CN112010902A - Method for preparing formacyl methylene triphenylphosphine - Google Patents
Method for preparing formacyl methylene triphenylphosphine Download PDFInfo
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- CN112010902A CN112010902A CN201910454714.2A CN201910454714A CN112010902A CN 112010902 A CN112010902 A CN 112010902A CN 201910454714 A CN201910454714 A CN 201910454714A CN 112010902 A CN112010902 A CN 112010902A
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- phosphonium salt
- quaternary phosphonium
- triphenylphosphine
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- catalyst
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- 238000000034 method Methods 0.000 title claims abstract description 21
- XYDYWTJEGDZLTH-UHFFFAOYSA-N methylenetriphenylphosphorane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=C)C1=CC=CC=C1 XYDYWTJEGDZLTH-UHFFFAOYSA-N 0.000 title abstract description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims abstract description 36
- 150000004714 phosphonium salts Chemical group 0.000 claims abstract description 34
- 239000003054 catalyst Substances 0.000 claims abstract description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 11
- CRZJPEIBPQWDGJ-UHFFFAOYSA-N 2-chloro-1,1-dimethoxyethane Chemical compound COC(CCl)OC CRZJPEIBPQWDGJ-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000003513 alkali Substances 0.000 claims abstract description 4
- 238000001914 filtration Methods 0.000 claims abstract description 4
- 238000007796 conventional method Methods 0.000 claims abstract description 3
- 150000007522 mineralic acids Chemical class 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 8
- WLNHKVMQWPCCER-UHFFFAOYSA-N 2-[methylidene(diphenyl)-$l^{5}-phosphanyl]benzaldehyde Chemical compound C=1C=CC=CC=1P(C=1C(=CC=CC=1)C=O)(=C)C1=CC=CC=C1 WLNHKVMQWPCCER-UHFFFAOYSA-N 0.000 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 7
- 239000007787 solid Substances 0.000 claims description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 claims description 5
- 229940107816 ammonium iodide Drugs 0.000 claims description 3
- 230000003301 hydrolyzing effect Effects 0.000 claims description 3
- 125000001453 quaternary ammonium group Chemical group 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 239000000758 substrate Substances 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 2
- 230000003197 catalytic effect Effects 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- 230000007062 hydrolysis Effects 0.000 claims description 2
- 238000006460 hydrolysis reaction Methods 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 5
- 239000007864 aqueous solution Substances 0.000 abstract description 2
- 238000006555 catalytic reaction Methods 0.000 abstract description 2
- 239000002244 precipitate Substances 0.000 abstract 1
- 238000005406 washing Methods 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- NMPVEAUIHMEAQP-UHFFFAOYSA-N 2-Bromoacetaldehyde Chemical compound BrCC=O NMPVEAUIHMEAQP-UHFFFAOYSA-N 0.000 description 8
- QSKPIOLLBIHNAC-UHFFFAOYSA-N 2-chloro-acetaldehyde Chemical compound ClCC=O QSKPIOLLBIHNAC-UHFFFAOYSA-N 0.000 description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- HLVFKOKELQSXIQ-UHFFFAOYSA-N 1-bromo-2-methylpropane Chemical compound CC(C)CBr HLVFKOKELQSXIQ-UHFFFAOYSA-N 0.000 description 2
- XYHKNCXZYYTLRG-UHFFFAOYSA-N 1h-imidazole-2-carbaldehyde Chemical compound O=CC1=NC=CN1 XYHKNCXZYYTLRG-UHFFFAOYSA-N 0.000 description 2
- IXEVDYXYWYOASC-UHFFFAOYSA-N CO.CO.ClCC=O Chemical compound CO.CO.ClCC=O IXEVDYXYWYOASC-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000002386 leaching Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 238000007239 Wittig reaction Methods 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000022244 formylation Effects 0.000 description 1
- 238000006170 formylation reaction Methods 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 239000012434 nucleophilic reagent Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/54—Quaternary phosphonium compounds
- C07F9/5442—Aromatic phosphonium compounds (P-C aromatic linkage)
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for preparing formacyl methylene triphenylphosphine, which comprises the steps of firstly, reacting triphenylphosphine with excessive chloroacetaldehyde dimethyl acetal under the catalysis of a proper catalyst to obtain corresponding quaternary phosphonium salt; then dissolving the quaternary phosphonium salt in water, adding a trace amount of inorganic acid to hydrolyze the quaternary phosphonium salt, then dropping the quaternary phosphonium salt into an aqueous solution of alkali according to a conventional method, filtering and washing precipitates to directly obtain the formylmethylene triphenylphosphine. The method does not use expensive reagents, has simple and convenient operation, high yield and less three wastes, and is easy to realize industrialization.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a method for preparing formacyl methylene triphenylphosphine.
Background
Formyl methylene triphenylphosphine, also known as formyl methylene triphenylphosphine (CAS:2136-75-6), is a Wittig reagent for the construction of α, β -unsaturated aldehydes. The Wittig reagent contains formyl radicals, is relatively stable, has low reaction activity, and can selectively react with aldehyde carbonyl in substrate molecules to generate Wittig reaction.
The existing preparation method of formylmethylenetriphenylphosphine mainly comprises a methylenetriphenylphosphine formylation method, a bromoacetaldehyde method and a chloroacetaldehyde method, wherein the formylmethylenetriphenylphosphine (Ph) is adopted as the former method3P＝CH2) With ethyl formate or other formylating agents (e.g. formylimidazole) in benzene to produce formylmethylenetriphenylphosphine, however, such processes are primarily costly, harsh, involving expensive reagents such as butyllithium, formylimidazole, etc., and the intermediate methyleneTriphenylphosphine radical is very active and sensitive to water vapor; the latter two methods are to react triphenylphosphine with bromoacetaldehyde or chloroacetaldehyde first to give the corresponding quaternary phosphonium salt, which is then neutralized with a base to give formylmethylenetriphenylphosphine.
For example: chinese patent No. CN:107793450, which is to hydrolyze bromoacetaldehyde dimethyl acetal to obtain bromoacetaldehyde, and then perform nucleophilic substitution reaction between the bromoacetaldehyde and triphenylphosphine to obtain quaternary phosphonium salt, wherein the bromoacetaldehyde dimethyl acetal is expensive in raw material, and the solvent is extracted and evaporated to obtain anhydrous bromoacetic acid; mscromolecules,1999,32(15), 4751-. [ J.chem.Soc.1961,1266 ] triphenylphosphine is reacted with chloroacetaldehyde and then neutralized with triethylamine in ethanol; lett,17(24),5974-3P+CH2CHOCl-) Then removing hydrogen chloride under the action of sodium hydroxide, triethylamine or potassium hydroxide to obtain the formacyl methylene triphenylphosphine. The chloroacetaldehyde method is most economical and practical because the chloroacetaldehyde aqueous solution is relatively cheap and easy to obtain, and is also a method frequently adopted at present. However, in the literature related to the method, an azeotropic agent is added to remove water in chloroacetaldehyde, otherwise, the reaction effect is not ideal. In addition, during the azeotropic dehydration, partial chloroacetaldehyde undergoes side reactions such as condensation due to long-term heating, and finally a quaternary phosphonium salt (Ph) is formed3P+CH2CHOCl-) The yield is low and the purity is poor.
Disclosure of Invention
The present invention has been made to solve the above problems occurring in the prior art, and an object of the present invention is to provide a process for preparing formylmethylenetriphenylphosphine.
In order to realize the purpose, the invention selects the convenient and easily obtained chloroacetaldehyde dimethyl acetal to firstly carry out nucleophilic substitution reaction with triphenylphosphine to generate the corresponding quaternary phosphonium salt I, and the quaternary ammonium iodide salt is used as the catalyst in consideration of the relatively low activity of the chloroacetaldehyde dimethyl acetal on nucleophilic reagents, so that the reaction temperature is reduced, and the reaction time is shortened; the quaternary phosphonium salt I is a solid, insoluble in excess chloroacetaldehyde dimethanol and therefore easily separable by filtration; then under the catalysis of a small amount of hydrochloric acid and sulfuric acid, due to the electron-withdrawing induction effect of triphenylphosphine positive ions in the quaternary phosphonium salt I, the quaternary phosphonium salt I is easily hydrolyzed at room temperature to obtain a quaternary phosphonium salt II; the hydrolysis product is not treated, and is directly neutralized by alkali to obtain the target product formyl methylene triphenylphosphine.
The reaction formula involved in the method of the patent is as follows:
a process for preparing formylmethylenetriphenylphosphine comprising the steps of:
(1) dissolving triphenylphosphine in excessive chloroacetaldehyde dimethyl acetal, adding a catalyst, and reacting for a certain time at a certain temperature;
(2) cooling to room temperature, filtering and separating to obtain quaternary phosphonium salt I: Ph3P+CH2CH(OCH3)2Cl-Then dissolving the solid of the quaternary phosphonium salt I in water, adding a catalytic amount of inorganic acid, and hydrolyzing to obtain quaternary phosphonium salt II Ph3P+CH2CHOCl-；
(3) Finally, the formyl methylene triphenylphosphine is obtained by alkali treatment according to the conventional method.
As a further scheme of the invention: the mass ratio of the triphenylphosphine to the chloroacetaldehyde dimethyl acetal is controlled to be 1:3-10, and the optimal mass ratio is 1:3, and the chloroacetaldehyde dimethyl acetal is used as a substrate and a solvent.
As a further scheme of the invention: the catalyst used in the above reaction is tetrabutylammonium iodide [311-28-4] or other similar quaternary ammonium iodide salt, and the amount of the catalyst is 0.5-5% of the mass of triphenylphosphine.
As a further scheme of the invention: the reaction temperature for preparing the quaternary phosphonium salt I is 60-100 ℃, and the optimal temperature is 75-85 ℃; the reaction time is 8-12 h.
As a further scheme of the invention: the catalyst for hydrolyzing the quaternary phosphonium salt I into the quaternary phosphonium salt II is sulfuric acid, hydrochloric acid or other strong acid, and the addition amount of the catalyst is 1-5% of the weight of the quaternary phosphonium salt I.
Compared with the prior art, the method does not use expensive reagents, has simple and convenient operation, high yield and less three wastes, and is easy to realize industrialization.
Detailed Description
The technical solution of the present patent will be described in further detail with reference to the following embodiments.
Example one
A process for preparing formylmethylenetriphenylphosphine comprising the steps of:
1. 500g of chloroacetaldehyde dimethanol [ FW124.6], 52.5g of triphenylphosphine (0.20mol) and 0.74g of tetrabutylammonium iodide were charged in a 1L three-necked flask equipped with a mechanical stirrer, a thermometer and a dropping funnel, and the mixture was heated at 80 ℃ for 10 hours with stirring.
2. Naturally cooled to room temperature and the resulting white solid was filtered to give 72g of quaternary phosphonium salt I in 93% yield from the first step.
3. The solid of quaternary phosphonium salt I described above was added to 200mL of water, 1g of 30% HC1 was added, heated to 40 deg.C, and stirred for 2h to hydrolyze it to a homogeneous solution of quaternary phosphonium salt II.
4. And (2) dropwise adding the solution of the quaternary phosphonium salt II into 100mL of water dissolved with 7.7g of NaOH, controlling the temperature to be 20-30 ℃, completing dropwise adding within about 30 minutes, performing vacuum filtration by using a Buchner funnel, leaching with a small amount of water, and naturally airing to obtain 54.2g of a light yellow formyl methylene triphenylphosphine product, wherein the yield of the second step is 95.6%, the total yield of the two steps is 88.9%, and mp:186 ℃ and 188 ℃.
Example two
A process for preparing formylmethylenetriphenylphosphine comprising the steps of:
1. A1L three-necked flask equipped with a mechanical stirrer, a thermometer and a dropping funnel was charged with the mother liquor obtained in the step 1 of the above example I and 25g of chloroacetaldehyde dimethyl acetal [ FW124.6] and 52.5g of triphenylphosphine (0.20mol), and the mixture was heated at 80 ℃ for 10 hours under stirring.
2. Naturally cooled to room temperature and the resulting white solid was filtered to give 73.5g of quaternary phosphonium salt I in 95% yield from the first step.
3. The solid of the above quaternary phosphonium salt I was added to 200mL of water, and 1g of 98% H was added2S04Heating to 40 ℃, and stirring for 2h to hydrolyze the quaternary phosphonium salt II into a uniform solution.
4. And (3) dropwise adding the solution of the quaternary phosphonium salt II into 100mL of water dissolved with 7.9g of NaOH, controlling the temperature to be 20-30 ℃, completing dropwise adding within about 30 minutes, performing reduced pressure suction filtration by using a Buchner funnel, leaching with a small amount of water, and naturally drying to obtain 56.1g of a light yellow formyl methylene triphenylphosphine product, wherein the yield of the second step is 97%, the total yield of the two steps is 92.1%, and the mp is 186-.
Although the preferred embodiments of the present patent have been described in detail, the present patent is not limited to the above embodiments, and various changes can be made without departing from the spirit of the present patent within the knowledge of those skilled in the art.
Claims (5)
1. A method for preparing formylmethylene triphenylphosphine, which is characterized by comprising the following steps:
(1) dissolving triphenylphosphine in excessive chloroacetaldehyde dimethyl acetal, adding a catalyst, and reacting for a certain time at a certain temperature;
(2) cooling to room temperature, filtering and separating to obtain quaternary phosphonium salt I: Ph3P+CH2CH(OCH3)2Cl-Then dissolving the solid of the quaternary phosphonium salt I in water, adding a catalytic amount of inorganic acid, and hydrolyzing to obtain quaternary phosphonium salt II Ph3P+CH2CHOCl-；
(3) Finally, the formyl methylene triphenylphosphine is obtained by alkali treatment according to the conventional method.
2. The method for preparing formylmethylenetriphenylphosphine as claimed in claim 1, wherein the ratio of the substances of triphenylphosphine to chloroacetaldehyde dimethyl acetal is controlled to 1:3-10, preferably 1:3, and chloroacetaldehyde dimethyl acetal is both a substrate and a solvent.
3. The process of claim 1, wherein the catalyst used in the reaction is tetrabutylammonium iodide [311-28-4] or other similar quaternary ammonium iodide salt, and the amount of the catalyst is 0.5-5% by mass of the triphenylphosphine.
4. The method for preparing formylmethylenetriphenylphosphine as claimed in claim 1, wherein the temperature of the reaction for preparing the quaternary phosphonium salt I is from 60 to 100 ℃, preferably from 75 to 85 ℃; the reaction time is 8-12 h.
5. The method for preparing formylmethylenetriphenylphosphine as claimed in claim 1, wherein the catalyst for the hydrolysis of the quaternary phosphonium salt I to the quaternary phosphonium salt II is sulfuric acid, hydrochloric acid or other strong acid, and is added in an amount of 1-5% by weight of the quaternary phosphonium salt I.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201910454714.2A CN112010902A (en) | 2019-05-29 | 2019-05-29 | Method for preparing formacyl methylene triphenylphosphine |
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| CN201910454714.2A CN112010902A (en) | 2019-05-29 | 2019-05-29 | Method for preparing formacyl methylene triphenylphosphine |
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| CN201910454714.2A Pending CN112010902A (en) | 2019-05-29 | 2019-05-29 | Method for preparing formacyl methylene triphenylphosphine |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103910759A (en) * | 2012-12-29 | 2014-07-09 | 安徽贝克生物制药有限公司 | Preparation method of (carbethoxyethylidene)triphenylphosphorane |
| CN107973818A (en) * | 2017-11-23 | 2018-05-01 | 江苏大学 | A kind of preparation method of cremart |
| CN109678662A (en) * | 2018-12-29 | 2019-04-26 | 云南大学 | A kind of synthetic method of 12 carbon of acetic acid 7E, 9Z-, two enester |
-
2019
- 2019-05-29 CN CN201910454714.2A patent/CN112010902A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103910759A (en) * | 2012-12-29 | 2014-07-09 | 安徽贝克生物制药有限公司 | Preparation method of (carbethoxyethylidene)triphenylphosphorane |
| CN107973818A (en) * | 2017-11-23 | 2018-05-01 | 江苏大学 | A kind of preparation method of cremart |
| CN109678662A (en) * | 2018-12-29 | 2019-04-26 | 云南大学 | A kind of synthetic method of 12 carbon of acetic acid 7E, 9Z-, two enester |
Non-Patent Citations (2)
| Title |
|---|
| HONGBO WEI ET AL.: "Synthesis of Polysubstituted Pyridines via a One-Pot Metal-Free Strategy", 《ORG. LETT. 》 * |
| 曾步兵 等: "《药物合成反应学习指导》", 31 October 2013, 华东理工大学出版社 * |
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