CN105712894A - 3-methoxy-4-aminobenzoic acid and preparing method thereof - Google Patents
3-methoxy-4-aminobenzoic acid and preparing method thereof Download PDFInfo
- Publication number
- CN105712894A CN105712894A CN201610171928.5A CN201610171928A CN105712894A CN 105712894 A CN105712894 A CN 105712894A CN 201610171928 A CN201610171928 A CN 201610171928A CN 105712894 A CN105712894 A CN 105712894A
- Authority
- CN
- China
- Prior art keywords
- methoxyl group
- paba
- nitrobenzoic acid
- preparation
- hydroxyl
- 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.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/04—Formation of amino groups in compounds containing carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention aims at providing a 3-methoxy-4-aminobenzoic acid and a preparing method thereof. The preparing method includes the steps that 3-hydroxy-4-nitrobenzoic acid serves as a raw material and is reacted with bromomethane to generate 3-methoxy-4-nitrobenzoic acid, active carbon serves as a reducing agent, the pressure and the temperature are controlled, and the 3-methoxy-4-aminobenzoic acid is prepared. According to the preparing method, the suitable catalyst is used, the reaction temperature and the reaction pressure are controlled, the purity and the yield of the product are increased, and the whole procedure is low in cost, convenient to operate and suitable for large-scale industrial production.
Description
Technical field:
The present invention relates to biomedicine technical field, particularly relate to a kind of 3-methoxyl group-4-ammonia
Yl benzoic acid and preparation method thereof.
Background technology:
Para-amino benzoic acid is a kind of important organic synthesis intermediate, due to the biology of its uniqueness
Activity, serves the most prominent effect in medicine synthesizes.It is synthesis NSAID (non-steroidal anti-inflammatory drug)
The important intermediate of felbinac, felbinac is pacified in terms for the treatment of joint disease and myalgia
Overall height is imitated.Additionally, the derivant of para-amino benzoic acid or wide variety of anesthetis, permissible
Alleviate the symptom such as anemia, diarrhoea.Meanwhile, the derivant of para-amino benzoic acid can be also used for controlling
Treat the diseases such as rickets, arthritis, rheumatism and tuberculosis.3 methoxy substitutions among these
Para-amino benzoic acid medicine synthesize in also play highly important effect.
3-methoxyl group-PABA is prepared the fewer of introduction by domestic patent document,
Chinese patent 200810024327.7 describes the synthesis side of a kind of 2,6-dimethoxybenzoic acid
Method, utilizes sodium phenide and a phenylene dimethyl ether to react preparation 2,6-Dimethoxyphenyl sodium, the most again
With CO2Reaction prepares 2, and 6-dimethoxybenzoic acid sodium, after further acid out, through recrystallization
Prepare 2,6-dimethoxybenzoic acid product.Program reaction is gentleer, improves yield,
The quality better of product.But for 3-methoxyl group-PABA, due to both structures
Difference, the operational reaction conditions and the catalyst choice that should be noted that in concrete preparation process have
The biggest difference.
Summary of the invention:
It is an object of the invention to provide a kind of 3-methoxyl group-PABA and preparation method thereof,
The method utilizes suitable catalyst, controls reaction temperature and pressure, improve the purity of product with
And yield, whole process cost is low, simple to operate, is suitable for industrialized large-scale production.
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-PABA, comprises the following steps, with 3-
Hydroxyl-4-nitrobenzoic acid is raw material, first reacts with bromomethane, generates 3-methoxyl group-4-
Nitrobenzoic acid, then be reducing agent with activated carbon, control pressure and temp, prepare 3-methoxyl group
-PABA.
Preferred as technique scheme, the concrete operation step of described course of reaction is:
1,3-hydroxyl-4-nitrobenzoic acid is dissolved in dehydrated alcohol in addition reactor,
Being added thereto to NaOH again, stirring makes it dissolve, drips bromomethane the most wherein, controls
Temperature is at 40-60 DEG C, and after sustained response 2h, adding dilute hydrochloric acid regulation pH is 5-7, adds
Saturated aqueous common salt, separates out crystallization i.e. 3-methoxyl group-4-nitrobenzoic acid；
2, the 3-methoxyl group-4-nitrobenzoic acid prepared in previous step is dissolved in anhydrous THF
In, add carbon nano-particle, and be passed through hydrogen with the speed of 60-80mL/min, regulate pressure,
And control temperature at 120-150 DEG C, after sustained response 2h, temperature is reduced, filter, be evaporated off
THF obtains yellow crystal, with the petrol ether/ethyl acetate mixture that mass fraction is 5:1
Carry out being recrystallized to give sterling 3-methoxyl group-PABA.
Preferred as technique scheme ,-4-the nitrobenzoic acid of 3-hydroxyl described in step 1
The volume ratio of molal quantity and dehydrated alcohol be 0.04-0.06mol/L.
Preferred as technique scheme, the quality of NaOH described in step 1 and anhydrous second
The volume ratio of alcohol is 0.8-1.2g/L.
Preferred as technique scheme ,-4-the nitrobenzoic acid of 3-hydroxyl described in step 1
It is 1:1.5-2 with the mol ratio of bromomethane.
Preferred as technique scheme ,-4-the nitrobenzoic acid of 3-hydroxyl described in step 1
Molal quantity and step 2 described in the volume ratio of THF be 0.05-0.07mol/L.
Preferred as technique scheme, the quality of carbon nano-particle described in step 2 with
The volume ratio of THF is 0.2-0.5g/L.
Preferred as technique scheme, pressure described in step 2 is 0.15-1Mpa.
The method have the advantages that
Utilizing 3-hydroxyl-4-nitrobenzoic acid is raw material, utilizes the reproducibility of carbon nano-particle,
By regulation pressure and temperature, reduction nitro.Whole course of reaction by-product is few, and is prone to
Separating, the product purity obtained is high, and productivity is high.And course of reaction step is less, operation letter
Single, the requirement to reaction environment condition is gentle, is suitable for industrialized large-scale production.
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-hydroxyl-4-nitrobenzoic acid is dissolved in 17L dehydrated alcohol addition reaction
In still, then being added thereto to 20gNaOH, stirring makes it dissolve, and drips 1.5mol the most wherein
Bromomethane, control temperature is at 40 DEG C, and after sustained response 2h, adding dilute hydrochloric acid regulation pH is
5, add saturated aqueous common salt, separate out crystallization i.e. 3-methoxyl group-4-nitrobenzoic acid；Will preparation
3-methoxyl group-4-nitrobenzoic acid be dissolved in the anhydrous THF of 15L, add 7g carbon nanometer
Granule, and it is passed through hydrogen with the speed of 60mL/min, regulation pressure is 0.5MPa, and controls
Temperature is at 120 DEG C, after sustained response 2h, temperature is reduced, filters, THF is evaporated off and obtains
Yellow crystal, is carrying out recrystallization with the petrol ether/ethyl acetate mixture that mass fraction is 5:1
Obtain sterling 3-methoxyl group-PABA.
The purity of the product prepared is 80.2%, and productivity is 87.4%.
Embodiment 2
1mol 3-hydroxyl-4-nitrobenzoic acid is dissolved in 18L dehydrated alcohol addition reaction
In still, then being added thereto to 16.2gNaOH, stirring makes it dissolve, and drips the most wherein
1.6mol bromomethane, control temperature is at 45 DEG C, after sustained response 2h, adds dilute hydrochloric acid regulation
PH is 6, adds saturated aqueous common salt, separates out crystallization i.e. 3-methoxyl group-4-nitrobenzoic acid；Will
3-methoxyl group-4-the nitrobenzoic acid of preparation is dissolved in the anhydrous THF of 17L, adds 5g carbon
Nano-particle, and it is passed through hydrogen with the speed of 65mL/min, regulation pressure is 1MPa, and
Control temperature is at 120 DEG C, after sustained response 2h, temperature is reduced, filters, THF is evaporated off
Obtain yellow crystal, carry out weight with the petrol ether/ethyl acetate mixture that mass fraction is 5:1
Crystallization obtains sterling 3-methoxyl group-PABA.
The purity of the product prepared is 82.3%, and productivity is 89.9%.
Embodiment 3
1mol 3-hydroxyl-4-nitrobenzoic acid is dissolved in 20L dehydrated alcohol addition reaction
In still, then being added thereto to 16gNaOH, stirring makes it dissolve, and drips 1.7mol the most wherein
Bromomethane, control temperature is at 55 DEG C, and after sustained response 2h, adding dilute hydrochloric acid regulation pH is
6, add saturated aqueous common salt, separate out crystallization i.e. 3-methoxyl group-4-nitrobenzoic acid；Will preparation
3-methoxyl group-4-nitrobenzoic acid be dissolved in the anhydrous THF of 16L, add 6.5g carbon receive
Rice grain, and it is passed through hydrogen with the speed of 70mL/min, regulation pressure is 0.2MPa, and controls
Temperature processed is at 120 DEG C, after sustained response 2h, temperature is reduced, filters, THF is evaporated off and obtains
To yellow crystal, heavily tying with the petrol ether/ethyl acetate mixture that mass fraction is 5:1
Crystalline substance obtains sterling 3-methoxyl group-PABA.
The purity of the product prepared is 86.8%, and productivity is 92.7%.
Embodiment 4
1mol 3-hydroxyl-4-nitrobenzoic acid is dissolved in 22L dehydrated alcohol addition reaction
In still, then being added thereto to 22gNaOH, stirring makes it dissolve, and drips 1.9mol the most wherein
Bromomethane, control temperature is at 55 DEG C, and after sustained response 2h, adding dilute hydrochloric acid regulation pH is
7, add saturated aqueous common salt, separate out crystallization i.e. 3-methoxyl group-4-nitrobenzoic acid；Will preparation
3-methoxyl group-4-nitrobenzoic acid be dissolved in the anhydrous THF of 18L, add 4g carbon nanometer
Granule, and it is passed through hydrogen with the speed of 75mL/min, regulation pressure is 0.75MPa, and controls
Temperature processed is at 140 DEG C, after sustained response 2h, temperature is reduced, filters, THF is evaporated off and obtains
To yellow crystal, heavily tying with the petrol ether/ethyl acetate mixture that mass fraction is 5:1
Crystalline substance obtains sterling 3-methoxyl group-PABA.
The purity of the product prepared is 83.4%, and productivity is 88.7%.
Embodiment 5
1mol 3-hydroxyl-4-nitrobenzoic acid is dissolved in 25L dehydrated alcohol addition reaction
In still, then being added thereto to 20gNaOH, stirring makes it dissolve, and drips 2.0mol the most wherein
Bromomethane, control temperature is at 45 DEG C, and after sustained response 2h, adding dilute hydrochloric acid regulation pH is
6, add saturated aqueous common salt, separate out crystallization i.e. 3-methoxyl group-4-nitrobenzoic acid；Will preparation
3-methoxyl group-4-nitrobenzoic acid be dissolved in the anhydrous THF of 20L, add 6g carbon nanometer
Granule, and it is passed through hydrogen with the speed of 80mL/min, regulation pressure is 1MPa, and controls
Temperature is at 150 DEG C, after sustained response 2h, temperature is reduced, filters, THF is evaporated off and obtains
Yellow crystal, is carrying out recrystallization with the petrol ether/ethyl acetate mixture that mass fraction is 5:1
Obtain sterling 3-methoxyl group-PABA.
The purity of the product prepared is 80.2%, and productivity is 87.4%.
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 (9)
1. the preparation method of 3-methoxyl group-PABA, it is characterised in that include
Following steps, with 3-hydroxyl-4-nitrobenzoic acid as raw material, first react with bromomethane, raw
Become 3-methoxyl group-4-nitrobenzoic acid, then be reducing agent with activated carbon, control pressure and temp,
Prepare 3-methoxyl group-PABA.
The preparation method of 3-methoxyl group-PABA the most according to claim 1,
It is characterized in that, the concrete operation step of described course of reaction is:
(1) 3-hydroxyl-4-nitrobenzoic acid is dissolved in dehydrated alcohol in addition reactor,
Being added thereto to NaOH again, stirring makes it dissolve, drips bromomethane the most wherein, controls
Temperature is at 40-60 DEG C, and after sustained response 2h, adding dilute hydrochloric acid regulation pH is 5-7, adds
Saturated aqueous common salt, separates out crystallization i.e. 3-methoxyl group-4-nitrobenzoic acid；
(2) the 3-methoxyl group-4-nitrobenzoic acid prepared in previous step is dissolved in anhydrous THF
In, add carbon nano-particle, and be passed through hydrogen with the speed of 60-80mL/min, regulate pressure,
And control temperature at 120-150 DEG C, after sustained response 2h, temperature is reduced, filter, be evaporated off
THF obtains yellow crystal, with the petrol ether/ethyl acetate mixture that mass fraction is 5:1
Carry out being recrystallized to give sterling 3-methoxyl group-PABA.
The preparation method of 3-methoxyl group-PABA the most according to claim 2,
It is characterized in that, the molal quantity of-4-nitrobenzoic acid of 3-hydroxyl described in step 1 and anhydrous second
The volume ratio of alcohol is 0.04-0.06mol/L.
The preparation method of 3-methoxyl group-PABA the most according to claim 2,
It is characterized in that, the quality of NaOH described in step 1 with the volume ratio of dehydrated alcohol is
0.8-1.2g/L。
The preparation method of 3-methoxyl group-PABA the most according to claim 2,
It is characterized in that ,-4-the nitrobenzoic acid of 3-hydroxyl described in step 1 and the mol ratio of bromomethane
For 1:1.5-2.
The preparation method of 3-methoxyl group-PABA the most according to claim 2,
It is characterized in that, the molal quantity of-4-nitrobenzoic acid of 3-hydroxyl described in step 1 and step 2
Described in the volume ratio of THF be 0.05-0.07mol/L.
The preparation method of 3-methoxyl group-PABA the most according to claim 2,
It is characterized in that, the quality of carbon nano-particle described in step 2 with the volume ratio of THF is
0.2-0.5g/L。
The preparation method of 3-methoxyl group-PABA the most according to claim 2,
It is characterized in that, pressure described in step 2 is 0.15-1Mpa.
9. prepared by the preparation method of the 3-methoxyl group-PABA described in claim 1-8
3-methoxyl group-the PABA obtained.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610171928.5A CN105712894A (en) | 2016-03-23 | 2016-03-23 | 3-methoxy-4-aminobenzoic acid and preparing method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610171928.5A CN105712894A (en) | 2016-03-23 | 2016-03-23 | 3-methoxy-4-aminobenzoic acid and preparing method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105712894A true CN105712894A (en) | 2016-06-29 |
Family
ID=56159044
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610171928.5A Pending CN105712894A (en) | 2016-03-23 | 2016-03-23 | 3-methoxy-4-aminobenzoic acid and preparing method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105712894A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101284778A (en) * | 2008-05-19 | 2008-10-15 | 江苏中丹集团股份有限公司 | Synthetic method of 2, 6-dimethoxy benzoic acid |
| CN102285927A (en) * | 2011-06-29 | 2011-12-21 | 青岛康地恩药业股份有限公司 | Method for preparing ponazuril serving as anticoccidiosis medicament |
| WO2015003816A2 (en) * | 2013-07-12 | 2015-01-15 | Helmholtz-Zentrum für Infektionsforschung GmbH | Cystobactamides |
-
2016
- 2016-03-23 CN CN201610171928.5A patent/CN105712894A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101284778A (en) * | 2008-05-19 | 2008-10-15 | 江苏中丹集团股份有限公司 | Synthetic method of 2, 6-dimethoxy benzoic acid |
| CN102285927A (en) * | 2011-06-29 | 2011-12-21 | 青岛康地恩药业股份有限公司 | Method for preparing ponazuril serving as anticoccidiosis medicament |
| WO2015003816A2 (en) * | 2013-07-12 | 2015-01-15 | Helmholtz-Zentrum für Infektionsforschung GmbH | Cystobactamides |
Non-Patent Citations (3)
| Title |
|---|
| KWAN-YOUNG JUNG等: "Perturbation of the c-Myc-Max Protein-Protein Interaction via Synthetic α-Helix Mimetics", 《J. MED. CHEM.》 * |
| S. R. ADAMS等: "Biologically Useful Chelators That Take Up Ca2+ upon Illumination", 《J.AM.CHEM.SOC.》 * |
| 苏州丝绸工学院染整教研室: "《丝织物染整工艺学 上》", 31 December 1984, 北京：纺织工业出版社 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN112062712A (en) | Preparation method of 2- (5-bromo-3-methylpyridin-2-yl) acetic acid hydrochloride | |
| CN105618126B (en) | A kind of catalyst of high activity preparing dimethyl carbonate and its preparation method and application | |
| CN105968008A (en) | Synthetic method of trans-4-acetoxyl-2-methyl-2-butene-1-aldehyde | |
| CN101993447A (en) | Method for synthesizing Prasugrel artificially | |
| CN103588765B (en) | The synthetic method of the synthetic method of Azilsartan or its salt and intermediate and intermediate | |
| CN105712894A (en) | 3-methoxy-4-aminobenzoic acid and preparing method thereof | |
| CN108658733B (en) | Preparation method of 2,4, 6-triiodoresorcinol | |
| CN102557967A (en) | Preparation method of ambroxol hydrochloride | |
| CN110437125A (en) | A kind of preparation method of Tezacaftor intermediate II | |
| CN103102324A (en) | Preparation method of leucongen | |
| CN113329994B (en) | Method for continuously preparing 5-cyanodiol | |
| CN108084238A (en) | A kind of preparation method of canrenone intermediate | |
| CN113816837A (en) | Synthesis method of 4,4' -dimethoxy triphenylchloromethane | |
| CN107129472B (en) | A kind of technique preparing acetazolamide intermediate | |
| CN102942553B (en) | Preparation method for 6-carboxylfluorescein | |
| CN105085526B (en) | A kind of improved silaenafil preparation method | |
| CN101747316B (en) | High-purity strontium ranelate and preparation method thereof | |
| CN112645945A (en) | Preparation method of Wumei ammonium bromide intermediate | |
| CN107827786A (en) | The production method of N methyl N isopropyl amido sulfonamide | |
| CN103896859A (en) | Process for synthesizing cytosine | |
| CN103664700B (en) | A kind of 1-ethyl-3-(3-dimethylaminopropyl) synthetic method of-carbodiimides methiodide salt | |
| CN113354522B (en) | Improved synthesis method of phorone | |
| CN115785182B (en) | Preparation method of 1 alpha-hydroxycholesterol | |
| CN111187223B (en) | Synthetic method of linagliptin intermediate 2-chloromethyl-4-methyl quinazoline | |
| CN104370807B (en) | The synthetic method of a kind of 6-hydroxyl-5-nitronicotinic acid and process for separation and purification thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20160629 |