CN105523911A - Synthesis method of high-purity o-bromoacetophnones - Google Patents
Synthesis method of high-purity o-bromoacetophnones Download PDFInfo
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- CN105523911A CN105523911A CN201410518187.4A CN201410518187A CN105523911A CN 105523911 A CN105523911 A CN 105523911A CN 201410518187 A CN201410518187 A CN 201410518187A CN 105523911 A CN105523911 A CN 105523911A
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Abstract
The present invention discloses a synthesis method of a high-purity o-bromoacetophnones. The preparation method comprises the following steps: a methylmagnesium bromide Grignard reagent is added into a container, tetrahydrofuran and 2-Bromobenzonitrile are dropwise added into the container at room temperature, and then a lot of white solids appear; a reaction is stopped until no raw material is detected by HPLC spectrum; reaction solution is dropwise added into hydrochloric acid solution, and the hydrochloric acid solution treated reaction solution is subjected to skimming, spin drying and reduced pressure distillation processes, thereby obtaining colorless liquid products--high-purity o-bromoacetophnones. The preparation method improves the production and operation environment, can synthesize the high-purity o-bromoacetophnones under the condition of normal temperature, is easy to operate and control, shortens reaction time, reduces costs, and is beneficial to industrial production.
Description
Technical field
The present invention relates to a kind of synthetic method, particularly relate to a kind of high-purity o bromoacetophenone synthetic method.
Background technology
Adjacent bromoacetophenone is important organic synthesis intermediate, is widely used in the fields such as spices, medicine, agricultural chemicals, dyestuff, organic photoelectric.The preparation method of current adjacent bromoacetophenone mainly contains: friedel-crafts acylation method, 1-(2-bromophenyl) oxidation of ethanol method, and adjacent bromine ethylbenzene oxidation method.Wherein the most product of friedel-crafts acylation method is contraposition product, and yield is very low, bad purification; 1-(2-bromophenyl) oxidation of ethanol method raw material ratio costly, and step is longer, so do not possess working condition; Adjacent bromine ethylbenzene oxidation fado uses High Temperature High Pressure and expensive catalyzer, and oxidation is not thorough, and make the bad removing of the adjacent bromine ethylbenzene of raw material, purity is not high.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of economical and convenient, reaction conditions gentleness, good operational environment, high-purity o bromoacetophenone synthetic method that yield is high.
The present invention solves above-mentioned technical problem by following technical proposals: a kind of high-purity o bromoacetophenone synthetic method, it is characterized in that, it comprises the following steps: in a container, add methyl-magnesium-bromide Grignard reagent, under normal temperature condition, drip the tetrahydrofuran solution of adjacent bromoxynil, have a large amount of white solids after adding and occur; HPLC(HighPerformanceLiquidChromatography, high performance liquid chromatography; Also known as " high pressure liquid chromatography ") detect when there is no a raw material, stopped reaction; Be added drop-wise in hydrochloric acid soln, separatory, be spin-dried for, underpressure distillation just can obtain colourless liquid product, this colourless liquid product is high-purity o bromoacetophenone.
Preferably, the mol ratio of described adjacent bromoxynil and methyl-magnesium-bromide is 1:1.05.
Preferably, described adjacent bromoacetophenone has following structural formula:
.
Positive progressive effect of the present invention is: the present invention adopts THF(tetrahydrofuran (THF)) make solvent, improve production operation environment, under normal temperature condition, get final product the adjacent bromoacetophenone of synthesis of high purity, easy handling controls, and shorten the reaction times, reduce cost, be conducive to suitability for industrialized production.
Accompanying drawing explanation
The present invention is further described below in conjunction with the drawings and specific embodiments:
Fig. 1 is HPLC collection of illustrative plates (HighPerformanceLiquidChromatography, the high performance liquid chromatography of highly purified adjacent bromoacetophenone (embodiment one) prepared by the present invention; Also known as " high pressure liquid chromatography ") schematic diagram.
Fig. 2 is GC collection of illustrative plates ((GasChromatography(vapor-phase chromatography) schematic diagram of highly purified adjacent bromoacetophenone (embodiment one) prepared by the present invention.
Fig. 3 is HPLC collection of illustrative plates (HighPerformanceLiquidChromatography, the high performance liquid chromatography of highly purified adjacent bromoacetophenone (embodiment two) prepared by the present invention; Also known as " high pressure liquid chromatography ") schematic diagram.
Fig. 4 is GC collection of illustrative plates ((GasChromatography(vapor-phase chromatography) schematic diagram of highly purified adjacent bromoacetophenone (embodiment two) prepared by the present invention.
Embodiment
Present pre-ferred embodiments is provided, to describe technical scheme of the present invention in detail below in conjunction with accompanying drawing.
High-purity o bromoacetophenone has following structural formula:
.
Synthetic route of the present invention is as follows:
.
High-purity o bromoacetophenone synthetic method of the present invention comprises the following steps: in a container, add methyl-magnesium-bromide Grignard reagent, under normal temperature condition, drips the tetrahydrofuran solution of adjacent bromoxynil, has a large amount of white solids and occur after adding; When HPLC collection of illustrative plates detects and does not have raw material, stopped reaction; Be added drop-wise in hydrochloric acid soln, separatory, be spin-dried for, underpressure distillation just can obtain colourless liquid product (highly purified adjacent bromoacetophenone product).The mol ratio of adjacent bromoxynil and methyl-magnesium-bromide is 1:1.05.
The detailed step of the present invention is as follows: wherein, charging capacity is as follows: adjacent bromoxynil: 91g, methyl-magnesium-bromide (2M): 262.5ml, THF(Tetrahydrofuran, tetrahydrofuran (THF)): 90ml, concentrated hydrochloric acid: 60ml, toluene: 300ml.In 500ml reaction flask, add methyl-magnesium-bromide (2M) 262.5ml, control temperature of reaction and drip the adjacent bromoxynil of 91g and 90mlTHF solution at 20-25 DEG C, control temperature of reaction at 20-25 DEG C, within about 2 hours, drip, have a large amount of white solids after adding and occur.React 1 hour at this temperature again.Response situation is monitored with HPLC, when reaction solution raw material disappears, stopped reaction, be added drop-wise to by reaction solution in 60ml concentrated hydrochloric acid and 300ml water, separatory, aqueous phase 300ml toluene extracts, merge organic phase, then with 200ml washing, decompression-0.095MPa is concentrated into and no longer includes liquid and distillate.Underpressure distillation, collects 131-135 DEG C of (-0.095MPa) cut, obtains the adjacent bromoacetophenone of 95g colourless transparent liquid.Measure density: 1.48(20 DEG C), it is 99.21% that the HPLC collection of illustrative plates of adjacent bromoacetophenone as shown in Figure 1 and table 1 show adjacent bromoacetophenone content, the GC collection of illustrative plates of adjacent bromoacetophenone and table 2 show adjacent bromoacetophenone content is as shown in Figure 2 99.91%, reaction yield (in adjacent bromoxynil) 95.5%.
Table 1
Table 2
Example two: charging capacity is as follows: adjacent bromoxynil: 91g, methyl-magnesium-bromide (2M): 275ml, THF(Tetrahydrofuran, tetrahydrofuran (THF)): 90ml, concentrated hydrochloric acid: 70ml, toluene: 300ml.
Methyl-magnesium-bromide (2M) 275ml(0.55 is added) in 500ml reaction flask, control temperature of reaction and drip 91g(0.5mol at 20-25 DEG C) adjacent bromoxynil and 90mlTHF solution, control temperature of reaction at 20-25 DEG C, within about 2 hours, drip, have a large amount of white solids after adding and occur.React 1 hour at this temperature again.Response situation is monitored with HPLC, when reaction solution raw material disappears, stopped reaction, be added drop-wise to by reaction solution in 70ml concentrated hydrochloric acid and 300ml water, separatory, aqueous phase 300ml toluene extracts, merge organic phase, then with 200ml washing, decompression-0.095MPa is concentrated into and no longer includes liquid and distillate.Underpressure distillation, collects 131-135 DEG C of (-0.095MPa) cut, obtains the adjacent bromoacetophenone of 96g colourless transparent liquid.Measuring density: 1.49(20 DEG C) to show adjacent bromoacetophenone content be 99.36% for the HPLC collection of illustrative plates of adjacent bromoacetophenone as shown in Figure 3 and table 3, the GC collection of illustrative plates of adjacent bromoacetophenone and table 4 show adjacent bromoacetophenone content is as shown in Figure 4 99.88%, reaction yield (in adjacent bromoxynil) 96.5%.
Table 3
Table 4
The adjacent bromoxynil that the present invention utilizes market at prices relatively low does raw material, and the reaction of methyl-magnesium-bromide Grignard reagent, obtains highly purified adjacent bromoacetophenone after hydrolysis.This preparation method has: with low cost, temperature of reaction is low, product yield is high, the recyclable advantage such as to recycle of solvent.There is directive function to industrial production, have vast potential for future development, and there is not yet domestic and international report.
Those skilled in the art can carry out various remodeling and change to the present invention.Therefore, present invention covers the various remodeling in the scope falling into appending claims and equivalent thereof and change.
Claims (3)
1. a high-purity o bromoacetophenone synthetic method, is characterized in that, it comprises the following steps: in a container, add methyl-magnesium-bromide Grignard reagent, under normal temperature condition, drips the tetrahydrofuran solution of adjacent bromoxynil, has a large amount of white solids and occur after adding; When HPLC detects and does not have raw material, stopped reaction; Be added drop-wise in hydrochloric acid soln, separatory, be spin-dried for, underpressure distillation just can obtain colourless liquid product, this colourless liquid product is high-purity o bromoacetophenone.
2. high-purity o bromoacetophenone synthetic method as claimed in claim 1, it is characterized in that, the mol ratio of described adjacent bromoxynil and methyl-magnesium-bromide is 1:1.05.
3. high-purity o bromoacetophenone synthetic method as claimed in claim 1, it is characterized in that, described high-purity o bromoacetophenone has following structural formula:
.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112194622A (en) * | 2020-09-24 | 2021-01-08 | 上海毕得医药科技有限公司 | Synthesis method of 5-chloroquinoline-4-alcohol |
| CN114746406A (en) * | 2019-12-02 | 2022-07-12 | Fmc公司 | Method for synthesizing 2- (5-isoxazolyl) -phenol |
-
2014
- 2014-10-01 CN CN201410518187.4A patent/CN105523911A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114746406A (en) * | 2019-12-02 | 2022-07-12 | Fmc公司 | Method for synthesizing 2- (5-isoxazolyl) -phenol |
| CN112194622A (en) * | 2020-09-24 | 2021-01-08 | 上海毕得医药科技有限公司 | Synthesis method of 5-chloroquinoline-4-alcohol |
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Application publication date: 20160427 |