AU2018100526A4 - Drug intermediates p-benzoylbenzoic acid synthesis method - Google Patents
Drug intermediates p-benzoylbenzoic acid synthesis method Download PDFInfo
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- AU2018100526A4 AU2018100526A4 AU2018100526A AU2018100526A AU2018100526A4 AU 2018100526 A4 AU2018100526 A4 AU 2018100526A4 AU 2018100526 A AU2018100526 A AU 2018100526A AU 2018100526 A AU2018100526 A AU 2018100526A AU 2018100526 A4 AU2018100526 A4 AU 2018100526A4
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- benzoylbenzoic acid
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- IFQUPKAISSPFTE-UHFFFAOYSA-N OC(c(cc1)ccc1C(c1ccccc1)=O)=O Chemical compound OC(c(cc1)ccc1C(c1ccccc1)=O)=O IFQUPKAISSPFTE-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/16—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation
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- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Abstract The present invention discloses p-benzoylbenzoic acid synthesis method, comprises the following steps: 3 -amino-4-hydroxymethylbenzophenone and 5 potassium nitrate solution were added to the reaction vessel, controlled the stirring speed, raised the temperature of the solution, added 2-methyl-1-butanol solution, added terbium oxide powder in batches; maintain reflux, added potassium bromide solution, precipitateed the crystals, filter, washed with o-xylene solution for several times, washed with hexachloroethane solution for several times, recrystallized in 10 thionyl chloro solution, dehydrated with dehydration, got the finished product of p-benzoylbenzoic acid.
Description
The present invention discloses p-benzoylbenzoic acid synthesis method, comprises the following steps: 3-amino-4-hydroxymethylbenzophenone and potassium nitrate solution were added to the reaction vessel, controlled the stirring speed, raised the temperature of the solution, added 2-methyl-1-butanol solution, added terbium oxide powder in batches; maintain reflux, added potassium bromide solution, precipitateed the crystals, filter, washed with o-xylene solution for several times, washed with hexachloroethane solution for several times, recrystallized in thionyl chloro solution, dehydrated with dehydration, got the finished product of p-benzoylbenzoic acid.
ι
2018100526 24 Apr 2018
Drug intermediates p-benzoylbenzoic acid 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 p-benzoylbenzoic acid synthesis method.
GENERAL BACKGROUND
P-benzoylbenzoic acid as an organic synthesis intermediate, it can be used for the production of drugs and dyes. However, most of the existing synthetic methods are using the method that carbon dioxide and 4-bromobenzoylbenzene as reactants, genarate p-benzoylbenzoic acid, which is complicated and the final yield is not very high. Therefore, it is necessary to propose 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 p-benzoylbenzoic acid synthesis method, comprises the following steps:
A: 3-amino-4-hydroxymethylbenzophenone and potassium nitrate solution were 20 added to the reaction vessel, controlled the stirring speed at 130-160 rpm, raised the temperature of the solution to 40-46 °C, added 2-methyl-1-butanol solution, added terbium oxide powder in batches;
B: maintain reflux for 90-120 min after the addition, added 800-900 ml potassium bromide solution, precipitated the crystals, filter, washed with o-xylene solution for several times, washed with hexachloroethane solution for several times, recrystallized in thionyl chloro solution, dehydrated with dehydration, got the finished product of p-benzoylbenzoic acid.
Preferably, the potassium nitrate solution has a mass fraction of 30-38%. Preferably, the mass fraction of the 2-methyl-1-butanol solution is 50-56%.
Preferably, the potassium bromide solution has a mass fraction of 35-42%.
2018100526 24 Apr 2018
Preferably, the o-xylene solution has a mass fraction of 60-68%. Preferably, the mass fraction of hexachloroethane solution is 75-82%. Preferably, the mass fraction of thionyl chloro solution is 80-86%. 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 p-benzoylbenzoic acid synthesis method, it is unnecessary to use carbon dioxide and 4-bromobenzoylbenzene as reactants, reducing intermediate links reaction, decreasing the reaction time and improving 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.
DESCRIPTION OF THE DRAWINGS
Figure 1 is the infrared analysis spectrum of finished product p-benzoylbenzoic acid.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
The following examples with reference to specific embodiments of the present invention are further illustrated:
Embodiment 1
Drug intermediates p-benzoylbenzoic acid synthesis method, comprises the following steps:
A: 2 mol 3-amino-4-hydroxymethylbenzophenone and potassium nitrate solution with a mass fraction of 30% were added to the reaction vessel, controlled the stirring speed at 130 rpm, raised the temperature of the solution to 40 °C, added 3 mol 2-methyl-1-butanol solution with a mass fraction of 50%, added 2 mol terbium oxide
2018100526 24 Apr 2018 powder in 3 times;
B: maintain reflux for 90 min after the addition, added 800 ml potassium bromide solution with a mass fraction of 35%, precipitated the crystals, filter, washed with o-xylene solution with a mass fraction of 60% for 3 times, washed with hexachloroethane solution with a mass fraction of 75% for 5 times, recrystallized in thionyl chloro solution with a mass fraction of 80%, dehydrated with anhydrous magnesium sulfate dehydration, got the finished product of p-benzoylbenzoic acid 397.76g, yield of 88%.
Embodiment 2
Drug intermediates p-benzoylbenzoic acid synthesis method, comprises the following steps:
A: 2 mol 3-amino-4-hydroxymethylbenzophenone and potassium nitrate solution with a mass fraction of 35% were added to the reaction vessel, controlled the stirring speed at 140 rpm, raised the temperature of the solution to 43 °C, added 3.5 mol 2-methyl-l-butanol solution with a mass fraction of 53%, added 2.5 mol terbium oxide powder in 4 times;
B: maintain reflux for 110 min after the addition, added 850 ml potassium bromide solution with a mass fraction of 40%, precipitated the crystals, filter, washed with o-xylene solution with a mass fraction of 64% for 4 times, washed with hexachloroethane solution with a mass fraction of 78% for 6 times, recrystallized in thionyl chloro solution with a mass fraction of 83%, dehydrated with anhydrous calcium chloride dehydration, got the finished product of p-benzoylbenzoic acid 411.32g, yield of 91%.
Embodiment 3
Drug intermediates p-benzoylbenzoic acid synthesis method, comprises the following steps:
A: 2 mol 3-amino-4-hydroxymethylbenzophenone and potassium nitrate solution with a mass fraction of 38% were added to the reaction vessel, controlled the stirring
2018100526 24 Apr 2018 speed at 160 rpm, raised the temperature of the solution to 46 °C, added 4 mol 2-methyl-1-butanol solution with a mass fraction of 56%, added 3 mol terbium oxide powder in 6 times;
B: maintain reflux for 120 min after the addition, added 900 ml potassium 5 bromide solution with a mass fraction of 42%, precipitated the crystals, filter, washed with o-xylene solution with a mass fraction of 68% for 5 times, washed with hexachloroethane solution with a mass fraction of 82% for 7 times, recrystallized in thionyl chloro solution with a mass fraction of 86%, dehydrated with dehydration, got the finished product of p-benzoylbenzoic acid 429.4g, yield of 95%.
Infrared analysis of finished product p-benzoylbenzoic acid, the infrared spectrum is shown in figure 1, the analysis of data is shown in table 1:
Table 1 Infrared spectrum data
| Serial | Peak position | Transmittance | Half width | Peak difference |
| number | (cnf1) | (%) | (cm'1) | (%) |
| 1 | 690 | 40 | 13 | 27 |
| 2 | 705 | 27 | 17 | 40 |
| 3 | 761 | 68 | 11 | 21 |
| 4 | 923 | 51 | 15 | 20 |
| 5 | 938 | 55 | 14 | 19 |
| 6 | 1274 | 19 | 52 | 49 |
| 7 | 1315 | 49 | 19 | 18 |
| 8 | 1424 | 48 | 37 | 24 |
| 9 | 1440 | 66 | 14 | 10 |
| 10 | 1495 | 62 | 10 | 28 |
| 11 | 1652 | 9 | 22 | 47 |
| 12 | 1680 | 20 | 27 | 19 |
| 13 | 1702 | 26 | 26 | 16 |
| 14 | 3061 | 54 | 333 | 26 |
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
2018100526 24 Apr 2018 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.
2018100526 24 Apr 2018
Claims (4)
- Claims1. Drug intermediates p-benzoylbenzoic acid synthesis method, comprises the following steps:5 A: 3-amino-4-hydroxymethylbenzophenone and potassium nitrate solution were added to the reaction vessel, controlled the stirring speed at 130-160 rpm, raised the temperature of the solution to 40-46 °C, added
- 2-methyl-l -butanol solution, added terbium oxide powder in batches;B: maintain reflux for 90-120 min after the addition, added 800-900 ml 10 potassium bromide solution, precipitated the crystals, fdter, washed with o-xylene solution for several times, washed with hexachloroethane solution for several times, recrystallized in thionyl chloro solution, dehydrated with dehydration, got the finished product of p-benzoylbenzoic acid.15 2. Drug intermediates p-benzoylbenzoic acid synthesis method according to claim 1 wherein the potassium nitrate solution has a mass fraction of 30-38%.
- 3. Drug intermediates p-benzoylbenzoic acid synthesis method according to claim 1 wherein the mass fraction of the 2-methyl-l-butanol solution is 50-56%.
- 4. Drug intermediates p-benzoylbenzoic acid synthesis method according to claim 1 wherein the potassium bromide solution has a mass fraction of 35-42%.2018100526 24 Apr 20181/1Figure 1
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710457417.4A CN108238901A (en) | 2017-06-16 | 2017-06-16 | Pharmaceutical intermediate is to the synthetic method of benzoyl benzoic acid |
| CN2017104574174 | 2017-06-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2018100526A4 true AU2018100526A4 (en) | 2018-05-24 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2018100526A Ceased AU2018100526A4 (en) | 2017-06-16 | 2018-04-24 | Drug intermediates p-benzoylbenzoic acid synthesis method |
Country Status (4)
| Country | Link |
|---|---|
| CN (1) | CN108238901A (en) |
| AU (1) | AU2018100526A4 (en) |
| GB (1) | GB201709978D0 (en) |
| IE (1) | IES20180113A2 (en) |
-
2017
- 2017-06-16 CN CN201710457417.4A patent/CN108238901A/en active Pending
- 2017-06-22 GB GBGB1709978.9A patent/GB201709978D0/en not_active Ceased
-
2018
- 2018-04-04 IE IES20180113 patent/IES20180113A2/en not_active Application Discontinuation
- 2018-04-24 AU AU2018100526A patent/AU2018100526A4/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| GB201709978D0 (en) | 2017-08-09 |
| CN108238901A (en) | 2018-07-03 |
| IES20180113A2 (en) | 2019-11-13 |
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