CN113024485A - Synthesis method of 4-acryloyl morpholine - Google Patents
Synthesis method of 4-acryloyl morpholine Download PDFInfo
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- CN113024485A CN113024485A CN201911347990.5A CN201911347990A CN113024485A CN 113024485 A CN113024485 A CN 113024485A CN 201911347990 A CN201911347990 A CN 201911347990A CN 113024485 A CN113024485 A CN 113024485A
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- morpholine
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- acryloyl morpholine
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- XLPJNCYCZORXHG-UHFFFAOYSA-N 1-morpholin-4-ylprop-2-en-1-one Chemical compound C=CC(=O)N1CCOCC1 XLPJNCYCZORXHG-UHFFFAOYSA-N 0.000 title claims abstract description 39
- 238000001308 synthesis method Methods 0.000 title claims description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 46
- DLEWDCPFCNLJEY-UHFFFAOYSA-N 1-morpholin-4-ylpropan-1-one Chemical compound CCC(=O)N1CCOCC1 DLEWDCPFCNLJEY-UHFFFAOYSA-N 0.000 claims abstract description 33
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims abstract description 22
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 22
- 238000000034 method Methods 0.000 claims abstract description 21
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000000047 product Substances 0.000 claims abstract description 17
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims abstract description 13
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 11
- 239000001301 oxygen Substances 0.000 claims abstract description 11
- 235000019260 propionic acid Nutrition 0.000 claims abstract description 11
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims abstract description 11
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 77
- 239000002994 raw material Substances 0.000 claims description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 17
- 239000002904 solvent Substances 0.000 claims description 16
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 14
- 238000003756 stirring Methods 0.000 claims description 13
- 238000004821 distillation Methods 0.000 claims description 9
- JBTWLSYIZRCDFO-UHFFFAOYSA-N ethyl methyl carbonate Chemical compound CCOC(=O)OC JBTWLSYIZRCDFO-UHFFFAOYSA-N 0.000 claims description 8
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 8
- 239000000706 filtrate Substances 0.000 claims description 7
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical group CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 6
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 6
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 6
- IWDCLRJOBJJRNH-UHFFFAOYSA-N p-cresol Chemical compound CC1=CC=C(O)C=C1 IWDCLRJOBJJRNH-UHFFFAOYSA-N 0.000 claims description 6
- NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 claims description 6
- 239000002530 phenolic antioxidant Substances 0.000 claims description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 5
- 239000012074 organic phase Substances 0.000 claims description 5
- 238000010791 quenching Methods 0.000 claims description 5
- 230000000171 quenching effect Effects 0.000 claims description 5
- 239000000376 reactant Substances 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- QHPQWRBYOIRBIT-UHFFFAOYSA-N 4-tert-butylphenol Chemical compound CC(C)(C)C1=CC=C(O)C=C1 QHPQWRBYOIRBIT-UHFFFAOYSA-N 0.000 claims description 3
- 238000005837 enolization reaction Methods 0.000 claims description 3
- LZWQNOHZMQIFBX-UHFFFAOYSA-N lithium;2-methylpropan-2-olate Chemical compound [Li+].CC(C)(C)[O-] LZWQNOHZMQIFBX-UHFFFAOYSA-N 0.000 claims description 3
- 238000007254 oxidation reaction Methods 0.000 claims description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 239000013067 intermediate product Substances 0.000 claims description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 239000006227 byproduct Substances 0.000 abstract description 3
- 239000007809 chemical reaction catalyst Substances 0.000 abstract description 2
- 238000006727 Saegusa oxidation reaction Methods 0.000 abstract 1
- 239000003513 alkali Substances 0.000 abstract 1
- 238000009833 condensation Methods 0.000 abstract 1
- 230000005494 condensation Effects 0.000 abstract 1
- 230000018044 dehydration Effects 0.000 abstract 1
- 238000006297 dehydration reaction Methods 0.000 abstract 1
- 235000019439 ethyl acetate Nutrition 0.000 description 20
- 239000000243 solution Substances 0.000 description 10
- 239000012295 chemical reaction liquid Substances 0.000 description 9
- 239000012043 crude product Substances 0.000 description 9
- -1 acrylamide compound Chemical class 0.000 description 5
- 239000000463 material Substances 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000005336 cracking Methods 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000000967 suction filtration Methods 0.000 description 3
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- ZSWFCLXCOIISFI-UHFFFAOYSA-N cyclopentadiene Chemical compound C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 2
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 2
- 238000010146 3D printing Methods 0.000 description 1
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 1
- 238000003848 UV Light-Curing Methods 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 238000007098 aminolysis reaction Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000012567 medical material Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- KDLHZDBZIXYQEI-VENIDDJXSA-N palladium-100 Chemical compound [100Pd] KDLHZDBZIXYQEI-VENIDDJXSA-N 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000007639 printing Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 238000007158 vacuum pyrolysis Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
The invention discloses a method for synthesizing 4-acryloyl morpholine, which mainly comprises the following two steps: 1) carrying out dehydration condensation on propionic acid and morpholine under the action of DCC to obtain an intermediate 4-propionyl morpholine; 2) under the condition of strong alkali, 4-propionyl morpholine and oxygen are subjected to Saegusa reaction under the catalysis of palladium acetate to form a target product, namely 4-acryloyl morpholine. The synthesis process of 4-acryloyl morpholine can be implemented under normal pressure, the reaction temperature is mild, the byproducts are few, the reaction catalyst can be recycled, and the industrial prospect is good.
Description
Technical Field
The invention relates to a synthesis method of 4-acryloyl morpholine, in particular to a synthesis process of a compound named 4-acryloyl morpholine.
Background
The acrylamide compound has high-activity carbon-carbon conjugated double bonds and can well homopolymerize or copolymerize at normal temperature, so that the acrylamide compound can be used as a key raw material and widely applied to UV curing materials, such as UV coatings, UV printing ink, UV adhesives and other UV polymerization reaction fields of various unsaturated systems; they can also be used in industries such as 3D printing materials, food additives and the like. 4-acryloyl morpholine has many excellent characteristics, is a low-odor and low-irritation monofunctional monomer, can be mutually dissolved with water, and can also be used in a water-based UV system; in addition, 4-acryloyl morpholine and high-functional oligomer are matched for use, so that a high-end product which can ensure hardness and has excellent toughness can be produced, and the high-end product can be applied to the fields of new medical materials and the like and has a very wide application prospect.
The existing synthesis methods of 4-acryloyl morpholine mainly comprise the following steps:
1) chinese patent publication No. CN107417644A and japanese patent publication nos. JP09-279395, JP49-66625, JP05-163279, and JP 2015101554 disclose a method of first preparing heteroatom-substituted propionyl morpholine such as morpholinyl propylene morpholine, diethylamino propionyl morpholine, butoxy propionyl morpholine, etc., and then performing vacuum pyrolysis to obtain the target product, and the specific synthetic route is as follows:
2) japanese patent publication No. JP2015101553 and International patent publication No. WO2015146876 disclose a method for obtaining a target product by reacting ethyl acrylate and cyclopentadiene with D-A, then morpholino aminolysis, and then vacuum cracking, wherein the specific synthetic route is as follows:
the synthesis methods all involve vacuum and high-temperature cracking conditions, the cracking temperature is as high as 400 ℃, the requirements on equipment are high, and the production cost and the safety risk are high; and the reaction conditions are harsh, so that the generation of addition byproducts is difficult to avoid in the process, and great troubles are brought to the purification of the product.
Therefore, it is necessary to design and develop a new synthesis method of 4-acryloyl morpholine with simple preparation process and high safety.
Disclosure of Invention
Aiming at the problems in the prior art, the invention discloses a method for synthesizing 4-acryloyl morpholine, which comprises the steps of generating an intermediate 4-propionyl morpholine by propionic acid and morpholine under the action of a condensing agent DCC, carrying out enolization on the 4-propionyl morpholine under the action of strong base, and carrying out Saegusa-Ito oxidation reaction under the catalysis of palladium acetate to be oxidized into a carbon-carbon double bond by oxygen. Thereby obtaining the target product 4-acryloyl morpholine, and can avoid harsh reaction conditions such as high temperature, vacuum and the like because the synthesis strategy is different from the traditional method.
The technical scheme of the invention is as follows: a synthesis method of 4-acryloyl morpholine comprises the following specific synthetic route:
wherein DCC is dicyclohexylcarbodiimide;tBuONa denotes a strong base, Pd (OAc)2Denotes palladium acetate, O2Is oxygen.
The specific synthesis steps are as follows:
1) synthesizing an intermediate 4-propionyl morpholine: dissolving propionic acid and morpholine serving as starting raw materials in an ester solvent at 0-30 ℃, slowly dropwise adding an ethyl acetate solution of DCC, reacting after dropwise adding, stirring at room temperature for a certain time, filtering to remove an intermediate product dicyclohexylurea after the reaction is finished, removing ethyl acetate from filtrate through reduced pressure concentration, and finally reacting to generate an intermediate 4-propionyl morpholine through reduced pressure distillation;
2) synthesizing a target product 4-acryloyl morpholine: at room temperature, taking 4-propionyl morpholine as a reaction raw material, adding the reaction raw material, palladium acetate and strong base into a DMSO (dimethyl sulfoxide) solvent, introducing oxygen, heating the reaction to a certain temperature, stirring and reacting for a certain time, carrying out enolization on the 4-propionyl morpholine under the action of the strong base, carrying out Saegusa-Ito oxidation reaction under the catalysis of the palladium acetate, quenching the reactant in cold water, extracting the quenched reactant with an ester solvent, washing an organic phase with a saturated ammonium chloride solution, drying anhydrous sodium sulfate, carrying out vacuum concentration to remove the solvent, adding a phenolic antioxidant, and carrying out reduced pressure distillation to obtain the target product, namely 4-acryloyl morpholine.
In the step 1), the ester solvent is selected from methyl acetate, ethyl acetate and butyl acetate, and ethyl acetate is preferred.
In step 1), the molar ratio of propionic acid to morpholine is preferably 1: 1.
in the step 1), the ratio of the number of moles of DCC to the number of moles of the raw material propionic acid is preferably 1.00: 1 to 1.50: 1.
In the step 1), the preferable range of the stirring reaction time is 4-24 hours, and the concentration selection range of DCC in the acetic ether is 1-10 mol/L.
In the step 2), the preferable range of the ester solvent comprises methyl acetate, ethyl acetate and butyl acetate; the selection range of the phenolic antioxidant comprises 4-methoxyphenol, 4-tert-butylphenol and 4-methylphenol; preferred ranges of strong bases include lithium tert-butoxide, sodium tert-butoxide, potassium tert-butoxide.
In the step 2), the concentration of the reaction raw material 4-propionyl morpholine in DMSO is preferably 1-10 mol/L.
In the step 2), the dosage of the catalyst palladium acetate is preferably 0.001-0.05 times of the mole number of the reaction raw material 4-propionyl morpholine; the dosage of the strong base is preferably 0.5 to 2.0 times of the mole number of the reaction raw material 4-propionyl morpholine; the mole number of the phenolic antioxidant is preferably 0.01-0.2% of the consumption of the reaction raw material 4-propionyl morpholine.
In the step 2), the oxygen pressure is 1 atmosphere; the preferable range of a certain temperature is 60-120 ℃; the preferable range of the stirring reaction time is 6-36 hours.
The invention has the beneficial effects that:
the invention discloses a method for synthesizing 4-acryloyl morpholine, which can be implemented under normal pressure by utilizing the synthesis process of the 4-acryloyl morpholine, has mild reaction temperature, less byproducts, recyclable reaction catalyst and better industrial prospect.
Drawings
FIG. 1 is a GC-MS total ion flow diagram of 4-acryloyl morpholine with a retention time of 12.779 min.
FIG. 2 is a GC-MS mass spectrum of 4-acryloylmorpholine of the invention.
Detailed Description
The following examples further illustrate the present invention but are not to be construed as limiting the invention. Modifications and substitutions to methods, procedures, or conditions of the invention may be made without departing from the spirit of the invention.
Example 1:
step one, synthesizing an intermediate 4-propionyl morpholine:
at 25 ℃, 74 g (1 mol) of propionic acid and 87 g of morpholine are sequentially added into a 1000ml reaction bottle with a mechanical stirrer as starting materials, the materials are dissolved in 200 ml of ethyl acetate to prepare a 5 mol/L aqueous solution, then 216 g (1.05 mol) of ethyl acetate (300 ml) solution of DCC is dropwise added under stirring, after the dropwise addition, the reaction is stirred at room temperature for 12 hours, after the reaction is finished, suction filtration is carried out, the reaction solid is washed by cold ethyl acetate solvent, the filtrate is collected, then the ethyl acetate solvent is removed by vacuum concentration on a rotary evaporator to obtain a crude product of 4-propionyl morpholine, the crude product is subjected to vacuum distillation to obtain 131.5 g of pure 4-propionyl morpholine, and the yield is 92%.
Step two, synthesizing a target product 4-acryloyl morpholine:
a1000 ml three-necked reaction flask equipped with a mechanical stirrer and a thermometer was charged with 131.5 g (1.0 mol) of 4-propionylmorpholine, 96 g (1.0 mol) of sodium t-butoxide, 4.5 g (0.02 mol) of palladium acetate and 400 ml of DMSO solvent, heated to 90 ℃ with stirring and oxygen (1.0 atm) continuously introduced into the reaction flask, and then the reaction system was reacted at 90 ℃ for 30 hours. After the reaction is finished, cooling the reaction liquid to room temperature, then slowly pouring the reaction liquid into 2000 ml of ice-water bath for quenching, and extracting the reaction liquid (3100 ml times) by using ethyl acetate after the reaction is quenched; the organic phases were combined, washed with a saturated ammonium chloride solution (5 ml), washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated by a rotary evaporator to remove the ethyl acetate solvent to give a crude 4-acrylamide product, and finally, 124 mg (1.0 mmol) of 4-methoxyphenol was added to the crude product, followed by distillation under reduced pressure to give 4-acryloylmorpholine in 84% yield and 97% purity.
Example 2:
step one, synthesizing an intermediate 4-propionyl morpholine:
at 0 ℃, 70 g (1 mol) of propionic acid and 70 g of morpholine are sequentially added into a 1000ml reaction bottle with a mechanical stirrer as starting materials, the starting materials are dissolved into 200 ml of methyl acetate to prepare a 5 mol/L aqueous solution, then 100 g (1 mol) of ethyl acetate (100 ml) of DCC is dropwise added under stirring, after the dropwise addition, the reaction is stirred at room temperature for 4 hours, after the reaction is finished, suction filtration is carried out, the reaction solid is washed by cold ethyl acetate solvent, filtrate is collected, then the filtrate is subjected to reduced pressure concentration on a rotary evaporator to remove the ethyl acetate solvent, a crude product of the 4-propionyl morpholine is obtained, the crude product is subjected to reduced pressure distillation to obtain 120 g of a pure product of the 4-propionyl morpholine, and the yield is 90%.
Step two, synthesizing a target product 4-acryloyl morpholine:
in a 2000 ml three-necked reaction flask equipped with a mechanical stirrer and a thermometer were charged 120 g (1 mol) of 4-propionylmorpholine, 80 g (0.5 mol) of lithium tert-butoxide, 3 g (0.001 mol) of palladium acetate and 1000ml of DMSO solvent, heated to 60 ℃ and stirred while continuously introducing oxygen (1.0 atm) into the reaction flask, and then the reaction system was reacted at 60 ℃ for 6 hours. After the reaction is finished, cooling the reaction liquid to room temperature, slowly pouring the reaction liquid into 2000 ml of ice-water bath for quenching, and extracting the reaction liquid (3120 ml times) by using methyl acetate after the reaction is quenched; the organic phases were combined, washed with a saturated ammonium chloride solution (6 ml), with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated by a rotary evaporator to remove the ethyl acetate solvent to give a crude 4-acrylamide product, and finally, to the crude product was added 124 mg (0.1 mmol) of 4-tert-butylphenol, followed by distillation under reduced pressure to give 4-acryloylmorpholine in 80% yield and 91% purity.
Example 3:
step one, synthesizing an intermediate 4-propionyl morpholine:
at 30 ℃, adding 80 g (1 mol) of propionic acid and 80 g of morpholine serving as starting raw materials into a 2000 ml reaction bottle with a mechanical stirrer in sequence, dissolving the materials in 250ml of butyl acetate to prepare a 4 mol/L aqueous solution, then dropwise adding 220 g (1.5 mol) of ethyl acetate (1000 ml) solution of DCC under stirring, stirring and reacting at room temperature for 24 hours after dropwise adding, after the reaction is finished, carrying out suction filtration, washing the reaction solid with cold ethyl acetate solvent, collecting filtrate, then carrying out reduced pressure concentration on the filtrate on a rotary evaporator to remove the ethyl acetate solvent, obtaining a crude product of 4-propionyl morpholine, and carrying out reduced pressure distillation on the crude product to obtain 140 g of pure 4-propionyl morpholine with the yield of 94%.
Step two, synthesizing a target product 4-acryloyl morpholine:
a1000 ml three-necked reaction flask equipped with a mechanical stirrer and a thermometer was charged with 140 g (1.0 mol) of 4-propionylmorpholine, 100 g (2.0 mol) of potassium t-butoxide, 4.5 g (0.05 mol) of palladium acetate and 100 ml of DMSO solvent, heated to 90 ℃ and stirred while continuously introducing oxygen (1.0 atm) into the reaction flask, and then the reaction system was reacted at 120 ℃ for 36 hours. After the reaction is finished, cooling the reaction liquid to room temperature, then slowly pouring the reaction liquid into 2000 ml of ice-water bath for quenching, and extracting the reaction liquid (3100 ml times) by using butyl acetate after the reaction is quenched; the organic phases were combined, washed with a saturated ammonium chloride solution (8 ml), washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, concentrated by a rotary evaporator to remove the ethyl acetate solvent to give a crude 4-acrylamide product, and finally, 124 mg (2.0 mmol) of 4-methylphenol was added to the crude product, followed by distillation under reduced pressure to give 4-acryloylmorpholine in 90% yield and 95% purity.
By combining fig. 1 and fig. 2, it can be obtained that the target product is 4-acryloyl morpholine.
Claims (10)
1. The synthesis method of 4-acryloyl morpholine is characterized in that the specific synthetic route is as follows:
wherein DCC is dicyclohexylcarbodiimide;tBuONa denotes a strong base, Pd (OAc)2Denotes palladium acetate, O2Is oxygen.
2. The method for synthesizing 4-acryloyl morpholine according to claim 1, comprising the following steps:
1) synthesizing an intermediate 4-propionyl morpholine: dissolving propionic acid and morpholine serving as starting raw materials in an ester solvent at 0-30 ℃, slowly dropwise adding an ethyl acetate solution of DCC, reacting after dropwise adding, stirring at room temperature for a certain time, filtering to remove an intermediate product dicyclohexylurea after the reaction is finished, removing ethyl acetate from filtrate through reduced pressure concentration, and finally reacting to generate an intermediate 4-propionyl morpholine through reduced pressure distillation;
2) synthesizing a target product 4-acryloyl morpholine: at room temperature, taking 4-propionyl morpholine as a reaction raw material, adding the reaction raw material, palladium acetate and strong base into a DMSO (dimethyl sulfoxide) solvent, introducing oxygen, heating the reaction to a certain temperature, stirring and reacting for a certain time, carrying out enolization on the 4-propionyl morpholine under the action of the strong base, carrying out Saegusa-Ito oxidation reaction under the catalysis of the palladium acetate, quenching the reactant in cold water, extracting the quenched reactant with an ester solvent, washing an organic phase with a saturated ammonium chloride solution, drying anhydrous sodium sulfate, carrying out vacuum concentration to remove the solvent, adding a phenolic antioxidant, and carrying out reduced pressure distillation to obtain the target product, namely 4-acryloyl morpholine.
3. The method for synthesizing 4-acryloyl morpholine according to claim 2, wherein in step 1), the ester solvent is selected from methyl acetate, ethyl acetate, butyl acetate, preferably ethyl acetate.
4. The method for synthesizing 4-acryloyl morpholine according to claim 2, wherein in step 1), the molar ratio of propionic acid to morpholine is preferably 1: 1.
5. the method for synthesizing 4-acryloylmorpholine according to claim 2, wherein in the step 1), the ratio of the number of moles of DCC to the number of moles of the raw material propionic acid is preferably 1.00: 1 to 1.50: 1.
6. The method for synthesizing 4-acryloyl morpholine according to claim 2, wherein in step 1), the stirring reaction time is preferably in the range of 4-24 hours, and the concentration selection range of DCC in ethyl acetate includes 1-10 mol/L.
7. The method for synthesizing 4-acryloylmorpholine according to claim 2 wherein in step 2), the ester solvent preferably comprises methyl acetate, ethyl acetate, butyl acetate; the selection range of the phenolic antioxidant comprises 4-methoxyphenol, 4-tert-butylphenol and 4-methylphenol; preferred ranges of strong bases include lithium tert-butoxide, sodium tert-butoxide, potassium tert-butoxide.
8. The method for synthesizing 4-acryloyl morpholine according to claim 2, wherein in step 2), the concentration of the reaction raw material 4-propionyl morpholine in DMSO is preferably in the range of 1-10 mol/L.
9. The method for synthesizing 4-acryloyl morpholine according to claim 2, wherein in step 2), the amount of palladium acetate used as a catalyst is preferably 0.001-0.05 times of the mole number of 4-propionyl morpholine serving as a reaction raw material; the dosage of the strong base is preferably 0.5 to 2.0 times of the mole number of the reaction raw material 4-propionyl morpholine; the mole number of the phenolic antioxidant is preferably 0.01-0.2% of the consumption of the reaction raw material 4-propionyl morpholine.
10. The method for synthesizing 4-acryloylmorpholine according to claim 2 wherein in the step 2), the oxygen pressure is 1 atm; the preferable range of a certain temperature is 60-120 ℃; the preferable range of the stirring reaction time is 6-36 hours.
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| CN101293880A (en) * | 2007-04-28 | 2008-10-29 | 中国石油天然气集团公司 | Synthesizing method for preparing N-acryloyl morpholine |
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| JPH06345749A (en) * | 1993-06-08 | 1994-12-20 | Mitsubishi Rayon Co Ltd | Production of n-(meth)acryloylmorpholine |
| JPH11100375A (en) * | 1997-09-29 | 1999-04-13 | Kohjin Co Ltd | Production of (meth) acryloylmorpholine |
| CN101293880A (en) * | 2007-04-28 | 2008-10-29 | 中国石油天然气集团公司 | Synthesizing method for preparing N-acryloyl morpholine |
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