CN106631911A - Method for synthesizing cis-tritosylate - Google Patents
Method for synthesizing cis-tritosylate Download PDFInfo
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- CN106631911A CN106631911A CN201611211877.0A CN201611211877A CN106631911A CN 106631911 A CN106631911 A CN 106631911A CN 201611211877 A CN201611211877 A CN 201611211877A CN 106631911 A CN106631911 A CN 106631911A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/26—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids
- C07C303/28—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids by reaction of hydroxy compounds with sulfonic acids or derivatives thereof
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Abstract
The invention discloses a method for preparing cis-tritosylate. The cis-tritosylate shown in structural formula (II) is obtained by carrying out a reaction between a compound shown in structural formula (I) and toluene sulfonyl chloride in an anhydrous pyridine solvent according to an equal molar ratio. According to the method, use of an inorganic alkali catalyst Na2CO3 or K2CO3 is avoided, problems about hydrolysis of the toluene sulfonyl chloride are solved, and an obtained product is high in yield and free of other side reaction, and is not required to be separated by virtue of a method of column chromatography and the like.
Description
Technical field
The present invention relates to a kind of synthetic method of p-methyl benzenesulfonic acid ester, belongs to technical field of organic synthesis.
Background technology
Protection or general of the p-methyl benzenesulfonic acid ester generally in organic chemical reactionses as alcohols or phenolic hydroxy group analog derivative
This kind of material is changed into containing alkane（Benzene）The electrophilic reagent of epoxide, to be further used for other organic reactions.
The method of generally synthesis p-methyl benzenesulfonic acid ester is using Schotten-Baumann method methods.This method profit
With substrate and excessive paratoluensulfonyl chloride in pure organic solvent（Such as tetrahydrofuran, tetrahydrofuran and pyridine mixed liquor）Or two mix
Agent（Organic solvent and water）Middle reaction, reaction needs to add sodium carbonate as catalyst, this method yield generally all than relatively low,
Particularly need paratoluensulfonyl chloride significantly excessive when as hydroxyl protection.Need Effective Regulation aqueous solution pH in reaction in addition
Value, to reduce the hydrolysis of paratoluensulfonyl chloride.
Non-organic solvent is generally adopted to its improved method, such as water is used as solvent.This improvement needs to use imidazolidine（Such as
N- cetyl imidazoles）With potassium carbonate as catalyst.Imidazolidine has dissolved paratoluensulfonyl chloride and has formed hydrophobic environment, reduces
The hydrolysis of paratoluensulfonyl chloride, improves yield.Toluene sulfochloride is generally excessive in reaction（Typically 1.5 times of substrate）,
Longer alkyl chain can only be used when being catalyzed using alkyl imidazole（Such as N- cetyl imidazoles）, N- methyl or N- butyl imidazoles are used as urging
Agent, although this reaction yield increases, last separating-purifying is cumbersome, needs silicagel column to remove imidazoles
Alkane and paratoluensulfonyl chloride and its hydrolysate.
The content of the invention
It is an object of the invention to provide a kind of high yield, the synthetic method of highly purified p-methyl benzenesulfonic acid ester, can apply
It is changed into electrophilic reagent or in organic reaction as the guard method of alcoholic extract hydroxyl group or phenolic hydroxyl group in alcohols or aldehydes matter.
The present invention realizes that process is as follows：
Structural formula（II）The preparation method of shown p-methyl benzenesulfonic acid ester, comprises the following steps：
R for C1-C8 alkyl, the thiazolinyl of C3-C11, the alkynyl of C3-C11, phenyl, the alkyl phenyl Ph (CH of C1-C62)nCH2-,
Alkyl ester group-the CH of C2-C112(CH2)nOCmH2m+1, wherein n be 0-5, m for 1-5 integer；
R is preferably the alkyl of C1-C3, phenyl, the alkyl ester group of C3-C8；
By the structural formula of equimolar ratio（I）Shown compound reacts in anhydrous pyridine solvent with paratoluensulfonyl chloride and obtains structure
Formula（II）Shown p-methyl benzenesulfonic acid ester, reaction temperature is -4～4 DEG C.
Reaction terminates to be added water in backward mixed liquor and is extracted with dichloromethane, and extract is molten with hydrochloric acid, sodium acid carbonate successively
Liquid, sodium chloride solution washing, organic layer anhydrous sodium sulfate drying after separation, vacuum rotary steam removes solvent and product is obtained.
It is an advantage of the current invention that：（1）Na need not be used2CO3Or K2CO3This kind of inorganic base catalyst；（2）The reaction
Use pure anhydrous pyridine as solvent, there is no paratoluensulfonyl chloride hydrolysis problem；（3）The product that the inventive method is obtained is produced
Rate height, such as carbochain are in the alkylol of C1-C8 more than 90%；（4）The inventive method substrate is 1 with tolysulfonyl cl molar ratio:
1, yield is high, and without other side reactions, final product purity is very high（>98%）, it is not necessary to crossing the methods such as post carries out separation product.
Specific embodiment
Illustrate the synthetic method of the present invention below by instantiation, its object is to be best understood from present disclosure and
Unrestricted protection scope of the present invention.
Embodiment 1
200ml three-necked bottles are positioned in 0 DEG C of ice-water bath, add 3.82g (20mmol) paratoluensulfonyl chlorides and 50mL pyridines（It is dry
It is dry）, electromagnetic agitation is simultaneously added dropwise 1.02mL (20mmol) ethanol, reacts 3 hours.Reaction is finished, and adds 100mL distilled water, is used
Dichloromethane is extracted（3*20mL）, organic layer washes twice with 6M HCl（2*30mL）, then saturation NaHCO is used successively3（30mL）
And 20%NaCl（30mL）Solution respectively washed once, and separate.The appropriate anhydrous Na of organic layer2SO48h is dried, is filtered to remove anhydrous
Na2SO4, organic liquor rotate colorless oil final product 4- toluene sulfonic acide ethyl esters（Yield 90%）.
4- toluene sulfonic acides ethyl ester is constituted：C9H12O3S（Mol.Wt: 200.25）, nuclear-magnetism spectrum：1H NMR(CDCl3, 500
MHz): δ ppm 7.80 (dt, J = 8.5 Hz, 2.0Hz, 2H), 7.35 (m, 2H), 4.10 (q, J = 7.0
Hz, 2H), 2.46 (s, 3H), 1.30 (t, J = 7.0 Hz, 3H)。
Comparison example：N- cetyls imidazoles is adopted for solvent, potassium carbonate is 35% as catalyst production.
Embodiment 2
200ml three-necked bottles are positioned in 0 DEG C of ice-water bath, add 3.82g (20mmol) paratoluensulfonyl chlorides and 50mL pyridines（It is dry
It is dry）, electromagnetic agitation is simultaneously added dropwise 2.64g (20mmol) 6- methoxyl groups alcohol, reacts 4 hours.Reaction is finished, and adds 100mL to steam
Distilled water, is extracted with dichloromethane（3*20mL）, organic layer washes twice with 6M HCl（2*30mL）, then saturation NaHCO is used successively3
（30mL）And 20%NaCl（30mL）Solution respectively washed once, and separate.The appropriate anhydrous Na of organic layer2SO48h is dried, is filtered to remove
Anhydrous Na2SO4, organic liquor rotate colorless oil final product 6- methoxyethyl -4- toluene sulfonic acide esters（Yield 92%）.
6- methoxyethyl -4- toluene sulfonic acides ester is constituted：C14H22O4S（Mol.Wt: 286.39）, nuclear-magnetism spectrum：1H NMR
(CDCl3, 500 MHz): δ ppm 7.79 (dt, J = 8.0 Hz, 2.0 Hz, 2H), 7.34 (m, 2H), 4.01
(t, J = 6.49 Hz, 2H), 3.33 (t, J = 6.5 Hz, 2H), 3.31 (s, 3H), 2.45 (s, 3H),
1.65 (m, 2H), 1.52 (m, 2H), 1.31 (m, 4H)。
Comparison example：N- cetyls imidazoles is adopted for solvent, potassium carbonate is 61% as catalyst production.
Embodiment 3
200ml three-necked bottles are positioned in 0 DEG C of ice-water bath, add 3.82g (20mmol) paratoluensulfonyl chlorides and 50mL pyridines（It is dry
It is dry）, electromagnetic agitation adds 4.97g (20mmol) phenol, reacts 3 hours.Reaction is finished, and adds 100mL distilled water, is used
Dichloromethane is extracted（3*20mL）, organic layer washes twice with 6M HCl（2*30mL）, then saturation NaHCO is used successively3（30mL）
And 20%NaCl（30mL）Solution respectively washed once, and separate.The appropriate anhydrous Na of organic layer2SO48h is dried, is filtered to remove anhydrous
Na2SO4, organic liquor rotate white powder final product：Phenyl -4- toluene sulfonic acide esters（Yield 95%）.
Phenyl -4- toluene sulfonic acides ester is constituted：C13H12O3S（Mol.Wt: 248.3）, nuclear-magnetism spectrum：1H NMR(CDCl3,
500 MHz): δ ppm 7.72 (dt, J = 8.0 Hz, 2.0 Hz, 2H), 7.32–7.20 (m, 5H), 6.70
(m, 2H), 2.45 (s, 3H)。
Comparison example：N- cetyls imidazoles is adopted for solvent, potassium carbonate is 40% as catalyst production.
Claims (4)
1. structural formula（II）The preparation method of shown p-methyl benzenesulfonic acid ester, it is characterised in that comprise the following steps：
R for C1-C8 alkyl, the thiazolinyl of C3-C11, the alkynyl of C3-C11, phenyl, the alkyl phenyl Ph (CH of C1-C62)nCH2-,
Alkyl ester group-the CH of C2-C112(CH2)nOCmH2m+1, wherein n be 0-5, m for 1-5 integer；
By the structural formula of equimolar ratio（I）Shown compound reacts in anhydrous pyridine solvent with paratoluensulfonyl chloride and obtains structure
Formula（II）Shown p-methyl benzenesulfonic acid ester.
2. preparation method according to claim 1, it is characterised in that：R for C1-C3 alkyl, phenyl, benzyl, C3-C8's
Alkyl ester group.
3. preparation method according to claim 1 and 2, it is characterised in that：Reaction temperature is -4～4 DEG C.
4. preparation method according to claim 3, it is characterised in that：Reaction terminates the dichloro that adds water in backward mixed liquor and use
Methane is extracted, and extract is washed successively with hydrochloric acid, sodium bicarbonate solution, sodium chloride solution, organic layer anhydrous slufuric acid after separation
Sodium is dried, and vacuum rotary steam removes solvent and product is obtained.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201611211877.0A CN106631911A (en) | 2016-12-25 | 2016-12-25 | Method for synthesizing cis-tritosylate |
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| CN201611211877.0A CN106631911A (en) | 2016-12-25 | 2016-12-25 | Method for synthesizing cis-tritosylate |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109456235A (en) * | 2018-12-17 | 2019-03-12 | 苏州华道生物药业股份有限公司 | A kind of green synthesis method of benzene sulfonic acid alkynes propyl ester |
| WO2019095636A1 (en) * | 2017-11-14 | 2019-05-23 | 石家庄圣泰化工有限公司 | Method for synthesizing benzenesulfonate derivative |
-
2016
- 2016-12-25 CN CN201611211877.0A patent/CN106631911A/en active Pending
Non-Patent Citations (3)
| Title |
|---|
| GEORGE W. KABALKA,ET AL.: "Tosylation of Alcohols", 《J.ORG.CHEM》 * |
| R. STUART TIPSON: "On Esters of p-Toluenesulfonic Acid", 《J.ORG.CHEM.》 * |
| VLADIMIR C.SEKERA,ET AL.: "Higher Alkyl Sulfonates", 《J.AM.CHEM.SOC.》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019095636A1 (en) * | 2017-11-14 | 2019-05-23 | 石家庄圣泰化工有限公司 | Method for synthesizing benzenesulfonate derivative |
| KR20190105493A (en) * | 2017-11-14 | 2019-09-17 | 스자좡 에스에이엔 타이 케미컬 컴퍼니 리미티드 | A method for synthesis of benzene sulfonate derivatives |
| KR102144626B1 (en) * | 2017-11-14 | 2020-08-28 | 스자좡 에스에이엔 타이 케미컬 컴퍼니 리미티드 | A method for synthesis of benzene sulfonate derivatives |
| JP2021502950A (en) * | 2017-11-14 | 2021-02-04 | 石家庄▲聖▼泰化工有限公司 | Method for synthesizing benzenesulfonic acid ester derivative |
| CN109456235A (en) * | 2018-12-17 | 2019-03-12 | 苏州华道生物药业股份有限公司 | A kind of green synthesis method of benzene sulfonic acid alkynes propyl ester |
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