CN102924352B - Method for synthesizing 4-mercaptobenzoate - Google Patents
Method for synthesizing 4-mercaptobenzoate Download PDFInfo
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Abstract
The invention relates to a method for preparing 4-mercaptobenzoate represented by a structure formula I, wherein a compound represented by a structure formula II and a C1-C8 alcohol are subjected to a mixing reaction to obtain the 4-mercaptobenzoate. With the method, the high yield 4-mercaptobenzoate compound can be obtained through a one-step reaction.
Description
Technical field
The present invention relates to methodology of organic synthesis, especially a kind of synthetic method of 4-mercaptobenzoates.
Background technology
4-Thiosalicylic acid ester compound is a kind of important fine chemistry intermediate, can be used for pharmaceutical composition, Pestcidal compositions, the preparation of the various materials such as functional materials, research about this compounds is more, the present known five kinds of preparation methods that have: method 1: by the 4-Thiosalicylic acid, under sulfuric acid catalysis, with methanol eddy, reacted 13 hours, the esterification reaction of organic acid of generation, obtain 4-Thiosalicylic acid methyl esters.See Chemical formula 1.
Document: Bulletin of the Chemical Society of Japan, 81 (3), 361-368; 2008
Method 2: under the catalysis of butyllithium, the permutoid reaction that form salt occurs generates 4-sulfydryl phenyl-magnesium-chloride by 4-sulfydryl bromobenzene and methylmagnesium-chloride, then with methyl-chloroformate at base catalyzed reactions, through acidifying, obtain 4-Thiosalicylic acid methyl esters.See Chemical formula 2.Document: Synthetic Communications, 25 (16), 2497-505; 1995
Method 3: by 4-cyano group fluorobenzene and potassium sulphide, DMF, be solvent reaction, in acid adjustment, generate 4,4 '-cyano group diphenyl sulfide and 4-cyano group thiophenol, then generate 4,4 with methyl alcohol, sulfuric acid reaction '-methoxycarbonyl diphenyl sulfide and 4-sulfydryl yl benzoic acid methyl esters.See chemical formula 3.
Document: Synthetic Communications, 25 (16), 2497-505; 1995
Method 4: the alkaline hydrolysis reaction by 4-methoxycarbonyl thiobenzoic acid methyl esters obtains 4-Thiosalicylic acid methyl esters.See chemical formula 4.
Document: Synthetic Communications, 25 (16), 2497-505; 1995
Method 5: the method for Chinese patent CN1139428 is chlorination 4-methylthio-benzoic acid, obtains one, two or three chloro methyl thiobenzoic acids, then with the water reaction that is hydrolyzed, generate the 4-Thiosalicylic acid and see chemical formula 5.
Document: CN1139428
Wherein, m=1,2,3.
Yet all there is shortcoming separately in these methods in application, be unfavorable for industrializing implementation.
The shortcoming of method 1 is, expensive raw material price is not easy to obtain, and reaction can't be carried through to the end, and the aftertreatment purifying is more difficult.Initial feed just has sulfydryl, in reaction and treating processes, does not do protection and is easy to even sulphur impurity of oxidation generation.
The shortcoming of method 2 is, severe reaction conditions is used expensive and not easy-operating butyllithium, and same raw material has sulfydryl, in reaction and aftertreatment, do not do protection and being easy to the company's of generation sulphur impurity.
The shortcoming of method 3 is, raw material is not easy to obtain, and reactions steps is too much, and the reaction final product is mixture, and yield is not high.
The shortcoming of method 4 is that synthesizing of raw material is more complicated.
Method 5: obtain be 4-Thiosalicylic acid and 4,4 '-mixture of carboxyl diphenyl disulfide, wherein the latter's ratio reaches 10-30%, and two kinds of materials are similar because of character, is difficult to separate, and can not obtain pure 4-Thiosalicylic acid; Again the 4-Thiosalicylic acid is carried out in the process of esterification simultaneously, find that its structural sulfydryl can methylate under the acid catalyst effect of esterification, form a large amount of by products, so the method is unsuitable for preparing 4-Thiosalicylic acid ester compound.
As mentioned above, do not have at present a kind of method can be suitable for suitability for industrialized production and obtain economically the 4-mercaptobenzoates.
Summary of the invention
The object of the present invention is to provide a kind of commercial cost low, easy and simple to handle and be beneficial to the method for preparing the 4-mercaptobenzoates of suitability for industrialized production.
The present invention, take the 4-chloro-benzoic acid that is easy to get as starting raw material, with the sodium methyl mercaptide reaction, obtains the 4-methylthio-benzoic acid, then obtains one, two or the trihalomethyl group thiobenzoic acid through halogenation, and last and alcohol reacts and obtains the 4-mercaptobenzoates.As chemical formula 6.
M=1 wherein, 2,3, X is chlorine or bromine, R is saturated alkyl.
The inventive method is as follows:
4-chloro-benzoic acid and sodium hydroxide, sodium methyl mercaptide reacting by heating in the DMF solvent prepares 4-methylthio-benzoic acid sodium, then acid adjustment obtains the 4-methylthio-benzoic acid.
4-methylthio-benzoic acid low temperature or normal temperature halogenation, obtain the compound of structural formula II, and wherein X is chlorine or bromine, and m is 1,2 or 3.Wherein X is preferably chlorine, and m is preferably 3.Halogenation solvent used is not particularly limited, alkane such as hexane, hexanaphthene and heptane, aromatic hydrocarbons such as benzene,toluene,xylene and chlorobenzene, dichlorobenzene, halogenated alkane such as methylene dichloride, ethylene dichloride, chloroform.Preferred ethylene dichloride.
4-halogenated methyl methylthio benzoic acid shown in the structural formula II, obtain structural formula I compound with alcohol compound ROH reaction, and wherein R is saturated alkyl, preferred C1-C8 saturated alkyl.The molar weight of alcohol is 3-30 times of the halogenated methyl methylthio benzoic acid molar weight shown in the structural formula II, is preferably 5-20 times.Temperature of reaction, between 20-100 ℃, is preferably 50-70 ℃.The product that obtains can be by crystallization or distilation.
The inventive method advantage is in single step reaction namely to obtain the mercapto groups ester group group of getting back, and technique is simple, has avoided again sulfydryl that the methyl etherified side reaction of Denging occurs under the acid catalyst effect of esterification.Operating process of the present invention is easy, is easy to realize industrialization, and raw material is easy to get, and yield is higher, almost there is no side reaction.
Specific embodiment
Embodiment 1
In the 100ml reaction flask that thermometer, stirring rake are housed, add 4-chloro-benzoic acid 15.6g, sodium hydroxide 4.4g and DMF78g, stirring at normal temperature adds the solid sodium methyl mercaptide 15.2g of 55% content again after 30 minutes, be warming up to 70 ℃ of reactions, the liquid phase trace analysis, react completely to the 4-chloro-benzoic acid, reacted in 5 hours.After the decompression precipitation, solid is added to the water, and with hydrochloric acid, adjusts PH=2, after the crude product drying that filtration obtains, adds crystallization in ethylene dichloride, obtains 4-methylthio-benzoic acid solid 14.8g, yield 88%.Fusing point: 192～196 ℃.
Embodiment 2
In the 50ml reaction flask that stirring rake, thermometer, dry breather are housed, add 4-methylthio-benzoic acid 5g and ethylene dichloride 60g, keep 10-20 ℃ of temperature to pass into chlorine, the liquid phase trace analysis, complete to raw material reaction, generate the 4-methylthio-benzoic acid.Filter, solid joins in 5% sodium sulfite solution, stirs 30 minutes, filters, and water wash twice, dry and obtain 4-trichloro-methylthio phenylformic acid 7.0g, yield 87.5%.Fusing point: 195.8～196.7 ℃.
Embodiment 3
In the 50ml single port bottle that prolong and the threeway that is connected with the nitrogen ball are housed, add 4-tri-chloro methylthio-benzoic acid 5g and anhydrous methanol 10g, after the nitrogen replacement sealing, keep 60 ℃ of reactions 6 hours.It is complete that liquid phase is followed the tracks of reaction, and decompression precipitation to solvent remains 10g, and decrease temperature crystalline, obtain crystal 2.8g, yield 90%.Fusing point: 33～35 ℃;
1H-NMR (CDCl3) δ: 3.64(s, 1H, SH); 3.89(s, 3H, CH3); 7.27(d, 2H, ArH); (7.87 d, 2H, ArH).
Claims (4)
1. a method for preparing the 4-mercaptobenzoates shown in the structural formula I, adopt fragrant halogenated methyl sulfide and the alcohol compound hybrid reaction shown in the structural formula II to obtain,
Wherein X is chlorine or bromine, and m is 1-3 integer, and R is saturated alkyl.
2. according to the method for claims 1, wherein the X in the structural formula II is the chlorine atom.
3. according to the method for claims 1, wherein alcohol compound is the C1-C8 fatty alcohol.
4. according to the method for claims 3, alcohol used is methyl alcohol.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1063230A (en) * | 1962-01-05 | 1967-03-30 | Merck & Co Inc | (3-indolyl)-aliphatic acids and esters and amides thereof |
| CN87107367A (en) * | 1986-12-12 | 1988-12-28 | Ici美国有限公司 | Preparation method of mercaptobenzoate |
| US5741933A (en) * | 1994-11-24 | 1998-04-21 | Sumitomo Seika Chemicals Co., Ltd. | Process for preparing aromatic or heteroaromatic sulfur compound |
| JPH11269141A (en) * | 1998-03-19 | 1999-10-05 | Sumitomo Seika Chem Co Ltd | Fluorobenzoic acid containing sulfur and its production |
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2011
- 2011-08-10 CN CN2011102278412A patent/CN102924352B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1063230A (en) * | 1962-01-05 | 1967-03-30 | Merck & Co Inc | (3-indolyl)-aliphatic acids and esters and amides thereof |
| CN87107367A (en) * | 1986-12-12 | 1988-12-28 | Ici美国有限公司 | Preparation method of mercaptobenzoate |
| US5741933A (en) * | 1994-11-24 | 1998-04-21 | Sumitomo Seika Chemicals Co., Ltd. | Process for preparing aromatic or heteroaromatic sulfur compound |
| JPH11269141A (en) * | 1998-03-19 | 1999-10-05 | Sumitomo Seika Chem Co Ltd | Fluorobenzoic acid containing sulfur and its production |
Non-Patent Citations (2)
| Title |
|---|
| 战宇等.苯甲酸甲酯的合成及抑菌效果研究.《华南农业大学学报》.2002,(第01期), |
| 苯甲酸甲酯的合成及抑菌效果研究;战宇等;《华南农业大学学报》;20020130(第01期);第82页 * |
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