CN100400491C - 2,4,5-trimethoxy-alpha-halogenated acetophenone synthesis method - Google Patents
2,4,5-trimethoxy-alpha-halogenated acetophenone synthesis method Download PDFInfo
- Publication number
- CN100400491C CN100400491C CNB2005100457501A CN200510045750A CN100400491C CN 100400491 C CN100400491 C CN 100400491C CN B2005100457501 A CNB2005100457501 A CN B2005100457501A CN 200510045750 A CN200510045750 A CN 200510045750A CN 100400491 C CN100400491 C CN 100400491C
- Authority
- CN
- China
- Prior art keywords
- trimethoxy
- alpha
- reaction
- synthetic method
- product
- 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
Images
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The present invention relates to a synthesis method of 2, 4, 5-trimethoxy-alpha-halogenoacetophenone. Lewis acids comprising ZnCl2AlCl3, FeCl3, BF3 and the like are used as catalysts, ether is used as a solvent, and hydrogen chloride is introduced into a mixture system of 1, 2, 4-trimethoxybenzene and ICH2CN or ClCH2CN or BrCH2CN till the end of the reaction; a reaction product is hydrolyzed, preferably refluxed and hydrolyzed, and filtered, and the obtained solid is recrystallized with alcohol to obtain white needle crystals. Stirring for 4 to 6 hours is preferable in the reaction process till the end of the reaction, after deposition, an amount of ice water is added, the product is stirred to room temperature, refluxed, hydrolyzed and filtered to remove the solvent, and the product is recrystallized with alcohol to obtain a pure product with high yield. Thus, an important intermediate with high quality and low price for medicaments and an intermediate for organic chemical products are provided for the market.
Description
Technical field:
The present invention relates to the intermediate 2,4 of a kind of medicine intermediate and organic chemical industry's product, the synthetic method of 5-trimethoxy-alpha-halo acetophenone, particularly adopt 1,2,4-trimethoxy-benzene and chloromethyl cyanide be Synthetic 2 under catalyst action, 4, the synthetic method of 5-trimethoxy-alpha-halo acetophenone.
Background technology:
I) at Acta.Lit.Sci.Univ.Hung.Francisco-Josephinae, Sect.Chem.Mineral.Phys.2,165-81 has reported 2,4, the synthetic method of 5-trimethoxy-alpha-chloro acetophenone on (in German 182-5) (1932).Adopt 1,2,4-trimethoxy-benzene and chloroacetyl chloride are at anhydrous AlCl
3Under the condition acylation reaction takes place, obtain yellow oil (mixture), this method is difficult to separation and obtains purified product.
II) nineteen sixty-eight has reported 2,4 in addition, and synthesizing of 5-trimethoxy-alpha-chloro acetophenone only narrated employing Hoesch-Keton-synthese method, but do not seen the report of detailed synthesis step.
Summary of the invention:
The present invention is intended to solve 2,4, the problem that the 5-trimethoxy-the alpha-halo acetophenone Synthesis conversion is lower and purity is lower, provide a kind of obtain that yield is higher, purity is higher 2,4, the white needle-like crystals 2,4 that the synthetic method of 5-trimethoxy-alpha-halo acetophenone and this method obtain, 5-trimethoxy-alpha-halo acetophenone.
Of the present invention 2,4, the synthetic method of 5-trimethoxy-alpha-halo acetophenone is with ZnCl
2AlCl
3, FeCl
3, BF
3Deng Louis's acid as catalyst, ether is made solvent, with 1,2, and 4-trimethoxy-benzene and ICH
2CN or ClCH
2CN or BrCH
2Logical hcl reaction in the mixed system of CN finishes to be hydrolyzed to reaction again, preferably passes through back hydrolysis, filters the solid ethyl alcohol recrystallization that obtains, and obtains white needle-like crystals.Preferably stirred in reaction process 4-6 hour, reaction can be left standstill after finishing, and preferably leaves standstill about 12 hours, add a certain amount of frozen water again and be stirred to back hydrolysis after the room temperature, the hydrolysis after-filtration is removed solvent, and the yellow solid that obtains is used ethyl alcohol recrystallization again, obtains white needle-like crystals.Temperature of reaction of the present invention can not have special restriction, but this is reflected at and is optimal reaction temperature, easier grasp of such temperature range and control in-15～30 ℃ of temperature ranges.1,2,4-trimethoxy-benzene, catalyzer and ICH
2CN or ClCH
2CN or BrCH
2The blending ratio of CN generally can be according to identical mol ratio, but in order to react fully, and particularly 1,2, the 4-trimethoxy-benzene is fully used, and 1,2,4-trimethoxy-benzene: ClCH
2CN: the molar ratio range of catalyzer is preferably 1: 1-2: 1-3.The benefit that such ratio is selected is: 1) improve 1,2, the transformation efficiency of 4-trimethoxy-benzene; 2) catalytic efficiency height in this scope is higher than this scope and cost is raise and the aftertreatment of product is made troubles.
Total equation of the present invention:
The present invention compared with the prior art, it is as follows to have advantage: obtain the high pure substance of yield, thereby for market provide super quality and competitive price important medicine intermediate and Organic Chemical Plant's product intermediate.
Description of drawings:
Accompanying drawing has been represented the product liquid chromatogram that method of the present invention synthesizes, and further specifies the present invention below in conjunction with the example of accompanying drawing.
Specific embodiment:
Embodiment one, a kind of of the present invention 2,4, the synthetic method of 5-trimethoxy-alpha-halo acetophenone, when temperature is 0 ℃, to 2.5g 1,2,4-trimethoxy-benzene and 1.6ml BrCH
2Logical hydrogenchloride reacts in the CN mixed system, finishes until reaction, and reaction process adds 2.3gZnCl
2Make catalyzer (the concrete mol ratio of three kinds of compositions is 1: 1.5: 1), the 35ml ether makees solvent and whole system is all operated under anhydrous condition, and reaction process stirs and stopped in 4-6 hour.Reaction product leaves standstill the frozen water that adds 100g after 12 hours and is stirred to 25 ℃ of room temperatures, and back hydrolysis, filters the solid ethyl alcohol recrystallization that obtains, obtain white needle-like crystals 2,4,5-trimethoxy-alpha-halo acetophenone 4.2g, fusing point 164-165 ℃, productive rate is 85%.The product liquid chromatogram as shown in drawings.Liquid chromatogram has only the explanation of peak only to be a kind of compound, does not have other by product, below similar.
Embodiment two, a kind of of the present invention 2,4, the synthetic method of 5-trimethoxy-alpha-halo acetophenone, when temperature is 30 ℃, to 2.5ml 1,2,4-trimethoxy-benzene and 2.4ml BrCH
2Logical hydrogenchloride in the CN system, and the ZnCl of adding 1.1g
2Make solvent for catalyzer (the concrete mol ratio of three kinds of raw materials 1: 2: 0.5), 35ml ether, react.Whole system is all operated under anhydrous condition, and reaction process stirs and stopped in 4-6 hour.Finish until reaction, in addition frozen water is stirred to after 25 ℃ of the room temperatures and refluxes until whole hydrolysis, filters the yellow solid ethyl alcohol recrystallization that obtains through filter, obtains white needle-like crystals product 3.3g of the present invention, and productive rate is 68%.Obtain 2,4,5-trimethoxy-alpha-halo acetophenone, fusing point 151-152 ℃.
Embodiment three, a kind of of the present invention 2,4, the synthetic method of 5-trimethoxy-alpha-halo acetophenone is when temperature is-13 ℃, to the 1.2.4-of 2.5ml trimethoxy-benzene and ICH
2Logical hydrogenchloride finishes until reaction in the CN system, and adds the ZnCl of 6.8g
2Be catalyzer (the concrete mol ratio of three kinds of raw materials 1: 1.5: 3) that the 35ml ether is made solvent, whole reaction system is all operated under anhydrous condition, reaction is stirred and was stopped in 4-6 hour, product leaves standstill and constantly adds water after 12 hours and be stirred to room temperature-25 ℃, and back hydrolysis then is until whole hydrolysis.The solid ethyl alcohol recrystallization that filtration obtains obtains white needle-like crystals 2,4,5-trimethoxy-alpha-halo acetophenone 4.5g.The productive rate of this process is 80%.
Embodiment four, a kind of of the present invention 2,4, the synthetic method of 5-trimethoxy-alpha-halo acetophenone is when temperature is 0 ℃, to 2.5ml 1.2.4-trimethoxy-benzene and 2.1ml ClCH
2Logical hydrogenchloride reacts in the CN mixed system, with the ZnCl of 6.8g
2Make catalyzer (the concrete mol ratio of three kinds of raw materials 1: 2: 3), the 30ml ether is made solvent, and whole system is all operated under anhydrous condition, stops in stirring reaction 4-6 hour.After reaction finished, reaction product left standstill the ice that adds 100g after 12 hours and is stirred to back hydrolysis after 25 ℃ of the room temperatures, filters the solid ethyl alcohol recrystallization that obtains, and obtains white needle-like crystals product 3.78g.The fusing point 164-165 of product ℃.Its productive rate is 92%.
Embodiment five, a kind of of the present invention 2,4, the synthetic method of 5-trimethoxy-alpha-halo acetophenone is when temperature is 0 ℃, to 2.5ml 1.2.4-trimethoxy-benzene and 2.1ml ClCH
2Logical hydrogenchloride finishes until reaction in the CN mixed system, with AlCl
3Make catalyzer (the concrete mol ratio of three kinds of raw materials 1: 2: 3), the 35ml ether is made solvent and whole system is all operated under anhydrous condition.React and stopped in 8 hours, reaction system leaves standstill and on the rocksly was stirred to constantly hydrolysis after 25 ℃ of the room temperatures in 12 hours, filters the solid ethyl alcohol recrystallization that obtains with strainer after the hydrolysis, obtains white needle-like crystals 3.5g.This 2,4, the fusing point of 5-trimethoxy-alpha-halo acetophenone is 164-165 ℃.Productive rate is 85%.
Claims (5)
1. one kind 2,4, the synthetic method of 5-trimethoxy-alpha-halo acetophenone, with Louis's acid as catalyst, ether is made solvent, to 1,2,4-trimethoxy-benzene and ICH
2CN or ClCH
2CN or BrCH
2Logical hydrogen chloride gas finishes until reaction in the CN hybrid reaction system, and water or ice or frozen water decompose, and resulting after filtration solid is used ethyl alcohol recrystallization again, obtains white needle-like crystals.
2. said 2,4 as claim 1, the synthetic method of 5-trimethoxy-alpha-halo acetophenone is characterized in that: lewis acid catalyst is ZnCl
2, AlCl
3, FeCl
3Or BF
3
3. as claim 1 said 2,4, the synthetic method of 5-trimethoxy-alpha-halo acetophenone, it is characterized in that: reaction process stirred 4-6 hour, choose wantonly and add frozen water again be stirred to room temperature after placement, the strainer suction filtration is used in the further hydrolysis that refluxes, the yellow solid ethyl alcohol recrystallization that obtains obtains white needle-like crystals.
4. said 2,4 as claim 1, the synthetic method of 5-trimethoxy-alpha-halo acetophenone is characterized in that: at-15～30 ℃ of temperature range internal reactions.
5. said 2,4 as claim 1, the synthetic method of 5-trimethoxy-alpha-halo acetophenone is characterized in that: 1,2, and 4-trimethoxy-benzene: ClCH
2CN: the molar ratio range of catalyzer is 1: 1-2: 1-3.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100457501A CN100400491C (en) | 2005-01-21 | 2005-01-21 | 2,4,5-trimethoxy-alpha-halogenated acetophenone synthesis method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100457501A CN100400491C (en) | 2005-01-21 | 2005-01-21 | 2,4,5-trimethoxy-alpha-halogenated acetophenone synthesis method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1807385A CN1807385A (en) | 2006-07-26 |
| CN100400491C true CN100400491C (en) | 2008-07-09 |
Family
ID=36839503
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2005100457501A Expired - Fee Related CN100400491C (en) | 2005-01-21 | 2005-01-21 | 2,4,5-trimethoxy-alpha-halogenated acetophenone synthesis method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100400491C (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110498739A (en) * | 2019-09-12 | 2019-11-26 | 南华大学 | A method of synthesis 6- hydroxyl -2,3,4- trimethoxy-alpha-chloro acetophenone |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1128779A (en) * | 1995-02-07 | 1996-08-14 | 青州铝箔纸总公司 | Glue for pretreatment of raw material paper for solid state vacuum aluminium plating |
-
2005
- 2005-01-21 CN CNB2005100457501A patent/CN100400491C/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1128779A (en) * | 1995-02-07 | 1996-08-14 | 青州铝箔纸总公司 | Glue for pretreatment of raw material paper for solid state vacuum aluminium plating |
Non-Patent Citations (2)
| Title |
|---|
| Zur Analytik einiger Hydroxycumaranone-(3) II. G.Schenck et al.Tetrahedron Letters,Vol.19 . 1968 |
| Zur Analytik einiger Hydroxycumaranone-(3) II. G.Schenck et al.Tetrahedron Letters,Vol.19 . 1968 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1807385A (en) | 2006-07-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1326826C (en) | Continuous method for preparing ethyl lactate | |
| CN100400491C (en) | 2,4,5-trimethoxy-alpha-halogenated acetophenone synthesis method | |
| CN101631781A (en) | Improved process for preparing ethyl (s)-2-ethoxy-4-[n-[1-(2- piperidinophenyl)-3-methyl-1-butyl]aminocarbonyl methyl]benzoate and use thereof for the preparation of repaglinide | |
| JP2004313984A (en) | Dimethycarbonate synthetic catalyst | |
| Davoodnia et al. | A Modified and Green Procedure for the Synthesis of β‐Amido Ketones Using a Br? nsted‐Acidic Ionic Liquid as Novel and Reusable Catalyst | |
| CN103073421A (en) | High-efficiency simple synthetic method for delta-chlorobutyl ester | |
| CN1491927A (en) | Process for preparing phloroglucinol | |
| CN101565436A (en) | 3, 3'-position biaryl group binaphthyl shaft chiral phosphoramidite ligand and preparation method thereof | |
| CN102791677A (en) | Preparation method of 4-aminomethylbenzoic acid | |
| CN108191814B (en) | Method for synthesizing cyclohexanone ethylene ketal under catalysis of titanium ammonium phosphotungstate composite salt | |
| CN102675415A (en) | Method for preparing bortezomib | |
| CN101993363B (en) | Method for preparing oxalic ester by CO coupling | |
| CN101302291B (en) | Catalyst for synthesizing polyketone by copolymerization of carbon monooxide and phenyl ethylene | |
| CN112062705A (en) | Synthesis method of 7-methyltryptophan | |
| CN1377874A (en) | Process for preparing sorbic acid | |
| CN101657419A (en) | Novel crystal forms of pyrrolylheptanoic acid derivatives | |
| CN113620761B (en) | Preparation method for synthesizing aryl aldehyde compound by reducing aryl secondary amide or aryl secondary amide derivative with phenylsilane | |
| CA2502360C (en) | Process for producing acetylene compound | |
| CN113149868B (en) | Method for synthesizing axichiral diene compound by trivalent rhodium catalysis | |
| CN103274958B (en) | Method for preparing amide compound through catalysis of ligand-assisted zirconium oxychloride | |
| CN114671869B (en) | Synthesis method of compound Tomivosertib | |
| CN1442405A (en) | Method of preparing 3-amino propane sulfonic acid | |
| CN102718663A (en) | Synthesis method of 5-chloro-1-indene amine | |
| CN1052301A (en) | The improvement of synthesis method for " fenbufen " | |
| CN102219678B (en) | Starting-up method for producing oxalic acid ester with CO |
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 | ||
| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |