CN114456038A - Synthesis method of para-substituted chlorobenzyl compound - Google Patents
Synthesis method of para-substituted chlorobenzyl compound Download PDFInfo
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- CN114456038A CN114456038A CN202110215315.8A CN202110215315A CN114456038A CN 114456038 A CN114456038 A CN 114456038A CN 202110215315 A CN202110215315 A CN 202110215315A CN 114456038 A CN114456038 A CN 114456038A
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- chloride
- chloromethylation
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- -1 chlorobenzyl compound Chemical class 0.000 title claims abstract description 20
- 238000001308 synthesis method Methods 0.000 title abstract description 5
- 239000003054 catalyst Substances 0.000 claims abstract description 54
- 238000007265 chloromethylation reaction Methods 0.000 claims abstract description 33
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 20
- 238000000034 method Methods 0.000 claims abstract description 19
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims abstract description 16
- 239000002841 Lewis acid Chemical class 0.000 claims abstract description 10
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims abstract description 10
- 150000007517 lewis acids Chemical class 0.000 claims abstract description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 8
- 150000001335 aliphatic alkanes Chemical class 0.000 claims abstract description 7
- 125000004803 chlorobenzyl group Chemical class 0.000 claims abstract description 7
- 229920001744 Polyaldehyde Polymers 0.000 claims abstract description 4
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims abstract 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 26
- 238000006243 chemical reaction Methods 0.000 claims description 23
- 239000000243 solution Substances 0.000 claims description 16
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 15
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 8
- 239000000463 material Substances 0.000 claims description 8
- 235000005074 zinc chloride Nutrition 0.000 claims description 8
- 239000011592 zinc chloride Substances 0.000 claims description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 230000002194 synthesizing effect Effects 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 3
- FAPDDOBMIUGHIN-UHFFFAOYSA-K antimony trichloride Chemical compound Cl[Sb](Cl)Cl FAPDDOBMIUGHIN-UHFFFAOYSA-K 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- 239000003929 acidic solution Substances 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims description 2
- GVPFVAHMJGGAJG-UHFFFAOYSA-L cobalt dichloride Chemical compound [Cl-].[Cl-].[Co+2] GVPFVAHMJGGAJG-UHFFFAOYSA-L 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 2
- 239000012074 organic phase Substances 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 abstract description 4
- 150000004396 para substituted benzyl chlorides Chemical class 0.000 abstract description 4
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 abstract description 3
- 150000005524 benzylchlorides Chemical class 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 abstract description 2
- 229940073608 benzyl chloride Drugs 0.000 abstract 1
- 239000000047 product Substances 0.000 description 24
- YTZKOQUCBOVLHL-UHFFFAOYSA-N tert-butylbenzene Chemical compound CC(C)(C)C1=CC=CC=C1 YTZKOQUCBOVLHL-UHFFFAOYSA-N 0.000 description 16
- 238000003756 stirring Methods 0.000 description 13
- 239000007789 gas Substances 0.000 description 10
- 239000010410 layer Substances 0.000 description 10
- 238000005406 washing Methods 0.000 description 10
- 239000002608 ionic liquid Substances 0.000 description 9
- 238000010606 normalization Methods 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 238000001816 cooling Methods 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- 229930040373 Paraformaldehyde Natural products 0.000 description 5
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 5
- 239000012535 impurity Substances 0.000 description 5
- 229920002866 paraformaldehyde Polymers 0.000 description 5
- QZWCABOLGIVZCP-UHFFFAOYSA-N 1-tert-butyl-3-(chloromethyl)benzene Chemical compound CC(C)(C)C1=CC=CC(CCl)=C1 QZWCABOLGIVZCP-UHFFFAOYSA-N 0.000 description 4
- WAXIFMGAKWIFDQ-UHFFFAOYSA-N 1-tert-butyl-4-(chloromethyl)benzene Chemical compound CC(C)(C)C1=CC=C(CCl)C=C1 WAXIFMGAKWIFDQ-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- UQFQONCQIQEYPJ-UHFFFAOYSA-N N-methylpyrazole Chemical compound CN1C=CC=N1 UQFQONCQIQEYPJ-UHFFFAOYSA-N 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 150000004996 alkyl benzenes Chemical class 0.000 description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- 239000002351 wastewater Substances 0.000 description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- BGJSXRVXTHVRSN-UHFFFAOYSA-N 1,3,5-trioxane Chemical group C1OCOCO1 BGJSXRVXTHVRSN-UHFFFAOYSA-N 0.000 description 1
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical class CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical class CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000003934 aromatic aldehydes Chemical class 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000012822 chemical development Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 125000006575 electron-withdrawing group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- JEGUKCSWCFPDGT-UHFFFAOYSA-N h2o hydrate Chemical compound O.O JEGUKCSWCFPDGT-UHFFFAOYSA-N 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical class CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 description 1
- 239000011968 lewis acid catalyst Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical class CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- FWFGVMYFCODZRD-UHFFFAOYSA-N oxidanium;hydrogen sulfate Chemical compound O.OS(O)(=O)=O FWFGVMYFCODZRD-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- HBBBDGWCSBWWKP-UHFFFAOYSA-J tetrachloroantimony Chemical compound Cl[Sb](Cl)(Cl)Cl HBBBDGWCSBWWKP-UHFFFAOYSA-J 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/26—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton
- C07C17/263—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions
-
- 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
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0277—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides comprising ionic liquids, as components in catalyst systems or catalysts per se, the ionic liquid compounds being used in the molten state at the respective reaction temperature
- B01J31/0278—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides comprising ionic liquids, as components in catalyst systems or catalysts per se, the ionic liquid compounds being used in the molten state at the respective reaction temperature containing nitrogen as cationic centre
- B01J31/0281—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides comprising ionic liquids, as components in catalyst systems or catalysts per se, the ionic liquid compounds being used in the molten state at the respective reaction temperature containing nitrogen as cationic centre the nitrogen being a ring member
- B01J31/0284—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides comprising ionic liquids, as components in catalyst systems or catalysts per se, the ionic liquid compounds being used in the molten state at the respective reaction temperature containing nitrogen as cationic centre the nitrogen being a ring member of an aromatic ring, e.g. pyridinium
-
- 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
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
- B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
- B01J2231/4205—C-C cross-coupling, e.g. metal catalyzed or Friedel-Crafts type
-
- 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
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
- B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
- B01J2231/4277—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a synthesis method of para-substituted chlorobenzyl compounds, belonging to the field of organic synthesis. The para-position electron-donating substituted benzene ring compound is adopted to generate chloromethylation reaction with aldehyde or polyaldehyde and other aldehydes with different forms and hydrogen chloride in the presence of a novel mixed catalyst to obtain the corresponding para-position substituted benzyl chloride compound. The novel mixed catalyst is composed of quaternary ammonium salt formed by N-substituted imidazole/pyrazole/piperazine and other double-nitrogen heterocyclic compounds and halogenated alkane, and Lewis acid. The para-substituted benzyl chloride compound is obtained by the method, and the isomers of the compound are in a controllable proportion range.
Description
Technical Field
The invention relates to a novel mixed chloromethylation catalyst and application of the catalyst in synthesis of para-substituted chlorobenzyl compounds, and belongs to the technical field of organic synthesis.
Technical Field
The chloromethylation process is an economic method for constructing carbon chains, and is widely applied to the production of benzyl alcohol, benzonitrile, aromatic aldehydes or acid compounds.
At present, two methods for synthesizing chlorobenzyl compounds after chloromethylation mainly comprise:
firstly, the method adopts sulfuric acid as a catalyst and a dehydrating agent, has the advantages of simplicity, but has obvious defects, particularly large amount of waste acid and great difficulty in treatment.
Secondly, aluminum trichloride or zinc chloride is adopted as a Lewis acid catalyst, the method generally reacts under the condition of an anhydrous method, the byproducts of the product are more, and a plurality of waste water containing high-concentration salt or heavy metal, such as aluminum chloride/zinc chloride, and the like, can be generated in the post-treatment process.
Aiming at the current trend of green chemical development, the two traditional methods have large treatment difficulty due to large amount of waste water, and can not realize continuous and stable production, so that a new synthetic method needs to be developed.
Disclosure of Invention
In order to solve the problems, the invention discloses a mixed chloromethylation catalyst. The novel mixed catalyst is composed of quaternary ammonium salt formed by N-substituted imidazole, pyrazole or piperazine and other double-nitrogen heterocyclic compounds and halogenated alkane, and Lewis acid. The electron-substituted benzene ring compound reacts with methylene chloride generated by aldehydes or polyaldehydes and hydrogen chloride in different forms in the presence of the mixed chloromethylation catalyst to obtain the corresponding para-substituted chlorobenzyl compound. The para-substituted benzyl chloride compound is obtained by the method, and the isomers of the compound are in a controllable proportion range.
The mixed chloromethylation catalyst comprises quaternary ammonium salt and Lewis acid.
Further, in the above technical solution, water or an acidic solution is also included.
Furthermore, in the above technical scheme, in the mixed chloromethylation catalyst, the weight ratio of the quaternary ammonium salt, the Lewis acid and the water or the acid solution is 10-80%, 10-80% and 10-80%.
Further, in the above technical solution, the acidic aqueous solution is selected from an aqueous hydrochloric acid solution, an aqueous sulfuric acid solution, or an aqueous phosphoric acid solution. Aqueous hydrochloric acid is preferred.
Further, in the above technical scheme, the quaternary ammonium salt has the following general formula:
wherein R is2、R3、R4、R5、R6Each independently is H, C1-C20 alkyl or C1-C20 alkoxy C1-C20 alkyl; x is F, Cl, Br or I; the quaternary ammonium salt is generated by the reaction of a double-nitrogen heterocyclic compound and halogenated alkane or halogenated aromatic hydrocarbon, wherein the double-nitrogen heterocyclic compound is selected from N-substituted imidazole, N-substituted pyrazole or N-substituted piperazine;
the halogenated alkane is selected from halogenated C1-C20 alkane, and the halogen is fluorine, chlorine, bromine or iodine; fluorine, chlorine or bromine are preferred. The halogenated aromatic hydrocarbon is selected from chlorinated aromatic hydrocarbon, brominated aromatic hydrocarbon or fluorinated aromatic hydrocarbon. Among them, halogenated propane, halogenated butane, halogenated isobutane or halogenated pentane is preferable.
The bis-nitrogen heterocyclic compounds forming the quaternary ammonium salts are as follows:
further, in a preferred embodiment, methyl or ethyl substituted imidazole or pyrazole is preferable (R)2＝Me,Et)。
Further, in the above technical solution, the lewis acid is selected from tin chloride, antimony chloride, zinc chloride, magnesium chloride, aluminum chloride or cobalt chloride. Tin chloride, antimony chloride, aluminum chloride, zinc chloride are preferred.
The invention discloses a synthesis method of a para-substituted benzyl chloride compound, which comprises the following steps: reacting electron-substituted benzene ring compounds with methylene chloride in the presence of a mixed chloromethylation catalyst as claimed in claim 1 to obtain corresponding para-substituted chlorobenzyl compounds.
A typical operation is as follows:
adding the mixed chloromethylation catalyst into a reaction kettle, sequentially adding benzene containing substituent groups, and then adding formaldehyde or paraformaldehyde (including dimeric and trioxymethylene). Then the temperature is raised to 50-90 ℃ by stirring. Dripping hydrochloric acid into the reaction system or introducing hydrogen chloride gas into the system, preferably introducing hydrogen chloride gas. As the reaction proceeded, the gas chromatography monitored the alkylbenzene content and stopped the reaction when a certain value was reached. And then cooling, standing for layering, separating out a lower layer mixed chloromethylation catalyst, and carrying out alkali washing, water washing and desolventizing on an upper layer of the product to obtain the para-substituted benzyl chloride compound. The separated mixed chloromethylation catalyst is directly used for the synthesis of the para-substituted chlorobenzyl compound of the next batch.
The reaction equations of the para-substituted chlorobenzyl and alkyl substituted benzene related by the invention are as follows:
wherein R is selected from H, C1-C6 alkyl and C1-C6 alkoxy.
Further, in the above technical scheme, the methylene chloride is generated by reacting aldehyde or polyaldehyde with hydrogen chloride.
Further, in the above technical scheme, after the reaction is completed, the mixed chloromethylation catalyst and the organic phase material are subjected to layering separation after standing, and the catalyst is continuously applied for more than 100 times.
In practice, the mixed chloromethylation catalyst will add about 3-5% water to the system for each use. When the weight of the water in the system is increased to more than 50% of the weight of the water in the first use, the water in the system can be removed by reduced pressure distillation, and the water can be reused after the weight of the water is recovered to the weight of the water in the first use.
The use frequency of the mixed catalyst is determined by the chloromethylation effect, and when the chloromethylation effect is poor, the reaction speed is slow, or the impurity generation speed is high, the catalyst can be regarded as invalid and is not used any more, and the treatment is carried out according to danger. Specific number of uses data collected in accordance with the present invention indicate that 200 cycles of use is a reasonable number.
Further, in the above technical scheme, when the water content ratio in the chloromethylation catalyst is high, the catalyst is distilled to remove water and then is continuously used.
The mixed chloromethylation catalyst prepared by the method is used for synthesizing para-substituted chlorobenzyl compounds, the ortho-position isomers and the meta-position isomers are less, the ortho-position isomers and the meta-position isomers are generally controlled to be 4.0-5.0%, and the main product is a para-position product.
The key point of the invention is the synthesis of the mixed chloromethylation catalyst, which comprises the following steps:
the type of quaternary ammonium salt and the synthesis method thereof are one of the technical keys of the invention. The molar ratio of the multi-nitrogen heterocyclic compound to the halogenated alkane is 1.0-5.0: 1, preferably 1.1: 1. the reaction temperature is 50-120 deg.C, preferably 70-90 deg.C.
After the quaternary ammonium salt is synthesized, the quaternary ammonium salt can be solidified at the temperature lower than 50 ℃, and water or hydrochloric acid water solution, sulfuric acid water solution or phosphoric acid water solution which is 1.0 to 20 times of the weight of the quaternary ammonium salt is added into the system. Wherein the concentration of the hydrochloric acid is 1-32%, and the concentration of the sulfuric acid aqueous solution is 1-50%.
The Lewis acid as the component of the mixed chloromethylation catalyst is any one of aluminum trichloride, tin chloride, antimony tetrachloride, zinc chloride and the like. The Lewis acid is added in an amount of 0.5 to 3.0 times, preferably 1.0 to 2.0 times, the weight of the quaternary ammonium salt.
Advantageous effects of the invention
1. The para-chloromethylation with the main chloromethylation product as a substituent has less ortho-meta isomer by using the method. In the reaction process, the isomer ratio is stable and controllable.
2. The mixed catalyst can be recovered and used for hundreds of times. When the catalyst is deactivated, the water in the system is distilled out and the catalyst can be reused.
3. No other waste is generated in the production process, the environment is friendly, and the production cost is low.
DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION
Example 1:
500g of 1-methylpyrazole and 540g of n-butyl chloride were charged into a 5L reactor, and the reactor was heated with stirring. The reaction was refluxed at 90 ℃ for 24 hours, and the starting material was cooled to 50 ℃ by GC or HPLC to monitor completion of the reaction. 1500g of water are added and stirred evenly. Adding 2000g of zinc chloride, and uniformly stirring to obtain the mixed ionic liquid catalyst.
The mixed ionic liquid catalyst obtained above was transferred to a 10L reactor, and 1500g of tert-butyl benzene and 297g of paraformaldehyde were added. Starting stirring and heating to 60-80 ℃. Hydrogen chloride gas was initially introduced into the kettle. And gas escapes from the reflux evacuation port and needs to be connected into the absorption tower. The product content was monitored by GC and the reaction was stopped when the product content reached more than 50% (area normalization). And (3) cooling and layering, separating a lower catalyst layer (used in example 2), adding a saturated sodium bicarbonate solution into an upper material layer, washing, standing and layering. And adding water into the organic layer for washing, and standing for layering. The organic layer was desolventized to obtain 1090g of p-tert-butyl benzyl chloride. 690g of tert-butylbenzene as a raw material was recovered. Product analysis shows that the content of the product is 95 percent by an area normalization method, the content of the m-tert-butyl benzyl chloride is 4.50 percent, and the content of the dimeric impurity is 0.41 percent.
Example 2:
the ionic liquid catalyst obtained by separation in example 1 was transferred to a 10L reactor, and 1500g of t-butyl benzene and 297g of paraformaldehyde were again added. Starting stirring and heating to 60-80 ℃. Hydrogen chloride gas was initially introduced into the kettle. And gas escapes from the reflux evacuation port and needs to be connected into the absorption tower. The product content was monitored by GC and the reaction was stopped when the product content reached more than 50% (area normalization). Cooling and layering, separating out a lower catalyst layer, adding a saturated sodium bicarbonate solution into an upper material layer, washing, standing and layering. And adding water into the organic layer for washing, and standing for layering. The organic layer was desolventized to obtain 1084g of p-tert-butylbenzyl chloride. 694.5g of tert-butylbenzene as a raw material was recovered. Product analysis shows that the content of the product is 94.8 percent by an area normalization method, 4.40 percent of m-tert-butyl benzyl chloride and 0.21 percent of dimeric impurity. The number of times of the mixed ionic liquid catalyst is used repeatedly reaches more than 100 times. The product quality is not obviously reduced. Specific data are not listed.
Example 3:
500g of 1-methylpyrazole and 540g of n-butyl chloride were charged into a 5L reactor, and the reactor was heated with stirring. Heating to 80-90 deg.c, reflux reaction for 24 hr, GC or HPLC monitoring the material reaction, and cooling to 50 deg.c. 1500g of water were added. After stirring, 2000g of aluminum chloride was added. And stirring uniformly to obtain the mixed ionic liquid catalyst.
The mixed ionic liquid catalyst obtained above was transferred to a 10L reactor, and 1500g of tert-butyl benzene and 297g of paraformaldehyde were added. Starting stirring and heating to 60-80 ℃. Hydrogen chloride gas was initially introduced into the kettle. And gas escapes from the reflux evacuation port and needs to be connected into the absorption tower. The product content was monitored by GC and the reaction was stopped when the product content reached more than 50% (area normalization). Cooling and layering, separating out a lower catalyst layer, adding a saturated sodium bicarbonate solution into an upper material layer, washing, standing and layering. And adding water into the organic layer for washing, and standing for layering. The organic layer was desolventized to obtain 1094g of p-tert-butylbenzyl chloride. The starting material tert-butylbenzene 681g was recovered. Product analysis shows that the content of the product is 95.4 percent by an area normalization method, 4.2 percent by m-tert-butyl benzyl chloride and 0.3 percent by dimeric impurity.
The catalyst has good effect on the synthesis of various substituted benzyl chlorides containing para-electron-donating groups, but the occupation ratio of ortho-position isomers can be increased along with the reduction of the number of carbon atoms of electron-donating substituents. And the effect of the tertiary carbon substituent is better than that of the secondary carbon substituent, and the effect of the secondary carbon substituent is better than that of the primary carbon substituent. Specific data are shown in table 1 below:
TABLE 1 reaction conditions for different substituted substrates
Example 4:
500g of 1-methylimidazole and 540g of n-butyl chloride were charged into a 5-liter vessel, and heating was started with stirring. Reflux reaction at 80-90 deg.c for 24 hr, GC or HPLC monitoring the reaction of the material and cooling to 50 deg.c. 1500g of water were added. Stirring evenly, adding 2000g of zinc chloride. And stirring uniformly to obtain the mixed ionic liquid catalyst.
The mixed ionic liquid catalyst is transferred into a 10L reaction kettle, and 1500g of tert-butyl benzene and 297g of paraformaldehyde are added. Starting stirring and heating to 60-80 ℃. Hydrogen chloride gas was initially introduced into the kettle. And gas escapes from the reflux evacuation port and needs to be connected into the absorption tower. The product content was monitored by GC and the reaction was stopped when the product content reached more than 50% (area normalization). Cooling and layering, separating out a lower catalyst layer, adding a saturated sodium bicarbonate solution into an upper material layer, washing, standing and layering. And adding water into the organic layer for washing, and standing for layering. The organic layer was desolventized to obtain 1101g of p-tert-butyl benzyl chloride. 672g of tert-butyl benzene as a raw material are recovered. Product analysis shows that the content of the product is 94.5 percent by an area normalization method, 4.9 percent of m-tert-butyl benzyl chloride and 0.5 percent of dimeric impurity. The number of times of the mixed ionic liquid catalyst is used repeatedly reaches more than 30 times. The product quality is not obviously reduced. The data are not listed. The same applies to the present embodiment for the case described in table 1 above.
The catalyst has good chloromethylation effect on pure benzene and single product. But is less effective for benzene rings having electron-withdrawing groups, and substantially no or little chloromethylation reaction occurs.
The above examples are only intended to illustrate the technical solution of the present invention, but not to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, it should be understood by those skilled in the art that various changes and modifications may be made in the embodiments described in the foregoing embodiments, or equivalent changes and modifications may be made to some of the technical features of the embodiments without departing from the scope of the embodiments of the present invention.
Claims (10)
1. A mixed chloromethylation catalyst, which is characterized in that: comprises quaternary ammonium salt and Lewis acid.
2. The hybrid chloromethylation catalyst as recited in claim 1 wherein: water or acidic solutions are also included.
3. The hybrid chloromethylation catalyst according to claim 2, wherein: in the mixed catalyst, the weight ratio of quaternary ammonium salt, Lewis acid and water or acid solution is 10-80%, 10-80% and 10-80%.
4. The hybrid chloromethylation catalyst according to claim 2, wherein: the acidic aqueous solution is selected from hydrochloric acid aqueous solution, sulfuric acid aqueous solution or phosphoric acid aqueous solution.
5. The hybrid chloromethylation catalyst as recited in claim 1 wherein: the quaternary ammonium salt has the following general formula:
wherein R is2、R3、R4、R5、R6Each independently is H, C1-C20 alkyl or C1-C20 alkoxy C1-C20 alkyl; x is F, Cl, Br or I; the quaternary ammonium salt is generated by the reaction of a double-nitrogen heterocyclic compound and halogenated alkane, wherein the double-nitrogen heterocyclic compound is selected from N-substituted imidazole, N-substituted pyrazole or N-substituted piperazine; the halogenated alkane is selected from halogenated C1-C20 alkane, and the halogen is fluorine, chlorine, bromine or iodine.
6. The hybrid catalyst according to claim 1, characterized in that: the Lewis acid is selected from tin chloride, antimony chloride, zinc chloride, magnesium chloride, aluminum chloride or cobalt chloride.
7. A method for synthesizing para-substituted chlorobenzyl compounds is characterized by comprising the following steps: reacting a benzene ring compound containing a para-position electron-donating substituent with methylene chloride in the presence of the mixed chloromethylation catalyst disclosed in claim 1 to obtain a corresponding para-position substituted chlorobenzyl compound.
8. The method for synthesizing the para-substituted chlorobenzyl compound according to claim 7, wherein the method comprises the following steps: methylene chloride is generated by reacting aldehyde or polyaldehyde with hydrogen chloride.
9. The method for synthesizing the para-substituted chlorobenzyl compound according to claim 7, wherein the method comprises the following steps: after the reaction is finished, standing the mixed chloromethylation catalyst and the organic phase material, and then carrying out layered separation, wherein the catalyst is continuously applied for more than 100 times.
10. The method for synthesizing the para-substituted chlorobenzyl compound according to claim 9, wherein the method comprises the following steps: when the water content ratio in the mixed chloromethylation catalyst is high, the mixed chloromethylation catalyst is distilled to remove water and then is continuously used.
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| CN1931804A (en) * | 2006-10-13 | 2007-03-21 | 广东工业大学 | Chloromethylation reaction process |
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| CN1931804A (en) * | 2006-10-13 | 2007-03-21 | 广东工业大学 | Chloromethylation reaction process |
| CN101774880A (en) * | 2009-12-18 | 2010-07-14 | 中国科学院新疆理化技术研究所 | Method for catalytic reaction of chloromethylation of aromatic cyclic compound |
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