CN110563671A - Preparation method of photoinitiator 2-methyl-1- (4-methylthiophenyl) -2-morpholinyl-1-acetone - Google Patents
Preparation method of photoinitiator 2-methyl-1- (4-methylthiophenyl) -2-morpholinyl-1-acetone Download PDFInfo
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- CN110563671A CN110563671A CN201910936375.1A CN201910936375A CN110563671A CN 110563671 A CN110563671 A CN 110563671A CN 201910936375 A CN201910936375 A CN 201910936375A CN 110563671 A CN110563671 A CN 110563671A
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- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Substances CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 title claims abstract description 43
- -1 4-methylthiophenyl Chemical group 0.000 title claims abstract description 38
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- 239000000460 chlorine Substances 0.000 claims abstract description 48
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 48
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 47
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims abstract description 44
- 238000006467 substitution reaction Methods 0.000 claims abstract description 37
- 238000000034 method Methods 0.000 claims abstract description 29
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims abstract description 28
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000004593 Epoxy Substances 0.000 claims abstract description 17
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims abstract description 17
- 238000005863 Friedel-Crafts acylation reaction Methods 0.000 claims abstract description 15
- 239000002994 raw material Substances 0.000 claims abstract description 11
- DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000002841 Lewis acid Substances 0.000 claims abstract description 6
- 238000006735 epoxidation reaction Methods 0.000 claims abstract description 6
- 150000007517 lewis acids Chemical class 0.000 claims abstract description 6
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 4
- 238000007670 refining Methods 0.000 claims abstract description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 104
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 66
- 239000007788 liquid Substances 0.000 claims description 55
- 229910052757 nitrogen Inorganic materials 0.000 claims description 49
- 238000003756 stirring Methods 0.000 claims description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 34
- 238000004821 distillation Methods 0.000 claims description 26
- 238000010438 heat treatment Methods 0.000 claims description 23
- 230000010933 acylation Effects 0.000 claims description 20
- 238000005917 acylation reaction Methods 0.000 claims description 20
- 238000001816 cooling Methods 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 238000005406 washing Methods 0.000 claims description 17
- 238000006460 hydrolysis reaction Methods 0.000 claims description 15
- 239000007864 aqueous solution Substances 0.000 claims description 14
- 239000007789 gas Substances 0.000 claims description 14
- 230000007062 hydrolysis Effects 0.000 claims description 14
- 238000007599 discharging Methods 0.000 claims description 13
- 239000000243 solution Substances 0.000 claims description 12
- 229930182817 methionine Natural products 0.000 claims description 11
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 claims description 11
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- 238000001914 filtration Methods 0.000 claims description 9
- 239000012530 fluid Substances 0.000 claims description 8
- 239000000463 material Substances 0.000 claims description 8
- 125000002757 morpholinyl group Chemical group 0.000 claims description 8
- 239000008367 deionised water Substances 0.000 claims description 6
- 229910021641 deionized water Inorganic materials 0.000 claims description 6
- 238000000605 extraction Methods 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- DDFYFBUWEBINLX-UHFFFAOYSA-M tetramethylammonium bromide Chemical compound [Br-].C[N+](C)(C)C DDFYFBUWEBINLX-UHFFFAOYSA-M 0.000 claims description 6
- 239000003513 alkali Substances 0.000 claims description 5
- 238000005086 pumping Methods 0.000 claims description 5
- 239000012295 chemical reaction liquid Substances 0.000 claims description 4
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 3
- 239000000706 filtrate Substances 0.000 claims description 3
- NNAHKQUHXJHBIV-UHFFFAOYSA-N 2-methyl-1-(4-methylthiophen-2-yl)-2-morpholin-4-ylpropan-1-one Chemical compound CC1=CSC(C(=O)C(C)(C)N2CCOCC2)=C1 NNAHKQUHXJHBIV-UHFFFAOYSA-N 0.000 claims description 2
- 238000002425 crystallisation Methods 0.000 claims description 2
- 230000008025 crystallization Effects 0.000 claims description 2
- 239000000110 cooling liquid Substances 0.000 claims 1
- 238000005660 chlorination reaction Methods 0.000 abstract description 27
- 239000000047 product Substances 0.000 abstract description 27
- 230000009286 beneficial effect Effects 0.000 abstract description 8
- 125000001309 chloro group Chemical group Cl* 0.000 abstract description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 5
- 239000001257 hydrogen Substances 0.000 abstract description 5
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 5
- 239000006227 byproduct Substances 0.000 abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 2
- 239000000543 intermediate Substances 0.000 description 73
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- 230000001276 controlling effect Effects 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 19
- 210000003298 dental enamel Anatomy 0.000 description 16
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 9
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 9
- 238000000016 photochemical curing Methods 0.000 description 9
- 235000011121 sodium hydroxide Nutrition 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 125000006217 methyl sulfide group Chemical group [H]C([H])([H])S* 0.000 description 7
- 230000000052 comparative effect Effects 0.000 description 6
- 229910001873 dinitrogen Inorganic materials 0.000 description 6
- 238000004090 dissolution Methods 0.000 description 5
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 5
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000002351 wastewater Substances 0.000 description 4
- 238000009835 boiling Methods 0.000 description 3
- 238000005658 halogenation reaction Methods 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 3
- 238000007039 two-step reaction Methods 0.000 description 3
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- UEDJYLPHSHWCAB-UHFFFAOYSA-K aluminum chlorobenzene trichloride Chemical compound [Al+3].[Cl-].[Cl-].[Cl-].ClC1=CC=CC=C1 UEDJYLPHSHWCAB-UHFFFAOYSA-K 0.000 description 2
- 150000001412 amines Chemical group 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000001723 curing Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
- 239000003444 phase transfer catalyst Substances 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- 238000010025 steaming Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000005732 thioetherification reaction Methods 0.000 description 2
- IIWLVHAOFQNHDW-UHFFFAOYSA-N 1-(4-chlorophenyl)-2-methyl-2-morpholin-4-ylpropan-1-one Chemical compound C=1C=C(Cl)C=CC=1C(=O)C(C)(C)N1CCOCC1 IIWLVHAOFQNHDW-UHFFFAOYSA-N 0.000 description 1
- 229920000049 Carbon (fiber) Polymers 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 239000004917 carbon fiber Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 238000004807 desolvation Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- YSVZADAAWQNYCF-UHFFFAOYSA-N methylsulfanylmethane;sodium Chemical compound [Na].CSC YSVZADAAWQNYCF-UHFFFAOYSA-N 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 238000007344 nucleophilic reaction Methods 0.000 description 1
- 230000005693 optoelectronics Effects 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 238000007639 printing Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
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
- C07D295/04—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 with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/10—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 with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms
- C07D295/112—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 with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
Abstract
the invention relates to a preparation method of a photoinitiator 2-methyl-1- (4-methylthiophenyl) -2-morpholinyl-1-acetone, which comprises the following steps: (1) friedel-crafts acylation; (2) chloro-substituted; (3) epoxidation; (4) morpholinyl substitution; (5) methylthio substitution; (6) refining; isobutyryl chloride is used as an initial raw material and is subjected to Friedel-crafts acylation reaction with chlorobenzene under the catalysis of Lewis acid to prepare an intermediate 2-methyl-1- (4-chlorphenyl) -1-acetone; substituting beta hydrogen on a branched chain with simple substance chlorine, then reacting with a sodium methoxide solution to prepare an epoxy intermediate, reacting with morpholine to realize that the branched chain is substituted with beta hydrogen by morpholine, and finally substituting chlorine on a benzene ring with methylthio to obtain a product; the method is beneficial to improving the sufficiency of the chlorination reaction, simultaneously reduces the residue of chlorine in the chlorination reaction process, can reduce the formation of the chlorine and subsequent intermediate halogenated byproducts, and is beneficial to obviously improving the yield of target products.
Description
Technical Field
the invention relates to the technical field of photoinitiators, in particular to a preparation method of a photoinitiator 2-methyl-1- (4-methylthiophenyl) -2-morpholinyl-1-acetone.
background
The photoinitiator is an active intermediate (free radical, cation or anion) which absorbs radiation energy and generates chemical change through excitation to generate the initiating polymerization capability, and plays an important role in a photocuring system, so the development of the photoinitiator is closely independent of the development of an ultraviolet curing technology.
The development of photoinitiators relies on the development of photocuring techniques. The industrialization of the photo-curing technology has been realized as early as bayer in germany, and then enterprises engaged in photo-curing production in regions and countries such as north america, europe, and japan have been rapidly developed, and in the last two decades, with increasing emphasis on environmental protection issues in various countries, the application field of the photo-curing technology has been rapidly expanded, and has been developed from the initial manufacturing of printed boards to the optoelectronic, information, and communication industries, and has formed a cross-country company for the production of photo-curing products including basf, bayer, dow chemical, and the like.
The photocuring technology has gradually developed in China from the 20 th century in the 80 th year, and enters the 21 st century, the photocuring industry in China has rapidly developed, and is a major producing country of photocuring raw materials and formula products second to the United states and Japan, particularly, photoinitiators have become a major producing and exporting country in the world, and at present, in China, the main curing material field of application of the photoinitiators is PCB printing ink, fine processing of electronic products (such as integrated circuits, liquid crystal displays, LEDs and the like), UV coatings and the like.
At present, the demand of photoinitiators is increasing, and those skilled in the art are working on photoinitiators with simple process, mild reaction conditions and high yield. Bear Wei published in the research on the novel synthesis process of photoinitiator MMMP discloses that 2-methyl-1- (4-methylthiophenyl) -2-morpholinyl-1-acetone is prepared from methyl phenyl thioether as a raw material through Friedel-crafts acylation and amine substitution two-step reaction, the total yield of the two-step reaction reaches 85 percent, the novel process is simple, the reaction condition is mild, the cost is low, and the method is suitable for industrial production.
However, the raw material of the thiobenzol is high in cost, a large amount of wastewater is generated in the manufacturing process, and the aromatic hydrocarbon intermediate 2-methyl-1- (4-methylthio) phenyl-1-acetone with methylthio has numerous side reactions in the subsequent chlorination reaction, so that the purity and the yield of the step are low.
In addition, the Japanese company synthesizes chlorobenzene as a raw material to obtain 2-methyl-1- (4-chlorophenyl) -1-acetone, methyl mercaptan gas is introduced into a chlorobenzene and sodium hydroxide aqueous solution two-phase system, tetrabutylammonium bromide is used as a phase transfer catalyst, and thioetherification reaction is carried out at 90-102 ℃ to obtain a target product.
Although the method avoids the use of the thioanisole, the chlorine is used for halogenation reaction, excessive chlorine is remained after the halogenation reaction, and the remained chlorine is continuously reacted with a subsequent intermediate, so that a plurality of byproducts are generated, and the yield of a target product is greatly reduced.
Disclosure of Invention
The invention aims to provide a preparation method of a photoinitiator 2-methyl-1- (4-methylthiophenyl) -2-morpholinyl-1-acetone, which reduces chlorine residue in chlorination reaction, minimizes the continuous halogenation reaction of subsequent intermediates and finally improves the yield of a target product.
The above object of the present invention is achieved by the following technical solutions:
A preparation method of 2-methyl-1- (4-methylthiophenyl) -2-morpholinyl-1-acetone serving as a photoinitiator comprises the following steps:
(1) friedel-crafts acylation: taking isobutyryl chloride as a raw material, and carrying out Friedel-crafts acylation reaction with chlorobenzene under the catalysis of Lewis acid to obtain an acylation intermediate 2-methyl-1- (4-chlorphenyl) -1-acetone;
(2) chlorination: the chlorination adopts a positive-side alternate two-stage series device, after chlorine is reacted and absorbed by a positive kettle, positive tail gas is absorbed by reaction liquid in a secondary kettle, and tail gas of the secondary kettle is absorbed in an environment-friendly way; (a) starting a positive and a negative chlorinated kettles for stirring, introducing steam for heating, controlling the temperature to be 48-51 ℃, opening a positive kettle chlorine introducing valve and a negative kettle tail gas emptying valve, and introducing chlorine for 15-25 h; (b) introducing nitrogen into the positive kettle to replace excessive chlorine in the positive kettle, discharging chlorinated intermediate in the positive kettle, and continuously adding the acylated intermediate into the positive kettle to change the positive kettle into an auxiliary kettle; (c) putting the chloro intermediate into a nitrogen-introducing residue-removing kettle, controlling the temperature of the kettle to be 25-35 ℃, and introducing nitrogen into the nitrogen-introducing residue-removing kettle for 6-8 hours to obtain a chloro intermediate after chlorine removal;
(3) Epoxidation: adding the chlorinated intermediate subjected to chlorine removal into an epoxy kettle, controlling the temperature of the kettle to be 28-35 ℃, dropwise adding excessive sodium methoxide solution, controlling the temperature of the kettle to be 36-40 ℃ after dropwise adding, and preserving heat for at least 2 hours to obtain an epoxy intermediate;
(4) morpholino substitution: receiving an epoxy intermediate, adding morpholine and liquid caustic soda into a morpholine substitution kettle, wherein the mass ratio of morpholine to liquid caustic soda is 8-12: 1, distilling under negative pressure, ending distillation when the temperature of the kettle reaches 135 ℃, introducing nitrogen to enable the pressure in the kettle to be positive, and cooling to 78-82 ℃ to obtain the morpholine intermediate;
(5) And (2) methylthio substitution: pumping the morpholino intermediate into a methionine substitution kettle, keeping the temperature of the kettle at 80-85 ℃, adding a sodium methyl mercaptide aqueous solution with the mass concentration of 20-30% and a tetramethyl ammonium bromide aqueous solution with the mass concentration of 50-80%, controlling the temperature of the kettle at 85-90 ℃, and preserving the heat for 8-12 hours to obtain a methionine substitution feed liquid;
(6) refining: filtering the methionine substituted feed liquid, introducing refrigerating liquid for cooling after filtering, centrifugally discharging, and drying to obtain the 2-methyl-1- (4-methylthiophenyl) -2-morpholinyl-1-acetone.
By adopting the technical scheme, the method takes isobutyryl chloride as an initial raw material, and performs Friedel-crafts acylation reaction with chlorobenzene under the catalysis of Lewis acid to obtain an acylation intermediate 2-methyl-1- (4-chlorphenyl) -1-acetone; substituting beta hydrogen on an intermediate 2-methyl-1- (4-chlorphenyl) -1-acetone branched chain by elemental chlorine to prepare an intermediate 2-methyl-2-chloro-1- (4-chlorphenyl) -1-acetone, then reacting with a sodium methoxide solution to prepare an epoxy intermediate, and reacting with morpholine to realize beta hydrogen on a morpholinyl substituted branched chain to prepare an intermediate 2-methyl-1- (4-chlorphenyl) -2-morpholinyl-1-acetone; and finally, substituting the chlorine group on the benzene ring with methylthio to obtain 2-methyl-1- (4-methylthiophenyl) -2-morpholinyl-1-acetone by using a sodium methylthio alkoxide aqueous solution as a substituting agent and a tetrabutyl ammonium bromide aqueous solution as a catalyst.
in particular, the yield of chlorinated intermediates directly affects the yield of the target product. In the chlorination reaction, a primary kettle and a secondary kettle are alternately connected in series, chlorine gas is introduced into the primary kettle, the chlorine gas and an acylation intermediate in the primary kettle carry out chlorination reaction, after the reaction is finished, nitrogen gas is introduced into the primary kettle to replace excessive chlorine gas in the primary kettle, the chlorination intermediate in the primary kettle is collected, the acylation intermediate is added into the primary kettle, and the primary kettle is changed into the secondary kettle; changing the original auxiliary kettle into a positive kettle, continuously introducing chlorine gas into the positive kettle, and carrying out secondary chlorination on the acylation intermediate in the positive kettle, so that the sufficiency of the chlorination is improved, then introducing nitrogen gas to replace excessive chlorine gas, circulating the above processes, being beneficial to improving the sufficiency of the chlorination, reducing the residue of chlorine gas in the chlorination process, reducing the continuous reaction of the chlorine gas and the subsequent intermediate, and being beneficial to improving the yield of the target product.
in addition, a sodium methoxide solution is added in the epoxidation reaction, which is helpful for improving the reaction uniformity of the chloro intermediate and the sodium methoxide solution, and prevents overhigh local concentration and more reaction byproducts caused by direct input of sodium methoxide; sodium methoxide is easy to absorb water, and if the sodium methoxide is directly fed, the effect is not volatile; in the morpholine reaction, morpholine and caustic soda liquid are added, the caustic soda liquid is used as a catalyst, the nucleophilic reaction of morpholine and an epoxy intermediate is facilitated, the epoxy structure on the epoxy intermediate is damaged, the morpholine replaces beta hydrogen on a branched chain, and the stability of the morpholine intermediate can be maintained.
the invention is further configured to: in the step (2), when the chlorine valve at the bottom of the primary kettle is opened, the nitrogen valve at the bottom of the secondary kettle is synchronously opened, and the ratio of the nitrogen flow to the chlorine flow is adjusted to be 1: 1-2.
through adopting above-mentioned technical scheme, among the chlorination, when opening positive cauldron bottom and lead to the chlorine valve, open vice cauldron bottom simultaneously and lead to the nitrogen valve, lead to the nitrogen gas in the vice cauldron, nitrogen gas has increased vice cauldron internal gas pressure, goes into vice cauldron to the chlorine air current and plays the slow down effect, helps chlorine dwell time longer in positive cauldron, helps fully going on of chlorination, improves the yield of chlorinated midbody.
The invention is further configured to: in the step (1), the acylation intermediate is put into a Friedel-crafts hydrolysis kettle, excessive deionized water and hydrochloric acid are added, the volume ratio of the deionized water to the hydrochloric acid is 25-35: 1, stirring is started, a jacket is opened to introduce refrigerating fluid, the temperature of the kettle is reduced to 2-4 ℃, and hydrolysis is carried out for 1-2 hours for later use.
by adopting the technical scheme, deionized water is added into the acylation intermediate, and the Lewis acid complex doped in the acylation intermediate can be removed by hydrolysis, so that the Lewis acid is separated from the acylation intermediate, and the conversion rate of the intermediate 2-methyl-1- (4-chlorphenyl) -1-acetone is improved.
the invention is further configured to: desolventizing the hydrolyzed acylated intermediate, controlling the vacuum degree to be-0.08 to-0.085 Mpa, slowly heating at 10 ℃/h, stopping distillation when the temperature is raised to 135-140 ℃, then replacing with nitrogen to positive pressure, and finishing desolventizing when the temperature is lowered to 95-100 ℃.
By adopting the technical scheme, the hydrolyzed acylation intermediate contains excessive chlorobenzene, and because the boiling point of the chlorobenzene is relatively high, negative pressure pre-steaming is required, the boiling point of the chlorobenzene is reduced under the negative pressure condition, and the chlorobenzene can be quickly removed, so that the yield of the intermediate 2-methyl-1- (4-chlorphenyl) -1-acetone is improved.
The invention is further configured to: transferring the desolventized material into a distillation still, adjusting the negative pressure in the distillation still to be less than or equal to 500pa, raising the temperature through steam, stopping distillation when the steam pressure reaches 0.35-0.45 Mpa and no liquid flows out of a liquid outlet of a condenser, changing the pressure in the distillation still to be positive through nitrogen, keeping the positive pressure and reducing the temperature to 75-80 ℃.
By adopting the technical scheme, the negative pressure in the distillation kettle is continuously increased, and impurities with high boiling point in the desolventized material are distilled and removed by raising the temperature of steam, so that the yield of the intermediate 2-methyl-1- (4-chlorphenyl) -1-acetone is further improved.
The invention is further configured to: in the step (4), adding excessive methanol into the morpholino intermediate, starting stirring, heating to 60-65 ℃ for dissolving for 30min, filtering the dissolved solution, stirring the filtered filtrate, introducing the refrigerating solution for cooling, and crystallizing and discharging when the temperature of the kettle is reduced to 0-2 ℃.
by adopting the technical scheme, the morpholino intermediate contains sodium chloride and liquid alkali, the sodium chloride and the liquid alkali are insoluble in methanol, and the intermediate 2-methyl-1- (4-chlorphenyl) -2-morpholinyl-1-acetone generated after morpholino reaction is dissolved in the methanol, and the methanol and the intermediate are firstly mutually dissolved to realize the separation from the sodium chloride and the liquid alkali; then, the intermediate 2-methyl-1- (4-chlorophenyl) -2-morpholinyl-1-propanone is precipitated by recrystallization, which contributes to the improvement of the yield of the intermediate.
the invention is further configured to: in the methylthio substitution reaction in the step (5), the methylthio substitution feed liquid is put into excessive toluene for extraction and washing.
by adopting the technical scheme, in the methylthio substitution reaction, because a water phase exists and toluene is added, impurities such as sodium chloride and sodium hydroxide generated in the methylthio substitution reaction can be dissolved in the water phase, and the methylthio substitution intermediate can be dissolved in the toluene, so that the effective separation of the methylthio substitution intermediate and the impurities is realized, the yield of the methylthio substitution intermediate is improved, and the yield of a target product is improved.
The invention is further configured to: stirring the extracted and washed feed liquid, heating and distilling toluene under negative pressure, and ending distillation when the temperature of the kettle reaches 135 ℃ and the vacuum degree reaches-0.095 Mpa and no toluene oil droplets exist at the lower outlet of a condenser; and introducing nitrogen, keeping the temperature of the kettle at 105-110 ℃, and finishing introducing nitrogen after a lower liquid outlet of the condenser is transparent and has no vapor fog.
by adopting the technical scheme, because toluene is remained in the methyl sulfide substituted intermediate after extraction, the toluene can influence the purity of the target product, so the residual toluene is removed by adopting a negative pressure distillation mode, and after the lower liquid opening of the condenser is transparent and has no vapor fog, the toluene is completely evaporated, thereby being beneficial to improving the purity of the target product.
The application has the following beneficial effects:
1. The yield of the target product is high: in the chlorination reaction, a primary kettle and a secondary kettle are connected in series, an acylation intermediate is circularly reacted in the primary kettle and the secondary kettle, the sufficiency of the chlorination reaction is improved, excessive chlorine in the primary kettle is removed by using nitrogen, the chlorination intermediate is introduced into a nitrogen-introducing residue-removing kettle and filled with nitrogen, the residual chlorine in the chlorination intermediate can be completely discharged, the generation of byproducts in subsequent steps of the residual chlorine is reduced, and the yield of target products is improved;
2. The chlorination reaction is more complete: in the chlorination reaction, a primary kettle and a secondary kettle are connected in series, when chlorine is introduced into the primary kettle, nitrogen is introduced into the secondary kettle, the air pressure in the secondary kettle is increased, the flowing of the chlorine is slowed, the reaction of the chlorine and an acylation intermediate in the primary kettle is promoted, and the yield of the chlorination intermediate and a target product is improved;
3. The purity of the target product is high: after Friedel-crafts acylation, the acylation product is treated by hydrolysis, desolventization and rectification, which is beneficial to improving the purity of the target product; after morpholine substitution reaction, methanol is added for dissolution, filtration and recrystallization, which is beneficial to improving the purity of the target product; after the methionine substitution reaction, extracting, washing and distilling the methionine substitution feed liquid to further improve the purity of the target product;
4. the reaction conditions are mild: the reaction process has the advantages of simple conditions, low reaction temperature, easy realization of reaction and high safety.
The reaction formula of the present application is as follows:
(1) Friedel-crafts acylation:
(2) Chlorination:
(3) epoxidation:
(4) morpholine:
(5) and (2) methylthio substitution:
Detailed Description
The present invention will be described in further detail with reference to examples.
the first embodiment is as follows:
A preparation method of 2-methyl-1- (4-methylthiophenyl) -2-morpholinyl-1-acetone serving as a photoinitiator comprises the following steps:
1. friedel-crafts acylation reaction:
(1) friedel-crafts feeding: the method comprises the following steps of adopting a 5000L steam heating enamel reaction kettle as a Friedel-crafts dissolution kettle which is matched with an on-kettle condenser, a stirring device and a jacket device;
(a) Putting 3000L of anhydrous chlorobenzene into a Friedel-crafts dissolution kettle, starting stirring, introducing refrigerating fluid and cooling, wherein the temperature of the refrigerating fluid is-20 ℃;
(b) Putting 1300kg of aluminum trichloride into a Friedel-crafts dissolution kettle, keeping stirring and cooling for 1h after the aluminum trichloride is put into the dissolution kettle, and obtaining chlorobenzene aluminum trichloride liquid;
(2) friedel-crafts acylation: the step adopts 5000L steam heating enamel reaction kettle as a Friedel-crafts reaction kettle which is provided with a condenser on the kettle, a stirring device and a jacket device;
(a) Pumping the chlorobenzene aluminum trichloride feed liquid into a Friedel-crafts reaction kettle, starting stirring, introducing a refrigerating liquid into a jacket for cooling, and controlling the temperature of the kettle to be 0-5 ℃;
(b) Dropwise adding 1000kg of isobutyryl chloride into a Friedel-crafts reaction kettle for 6 hours, and keeping the kettle temperature at 0-5 ℃ in the dropwise adding process;
(c) after the dropwise addition is finished, controlling the Friedel-crafts reaction kettle to keep the temperature for 6 hours at 5-7 ℃, and controlling the kettle temperature to keep the temperature for 6 hours at 7-9 ℃; and controlling the kettle temperature to be 9-13 ℃ and preserving the temperature for 6h to obtain the Friedel-crafts acylation intermediate.
2. chlorination reaction:
(1) chlorination reaction: selecting 5000L steam heating enamel kettles as chlorinated kettles, adopting a positive chlorinated kettle and a negative chlorinated kettle which are alternately connected in series in two stages, wherein the chlorinated kettles are matched with a stirring device, a jacket device, a kettle bottom chlorine valve, a tail gas emptying valve and a nitrogen gas introducing device;
(a) 4000kg of acylated intermediates are respectively prepared into the primary and secondary chlorinated kettles, chlorine is introduced into the primary kettle, after the chlorine is reacted and absorbed by the primary kettle, the primary tail gas is captured and absorbed by the acylated intermediates in the secondary kettle, and the secondary tail gas is subjected to environment-friendly absorption;
(b) Starting a primary and secondary chlorinated kettle for stirring, regulating the rotation speed to 85 revolutions per minute, controlling the temperature to be 48-51 ℃, opening a chlorine introducing valve at the bottom of the primary kettle and a tail gas emptying valve of the secondary kettle, introducing chlorine into the primary kettle at the chlorine introducing amount of 60kg/h, and controlling the temperature of the kettle to be 48-51 ℃ in the chlorine introducing process;
(c) When the chlorine gas introduction amount reaches 1500kg, stopping introducing chlorine, and introducing nitrogen into the positive kettle for 45 minutes to replace the excessive chlorine gas in the kettle; after the replacement is finished, putting the reaction liquid in the positive kettle into a nitrogen-introducing residue-removing kettle, and then putting 4000kg of the acylated intermediate again, wherein the positive kettle is changed into a secondary kettle;
(2) Introducing nitrogen to remove residues: selecting a 5000L enamel kettle as a nitrogen-introducing residue-removing kettle, and matching with a nitrogen-introducing device;
and (3) introducing the reaction liquid in the positive kettle into a nitrogen-introducing residue-removing kettle, controlling the temperature of the kettle to be 25-35 ℃, and introducing nitrogen gas from the bottom of the kettle for 6-8 hours to obtain the chlorinated intermediate after chlorine removal.
3. Epoxidation reaction: selecting a 5000L steam heating enamel kettle as an epoxy kettle, wherein the epoxy kettle is matched with a stirring device, a jacket device and a nitrogen introducing device;
(1) preparing 1850kg of chloro intermediate in an epoxy kettle, additionally preparing 1600kg of sodium methoxide solution, and replacing the air in the epoxy kettle with nitrogen;
(2) and starting an epoxy kettle for stirring, dropwise adding 1600kg of sodium methoxide solution at the temperature of 28-35 ℃ for 2.5-3.5 h, and keeping the temperature of the kettle at 36-40 ℃ for 2h after dropwise adding is finished to obtain an epoxy intermediate.
4. morpholinyl substitution reaction:
selecting a 5000L steam heating enamel kettle as a morpholine replacement kettle, wherein the morpholine replacement kettle is matched with an on-kettle vacuum system, a stirring device, an on-kettle condenser and a jacket device;
(1) receiving a batch of epoxy intermediate, starting vacuum, adjusting the vacuum degree to-0.06 Mpa, gradually heating, taking the liquid outlet of a condenser as the proper condition that liquid normally flows out, finally controlling the kettle temperature to 64-66 ℃, adjusting the vacuum degree in the kettle to be less than or equal to-0.095 Mpa when the kettle temperature reaches 64-66 ℃, draining methanol after the liquid outlet of the condenser basically does not flow out, and continuing negative pressure heat preservation for 1 hour;
(2) Adding 2300kg of morpholine into a kettle, adding 250kg of liquid caustic soda with the mass concentration of 30%, introducing steam to slowly raise the temperature at the speed of 10 ℃/h after the morpholine and the liquid caustic soda are added, controlling the temperature raising speed to be 1 ℃/2h when the temperature of the kettle reaches 100 ℃, and preserving the temperature for 1-2 h when the temperature of the kettle rises to 110 ℃;
(3) carrying out negative pressure distillation, slowly adjusting the vacuum degree on the kettle to-0.06 Mpa, preferably enabling liquid to flow out of a liquid outlet of the condenser, adjusting the vacuum degree to-0.095 Mpa when the liquid flows out slowly from the liquid outlet of the condenser, and ending the negative pressure distillation when the temperature of the kettle reaches 135 ℃ and no liquid flows out from the liquid outlet of the condenser; introducing nitrogen to break negative pressure until the pressure in the kettle becomes positive pressure, and cooling to 80 ℃ to obtain the morpholino intermediate.
5. and (3) carrying out a methionine substitution reaction:
(1) Methanol removal: a 3000L steam heating enamel kettle is selected as a melting dealcoholization kettle, and is matched with an on-kettle vacuum system, a stirring device, a nitrogen introducing device and a jacket device;
(a) 1200kg of crystallized and discharged morpholino intermediate is put into a melting dealcoholization kettle, methanol is removed by negative pressure distillation, when the vacuum degree is less than or equal to-0.09 Mpa and the kettle temperature is raised to 90 ℃, no fraction is discharged, and then the temperature is kept, the pressure is maintained and the negative pressure is pumped for 1 hour;
(b) after distillation is finished, introducing nitrogen to break the negative pressure until the pressure in the kettle becomes positive pressure, and obtaining a molten methanol removal material;
(2) methionine substitution: selecting a 5000L steam heating enamel kettle as a methyl sulfide substitution kettle, and matching with an on-kettle vacuum system, a stirring device and a nitrogen introducing device; a 500L steam heating enamel kettle is selected as a catalyst preparation kettle, and a stirring device and a jacket device are matched;
(a) adding 200L of water into a catalyst preparation kettle, stirring and adding 100kg of tetramethylammonium bromide, and dissolving for 1h at the temperature of 40-50 ℃ to prepare a tetramethylammonium bromide aqueous solution with the mass concentration of 50%; 1600kg of a sodium methanethiolate aqueous solution with the mass concentration of 20 percent is prepared;
(b) Starting a vacuum system on a methyl sulfide substitution kettle, pumping a molten de-methanol material into the methyl sulfide substitution kettle, closing the vacuum system on the kettle, keeping the temperature of the kettle at 80-85 ℃, slowly adding a sodium methyl sulfide aqueous solution into the methyl sulfide substitution kettle by utilizing the residual negative pressure in the kettle, using for 30-60 min, then adding a tetramethyl ammonium bromide aqueous solution, and controlling the temperature of the kettle at 85-90 ℃;
(c) And after adding a sodium methyl mercaptide aqueous solution and a tetramethyl ammonium bromide aqueous solution, controlling the temperature of the kettle to be 86-90 ℃, and preserving the temperature for 10 hours to obtain a methyl mercaptide substituted feed liquid.
6. the refining process comprises the following steps:
Starting a coarse filtration pump, controlling the temperature of the kettle to be 55-60 ℃, transferring the methionine substituted feed liquid into a pre-cooling kettle through a coarse filter and a carbon fiber filter, introducing circulating water into the pre-cooling kettle, cooling to 40 ℃, then placing the pre-cooling kettle into a crystallization kettle, and introducing refrigerating liquid for cooling; discharging and centrifuging when the temperature of the kettle is reduced to 0-2 ℃; preparing 8000L of centrifugal mother liquor into a distillation kettle, opening a water inlet and outlet valve of a condenser, replacing air in the kettle with nitrogen, stirring, heating, distilling and concentrating at normal pressure, introducing nitrogen, cooling to 50 ℃, stirring with a refrigerating fluid, cooling to 0-5 ℃, discharging and centrifuging; and (4) carrying out rotary drying on the centrifugal wet material under a vacuum condition, and discharging a dry product.
example two:
A preparation method of a photoinitiator 2-methyl-1- (4-methylthiophenyl) -2-morpholinyl-1-acetone is different from that of the first embodiment in that in a chlorination reaction, when a chlorine introducing valve at the bottom of a main kettle is opened, a nitrogen introducing valve at the bottom of an auxiliary kettle is synchronously opened, the ratio of nitrogen introducing flow to chlorine introducing flow is adjusted to be 1:1, and other steps are the same.
Example three:
A photoinitiator 2-methyl-1- (4-methylthiophenyl) -2-morpholinyl-1-acetone preparation method, with the difference of example two, after Friedel-crafts acylation reaction, carry on the hydrolysis to the acylation midbody, the hydrolysis stage adopts 8000L steam heating enamel kettle as the hydrolysis kettle, the auxiliary apparatus of the hydrolysis kettle has stirring apparatuses, jacket apparatuses; the hydrolysis process comprises the following steps:
(a) Adding 3000L of deionized water and 100L of hydrochloric acid into a hydrolysis kettle, starting stirring, opening a jacket to introduce refrigerating fluid, and cooling the kettle to 3 ℃;
(b) And (3) dropwise adding the acylated intermediate into the hydrolysis kettle, and controlling the kettle temperature to be less than or equal to 52 ℃ in the hydrolysis process.
example four:
A preparation method of 2-methyl-1- (4-methylthiophenyl) -2-morpholinyl-1-acetone serving as a photoinitiator is different from the third embodiment in that after hydrolysis reaction, desolvation and rectification are carried out on a hydrolyzed acylation intermediate; in the desolventizing stage, a 5000L steam heating enamel kettle is used as a desolventizing kettle, and the desolventizing kettle is matched with an on-kettle vacuum system, a stirring device, an on-kettle condenser, a jacket device and a nitrogen introducing device; in the rectification stage, a 5000L steam heating enamel kettle is used as a rectification kettle, and the rectification kettle is matched with an on-kettle vacuum system, a stirring device, an on-kettle condenser, a jacket device and a nitrogen introducing device;
the desolventizing process comprises the following steps:
(a) Pre-steaming the water-washed acylation intermediate, starting stirring, opening a water inlet valve and a water outlet valve of a condenser, opening a vacuum system to perform negative pressure distillation, slowly raising the temperature at 10 ℃/h, wherein the pressure of a jacket steam is less than or equal to 0.1MPa in the early stage and less than or equal to 0.3MPa in the later stage, and finally stopping the negative pressure distillation after no fraction flows out of a liquid outlet of the condenser when the temperature of a kettle is 135 ℃;
(b) replacing the inside of the kettle with nitrogen to positive pressure, and reducing the temperature of the kettle to 95 ℃ under the positive pressure of the nitrogen to obtain a desolventized acylation intermediate;
the rectification process comprises the following steps:
receiving two batches of desolventized acylated intermediates, starting a rectifying still for stirring, introducing steam into a jacket for heating when the negative pressure in the rectifying still is regulated to be less than or equal to 500pa, and controlling the steam pressure to be less than or equal to 0.2Mpa in the early stage; when the steam pressure reaches 0.4MPa and no liquid flows out from the liquid outlet of the condenser, the rectification is stopped, the vacuum system on the kettle is closed, a nitrogen valve is opened to replace the pressure in the kettle to positive pressure, the positive pressure in the kettle is kept to be cooled to 75 ℃, and the rectified acylation intermediate is collected.
Example five:
a preparation method of a photoinitiator 2-methyl-1- (4-methylthiophenyl) -2-morpholinyl-1-acetone is different from that of the first embodiment in that after a morpholinyl substitution reaction, a morpholino intermediate is dissolved, filtered and recrystallized; in the dissolving and recrystallization step, an enamel kettle heated by 8000L steam is selected, and the enamel kettle is matched with a stirring device, a nitrogen introducing device and a jacket device; the filtering step selects a DL duplex bag three-in-one filter manufactured by Jingjiang Yitai; the specific process comprises the following steps:
(a) Adding 4000L of methanol into a dissolving kettle, starting stirring, receiving the morpholino intermediate, and heating to 60 ℃ to dissolve for 30min to obtain a dissolving mixed solution;
(b) when the temperature of the dissolving kettle is reduced to 55 ℃, putting the dissolved mixed solution into a filter for filtering;
(c) and pumping the filtrate flowing out of the filter into a recrystallization kettle, starting stirring, opening a half of the refrigerating fluid inlet valve at first to slowly cool, gradually enlarging the refrigerating fluid inlet valve along with the continuous decrease of the temperature of the kettle, and crystallizing and discharging when the temperature of the kettle is reduced to 0 ℃.
Example six:
a preparation method of a photoinitiator 2-methyl-1- (4-methylthiophenyl) -2-morpholinyl-1-acetone is different from the fifth embodiment in that after the methionine substitution reaction, the methionine substitution feed liquid is extracted, washed and desolventized; selecting a 8000L steam heating enamel kettle as a washing kettle, and matching with a stirring device and a jacket device; the extraction washing process comprises the following steps:
(a) Adding excessive toluene into a methyl sulfide substitution kettle for extraction, then putting the extracted methyl sulfide substitution intermediate into a 8000L washing kettle, controlling the temperature of the washing kettle to be 40 ℃, stirring for 30min, standing for 60min, discharging the lower layer, and leaving the upper layer in the kettle;
(b) washing for the first time, adding 1200L of water into a washing kettle, controlling the kettle temperature at 40 ℃, stirring and washing for 30min, standing for 60min for layering, discharging wastewater at the lower layer, and leaving toluene feed liquid at the upper layer in the kettle;
(c) Washing for the second time, adding 1200L of water into the washing kettle, controlling the kettle temperature at 45 ℃, stirring and washing for 30min, standing for 60min for layering, discharging the wastewater at the lower layer, and leaving the toluene feed liquid at the upper layer in the kettle;
(d) washing for the third time, adding 1200L of water into the washing kettle, controlling the kettle temperature to be 43 ℃, stirring and washing for 30min, standing for 60min for layering, discharging the lower layer wastewater, transferring the upper layer toluene feed liquid into a heat-preservation transfer tank, and preserving heat at 45 ℃ for later use;
Desolventizing the extracted and washed toluene feed liquid, selecting a 5000L steam heating enamel kettle as a desolventizing kettle, and matching with an on-kettle condenser, an on-kettle vacuum system, a stirring device, an on-kettle nitrogen introducing device, an in-kettle steam introducing device and a jacket device; the desolventizing process comprises the following steps:
(a) putting 4000L of water-washed toluene feed liquid into a desolventizing kettle, starting stirring, and heating to distill toluene under negative pressure; (b) gradually increasing the steam pressure and the vacuum degree, keeping stable distillation, when the temperature of the kettle reaches 135 ℃ and the vacuum degree reaches-0.095 Mpa, no liquid is discharged from a lower outlet of the condenser, closing a vacuum valve, introducing nitrogen, breaking negative pressure and finishing distillation;
(c) After the negative pressure distillation is finished, discharging the toluene in the negative pressure receiving tank; then introducing steam into the kettle, evaporating residual toluene completely, and finishing introducing the steam when a lower liquid port of the condenser does not contain small toluene oil droplets;
(d) closing steam, introducing nitrogen into the kettle for about 2 hours, ensuring the temperature of the kettle to be 105-110 ℃ in the nitrogen introducing process, and finishing nitrogen introduction when a lower liquid opening of a condenser is transparent and has no vapor fog;
(e) And opening a nitrogen valve on the kettle, introducing circulating water into a jacket under the condition of nitrogen maintenance, cooling to 80 ℃, and preserving heat at 80-85 ℃ for later use.
Comparative example one: according to the research on the novel synthesis process of the photoinitiator MMMP published by bear Wei, 2-methyl-1- (4-methylthiophenyl) -2-morpholinyl-1-acetone is prepared from methyl phenyl thioether serving as a raw material through Friedel-crafts acylation and amine substitution two-step reaction.
comparative example two: the method comprises the steps of synthesizing chlorobenzene as a raw material to obtain 2-methyl-1- (4-chlorophenyl) -1-acetone, introducing methyl mercaptan gas into a chlorobenzene and sodium hydroxide aqueous solution two-phase system, then performing a thioetherification reaction at 90-102 ℃ by using tetrabutylammonium bromide as a phase transfer catalyst to obtain a target product.
The detection method comprises the following steps:
(1) Calculating the yield: dry product mass/theoretical mass; (2) purity of the target product: measuring with gas chromatograph.
the results are shown in the following table:
| sample (I) | yield (%) | Purity (%) |
| Example one | 85 | 86.7 |
| Example two | 90.1 | 88.3 |
| EXAMPLE III | 90.8 | 90.5 |
| Example four | 91.6 | 92.1 |
| EXAMPLE five | 92.3 | 94.6 |
| EXAMPLE six | 93.5 | 97.3 |
| comparative example 1 | 85 | / |
| comparative example No. two | 87 | 91 |
as can be seen from the above table, the application provides a preparation method for 2-methyl-1- (4-methylthiophenyl) -2-morpholinyl-1-propanone as a photoinitiator, isobutyryl chloride and chlorobenzene are used as raw materials, the cost is low, residual chlorine after chlorination reaction is less, the yield of a target product is improved, the reaction process is mild, the quality control is stable, the yield and the purity can be further improved by optimizing process steps, the process is simple, and the method is suitable for industrial production. The yield of the comparative example is 87%, because the residual chlorine in the prior art represented by the comparative example is more, and the chlorine and the intermediate in the reaction process generate a plurality of side reactions, which affect the yield and the purity of the target product.
the embodiments of the present invention are preferred embodiments of the present invention, and the scope of the present invention is not limited by these embodiments, so: all equivalent changes made according to the structure, shape and principle of the invention are covered by the protection scope of the invention.
Claims (8)
1. a preparation method of 2-methyl-1- (4-methylthiophenyl) -2-morpholinyl-1-acetone serving as a photoinitiator is characterized by comprising the following steps:
(1) Friedel-crafts acylation: taking isobutyryl chloride as a raw material, and carrying out Friedel-crafts acylation reaction with chlorobenzene under the catalysis of Lewis acid to obtain an acylation intermediate 2-methyl-1- (4-chlorphenyl) -1-acetone;
(2) chlorine is replaced by a positive ~ auxiliary alternate two ~ stage series device, chlorine is reacted and absorbed by a positive kettle, positive tail gas is absorbed by reaction liquid in an auxiliary kettle, and tail gas of the auxiliary kettle is absorbed in an environment ~ friendly manner, (a) the positive ~ auxiliary chlorine kettle is started to stir, steam is introduced to raise the temperature, the temperature is controlled to be 48 ~ 51 ℃, a chlorine introducing valve of the positive kettle and a tail gas emptying valve of the auxiliary kettle are opened, chlorine is introduced for 15 ~ 25h, (b) then nitrogen is introduced into the positive kettle to replace excessive chlorine in the positive kettle, the chlorinated intermediate in the positive kettle is discharged, the acylated intermediate is continuously introduced into the positive kettle, and the positive kettle is changed into the auxiliary kettle, (c) the chlorinated intermediate is introduced into a nitrogen ~ introducing residue ~ removing kettle, the temperature of the kettle is controlled to be 25 ~ 35 ℃, and nitrogen is introduced into the nitrogen ~ introducing residue ~ removing kettle for 6 ~ 8 h;
(3) performing epoxidation, namely adding the chlorinated intermediate subjected to chlorine removal into an epoxy kettle, controlling the temperature of the kettle to be 28 ~ 35 ℃, dropwise adding excessive sodium methoxide solution, controlling the temperature of the kettle to be 36 ~ 40 ℃ after dropwise adding, and keeping the temperature for at least 2 hours to obtain the epoxy intermediate;
(4) morpholine and liquid alkali are added into a morpholine substitution kettle, the mass ratio of morpholine to liquid alkali is 8 ~ 12:1, negative pressure distillation is carried out, when the temperature of the kettle reaches 135 ℃, the distillation is finished, nitrogen is introduced to enable the interior of the kettle to be in positive pressure, and the temperature is reduced to 78 ~ 82 ℃ to obtain a morpholine intermediate;
(5) pumping the morpholino intermediate into a methylthio substitution kettle, keeping the temperature of the kettle at 80 ~ 85 ℃, adding a sodium methyl mercaptide aqueous solution with the mass concentration of 20 ~ 30% and a tetramethyl ammonium bromide aqueous solution with the mass concentration of 50 ~ 80%, controlling the temperature of the kettle at 85 ~ 90 ℃, and preserving the temperature for 8 ~ 12 hours to obtain a methylthio substitution feed liquid;
(6) refining: filtering the methionine substituted feed liquid, introducing refrigerating liquid for cooling after filtering, centrifugally discharging, and drying to obtain the 2-methyl-1- (4-methylthiophenyl) -2-morpholinyl-1-acetone.
2. the preparation method of the photoinitiator 2 ~ methyl ~ 1 ~ (4 ~ methylthiophenyl) ~ 2 ~ morpholinyl ~ 1 ~ acetone according to claim 1, wherein in the step (2), when a chlorine valve at the bottom of the primary kettle is opened, a nitrogen valve at the bottom of the secondary kettle is synchronously opened, and the ratio of the nitrogen flow to the chlorine flow is adjusted to be 1:1 ~ 2.
3. the preparation method of the photoinitiator 2 ~ methyl ~ 1 ~ (4 ~ methylthiophenyl) ~ 2 ~ morpholinyl ~ 1 ~ acetone according to claim 1 or 2, wherein in the step (1), the acylation intermediate is put into a Friedel ~ crafts hydrolysis kettle, excessive deionized water and hydrochloric acid are added, the volume ratio of the deionized water to the hydrochloric acid is 25 ~ 35:1, stirring is started, a jacket is opened to introduce a refrigerating fluid, the kettle temperature is reduced to 2 ~ 4 ℃, and hydrolysis is carried out for 1 ~ 2 hours for later use.
4. the preparation method of the photoinitiator 2-methyl-1- (4-methylthiophenyl) -2-morpholinyl-1-acetone according ~ claim 3, wherein desolventizing is carried out on the hydrolyzed acylated intermediate, the vacuum degree is controlled ~ be-0.08 ~ -0.085Mpa, the temperature is slowly increased at 10 ℃/h, distillation is stopped when the temperature is increased ~ 135 ~ 140 ℃, then positive pressure is replaced by nitrogen, and the desolventizing is finished when the temperature is reduced ~ 95 ~ 100 ℃.
5. the preparation method of the photoinitiator 2 ~ methyl ~ 1 ~ (4 ~ methylthiophenyl) ~ 2 ~ morpholinyl ~ 1 ~ acetone according to claim 4, wherein the desolventizing material is transferred into a distillation kettle, when the negative pressure in the distillation kettle is adjusted to be less than or equal to 500pa, the temperature is raised through steam, when the steam pressure reaches 0.35 ~ 0.45MPa and no liquid flows out from a liquid outlet of a condenser, the distillation is stopped, the positive pressure in the kettle is changed to be maintained through nitrogen, and the temperature is reduced to 75 ~ 80 ℃.
6. the preparation method of the photoinitiator 2 ~ methyl ~ 1 ~ (4 ~ methylthiophenyl) ~ 2 ~ morpholinyl ~ 1 ~ acetone according to claim 1 or 2, wherein in the step (4), excessive methanol is added into the morpholino intermediate, stirring is started, the temperature is raised to 60 ~ 65 ℃ for dissolving for 30min, the dissolved solution is filtered, the filtered filtrate is stirred, the cooling liquid is introduced for cooling, and crystallization is carried out when the temperature of the kettle is lowered to 0 ~ 2 ℃, and then the material is discharged.
7. the method for preparing 2-methyl-1- (4-methylthiophenyl) -2-morpholinyl-1-propanone as the photoinitiator according to claim 1, wherein the method comprises the following steps: in the methylthio substitution reaction in the step (5), the methylthio substitution feed liquid is put into excessive toluene for extraction and washing.
8. the preparation method of the photoinitiator 2 ~ methyl ~ 1 ~ (4 ~ methylthiophenyl) ~ 2 ~ morpholinyl ~ 1 ~ acetone according to claim 7, wherein the solution obtained after extraction and washing is stirred, toluene is distilled under negative pressure by heating, distillation is finished when the temperature of a kettle reaches 135 ℃ and the vacuum degree reaches ~ 0.095Mpa and no small toluene oil drops exist at the lower outlet of a condenser, nitrogen is introduced, the temperature of the kettle is kept at 105 ~ 110 ℃, and nitrogen introduction is finished when the lower liquid outlet of the condenser is transparent and has no vapor fog.
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| CN112552259A (en) * | 2020-12-28 | 2021-03-26 | 湖南久日新材料有限公司 | Preparation method of 2-methyl-1- (4-substituted phenyl) -2-morpholinyl-1-acetone |
| CN114426525A (en) * | 2021-12-29 | 2022-05-03 | 天津久日新材料股份有限公司 | White solid photoinitiator and preparation method and application thereof |
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| CN114426525A (en) * | 2021-12-29 | 2022-05-03 | 天津久日新材料股份有限公司 | White solid photoinitiator and preparation method and application thereof |
| CN114426525B (en) * | 2021-12-29 | 2024-03-29 | 天津久日新材料股份有限公司 | White solid photoinitiator and preparation method and application thereof |
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Application publication date: 20191213 |