CN105732366A - 3-methoxy-4-chlorobenzoic acid and preparation method thereof - Google Patents
3-methoxy-4-chlorobenzoic acid and preparation method thereof Download PDFInfo
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- CN105732366A CN105732366A CN201610171915.8A CN201610171915A CN105732366A CN 105732366 A CN105732366 A CN 105732366A CN 201610171915 A CN201610171915 A CN 201610171915A CN 105732366 A CN105732366 A CN 105732366A
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- methoxyl group
- chlorobenzoic acid
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- hydroxy benzoic
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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
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
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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
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/363—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
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Abstract
The invention discloses 3-methoxy-4-chlorobenzoic acid and a preparation method thereof. The preparation method comprises the following steps: by taking 3-hydroxybenzoic acid as a raw material, firstly halogenating with Cl2, and then directly reacting with monochloromethane for carrying out hydrocarbylation on phenolic hydroxyl group, so that the 3-methoxy-4-chlorobenzoic acid is obtained. The preparation method has the advantages of cheap and available raw materials, simple operation steps, good substituent group location capacity, high product purity and high yield, can be applicable to large-scale industrial production and can produce relatively high economic benefit.
Description
Technical field:
The present invention relates to biomedicine technical field, particularly relate to a kind of 3-methoxyl group-4-chlorine
Benzoic preparation method.
Background technology:
3-methoxyl group-4-chlorobenzoic acid is a kind of to apply quite varied organic synthesis raw material, due to
Its special structure, have uniqueness biological activity, from but highly important medicine intermediate,
The medicine of a lot of different efficacies can be synthesized based on it.
But, Chinese patent about the synthesis of 3-methoxyl group-4-chlorobenzoic acid introduction very
Few.Chinese patent 200810024327.7 describes the synthesis of a kind of 2,6-dimethoxybenzoic acid
Method, utilizes sodium phenide and a phenylene dimethyl ether to react preparation 2,6-Dimethoxyphenyl sodium, afterwards
Again with CO2Reaction prepares 2, and 6-dimethoxybenzoic acid sodium, after further acid out, through heavily tying
Brilliant prepared 2,6-dimethoxybenzoic acid product.Program reaction is gentleer, improves yield,
The quality better of product.But for 3-methoxyl group-4-chlorobenzoic acid, owing to both structures are poor
, the operational reaction conditions and the catalyst choice that not should be noted that in concrete preparation process have very
Big difference.
Summary of the invention:
It is an object of the invention to provide the preparation method of a kind of 3-methoxyl group-4-chlorobenzoic acid, should
Method cheaper starting materials is easy to get, and operating procedure is simple, and the polarization of substituent group is good, the purity of product
Height, productivity is high.It is adapted to large-scale industrial production, higher economic benefit can be produced.
For solving above-mentioned technical problem, the technical solution adopted in the present invention is as follows:
The preparation method of a kind of 3-methoxyl group-4-chlorobenzoic acid, comprises the following steps, with 3-hydroxyl
Yl benzoic acid is raw material, first passes through and Cl2There is halogenating reaction, more anti-with monochloro methane
Phenolic hydroxyl group hydrocarbylation should be prepared 3-methoxyl group-4-chlorobenzoic acid.
Preferred as technique scheme, the concrete operation step of above-mentioned course of reaction is: will
3-hydroxy benzoic acid is dissolved in CS2In, add reactor, in reactor, addition has loaded secondary
The sieve particle of chloric acid and nanogold particle, control temperature is at 50-60 DEG C, with 80-100
Turn/the speed of min stirring, after sustained response 3h, be 9-11 with NaOH regulation pH, add
Monochloro methane, at room temperature after reaction 4h, by CS2It is evaporated off, separates out crystallization, after filtration drying,
It is 3-methoxyl group-4-chlorobenzoic acid crude product, after ethyl alcohol recrystallization, prepares 3-methoxyl group-4-chlorine
Benzoic acid.
Preferred as technique scheme, the molal quantity of described 3-hydroxy benzoic acid and CS2
Volume number than for 0.4-0.6mol/L.
Preferred as technique scheme, described 3-hydroxy benzoic acid with hypochlorous mole
Ratio is 1:2-3.
Preferred as technique scheme, the quality of described nanogold particle and CS2Volume
The ratio of number is 0.02-0.04g/L.
Preferred as technique scheme, described 3-hydroxy benzoic acid rubs with monochloro methane
That ratio is 1:1.2-2.
The method have the advantages that
This programme first carries out halogenating reaction, carries out hydrocarbyl reaction the most again, can be effectively
Control when halogenating reaction, hydrogen on chlorine methoxyl group displacement and produce by-product.Owing to hydroxyl has
Have stronger to electronic effect, and carboxyl has sucting electronic effect, so having during electrophilic addition
Significantly substituent group locating effect, so that it is guaranteed that the by-product in course of reaction is less, product is pure
Degree height, productivity is high.Simultaneously for catalyst nano gold grain in course of reaction, and reaction pressure
Power and the suitable control of temperature, can further improve reaction yield, promote substitution reaction
Polarization.Sum it up, whole production process step is simple, easily operate, in large-scale work
Industry metaplasia is with low cost in producing, and easily implements.
Detailed description of the invention:
In order to be better understood from the present invention, below by embodiment, the present invention is further described,
Embodiment is served only for explaining the present invention, and the present invention will not constitute any restriction.
Embodiment 1
1mol 3-hydroxy benzoic acid is dissolved in 1.7L CS2In, add reactor, to reaction
Still adds and has loaded the hypochlorous sieve particle of 2mol and 0.04g nanogold particle,
Control temperature, at 55 DEG C, stirs with the speed of 80 turns/min, after sustained response 3h, uses NaOH
Regulation pH is 11, adds 1.2mol monochloro methane, at room temperature after reaction 4h, by CS2
It is evaporated off, separates out crystallization, after filtration drying, be 3-methoxyl group-4-chlorobenzoic acid crude product, warp
3-methoxyl group-4-chlorobenzoic acid is prepared after ethyl alcohol recrystallization.
The product purity of output is 82.3%, and productivity is 84.2%.
Embodiment 2
1mol 3-hydroxy benzoic acid is dissolved in 2.0L CS2In, add reactor, to reaction
Still adds and has loaded the hypochlorous sieve particle of 2.5mol and 0.08g nanogold particle,
Control temperature, at 50 DEG C, stirs with the speed of 90 turns/min, after sustained response 3h, uses NaOH
Regulation pH is 10, adds 1.7mol monochloro methane, at room temperature after reaction 4h, by CS2
It is evaporated off, separates out crystallization, after filtration drying, be 3-methoxyl group-4-chlorobenzoic acid crude product, warp
3-methoxyl group-4-chlorobenzoic acid is prepared after ethyl alcohol recrystallization.
The product purity of output is 85.7%, and productivity is 88.3%.
Embodiment 3
1mol 3-hydroxy benzoic acid is dissolved in 2.2L CS2In, add reactor, to reaction
Still adds and has loaded the hypochlorous sieve particle of 3mol and 0.06g nanogold particle,
Control temperature, at 60 DEG C, stirs with the speed of 80 turns/min, after sustained response 3h, uses NaOH
Regulation pH is 9, adds 1.5mol monochloro methane, at room temperature after reaction 4h, by CS2
It is evaporated off, separates out crystallization, after filtration drying, be 3-methoxyl group-4-chlorobenzoic acid crude product, warp
3-methoxyl group-4-chlorobenzoic acid is prepared after ethyl alcohol recrystallization.
The product purity of output is 87.9%, and productivity is 89.9%.
Embodiment 4
1mol 3-hydroxy benzoic acid is dissolved in 2.4L CS2In, add reactor, to reaction
Still adds and has loaded the hypochlorous sieve particle of 2.5mol and 0.07g nanogold particle,
Control temperature, at 60 DEG C, stirs with the speed of 95 turns/min, after sustained response 3h, uses NaOH
Regulation pH is 10, adds 1.3mol monochloro methane, at room temperature after reaction 4h, by CS2
It is evaporated off, separates out crystallization, after filtration drying, be 3-methoxyl group-4-chlorobenzoic acid crude product, warp
3-methoxyl group-4-chlorobenzoic acid is prepared after ethyl alcohol recrystallization.
The product purity of output is 84.6%, and productivity is 91.3%.
Embodiment 5
1mol 3-hydroxy benzoic acid is dissolved in 2.5L CS2In, add reactor, to reaction
Still adds and has loaded the hypochlorous sieve particle of 2mol and 0.05g nanogold particle,
Control temperature, at 50 DEG C, stirs with the speed of 85 turns/min, after sustained response 3h, uses NaOH
Regulation pH is 11, adds 2mol monochloro methane, at room temperature after reaction 4h, by CS2Steam
Remove, separate out crystallization, after filtration drying, be 3-methoxyl group-4-chlorobenzoic acid crude product, through second
3-methoxyl group-4-chlorobenzoic acid is prepared after alcohol recrystallization.
The product purity of output is 83.8%, and productivity is 85.1%.
It can thus be seen that production method of the present invention, simple to operate, productivity is higher,
It is suitable for large-scale commercial production.
Claims (7)
1. the preparation method of a 3-methoxyl group-4-chlorobenzoic acid, it is characterised in that include with
Lower step, with 3-hydroxy benzoic acid as raw material, first passes through and Cl2Generation halogenating reaction, more directly
Connect and react phenolic hydroxyl group hydrocarbylation with monochloro methane, prepare 3-methoxyl group-4-chlorobenzoic acid.
The preparation method of 3-methoxyl group-4-chlorobenzoic acid the most according to claim 1, its
Being characterised by, the concrete operation step of above-mentioned course of reaction is: dissolved by 3-hydroxy benzoic acid
In CS2In, add reactor, add in reactor and loaded hypochlorous sieve particle
And nanogold particle, control temperature at 50-60 DEG C, with 80-100 turn/speed of min stirs
Mix, after sustained response 3h, be 9-11 with NaOH regulation pH, add monochloro methane, in room
After the lower reaction 4h of temperature, by CS2It is evaporated off, separates out crystallization, after filtration drying, be 3-methoxy
Base-4-chlorobenzoic acid crude product, prepares 3-methoxyl group-4-chlorobenzoic acid after ethyl alcohol recrystallization.
The preparation method of 3-methoxyl group-4-chlorobenzoic acid the most according to claim 2, its
It is characterised by, the molal quantity of described 3-hydroxy benzoic acid and CS2Volume number ratio be
0.4-0.6mol/L。
The preparation method of 3-methoxyl group-4-chlorobenzoic acid the most according to claim 2, its
Being characterised by, described 3-hydroxy benzoic acid and hypochlorous mol ratio are 1:2-3.
The preparation method of 3-methoxyl group-4-chlorobenzoic acid the most according to claim 2, its
It is characterised by, the quality of described nanogold particle and CS2The ratio of volume number be
0.02-0.04g/L。
The preparation method of 3-methoxyl group-4-chlorobenzoic acid the most according to claim 2, its
Being characterised by, described 3-hydroxy benzoic acid is 1:1.2-2 with the mol ratio of monochloro methane.
7. a kind of 3-methoxyl group-4-chlorobenzoic acid according to any one of claim 1-6
The preparation-obtained a kind of 3-methoxyl group-4-chlorobenzoic acid of preparation method.
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| CN201610171915.8A CN105732366A (en) | 2016-03-23 | 2016-03-23 | 3-methoxy-4-chlorobenzoic acid and preparation method thereof |
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| CN201610171915.8A CN105732366A (en) | 2016-03-23 | 2016-03-23 | 3-methoxy-4-chlorobenzoic acid and preparation method thereof |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101811942A (en) * | 2010-04-29 | 2010-08-25 | 浙江大学 | Synthesizing method for 1,2-dimethoxy benzene |
| CN102838483A (en) * | 2012-09-20 | 2012-12-26 | 山东潍坊润丰化工有限公司 | Synthesis method of dicamba |
-
2016
- 2016-03-23 CN CN201610171915.8A patent/CN105732366A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101811942A (en) * | 2010-04-29 | 2010-08-25 | 浙江大学 | Synthesizing method for 1,2-dimethoxy benzene |
| CN102838483A (en) * | 2012-09-20 | 2012-12-26 | 山东潍坊润丰化工有限公司 | Synthesis method of dicamba |
Non-Patent Citations (2)
| Title |
|---|
| HIROYUKI AKITA ET AL.: "DETERMINATION OF ABSOLUTE STRUCTURE OF (-)-OUDEMAN SIN B", 《TETRAHEDRON LETTERS》 * |
| THI-HUU NGUYEN ET AL.: "First General, Direct, and Regioselective Synthesis of Substituted Methoxybenzoic Acids by Ortho Metalation", 《J. ORG. CHEM.》 * |
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