CN100436396C - New method for synthesizing p-isopropyl benzoic acid - Google Patents
New method for synthesizing p-isopropyl benzoic acid Download PDFInfo
- Publication number
- CN100436396C CN100436396C CNB2006100533302A CN200610053330A CN100436396C CN 100436396 C CN100436396 C CN 100436396C CN B2006100533302 A CNB2006100533302 A CN B2006100533302A CN 200610053330 A CN200610053330 A CN 200610053330A CN 100436396 C CN100436396 C CN 100436396C
- Authority
- CN
- China
- Prior art keywords
- acid
- formula
- cuminic
- pinene
- nopinic
- 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.)
- Expired - Fee Related
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
Abstract
This invention relates to a method for synthesizing cuminic acid. The method comprises: oxidizing beta-pinene with an oxidant to obtain nopinic acid, dehydrating and ring-opening nopinic acid with sulfuric acid to obtain dihydrocumic acid, and catalytically dehydrogenating to obtain cuminic acid. The method uses recycleable natural product of beta-pinene as the raw material, thus has such advantages as wide raw materials, easy operation, low cost and high utility of beta-pinene.
Description
Technical field
The present invention relates to a kind of novel method of synthetic cuminic acid.
Background technology
Cuminic acid is a kind of important fine chemicals, as sanitas and protective material, can be used for the processing of waste water and the corrosion of inhibition automobile antifreezing agent on timber industry; It still is the starting material of no-clean scaling powder and some macromolecular thermosensitive resistor.Particularly cuminic acid has obtained widespread use in chemical industry such as medicine in recent years, it is important chemical material, as 1999 at the anti-diabetic new drug nateglinide of Japan listing be in clinical first selective N HE-1 inhibitor C ariporide (HOE-642) of II phase, all be that raw material synthesizes with the cuminic acid.
The synthetic of cuminic acid is raw material with isopropyl benzene or cymene generally now.Be that raw material synthetic mainly contains following 4 routes: (1) isopropyl benzene chloromethylation with the isopropyl benzene, with the urotropine reaction, obtain cumic aldehyde then, reoxidize and obtain cuminic acid (chemical reagent through hydrolysis, 1988,10 (6): 373-375); (2) the Fu Shi acylation reaction takes place with chloroacetyl chloride in isopropyl benzene under aluminum chloride catalysis, and then with the pyridine salify, acidifying obtains cuminic acid (J.Am.Chem.Soc., 1955,77 (14): 3763-3766) after basic hydrolysis; (3) isopropyl benzene is under aluminum chloride catalysis and the reaction of anhydrous monochloroacetaldehyde, then under alkaline condition through H
2O
2Oxidation generates cuminic acid (Synth.Commun., 1987,17 (4): 457-464) after the acidifying; (4) the Fu Shi acylation reaction takes place with aceticanhydride in isopropyl benzene under aluminum chloride catalysis, again through bromoform reaction, generates cuminic acid (chemical reagent, 2005,27 (2): 107-108) after the acidifying.All there is the separation problem of ortho para isomer in aforesaid method, and selectivity is relatively poor.The synthetic method that with the cymene is raw material is in the diacetyl oxide solvent, makes catalyzer with Cobaltous diacetate, the aerating oxygen oxidation obtain cuminic acid (fine chemistry industry, 1997,14:45-46).Reaction yield is higher, but uses solvent acetic acid acid anhydride price more expensive, and diacetyl oxide reclaims difficulty, pollutes big; And be reflected at and carried out under 90 ℃ 24 hours, energy consumption is big, and the time is long.
China's turps aboundresources, but deep processed product is few, and (β-pinene) never obtain large high value added utilization mostly exports with low price raw material therefrom isolated high purity beta-pinene, be processed into high value fine chemicals and anti-market China, cause flow-away of foreign exchange.With the beta-pinene be raw material through peroxidation, dehydration open loop, dehydrogenation, the operational path of preparation cuminic acid, abundant raw material, cheap, whole process operation is simple, realization easily, selectivity height, cost are low, and industrial prospect is arranged.
Summary of the invention
The object of the present invention is to provide a kind of from the reproducible natural product beta-pinene (method of the synthetic cuminic acid of β-pinene).
The present invention with beta-pinene (β-pinene) is a raw material, through peroxidation, open loop, dehydrogenation, synthetic cuminic acid, process is simple, the raw material cheapness.
The novel method of a kind of synthetic cuminic acid of the present invention, form by following steps:
(1) beta-pinene obtains Nopinic acid (nopinic acid) through the oxygenant oxidation, and wherein beta-pinene is with formula (1) expression, and Nopinic acid is represented with formula (2);
(2) the Nopinic acid open loop of dewatering under effect of sulfuric acid obtains dihydrocumic acid (dihydrocumic acid), and dihydrocumic acid is represented with formula (3);
(3) the dihydrocumic acid catalytic dehydrogenation obtains cuminic acid, and cuminic acid is represented with formula (4).
Formula (1) formula (2) formula (3) formula (4)
Oxidizing reaction in the described step (1) can adopt prior art, as reference US Patent 3520920, reacts in the presence of oxidant potassium permanganate and sodium hydroxide, gets Nopinic acid sodium earlier, obtains Nopinic acid after acidifying, and temperature of reaction is controlled at 20～30 ℃.
Dehydration ring-opening reaction in the described step (2) can adopt prior art, as reference: Herz Wernwe, Wahlborg H J.Acid-catalyzed rearrangement of nopinic acid.J Org Chem, 1962,27:1032-1034.
Dehydrogenation reaction operation in the described step (3) is that dihydrocumic acid is dissolved in the cymene, reflux under the katalysis of catalyst P d-C, and cooling is filtered, and sodium hydroxide solution transfers to strong basicity, and aqueous phase as acidified is separated out white solid to pH 1.Filter, wash with water, get cuminic acid to neutrality.
It is raw material that the inventive method adopts reproducible natural product beta-pinene, abundant raw material, and cheap, method steps is few, and is easy and simple to handle, and cost is low, and industrial prospect is arranged, and can make turps obtain the utilization of high added value.
Embodiment
Following examples are to further specify of the present invention, are not limitations of the present invention.
Embodiment 1
4g sodium hydroxide and 45g potassium permanganate are dissolved in the 450mL water, under vigorous stirring, the 13.6g beta-pinene are added in batches.Keep temperature of reaction at 25～30 ℃ with water-bath, reaction 3～5h, having reacted with potassium permanganate is terminal point.The filtering manganese dioxide precipitate, and water repeatedly washs.Filtrate evaporated under reduced pressure is concentrated into 150mL, and refrigerator is placed and spent the night.Filtration under diminished pressure, and, get white Nopinic acid sodium crystal with a small amount of frozen water washing.
The Nopinic acid sodium of top gained is added in 20mL water and the 25mL dichloromethane mixture, transfer to strongly-acid with the 6mol/L hydrochloric acid soln, tell methylene dichloride, water 7mL washed with dichloromethane three times, merge organic phase, add 5g anhydrous sodium sulfate drying 1h, reduction vaporization gets white product Nopinic acid 6.4g to doing.
The 10g Nopinic acid adds 200mL 20% aqueous sulfuric acid backflow 2h, and cold filtration obtains the 8g dihydrocumic acid.
80g dihydrocumic acid, 4.0g 7.5%Pd-C catalyzer, 100mL cymene are put into the 250mL there-necked flask that thermometer is housed, stirs magneton, prolong, and mixture stirred following back flow reaction after 2 hours, stopped reaction.Cooling elimination catalyzer, catalyzer reclaim with ether washing back and use.Filtrate transfers to strong basicity with 20% sodium hydroxide solution, tells organic phase (recovery), after water adds the dilution of 200mL water, adds hcl acidifying to pH 1, separates out white solid.Filter, wash with water, obtain 56g white cuminic acid solid to neutrality.By fusing point, hydrogen spectrum and mass spectral analysis, confirmation is a cuminic acid.
Embodiment 2
6g sodium hydroxide and 45g potassium permanganate are dissolved in the 350mL water, under vigorous stirring, the 13.6g beta-pinene are added in batches.Keep temperature of reaction at 25～30 ℃ with water-bath, reaction 3～5h, having reacted with potassium permanganate is terminal point.The filtering manganese dioxide precipitate, and water repeatedly washs.Filtrate evaporated under reduced pressure is concentrated into 150mL, and refrigerator is placed and spent the night.Filtration under diminished pressure, and, get white Nopinic acid sodium crystal 6.5g with a small amount of frozen water washing.
10g Nopinic acid sodium adds 200mL 20% aqueous sulfuric acid backflow 2h, and cold filtration obtains the 7g dihydrocumic acid.
80g dihydrocumic acid, 3.0g 7.5%Pd-C catalyzer, 150mL cymene are put into the 250mL there-necked flask that thermometer is housed, stirs magneton, prolong, and mixture stirred following back flow reaction after 2 hours, stopped reaction.Cooling elimination catalyzer, catalyzer reclaim with ether washing back and use.Filtrate transfers to strong basicity with 20% sodium hydroxide solution, tells organic phase (recovery), after water adds the dilution of 200mL water, adds hcl acidifying to pH 1, separates out white solid.Filter, wash with water, obtain 60g white cuminic acid solid to neutrality.By fusing point, hydrogen spectrum and mass spectral analysis, confirmation is a cuminic acid.
Embodiment 3
The fusing point of the product of embodiment 1,2, hydrogen spectrum and mass-spectrometric data are as follows:
Fusing point: 117～119 ℃
The hydrogen spectrum:
1H NMR (CDCl
3): δ=1.26 (d, 6H, J=6.9Hz); 2.97 (m, 1H, J=6.9Hz); 7.30 (d, 2H, J=8.2Hz); 8.02 (d, 2H, J=8.2Hz).
Mass spectrum: MS (m/z): 164 (M
+, 42.0), 149 (100), 131 (22.4), 119 (51.8), 105 (47.2), 91 (18.7), 77 (28.2), 65 (4.8), 51 (7.4), 39 (8.0), 27 (5.0).
Claims (2)
1. the novel method of a synthetic cuminic acid, form by following steps:
(1) beta-pinene obtains Nopinic acid through the oxygenant oxidation, and wherein beta-pinene is with formula (1) expression, and Nopinic acid is represented with formula (2);
(2) the Nopinic acid open loop of dewatering under effect of sulfuric acid obtains dihydrocumic acid, and dihydrocumic acid is represented with formula (3);
(3) the dihydrocumic acid catalytic dehydrogenation obtains cuminic acid, and cuminic acid is represented with formula (4);
Formula (1) formula (2) formula (3) formula (4).
2. according to the novel method of a kind of synthetic cuminic acid of claim 1, the dehydrogenation reaction that it is characterized in that described step (3) is that dihydrocumic acid is dissolved in the cymene, reflux under the katalysis of catalyst P d-C, cooling is filtered, sodium hydroxide solution transfers to strong basicity, aqueous phase as acidified is separated out white solid to pH 1, filters, wash with water to neutrality, get cuminic acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100533302A CN100436396C (en) | 2006-09-11 | 2006-09-11 | New method for synthesizing p-isopropyl benzoic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100533302A CN100436396C (en) | 2006-09-11 | 2006-09-11 | New method for synthesizing p-isopropyl benzoic acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1915959A CN1915959A (en) | 2007-02-21 |
| CN100436396C true CN100436396C (en) | 2008-11-26 |
Family
ID=37737057
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2006100533302A Expired - Fee Related CN100436396C (en) | 2006-09-11 | 2006-09-11 | New method for synthesizing p-isopropyl benzoic acid |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100436396C (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106117037B (en) * | 2016-06-20 | 2018-07-31 | 苏州艾缇克药物化学有限公司 | The preparation method of cumfrey |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3520920A (en) * | 1964-07-06 | 1970-07-21 | Pharmatic Inc | Amine salts of nopinic acid |
| JPH08134013A (en) * | 1994-11-02 | 1996-05-28 | T Hasegawa Co Ltd | Production of 4-alkylbenzonic acids |
| JP2002212132A (en) * | 2001-01-23 | 2002-07-31 | Mitsubishi Gas Chem Co Inc | Method for producing aromatic carboxylic acids |
-
2006
- 2006-09-11 CN CNB2006100533302A patent/CN100436396C/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3520920A (en) * | 1964-07-06 | 1970-07-21 | Pharmatic Inc | Amine salts of nopinic acid |
| JPH08134013A (en) * | 1994-11-02 | 1996-05-28 | T Hasegawa Co Ltd | Production of 4-alkylbenzonic acids |
| JP2002212132A (en) * | 2001-01-23 | 2002-07-31 | Mitsubishi Gas Chem Co Inc | Method for producing aromatic carboxylic acids |
Non-Patent Citations (6)
| Title |
|---|
| 《Acid-Catalyzed Rearrangements of Nopinic Acid》. Werner，Herz，H.，J.，Wahlborg.《J. Org. Chem.》，第27卷. 1962 |
| 《Acid-Catalyzed Rearrangements of Nopinic Acid》. Werner，Herz，H.，J.，Wahlborg.《J. Org. Chem.》，第27卷. 1962 * |
| 《对异丙基苯甲酸合成方法的改进》. 李强等.《化学试剂》，第27卷第2期. 2005 |
| 《对异丙基苯甲酸合成方法的改进》. 李强等.《化学试剂》，第27卷第2期. 2005 * |
| 《用β－蒎烯为原料合成高纯度对异丙基苯酚》. 姜红宇等.《林产化学与工业》，第24卷第4期. 2004 |
| 《用β－蒎烯为原料合成高纯度对异丙基苯酚》. 姜红宇等.《林产化学与工业》，第24卷第4期. 2004 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1915959A (en) | 2007-02-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109384657B (en) | Synthetic method of p-hydroxyacetophenone | |
| CN101830821B (en) | Chemical synthesis method of N-alcoxyloxalyl alanine ester | |
| CN107827730B (en) | Method for synthesizing p-hydroxymethyl benzoic acid by taking p-xylene (PX) as raw material | |
| CN103086964A (en) | Preparation method of 6-bromine-2-pyridine methyl formate | |
| CN100436396C (en) | New method for synthesizing p-isopropyl benzoic acid | |
| CN102898328B (en) | Synthesis method of diethyl azodicarboxylate and intermediate of diethyl azodicarboxylate | |
| CN103553878B (en) | A kind of novel preparation method of cyclohexyl phenol class liquid crystal intermediates compound | |
| CN110526806B (en) | Method for preparing acetophenone compounds by catalyzing phenylacetylene with solid acid | |
| CN105601529B (en) | The synthetic method of pretilachlor | |
| CN112961030B (en) | Method for catalytic synthesis of 4- (trans-4-alkyl cyclohexyl) cyclohexanone | |
| CN112876359B (en) | Preparation method of dimethyl 2, 6-naphthalene dicarboxylate | |
| JPS6148492B2 (en) | ||
| CN101270041A (en) | Catalytic oxidation method of preparing a-methyl cinnamic acid | |
| CN111187146B (en) | Process for producing 2-methyl-3-buten-2-ol | |
| CN102992973B (en) | Industrial method for synthesizing p-hydroxy benzaldehyde in jet flow manner | |
| CN101747223B (en) | Method for preparing N-formanilide | |
| CN110128347A (en) | A kind of synthetic method of 1- methyl-1 H- indazole -6- formic acid | |
| CN103819418A (en) | Method for synthesizing carfentrazone-ethyl and carfentrazone-ethyl intermediate | |
| JPH03190837A (en) | Production of tertiary-butylbenzaldehyde isomer mixture | |
| CN101157627A (en) | New method for synthesizing nateglinide | |
| EP0461154B1 (en) | Iodo compounds | |
| CN1204105C (en) | Method for preparing dihydroxy-benzene | |
| US4384137A (en) | Process for preparation of hydroxyarylglyoxylic acids and their alkaline salts, and application thereof to preparation of sodium parahydroxyphenylglyoxylate | |
| CN111018695A (en) | Preparation method of tritenzoic acid | |
| CN117658864A (en) | Preparation method of key intermediate of sabatier |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20081126 Termination date: 20100911 |