CN103073421A - High-efficiency simple synthetic method for delta-chlorobutyl ester - Google Patents
High-efficiency simple synthetic method for delta-chlorobutyl ester Download PDFInfo
- Publication number
- CN103073421A CN103073421A CN 201110326576 CN201110326576A CN103073421A CN 103073421 A CN103073421 A CN 103073421A CN 201110326576 CN201110326576 CN 201110326576 CN 201110326576 A CN201110326576 A CN 201110326576A CN 103073421 A CN103073421 A CN 103073421A
- Authority
- CN
- China
- Prior art keywords
- chloride
- tetrahydrofuran
- acyl chlorides
- thf
- synthetic method
- 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
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention provides a preparation method for delta-chlorobutyl ester. A key point of the invention is as follows: tetrahydrofuran is used as a raw material to react with acyl chloride under catalysis of zinc chloride so as to rapidly and mildly synthesize delta-chlorobutyl ester with high yield and high purity. According to the invention, reduced pressure distillation and purification are directly carried out under the condition of no separation; unfavorable factors of low yield, long reaction time, excess usage amount of raw materials, need for expensive catalysts, severe reaction conditions and the like in conventional methods are avoided; the method is characterized by no use of a solvent or use of a small amount of the solvent, a small catalyst usage amount, a low price, mild reaction conditions and high yield; the whole process of preparation is simple and safe and costs little, and the method is applicable to industrial mass production.
Description
Technical field:
The invention belongs to field of fine chemical, relate to the preparation method of δ-chloro butyl ester.
Technical background:
δ-chloro butyl ester is widely used in the synthetic natural product that contains 4 carbon atom chains, medicine etc., is an important intermediate of synthesizing a lot of compounds.People notice for a long time at Lewis acid such as ZnCl
2, BCl
3, the lower tetrahydrofuran (THF)s of effect such as halogenation bismuth, organic lanthanum title complex and iodine can the cracking open loop.But the method for having reported has many deficiencies, low such as productive rate, cost is high or reagent is difficult to obtain, and the reaction times that certain methods need to be grown, harsh reaction conditions, needs to use solvent and reaction under the condition that refluxes, harmful catalyzer and the very loaded down with trivial details method of environment for use.Therefore the novel method of seeking preparation δ-chloro butyl ester is of great practical significance.(JACS 1939, and 2667-2669) open loop under zinc chloride catalysis generates the method for a series of δ-chloro butyl ester to the report tetrahydrofuran (THF) with different acyl chlorides, but the method productive rate is low, and reacting reflux time is long, and need are with excessive acyl chlorides for Jone Cloke etc.Pasha M.A. etc. (Ultrasonics sonochemistry, 2006,175-179) doing catalyzer high yield under ul-trasonic irradiation with zinc powder has obtained δ-chloro butyl ester, but uses zinc powder and ultrasonic wave to be unfavorable for industrial production.(the synthetic communication such as Pasha M.A., 2007,927-932) do the catalyzer tetrahydrofuran (THF) with iodine and acyl chlorides has generated δ-chloro butyl ester in the room temperature high yield, but it is more expensive to react used iodine, tetrahydrofuran (THF) is greatly excessive, has not only wasted expensive tetrahydrofuran (THF), also will remove iodine with Sulfothiorine simultaneously, aftertreatment is loaded down with trivial details, is not suitable for industrial production.Yadav J.S., Suresh V. philosophy with InBr (Journal of molecular Catalysis A:chemical, 2007,266-269), Bi (NO
3)
3(Canadian Journal of chemistry, 2007,1037-1040), La (NO
3)
3(synthetic communication2008,92-99) etc. makees catalyzer, and acyl chlorides successfully generates δ-chloro butyl ester with the tetrahydrofuran (THF) open loop, but these catalyzer are relatively expensive.Field etc. (JACS 1995,77,1206-7) reported the method for preparing 4-chlorobutyl p-toluenesulfonic esters, but the method productive rate low (34%), temperature is high, and long reaction time reacts too violent, dangerous property during beginning.
Summary of the invention:
In order to overcome the deficiency of above-mentioned technique, the object of the present invention is to provide the preparation method of a kind of δ-chloro butyl ester, compare with existing method, equipment requirements of the present invention is simple, easy to operate, the reaction process environmental protection, starting material are inexpensive, and easily control has good industrial prospect.
For achieving the above object, technical scheme of the present invention is:
The preparation method of a kind of δ-chloro butyl ester may further comprise the steps:
1) take tetrahydrofuran (THF) as raw material, under zinc chloride catalysis with acyl chloride reaction fast gentle, obtain δ-chloro butyl ester to high yield.
2) react rear direct underpressure distillation and got highly purified δ-chloro butyl ester
Preferably:
Described step 1) mol ratio of tetrahydrofuran (THF) and acyl chlorides is 1～1.1: 1 in; It is 0 ℃～30 ℃ for the fatty acid chloride temperature of reaction; For the aromatic acid temperature of reaction generally at 25 ℃～50 ℃; For Tosyl chloride, temperature is at 60 ℃～80 ℃; The consumption of zinc chloride and the mol ratio of tetrahydrofuran (THF) are 10%～0.1%.Here acyl chlorides can any acyl chlorides comprises the acyl chlorides of lipid acid, aromatic acid and sulfonic acid.Reaction times is short, and for fatty acid chloride, the reaction times is less than 1 hour, to the aromatic acid acyl chloride reaction time at 1-2 hour, for its reaction times of yellow acyl chlorides at 3-5 hour.
Route involved in the present invention is as follows:
Embodiment
Key point of the present invention is take tetrahydrofuran (THF) as raw material, under zinc chloride catalysis with acyl chloride reaction fast, gentleness, high yield, obtain δ-chloro butyl ester to high purity.Direct underpressure distillation purifying in unseparated situation.Existing methodical low-yield, long reaction time, the large excessive or unfavorable factors such as catalyzer that need to be more expensive or severe reaction conditions of raw material have been avoided.Characteristics of the present invention are not use or use a small amount of solvent, and catalyst levels is few, cheap, and the gentle productive rate of reaction conditions is high.Simultaneously simple, the safety of whole process, low cost are fit to that industry is large produces.The following examples can more specifically be understood the present invention, but in fact illustrate rather than limit the scope of the invention.
The preparation of embodiment 1:4-butylene-chlorohydrin ethyl ester
Add Zinc Chloride Anhydrous 1 gram in 250 milliliters of there-necked flasks, Acetyl Chloride 98Min. 78.5 grams stir lower tetrahydrofuran (THF) 72 grams that drip, ice bath cools off to maintain the temperature at below 30 degree, drips off rear insulation 1 hour, and the water pump underpressure distillation gets 4-butylene-chlorohydrin ethyl ester 145 grams, productive rate 96%, purity 99.5%.
The preparation of embodiment 2:4-butylene-chlorohydrin chloracetate
Add Zinc Chloride Anhydrous 1 gram in 250 milliliters of there-necked flasks, chloro-acetyl chloride 113 grams stir lower room temperature and drip tetrahydrofuran (THF) 72 grams, drip in the process and to keep being stabilized in 40 and spend, drip off rear insulation 1 hour, underpressure distillation gets 4-butylene-chlorohydrin chloracetate 166.6 grams, productive rate 90%, purity 99.2%.
The preparation of embodiment 3:4-butylene-chlorohydrin benzoic ether
Add Zinc Chloride Anhydrous 1 gram in 250 milliliters of there-necked flasks, Benzoyl chloride 141 grams stir lower room temperature and drip tetrahydrofuran (THF) 72 grams, drip in the process and to keep being stabilized in below 40 degree, drip off rear insulation 2 hours, underpressure distillation gets 4-butylene-chlorohydrin benzoic ether 200 grams, productive rate 94%, purity 99.35%.
The preparation of embodiment 4:4-butylene-chlorohydrin Chlorodracylic acid ester
Add Zinc Chloride Anhydrous 1 gram in 250 milliliters of there-necked flasks, parachlorobenzoyl chloride 175 grams, stir lower room temperature and drip tetrahydrofuran (THF) 72 grams, drip in the process and to keep being stabilized in 40 and spend, drip off rear insulation 2 hours, underpressure distillation gets 4-butylene-chlorohydrin Chlorodracylic acid ester 230 grams, productive rate 93%, purity 99.6%
The preparation of embodiment 5:4-butylene-chlorohydrin p-toluenesulfonic esters
Add Zinc Chloride Anhydrous 4 grams in 250 milliliters of there-necked flasks, to yellow acyl chlorides 76 grams of toluene, toluene 20ML, be heated with stirring to 80 degree, drip 37.5 gram tetrahydrofuran (THF)s, drip off rear insulation 2 hours, reaction solution is poured in the frozen water, adding toluene makes organic phase be inverted to the upper strata, branch vibration layer, organic phase is washed till neutrality with sodium hydrogen carbonate solution respectively, again with the saturated common salt washing, behind the anhydrous magnesium sulfate drying, toluene is reclaimed in underpressure distillation, the oil pump underpressure distillation gets 4-butylene-chlorohydrin p-toluenesulfonic esters 77 grams, productive rate 73%, purity 98% again
Claims (9)
1. the preparation method of δ-chloro butyl ester take tetrahydrofuran (THF) as raw material, obtains δ-chloro butyl ester with acyl chloride reaction under zinc chloride catalysis, has reacted rear direct underpressure distillation and has got highly purified δ-chloro butyl ester.
2. synthetic method according to claim 1 is characterized in that: tetrahydrofuran (THF) is produced δ-chloro butyl ester with acyl chlorides effect open loop under the condition that the anhydrous chlorine zinc of catalytic amount exists.
3. synthetic method according to claim 2, it is characterized in that: the mol ratio of tetrahydrofuran (THF) and acyl chlorides is 1～1.5: 1～1.2; Preferably 1～1.05: 1～1.05.
4. synthetic method according to claim 2 is characterized in that the consumption of zinc chloride and the mol ratio of tetrahydrofuran (THF) are 10%～0.1%.Here acyl chlorides can any acyl chlorides comprises the acyl chlorides of lipid acid, aromatic acid and sulfonic acid.
5. synthetic method according to claim 2 is characterized in that: be 0 ℃～30 ℃ for the fatty acid chloride temperature of reaction; For the aromatic acid temperature of reaction generally at 25 ℃～50 ℃; For Tosyl chloride, temperature is at 60 ℃～80 ℃.
6. synthetic method according to claim 2 is characterized in that:, or react in a small amount of inert solvent as can be solvent-free to the yellow acyl chloride reaction of toluene for SULPHURYL CHLORIDE, such as benzene, toluene etc.
7. according to claim 2,6 described synthetic methods, it is characterized in that: the mole-volume ratio of employed yellow acyl chlorides and quantity of solvent is 1 (mole): 0～200 (ml) is 0-200ml/mole, preferably: 20-100ml/mol, more preferably 20-50ml/mol.
8. synthetic method according to claim 2 is characterized in that for fatty acid chloride, and the reaction times is less than 1 hour, to the aromatic acid acyl chloride reaction time at 1-2 hour, for its reaction times of yellow acyl chlorides at 3-5 hour.
9. according to claim 1,2 described synthetic methods, it is characterized in that: the order of addition(of ingredients) of reactant is that tetrahydrofuran (THF) is added drop-wise in the mixture of acyl chlorides and zinc chloride.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110326576 CN103073421A (en) | 2011-10-25 | 2011-10-25 | High-efficiency simple synthetic method for delta-chlorobutyl ester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110326576 CN103073421A (en) | 2011-10-25 | 2011-10-25 | High-efficiency simple synthetic method for delta-chlorobutyl ester |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103073421A true CN103073421A (en) | 2013-05-01 |
Family
ID=48150144
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201110326576 Pending CN103073421A (en) | 2011-10-25 | 2011-10-25 | High-efficiency simple synthetic method for delta-chlorobutyl ester |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103073421A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105622407A (en) * | 2016-02-05 | 2016-06-01 | 中国海洋石油总公司 | Preparation method of acrylic acid-3-chloropropyl ester |
| CN105646213A (en) * | 2016-02-15 | 2016-06-08 | 南通市东昌化工有限公司 | Preparation method of acrylic acid-4-chlorobutyl ester compounds |
| CN109776484A (en) * | 2017-11-14 | 2019-05-21 | 石家庄圣泰化工有限公司 | The synthetic method of 1,4- butane sultones |
| CN111410600A (en) * | 2020-01-21 | 2020-07-14 | 安徽省诚联医药科技有限公司 | Preparation method of p-phenylbutoxy benzoic acid |
| CN112062677A (en) * | 2020-08-21 | 2020-12-11 | 温州国仕邦高分子材料有限公司 | Methacrylic acid-4-hydroxybutyl ester and preparation method thereof |
-
2011
- 2011-10-25 CN CN 201110326576 patent/CN103073421A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105622407A (en) * | 2016-02-05 | 2016-06-01 | 中国海洋石油总公司 | Preparation method of acrylic acid-3-chloropropyl ester |
| CN105646213A (en) * | 2016-02-15 | 2016-06-08 | 南通市东昌化工有限公司 | Preparation method of acrylic acid-4-chlorobutyl ester compounds |
| CN109776484A (en) * | 2017-11-14 | 2019-05-21 | 石家庄圣泰化工有限公司 | The synthetic method of 1,4- butane sultones |
| CN109776484B (en) * | 2017-11-14 | 2023-05-09 | 河北圣泰材料股份有限公司 | Synthesis method of 1, 4-butane sultone |
| CN111410600A (en) * | 2020-01-21 | 2020-07-14 | 安徽省诚联医药科技有限公司 | Preparation method of p-phenylbutoxy benzoic acid |
| CN112062677A (en) * | 2020-08-21 | 2020-12-11 | 温州国仕邦高分子材料有限公司 | Methacrylic acid-4-hydroxybutyl ester and preparation method thereof |
| CN112062677B (en) * | 2020-08-21 | 2022-12-23 | 温州国仕邦高分子材料有限公司 | Methacrylic acid-4-hydroxybutyl ester and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103073421A (en) | High-efficiency simple synthetic method for delta-chlorobutyl ester | |
| CN104448284B (en) | A kind of preparation method of diallyl end capped polyether | |
| CN101830821A (en) | Chemical synthesis method of N-alcoxyloxalyl alanine ester | |
| CN101671242B (en) | Method for synthesizing trans-4-(trans-4'-alkyl cyclohexyl) cyclohexanal | |
| CN107141258B (en) | Method for synthesizing side chain functionalized 4-acylpyrazole compound from cyclic ketohydrazone | |
| CN105418421A (en) | Synthesizing method for 3-methoxyacrylate | |
| JP5209183B2 (en) | Method for producing 2-cyanophenylboronic acid or ester thereof with reduced impurities | |
| CN101735118B (en) | Process method for synthesizing tertiary butyl sulfinyl amine by using silicohydride as protective reagent | |
| CN101591328A (en) | The chemical synthesis process of a kind of 2-bromothiophene and derivative thereof | |
| JP2009214039A (en) | Solid lewis acid catalyst and manufacturing method of diels-alder adduct using this catalyst | |
| CN106831281B (en) | Method for synthesizing 1, 2-diiodoolefin compound | |
| CN102627626B (en) | Preparation method of 2, 3-thiophenedicarboxaldehyde | |
| CN104277027A (en) | Preparation method of (R)-propylene carbonate | |
| CN111018899B (en) | Method for preparing 1, 1-boron alkyne compound by metal catalysis of terminal olefin | |
| CN104478768B (en) | A kind of fluoroform sulfo group fluorophenyl compound | |
| CN104672179B (en) | Preparation method of [(1S)-3-methyl-1-[[(2R)-2-methylepoxyethyl]carbonyl]butyl]tert-butyl carbamate | |
| CN112358442B (en) | Preparation method of 2-fluoro-5-formyl chloropyridine | |
| CN105646403B (en) | A kind of chemical synthesis process of the oxo octanoic acid methyl esters of 8 furans 8 | |
| CN104478799A (en) | Preparation method of 1,4-diallyl isoquinoline | |
| TWI542583B (en) | Oxidation process | |
| CN114950548B (en) | Application of eutectic ionic liquid in dealkylation of phenol alkyl ether compound to prepare phenol or derivative thereof | |
| CN103435634B (en) | A kind of preparation method of hexyllithium | |
| CN110724064B (en) | Method for synthesizing 2-cyclohexane substituted benzamide under catalysis of nickel | |
| CN101941930B (en) | Preparation method of 3-mercaptopropionic acid | |
| KR100763770B1 (en) | Process for preparing chiral intermediates useful in synthesis of atorvastatin |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20130501 |