CN102276557A - Preparation method of pyrrolidine 5-substituted pentadiene amide compound - Google Patents
Preparation method of pyrrolidine 5-substituted pentadiene amide compound Download PDFInfo
- Publication number
- CN102276557A CN102276557A CN2010101978723A CN201010197872A CN102276557A CN 102276557 A CN102276557 A CN 102276557A CN 2010101978723 A CN2010101978723 A CN 2010101978723A CN 201010197872 A CN201010197872 A CN 201010197872A CN 102276557 A CN102276557 A CN 102276557A
- Authority
- CN
- China
- Prior art keywords
- tetramethyleneimine
- pyrrolidine
- alpha
- replaces
- substituted
- 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)
Abstract
The invention relates to a preparation method of a pyrrolidine 5-substituted pentadiene amide compound. The preparation method concretely comprises the following steps: generating pyrrolidine alpha-halogenated acetamide (3) by reacting pyrrolidine (1) with alpha-halogenated acetic halide or alpha-halogenated acetic acid (2) in an a proper alkali or a proper condensing agent and a certain solvent; generating a compound (5) by reacting pyrrolidine alpha-halogenated acetamide (3) with phosphonic acid trisubstituted ester or trisubstituted phosphine (4) at a temperature of 60-180DEG C; and obtaining the pyrrolidine 5-substituted pentadiene amide compound by reacting the compound (5) with (E)-3-substituted acrolein (6) in a proper alkali and a certain solvent. The preparation method of the pyrrolidine 5-substituted pentadiene amide compound has the advantages of high selectivity, simple operation process, low cost and suitability of industrial production.
Description
Technical field
The invention belongs to the organic compound preparing technical field, specifically, the present invention relates to the preparation method that a kind of tetramethyleneimine 5-replaces the Pentadienamide compounds.
Background technology
Be rich in tetramethyleneimine 5-in the piperaceae plant and replace the Pentadienamide compounds, this compounds has wide biological activity, as anti-oxidant, anti-platelet aggregation, tuberculosis, kill plasmodium etc., therefore causes people's extensive concern.But its content in natural is very low, as the content of Jia Betel booth alkali (Sarmentine) in Pipersarmentosum less than 0.1%.Therefore, it is with practical value to explore its chemical synthesis process.
Existing study on the synthesis report in the document about tetramethyleneimine 5-replacement Pentadienamide compounds, Yi Jia Betel booth alkali is example:
1. document Tetrahedron Letters (1987), 28 (19), reported with the arsenic ylide to be the synthetic method of important intermediate among the 2159-2162., arsenic toxicity is bigger, is difficult for industrialization, and environmental pollution is bigger.
2. document Tetrahedron Letters (1995), 36 (22), the following method of report among the 3901-390462.:
The Grignard reagent that this route is used is responsive, be unfavorable for suitability for industrialized production, and route is also longer.
3. document Can.J.Chem.2004 makes up the two keys adjacent with carbonyl with the Ramber-Backlund reaction among the 82:622-630..
This synthetic route is longer, and reagent is expensive.
4. document Can.J.Chem.1996 mainly is that agents useful for same is expensive with two two keys in the acetylene bond reaction generation Jia Betel booth alkali among the 74:419-432..
More than all synthetic routes all have certain defective, be not easy to obtain, react defectives such as complexity, complex operation as raw material, be difficult for industrialization.Do not see at present to be that the Witting of important intermediate reacts synthesis of pyrrolidine 5-to replace the report of Pentadienamide compounds in addition with the phosphorus ylide.
Summary of the invention
The invention provides a kind of method that tetramethyleneimine 5-replaces the Pentadienamide compounds for preparing.
Particularly, the invention provides a kind of method that tetramethyleneimine 5-replaces the Pentadienamide compounds for preparing, this method may further comprise the steps:
1, a kind of method for preparing tetramethyleneimine 5-replacement Pentadienamide compounds, this method may further comprise the steps:
(1) tetramethyleneimine (1) and alpha-halogen acetyl halide or alpha-halogen acetate (2) are at suitable alkali or suitable condensing agent, and reaction generates tetramethyleneimine α-Lu Daiyixianan (3) in certain solvent;
(2) tetramethyleneimine α-Lu Daiyixianan (3) replaces ester or three with phosphonic acids three and replaces phosphine (4) reacting generating compound (5) under 60 ℃ of-180 ℃ of temperature;
(3) compound (5) with (E)-3-substituted acrylic aldehyde (6) reacts to such an extent that tetramethyleneimine 5-replaces Pentadienamide compounds (7) in suitable alkali and certain solvent.
2, method according to claim 1, wherein the halo atom can be chlorine, bromine or iodine.
3, method according to claim 1, substituent R wherein can be the straight or branched alkoxyl group of the straight or branched alkyl of phenyl, substituted-phenyl, a 1-8 carbon atom or phenoxy group, substituent phenoxy, a 1-8 carbon atom.
4, method according to claim 1, wherein substituting group Y can be hydrogen, alkyl, cycloalkyl, thiazolinyl, alkynyl, aryl, alkylaryl, arylalkyl, aryl alkenyl, aromatic yl polysulfide yl or heterocyclic radical.
5, according to the described method of claim 1 (1), wherein suitable alkali can be organic bases (pyridine, triethylamine, diisopropyl ethyl amine) or mineral alkali (salt of wormwood, yellow soda ash, lime carbonate, cesium carbonate, saleratus, sodium bicarbonate).Certain solvent can be methylene dichloride, chloroform, 1,2-ethylene dichloride, tetrahydrofuran (THF), benzene,toluene,xylene.
6, according to the described method of claim 1 (3), wherein suitable alkali can be salt of wormwood, sodium hydroxide, sodium hydride, n-Butyl Lithium, isobutyl-lithium, lithium diisopropylamine, hexamethyl two silica-based amido lithiums, sodium hexamethyldisilazide, potassium hexamethyldisilazide.Solvent is preferably tetrahydrofuran (THF), methylene dichloride, 1,2 ethylene dichloride, benzene, toluene, acetonitrile.
Beneficial effect
The preparation method of tetramethyleneimine 5-replacement Pentadienamide compounds provided by the invention has solved the defective of tetramethyleneimine 5-replacement Pentadienamide compounds preparation process complexity, tetramethyleneimine 5-provided by the present invention replaces the preparation method of Pentadienamide compounds, selectivity height, operating process are simple, are easy to industrialization.
Embodiment
In order to understand the present invention, further specify the present invention with embodiment below, but do not limit the present invention.
The preparation of embodiment: Jia Betel booth alkali
In the suspension liquid of tetramethyleneimine (100g), sodium bicarbonate (590.6g), methylene dichloride (2L), add chloroacetyl chloride (190.5g), stirring at room reaction 2 hours, filter, concentrate silica gel column chromatography, eluent is a sherwood oil: the mixing solutions of ethyl acetate=2: 1, get faint yellow solid 186g, yield, 90%.
Above-mentioned gained solid (166g) is heated to 110 ℃ with triethoxy phosphonic acid ester (242g), and TLC follows the tracks of to detect and finishes until raw material reaction, and silica gel column chromatography gets yellow liquid (251g), and yield is 90%.
Under ice-water bath, tetrahydrofuran solution with above-mentioned yellow liquid (135g), dropwise join in the tetrahydrofuran (THF) suspension liquid of sodium hydride (11.8g), 0.5 reinforced finishing after hour, tetrahydrofuran solution with anti--2-octenal (62g) dropwise joins in the above-mentioned mixed solution then, added finish after, reaction solution is warming up to room temperature, TLC follows the tracks of to detect and finishes until raw material reaction, SODIUM PHOSPHATE, MONOBASIC cancellation reaction, mixed solution extracts with methyl tertiary butyl ether, the organic layer anhydrous sodium sulfate drying concentrates, silica gel column chromatography (sherwood oil: ethyl acetate=5: 1) get yellow liquid, this yellow liquid recrystallization (10 ℃) in normal hexane gets white solid 55.6g, yield 51%.
1H?NMR(400MHz,CDCl
3)δ7.26(1H,dd,J=15.0,9.9Hz),6.17(1H,dd,J=15.0,9.9Hz),6.07(1H,d,J=15.0Hz),6.07(1H,dt,J=15.0,7.5Hz),3.51-3.55(4H,m),2.16-2.18(2H,m),1.87-1.99(4H,m),1.25-1.48(6H,m),0.88(3H,t,J=6.3Hz);
13C?NMR(100MHz,CDCl
3)δ165.3,143.3,142.3,128.7,1199,46.4,45.8,32.9,31.2,28.4,26.0,24.4,22.4,14.1;MS(ESI)m/z?244[M+Na]
+.
Method of the present invention is described by specific embodiment.Those skilled in the art can use for reference link such as content appropriate change processing condition of the present invention and realize corresponding other purpose, its relevant change does not all break away from content of the present invention, all similar replacements and change will become apparent to those skilled in the art that and all be regarded as comprising within the scope of the present invention.
Claims (6)
1. one kind prepares the method that tetramethyleneimine 5-replaces the Pentadienamide compounds, and this method may further comprise the steps:
(1) tetramethyleneimine (1) and alpha-halogen acetyl halide or alpha-halogen acetate (2) are at suitable alkali or suitable condensing agent, and reaction generates tetramethyleneimine α-Lu Daiyixianan (3) in certain solvent;
(2) tetramethyleneimine α-Lu Daiyixianan (3) replaces ester or three with phosphonic acids three and replaces phosphine (4) reacting generating compound (5) under 60 ℃ of-180 ℃ of temperature;
(3) compound (5) with (E)-3-substituted acrylic aldehyde (6) reacts to such an extent that tetramethyleneimine 5-replaces Pentadienamide compounds (7) in suitable alkali and certain solvent.
2. method according to claim 1, wherein the halo atom can be chlorine, bromine or iodine.
3. method according to claim 1, substituent R wherein can be the straight or branched alkoxyl group of the straight or branched alkyl of phenyl, substituted-phenyl, a 1-8 carbon atom or phenoxy group, substituent phenoxy, a 1-8 carbon atom.
4. method according to claim 1, wherein substituting group Y can be hydrogen, alkyl, cycloalkyl, thiazolinyl, alkynyl, aryl, alkylaryl, arylalkyl, aryl alkenyl, aromatic yl polysulfide yl or heterocyclic radical.
5. according to the described method of claim 1 (1), wherein suitable alkali can be organic bases (pyridine, triethylamine, diisopropyl ethyl amine) or mineral alkali (salt of wormwood, yellow soda ash, lime carbonate, cesium carbonate, saleratus, sodium bicarbonate).Certain solvent can be methylene dichloride, chloroform, 1,2-ethylene dichloride, tetrahydrofuran (THF), benzene,toluene,xylene.
6. according to the described method of claim 1 (3), wherein suitable alkali can be salt of wormwood, sodium hydroxide, sodium hydride, n-Butyl Lithium, isobutyl-lithium, lithium diisopropylamine, hexamethyl two silica-based amido lithiums, sodium hexamethyldisilazide, potassium hexamethyldisilazide.Solvent is preferably tetrahydrofuran (THF), methylene dichloride, 1,2 ethylene dichloride, benzene, toluene, acetonitrile.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2010101978723A CN102276557A (en) | 2010-06-11 | 2010-06-11 | Preparation method of pyrrolidine 5-substituted pentadiene amide compound |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2010101978723A CN102276557A (en) | 2010-06-11 | 2010-06-11 | Preparation method of pyrrolidine 5-substituted pentadiene amide compound |
Publications (1)
Publication Number | Publication Date |
---|---|
CN102276557A true CN102276557A (en) | 2011-12-14 |
Family
ID=45102345
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN2010101978723A Pending CN102276557A (en) | 2010-06-11 | 2010-06-11 | Preparation method of pyrrolidine 5-substituted pentadiene amide compound |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN102276557A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103788022A (en) * | 2012-10-30 | 2014-05-14 | 天津卡普希科技有限公司 | Novel preparation method of (2E,4E)-1-(1-pyrrolidinyl)-2,4-decadien-1-one (sarmentine) |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101423501A (en) * | 2008-12-10 | 2009-05-06 | 中国农业大学 | Heterocycle-containing 5-phenyl-2,4-pentadienyl-1-ones compounds as well as preparation method and application thereof |
US20090124701A1 (en) * | 2007-11-08 | 2009-05-14 | Symrise Gmbh & Co. Kg | Use of alkamides for masking an unpleasant flavor |
CN101544619A (en) * | 2009-03-03 | 2009-09-30 | 黑龙江省华信药业有限公司 | Method for synthesizing Piberacine precursor |
CN101723918A (en) * | 2008-10-24 | 2010-06-09 | 重庆医科大学医药研究所 | Process for preparing cinepazide maleate |
-
2010
- 2010-06-11 CN CN2010101978723A patent/CN102276557A/en active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20090124701A1 (en) * | 2007-11-08 | 2009-05-14 | Symrise Gmbh & Co. Kg | Use of alkamides for masking an unpleasant flavor |
CN101723918A (en) * | 2008-10-24 | 2010-06-09 | 重庆医科大学医药研究所 | Process for preparing cinepazide maleate |
CN101423501A (en) * | 2008-12-10 | 2009-05-06 | 中国农业大学 | Heterocycle-containing 5-phenyl-2,4-pentadienyl-1-ones compounds as well as preparation method and application thereof |
CN101544619A (en) * | 2009-03-03 | 2009-09-30 | 黑龙江省华信药业有限公司 | Method for synthesizing Piberacine precursor |
Non-Patent Citations (8)
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103788022A (en) * | 2012-10-30 | 2014-05-14 | 天津卡普希科技有限公司 | Novel preparation method of (2E,4E)-1-(1-pyrrolidinyl)-2,4-decadien-1-one (sarmentine) |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN107739333A (en) | A kind of preparation method of green quinoline compound | |
CN105330643A (en) | Preparation method of cobimetinib | |
CN102206178B (en) | Method for preparing imrecoxib | |
CN104761583A (en) | Method for producing phosphorus-containing alpha-keto acid | |
CN101735198A (en) | Novel method for preparing c-Met inhibitor PF22341066 | |
PL144594B1 (en) | Method of obtaining novel derivatives of 3,5-dihydroxyvaleric acid | |
CN102993259A (en) | Preparation method of fulvestrant intermediate | |
CN102276557A (en) | Preparation method of pyrrolidine 5-substituted pentadiene amide compound | |
CN103804232B (en) | A kind of 1-cyano group-1-(7-methoxyl-3,4-dihydro-1-naphthyl) methanol esters compounds and its preparation method and application | |
CN101544682A (en) | 11-keto-16,17-epoxyprogesterone and industrial production method | |
CN107513056B (en) | A kind of synthetic method of the quinolines of the group containing tetrahydrofuran | |
CN102153522B (en) | Novel method for preparing N-substituted 2-hydroxy-morpholin-3-one compound | |
WO2004026224A2 (en) | Process for preparing prostaglandin derivatives and starting materials for the same | |
Ordonez et al. | Diastereoselective reduction of dimethyl γ-[(Np-toluenesulfonyl) amino]-β-ketophosphonates derived from amino acids | |
CN110156721A (en) | Utilize diazotate, cyclic ethers, amine and CO2The method of synthesis of carbamates | |
CN105315284A (en) | Preparation method of Anagliptin intermediate | |
CN101948484B (en) | Method for preparing travoprost intermediate | |
CN106946724A (en) | The synthetic method of the benzyl malonic acid mono ethyl ester of 2 acetylamino of monoamine base inhibitor class intermediate 2 | |
CN102219792A (en) | Novel method for preparing prasugrel | |
CN101486696B (en) | Preparation of 2,5-dimethyl furan-3,4-dicarboxylic acid | |
CN110256492A (en) | One kind compound containing phosphine carboxylic acid and preparation method thereof | |
CN109574778A (en) | A kind of preparation method of Bu Waxitan and its intermediate | |
CN102993080B (en) | A kind of synthetic method of gliclazide | |
CN103102280A (en) | Preparation method of optical pure 1-(alpha-amino benzyl)-2-naphthol | |
CN103508987A (en) | Method for synthetizing 2,3-disubstituted dihydrobenzofuran |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
DD01 | Delivery of document by public notice |
Addressee: Accenda Tech Co., Ltd. He Feng Document name: Notification of Publication of the Application for Invention |
|
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20111214 |