CN117326920A - Method for continuously preparing p-chlorobenzaldehyde - Google Patents
Method for continuously preparing p-chlorobenzaldehyde Download PDFInfo
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- CN117326920A CN117326920A CN202210731277.6A CN202210731277A CN117326920A CN 117326920 A CN117326920 A CN 117326920A CN 202210731277 A CN202210731277 A CN 202210731277A CN 117326920 A CN117326920 A CN 117326920A
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- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 title claims abstract description 87
- 238000000034 method Methods 0.000 title claims abstract description 64
- 239000012456 homogeneous solution Substances 0.000 claims abstract description 116
- 238000006243 chemical reaction Methods 0.000 claims abstract description 115
- PTHGDVCPCZKZKR-UHFFFAOYSA-N (4-chlorophenyl)methanol Chemical compound OCC1=CC=C(Cl)C=C1 PTHGDVCPCZKZKR-UHFFFAOYSA-N 0.000 claims abstract description 43
- 239000003054 catalyst Substances 0.000 claims abstract description 33
- 239000007800 oxidant agent Substances 0.000 claims abstract description 28
- 239000002904 solvent Substances 0.000 claims abstract description 26
- 230000003197 catalytic effect Effects 0.000 claims abstract description 20
- 230000001590 oxidative effect Effects 0.000 claims abstract description 16
- 239000012752 auxiliary agent Substances 0.000 claims abstract description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims abstract description 5
- 238000005086 pumping Methods 0.000 claims abstract description 5
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 92
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 82
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 claims description 82
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 38
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 26
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 24
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- 230000008569 process Effects 0.000 claims description 12
- 239000007864 aqueous solution Substances 0.000 claims description 9
- 238000002156 mixing Methods 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 claims description 4
- KMUONIBRACKNSN-UHFFFAOYSA-N potassium dichromate Chemical compound [K+].[K+].[O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O KMUONIBRACKNSN-UHFFFAOYSA-N 0.000 claims description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 claims description 2
- 229910001623 magnesium bromide Inorganic materials 0.000 claims description 2
- 239000012286 potassium permanganate Substances 0.000 claims description 2
- CZPZWMPYEINMCF-UHFFFAOYSA-N propaneperoxoic acid Chemical compound CCC(=O)OO CZPZWMPYEINMCF-UHFFFAOYSA-N 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 abstract description 12
- 239000002994 raw material Substances 0.000 abstract description 10
- 239000002351 wastewater Substances 0.000 abstract description 3
- 238000002347 injection Methods 0.000 description 67
- 239000007924 injection Substances 0.000 description 67
- 239000000243 solution Substances 0.000 description 37
- 239000012295 chemical reaction liquid Substances 0.000 description 33
- 238000004440 column chromatography Methods 0.000 description 18
- 238000004128 high performance liquid chromatography Methods 0.000 description 18
- 238000000926 separation method Methods 0.000 description 11
- 238000006460 hydrolysis reaction Methods 0.000 description 10
- 238000007254 oxidation reaction Methods 0.000 description 9
- 238000006467 substitution reaction Methods 0.000 description 9
- 230000009286 beneficial effect Effects 0.000 description 8
- NPDACUSDTOMAMK-UHFFFAOYSA-N 4-Chlorotoluene Chemical compound CC1=CC=C(Cl)C=C1 NPDACUSDTOMAMK-UHFFFAOYSA-N 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 230000003647 oxidation Effects 0.000 description 7
- 238000005660 chlorination reaction Methods 0.000 description 5
- 230000007547 defect Effects 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- VWHNJDGWDOQJRM-UHFFFAOYSA-N 1-chloro-4-(dichloromethyl)benzene Chemical compound ClC(Cl)C1=CC=C(Cl)C=C1 VWHNJDGWDOQJRM-UHFFFAOYSA-N 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- JQZAEUFPPSRDOP-UHFFFAOYSA-N 1-chloro-4-(chloromethyl)benzene Chemical compound ClCC1=CC=C(Cl)C=C1 JQZAEUFPPSRDOP-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000000575 pesticide Substances 0.000 description 3
- ZPTVNYMJQHSSEA-UHFFFAOYSA-N 4-nitrotoluene Chemical compound CC1=CC=C([N+]([O-])=O)C=C1 ZPTVNYMJQHSSEA-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000012954 diazonium Substances 0.000 description 2
- 150000001989 diazonium salts Chemical class 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 238000006056 electrooxidation reaction Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- VATYWCRQDJIRAI-UHFFFAOYSA-N p-aminobenzaldehyde Chemical compound NC1=CC=C(C=O)C=C1 VATYWCRQDJIRAI-UHFFFAOYSA-N 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- 238000004065 wastewater treatment Methods 0.000 description 2
- YNWVFADWVLCOPU-MDWZMJQESA-N (1E)-1-(4-chlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl)pent-1-en-3-ol Chemical compound C1=NC=NN1/C(C(O)C(C)(C)C)=C/C1=CC=C(Cl)C=C1 YNWVFADWVLCOPU-MDWZMJQESA-N 0.000 description 1
- RMOGWMIKYWRTKW-UONOGXRCSA-N (S,S)-paclobutrazol Chemical compound C([C@@H]([C@@H](O)C(C)(C)C)N1N=CN=C1)C1=CC=C(Cl)C=C1 RMOGWMIKYWRTKW-UONOGXRCSA-N 0.000 description 1
- GPOFSFLJOIAMSA-UHFFFAOYSA-N 1-chloro-4-ethylbenzene Chemical compound CCC1=CC=C(Cl)C=C1 GPOFSFLJOIAMSA-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- DKIDEFUBRARXTE-UHFFFAOYSA-N 3-mercaptopropanoic acid Chemical compound OC(=O)CCS DKIDEFUBRARXTE-UHFFFAOYSA-N 0.000 description 1
- XRHGYUZYPHTUJZ-UHFFFAOYSA-N 4-chlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1 XRHGYUZYPHTUJZ-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 239000005985 Paclobutrazol Substances 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- XEFQLINVKFYRCS-UHFFFAOYSA-N Triclosan Chemical compound OC1=CC(Cl)=CC=C1OC1=CC=C(Cl)C=C1Cl XEFQLINVKFYRCS-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000980 acid dye Substances 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- -1 aldehyde hydrogen Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 238000010923 batch production Methods 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- SOYKEARSMXGVTM-UHFFFAOYSA-N chlorphenamine Chemical compound C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 SOYKEARSMXGVTM-UHFFFAOYSA-N 0.000 description 1
- 229960003291 chlorphenamine Drugs 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical compound [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 238000005868 electrolysis reaction Methods 0.000 description 1
- 238000010812 external standard method Methods 0.000 description 1
- 239000003063 flame retardant Substances 0.000 description 1
- 230000002363 herbicidal effect Effects 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 230000033116 oxidation-reduction process Effects 0.000 description 1
- 238000005502 peroxidation Methods 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 239000005648 plant growth regulator Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000004753 textile Substances 0.000 description 1
- 229960003500 triclosan Drugs 0.000 description 1
- AAAQKTZKLRYKHR-UHFFFAOYSA-N triphenylmethane Chemical compound C1=CC=CC=C1C(C=1C=CC=CC=1)C1=CC=CC=C1 AAAQKTZKLRYKHR-UHFFFAOYSA-N 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
- C07C45/29—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation of hydroxy groups
- C07C45/294—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation of hydroxy groups with hydrogen peroxide
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
-
- 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)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to the technical field of p-chlorobenzaldehyde preparation and discloses a method for continuously preparing p-chlorobenzaldehyde. The method comprises the following steps: dissolving p-chlorobenzyl alcohol in a first solvent to obtain a homogeneous solution A; dissolving an oxidant, a catalytic auxiliary agent and a catalyst in a second solvent to obtain a homogeneous solution B; and pumping the homogeneous solution A and the homogeneous solution B into a micro-channel reaction device respectively for reaction. The method for continuously preparing the p-chlorobenzaldehyde provided by the invention adopts the p-chlorobenzyl alcohol as the raw material, and combines the microchannel reaction device to continuously react in one step to prepare the p-chlorobenzaldehyde, so that the reaction efficiency can be improved, the reaction time can be shortened, the reaction temperature is low, the product yield is high, and the hydrochloric acid wastewater is basically not generated.
Description
Technical Field
The invention relates to the technical field of p-chlorobenzaldehyde preparation, in particular to a method for continuously preparing p-chlorobenzaldehyde.
Background
P-chlorobenzaldehyde is a fine organic chemical intermediate with very wide application, and has important application value in the aspects of medicines, pesticides, dyes and the like. In medicine, the p-chlorobenzaldehyde is subjected to condensation and mercaptopropionic acid cyclization reaction to prepare the fenazamide syrup, and the medicine chlorpheniramine acid can be synthesized; in pesticides, p-chlorobenzaldehyde is an important intermediate for synthesizing plant growth regulators uniconazole, paclobutrazol and herbicide triclosan; on the dye, the triphenylmethane type acid dye taking p-chlorobenzaldehyde as an intermediate has good vividness and high staining degree, and is widely used in the industries of wool silk dyeing and the like. In addition, p-chlorobenzaldehyde can be used as an intermediate for textile auxiliaries, flame retardants and photosensitive materials. In recent years, with the continuous development of downstream p-chlorobenzaldehyde products, the demand thereof has been rising year by year.
Many p-chlorobenzaldehyde synthesis methods adopt the synthesis route of p-chlorotoluene as raw material, and mainly comprise a chlorination catalytic hydrolysis method, a manganese dioxide oxidation method, an air catalytic oxidation method, an electrochemical oxidation method and the like; in addition, there is a synthetic route using paranitrotoluene as raw material. In the synthetic route adopting p-chlorotoluene as a raw material, the chlorination catalytic hydrolysis method has the defects of high equipment requirement, difficult control of chlorination depth and oxidation degree, complex production process, large hydrolysis wastewater amount, long reaction time, serious equipment corrosion and the like; the manganese dioxide oxidation method also has the defects of difficult control of oxidation degree and easy obtaining of p-chlorobenzoic acid by peroxidation, and also has the defects of Mn 2+ Is to solve the problem of wastewater treatment; the air catalytic oxidation method requires a high-efficiency catalyst and has the defects of difficult catalyst preparation, high reaction temperature and low yield; electrochemical oxidation has been a distance from industrialization due to the great difficulty of electrolysis technology. In the synthetic route using paranitrotoluene as the starting material, alkali sulfide (Na 2 S X ) Is used as an oxidation-reduction agent to prepare diazonium salt solution of the para-aminobenzaldehyde, and the diazonium salt solution is subjected to Mordetmeier reactionThe p-chlorobenzaldehyde is finally obtained, the process of the method is more complicated, and the amount of three wastes is larger.
CN109651111a discloses a process for preparing p-chlorobenzaldehyde, which comprises the steps of, using p-chlorotoluene as raw material, carrying out substitution reaction with chlorine under the action of catalyst to obtain a mixture of p-chlorobenzyl chloride and p-chlorobenzylidene dichloride, carrying out hydrolysis reaction and air catalytic oxidation reaction on the mixture under the action of catalyst to obtain p-chlorobenzaldehyde. The method reduces the reaction temperature of the substitution reaction through the action of the catalyst, and improves the yield of the p-chlorobenzaldehyde by adopting a combination mode of hydrolysis reaction and air catalytic oxidation reaction, but the total reaction time is longer than 10 hours, and the production process is complicated.
Disclosure of Invention
The invention aims to solve the problems of long reaction time, troublesome wastewater treatment, complicated operation and low product yield of p-chlorobenzaldehyde in the prior art, and provides a method for continuously preparing p-chlorobenzaldehyde.
In order to achieve the above object, the present invention provides a method for continuously preparing p-chlorobenzaldehyde, comprising:
(1) Dissolving p-chlorobenzyl alcohol in a first solvent to obtain a homogeneous solution A; dissolving an oxidant, a catalytic auxiliary agent and a catalyst in a second solvent to obtain a homogeneous solution B;
(2) Pumping the homogeneous solution A and the homogeneous solution B obtained in the step (1) into a micro-channel reaction device respectively for reaction.
In the prior art, the method for producing the p-chlorobenzaldehyde mainly adopts a p-chlorotoluene chlorination catalytic hydrolysis method which takes p-chlorotoluene as a raw material, and the method still mainly adopts batch production of batch kettles in large-scale production, so that the problems of high equipment requirement, difficult control of chlorination depth and oxidation degree, complex production process, long reaction time, low product yield, large three-waste amount and the like exist. The micro-chemical technology is a green synthesis technology for preparing pesticides and pharmaceutical intermediates through process enhancement, and micro-functional equipment is the core of the micro-chemical technology and can be divided into a micro heat exchanger, a micro mixer, a micro dispenser, a micro reactor, a micro detector and the like according to functions. Wherein, the characteristics of small size, large specific surface area, ordered flow and the like of the micro-reactor lead the micro-chemical reaction to have the following unique properties: the reaction is carried out intrinsically safely, the homogeneous phase and heterogeneous phase rapid mixing and the efficient and rapid heat exchange capability are realized, the temperature distribution is narrow, the residence time is short, the residence time distribution is narrow, the process can be controlled accurately, and the amplification effect is avoided.
Based on the above, the inventor creatively adopts p-chlorobenzyl alcohol as a raw material, and combines a microchannel reaction device to continuously react in one step to prepare p-chlorobenzaldehyde, so that the reaction efficiency can be improved, the reaction time can be shortened, the reaction temperature is low, the product yield is high, and no hydrochloric acid wastewater is basically generated.
Through the technical scheme, the method provided by the invention has the following advantages:
(1) Compared with the traditional intermittent production method, the method provided by the invention adopts the micro-channel reaction device to realize the continuous production of the p-chlorobenzaldehyde, can shorten the reaction time from tens of hours to tens of minutes or even minutes, has high reaction efficiency, mild reaction conditions and high product yield which can reach 86% at most;
(2) The method provided by the invention uses relatively cheap and easily available p-chlorobenzyl alcohol as the initial raw material, and has high atom economy and good substrate universality;
(3) Preferably, the method provided by the invention uses hydrogen peroxide as an oxidant, does not need to add an expensive organic catalyst or metal catalyst in the reaction process, and has the advantages of simple operation and low cost.
In a word, the method provided by the invention prepares the p-chlorobenzaldehyde by adopting a microchannel reaction device to continuously react the homogeneous solution A containing the p-chlorobenzyl alcohol and the homogeneous solution B containing the oxidant, the catalytic auxiliary agent and the catalyst in one step, and the reaction process is easy to control, high in safety, mild in reaction condition and better in industrial scale-up potential.
Drawings
FIG. 1 is a schematic illustration of the reaction scheme of a preferred embodiment of the present invention;
FIG. 2 is a p-chlorobenzaldehyde product prepared in example 1 1 H nuclear magnetic spectrogram;
FIG. 3 is a p-chlorobenzaldehyde product prepared in example 1 13 C nuclear magnetic spectrogram.
Description of the reference numerals
1. Homogeneous phase solution A2, homogeneous phase solution B3 and first injection pump
4. Second syringe pump 5, micromixer 6, microchannel reactor
7. Separation unit
Detailed Description
The endpoints and any values of the ranges disclosed herein are not limited to the precise range or value, and are understood to encompass values approaching those ranges or values. For numerical ranges, one or more new numerical ranges may be found between the endpoints of each range, between the endpoint of each range and the individual point value, and between the individual point value, in combination with each other, and are to be considered as specifically disclosed herein.
The invention provides a method for continuously preparing p-chlorobenzaldehyde, which comprises the following steps:
(1) Dissolving p-chlorobenzyl alcohol in a first solvent to obtain a homogeneous solution A; dissolving an oxidant, a catalytic auxiliary agent and a catalyst in a second solvent to obtain a homogeneous solution B;
(2) Pumping the homogeneous solution A and the homogeneous solution B obtained in the step (1) into a micro-channel reaction device respectively for reaction.
The existing method for preparing p-chlorobenzaldehyde by using p-chlorotoluene as a raw material through substitution and hydrolysis mainly comprises the following steps: 1. the p-chlorobenzol is subjected to substitution reaction with chlorine under the irradiation of ultraviolet light to synthesize p-chlorobenzyl chloride, and the p-chlorobenzaldehyde is obtained through hydrolysis reaction, the yield of the p-chlorobenzaldehyde synthesized by the method is only 60%, and the synthetic reaction time of the p-chlorobenzaldehyde is long; 2. the p-chlorobenzol is subjected to substitution reaction with chlorine to synthesize p-chlorobenzylidene dichloride under the irradiation of ultraviolet light, and the p-chlorobenzylidene dichloride is refined and then subjected to hydrolysis reaction to obtain p-chlorobenzaldehyde, so that the method has high yield, but the refining process has high cost, and the defect of long synthetic reaction time of the p-chlorobenzaldehyde still exists; 3. the p-chlorobenzol and chlorine gas are subjected to substitution reaction under the irradiation of ultraviolet light to synthesize a mixture of p-chlorobenzyl chloride and p-chlorobenzylidene dichloride, and the mixture is subjected to hydrolysis reaction to obtain the p-chlorobenzaldehyde. In addition, the substitution reaction of p-chlorotoluene and chlorine is severe, and the reaction usually needs to be carried out under the irradiation of light or ultraviolet light at a temperature of above 120-140 ℃. Meanwhile, three hydrogen atoms of methyl p-chlorotoluene can be replaced by chlorine atoms, and the degree of substitution reaction is difficult to control under the high temperature and illumination or ultraviolet light irradiation.
The method provided by the invention prepares the p-chlorobenzaldehyde by adopting a microchannel reaction device to continuously react a homogeneous solution A containing p-chlorobenzyl alcohol with a homogeneous solution B containing an oxidant, a catalytic auxiliary agent and a catalyst in one step, and preferably, hydrogen peroxide is used as the oxidant, and a specific reaction equation in the reaction process is shown as follows:
the method provided by the invention has the advantages that the reaction process is easy to control, the reaction efficiency is improved, the reaction time is shortened, and the higher yield of the p-chlorobenzaldehyde product can be realized at a milder reaction temperature.
According to some embodiments of the invention, preferably, in step (1), the concentration of p-chlorobenzyl alcohol in the homogeneous solution A is 0.05-0.5mmol/mL, preferably 0.2-0.4mmol/mL. The concentration of the p-chlorobenzyl alcohol in the homogeneous solution A is limited to the above range, which is beneficial to improving the utilization rate of the p-chlorobenzyl alcohol.
According to some embodiments of the invention, preferably, in step (1), the concentration of the oxidizing agent in the homogeneous solution B is between 0.2 and 2mmol/mL, preferably between 0.5 and 1mmol/mL. The concentration of the oxidizing agent in the homogeneous solution B is limited to the above-described range, which is advantageous in improving the reaction selectivity.
According to some embodiments of the invention, preferably, the molar mass ratio of the oxidizing agent to p-chlorobenzyl alcohol is (1-5): 1, preferably (2-3): 1, more preferably (2.5-3): 1. the adoption of the preferred embodiment is beneficial to further improving the yield and the product selectivity of the p-chlorobenzaldehyde product.
The variety of oxidizing agents may be selected within a wide range according to some embodiments of the present invention, provided that the oxidizing agent is capable of oxidizing the hydroxyl group of p-chlorobenzyl alcohol to an aldehyde group, and is within the scope of the present invention. Preferably, the oxidizing agent is selected from at least one of hydrogen peroxide, peracetic acid, peroxypropionic acid, potassium permanganate and potassium dichromate, preferably hydrogen peroxide; more preferably, the oxidizing agent is provided in the form of hydrogen peroxide; further preferably, the mass fraction of the hydrogen peroxide is 30% -100%, and preferably 50% -100%. Preferably, the oxidant is provided in the form of hydrogen peroxide, which is beneficial to simplifying operation and reducing production cost. In addition, the mass fraction of the hydrogen peroxide is in the preferable range, so that the yield of p-chlorobenzaldehyde products is further improved.
According to some embodiments of the present invention, the catalyst promoter preferably accounts for 1% -10%, preferably 2% -8%, more preferably 3% -4% of the mass of the p-chlorobenzyl alcohol. The adoption of the preferred embodiment is beneficial to improving the catalytic rate of the reaction and further improving the yield of p-chlorobenzaldehyde products.
According to some embodiments of the present invention, the types of the catalyst auxiliary may be selected in a wide range, so long as the catalyst auxiliary capable of accelerating the catalytic action is within the usable range of the present invention. Preferably, the catalyst promoter is selected from at least one of sodium bromide, potassium bromide and magnesium bromide, preferably sodium bromide; more preferably, the sodium bromide is provided in the form of an aqueous solution; further preferably, the mass fraction of sodium bromide in the aqueous solution is 1% -10%, preferably 5% -10%. The use of the catalyst auxiliary within the above-mentioned preferred range is advantageous in improving the catalytic rate of the reaction.
According to some embodiments of the present invention, the catalyst preferably comprises 1% to 20%, preferably 1.5% to 15%, more preferably 2% to 6% by mass of p-chlorobenzyl alcohol. The adoption of the preferred embodiment is beneficial to accelerating the reaction rate and further improving the yield of p-chlorobenzaldehyde products.
According to some embodiments of the invention, the types of catalysts may be selected within a wide range, provided that the catalysts are capable of providing acidity are within the useful scope of the invention. Preferably, the catalyst is selected from at least one of sulfuric acid, hydrochloric acid and phosphoric acid, preferably sulfuric acid; more preferably, the sulfuric acid is provided in the form of an aqueous solution; further preferably, the mass fraction of the sulfuric acid in the aqueous solution is 1% -10%, preferably 1% -5%. Catalysts within the above preferred ranges are advantageous for accelerating the reaction rate.
According to some embodiments of the present invention, the types of the first solvent and the second solvent may be selected in a wide range as long as they are miscible and dissolve p-chlorobenzyl alcohol, an oxidizing agent, a catalytic promoter, and a catalyst. Preferably, the first solvent and the second solvent are the same or different and are each independently selected from at least one of acetonitrile, dimethyl sulfoxide (DMSO), dioxane and N, N-Dimethylformamide (DMF), preferably at least one of dimethyl sulfoxide, dioxane and N, N-dimethylformamide, more preferably dimethyl sulfoxide and/or dioxane, further preferably dioxane; still more preferably, the first solvent and the second solvent are the same. The selection of the first solvent and the second solvent within the above preferred ranges is advantageous for improving the reaction efficiency and further improving the yield of p-chlorobenzaldehyde products.
According to some embodiments of the invention, preferably, in step (2), the microchannel reaction device comprises a micromixer and a microreactor (microchannel reactor). The microchannel reaction device can effectively increase the contact area between reactants, enhance the mass and heat transfer effect, improve the utilization rate of the oxidant, shorten the reaction time, and greatly improve the stability of the oxidant and the selectivity of target products.
According to some embodiments of the invention, the microreactor preferably has a reaction volume of 3-10mL, preferably 5-8mL. The adoption of the preferred embodiment is beneficial to further improving the yield of the p-chlorobenzaldehyde product.
According to some embodiments of the invention, the microreactor preferably has an inner diameter of 0.3 to 1mm, preferably 0.5 to 0.8mm. The adoption of the preferred embodiment is beneficial to further improving the yield of the p-chlorobenzaldehyde product.
According to some embodiments of the present invention, preferably, in step (2), the homogeneous solution a and the homogeneous solution B obtained in step (1) are pumped into the micromixer simultaneously to be mixed, and then the obtained mixture is sent into the microreactor to be reacted.
According to some embodiments of the invention, preferably, the mixing is performed at normal temperature and pressure; the mixing time is 1-20ms. Wherein, the normal temperature is 20-30 ℃, and the normal pressure is 1 standard atmospheric pressure. In the present invention, the pressures mentioned are gauge pressures.
According to some embodiments of the invention, preferably, the micromixer has a hydraulic radius of 5-50 microns.
According to some embodiments of the present invention, preferably, in step (2), the flow rates of the homogeneous solution a and the homogeneous solution B are the same or different, and each is independently 0.1 to 0.5mL/min, preferably 0.2 to 0.4mL/min; more preferably, the flow rates of the homogeneous solution a and the homogeneous solution B are the same. The adoption of the preferred embodiment is beneficial to improving the reaction effect and further improving the yield of p-chlorobenzaldehyde products.
According to some embodiments of the present invention, the flow rates of the homogeneous solution a and the homogeneous solution B may be regulated using a flow rate control/metering device conventional in the art, and there is no particular limitation thereto, and for example, the flow rates of the homogeneous solution a and the homogeneous solution B may be regulated using a metering pump and/or a syringe pump.
According to some embodiments of the invention, preferably, in step (2), the reaction conditions include: the reaction temperature is 50-90 ℃, preferably 60-80 ℃; the reaction residence time is 5 to 30min, preferably 10 to 25min. The reaction conditions are within the above preferred ranges to facilitate the improvement of the reaction effect and further improve the yield of p-chlorobenzaldehyde product.
According to some embodiments of the invention, preferably, the method further comprises a step of separating the product obtained by the reaction of step (2). The separation may be performed with reference to the prior art, which is not particularly limited. More preferably, the separation is a column chromatography separation.
According to a particularly preferred embodiment of the present invention, the process for continuously preparing p-chlorobenzaldehyde comprises the steps of:
(1-1) dissolving p-chlorobenzyl alcohol in a first solvent to obtain a homogeneous solution A; dissolving an oxidant, a catalytic auxiliary agent and a catalyst in a second solvent to obtain a homogeneous solution B;
(2-1) pumping the homogeneous solution A and the homogeneous solution B obtained in the step (1-1) into a micro-channel reaction device respectively for reaction;
wherein the first solvent and the second solvent are the same and are selected from at least one of acetonitrile, dimethyl sulfoxide, dioxane and N, N-dimethylformamide, preferably at least one of dimethyl sulfoxide, dioxane and N, N-dimethylformamide, more preferably dimethyl sulfoxide and/or dioxane, further preferably dioxane; the oxidant is 30-100% hydrogen peroxide by mass fraction; the catalyst auxiliary agent is sodium bromide; the catalyst is sulfuric acid aqueous solution with the mass fraction of 1% -10%.
FIG. 1 is a schematic reaction scheme of a preferred embodiment of the present invention, wherein the process comprises:
(1-2) dissolving p-chlorobenzyl alcohol in a first solvent to obtain a homogeneous solution A1; dissolving an oxidant, a catalytic auxiliary agent and a catalyst in a second solvent to obtain a homogeneous solution B2;
(2-2) the homogeneous solution A1 and the homogeneous solution B2 are respectively metered by a first injection pump 3 and a second injection pump 4 and then enter a micro mixer 5 for mixing, then enter a micro channel reactor 6 for reaction, and then the products obtained by the reaction are sent to a separation unit 7 for column chromatography separation, thus obtaining the p-chlorobenzaldehyde product.
The present invention will be described in detail by examples.
In the following examples, all the raw materials used were commercially available ones unless otherwise specified.
The yield of p-chlorobenzaldehyde is determined by a high performance liquid chromatography external standard method (HPLC) to determine the content of the p-chlorobenzaldehyde in the reaction liquid. The calculation formula is as follows: yield of p-chlorobenzaldehyde = molar mass of p-chlorobenzaldehyde formed/(molar mass of p-chlorobenzyl alcohol added by reaction x 100%).
Reaction residence time = reaction volume/total feed (where total feed is the total flow of the first and second syringe pumps).
The following examples all follow the reaction scheme shown in FIG. 1 for the preparation of p-chlorobenzaldehyde.
Example 1
3mmol (0.428 g) of p-chlorobenzyl alcohol was dissolved in 10mL dioxane to give a homogeneous solution A; 50wt% hydrogen peroxide (containing 7.5mmol (0.255 g) of hydrogen peroxide), 5wt% sodium bromide solution (containing 0.015g of sodium bromide) and 1wt% sulfuric acid solution (containing 0.01g of sulfuric acid) were dissolved in 10mL of dioxane to obtain a homogeneous solution B. The homogeneous solution A and the homogeneous solution B are respectively metered by a first injection pump and a second injection pump, then enter a micromixer (with the hydraulic radius of 20 microns), are rapidly mixed at normal temperature and normal pressure, then enter a microchannel reactor for reaction, and analyze the reaction liquid. Wherein: the flow rates of the first injection pump and the second injection pump are 0.2mL/min, the reaction volume V=5 mL of the microchannel reactor, the inner diameter is 0.5mm, and the reactor temperature is 70 ℃. After the reaction of the microchannel reactor has passed through two cycles, collecting reaction liquid, calculating the product yield to be 86% by using an HPLC method, and obtaining p-chlorobenzaldehyde product after column chromatography separation.
FIG. 2 is a graph of the p-chlorobenzaldehyde product 1 From the H-NMR spectrum, it was found that (400 MHz, deuterated chloroform) δ9.91 (s, 1H), 7.78-7.71 (m, 2H), 7.46-7.41 (m, 2H), and proved that the p-chlorobenzaldehyde product contained five hydrogens in total, wherein one single peak of chemical shift 9.91 was aldehyde hydrogen, and the remaining four hydrogens represented two groups of two hydrogens each, and four aromatic hydrogens after para-substitution on the benzene ringCorrespondingly, the structure is matched with that of p-chlorobenzaldehyde.
FIG. 3 is a graph of the p-chlorobenzaldehyde product 13 C-NMR spectra, from the figures, (101 MHz, deuterated chloroform) delta 189.85,139.93,133.70,129.89,128.44, demonstrates that the p-chlorobenzaldehyde product has five carbons in total, where delta 189.85 is carbonyl carbon, matching the nuclear magnetic carbon spectrum of p-chlorobenzaldehyde. HRMS (TOF) M/z [ M+H]+Calcd for C 7 H 6 ClO + 141.0107found 141.0152 the molecular weight of this material was found to be that of p-chlorobenzaldehyde.
Example 2
3mmol of p-chlorobenzyl alcohol was dissolved in 10mL of dioxane to give a homogeneous solution A; 50wt% hydrogen peroxide (containing 6mmol (0.204 g) of hydrogen peroxide), 5wt% sodium bromide solution (containing 0.015g of sodium bromide) and 1wt% sulfuric acid solution (containing 0.01g of sulfuric acid) were dissolved in 10mL of dioxane to obtain a homogeneous solution B. The homogeneous solution A and the homogeneous solution B are respectively metered by a first injection pump and a second injection pump, then enter a micromixer (with the hydraulic radius of 20 microns), are rapidly mixed at normal temperature and normal pressure, then enter a microchannel reactor for reaction, and analyze the reaction liquid. Wherein: the flow rates of the first injection pump and the second injection pump are 0.2mL/min, the reaction volume V=5 mL of the microchannel reactor, the inner diameter is 0.5mm, and the reactor temperature is 70 ℃. After the reaction of the microchannel reactor has passed through two cycles, collecting reaction liquid, calculating the yield of the product by using an HPLC method to obtain the p-chlorobenzaldehyde product after column chromatography separation.
Example 3
3mmol of p-chlorobenzyl alcohol was dissolved in 10mL of dioxane to give a homogeneous solution A; 50wt% hydrogen peroxide (containing 9mmol (0.306 g) of hydrogen peroxide), 5wt% sodium bromide solution (containing 0.015g of sodium bromide) and 1wt% sulfuric acid solution (containing 0.01g of sulfuric acid) were dissolved in 10mL of dioxane to obtain a homogeneous solution B. The homogeneous solution A and the homogeneous solution B are respectively metered by a first injection pump and a second injection pump, then enter a micromixer (with the hydraulic radius of 20 microns), are rapidly mixed at normal temperature and normal pressure, then enter a microchannel reactor for reaction, and analyze the reaction liquid. Wherein: the flow rates of the first injection pump and the second injection pump are 0.2mL/min, the reaction volume V=5 mL of the microchannel reactor, the inner diameter is 0.5mm, and the reactor temperature is 70 ℃. After two cycles of the reaction in the microchannel reactor, collecting the reaction liquid, calculating the yield of the product to be 85% by an HPLC method, and separating by column chromatography to obtain the p-chlorobenzaldehyde product.
Example 4
3mmol of p-chlorobenzyl alcohol was dissolved in 10mL of dioxane to give a homogeneous solution A; 50wt% hydrogen peroxide (containing 7.5mmol (0.255 g) of hydrogen peroxide), 10wt% sodium bromide solution (containing 0.03g of sodium bromide) and 1wt% sulfuric acid solution (containing 0.01g of sulfuric acid) were dissolved in 10mL of dioxane to obtain a homogeneous solution B. The homogeneous solution A and the homogeneous solution B are respectively metered by a first injection pump and a second injection pump, then enter a micromixer (with the hydraulic radius of 20 microns), are rapidly mixed at normal temperature and normal pressure, then enter a microchannel reactor for reaction, and analyze the reaction liquid. Wherein: the flow rates of the first injection pump and the second injection pump are 0.2mL/min, the reaction volume V=5 mL of the microchannel reactor, the inner diameter is 0.5mm, and the reactor temperature is 70 ℃. After the reaction of the microchannel reactor has passed through two cycles, collecting reaction liquid, calculating the yield of the product by using an HPLC method to obtain the p-chlorobenzaldehyde product after column chromatography separation.
Example 5
3mmol of p-chlorobenzyl alcohol was dissolved in 10mL of dioxane to give a homogeneous solution A; 50wt% hydrogen peroxide (containing 7.5mmol (0.255 g) of hydrogen peroxide), 5wt% sodium bromide solution (containing 0.015g of sodium bromide) and 5wt% sulfuric acid solution (containing 0.05g of sulfuric acid) were dissolved in 10mL of dioxane to obtain a homogeneous solution B. The homogeneous solution A and the homogeneous solution B are respectively metered by a first injection pump and a second injection pump, then enter a micromixer (with the hydraulic radius of 20 microns), are rapidly mixed at normal temperature and normal pressure, then enter a microchannel reactor for reaction, and analyze the reaction liquid. Wherein: the flow rates of the first injection pump and the second injection pump are 0.2mL/min, the reaction volume V=5 mL of the microchannel reactor, the inner diameter is 0.5mm, and the reactor temperature is 70 ℃. After two cycles of the reaction in the microchannel reactor, collecting the reaction liquid, calculating the product yield to be 80% by an HPLC method, and separating by column chromatography to obtain the p-chlorobenzaldehyde product.
Example 6
3mmol of p-chlorobenzyl alcohol was dissolved in 10mL of acetonitrile to give a homogeneous solution A; 50wt% hydrogen peroxide (containing 7.5mmol (0.255 g) of hydrogen peroxide), 5wt% sodium bromide solution (containing 0.015g of sodium bromide) and 1wt% sulfuric acid solution (containing 0.01g of sulfuric acid) were dissolved in 10mL of acetonitrile to obtain a homogeneous solution B. The homogeneous solution A and the homogeneous solution B are respectively metered by a first injection pump and a second injection pump, then enter a micromixer (with the hydraulic radius of 20 microns), quickly mixed and then enter a microchannel reactor for reaction, and the reaction liquid is analyzed. Wherein: the flow rates of the first injection pump and the second injection pump are 0.2mL/min, the reaction volume V=5 mL of the microchannel reactor, the inner diameter is 0.5mm, and the reactor temperature is 70 ℃. After two cycles of the reaction in the microchannel reactor, collecting the reaction liquid, calculating the yield of the product by an HPLC method to be 46%, and separating by column chromatography to obtain the p-chlorobenzaldehyde product.
Example 7
3mmol of p-chlorobenzyl alcohol was dissolved in 10mL of dimethyl sulfoxide (DMSO) to give a homogeneous solution A; 50wt% hydrogen peroxide (containing 7.5mmol (0.255 g) of hydrogen peroxide), 5wt% sodium bromide solution (containing 0.015g of sodium bromide) and 1wt% sulfuric acid solution (containing 0.01g of sulfuric acid) were dissolved in 10mL of dimethyl sulfoxide to obtain a homogeneous solution B. The homogeneous solution A and the homogeneous solution B are respectively metered by a first injection pump and a second injection pump, then enter a micromixer (with the hydraulic radius of 20 microns), are rapidly mixed at normal temperature and normal pressure, then enter a microchannel reactor for reaction, and analyze the reaction liquid. Wherein: the flow rates of the first injection pump and the second injection pump are 0.2mL/min, the reaction volume V=5 mL of the microchannel reactor, the inner diameter is 0.5mm, and the reactor temperature is 70 ℃. After two cycles of the reaction in the microchannel reactor, collecting the reaction liquid, calculating the product yield to be 76% by an HPLC method, and separating by column chromatography to obtain the p-chlorobenzaldehyde product.
Example 8
3mmol of p-chlorobenzyl alcohol was dissolved in 10mL of N, N-Dimethylformamide (DMF) to give a homogeneous solution A; 50wt% hydrogen peroxide (containing 7.5mmol (0.255 g) of hydrogen peroxide), 5wt% sodium bromide solution (containing 0.015g of sodium bromide) and 1wt% sulfuric acid solution (containing 0.01g of sulfuric acid) were dissolved in 10mL of DMF to obtain a homogeneous solution B. The homogeneous solution A and the homogeneous solution B are respectively metered by a first injection pump and a second injection pump, then enter a micromixer (with the hydraulic radius of 20 microns), are rapidly mixed at normal temperature and normal pressure, then enter a microchannel reactor for reaction, and analyze the reaction liquid. Wherein: the flow rates of the first injection pump and the second injection pump are 0.2mL/min, the reaction volume V=5 mL of the microchannel reactor, the inner diameter is 0.5mm, and the reactor temperature is 70 ℃. After two cycles of the reaction in the microchannel reactor, collecting the reaction liquid, calculating the product yield to be 62% by an HPLC method, and separating by column chromatography to obtain the p-chlorobenzaldehyde product.
Example 9
3mmol of p-chlorobenzyl alcohol was dissolved in 10mL of dioxane to give a homogeneous solution A; 50wt% hydrogen peroxide (containing 7.5mmol (0.255 g) of hydrogen peroxide), 5wt% sodium bromide solution (containing 0.015g of sodium bromide) and 1wt% sulfuric acid solution (containing 0.01g of sulfuric acid) were dissolved in 10mL of dioxane to obtain a homogeneous solution B. The homogeneous solution A and the homogeneous solution B are respectively metered by a first injection pump and a second injection pump, then enter a micromixer (with the hydraulic radius of 20 microns), are rapidly mixed at normal temperature and normal pressure, then enter a microchannel reactor for reaction, and analyze the reaction liquid. Wherein: the flow rates of the first injection pump and the second injection pump are 0.1mL/min, the reaction volume V=5 mL of the microchannel reactor, the inner diameter is 0.5mm, and the reactor temperature is 70 ℃. After two cycles of the reaction in the microchannel reactor, collecting the reaction liquid, calculating the product yield to be 76% by an HPLC method, and separating by column chromatography to obtain the p-chlorobenzaldehyde product.
Example 10
3mmol of p-chlorobenzyl alcohol was dissolved in 10mL of dioxane to give a homogeneous solution A; 50wt% hydrogen peroxide (containing 7.5mmol (0.255 g) of hydrogen peroxide), 5wt% sodium bromide solution (containing 0.015g of sodium bromide) and 1wt% sulfuric acid solution (containing 0.01g of sulfuric acid) were dissolved in 10mL of dioxane to obtain a homogeneous solution B. The homogeneous solution A and the homogeneous solution B are respectively metered by a first injection pump and a second injection pump, then enter a micromixer (with the hydraulic radius of 20 microns), are rapidly mixed at normal temperature and normal pressure, then enter a microchannel reactor for reaction, and analyze the reaction liquid. Wherein: the flow rates of the first injection pump and the second injection pump are 0.3mL/min, the reaction volume V=5 mL of the microchannel reactor, the inner diameter is 0.5mm, and the reactor temperature is 70 ℃. After the reaction of the microchannel reactor has passed through two cycles, collecting reaction liquid, calculating the yield of the product by using an HPLC method to obtain the p-chlorobenzaldehyde product after separation by column chromatography.
Example 11
3mmol of p-chlorobenzyl alcohol was dissolved in 10mL of dioxane to give a homogeneous solution A; 50wt% hydrogen peroxide (containing 7.5mmol (0.255 g) of hydrogen peroxide), 5wt% sodium bromide solution (containing 0.015g of sodium bromide) and 1wt% sulfuric acid solution (containing 0.01g of sulfuric acid) were dissolved in 10mL of dioxane to obtain a homogeneous solution B. The homogeneous solution A and the homogeneous solution B are respectively metered by a first injection pump and a second injection pump, then enter a micromixer (with the hydraulic radius of 20 microns), are rapidly mixed at normal temperature and normal pressure, then enter a microchannel reactor for reaction, and analyze the reaction liquid. Wherein: the flow rates of the first injection pump and the second injection pump are 0.2mL/min, the reaction volume V=5 mL of the microchannel reactor, the inner diameter is 0.5mm, and the reactor temperature is 50 ℃. After the reaction of the microchannel reactor has passed through two cycles, collecting reaction liquid, calculating the yield of the product by using an HPLC method to obtain the p-chlorobenzaldehyde product after column chromatography separation.
Example 12
3mmol of p-chlorobenzyl alcohol was dissolved in 10mL of dioxane to give a homogeneous solution A; 50wt% hydrogen peroxide (containing 7.5mmol (0.255 g) of hydrogen peroxide), 5wt% sodium bromide solution (containing 0.015g of sodium bromide) and 1wt% sulfuric acid solution (containing 0.01g of sulfuric acid) were dissolved in 10mL of dioxane to obtain a homogeneous solution B. The homogeneous solution A and the homogeneous solution B are respectively metered by a first injection pump and a second injection pump, then enter a micromixer (with the hydraulic radius of 20 microns), are rapidly mixed at normal temperature and normal pressure, then enter a microchannel reactor for reaction, and analyze the reaction liquid. Wherein: the flow rates of the first injection pump and the second injection pump are 0.2mL/min, the reaction volume V=5 mL of the microchannel reactor, the inner diameter is 0.5mm, and the reactor temperature is 90 ℃. After two cycles of the reaction in the microchannel reactor, collecting the reaction liquid, calculating the yield of the product by using an HPLC method to be 79%, and separating by column chromatography to obtain the p-chlorobenzaldehyde product.
Example 13
3mmol of p-chlorobenzyl alcohol was dissolved in 10mL of dioxane to give a homogeneous solution A; 30wt% hydrogen peroxide (containing 7.5mmol (0.255 g) of hydrogen peroxide), 5wt% sodium bromide solution (containing 0.015g of sodium bromide) and 1wt% sulfuric acid solution (containing 0.01g of sulfuric acid) were dissolved in 10mL of dioxane to obtain a homogeneous solution B. The homogeneous solution A and the homogeneous solution B are respectively metered by a first injection pump and a second injection pump, then enter a micromixer (with the hydraulic radius of 20 microns), are rapidly mixed at normal temperature and normal pressure, then enter a microchannel reactor for reaction, and analyze the reaction liquid. Wherein: the flow rates of the first injection pump and the second injection pump are 0.2mL/min, the reaction volume V=5 mL of the microchannel reactor, the inner diameter is 0.5mm, and the reactor temperature is 70 ℃. After two cycles of the reaction in the microchannel reactor, collecting the reaction liquid, calculating the product yield to be 75% by an HPLC method, and separating by column chromatography to obtain the p-chlorobenzaldehyde product.
Example 14
3mmol of p-chlorobenzyl alcohol was dissolved in 10mL of dioxane to give a homogeneous solution A; 100wt% hydrogen peroxide (containing 7.5mmol (0.255 g) of hydrogen peroxide), 5wt% sodium bromide solution (containing 0.015g of sodium bromide) and 1wt% sulfuric acid solution (containing 0.01g of sulfuric acid) were dissolved in 10mL of dioxane to obtain a homogeneous solution B. The homogeneous solution A and the homogeneous solution B are respectively metered by a first injection pump and a second injection pump, then enter a micromixer (with the hydraulic radius of 20 microns), are rapidly mixed at normal temperature and normal pressure, then enter a microchannel reactor for reaction, and analyze the reaction liquid. Wherein: the flow rates of the first injection pump and the second injection pump are 0.2mL/min, the reaction volume V=5 mL of the microchannel reactor, the inner diameter is 0.5mm, and the reactor temperature is 70 ℃. After two cycles of the reaction in the microchannel reactor, collecting the reaction liquid, calculating the product yield to be 82% by an HPLC method, and separating by column chromatography to obtain the p-chlorobenzaldehyde product.
Example 15
3mmol of p-chlorobenzyl alcohol was dissolved in 10mL of dioxane to give a homogeneous solution A; 50wt% hydrogen peroxide (containing 7.5mmol (0.255 g) of hydrogen peroxide), 5wt% sodium bromide solution (containing 0.015g of sodium bromide) and 1wt% sulfuric acid solution (containing 0.01g of sulfuric acid) were dissolved in 10mL of dioxane to obtain a homogeneous solution B. The homogeneous solution A and the homogeneous solution B are respectively metered by a first injection pump and a second injection pump, then enter a micromixer (with the hydraulic radius of 20 microns), are rapidly mixed at normal temperature and normal pressure, then enter a microchannel reactor for reaction, and analyze the reaction liquid. Wherein: the flow rates of the first injection pump and the second injection pump are 0.2mL/min, the reaction volume V=5 mL of the microchannel reactor, the inner diameter is 1mm, and the reactor temperature is 70 ℃. After two cycles of the reaction in the microchannel reactor, collecting the reaction liquid, calculating the product yield to be 76% by an HPLC method, and separating by column chromatography to obtain the p-chlorobenzaldehyde product.
Example 16
3mmol of p-chlorobenzyl alcohol was dissolved in 10mL of dioxane to give a homogeneous solution A; 50wt% hydrogen peroxide (containing 7.5mmol (0.255 g) of hydrogen peroxide), 5wt% sodium bromide solution (containing 0.015g of sodium bromide) and 1wt% sulfuric acid solution (containing 0.01g of sulfuric acid) were dissolved in 10mL of dioxane to obtain a homogeneous solution B. The homogeneous solution A and the homogeneous solution B are respectively metered by a first injection pump and a second injection pump, then enter a micromixer (with the hydraulic radius of 20 microns), are rapidly mixed at normal temperature and normal pressure, then enter a microchannel reactor for reaction, and analyze the reaction liquid. Wherein: the flow rates of the first injection pump and the second injection pump are 0.2mL/min, the reaction volume V=10mL of the microchannel reactor, the inner diameter is 0.5mm, and the reactor temperature is 70 ℃. After two cycles of the reaction in the microchannel reactor, collecting the reaction liquid, calculating the product yield to be 80% by an HPLC method, and separating by column chromatography to obtain the p-chlorobenzaldehyde product.
The results show that the method for continuously preparing the p-chlorobenzaldehyde has the advantages of high reaction efficiency, short reaction time, low reaction temperature and high product yield.
As is clear from comparison of the results of examples 1 to 3, the molar mass ratio of the oxidizing agent to p-chlorobenzyl alcohol was higher in the yield of p-chlorobenzaldehyde product obtained in the preferred range.
Comparing the results of example 1 and example 4, it is seen that the molar mass ratio of the catalyst promoter to p-chlorobenzyl alcohol is higher in the yield of p-chlorobenzaldehyde product obtained in the preferred range.
As is clear from comparing the results of example 1 and example 5, the molar mass ratio of the catalyst to p-chlorobenzyl alcohol was higher in the yield of p-chlorobenzaldehyde product obtained in the preferred range.
As is apparent from a comparison of the results of example 1 and examples 6 to 8, the yields of p-chlorobenzaldehyde products were higher with the first and second solvents in the preferred ranges.
Comparing the results of example 1 and examples 9-10, it is seen that the yields of p-chlorobenzaldehyde products are higher when the flow rates of homogeneous solution A and homogeneous solution B are within the preferred ranges.
As is clear from comparing the results of example 1 and examples 11 to 12, the reaction conditions and the temperature are within the preferable range, and the yield of p-chlorobenzaldehyde product is higher.
As is clear from the comparison between the results of example 1 and examples 13 to 14, when the oxidizing agent is hydrogen peroxide, the yield of p-chlorobenzaldehyde product obtained in the preferred range is higher.
Comparing the results of example 1 and examples 15-16, it is seen that the reaction volume and/or the inner diameter of the microreactor (microchannel reactor) is higher in the yield of p-chlorobenzaldehyde product obtained within the preferred range.
The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited thereto. Within the scope of the technical idea of the invention, a number of simple variants of the technical solution of the invention are possible, including combinations of the individual technical features in any other suitable way, which simple variants and combinations should likewise be regarded as being disclosed by the invention, all falling within the scope of protection of the invention.
Claims (10)
1. A process for the continuous preparation of p-chlorobenzaldehyde, comprising:
(1) Dissolving p-chlorobenzyl alcohol in a first solvent to obtain a homogeneous solution A; dissolving an oxidant, a catalytic auxiliary agent and a catalyst in a second solvent to obtain a homogeneous solution B;
(2) Pumping the homogeneous solution A and the homogeneous solution B obtained in the step (1) into a micro-channel reaction device respectively for reaction.
2. A process according to claim 1, wherein in step (1) the concentration of p-chlorobenzyl alcohol in the homogeneous solution a is 0.05-0.5mmol/mL, preferably 0.2-0.4mmol/mL;
and/or the concentration of the oxidizing agent in the homogeneous solution B is 0.2-2mmol/mL, preferably 0.5-1mmol/mL.
3. The method of claim 1, wherein the molar mass ratio of the oxidizing agent to p-chlorobenzyl alcohol is (1-5): 1, preferably (2-3): 1, more preferably (2.5-3): 1, a step of; and/or
The oxidant is at least one selected from hydrogen peroxide, peracetic acid, peroxypropionic acid, potassium permanganate and potassium dichromate, preferably hydrogen peroxide; more preferably, the oxidizing agent is provided in the form of hydrogen peroxide; further preferably, the mass fraction of the hydrogen peroxide is 30% -100%, and preferably 50% -100%.
4. A process according to any one of claims 1 to 3, wherein in step (1) the catalytic promoter comprises 1% to 10%, preferably 2% to 8%, more preferably 3% to 4% by mass of p-chlorobenzyl alcohol; and/or
The catalyst auxiliary agent is at least one selected from sodium bromide, potassium bromide and magnesium bromide, preferably sodium bromide; more preferably, the sodium bromide is provided in the form of an aqueous solution; further preferably, the mass fraction of sodium bromide in the aqueous solution is 1% -10%, preferably 5% -10%.
5. A process according to any one of claims 1 to 3, wherein in step (1) the catalyst comprises 1% to 20%, preferably 1.5% to 15%, more preferably 2% to 6% by mass of p-chlorobenzyl alcohol; and/or
The catalyst is selected from at least one of sulfuric acid, hydrochloric acid and phosphoric acid, preferably sulfuric acid; more preferably, the sulfuric acid is provided in the form of an aqueous solution; further preferably, the mass fraction of the sulfuric acid in the aqueous solution is 1% -10%, preferably 1% -5%.
6. A process according to any one of claims 1 to 3, wherein in step (1), the first and second solvents are the same or different and are each independently selected from at least one of acetonitrile, dimethyl sulfoxide, dioxane and N, N-dimethylformamide, preferably at least one of dimethyl sulfoxide, dioxane and N, N-dimethylformamide, more preferably dimethyl sulfoxide and/or dioxane, further preferably dioxane; still more preferably, the first solvent and the second solvent are the same.
7. A method according to any one of claims 1 to 3, wherein in step (2), the microchannel reaction device comprises a micromixer and a microreactor;
preferably, the reaction volume of the microreactor is 3-10mL, preferably 5-8mL; and/or the microreactor has an inner diameter of 0.3 to 1mm, preferably 0.5 to 0.8mm.
8. The method according to claim 7, wherein in the step (2), the homogeneous solution A and the homogeneous solution B obtained in the step (1) are pumped into the micromixer simultaneously to be mixed, and then the obtained mixture is sent into the microreactor to be reacted;
preferably, the mixing is performed at normal temperature and pressure; the mixing time is 1-20ms;
preferably, the micromixer has a hydraulic radius of 5-50 microns.
9. A process according to any one of claims 1 to 3, wherein in step (2) the flow rates of homogeneous solution a and homogeneous solution B are the same or different, each independently being 0.1-0.5mL/min, preferably 0.2-0.4mL/min; preferably, the flow rates of the homogeneous solution A and the homogeneous solution B are the same.
10. A method according to any one of claims 1 to 3, wherein in step (2), the reaction conditions include: the reaction temperature is 50-90 ℃, preferably 60-80 ℃; the reaction residence time is 5 to 30min, preferably 10 to 25min.
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