CN108610247A - The preparation method of the chloro- 7- hydroxide radical-1-indenones of 6- - Google Patents
The preparation method of the chloro- 7- hydroxide radical-1-indenones of 6- Download PDFInfo
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- CN108610247A CN108610247A CN201611142486.8A CN201611142486A CN108610247A CN 108610247 A CN108610247 A CN 108610247A CN 201611142486 A CN201611142486 A CN 201611142486A CN 108610247 A CN108610247 A CN 108610247A
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- chloro
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- indenones
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- TVDOSSMKISEXMV-UHFFFAOYSA-N Oc(ccc(S(O)(=O)=O)c1)c1Cl Chemical compound Oc(ccc(S(O)(=O)=O)c1)c1Cl TVDOSSMKISEXMV-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/65—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups
-
- 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
- C07C303/02—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof
- C07C303/22—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of sulfonic acids or halides thereof from sulfonic acids, by reactions not involving the formation of sulfo or halosulfonyl groups; from sulfonic halides by reactions not involving the formation of halosulfonyl groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a kind of new synthetic method of 6 chlorine, 7 hydroxyl, 1 indone (compound IV), the technical problems such as reaction condition existing for current synthetic method is more harsh, and by-product is more, and post-processing is difficult, and raw material is difficult to obtain mainly are solved.The present invention is obtained by the reaction compound II, II with 3 chlorine, 4 hydroxy benzene sulfonic acid (compound I) and 3 chlorpromazine chlorides and compound III is obtained by the reaction in the presence of a lewis acid, and III sloughs sulfonic group and obtains IV.
Description
Technical field
The present invention relates to a kind of new preparation methods of the chloro- 7- hydroxide radical-1-indenones of 6-.
Background technology
The chloro- 7- hydroxide radical-1-indenones of 6- and relevant derivative have in pharmaceutical chemistry and organic synthesis field widely answers
With.There are complex process, problems with high costs for the preparation of the compound at present, it is therefore necessary to develop new preparation method with
Cost and optimize technique are reduced, a kind of preparation method of suitable industrialized production is obtained.
Invention content
The purpose of the present invention is develop a kind of highly selective to prepare the new preparation method of the chloro- 7- hydroxide radical-1-indenones of 6-.Mainly
Solve existing synthetic method craft complexity, technical problem with high costs.
Technical scheme of the present invention：
Compound II is obtained by the reaction with 3- chloro-4-hydroxyl benzene sulfonic acids (compound I) and 3- chlorpromazine chlorides in the present invention, and II is on road
Compound III is obtained by the reaction in the presence of Lewis acid, III sloughs sulfonic group and obtains IV, and reaction equation is as follows：
In above-mentioned technique, first step reaction condition is that 3- chloro-4-hydroxyl benzene sulfonic acids are dissolved in acetonitrile, and 1 equivalent, three second is added
Amine does alkali, and the addition equivalent of 3- chlorpromazine chlorides is 1.1 equivalents, is stirred 0.5 hour at 0 DEG C, then be stirred at room temperature 2 hours.The
Two step reaction conditions are that II is dissolved in dichloromethane, and 3 equivalent tetraethyl titanates are added and do lewis acid；It is handle that third, which walks reaction condition,
III is added in dilute sulfuric acid, and reaction temperature is 80~100 DEG C.
Beneficial effects of the present invention：
The present invention solves the preparation method complex process being currently known, disadvantage with high costs.With the common raw material of industry
3- chloro-4-hydroxyls benzene sulfonic acid is obtained by the reaction compound II, II with 3- chlorpromazine chlorides and chemical combination is obtained by the reaction in the presence of a lewis acid
Object III, III slough sulfonic group and obtain the chloro- 7- hydroxide radical-1-indenones of 6-, i.e. IV.The technique second step ring closure reaction high selectivity,
High income is easy to amplify, and the efficient quick preparation of the chloro- 7- hydroxide radical-1-indenones of 6- may be implemented.
Specific implementation mode
Specific embodiments of the present invention presented below to show possible implementation process, but are not intended to limit the present invention.
Embodiment 1
(1) preparation of compound II：
Compound I, that is, 3- chloro-4-hydroxyls benzene sulfonic acid (34.8g, 0.2mol) is dissolved in 500ml acetonitriles, triethylamine is added
(0.2mol) is cooled to 0 DEG C, and 3- chlorpromazine chlorides (25.2g, 0.2mol) are added dropwise, and 0 DEG C is stirred 0.5 hour, is stirred at room temperature 2 hours,
The detection reaction of TLC contact plates is finished, and successively by washing, 1M NaOH are washed reaction solution, are washed, saturated common salt washing, anhydrous sulphur
Sour sodium drying, is filtered to remove drier, is concentrated under reduced pressure to give compound II 47.52g, yield 90%.
(2) preparation of compound III：
Compound II (42g, 0.159mol) is added in 450ml dichloromethane, tetraethyl titanate is added
(108.7g, 0.477mol) is heated to 40 DEG C, is stirred to react 16 hours, and the detection reaction of TLC contact plates is finished, and water, extraction is added
It takes, stands, layering separates organic phase, dried with anhydrous sodium sulfate, be filtered to remove drier, is concentrated under reduced pressure to give compound III
Crude product, crude product re-crystallizing in ethyl acetate obtains white solid III29.7g, yield 82%.
(3) preparation of the chloro- 7- hydroxide radical-1-indenones of 6-
Compound III (22.8g, 0.1mol) is added in 500ml 1M sulfuric acid, 100 DEG C is heated to, it is small to be stirred to react 5
When, the detection reaction of TLC contact plates is finished, and reaction solution is cooled to room temperature, water and ethyl acetate is added, is extracted, is stood, point
Layer, separates organic phase, is washed three times with saturated salt solution and saturated sodium bicarbonate aqueous solution, dried with anhydrous sodium sulfate respectively,
It is filtered to remove drier i, is concentrated under reduced pressure to give the chloro- 7- hydroxide radical-1-indenones 8.14g of compound IV i.e. 6-, yield 96%.
Claims (3)
- The preparation method of the chloro- 7- hydroxide radical-1-indenones of 1.6-, it is characterized in that including the following steps：With 3- chloro-4-hydroxyl benzene sulfonic acids (compound I) is obtained by the reaction compound II, II with 3- chlorpromazine chlorides and compound III, III is obtained by the reaction in the presence of a lewis acid It sloughs sulfonic group and obtains IV, reaction equation is as follows：
- 2. the preparation method of the chloro- 7- hydroxide radical-1-indenones of 6- according to claim 1, it is characterized in that first step reaction condition It is dissolved in acetonitrile for 3- chloro-4-hydroxyl benzene sulfonic acids, and 1 eq of triethylamine is added and does alkali, the addition equivalent of 3- chlorpromazine chlorides is worked as 1.1 Amount；Second step reaction condition is that II is dissolved in dichloromethane, and 3 equivalent tetraethyl titanates are added and do lewis acid；Three-step reaction article Part is that III is added in dilute sulfuric acid.
- 3. the preparation method of the chloro- 7- hydroxide radical-1-indenones of 6- according to claim 1, it is characterized in that first step reaction is first 0 It stirs 0.5 hour, then is stirred at room temperature 2 hours at DEG C, second step reaction temperature is 30~40 DEG C, and third step reaction temperature is 80~100 DEG C.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201611142486.8A CN108610247A (en) | 2016-12-12 | 2016-12-12 | The preparation method of the chloro- 7- hydroxide radical-1-indenones of 6- |
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| CN201611142486.8A CN108610247A (en) | 2016-12-12 | 2016-12-12 | The preparation method of the chloro- 7- hydroxide radical-1-indenones of 6- |
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| CN201611142486.8A Withdrawn CN108610247A (en) | 2016-12-12 | 2016-12-12 | The preparation method of the chloro- 7- hydroxide radical-1-indenones of 6- |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105330525A (en) * | 2015-10-25 | 2016-02-17 | 湖南华腾制药有限公司 | Preparation method of 7-hydroxy-1-indanone |
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- 2016-12-12 CN CN201611142486.8A patent/CN108610247A/en not_active Withdrawn
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105330525A (en) * | 2015-10-25 | 2016-02-17 | 湖南华腾制药有限公司 | Preparation method of 7-hydroxy-1-indanone |
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Application publication date: 20181002 |