthesis method according to claim 1 wherein the sodium sulfate solution has a mass fraction of 10-17%.2018100835 19 Jun 20181/1Figure 1
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2017105368526 | 2017-07-04 | ||
| CN201710536852 | 2017-07-04 | ||
| CN201710551381.6A CN108238868A (en) | 2017-07-04 | 2017-07-07 | The synthetic method of pharmaceutical intermediate diphenylthanedione |
| CN2017105513816 | 2017-07-07 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2018100835A4 true AU2018100835A4 (en) | 2018-08-02 |
Family
ID=62700774
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2018100835A Ceased AU2018100835A4 (en) | 2017-07-04 | 2018-06-19 | Drug intermediates diphenyl acetone synthesis method |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN108238868A (en) |
| AU (1) | AU2018100835A4 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112300770B (en) * | 2020-09-25 | 2022-04-22 | 西南石油大学 | Preparation method of temperature-resistant salt-resistant foam scrubbing agent |
-
2017
- 2017-07-07 CN CN201710551381.6A patent/CN108238868A/en active Pending
-
2018
- 2018-06-19 AU AU2018100835A patent/AU2018100835A4/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| CN108238868A (en) | 2018-07-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2018100835A4 (en) | Drug intermediates diphenyl acetone synthesis method | |
| PL377380A1 (en) | A process for preparing duloxetine and intermediates for use therein | |
| CN108558884B (en) | Synthesis method of folic acid | |
| BRPI0507422A (en) | process for production of 2,5-dimethylphenylacetic acid | |
| JPH02304080A (en) | 6h-dibenzo(b,d)pyran-6-one derivative, its production and use thereof | |
| EP2081920A4 (en) | Method for preparing crystalline 3-0-alkyl-ascorbic acid | |
| ATE509117T1 (en) | PRODUCTION PROCESS FOR HYALURONIC ACID OR ITS DERIVATIVES | |
| AU2018100825A4 (en) | Trimethoprim drug intermediate p-nitrobenzene formaldehyde synthesis method | |
| BR9603728A (en) | Process for the production of a compound | |
| CN110642764A (en) | Preparation method of water-soluble florfenicol sodium salt | |
| CN102702135B (en) | Benzoyl thiourea compound with benzothiazole structure and preparation method and application of compound | |
| AU2018100842A4 (en) | Pharmaceutical intermediates adipic acid synthesis method | |
| AU2018101113A4 (en) | Leprosy drug intermediates p-isothiocyanolobutyl ether synthesis method | |
| EA200501361A1 (en) | METHOD FOR OBTAINING TIOACHE ACID AND ITS SALTS | |
| AU2018100823A4 (en) | Drug intermediates 3-ene hexenoic acid synthesis method | |
| AU2018100533A4 (en) | 3-trichloroacetyl-2, 2-dimethylcyclopropanecarboxylic acid ethyl ester drug synthesis method | |
| AU2018100532A4 (en) | Anti-arrhythmic drug intermediate 1-(2,6-dimethoxy)-2-acetone synthesis method | |
| MXPA05006938A (en) | Process for producing benzylamine derivative. | |
| AU2018101116A4 (en) | Vitamin drug intermediates diketone guluronic acid synthesis method | |
| BR0300877A (en) | Process for the preparation of cyclic diketones | |
| WO2006072375A3 (en) | Method for the production of substituted 2-alkoxycarbonyl-3-aminothiophenes | |
| AU2018100397A4 (en) | Antimalarial medicine intermediates 2,4-dichlorobenzoic acid synthesis method | |
| AU2018100849A4 (en) | Pharmaceutical intermediates 2-acetamido-5-sulfonyl chloride-1,3,4- thiadiazole synthesis method | |
| AU2018100525A4 (en) | Drug synthesis intermediates p-carboxybenzenesulfonic amide synthesis method | |
| BR112022010520A2 (en) | PROCESS FOR SYNTHESIS OF A 2-THIOALKYL PYRIMIDINE |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGI | Letters patent sealed or granted (innovation patent) | ||
| MK22 | Patent ceased section 143a(d), or expired - non payment of renewal fee or expiry |