CN112851527B - Preparation method of m-aminophenylacetylene - Google Patents
Preparation method of m-aminophenylacetylene Download PDFInfo
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- CN112851527B CN112851527B CN202011629407.2A CN202011629407A CN112851527B CN 112851527 B CN112851527 B CN 112851527B CN 202011629407 A CN202011629407 A CN 202011629407A CN 112851527 B CN112851527 B CN 112851527B
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- nitroacetophenone
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- aminophenylacetylene
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- triethyl phosphite
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- NNKQLUVBPJEUOR-UHFFFAOYSA-N 3-ethynylaniline Chemical group NC1=CC=CC(C#C)=C1 NNKQLUVBPJEUOR-UHFFFAOYSA-N 0.000 title claims abstract description 24
- 238000002360 preparation method Methods 0.000 title abstract description 6
- ARKIFHPFTHVKDT-UHFFFAOYSA-N 1-(3-nitrophenyl)ethanone Chemical compound CC(=O)C1=CC=CC([N+]([O-])=O)=C1 ARKIFHPFTHVKDT-UHFFFAOYSA-N 0.000 claims abstract description 25
- 238000000034 method Methods 0.000 claims abstract description 21
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 claims abstract description 19
- 150000002148 esters Chemical class 0.000 claims abstract description 16
- 239000003054 catalyst Substances 0.000 claims abstract description 11
- 230000009471 action Effects 0.000 claims abstract description 9
- 239000003513 alkali Substances 0.000 claims abstract description 7
- 230000009467 reduction Effects 0.000 claims abstract description 5
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical group [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 30
- 238000006243 chemical reaction Methods 0.000 claims description 18
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 15
- 239000002904 solvent Substances 0.000 claims description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- 238000006722 reduction reaction Methods 0.000 claims description 10
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 9
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical group [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 9
- 239000001110 calcium chloride Substances 0.000 claims description 9
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 9
- 239000012043 crude product Substances 0.000 claims description 9
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 claims description 9
- 229960000549 4-dimethylaminophenol Drugs 0.000 claims description 8
- 239000003638 chemical reducing agent Substances 0.000 claims description 8
- 238000009833 condensation Methods 0.000 claims description 7
- 230000005494 condensation Effects 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical group [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 239000002585 base Substances 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 238000006482 condensation reaction Methods 0.000 claims description 4
- 239000012074 organic phase Substances 0.000 claims description 4
- 238000000605 extraction Methods 0.000 claims description 3
- 238000005292 vacuum distillation Methods 0.000 claims description 3
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 abstract description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 abstract description 6
- 239000002994 raw material Substances 0.000 abstract description 5
- 238000005660 chlorination reaction Methods 0.000 abstract description 3
- 238000009776 industrial production Methods 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 abstract description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 2
- 230000008859 change Effects 0.000 abstract description 2
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 2
- 239000000460 chlorine Substances 0.000 abstract description 2
- 229910052801 chlorine Inorganic materials 0.000 abstract description 2
- 230000007613 environmental effect Effects 0.000 abstract description 2
- 229910052760 oxygen Inorganic materials 0.000 abstract description 2
- 239000001301 oxygen Substances 0.000 abstract description 2
- 238000001308 synthesis method Methods 0.000 abstract description 2
- 125000002587 enol group Chemical group 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 6
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 5
- 229960001433 erlotinib Drugs 0.000 description 5
- 239000000203 mixture Substances 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 150000002085 enols Chemical class 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- DHYHYLGCQVVLOQ-UHFFFAOYSA-N 3-bromoaniline Chemical compound NC1=CC=CC(Br)=C1 DHYHYLGCQVVLOQ-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 238000007239 Wittig reaction Methods 0.000 description 1
- XDZJJCSACPSBCP-UHFFFAOYSA-N [O-][N+](C1=CC=CC(C=COP(O)(O)=O)=C1)=O Chemical compound [O-][N+](C1=CC=CC(C=COP(O)(O)=O)=C1)=O XDZJJCSACPSBCP-UHFFFAOYSA-N 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/30—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of nitrogen-to-oxygen or nitrogen-to-nitrogen bonds
- C07C209/32—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of nitrogen-to-oxygen or nitrogen-to-nitrogen bonds by reduction of nitro groups
- C07C209/325—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of nitrogen-to-oxygen or nitrogen-to-nitrogen bonds by reduction of nitro groups reduction by other means than indicated in C07C209/34 or C07C209/36
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/08—Preparation of nitro compounds by substitution of hydrogen atoms by nitro groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
-
- 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
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4056—Esters of arylalkanephosphonic acids
-
- 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
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4071—Esters thereof the ester moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4075—Esters with hydroxyalkyl compounds
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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)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of m-aminophenylacetylene, belonging to the technical field of organic synthesis. The method takes m-nitroacetophenone as a raw material to react with triethyl phosphite under the action of a catalyst, and the m-nitroacetophenone is continuously converted into an enol form to be condensed with the triethyl phosphite to obtain a condensed ester; meanwhile, the condensed ester is easy to separate and has high purity. The ester generates m-nitroacetophenone under the action of strong alkali, and the m-aminophenylacetylene is obtained by reduction. Compared with an acetophenone chlorination method, the synthesis method does not need to change oxygen of m-nitroacetophenone into chlorine by phosphorus oxychloride, has the advantages of small pollution, high purity (reaching more than 98%), no use of high-pollution raw material reagents, simple operation, environmental protection and convenient realization of industrial production.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a preparation method of m-aminophenylacetylene.
Background
Erlotinib (erlotinib), chemical name is N- (3-ethynylphenyl) - [6, 7-bis (2-methoxyethoxy) ] quinazolin-4-amine, 2004 US FDA approved for marketing, for the treatment of pancreatic cancer and metastatic non-small cell lung cancer. The structural formula of erlotinib is:
many patents and documents relating to the synthesis of erlotinib are reported, and the erlotinib is synthesized by using a key intermediate m-aminophenylacetylene as a raw material, wherein the structural formula of the m-aminophenylacetylene is as follows:
the meta-aminophenylacetylene literature reports that the following synthetic methods are generally available;
coupling method:
the method directly couples alkyne and m-amino bromobenzene, needs a valuable coupling agent, uses sodium hydride for final reaction, is dangerous and not environment-friendly, and is not suitable for industrial production.
Bromine addition and reemination method:
the method uses liquid bromine, has large pollution, and uses sodium hydride, which is unsafe.
An acetophenone chlorination method:
the method uses a large amount of phosphorus oxychloride and pyridine, and is difficult to treat industrially.
wittig reaction method
A large amount of highly toxic carbon tetrabromide is used in the method, and the triphenylphosphine byproduct is difficult to remove.
Disclosure of Invention
In order to solve the above problems, the present invention provides a method for preparing m-aminophenylacetylene, which comprises the following steps:
the method comprises the following steps: performing condensation reaction of m-nitroacetophenone and triethyl phosphite (excessive and used as a solvent) under the action of a catalyst at 100-150 ℃, and separating triethyl phosphite and insoluble substances after the reaction is finished; the obtained intermediate condensed ester reacts with alkali to obtain m-nitroacetylene, and finally the m-aminophenylacetylene is obtained by reduction. Wherein the catalyst is potassium iodide, tetrabutyl ammonium iodide and DMAP; wherein the mass ratio of m-nitroacetophenone, triethyl phosphite, potassium iodide, tetrabutyl ammonium iodide and DMAP is 1:1-10:0.05-0.2:0.05-0.2:0.05-0.2. In the invention, m-nitroacetophenone is firstly changed into enol under the action of a catalyst, potassium iodide is used for replacing hydroxyl with iodide, and finally, the enol-nitroacetophenone is reacted with triethyl phosphite.
Specifically, the process of reacting the condensed ester with a base is as follows: and (3) dropwise adding the condensation ester into an organic solvent A with alkali, reacting at the temperature of not more than 60 ℃, adding water and an extracting agent for extraction after the reaction is finished, taking an organic phase, and recovering the solvent to obtain the m-nitroacetophenone. The process is similar to the prior art.
Wherein the base is selected from potassium tert-butoxide, sodium hydroxide or potassium hydroxide.
Preferably, the base is potassium tert-butoxide.
Wherein the organic solvent A is selected from dimethyl sulfoxide, tetrahydrofuran, methyltetrahydrofuran, N-methylpyrrolidone or hexamethyl phosphonic triamine.
Preferably, the organic solvent a is dimethyl sulfoxide.
Specifically, the process of the reduction reaction is as follows: carrying out reduction reaction on m-nitroacetophenone and a reducing agent in a solvent B at the temperature of 70-80 ℃, filtering and recovering the solvent after the reaction is finished to obtain a crude product, and collecting 90-96 ℃ fractions of the crude product under a vacuum condition to obtain m-aminophenylacetylene. Wherein the reducing agent is zinc powder and calcium chloride, and the mol ratio of the m-nitroacetylene to the zinc powder to the calcium chloride is 1:1.1-3.0:1.1-3.0.
Wherein, the solvent B is ethanol (such as 95wt% specifically).
Preferably, the preparation method of m-aminophenylacetylene provided by the invention comprises the following steps:
(1) The m-nitroacetophenone and triethyl phosphite are subjected to condensation reaction at the temperature of 100-150 ℃ under the action of a catalyst, after the reaction is finished, triethyl phosphite and insoluble substances are separated, and then the intermediate condensation ester is obtained by vacuum distillation. Wherein the catalyst is potassium iodide, tetrabutyl ammonium iodide and DMAP, and the mass ratio of m-nitroacetophenone, triethyl phosphite, potassium iodide, tetrabutyl ammonium iodide and DMAP is 1:1-10:0.05-0.2:0.05-0.2:0.05-0.2.
(2) And (2) dropwise adding the condensation ester obtained in the step (1) into a dimethyl sulfoxide solution of potassium tert-butoxide, reacting at the temperature of not more than 60 ℃, adding water and an extracting agent (such as dichloromethane) for extraction after the reaction is finished, taking an organic phase, and recovering the solvent to obtain the m-nitroacetophenone.
(3) Carrying out reduction reaction on m-nitroacetophenone in ethanol and a reducing agent at the temperature of 70-80 ℃, filtering and recovering a solvent to obtain a crude product after the reaction is finished, and collecting 90-96 ℃ fractions of the crude product under a vacuum condition to obtain m-aminophenylacetylene. The reducing agent is zinc powder and calcium chloride, and the molar ratio of the m-nitroacetylene to the zinc powder to the calcium chloride is 1:1.1-3.0:1.1-3.0.
The invention provides a preparation method of m-aminophenylacetylene, which comprises the steps of taking m-nitroacetophenone as a raw material, reacting the m-nitroacetophenone with triethyl phosphite under the action of a catalyst, continuously converting the m-nitroacetophenone into enol form, and condensing the enol form with the triethyl phosphite to obtain condensation ester; meanwhile, the condensed ester is easy to separate and has high purity. The ester generates m-nitroacetylene under the action of strong alkali, and m-aminophenylacetylene is obtained by reduction. Compared with an acetophenone chlorination method, the synthesis method does not need to change oxygen of m-nitroacetophenone into chlorine by phosphorus oxychloride, has the advantages of small pollution, high purity (reaching more than 98%), no use of high-pollution raw material reagents, simple operation, environmental protection and convenient realization of industrial production.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, embodiments of the present invention are described in further detail below.
Example 1
100g of m-nitroacetophenone, 5g of potassium iodide, 10g of tetrabutyl ammonium iodide, DMAP5g and 500g of triethyl phosphite are mixed at room temperature, the mixture is heated to 120 ℃, gas is discharged when the mixture is visible, the mixture is slowly refluxed to avoid over violent reaction, then the mixture is heated until the reflux temperature reaches 150 ℃, the reaction is carried out for 5 to 8 hours, the triethyl phosphite is recovered at the reduced pressure of 90 to 100 ℃, insoluble substances are removed by filtration to obtain m-nitroacetenyl phosphate, 96g of pure product is obtained by high vacuum distillation, and the yield is 82%.
Example 2
90g of m-nitrophenylvinyl phosphate is dripped into 200ml of DMSO solution containing 20g of potassium tert-butoxide, the reaction releases heat, the temperature is maintained to be not more than 60 ℃, the reaction is detected to be completed by stirring, 200ml of water is added, dichloromethane is extracted, and the solvent is recovered to obtain 64g of m-nitroacetylene with the yield of 81%.
Example 3
Adding 200ml of 95wt% ethanol into 60g of m-nitroacetylene, reducing 10g of zinc powder and 10g of calcium chloride, heating and refluxing until the reduction is finished, filtering, and recovering ethanol to obtain a crude product of m-aminophenylacetylene. Collecting 90-96 ° distillate under 2mmHg high vacuum to obtain over 98% m-aminophenylacetylene 42g with yield of 78%.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and should not be taken as limiting the scope of the present invention, which is intended to cover any modifications, equivalents, improvements, etc. within the spirit and scope of the present invention.
Claims (6)
1. A method for preparing m-aminophenylacetylene, characterized by comprising: performing condensation reaction on m-nitroacetophenone and triethyl phosphite under the action of a catalyst at the temperature of 100-150 ℃, and separating triethyl phosphite and insoluble substances after the reaction is finished; the obtained intermediate condensation ester reacts with alkali to obtain m-nitroacetophenone, and finally, the m-nitroacetophenone is obtained through reduction; the catalyst is potassium iodide, tetrabutyl ammonium iodide and DMAP, and the mass ratio of the m-nitroacetophenone to the triethyl phosphite to the potassium iodide to the tetrabutyl ammonium iodide to the DMAP is 1:1-10:0.05-0.2:0.05-0.2:0.05-0.2;
the reaction with alkali is as follows:
dropwise adding the condensed ester into an organic solvent A with alkali, reacting at the temperature of not more than 60 ℃, adding water and an extracting agent for extraction after the reaction is finished, taking an organic phase, and recovering the solvent to obtain m-nitroacetophenone; the base is potassium tert-butoxide;
the structural formula of the condensed ester is as follows:
2. the method for preparing m-aminophenylacetylene according to claim 1, wherein the organic solvent A is selected from dimethyl sulfoxide, tetrahydrofuran, methyltetrahydrofuran, N-methylpyrrolidone or hexamethyl phosphonic triamine.
3. The method for preparing m-aminophenylacetylene according to claim 1, wherein the organic solvent A is dimethyl sulfoxide.
4. The method for preparing m-aminophenylacetylene according to claim 1, wherein the reduction reaction is carried out by: carrying out reduction reaction on m-nitroacetylene and a reducing agent in a solvent B at the temperature of 70-80 ℃, filtering and recovering the solvent to obtain a crude product after the reaction is finished, collecting 90-96 ℃ fraction of the crude product under the vacuum condition to obtain m-aminophenylacetylene, wherein the reducing agent is zinc powder and calcium chloride, and the molar ratio of the m-nitroacetylene to the zinc powder to the calcium chloride is 1:1.1-3.0:1.1-3.0.
5. The method for producing m-aminophenylacetylene according to claim 4, wherein the solvent B is ethanol.
6. The method for preparing m-aminophenylacetylene according to claim 1, wherein the method comprises:
(1) Performing condensation reaction on m-nitroacetophenone and triethyl phosphite at the temperature of 100-150 ℃ under the action of a catalyst, separating triethyl phosphite and insoluble substances after the reaction is finished, and performing vacuum distillation to obtain intermediate condensation ester; the catalyst comprises potassium iodide, tetrabutyl ammonium iodide and DMAP, and the mass ratio of the m-nitroacetophenone to the triethyl phosphite to the potassium iodide to the tetrabutyl ammonium iodide to the DMAP is 1:1-10:0.05-0.2:0.05-0.2:0.05-0.2;
(2) Dropwise adding the condensation ester obtained in the step (1) into a dimethyl sulfoxide solution of potassium tert-butoxide, reacting at a temperature of no more than 60 ℃, adding water and an extracting agent to extract after the reaction is finished, taking an organic phase, and recovering a solvent to obtain m-nitroacetylene;
(3) Carrying out reduction reaction on m-nitroacetylene and a reducing agent in ethanol at 70-80 ℃, filtering and recovering a solvent to obtain a crude product after the reaction is finished, collecting 90-96 ℃ fraction of the crude product under a vacuum condition to obtain m-aminophenylacetylene, wherein the reducing agent is zinc powder and calcium chloride, and the molar ratio of the m-nitroacetylene to the zinc powder to the calcium chloride is 1:1.1-3.0:1.1-3.0.
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