CN104370766B - The method of industrialized production isophthalic acid derivatives - Google Patents
The method of industrialized production isophthalic acid derivatives Download PDFInfo
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- CN104370766B CN104370766B CN201310352349.7A CN201310352349A CN104370766B CN 104370766 B CN104370766 B CN 104370766B CN 201310352349 A CN201310352349 A CN 201310352349A CN 104370766 B CN104370766 B CN 104370766B
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- sylvite
- potassium formate
- pas
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- WUBBRNOQWQTFEX-UHFFFAOYSA-N Nc(cc1)cc(O)c1C(O)=O Chemical compound Nc(cc1)cc(O)c1C(O)=O WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 2
- 0 *C(CC(O)=CC(N)=C)C(O)=O Chemical compound *C(CC(O)=CC(N)=C)C(O)=O 0.000 description 1
- BLBBHFYLFBKYNA-UHFFFAOYSA-N Nc(c(C(O)=O)c1)cc(O)c1C(O)=O Chemical compound Nc(c(C(O)=O)c1)cc(O)c1C(O)=O BLBBHFYLFBKYNA-UHFFFAOYSA-N 0.000 description 1
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Abstract
A kind of method of industrialized production Formulas I, using PAS, sylvite and carbon dioxide as raw material, reacts and is carried out in the potassium formate of melting, polysubstituted phenyl ring is re-introduced into carboxyl under mild conditions.Compared with prior art, the present invention is reacted at ambient pressure, production operation safety, it is not necessary to expensive autoclave, saved cost；And while reaction pressure is reduced, the time required to need not only increasing reaction, the reaction time is substantially reduced on the contrary
Description
Technical field
The invention belongs to a kind of chemical synthesis process of isophthalic acid derivatives, more particularly to a kind of industrialized production 4-
The method of amino -6- hydroxyls-M-phthalic acid.
Background technology
4- amino -6- hydroxyls-M-phthalic acid（Formulas I）It is a kind of Phthalic acids compound, is one kind weight in pharmacy
Want intermediate.In its structure, phenyl ring is substituted by carboxyl, amino and hydroxyl four, and two carboxyls are in meta.
In the prior art, can be using Formula II PAS as raw material, by being re-introduced into another carboxyl on its phenyl ring
And obtain compound of formula I.
However, the carboxylation reaction on phenyl ring is not too much easily carried out.Except the relatively simple material of some structures such as unit or
Polyhydric phenols can react outer under low pressure or normal pressure, and being typically necessary can succeed under very high pressure.If on phenyl ring also
There are multiple substituents, then can bring the problem of more complicated.
Using Formula II as raw material prepare compound of formula I there is also it is above-mentioned the problem of.Due to raw material and amino, hydroxyl, carboxyl
The factor such as trisubstituted benzene derivative, its caused steric hindrance and electronic effect so that carry out carboxylation tool at the ortho position of amino
There is certain difficulty.4- amino -6- hydroxyls-M-phthalic acid is synthesized in the prior art（Formulas I）When being all long under elevated pressure conditions
Between reacted.
For example, US2555736A discloses the method using Formula II PAS as raw material formula I, it uses carbonic acid
Potassium and CO2Gas is reactant, in aqueous, is reacted 12 hours under the high pressure of 15 atmospheric pressure.
According to prior art reaction condition carry out the shortcomings that be：Prolonged reaction under high pressure is relatively hazardous, and consuming energy,
It is uneconomical, production efficiency and scale are limited, thus be difficult to be produced under the conditions of industrialization is extensive.
Therefore, it is necessary to change reaction condition, there is provided a kind of suitable industrialized production 4- amino -6- hydroxyls-isophthalic diformazan
The method of acid.
The content of the invention
The purpose of the present invention is by changing reaction condition, there is provided a kind of suitable industrialized production 4- amino -6- hydroxyls -
Phthalic acid（Formulas I）Method.Direct purpose is the method for synthesis type I under a kind of normal pressure of research.
The present inventor has carried out following change by exploring to reaction condition：
First, have selected suitable reaction medium, react and carried out in the potassium formate of melting, make polysubstituted phenyl ring can be
Carboxyl is re-introduced under conditions of gentle；
Carried out at ambient pressure second, reacting；
Three are the reduction of the reaction time, it is only necessary to 1-6 hours；
Fourth, with saleratus and/or potassium carbonate, and carbon dioxide is reactant；
The post processing of reaction is easy, and reaction is completed to add suitable solvent in backward reaction system（Such as DMSO）Enable product
After scattered, add water and ethyl acetate carries out extracting and demixing, phase of fetching water, product can be separated out after adding acid.
The technical scheme is that：A kind of industrialized production 4- amino -6- hydroxyls-M-phthalic acid（Formulas I）Method,
Using Formula II, sylvite and carbon dioxide as raw material：
It is characterized in that：
1）Reaction is carried out at ambient pressure；
2）Reaction medium is the potassium formate of melting；
3）The sylvite is saleratus and/or potassium carbonate；
4）Reaction time is 1-6 hours.
In this method, every mole of PAS uses 2-30 moles of potassium formate；
Every mole of PAS uses 1-5 moles of sylvite；
As long as reaction temperature can guarantee that potassium formate is in molten condition, generally 160-200 DEG C.
It is an advantage of the invention that：
1st, production operation safety
Avoid security risk caused by reaction under high pressure.
2nd, production equipment is simple, economical
Synthesis under normal pressure does not have to the expensive autoclave of purchase, has saved cost.
3rd, efficiency is improved
The present invention need not only increase the time required for reaction, contract significantly on the contrary while reaction pressure is reduced
The short reaction time.
Embodiment
Technical scheme is illustrated by way of examples below, but not formed to technical scheme
Limitation.
Embodiment 1
In three mouthfuls of reaction bulbs, PAS 30.6g, potassium carbonate 27.6g, potassium formate 184.9g are added, is mixed
Close uniformly, be passed through CO2 gas displacements and continue to be passed through CO2 under 1bar pressure twice afterwards, reaction system is heated to 190-195
DEG C, potassium formate melts completely, reacts 2.5 hours at this temperature.After the completion of reaction, DMSO is added into reaction system, is stirred
After pulp, add water and ethyl acetate carries out extracting and demixing, discard organic phase, aqueous phase is adjusted to acidity with 1M watery hydrochloric acid, analysis
Go out solid, filter, dry, obtain 4- amino -6- hydroxyls-M-phthalic acid 38.0g.
Embodiment 2
In three mouthfuls of reaction bulbs, PAS 25.0g, potassium carbonate 33.8g, saleratus 8.1g, first are added
Sour potassium 26.9g, be well mixed, be passed through CO2 gas displacements and continue to be passed through CO2 under 1bar pressure twice afterwards, by reaction system plus
To 185-190 DEG C, potassium formate melts heat completely, reacts 3.5 hours at this temperature.After the completion of reaction, add into reaction system
Enter DMSO, after stirring pulp, add water and ethyl acetate carries out extracting and demixing, discard organic phase, aqueous phase 1M watery hydrochloric acid
Acidity is adjusted to, separates out solid, is filtered, dries, obtains 4- amino -6- hydroxyls-M-phthalic acid 31.0g.
Embodiment 3
In three mouthfuls of reaction bulbs, PAS 20.1g, potassium carbonate 35.9g, saleratus 13.8g, first are added
Sour potassium 65.9g, be well mixed, be passed through CO2 gas displacements and continue to be passed through CO2 under 1bar pressure twice afterwards, by reaction system plus
To 171-178 DEG C, potassium formate melts heat completely, reacts 1 hour at this temperature.After the completion of reaction, added into reaction system
DMSO, after stirring pulp, add water and ethyl acetate carries out extracting and demixing, discard organic phase, aqueous phase is adjusted with 1M watery hydrochloric acid
To acidity, solid is separated out, is filtered, dries, obtains 4- amino -6- hydroxyls-M-phthalic acid 24.0g.Embodiment 4
In three mouthfuls of reaction bulbs, PAS 10.5g, potassium carbonate 19.0g, potassium formate 173.0g are added, is mixed
Close uniformly, be passed through CO2 gas displacements and continue to be passed through CO2 under 1bar pressure twice afterwards, reaction system is heated to 160-170
DEG C, potassium formate melts completely, reacts 4.5 hours at this temperature.After the completion of reaction, DMSO is added into reaction system, is stirred
After pulp, add water and ethyl acetate carries out extracting and demixing, discard organic phase, aqueous phase is adjusted to acidity with 1M watery hydrochloric acid, analysis
Go out solid, filter, dry, obtain 4- amino -6- hydroxyls-M-phthalic acid 12.2g.
Embodiment 5
In three mouthfuls of reaction bulbs, PAS 17.0g, saleratus 55.1g, potassium formate 192.4g are added,
It is well mixed, it is passed through CO2 gas displacements and continues to be passed through CO2 under 1bar pressure twice afterwards, reaction system is heated to 194-200
DEG C, potassium formate melts completely, reacts 6 hours at this temperature.After the completion of reaction, DMSO is added into reaction system, is stirred into
After pulpous state, add water and ethyl acetate carries out extracting and demixing, discard organic phase, aqueous phase is adjusted to acidity with 1M watery hydrochloric acid, separates out
Solid, filter, dry, obtain 4- amino -6- hydroxyls-M-phthalic acid 20.9g.
Claims (5)
- A kind of 1. industrial method that Formulas I is produced using Formula II PAS, sylvite and carbon dioxide as raw material：It is characterized in that：1) reaction is carried out at ambient pressure；2) reaction medium is the potassium formate of melting；3) sylvite is saleratus, or saleratus and potassium carbonate；4) reaction time is 1-6 hours；5) reaction temperature is in the temperature of molten condition to ensure potassium formate in reaction system.
- 2. the method described in claim 1, the dosage of the potassium formate are：Every mole of PAS uses 2-30 moles Potassium formate.
- 3. the method described in claim 1, the dosage of the sylvite are：Every mole of PAS uses 1-5 moles of potassium Salt.
- 4. any described method in claim 1-3, the sylvite is saleratus.
- 5. the method described in claim 1, the post-processing approach of reaction are：Reaction is completed to add DMSO in backward reaction system, After stirring pulp, add water and ethyl acetate carries out extracting and demixing, discard organic phase, aqueous phase is adjusted to acidity with acid, separates out Solid, filter, dry.
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| CN201310352349.7A CN104370766B (en) | 2013-08-14 | 2013-08-14 | The method of industrialized production isophthalic acid derivatives |
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| CN104370766A CN104370766A (en) | 2015-02-25 |
| CN104370766B true CN104370766B (en) | 2018-03-27 |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH273250A (en) * | 1949-02-14 | 1951-01-31 | Cilag Ag | Process for the preparation of a new derivative of p-amino-salicylic acid. |
| US2555736A (en) * | 1949-03-24 | 1951-06-05 | Cilag Ltd | 2-hydroxy, 4-amino isophthalic acid and a process for the production thereof |
| GB668674A (en) * | 1949-03-24 | 1952-03-19 | Cilag Ltd | 4-amino-2-hydroxybenzene-1.5-dicarboxylic acid and a process for the production thereof |
| WO1997017315A1 (en) * | 1995-11-10 | 1997-05-15 | Akzo Nobel N.V. | Process for dicarboxylating dihydric phenols |
| CN101613270A (en) * | 2009-07-30 | 2009-12-30 | 浙江大学 | A kind of salicylic preparation method |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002308839A (en) * | 2001-04-10 | 2002-10-23 | Daito Chemix Corp | Method for producing 2-amino-4-hydroxybenzoic acid |
-
2013
- 2013-08-14 CN CN201310352349.7A patent/CN104370766B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH273250A (en) * | 1949-02-14 | 1951-01-31 | Cilag Ag | Process for the preparation of a new derivative of p-amino-salicylic acid. |
| US2555736A (en) * | 1949-03-24 | 1951-06-05 | Cilag Ltd | 2-hydroxy, 4-amino isophthalic acid and a process for the production thereof |
| GB668674A (en) * | 1949-03-24 | 1952-03-19 | Cilag Ltd | 4-amino-2-hydroxybenzene-1.5-dicarboxylic acid and a process for the production thereof |
| WO1997017315A1 (en) * | 1995-11-10 | 1997-05-15 | Akzo Nobel N.V. | Process for dicarboxylating dihydric phenols |
| CN101613270A (en) * | 2009-07-30 | 2009-12-30 | 浙江大学 | A kind of salicylic preparation method |
Non-Patent Citations (2)
| Title |
|---|
| Kolbe-Schmitt制备多羟基对苯二甲酸类化合物中甲酸钾的回收利用研究;王坤 等;《绿色科技》;20120525(第5期);第167-168页 * |
| 芳酸的合成;王晓君 等;《化工进展》;20110915;第30卷(第S1期);第606-609页 * |
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