CN115772072A - Preparation method of m-phenoxy benzaldehyde - Google Patents
Preparation method of m-phenoxy benzaldehyde Download PDFInfo
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- CN115772072A CN115772072A CN202211507753.2A CN202211507753A CN115772072A CN 115772072 A CN115772072 A CN 115772072A CN 202211507753 A CN202211507753 A CN 202211507753A CN 115772072 A CN115772072 A CN 115772072A
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- MRLGCTNJRREZHZ-UHFFFAOYSA-N 3-phenoxybenzaldehyde Chemical compound O=CC1=CC=CC(OC=2C=CC=CC=2)=C1 MRLGCTNJRREZHZ-UHFFFAOYSA-N 0.000 title claims abstract description 37
- 238000002360 preparation method Methods 0.000 title claims abstract description 30
- 238000000034 method Methods 0.000 claims abstract description 39
- 238000006243 chemical reaction Methods 0.000 claims description 78
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 66
- 150000001875 compounds Chemical class 0.000 claims description 40
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 38
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 33
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 32
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 29
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 23
- 239000005457 ice water Substances 0.000 claims description 22
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 20
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 19
- 239000011259 mixed solution Substances 0.000 claims description 19
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 18
- 239000011777 magnesium Substances 0.000 claims description 18
- 229910052749 magnesium Inorganic materials 0.000 claims description 18
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 claims description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 15
- 239000000243 solution Substances 0.000 claims description 15
- 239000005751 Copper oxide Substances 0.000 claims description 14
- 238000003747 Grignard reaction Methods 0.000 claims description 14
- 229910000431 copper oxide Inorganic materials 0.000 claims description 14
- 238000002156 mixing Methods 0.000 claims description 13
- -1 m-phenoxyphenyl magnesium halide Chemical class 0.000 claims description 12
- 238000006266 etherification reaction Methods 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 10
- 230000002378 acidificating effect Effects 0.000 claims description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 239000000010 aprotic solvent Substances 0.000 claims description 9
- 239000003054 catalyst Substances 0.000 claims description 9
- 230000035484 reaction time Effects 0.000 claims description 9
- 239000003999 initiator Substances 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- FEWLNYSYJNLUOO-UHFFFAOYSA-N 1-Piperidinecarboxaldehyde Chemical compound O=CN1CCCCC1 FEWLNYSYJNLUOO-UHFFFAOYSA-N 0.000 claims description 6
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 6
- 229940045803 cuprous chloride Drugs 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 239000003513 alkali Substances 0.000 claims description 5
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims description 5
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
- 150000004820 halides Chemical class 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical group 0.000 claims description 3
- 229910052740 iodine Chemical group 0.000 claims description 3
- 239000011630 iodine Chemical group 0.000 claims description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- GBDYFPAHVXJQEP-UHFFFAOYSA-N n-ethyl-n-phenylformamide Chemical compound CCN(C=O)C1=CC=CC=C1 GBDYFPAHVXJQEP-UHFFFAOYSA-N 0.000 claims description 3
- JIKUXBYRTXDNIY-UHFFFAOYSA-N n-methyl-n-phenylformamide Chemical compound O=CN(C)C1=CC=CC=C1 JIKUXBYRTXDNIY-UHFFFAOYSA-N 0.000 claims description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-M phenolate Chemical compound [O-]C1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-M 0.000 claims description 3
- 229940031826 phenolate Drugs 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- JXASPPWQHFOWPL-UHFFFAOYSA-N Tamarixin Natural products C1=C(O)C(OC)=CC=C1C1=C(OC2C(C(O)C(O)C(CO)O2)O)C(=O)C2=C(O)C=C(O)C=C2O1 JXASPPWQHFOWPL-UHFFFAOYSA-N 0.000 claims description 2
- SYKNUAWMBRIEKB-UHFFFAOYSA-N [Cl].[Br] Chemical group [Cl].[Br] SYKNUAWMBRIEKB-UHFFFAOYSA-N 0.000 claims description 2
- RDHPKYGYEGBMSE-VQEHIDDOSA-N bromoethane Chemical group C[13CH2]Br RDHPKYGYEGBMSE-VQEHIDDOSA-N 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- 125000005936 piperidyl group Chemical group 0.000 claims description 2
- 239000012295 chemical reaction liquid Substances 0.000 claims 1
- 239000007788 liquid Substances 0.000 claims 1
- 238000007086 side reaction Methods 0.000 abstract description 6
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 4
- 238000009776 industrial production Methods 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 238000007254 oxidation reaction Methods 0.000 abstract description 3
- 230000003321 amplification Effects 0.000 abstract description 2
- 230000007613 environmental effect Effects 0.000 abstract description 2
- 238000003199 nucleic acid amplification method Methods 0.000 abstract description 2
- 230000003647 oxidation Effects 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 238000003756 stirring Methods 0.000 description 26
- ZPQOPVIELGIULI-UHFFFAOYSA-N 1,3-dichlorobenzene Chemical compound ClC1=CC=CC(Cl)=C1 ZPQOPVIELGIULI-UHFFFAOYSA-N 0.000 description 25
- 238000004821 distillation Methods 0.000 description 25
- 239000000047 product Substances 0.000 description 24
- BMURONZFJJPAOK-UHFFFAOYSA-N 1-chloro-3-phenoxybenzene Chemical compound ClC1=CC=CC(OC=2C=CC=CC=2)=C1 BMURONZFJJPAOK-UHFFFAOYSA-N 0.000 description 15
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 14
- 229960004643 cupric oxide Drugs 0.000 description 14
- SUAKHGWARZSWIH-UHFFFAOYSA-N N,N‐diethylformamide Chemical compound CCN(CC)C=O SUAKHGWARZSWIH-UHFFFAOYSA-N 0.000 description 13
- 239000012074 organic phase Substances 0.000 description 13
- 239000012071 phase Substances 0.000 description 13
- 238000010791 quenching Methods 0.000 description 13
- 230000000171 quenching effect Effects 0.000 description 13
- 239000007795 chemical reaction product Substances 0.000 description 12
- 238000001816 cooling Methods 0.000 description 12
- 238000010438 heat treatment Methods 0.000 description 12
- 238000004321 preservation Methods 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- 238000005070 sampling Methods 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- 239000002585 base Substances 0.000 description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 5
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- MYFJQPIZIVKRMR-UHFFFAOYSA-L C([O-])([O-])=O.[K+].[Cu]=O.[K+] Chemical compound C([O-])([O-])=O.[K+].[Cu]=O.[K+] MYFJQPIZIVKRMR-UHFFFAOYSA-L 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000002728 pyrethroid Substances 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- JSRLURSZEMLAFO-UHFFFAOYSA-N 1,3-dibromobenzene Chemical group BrC1=CC=CC(Br)=C1 JSRLURSZEMLAFO-UHFFFAOYSA-N 0.000 description 2
- JRGGUPZKKTVKOV-UHFFFAOYSA-N 1-bromo-3-chlorobenzene Chemical compound ClC1=CC=CC(Br)=C1 JRGGUPZKKTVKOV-UHFFFAOYSA-N 0.000 description 2
- SUISZCALMBHJQX-UHFFFAOYSA-N 3-bromobenzaldehyde Chemical compound BrC1=CC=CC(C=O)=C1 SUISZCALMBHJQX-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 230000031709 bromination Effects 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000007867 post-reaction treatment Methods 0.000 description 2
- ZGJADVGJIVEEGF-UHFFFAOYSA-M potassium;phenoxide Chemical compound [K+].[O-]C1=CC=CC=C1 ZGJADVGJIVEEGF-UHFFFAOYSA-M 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 229910052684 Cerium Inorganic materials 0.000 description 1
- XAJHEMRJDJTUOX-UHFFFAOYSA-N O=CC1=CC=CC(OC=2C=CC=CC=2)=C1.O=CC1=CC=CC(OC=2C=CC=CC=2)=C1 Chemical compound O=CC1=CC=CC(OC=2C=CC=CC=2)=C1.O=CC1=CC=CC(OC=2C=CC=CC=2)=C1 XAJHEMRJDJTUOX-UHFFFAOYSA-N 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- GWXLDORMOJMVQZ-UHFFFAOYSA-N cerium Chemical compound [Ce] GWXLDORMOJMVQZ-UHFFFAOYSA-N 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 229960003280 cupric chloride Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 150000004707 phenolate Chemical class 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- DXUZIOCXIJYYGO-UHFFFAOYSA-M potassium oxocopper hydroxide Chemical compound [Cu]=O.[OH-].[K+] DXUZIOCXIJYYGO-UHFFFAOYSA-M 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- NESLWCLHZZISNB-UHFFFAOYSA-M sodium phenolate Chemical compound [Na+].[O-]C1=CC=CC=C1 NESLWCLHZZISNB-UHFFFAOYSA-M 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The application discloses a preparation method of m-phenoxy benzaldehyde. In the application, the synthesis steps are few, the process is simple, expensive reagents are not needed, the cost is low, and the industrial production is facilitated; high-risk processes such as oxidation, reduction and the like are avoided, side reactions are few, and the safety of amplification production is improved; the three wastes in each step are less, the residual unreacted raw materials can be recycled, and the process has high environmental protection property.
Description
Technical Field
The invention relates to the field of chemical synthesis, in particular to a preparation method of m-phenoxy benzaldehyde.
Background
M-phenoxy benzaldehyde or 3-phenoxy benzaldehyde (m-phenoxy benzaldehyde), also known as etheraldehyde or MPA, is an important intermediate for synthesizing pyrethroid insecticides and other drugs. For example, in the synthesis of pyrethroid compounds and various stereoisomers thereof, the key intermediate is needed.
In the prior art, the method for preparing m-phenoxy benzaldehyde has high cost and low yield. For example, patent CN110256285a describes a method for synthesizing stable isotope labeled pyrethroid, in which potassium phenoxide, m-bromobenzaldehyde and cuprous chloride are used as reactants, and m-phenoxybenzaldehyde is obtained under closed temperature and pressure control. In general, m-bromobenzaldehyde is obtained by bromination of benzaldehyde, liquid bromine is required in the bromination process, the cost is high, the preparation cost of m-phenoxybenzaldehyde is increased, and the industrialization is difficult. Patent CN112661621A describes a method for preparing m-phenoxy benzaldehyde by oxidation reaction of m-cresol, halogenated benzene and inorganic base, and then by gas-phase catalytic hydrogenation by using cerium-based catalyst, the catalyst used in the method is expensive, and the catalytic hydrogenation reaction temperature is high (300-450 ℃), so that the industrial production has great potential safety hazard and is not beneficial to large-scale production.
Therefore, there is a need in the art to develop a safe and low-cost process for the preparation of m-phenoxybenzaldehyde.
Disclosure of Invention
The invention aims to provide a preparation method of m-phenoxy benzaldehyde.
In order to solve the above technical problems, a first aspect of the present invention provides a method for preparing m-phenoxybenzaldehyde, comprising the steps of:
reacting a compound of formula I and a compound of formula II,
wherein A is
Or Li, X is halogen;
b is
R 1 And R 2 Are each independently selected from C 1-6 Alkyl or aryl.
In some preferred embodiments, X is fluorine, chlorine bromine, or iodine;
in some preferred embodiments, the compound of formula I is a m-phenoxymagnesium halide; such as m-phenoxymagnesium chloride or m-phenoxymagnesium bromide.
In some preferred embodiments, in the compounds of formula II, R 1 And R 2 Are each independently C 1-6 An alkyl group.
In some preferred embodiments, C 1-6 Alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl; more preferably ethyl.
In some preferred embodiments, the aryl group is phenyl or piperidinyl.
In some preferred embodiments, the compound of formula II is N, N-dimethylformamide, N-diethylformamide or phenyl N-methylformamide, phenyl N-ethylformamide or N-formylpiperidine; more preferably, the compound of formula ii is N, N-diethylformamide.
In some preferred embodiments, the method comprises the steps of:
mixing a compound shown in a formula I and a compound shown in a formula II and reacting to obtain a reaction solution;
mixing the reaction solution with ice water to form a mixed solution; and
and (3) making the pH value of the mixed solution be subacidity to obtain the m-phenoxy benzaldehyde.
In some preferred embodiments, the step of combining the compound of formula I with the compound of formula ii comprises: gradually adding the compound of the formula II into a reaction system containing the compound of the formula I.
In some preferred embodiments, said combining a compound of formula I with a compound of formula ii comprises the steps of:
gradually adding the compound of the formula II into a reaction system containing the compound of the formula I.
In some preferred embodiments, the molar ratio of the compound of formula I to the compound of formula II is 1 (1-1.8), and more preferably, the molar ratio of the compound of formula I to the compound of formula II is 1 (1.05-1.2).
In some preferred embodiments, the method comprises the steps of:
nucleophilic substitution reaction of the compound of formula I and the compound of formula II.
In some preferred embodiments, the reaction temperature of the nucleophilic substitution reaction is from 0 to 8 ℃, e.g., 5 ℃.
In some preferred embodiments, the reaction time for the nucleophilic substitution reaction is 20 to 40 minutes, such as 30 minutes.
In some preferred embodiments, the step of mixing the reaction solution with ice water to form a mixed solution includes: the reaction solution was placed in ice water to form a mixed solution.
In some preferred embodiments, the step of making the pH of the mixture weak acidic comprises: adding an acid to the mixture.
In some preferred embodiments, the acid is hydrochloric acid, and more preferably, the acid is 1% by mass hydrochloric acid.
In some preferred embodiments, the preparation of the m-phenoxyphenylmagnesium halide comprises the steps of:
making m-phenoxy halogeno benzene and metal magnesium produce Grignard reaction to obtain m-phenoxy phenyl magnesium halide.
In some preferred embodiments, the grignard reaction is carried out in an aprotic solvent.
In some preferred embodiments, the preparation of the m-phenoxyphenyl magnesium halide comprises the steps of:
adding metal magnesium and an initiator into an aprotic solvent, and then adding m-phenoxy halogeno-benzene to carry out Grignard reaction to obtain m-phenoxy phenyl magnesium halide.
In some preferred embodiments, the aprotic solvent is tetrahydrofuran, diethyl ether, a mixture of tetrahydrofuran and toluene, or a mixture of diethyl ether and toluene, and more preferably, the aprotic solvent is tetrahydrofuran.
In some preferred embodiments, the initiator is bromoethane, 1,2-dibromoethane, iodine, or methyl iodide.
In some preferred embodiments, the reaction temperature of the grignard reaction is from-10 to 60 ℃, more preferably from 30 to 45 ℃, e.g., 35 ℃.
In some preferred embodiments, the reaction time of the grignard reaction is 1 to 8 hours, more preferably 3to 4 hours.
In some preferred embodiments, the preparation of the m-phenoxyhalobenzene comprises the steps of:
m-dihalobenzene and phenol or phenolate are subjected to etherification reaction in the presence of alkali to obtain m-phenoxyhalogenobenzene.
In some preferred embodiments, the etherification reaction is carried out in the presence of a catalyst selected from at least one of cupric oxide, cupric chloride, and cuprous chloride.
In some preferred embodiments, the etherification reaction is carried out for a reaction time of 1 to 12 hours, more preferably 4 to 10 hours, for example 6 hours.
In some preferred embodiments, the reaction temperature of the etherification reaction is 120 to 200 ℃, more preferably 160 to 180 ℃.
In some preferred embodiments, the base is sodium hydroxide, potassium carbonate, or sodium carbonate, more preferably potassium carbonate.
In some preferred embodiments, the m-dihalobenzene is m-dibromobenzene or m-bromochlorobenzene; more preferably m-dichlorobenzene.
In some preferred embodiments, the molar ratio of the m-dihalobenzene to the phenol or phenate charge is (0.1-5): 1 is more preferably (1-3): 1.
compared with the prior art, the invention has at least the following advantages:
(1) The preparation method of m-phenoxy benzaldehyde provided by the invention has the advantages of few synthesis steps, simple process, no need of expensive reagents, low cost and convenience for industrial production;
(2) The preparation method of m-phenoxy benzaldehyde provided by the invention avoids high-risk processes such as oxidation and reduction, has few side reactions, and improves the safety of amplification production;
(3) The preparation method of m-phenoxy benzaldehyde provided by the invention has the advantages of less three wastes in each step, recoverable and reusable residual unreacted raw materials and high process environmental friendliness.
It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments. Not to be reiterated herein, but to the extent of space.
Detailed Description
The present inventors have extensively and intensively studied and developed a novel method for producing m-phenoxybenzaldehyde, which comprises the steps of obtaining m-phenoxychlorobenzene by a condensation reaction, and obtaining m-phenoxybenzaldehyde by a Grignard-aldolization reaction. The reagent used in the method is cheap and easy to obtain, and high-temperature catalytic hydrogenation is not needed, so that the method is suitable for industrial production.
The invention provides a preparation method of m-phenoxy benzaldehyde, which comprises the following steps: reacting a compound of the formula I with a compound of the formula II (nucleophilic substitution reaction),
as compounds of formula I, they may be m-phenoxymagnesium halide Grignard reagents or m-phenoxylithium, preferably m-phenoxymagnesium chloride or m-phenoxymagnesium bromide.
As compounds of formula II, R 1 And R 2 Are each independently C 1-6 An alkyl or aryl group; said C is 1-6 Alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl, more preferablyIs selected as ethyl; the aryl is phenyl or piperidyl. More preferably, R 1 And R 2 Each independently is methyl, ethyl, n-propyl or isopropyl. For example: the compound of the formula II is N, N-dimethylformamide, N-diethylformamide or phenyl N-methylformamide, phenyl N-ethylformamide or N-formylpiperidine; most preferably, the compound of formula ii is N, N-diethylformamide.
In a preferred embodiment, the above reaction comprises the steps of: mixing and stirring a compound shown in a formula I and a compound shown in a formula II to obtain a reaction solution;
mixing the reaction solution with ice water to form a mixed solution; and
the pH value of the mixed solution is subacidity, and the m-phenoxy benzaldehyde is obtained.
In the step of "mixing and reacting the compound of formula I with the compound of formula II to obtain a reaction solution", the compound of formula I and the compound of formula II are first mixed in such a manner as to achieve contact between the two compounds. Preferably, the mixing is effected by stepwise addition of the compound of formula II to the reaction system containing the compound of formula I. Preferably, intimate mixing is achieved by stepwise addition of the compound of formula II to the reaction system containing the compound of formula I under agitation.
As starting materials for the reaction, preference is given to a slight excess of the compounds of the formula II. More preferably, the compound of formula I and the compound of formula II are fed in a molar ratio of 1 (1-1.8), and even more preferably, the compound of formula I and the compound of formula II are fed in a molar ratio of 1 (1.05-1.2).
In the step of mixing and reacting the compound of formula I with the compound of formula ii to obtain a reaction solution, the compound of formula I and the compound of formula ii are subjected to nucleophilic substitution reaction under stirring, preferably at a temperature of 0 to 8 ℃, for example 5 ℃; the reaction time is 20 to 40 minutes, for example 30 minutes.
In the step of mixing the reaction solution with ice water to form a mixed solution, optionally, the ice water mixture is placed in the reaction solution to form the mixed solution, but side reactions in such a quenching manner are obvious; preferably, the reaction solution is placed in an ice-water mixture to form a mixed solution, so that side reactions can be obviously reduced, and the yield is improved.
In the step of "making the pH of the mixed solution weakly acidic", the mixed solution may be treated to a pH of not higher than 7, preferably 3to 4.5, by a method of adjusting pH which is conventional in the art. Without limitation, by adding an acidic material, such as a strong acid, a weak acid, or a strong acid weak base salt, to the mixed liquor; preferably, the pH of the mixture is adjusted by adding hydrochloric acid or sulfuric acid. More preferably, the pH of the mixed solution is adjusted to 3.5-4.5 by 1% hydrochloric acid, which can reduce the occurrence of side reactions compared with the use of weak acids (e.g., acetic acid, carbonic acid) or other strong acids (e.g., sulfuric acid).
After the step of making the pH value of the mixed solution be weakly acidic, the method also comprises a step of purifying m-phenoxy benzaldehyde, namely extracting and distilling under reduced pressure. The extractant is preferably ethyl acetate, and the purified m-phenoxybenzaldehyde is obtained by extracting three times, taking an organic phase and carrying out reduced pressure distillation.
The compound of formula I is preferably a m-phenoxymagnesium halide, optionally prepared by a grignard reaction. In the present invention, "Grignard reaction" and "Grignard reaction" are used interchangeably and refer to a process of generating organic magnesium halide by reacting organic material (e.g., halogenated hydrocarbon) containing halogen and metallic magnesium in an anhydrous aprotic solvent. The reaction conditions of the Grignard reaction are carried out with reference to common knowledge in the art. In a preferred embodiment of the present invention, a magnesium metal and an initiator are added to an aprotic solvent, and m-phenoxyhalogenobenzene is added to perform a Grignard reaction to obtain a m-phenoxyphenylmagnesium halide.
The aprotic solvent is preferably tetrahydrofuran, diethyl ether, a mixture of tetrahydrofuran and toluene, or a mixture of diethyl ether and toluene.
As the initiator, at least one selected from the group consisting of bromoethane, 1,2-dibromoethane, iodine and iodomethane is preferable.
As the reaction temperature of the Grignard reaction, it is preferably from-10 to 60 ℃, more preferably from 30 to 45 ℃, for example, 35 ℃. The reaction time of the grignard reaction is preferably 1 to 8 hours, and more preferably 3to 4 hours.
In the present invention, the m-phenoxy halogenobenzene may be prepared by: in the presence of alkali, m-dihalobenzene and phenol or phenolate are etherified. As the base, sodium hydroxide, potassium carbonate or sodium carbonate can be used, and when the base used is potassium carbonate, the reaction yield is higher. The m-dihalobenzene is preferably m-dibromobenzene or m-bromochlorobenzene. As the phenolate salt, sodium phenolate or potassium phenolate is preferable. The m-dihalobenzene and the phenol or phenate 7 are preferably present in a molar ratio of (0.1-5): 1, more preferably (1-3): 1.
the reaction temperature as the etherification reaction is 120 to 200 ℃ and more preferably 160 to 180 ℃ and, when the temperature is 160 to 180 ℃, the reaction time is shorter and the side reaction is less. The reaction time of the etherification reaction is preferably 1 to 12 hours, more preferably 4 to 10 hours, for example, 6 hours.
In order to make the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the present invention is further described below with reference to specific embodiments. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Experimental procedures without specific conditions noted in the following examples, generally according to conventional conditions, or according to conditions recommended by the manufacturer. Unless otherwise indicated, percentages and parts are percentages and parts by weight. The test materials and reagents used in the following examples are commercially available without specific reference.
Unless otherwise defined, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs, and it is to be noted that the terms used herein are merely for describing particular embodiments and are not intended to limit example embodiments of the present application.
Example 1
In this example, m-phenoxybenzaldehyde was prepared. The preparation method comprises the following steps:
(1) 40g of phenol, 160g of m-dichlorobenzene, 3238 g of potassium carbonate and 3262 g of copper oxide are added into a 250ml three-necked bottle at an inner chamber temperature, and the temperature is raised to 175-180 ℃ for reflux and heat preservation for 6 hours to finish the reaction. Recovering m-dichlorobenzene and phenol by reduced pressure distillation, and collecting 90 ℃ fraction by reduced pressure distillation under the condition of 0.3torr to obtain 80.73g of product. (GC purity: 99.8%; yield: 93.09%).
(2) Adding 3.6g of magnesium chips, 50g of tetrahydrofuran and 1g of bromoethane into the inner chamber of the three-necked flask, heating to 40 ℃, and stirring for 30 minutes; 10g of m-phenoxychlorobenzene and 40g of THF were slowly added thereto, and the reaction was carried out at 40 ℃ for 3.5 hours.
Cooling the reaction bottle to about 5 ℃, adding 12.85g of N, N-diethylformamide, stirring for 30 minutes after the addition, sampling, pouring the reaction product into 50g of ice-water mixture for quenching, adjusting the pH value to subacidity by using 1.0% hydrochloric acid, extracting the water phase by using EA for three times, wherein the extraction is performed for 50g each time, combining the organic phases, and distilling under reduced pressure to obtain 8.23g of a product. (GC purity: 99.9%; yield: 84.93%)
The inventors found that the difference in the kind of the base, the kind of the catalyst and the reaction temperature used in the preparation of m-phenoxychlorobenzene in the step (1) affects the reaction process and the result. In examples 2 to 6 described below, the influence on the yield of m-phenoxychlorobenzene was investigated by changing the kind of the base used, the kind of the catalyst and the reaction temperature.
Example 2
In this example, m-phenoxybenzaldehyde was prepared by a method substantially the same as in example 1, except that potassium hydroxide was used instead of potassium carbonate in step (1), and in this example, the specific preparation method was as follows:
(1) 40g of phenol, 160g of m-dichlorobenzene, 23.76g of potassium hydroxide and 1.354g of copper oxide are added into a 250ml three-mouth bottle at an inner chamber temperature, and the temperature is raised to 175-180 ℃ for reflux and heat preservation for 6 hours to finish the reaction. The m-dichlorobenzene and the phenol are recovered by reduced pressure distillation, and then the product of 30.62g is obtained by collecting the fraction at 90 ℃ by reduced pressure distillation under the condition of 0.3 torr. (GC purity: 99.6%; yield: 30.62%).
(2) Adding 3.6g of magnesium chips, 50g of tetrahydrofuran and 1g of bromoethane into the inner chamber of the three-necked flask, heating to 40 ℃, and stirring for 30 minutes; 10g of m-phenoxychlorobenzene and 40g of THF were slowly added thereto, and the reaction was carried out at 40 ℃ for 3.5 hours. Cooling the reaction bottle to about 5 ℃, adding 12.85g of N, N-diethylformamide, stirring for 30 minutes after the addition, sampling, pouring the reaction product into 50g of ice-water mixture for quenching, adjusting the pH to be weakly acidic by using 1.0% hydrochloric acid, extracting the water phase by using EA for three times, wherein 50g of EA is used for each time, combining the organic phases, and distilling under reduced pressure to obtain 8.06g of the product. (GC purity: 99.6%, yield: 83.17%).
Example 3
In this example, m-phenoxybenzaldehyde was prepared by substantially the same method as in example 1, except that copper chloride was used instead of copper oxide in step (1), and in this example, the specific preparation method was as follows:
(1) 40g of phenol, 160g of m-dichlorobenzene, 3238 g of potassium carbonate and 3262 g of copper chloride are added into a 250ml three-mouth bottle at an inner chamber temperature, and the temperature is raised to 175-180 ℃ for reflux and heat preservation for 6 hours to finish the reaction. After recovering m-dichlorobenzene and phenol by distillation under reduced pressure, 30.46g of a product (HPLC purity: 99.4%; yield: 35.12%) was obtained by collecting 90 ℃ fractions by distillation under reduced pressure at 0.3 torr.
(2) Adding 3.6g of magnesium chips, 50g of tetrahydrofuran and 1g of bromoethane into the inner chamber of the three-necked flask, heating to 40 ℃, and stirring for 30 minutes; 10g of m-phenoxychlorobenzene and 40g of THF were slowly added thereto, and the reaction was carried out at 40 ℃ for 3.5 hours. Cooling the reaction bottle to about 5 ℃, adding 12.85g of N, N-diethylformamide, stirring for 30 minutes after the addition, sampling, pouring the reaction product into 50g of ice-water mixture for quenching, adjusting the pH to be weakly acidic by using 1.0% hydrochloric acid, extracting the water phase by using EA for three times, wherein 50g of EA is used for each time, combining the organic phases, and distilling under reduced pressure to obtain 8.24g of a product. (GC purity: 99.4%; yield: 85.09%).
Example 4
In this example, m-phenoxybenzaldehyde was prepared in substantially the same manner as in example 1, except that cuprous chloride was used instead of copper oxide in step (1), and in this example, the specific preparation method was as follows:
(1) 40g of phenol, 160g of m-dichlorobenzene, 3238 g of potassium carbonate and 3262 g of cuprous chloride are added into a 250ml three-necked bottle at the inner chamber temperature, and the temperature is raised to 175-180 ℃ for reflux and heat preservation for 6 hours to finish the reaction. After recovering m-dichlorobenzene and phenol by distillation under reduced pressure, 30.00g of a product (HPLC purity: 99.8%; yield: 34.59%) was obtained by collecting 90 ℃ fractions by distillation under reduced pressure at 0.3 torr.
(2) Adding 3.6g of magnesium chips, 50g of tetrahydrofuran and 1g of bromoethane into the inner chamber of the three-necked flask, heating to 40 ℃, and stirring for 30 minutes; then, 10g of m-phenoxy chlorobenzene and 40g of THF were slowly added thereto, and the reaction was carried out at 40 ℃ for 3.5 hours. Cooling the reaction bottle to about 5 ℃, adding 12.85g of N, N-diethylformamide, stirring for 30 minutes after the addition, sampling, pouring the reaction product into 50g of ice-water mixture for quenching, adjusting the pH to be weakly acidic by using 1.0% hydrochloric acid, extracting the water phase by using EA for three times, wherein 50g of EA is used for each time, combining the organic phases, and distilling under reduced pressure to obtain 8.20g of a product. (GC purity: 99.6%; yield: 84.62%).
Example 5
In this example, m-phenoxybenzaldehyde was prepared by a method similar to that of example 1, except that in step (1), the reaction temperature was different from that of example 1, and the specific preparation method in this example was as follows:
(1) 40g of phenol, 160g of m-dichlorobenzene, 3238 g of potassium carbonate and 3262 g of copper oxide are added into a 250ml three-necked bottle at the inner chamber temperature, and the temperature is raised to 120-140 ℃ for reflux and heat preservation for 12 hours to finish the reaction. The m-dichlorobenzene and the phenol are recovered by reduced pressure distillation, and then the product of 17.45g is obtained by collecting the fraction at 90 ℃ by reduced pressure distillation under the condition of 0.3 torr. (GC purity: 99.3%; yield: 20.12%).
(2) Adding 3.6g of magnesium chips, 50g of tetrahydrofuran and 1g of bromoethane into the inner chamber of the three-mouth bottle, heating to 40 ℃, and stirring for 30 minutes; 10g of m-phenoxychlorobenzene and 40g of THF were slowly added thereto, and the reaction was carried out at 40 ℃ for 3.5 hours.
Cooling the reaction bottle to about 5 ℃, adding 12.85g of N, N-diethylformamide, stirring for 30 minutes after the addition, sampling, pouring the reaction product into 50g of ice-water mixture for quenching, adjusting the pH value to subacidity by using 1.0% hydrochloric acid, extracting the water phase by using EA for three times, wherein the extraction is performed for 50g each time, combining the organic phases, and distilling under reduced pressure to obtain 8.18g of a product. (GC purity: 99.9%; yield: 84.43%)
Example 6
In this example, m-phenoxybenzaldehyde was prepared by a method similar to that of example 1, except that in step (1), the reaction temperature was different from that of example 1, and the specific preparation method in this example was as follows:
(1) 40g of phenol, 160g of m-dichlorobenzene, 3238 g of potassium carbonate and 3262 g of copper oxide are added into a 250ml three-necked bottle at an inner chamber temperature, and the temperature is increased to 200 ℃ for reflux and heat preservation for 6 hours to finish the reaction. Recovering m-dichlorobenzene and phenol by reduced pressure distillation, and collecting 90 ℃ fraction by reduced pressure distillation under the condition of 0.3torr to obtain 66.71g of product. (GC purity: 99.64%; yield: 76.93%).
(2) Adding 3.6g of magnesium chips, 50g of tetrahydrofuran and 1g of bromoethane into the inner chamber of the three-necked flask, heating to 40 ℃, and stirring for 30 minutes; then, 10g of m-phenoxy chlorobenzene and 40g of THF were slowly added thereto, and the reaction was carried out at 40 ℃ for 3.5 hours.
Cooling the reaction bottle to about 5 ℃, adding 12.85g of N, N-diethylformamide, stirring for 30 minutes after the addition, sampling, pouring the reaction product into 50g of ice-water mixture for quenching, adjusting the pH value to subacidity by using 1.0% hydrochloric acid, extracting the water phase by using EA for three times, wherein the extraction is performed for 50g each time, combining the organic phases, and distilling under reduced pressure to obtain 8.29g of a product. (GC purity: 99.9%; yield: 85.55%)
The following table 1 shows the influence of various factor changes on the yield of etherification reaction in step (1). It is known that when the type of the base used is potassium carbonate, the catalyst is copper oxide, and the reaction temperature is 175-180 ℃, the yield is significantly improved.
TABLE 1
| Group of | Alkali | Catalyst and process for producing the same | Reaction temperature/. Degree.C | Reaction time/h | Reaction yield |
| Example 1 | Potassium carbonate | Copper oxide | 175-180 | 6 | 93.09％ |
| Example 2 | Potassium hydroxide | Copper oxide | 175-180 | 6 | 30.62％ |
| Example 3 | Potassium carbonate | Copper chloride | 175-180 | 6 | 35.12％ |
| Example 4 | Potassium carbonate | Cuprous chloride | 175-180 | 6 | 34.59％ |
| Example 5 | Potassium carbonate | Copper oxide | 120-140 | 12 | 20.12 |
| Example 6 | Potassium carbonate | Copper oxide | 200 | 6 | 76.93 |
The inventors found that in step (2), the solvent used, the initiator, the reactants, the amount of magnesium turnings and the post-reaction treatment step all have an influence on the reaction result. In the following examples 7 to 9, the influence on the yield of m-phenoxybenzaldehyde was investigated by changing the solvent, initiator, reactants and post-reaction treatment steps used.
Example 7
In this example, m-phenoxybenzaldehyde was prepared in substantially the same manner as in example 1, except that DMF was used instead of N, N-diethylformamide in step (2), and the specific preparation method in this example was as follows:
(1) 40g of phenol, 160g of m-dichlorobenzene, 3238 g of potassium carbonate and 3262 g of copper oxide are added into a 250ml three-necked bottle at an inner chamber temperature, and the temperature is raised to 175-180 ℃ for reflux and heat preservation for 6 hours to finish the reaction. After recovering m-dichlorobenzene and phenol by distillation under reduced pressure, the product (81.12 g) was obtained by collecting the 90 ℃ fraction by distillation under reduced pressure at 0.3torr (HPLC purity: 99.6%; yield: 93.54%).
(2) Adding 3.6g of magnesium chips, 50g of tetrahydrofuran and 1g of bromoethane into the inner chamber of the three-necked flask, heating to 40 ℃, and stirring for 30 minutes; 10g of m-phenoxychlorobenzene and 40g of THF were slowly added thereto, and the reaction was carried out at 40 ℃ for 3.5 hours. Cooling the reaction flask to about 5 ℃, adding 4.3g of DMF, stirring for 30 minutes after the addition, sampling, pouring the reaction product into 50g of ice-water mixture for quenching, adjusting the pH to subacidity by using 1.0% hydrochloric acid, extracting the water phase by using EA for three times, extracting 50g of EA for each time, merging organic phases, and distilling under reduced pressure to obtain 7.28g of the product. (GC purity: 99.6%, yield: 75.11%).
Example 8
In this example, m-phenoxybenzaldehyde was prepared by a method similar to that of example 1, except that isopropyl magnesium chloride was used instead of ethyl bromide in step (2), and the specific preparation method in this example was as follows:
(1) 40g of phenol, 160g of m-dichlorobenzene, 3238 g of potassium carbonate and 3262 g of copper oxide are added into a 250ml three-necked bottle at an inner chamber temperature, and the temperature is raised to 175-180 ℃ for reflux and heat preservation for 6 hours to finish the reaction. After recovering m-dichlorobenzene and phenol by distillation under reduced pressure, the product (81.12 g) was obtained by collecting the 90 ℃ fraction by distillation under reduced pressure at 0.3torr (HPLC purity: 99.6%; yield: 93.54%).
(2) Adding 3.6g of magnesium chips, 50g of tetrahydrofuran and 1g of isopropyl magnesium chloride into the inner chamber of the three-mouth bottle, heating to 40 ℃, and stirring for 30 minutes; 10g of m-phenoxychlorobenzene and 40g of THF were slowly added thereto, and the reaction was carried out at 40 ℃ for 3.5 hours. Cooling the reaction bottle to about 5 ℃, adding 4.3g of DMF, stirring for 30 minutes after the addition, sampling, pouring the reaction product into 50g of ice-water mixture for quenching, adjusting the pH to weak acidity by using 1.0% hydrochloric acid, extracting the water phase by using EA for three times, wherein 50g of EA is used for each time, combining organic phases, and distilling under reduced pressure to obtain 7.79g of a product. (GC purity: 99.84%, yield: 80.43%).
Example 9
In this example, m-phenoxybenzaldehyde was prepared by a method similar to that of example 1, except that the solvent used in the grignard reaction in step (2) was different, and the specific preparation method in this example was as follows:
(1) 40g of phenol, 160g of m-dichlorobenzene, 3238 g of potassium carbonate and 3262 g of copper oxide are added into a 250ml three-necked bottle at an inner chamber temperature, and the temperature is raised to 175-180 ℃ for reflux and heat preservation for 6 hours to finish the reaction. After recovering m-dichlorobenzene and phenol by distillation under reduced pressure, the product (81.12 g) was obtained by collecting the 90 ℃ fraction by distillation under reduced pressure at 0.3torr (HPLC purity: 99.6%; yield: 93.54%).
(2) Adding a mixture (V) of 3.6g of magnesium chips, tetrahydrofuran and toluene into the inner chamber of the three-neck flask Tetrahydrofuran (THF) ：V Toluene =1: 1) 50g of bromoethane and 1g of bromoethane, heating to 40 ℃, and stirring for 30 minutes; then, 10g of m-phenoxychlorobenzene and 40g of THF were slowly added thereto at 40 ℃ to prepare a solutionThe reaction was carried out for 3.5 hours. Cooling the reaction bottle to about 5 ℃, adding 4.3g of N, N-diethylformamide, stirring for 30 minutes after the addition, sampling, pouring the reaction product into 50g of ice-water mixture for quenching, adjusting the pH to be weakly acidic by using 1.0% hydrochloric acid, extracting the water phase by using EA for three times, wherein 50g of EA is used for each time, combining the organic phases, and distilling under reduced pressure to obtain 5.96g of a product. (GC purity: 99.6%; yield: 61.55%).
Example 10
In this example, m-phenoxybenzaldehyde was prepared by a method similar to that in example 1, except that in step (2), the treatment step after the reaction was completed was different, and the specific preparation method in this example was as follows:
(1) 40g of phenol, 160g of m-dichlorobenzene, 3238 g of potassium carbonate and 3262 g of copper oxide are added into a 250ml three-necked bottle at an inner chamber temperature, and the temperature is raised to 175-180 ℃ for reflux and heat preservation for 6 hours to finish the reaction. After recovering m-dichlorobenzene and phenol by distillation under reduced pressure, 81.12g of a product (HPLC purity: 99.6%; yield: 93.54%) was obtained by distillation under reduced pressure at 0.3torr and collection of 90 ℃ fraction.
(2) Adding 3.6g of magnesium chips, 50g of tetrahydrofuran and 1g of bromoethane into the inner chamber of the three-necked flask, heating to 40 ℃, and stirring for 30 minutes; 10g of m-phenoxychlorobenzene and 40g of THF were slowly added thereto, and the reaction was carried out at 40 ℃ for 3.5 hours. Cooling the reaction flask to about 5 ℃, adding 4.3g of N, N-diethylformamide, stirring for 30 minutes after the addition, sampling, pouring an ice-water mixture into the reaction product for quenching, adjusting the pH value to subacidity by using 1.0% hydrochloric acid, extracting the water phase by using EA for three times, wherein 50g of EA is used for each time, merging organic phases, and distilling under reduced pressure to obtain 4.88g of a product. (GC purity: 99.53%; yield: 50.32%).
Example 11
In this example, m-phenoxybenzaldehyde was prepared by a method similar to that in example 1, except that in step (2), the treatment step after the reaction was completed was different, and the specific preparation method in this example was as follows:
(1) 40g of phenol, 160g of m-dichlorobenzene, 3238 g of potassium carbonate and 3262 g of copper oxide are added into a 250ml three-necked bottle at an inner chamber temperature, and the temperature is raised to 175-180 ℃ for reflux and heat preservation for 6 hours to finish the reaction. After recovering m-dichlorobenzene and phenol by distillation under reduced pressure, the product (81.12 g) was obtained by collecting the 90 ℃ fraction by distillation under reduced pressure at 0.3torr (HPLC purity: 99.6%; yield: 93.54%).
(2) Adding 3.6g of magnesium chips, 50g of tetrahydrofuran and 1g of bromoethane into the inner chamber of the three-necked flask, heating to 40 ℃, and stirring for 30 minutes; 10g of m-phenoxychlorobenzene and 40g of THF were slowly added thereto, and the reaction was carried out at 40 ℃ for 3.5 hours. Cooling the reaction bottle to about 5 ℃, adding 4.3g of N, N-diethylformamide, stirring for 30 minutes after the addition, sampling, pouring the reaction product into 50g of ice-water mixture for quenching, adjusting the pH to subacidity by using 1.0% sulfuric acid, extracting the water phase by using EA for three times, 50g each time, combining the organic phases, and distilling under reduced pressure to obtain 3.65g of a product. (GC purity: 99.89%; yield: 37.69%).
Example 12
In this example, m-phenoxybenzaldehyde was prepared by a method similar to that in example 1, except that in step (2), the amount of magnesium chips was different, and the specific preparation method in this example was as follows:
(1) 40g of phenol, 160g of m-dichlorobenzene, 3238 g of potassium carbonate and 3262 g of copper oxide are added into a 250ml three-necked bottle at an inner chamber temperature, and the temperature is raised to 175-180 ℃ for reflux and heat preservation for 6 hours to finish the reaction. After recovering m-dichlorobenzene and phenol by distillation under reduced pressure, 81.12g of a product (HPLC purity: 99.6%; yield: 93.54%) was obtained by distillation under reduced pressure at 0.3torr and collection of 90 ℃ fraction.
(2) Adding 4.8g of magnesium chips, 50g of tetrahydrofuran and 1g of bromoethane into the inner chamber of the three-necked flask, heating to 40 ℃, and stirring for 30 minutes; 10g of m-phenoxychlorobenzene and 40g of THF were slowly added thereto, and the reaction was carried out at 40 ℃ for 3.5 hours. Cooling the reaction bottle to about 5 ℃, adding 4.3g of N, N-diethylformamide, stirring for 30 minutes after the addition, sampling, pouring the reaction product into 50g of ice-water mixture for quenching, adjusting the pH to be weakly acidic by using 1.0% hydrochloric acid, extracting the water phase by using EA for three times, wherein 50g of EA is used for each time, combining the organic phases, and distilling under reduced pressure to obtain 6.82g of a product. (GC purity: 99.40%; yield: 70.54%).
Table 2 below shows the effect of varying various factors on the reaction yield in step (2).
TABLE 2
It will be understood by those of ordinary skill in the art that the foregoing embodiments are specific examples for carrying out the invention, and that various changes in form and details may be made therein without departing from the spirit and scope of the invention in practice.
Claims (10)
1. A preparation method of m-phenoxy benzaldehyde is characterized by comprising the following steps:
reacting a compound of formula I and a compound of formula II,
wherein A is
Or Li, X is halogen;
b is
R 1 And R 2 Are each independently selected from C 1-6 Alkyl or aryl.
2. The method of claim 1, wherein X is fluorine, chlorine bromine, or iodine;
and/or, C 1-6 Alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl;
and/or the aryl is phenyl or piperidyl.
3. The method of claim 1, wherein the compound of formula I is a m-phenoxymagnesium halide;
and/or the compound of the formula II is N, N-dimethylformamide, N-diethylformamide or phenyl N-methylformamide, phenyl N-ethylformamide or N-formylpiperidine.
4. The method according to claim 1, characterized in that it comprises the steps of:
mixing a compound shown in a formula I and a compound shown in a formula II and reacting to obtain a reaction solution;
mixing the reaction solution with ice water to form a mixed solution; and
and (3) making the pH value of the mixed solution be subacidity to obtain the m-phenoxy benzaldehyde.
5. The method of claim 4, wherein the step of combining the compound of formula I with the compound of formula II comprises: gradually adding a compound of formula II into a reaction system containing a compound of formula I;
and/or the step of mixing the reaction liquid and ice water to form a mixed liquid comprises the following steps: putting the reaction solution into ice water to form a mixed solution;
and/or the step of making the pH value of the mixed solution weak acidic comprises the following steps: adding an acid to the mixture.
6. The method of claim 5, wherein the acid is hydrochloric acid.
7. The method of claim 3, wherein the preparation of the m-phenoxyphenyl magnesium halide comprises the steps of:
adding metal magnesium and an initiator into an aprotic solvent, and then adding m-phenoxy halogeno-benzene to perform a Grignard reaction to obtain m-phenoxy phenyl magnesium halide.
8. The process of claim 7 wherein the initiator is selected from bromoethane, 1,2-dibromoethane, iodine, or methyl iodide;
and/or the aprotic solvent is tetrahydrofuran, diethyl ether, a mixed solution of tetrahydrofuran and toluene, or a mixed solution of diethyl ether and toluene.
9. The method of claim 7, wherein said preparation of m-phenoxy halogenobenzene comprises the steps of:
m-dihalobenzene and phenol or phenolate are subjected to etherification reaction in the presence of alkali to obtain m-phenoxyhalogenobenzene.
10. The process according to claim 9, characterized in that the reaction time of the etherification reaction is 1 to 12 hours;
and/or the reaction temperature of the etherification reaction is 120 to 200 ℃;
and/or the alkali is sodium hydroxide, potassium carbonate or sodium carbonate;
and/or the etherification reaction is carried out in the presence of a catalyst, wherein the catalyst is at least one selected from copper oxide, copper chloride and cuprous chloride.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080221353A1 (en) * | 2007-03-09 | 2008-09-11 | Nippon Chemical Industrial Co., Ltd. | Novel phosphonium salt ionic liquid and reaction solvent including the same |
| CN101423460A (en) * | 2008-11-25 | 2009-05-06 | 安徽立兴化工有限公司 | Method for preparing chlorinated diphenyl ether |
| CN104926633A (en) * | 2015-05-06 | 2015-09-23 | 江西力田维康科技有限公司 | Preparation method for 3-alkoxybenzaldehyde |
| CN112707801A (en) * | 2020-12-30 | 2021-04-27 | 锦州三丰科技有限公司 | Preparation method of m-phenoxy benzaldehyde |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080221353A1 (en) * | 2007-03-09 | 2008-09-11 | Nippon Chemical Industrial Co., Ltd. | Novel phosphonium salt ionic liquid and reaction solvent including the same |
| CN101423460A (en) * | 2008-11-25 | 2009-05-06 | 安徽立兴化工有限公司 | Method for preparing chlorinated diphenyl ether |
| CN104926633A (en) * | 2015-05-06 | 2015-09-23 | 江西力田维康科技有限公司 | Preparation method for 3-alkoxybenzaldehyde |
| CN112707801A (en) * | 2020-12-30 | 2021-04-27 | 锦州三丰科技有限公司 | Preparation method of m-phenoxy benzaldehyde |
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