CN104262220B - A kind of preparation method of dimethyl-β-DMPT - Google Patents
A kind of preparation method of dimethyl-β-DMPT Download PDFInfo
- Publication number
- CN104262220B CN104262220B CN201410403094.7A CN201410403094A CN104262220B CN 104262220 B CN104262220 B CN 104262220B CN 201410403094 A CN201410403094 A CN 201410403094A CN 104262220 B CN104262220 B CN 104262220B
- Authority
- CN
- China
- Prior art keywords
- dimethyl
- dmpt
- preparation
- propionic acid
- toluene
- 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.)
- Active
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention relates to a kind of preparation method of novel phagostimulant, especially relate to a kind of preparation method of dimethyl-β-DMPT.The present invention proposes a new synthetic route, raw materials used wide material sources are sufficient, and low price, the product purity be obtained by reacting are high, and color is good, have the stronger market competitiveness.Method of the present invention in turn includes the following steps: adopt 3-hydroxy-propionic acid to be raw material, first react with methylsulfonyl chloride and protect hydroxyl, then after reacting with dimethyl sulphide, acidifying prepares dimethyl-β-DMPT.
Description
Technical field
The present invention relates to a kind of preparation method of novel phagostimulant, especially relate to a kind of preparation method of dimethyl-β-DMPT.
Background technology
Dimethyl-β-DMPT (DMPT) is the pure natural compound extracted from marine alga the earliest.In fact find that the process of DMPT is also from marine alga: scientist observes discovery, seawater fish is liked to eat marine alga, the food calling factor just begun one's study in marine alga, finds afterwards to cause fish to like to eat the reason of marine alga, is exactly that marine alga contains natural DMPT.
DMPT be the effect that finds at present best the 5th generation aquatic attractant, even if there is experiment to prove to coat this thing on stone, fish also can remove the stone that bites.So someone describes its phagostimulating effect visually with " fish stings stone ".The most typical purposes of DMPT is bait when being used as fishing, improves the attractant of bait, makes the easy bite of fish.DMPT also as the green feeding additive aquatic animal of one, can promote that aquatic animal searches for food, improves its speed of growth.
The main at present synthetic method of DMPT is mainly reacted by halopropanoic acid and dimethyl sulphide and is prepared, but the starting halo propionic acid used in these class methods or price are too expensive, the inadequate yield of reactive behavior is too low, these all cause cost higher, are unfavorable for using on a large scale and promoting of product.
Summary of the invention
The present invention is to provide a kind of preparation method of dimethyl-β-DMPT, its synthetic method mainly solved existing for prior art is mainly reacted by halopropanoic acid and dimethyl sulphide and is prepared, its starting halo propionic acid price used is too expensive, the inadequate yield of reactive behavior is too low, make production cost higher, be unfavorable for the technical problem of the extensive use of product etc.
Above-mentioned technical problem of the present invention is mainly solved by following technical proposals:
The preparation method of a kind of dimethyl-β-DMPT of the present invention, is characterized in that described method comprises: obtain in accordance with the following steps with dimethyl-β-DMPT that formula (I) represents:
ⅡI
A.3-(mesyloxy) preparation of propionic acid (II):
Add the toluene of the 3-hydroxy-propionic acid of 1 weight part, the sodium bicarbonate of 1.8-1.9 weight part and 5-10 weight part in the reactor, after stirring, ice bath cools, and then drip the methylsulfonyl chloride of 1.27-1.40 weight part wherein, dropwise the bath of recession deicing, continue stirring reaction, after completion of the reaction, pH to 1.5-2.5 is regulated with dilute hydrochloric acid, separatory, organic phase is after anhydrous sodium sulfate drying, air distillation removing solvent toluene, obtains 3-(mesyloxy) propionic acid (II) crude product, crude product can be directly used in next step reaction without the need to being further purified;
B. the preparation of dimethyl-β-DMPT (I)
Add the 3-(mesyloxy of 1 weight part in the reactor) toluene of propionic acid (II) crude product and 4-8 weight part, after stirring, room temperature drips the toluene solution of dimethyl sulphide, wherein the add-on of dimethyl sulphide is 3-(mesyloxy) 0.36-0.41 of propionic acid (II) crude product weight is doubly, the add-on of toluene is 3-(mesyloxy) 1 times of propionic acid (II) weight weight, after dropwising, continue stirring reaction, after reaction terminates, pH to 1.5-2.5 is regulated with dilute hydrochloric acid, separatory, aqueous phase is product dimethyl-β-DMPT (I), the mixing solutions of methylsulfonic acid and hydrochloric acid, again mixing solutions is removed methylsulfonic acid and hydrochloric acid through ionic absorption with macroporous adsorbent resin, obtain the aqueous solution of dimethyl-β-DMPT (I), product dimethyl-β-DMPT (I) is obtained after evaporate to dryness.
Innovative point of the present invention is the synthetic route of design again, around some optimum configurations done of variation route, and finally prepared product.In experimentation, the DMPT that second step prepares is wherein containing a small amount of by-product acids and inorganic salt, the easy quality affecting product, ordinary method is difficult to purifying, so the present invention adopts and eliminates by-product acids and inorganic salt through ionic macroporous adsorbent resin, the good product purity obtained, proterties is good.
As preferably, in described step a, the lower temperature of ice bath cooling is down to 0-10 DEG C, and the process dripping methylsulfonyl chloride keeps mixture temperature between 0-10 DEG C, and the time of continuing stirring reaction after removing ice bath is 4-6 hour.
As preferably, the time of continuing stirring reaction after dripping the toluene solution of dimethyl sulphide in described step b is 2-4 hour.
As preferably, the concentration of described dilute hydrochloric acid is 5%.
Therefore, the route that the present invention adopts does not need the halopropanoic acid using price relatively high, and cost control advantageously, good reaction selectivity of the present invention, finally adopt macroporous adsorbent resin to carry out purifying, and the product purity obtained and outward appearance are compared with currently available products, improve a lot.
Embodiment
Below by embodiment, technical scheme of the present invention is described in further detail.
Embodiment 1: the preparation method of a kind of dimethyl-β-DMPT of this example, the steps include:
A.3-(mesyloxy) preparation of propionic acid (II):
Add 3-hydroxy-propionic acid (90g in the reactor, 1.0mol), sodium bicarbonate (171g) and toluene (900g), after stirring, ice bath cooling borehole cooling is to 0-10 DEG C, and then drip methylsulfonyl chloride (126g wherein, 1.10mol), dropping process keeps mixture temperature between 0-10 DEG C, dropwise the bath of recession deicing, continue stirring reaction 6 hours, after completion of the reaction, dilute hydrochloric acid with 5% regulates pH to 2, separatory, organic phase is after anhydrous sodium sulfate drying, air distillation removing solvent toluene, obtain 3-(mesyloxy) propionic acid (II) crude product, crude product can be directly used in next step reaction without the need to being further purified.For light yellow solid 137.2g, yield about 81.6%.Spectrum data is detected as follows after sampling purifying:
1HNMR(CDCl3，400MHz)δ：2.45（2H，t），3.13（3H，s），3.77（2H，t）；EI-MS(m/z)：169(M+H)；M.P.61.2-63.4℃。
B. the preparation of dimethyl-β-DMPT (I):
Add 3-(mesyloxy in the reactor) propionic acid (II) (84g, 0.5mol) with toluene (670g), after stirring room temperature drip dimethyl sulphide toluene solution (by 34.1g dimethyl sulphide and 84g toluene formulated), after dropwising, continue stirring reaction 4 hours, after reaction terminates, dilute hydrochloric acid with 5% regulates pH to 2, separatory, aqueous phase is product dimethyl-β-DMPT (I), the mixing solutions of methylsulfonic acid and hydrochloric acid, again mixing solutions is removed methylsulfonic acid and hydrochloric acid through ionic absorption with macroporous adsorbent resin, obtain the aqueous solution of dimethyl-β-DMPT (I), product dimethyl-β-DMPT (I) is obtained after evaporate to dryness, for white powder crystal 72.3g, yield about 84.8%.
1HNMR (D2O, 400MHz) δ: 2.11 (s, 6H), 2.60-2.73 (m, 4H); ESI-MS (m/z): 135 (M-Cl); M.P.130.5-134.1 DEG C (decomposition).
Embodiment 2: the preparation method of a kind of dimethyl-β-DMPT of this example, other steps are identical with embodiment 1, just the 3-(mesyloxy of step A) preparation method of propionic acid (II) is as follows:
Add 3-hydroxy-propionic acid (90g in the reactor, 1.0mol), sodium bicarbonate (162g) and toluene (450g), after stirring, ice bath cooling borehole cooling is to 0-10 DEG C, and then drip methylsulfonyl chloride (114.5g wherein, 1.0mol), dropping process keeps mixture temperature between 0-10 DEG C, dropwise the bath of recession deicing, continue stirring reaction 4 hours, after completion of the reaction, dilute hydrochloric acid with 5% regulates pH to 2, separatory, organic phase is after anhydrous sodium sulfate drying, air distillation removing solvent toluene, obtain 3-(mesyloxy) propionic acid (II) crude product, crude product can be directly used in next step reaction without the need to being further purified.For light yellow solid 116.4g, yield about 69.3%.
Embodiment 3: the preparation method of a kind of dimethyl-β-DMPT of this example, other steps are identical with embodiment 1, just the 3-(mesyloxy of step A) preparation method of propionic acid (II) is as follows:
Add 3-hydroxy-propionic acid (90g in the reactor, 1.0mol), sodium bicarbonate (167g) and toluene (700g), after stirring, ice bath cooling borehole cooling is to 0-10 DEG C, and then drip methylsulfonyl chloride (120.2g wherein, 1.05mol), dropping process keeps mixture temperature between 0-10 DEG C, dropwise the bath of recession deicing, continue stirring reaction 5 hours, after completion of the reaction, dilute hydrochloric acid with 5% regulates pH to 2, separatory, organic phase is after anhydrous sodium sulfate drying, air distillation removing solvent toluene, obtain 3-(mesyloxy) propionic acid (II) crude product, crude product can be directly used in next step reaction without the need to being further purified.For light yellow solid 129.6g, yield about 76.8%.
Embodiment 4: the preparation method of a kind of dimethyl-β-DMPT of this example, other steps are identical with embodiment 1, just the 3-(mesyloxy of step A) preparation method of propionic acid (II) is as follows:
Add 3-hydroxy-propionic acid (90g in the reactor, 1.0mol), sodium bicarbonate (170g) and toluene (800g), after stirring, ice bath cooling borehole cooling is to 0-10 DEG C, and then drip methylsulfonyl chloride (118g wherein, 1.03mol), dropping process keeps mixture temperature between 0-10 DEG C, dropwise the bath of recession deicing, continue stirring reaction 4 hours, after completion of the reaction, dilute hydrochloric acid with 5% regulates pH to 2, separatory, organic phase is after anhydrous sodium sulfate drying, air distillation removing solvent toluene, obtain 3-(mesyloxy) propionic acid (II) crude product, crude product can be directly used in next step reaction without the need to being further purified.For light yellow solid 120.9g, yield about 80.0%.
Embodiment 5: the preparation method of a kind of dimethyl-β-DMPT of this example, other steps are identical with embodiment 1, and just the preparation method of the dimethyl-β-DMPT (I) of step B is as follows:
Add 3-(mesyloxy in the reactor) propionic acid (II) (84g, 0.5mol) with toluene (338g), after stirring room temperature drip dimethyl sulphide toluene solution (by 31g dimethyl sulphide and 84g toluene formulated), after dropwising, continue stirring reaction 2 hours, after reaction terminates, dilute hydrochloric acid with 5% regulates pH to 2, separatory, aqueous phase is product dimethyl-β-DMPT (I), the mixing solutions of methylsulfonic acid and hydrochloric acid, again mixing solutions is removed methylsulfonic acid and hydrochloric acid through ionic absorption with macroporous adsorbent resin, obtain the aqueous solution of dimethyl-β-DMPT (I), product dimethyl-β-DMPT (I) is obtained after evaporate to dryness, for white powder crystal 64.4g, yield about 75.5%.
Embodiment 6: the preparation method of a kind of dimethyl-β-DMPT of this example, other steps are identical with embodiment 1, and just the preparation method of the dimethyl-β-DMPT (I) of step B is as follows:
Add 3-(mesyloxy in the reactor) propionic acid (II) (84g, 0.5mol) with toluene (500g), after stirring room temperature drip dimethyl sulphide toluene solution (by 32.6g dimethyl sulphide and 84g toluene formulated), after dropwising, continue stirring reaction 3 hours, after reaction terminates, dilute hydrochloric acid with 5% regulates pH to 2, separatory, aqueous phase is product dimethyl-β-DMPT (I), the mixing solutions of methylsulfonic acid and hydrochloric acid, again mixing solutions is removed methylsulfonic acid and hydrochloric acid through ionic absorption with macroporous adsorbent resin, obtain the aqueous solution of dimethyl-β-DMPT (I), product dimethyl-β-DMPT (I) is obtained after evaporate to dryness, for white powder crystal 66.8g, yield about 78.3%.
Embodiment 7: the preparation method of a kind of dimethyl-β-DMPT of this example, other steps are identical with embodiment 1, and just the preparation method of the dimethyl-β-DMPT (I) of step B is as follows:
Add 3-(mesyloxy in the reactor) propionic acid (II) (84g, 0.5mol) with toluene (400g), after stirring room temperature drip dimethyl sulphide toluene solution (by 33.5g dimethyl sulphide and 84g toluene formulated), after dropwising, continue stirring reaction 4 hours, after reaction terminates, dilute hydrochloric acid with 5% regulates pH to 2, separatory, aqueous phase is product dimethyl-β-DMPT (I), the mixing solutions of methylsulfonic acid and hydrochloric acid, again mixing solutions is removed methylsulfonic acid and hydrochloric acid through ionic absorption with macroporous adsorbent resin, obtain the aqueous solution of dimethyl-β-DMPT (I), product dimethyl-β-DMPT (I) is obtained after evaporate to dryness, for white powder crystal 68.5g, yield about 80.4%.
The foregoing is only specific embodiments of the invention, but constitutional features of the present invention is not limited thereto, any those skilled in the art is in the field of the invention, and the change done or modification are all encompassed among the scope of the claims of the present invention.
Claims (4)
1. a preparation method for dimethyl-β-DMPT, is characterized in that described method comprises: obtain in accordance with the following steps with dimethyl-β-DMPT that formula (I) represents:
ⅡI
A.3-(mesyloxy) preparation of propionic acid (II):
Add the toluene of the 3-hydroxy-propionic acid of 1 weight part, the sodium bicarbonate of 1.8-1.9 weight part and 5-10 weight part in the reactor, after stirring, ice bath cools, and then drip the methylsulfonyl chloride of 1.27-1.40 weight part wherein, dropwise the bath of recession deicing, continue stirring reaction, after completion of the reaction, pH to 1.5-2.5 is regulated with dilute hydrochloric acid, separatory, organic phase is after anhydrous sodium sulfate drying, air distillation removing solvent toluene, obtains 3-(mesyloxy) propionic acid (II) crude product, crude product can be directly used in next step reaction without the need to being further purified;
B. the preparation of dimethyl-β-DMPT (I)
Add the 3-(mesyloxy of 1 weight part in the reactor) toluene of propionic acid (II) crude product and 4-8 weight part, after stirring, room temperature drips the toluene solution of dimethyl sulphide, wherein the add-on of dimethyl sulphide is 3-(mesyloxy) 0.36-0.41 of propionic acid (II) crude product weight is doubly, the add-on of toluene is 3-(mesyloxy) 1 times of propionic acid (II) weight weight, after dropwising, continue stirring reaction, after reaction terminates, pH to 1.5-2.5 is regulated with dilute hydrochloric acid, separatory, aqueous phase is product dimethyl-β-DMPT (I), the mixing solutions of methylsulfonic acid and hydrochloric acid, again mixing solutions is removed methylsulfonic acid and hydrochloric acid through ionic absorption with macroporous adsorbent resin, obtain the aqueous solution of dimethyl-β-DMPT (I), product dimethyl-β-DMPT (I) is obtained after evaporate to dryness.
2. the preparation method of a kind of dimethyl-β-DMPT according to claim 1, it is characterized in that in described step a, the lower temperature of ice bath cooling is down to 0-10 DEG C, the process dripping methylsulfonyl chloride keeps mixture temperature between 0-10 DEG C, and the time of continuing stirring reaction after removing ice bath is 4-6 hour.
3. the preparation method of a kind of dimethyl-β-DMPT according to claim 1, the time of continuing stirring reaction after it is characterized in that dripping in described step b the toluene solution of dimethyl sulphide is 2-4 hour.
4. the preparation method of a kind of dimethyl-β-DMPT according to claim 1, is characterized in that the concentration of described dilute hydrochloric acid is 5%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410403094.7A CN104262220B (en) | 2014-08-18 | 2014-08-18 | A kind of preparation method of dimethyl-β-DMPT |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410403094.7A CN104262220B (en) | 2014-08-18 | 2014-08-18 | A kind of preparation method of dimethyl-β-DMPT |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104262220A CN104262220A (en) | 2015-01-07 |
| CN104262220B true CN104262220B (en) | 2016-03-30 |
Family
ID=52153840
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410403094.7A Active CN104262220B (en) | 2014-08-18 | 2014-08-18 | A kind of preparation method of dimethyl-β-DMPT |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104262220B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107382802A (en) * | 2017-06-21 | 2017-11-24 | 宜兴市天石饲料有限公司 | The preparation method of dimethyl beta DMPT |
| CN112778240B (en) * | 2021-01-15 | 2023-01-10 | 山东省海洋资源与环境研究院(山东省海洋环境监测中心、山东省水产品质量检验中心) | A method for simultaneously extracting feed additive rich in DMPT and fucoxanthin from Chrysophyta |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1261071A (en) * | 1999-01-19 | 2000-07-26 | 金湖石油化学株式会社 | Matte salts and production thereof |
| CN1762997A (en) * | 2005-10-18 | 2006-04-26 | 北京格林富诚科技有限公司 | Dialkyl-beta-propiothetin haloid acid salt and carboxylate preparation method |
| CN101880237A (en) * | 2010-06-08 | 2010-11-10 | 王永军 | Clean synthesis process of cyclopropane derivatives |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005029548A (en) * | 2003-07-11 | 2005-02-03 | Jsr Corp | Sulfonium compound, radiation-sensitive acid generator comprising the same and radiation-sensitive resin composition |
-
2014
- 2014-08-18 CN CN201410403094.7A patent/CN104262220B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1261071A (en) * | 1999-01-19 | 2000-07-26 | 金湖石油化学株式会社 | Matte salts and production thereof |
| CN1762997A (en) * | 2005-10-18 | 2006-04-26 | 北京格林富诚科技有限公司 | Dialkyl-beta-propiothetin haloid acid salt and carboxylate preparation method |
| CN101880237A (en) * | 2010-06-08 | 2010-11-10 | 王永军 | Clean synthesis process of cyclopropane derivatives |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104262220A (en) | 2015-01-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103193628A (en) | Alpha-ketophenylalanine calcium preparation method | |
| CN104262220B (en) | A kind of preparation method of dimethyl-β-DMPT | |
| CN101384547A (en) | Process for the crystallisation of mesotrione | |
| CN104876815B (en) | A kind of preparation method of sodium diformate | |
| CN102558080A (en) | Method for synthesizing thiotriazinone | |
| CN104230800A (en) | Preparation method of copper 8-hydroxyquinoline | |
| CN102229531B (en) | Preparation method of p-hydroxy benzal propane diacid derivative | |
| CN104822655A (en) | Method for producing 4-haloalkyl -3-mercapto-substituted 2-hydroxy-benzoic acid derivatives | |
| CN104447290B (en) | A kind of method preparing 2,4 dichlorophenoxyacetic acid | |
| CN102531983A (en) | Chemical synthesis method of S-phenyl-4-tosylate | |
| CN102432559A (en) | Synthetic method for preparing 2,6-dichlorobenzoxazole by photocuring | |
| CN106749003B (en) | A kind of preparation method of ethoxyquinoline | |
| CN104151161B (en) | A kind of 2-(2-allyl group) preparation method of amylene-4-acid methyl esters | |
| CN107382802A (en) | The preparation method of dimethyl beta DMPT | |
| CN102382000A (en) | Production method of D- para hydroxybenzene glycine | |
| CN104513182A (en) | Method for preparing (1R,2R)-1,2-cyclohexanedimethanol disulfonate | |
| CN103408418A (en) | Preparation and purification method of solid malonic acid | |
| WO2002079185A1 (en) | Process for producing (dioxolenon-4-yl)methyl ester derivative | |
| CN103214462A (en) | Preparation method of esomeprazole sodium salt | |
| CN107501127A (en) | The synthetic method of the fluorenylmethyloxycarbonyl O acetyl group L serines of N α 9 | |
| CN102442958A (en) | Preparation method of isomer-removed tebuconazole | |
| CN101633622B (en) | Method for preparing choline chloride | |
| CN101195611B (en) | Method for synthesizing (2S,3S,4S)-5-(3,4-diamino-tetrahydrothiophene-2-base) valeric acid | |
| CN102633753B (en) | Method for synthesizing carbobenzoxyserine-beta-lactone | |
| CN104987308A (en) | Preparation method for 5-bromine-2-picolinic acid |
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 | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: Dimethyl- b- Preparation method of thiophanate propionate Effective date of registration: 20221014 Granted publication date: 20160330 Pledgee: Xiaoshan Branch of Agricultural Bank of China Ltd. Pledgor: HEALTHY (HANGZHOU) HUSBANDRY SCI-TECH CO.,LTD. Registration number: Y2022980018382 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right |