CN112079697A - Preparation method of 5-methyl vanillin - Google Patents
Preparation method of 5-methyl vanillin Download PDFInfo
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- CN112079697A CN112079697A CN202010912382.0A CN202010912382A CN112079697A CN 112079697 A CN112079697 A CN 112079697A CN 202010912382 A CN202010912382 A CN 202010912382A CN 112079697 A CN112079697 A CN 112079697A
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- vanillin
- hydroxy
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- MGJSDNCLGHCTIL-UHFFFAOYSA-N 4-hydroxy-3-methoxy-5-methylbenzaldehyde Chemical compound COC1=CC(C=O)=CC(C)=C1O MGJSDNCLGHCTIL-UHFFFAOYSA-N 0.000 title claims abstract description 32
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 238000006243 chemical reaction Methods 0.000 claims abstract description 119
- 239000003054 catalyst Substances 0.000 claims abstract description 61
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 claims abstract description 32
- WBHAUHHMPXBZCQ-UHFFFAOYSA-N 2-methoxy-6-methylphenol Chemical compound COC1=CC=CC(C)=C1O WBHAUHHMPXBZCQ-UHFFFAOYSA-N 0.000 claims abstract description 28
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 21
- 238000000034 method Methods 0.000 claims abstract description 20
- 238000005984 hydrogenation reaction Methods 0.000 claims abstract description 16
- JJVNINGBHGBWJH-UHFFFAOYSA-N ortho-vanillin Chemical compound COC1=CC=CC(C=O)=C1O JJVNINGBHGBWJH-UHFFFAOYSA-N 0.000 claims abstract description 15
- 230000003647 oxidation Effects 0.000 claims abstract description 12
- 239000002994 raw material Substances 0.000 claims abstract description 12
- 230000009471 action Effects 0.000 claims abstract description 6
- 238000006482 condensation reaction Methods 0.000 claims abstract description 6
- 238000006722 reduction reaction Methods 0.000 claims abstract description 6
- 230000020477 pH reduction Effects 0.000 claims abstract description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 90
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 21
- 239000001301 oxygen Substances 0.000 claims description 21
- 229910052760 oxygen Inorganic materials 0.000 claims description 21
- 239000001257 hydrogen Substances 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 230000008569 process Effects 0.000 claims description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 9
- 230000035484 reaction time Effects 0.000 claims description 9
- 239000003513 alkali Substances 0.000 claims description 8
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 4
- 229910019020 PtO2 Inorganic materials 0.000 claims description 3
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 3
- 238000011946 reduction process Methods 0.000 claims 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 64
- 239000000243 solution Substances 0.000 description 38
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 36
- 229910052757 nitrogen Inorganic materials 0.000 description 32
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 239000007864 aqueous solution Substances 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- 238000004458 analytical method Methods 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 239000007791 liquid phase Substances 0.000 description 9
- FWFGVMYFCODZRD-UHFFFAOYSA-N oxidanium;hydrogen sulfate Chemical compound O.OS(O)(=O)=O FWFGVMYFCODZRD-UHFFFAOYSA-N 0.000 description 9
- JSQMVIWCOVENBB-UHFFFAOYSA-N 2-hydroxy-2-(4-hydroxy-3-methoxy-5-methylphenyl)acetic acid Chemical compound COC1=CC(C(O)C(O)=O)=CC(C)=C1O JSQMVIWCOVENBB-UHFFFAOYSA-N 0.000 description 8
- 238000004821 distillation Methods 0.000 description 7
- 150000002431 hydrogen Chemical class 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- -1 4-hydroxy-3-methoxy-5-methylbenzyl Chemical group 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 2
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 2
- 235000012141 vanillin Nutrition 0.000 description 2
- VEJMFTRVXMKVQD-UHFFFAOYSA-N (5-formyl-2-hydroxy-3-methoxyphenyl)methyl acetate Chemical compound C(C)(=O)OCC1=C(C(=CC(=C1)C=O)OC)O VEJMFTRVXMKVQD-UHFFFAOYSA-N 0.000 description 1
- VKEQLWUOIPAOPW-UHFFFAOYSA-N 2-[(dimethylazaniumyl)methyl]-4-formyl-6-methoxyphenolate Chemical compound COC1=CC(C=O)=CC(CN(C)C)=C1O VKEQLWUOIPAOPW-UHFFFAOYSA-N 0.000 description 1
- KEBGFIIPHINZFS-UHFFFAOYSA-N 2-methoxy-4,6-dimethylphenol Chemical compound COC1=CC(C)=CC(C)=C1O KEBGFIIPHINZFS-UHFFFAOYSA-N 0.000 description 1
- LNACAWAKOKCCKX-UHFFFAOYSA-N 3-(chloromethyl)-4-hydroxy-5-methoxybenzaldehyde Chemical compound COC1=CC(C=O)=CC(CCl)=C1O LNACAWAKOKCCKX-UHFFFAOYSA-N 0.000 description 1
- 101710138657 Neurotoxin Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 238000005902 aminomethylation reaction Methods 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229910044991 metal oxide Inorganic materials 0.000 description 1
- 150000004706 metal oxides Chemical group 0.000 description 1
- 239000002581 neurotoxin Substances 0.000 description 1
- 231100000618 neurotoxin Toxicity 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- UXYJCYXWJGAKQY-UHFFFAOYSA-N stylopine Chemical class C1C2=C3OCOC3=CC=C2CC2N1CCC1=C2C=C(OCO2)C2=C1 UXYJCYXWJGAKQY-UHFFFAOYSA-N 0.000 description 1
- 229940034208 thyroxine Drugs 0.000 description 1
- XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
- C07C45/54—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition of compounds containing doubly bound oxygen atoms, e.g. esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/353—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by isomerisation; by change of size of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/373—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of functional groups containing oxygen only in doubly bound form
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/41—Preparation of salts of carboxylic acids
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a preparation method of 5-methyl vanillin, which comprises the following steps: 1) taking ortho-vanillin as a raw material, and carrying out hydrogenation reduction reaction under the action of a hydrogenation catalyst to obtain 6-methyl guaiacol; 2) carrying out condensation reaction on 6-methyl guaiacol and glyoxylic acid under an alkaline condition to obtain 4-hydroxy-3-methoxy-5-methyl mandelate; 3) 4-hydroxy-3-methoxy-5-methyl mandelate is subjected to oxidation reaction under the action of an oxidation catalyst, and then 5-methyl vanillin is obtained after acidification. Compared with the prior art, the method has the advantages of easily available raw materials, mild reaction conditions and high yield.
Description
Technical Field
The invention belongs to the technical field of 5-methyl vanillin, and relates to a preparation method of 5-methyl vanillin.
Background
The 5-methyl vanillin is an important raw material for synthesizing tetrahydrocoptisine derivatives, polyethylene glycol and local anesthetic, 5-hydroxytryptamine neurotoxin analogue and thyroxine transferase ligand.
Currently, there are two routes for the synthesis of 5-methyl vanillin:
route one: performing aminomethylation reaction on vanillin, dimethylamine and formaldehyde to obtain 3- (dimethylaminomethyl) -4-hydroxy-5-methoxybenzaldehyde, reacting with acetic anhydride to generate 3- (acetoxymethyl) -4-hydroxy-5-methoxybenzaldehyde, acidifying with concentrated hydrochloric acid to obtain 3- (chloromethyl) -4-hydroxy-5-methoxybenzaldehyde, and adding SnCl2The method has the advantages of more complicated reaction steps, difficult product purification, more three wastes and low yield. The reaction process is as follows:
and a second route: using 2, 4-dimethyl-6-methoxyphenol, or 4-hydroxy-3-methoxy-5-methylbenzyl alcohol, or 2-methoxy-4- (methoxymethyl) -6-methyl-phenol, in Co (OAc)2Or Cu (OAc)2The method for preparing the 5-methyl vanillin by selective oxidation under the catalytic action has the advantages of difficult obtainment of raw materials and poor feasibility. The reaction process is as follows:
R＝H,_OCH3,_OH
therefore, it is highly desirable to develop a method for preparing 5-methyl vanillin with high yield, less three wastes and easily available raw materials.
Disclosure of Invention
The invention aims to provide a preparation method of 5-methyl vanillin, which adopts a new synthetic route, utilizes easily available raw material ortho-vanillin as a starting raw material, and synthesizes 6-methyl guaiacol by catalytic hydrogenation, wherein the yield is high and three wastes are avoided; the 6-methyl guaiacol and glyoxylic acid are condensed to obtain 4-hydroxy-3-methoxy-5-methyl mandelate, the yield is high, and the next reaction can be directly carried out without post-treatment; the 4-hydroxy-3-methoxy-5-methyl mandelate is catalyzed and oxidized to synthesize the 5-methyl vanillin, the yield is high, and three wastes are less. The whole synthesis route has the advantages of easily obtained raw materials, mild reaction conditions and high yield.
The purpose of the invention can be realized by the following technical scheme:
a preparation method of 5-methyl vanillin comprises the following steps:
1) taking ortho-vanillin as a raw material, and carrying out hydrogenation reduction reaction under the action of a hydrogenation catalyst to obtain 6-methyl guaiacol;
2) carrying out condensation reaction on 6-methyl guaiacol and glyoxylic acid under an alkaline condition to obtain 4-hydroxy-3-methoxy-5-methyl mandelate;
3) 4-hydroxy-3-methoxy-5-methyl mandelate is subjected to oxidation reaction under the action of an oxidation catalyst, and then the 5-methyl vanillin is obtained after acidification.
The reaction process is as follows:
further, in step 1), the hydrogenation catalyst comprises (5.0 wt% -10.0 wt%) Pd/C catalyst, (10 wt%) Rh/C catalyst, (10 wt%) Ru/C catalyst or PtO2One kind of catalyst.
Further, in the step 1), in the hydrogenation reduction reaction process, the hydrogen pressure is 1.0-4.0 MPa (preferably 2.0-2.5 MPa), the reaction temperature is 100.0-180.0 ℃, and the reaction time is 5.0-10.0 h (preferably 6.0-8.0 h). The hydrogenation reduction reaction process is carried out in an autoclave.
Further, in the step 1), the mass ratio of the o-vanillin to the hydrogenation catalyst is 100.0 (1.0-8.0).
Further, in the step 2), alkaline conditions are obtained by adding alkali, wherein the alkali comprises one of sodium hydroxide or potassium hydroxide; in the alkaline condition, the pH value is 10.0-14.0. The alkali is preferably alkali solution with the mass concentration of 20.0-50.0%.
Further, in the step 2), in the condensation reaction process, the reaction temperature is 15.0-50.0 ℃, and the reaction time is 10.0-20.0 h.
In step 2), the molar ratio of the 6-methyl guaiacol to the glyoxylic acid is 1.0 (1.0-1.2).
Further, in step 3), the oxidation catalyst includes one of a CuO catalyst, a NiO catalyst, or a CoO catalyst. The oxidation catalyst is preferably a metal oxide catalyst.
Further, in the step 3), in the oxidation reaction process, the reaction temperature is 70.0-100.0 ℃, the reaction time is 4.0-8.0 hours (preferably 6 hours), the oxygen pressure is 0.10-0.20 MPa (preferably 0.15MPa), the pH value of the reaction system is 10.0-14.0, and the mass ratio (4.0-12.0) of the oxidation catalyst to the 4-hydroxy-3-methoxy-5-methyl mandelate is 100.0.
Further, in the step 3), after the oxidation reaction, acidifying until the pH value is 3-4.
Compared with the prior art, the invention has the following characteristics:
1) ortho-vanillin is adopted as a raw material, and is a byproduct for synthesizing vanillin, so that the raw material is easy to obtain.
2) The catalytic hydrogenation and catalytic oxidation technologies are adopted, so that the three wastes are less, and the method is beneficial to environmental protection.
3) The adopted catalysts are common catalysts with mature markets, and are beneficial to product industrialization.
4) The product is easy to purify and has high yield.
Detailed Description
The present invention will be described in detail with reference to specific examples. The present embodiment is implemented on the premise of the technical solution of the present invention, and a detailed implementation manner and a specific operation process are given, but the scope of the present invention is not limited to the following embodiments.
Reaction 1) example:
example 1:
a1 liter autoclave was charged with 100.0g (0.66mol) of o-vanillin, 350ml of ethyl acetate, and 6.0g of 10% palladium on charcoal. Starting stirring for 400rmp, replacing air in the kettle with nitrogen, replacing the nitrogen with hydrogen, maintaining the pressure of the hydrogen at 2.0-2.5 MPa, and reacting for 6-8 h at 140 ℃. After the reaction is finished, the palladium-carbon is filtered out, the solvent is recovered, and the 6-methyl guaiacol 89.4g (with the content of 99.8%) is obtained by reduced pressure distillation with the yield of 98.0%.
MS(EI)，m/s，138(M+,89)，123.1(100)，95.2(19)，77.2(22)，67(13)，65(10)，39.2(9)。
1HNMR(500MHz,CDCI3)，2.66(3H,s,CH3)，3.88(3H,s,OCH3)，5.68(1H,s,OH)，6.70-6.78(3H,m,ArH)。
Example 2:
a1 liter autoclave was charged with 100.0g (0.66mol) of o-vanillin, 350ml of ethyl acetate, and 7.0g of 10% palladium on charcoal. Starting stirring for 400rmp, replacing air in the kettle with nitrogen, replacing the nitrogen with hydrogen, maintaining the pressure of the hydrogen at 2.0-2.5 MPa, and reacting for 6-8 h at 140 ℃. After the reaction is finished, the palladium-carbon is filtered out, the solvent is recovered, and the 6-methyl guaiacol 89.6g (with the content of 99.8%) is obtained by reduced pressure distillation with the yield of 98.2%.
Example 3:
a1 liter autoclave was charged with 100.0g (0.66mol) of o-vanillin, 350ml of ethyl acetate, and 5.0g of 10% palladium on charcoal. Starting stirring for 400rmp, replacing air in the kettle with nitrogen, replacing the nitrogen with hydrogen, maintaining the pressure of the hydrogen at 2.0-2.5 MPa, and reacting for 6-8 h at 140 ℃. After the reaction, the palladium-carbon is filtered out, the solvent is recovered, and 86.7g (with the content of 99.8%) of 6-methyl guaiacol is obtained by reduced pressure distillation with the yield of 95.0%.
Example 4:
a1 liter autoclave was charged with 100.0g (0.66mol) of o-vanillin, 350ml of ethyl acetate, and 6.0g of 10% palladium on charcoal. Starting stirring for 400rmp, replacing air in the kettle with nitrogen, replacing the nitrogen with hydrogen, maintaining the pressure of the hydrogen at 2.0-2.5 MPa, and reacting for 6-8 h at 130 ℃. After the reaction, the palladium-carbon is filtered out, the solvent is recovered, and the 6-methyl guaiacol is obtained by reduced pressure distillation, wherein the 6-methyl guaiacol is 77.6g (the content is 99.8 percent), and the yield is 85.0 percent.
Example 5:
a1 liter autoclave was charged with 100.0g (0.66mol) of o-vanillin, 350ml of ethyl acetate, and 6.0g of 10% palladium on charcoal. Starting stirring for 400rmp, replacing air in the kettle with nitrogen, replacing the nitrogen with hydrogen, maintaining the pressure of the hydrogen at 2.0-2.5 MPa, and reacting for 6-8 h at 150 ℃. After the reaction, the palladium-carbon is filtered out, the solvent is recovered, and the 6-methyl guaiacol 68.9g (with the content of 99.8%) is obtained by reduced pressure distillation with the yield of 75.5%.
Example 6:
a1 liter autoclave was charged with 100.0g (0.66mol) of o-vanillin, 350ml of ethyl acetate, and 6.0g of 10% palladium on charcoal. Starting stirring for 400rmp, replacing air in the kettle with nitrogen, replacing the nitrogen with hydrogen, maintaining the pressure of the hydrogen at 2.0-2.5 MPa, and reacting for 6-8 h at 140 ℃. After the reaction is finished, the palladium-carbon is filtered out, the solvent is recovered, and the 6-methyl guaiacol 89.2g (with the content of 99.8%) is obtained by reduced pressure distillation with the yield of 97.7%.
Example 7:
a1 liter autoclave was charged with 100.0g (0.66mol) of o-vanillin, 350ml of ethyl acetate, and 10% Rh/C6.0 g. Starting stirring for 400rmp, replacing air in the kettle with nitrogen, replacing the nitrogen with hydrogen, maintaining the pressure of the hydrogen at 2.0-2.5 MPa, and reacting for 6-8 h at 140 ℃. After the reaction, Rh/C was filtered out, the solvent was recovered, and 6-methyl guaiacol 82.1g (content: 99.8%) was obtained by distillation under reduced pressure with a yield of 90.1%.
Reaction 2) example:
example 8:
55.2g (0.40mol) of 6-methyl guaiacol was added to a reaction flask 1, 80.0g of a 20% aqueous solution of sodium hydroxide was added thereto and dissolved therein, and 62.2g (50% w/w, 0.42mol) of glyoxylic acid and 80.0g of an 20% aqueous solution of sodium hydroxide were added to a reaction flask 2; the reaction solution in the two reaction bottles was combined, and 41.6g of 20% aqueous sodium hydroxide solution was added thereto until the reaction system had a pH of 12.0. The reaction is carried out for 12h at the temperature of 30 ℃. The total amount of the reaction mixture was 319.0g, and by liquid phase analysis, 4-hydroxy-3-methoxy-5-methylmandelate was 20.8%, yield was 84.6%.
Example 9:
55.2g (0.40mol) of 6-methyl guaiacol was added to a reaction flask 1, 80.0g of a 20% aqueous solution of sodium hydroxide was added thereto and dissolved therein, and 62.2g (50% w/w, 0.42mol) of glyoxylic acid and 80.0g of an 20% aqueous solution of sodium hydroxide were added to a reaction flask 2; the reaction solution in the two reaction bottles was combined, and 84.0g of 20% aqueous sodium hydroxide solution was added to the reaction system until the pH was 13.0. The reaction is carried out for 12h at the temperature of 30 ℃. The total amount of the reaction mixture was 361.4g, and by liquid phase analysis, 4-hydroxy-3-methoxy-5-methylmandelate was 21.4% with a yield of 98.7%.
Example 10:
55.2g (0.40mol) of 6-methyl guaiacol was added to a reaction flask 1, 80.0g of a 20% aqueous solution of sodium hydroxide was added thereto and dissolved therein, and 62.2g (50% w/w, 0.42mol) of glyoxylic acid and 80.0g of an 20% aqueous solution of sodium hydroxide were added to a reaction flask 2; the reaction solution in the two reaction bottles was combined, and 105.6g of 20% aqueous sodium hydroxide solution was added thereto until the reaction system had a pH of 14.0. The reaction is carried out for 12h at the temperature of 30 ℃. The total amount of the reaction mixture was 383.0g, and by liquid phase analysis, 4-hydroxy-3-methoxy-5-methyl mandelate was 18.1%, yield was 88.4%.
Example 11:
55.2g (0.40mol) of 6-methyl guaiacol was added to a reaction flask 1, 80.0g of a 20% aqueous solution of sodium hydroxide was added thereto and dissolved therein, and 62.2g (50% w/w, 0.42mol) of glyoxylic acid and 80.0g of an 20% aqueous solution of sodium hydroxide were added to a reaction flask 2; the reaction solution in the two reaction bottles was combined, and 25.6g of 20% aqueous sodium hydroxide solution was added thereto until the reaction system had a pH of 11.0. The reaction is carried out for 12h at the temperature of 30 ℃. The total amount of the reaction mixture was 303.0g, and by liquid phase analysis, 4-hydroxy-3-methoxy-5-methylmandelate was 20.3%, yield was 78.5%.
Example 12:
55.2g (0.40mol) of 6-methyl guaiacol was added to a reaction flask 1, 80.0g of a 20% aqueous solution of sodium hydroxide was added thereto and dissolved therein, and 62.2g (50% w/w, 0.42mol) of glyoxylic acid and 80.0g of an 20% aqueous solution of sodium hydroxide were added to a reaction flask 2; the reaction solution in the two reaction bottles was combined, and 84.0g of 20% aqueous sodium hydroxide solution was added to the reaction system until the pH was 13.0. The reaction is carried out for 12h at 35 ℃. The total amount of the reaction mixture was 361.4g, and by liquid phase analysis, 4-hydroxy-3-methoxy-5-methylmandelate was 21.4% with a yield of 98.5%.
Example 13:
55.2g (0.40mol) of 6-methyl guaiacol was added to a reaction flask 1, 80.0g of a 20% aqueous solution of sodium hydroxide was added thereto and dissolved therein, and 62.2g (50% w/w, 0.42mol) of glyoxylic acid and 80.0g of an 20% aqueous solution of sodium hydroxide were added to a reaction flask 2; the reaction solution in the two reaction bottles was combined, and 84.0g of 20% aqueous sodium hydroxide solution was added to the reaction system until the pH was 13.0. The reaction is carried out for 12h at the temperature of 25 ℃. The total amount of the reaction mixture was 361.4g, and by liquid phase analysis, 4-hydroxy-3-methoxy-5-methylmandelate was 19.7%, yield 90.6%.
Example 14:
55.2g (0.40mol) of 6-methyl guaiacol was added to a reaction flask 1, 80.0g of a 20% aqueous solution of sodium hydroxide was added thereto and dissolved therein, and 59.2g (50% w/w, 0.40mol) of glyoxylic acid and 80.0g of an 20% aqueous solution of sodium hydroxide were added to a reaction flask 2; the reaction solution in the two reaction bottles was combined, and 84.0g of 20% aqueous sodium hydroxide solution was added to the reaction system until the pH was 13.0. The reaction is carried out for 12h at the temperature of 30 ℃. The total amount of the reaction mixture was 358.4g, and by liquid phase analysis, 4-hydroxy-3-methoxy-5-methylmandelate was 20.9% with a yield of 95.6%.
Example 15:
55.2g (0.40mol) of 6-methyl guaiacol was added to a reaction flask 1, 80.0g of a 20% aqueous solution of sodium hydroxide was added thereto and dissolved therein, and 62.2g (50% w/w, 0.42mol) of glyoxylic acid and 80.0g of an 20% aqueous solution of sodium hydroxide were added to a reaction flask 2; the reaction solution in the two reaction bottles was combined, and 84.0g of 20% aqueous sodium hydroxide solution was added to the reaction system until the pH was 13.0. The reaction is carried out for 10h at the temperature of 30 ℃. The total amount of the reaction mixture was 361.4g, and by liquid phase analysis, 4-hydroxy-3-methoxy-5-methylmandelate was 20.6% with a yield of 94.8%.
Example 16:
55.2g (0.40mol) of 6-methyl guaiacol was added to a reaction flask 1, 80.0g of a 20% aqueous solution of sodium hydroxide was added thereto and dissolved therein, and 62.2g (50% w/w, 0.42mol) of glyoxylic acid and 80.0g of an 20% aqueous solution of sodium hydroxide were added to a reaction flask 2; the reaction solution in the two reaction bottles was combined, and 84.0g of 20% aqueous sodium hydroxide solution was added to the reaction system until the pH was 13.0. The reaction is carried out for 14h at 30 ℃. The total amount of the reaction mixture was 361.4g, and by liquid phase analysis, 4-hydroxy-3-methoxy-5-methylmandelate was 21.4% with a yield of 98.7%.
Reaction 3) example:
example 17:
361.4g of the reaction mixture (containing 77.34g of 4-hydroxy-3-methoxy-5-methyl mandelate) synthesized in example 9 and 6.2g of CuO as a catalyst were charged into a 1 liter autoclave. Stirring is started to 400rmp, the air in the kettle is replaced by nitrogen, then the nitrogen is replaced by oxygen, the oxygen pressure is maintained at 0.15MPa, and the reaction is carried out for 6h at the temperature of 80 ℃. After the reaction is finished, filtering out the catalyst, acidifying the reaction solution by using 50% sulfuric acid water solution until the pH value is 3-4, and extracting by using chloroform; chloroform was recovered and distilled to obtain 57.7g (content: 99.5%) of 5-methyl vanillin with a yield of 87.5%.
mp:99.0-100.0℃；1HNMR(500MHz,CDCI3)，9.79(1H,s,CHO)，7.28-7.30(2H,m,ArH)，6.27(1H,s,OH)，3.95(3H,s,OCH3)，2.32(3H,s,CH3)。
Example 18:
361.4g of the reaction mixture (containing 77.34g of 4-hydroxy-3-methoxy-5-methyl mandelate) synthesized in example 9 and 6.2g of CuO as a catalyst were charged into a 1 liter autoclave, and then an appropriate amount of sulfuric acid was added to adjust the pH of the reaction system to 12.0. Stirring is started to 400rmp, the air in the kettle is replaced by nitrogen, then the nitrogen is replaced by oxygen, the oxygen pressure is maintained at 0.15MPa, and the reaction is carried out for 6h at the temperature of 80 ℃. After the reaction is finished, filtering out the catalyst, acidifying the reaction solution by using 50% sulfuric acid water solution until the pH value is 3-4, and extracting by using chloroform; chloroform was recovered and distilled to obtain 61.2g (content: 99.5%) of 5-methyl vanillin with a yield of 92.8%.
Example 19:
361.4g of the reaction mixture (containing 77.34g of 4-hydroxy-3-methoxy-5-methyl mandelate) synthesized in example 9 and 6.2g of CuO as a catalyst were charged into a 1 liter autoclave, and then an appropriate amount of sulfuric acid was added to adjust the pH of the reaction system to 11.0. Stirring is started to 400rmp, the air in the kettle is replaced by nitrogen, then the nitrogen is replaced by oxygen, the oxygen pressure is maintained at 0.15MPa, and the reaction is carried out for 6h at the temperature of 80 ℃. After the reaction is finished, filtering out the catalyst, acidifying the reaction solution by using 50% sulfuric acid water solution until the pH value is 3-4, and extracting by using chloroform; the chloroform was recovered and distilled to obtain 54.4g (content: 99.5%) of 5-methyl vanillin with a yield of 82.5%.
Example 20:
361.4g of the reaction mixture (containing 77.34g of 4-hydroxy-3-methoxy-5-methyl mandelate) synthesized in example 9 and 7.7g of CuO as a catalyst were charged into a 1 liter autoclave, and then an appropriate amount of sulfuric acid was added to adjust the pH of the reaction system to 12.0. Stirring is started to 400rmp, the air in the kettle is replaced by nitrogen, then the nitrogen is replaced by oxygen, the oxygen pressure is maintained at 0.15MPa, and the reaction is carried out for 6h at the temperature of 80 ℃. After the reaction is finished, filtering out the catalyst, acidifying the reaction solution by using 50% sulfuric acid water solution until the pH value is 3-4, and extracting by using chloroform; chloroform was recovered and distilled to obtain 61.3g (content: 99.5%) of 5-methyl vanillin with a yield of 93.0%.
Example 21:
361.4g of the reaction mixture (containing 77.34g of 4-hydroxy-3-methoxy-5-methyl mandelate) synthesized in example 9 and 4.6g of CuO as a catalyst were charged into a 1 liter autoclave, and then an appropriate amount of sulfuric acid was added to adjust the pH of the reaction system to 12.0. Stirring is started to 400rmp, the air in the kettle is replaced by nitrogen, then the nitrogen is replaced by oxygen, the oxygen pressure is maintained at 0.15MPa, and the reaction is carried out for 6h at the temperature of 80 ℃. After the reaction is finished, filtering out the catalyst, acidifying the reaction solution by using 50% sulfuric acid water solution until the pH value is 3-4, and extracting by using chloroform; chloroform was recovered and distilled to obtain 53.9g (content: 99.5%) of 5-methyl vanillin with a yield of 81.8%.
Example 22:
361.4g of the reaction mixture (containing 77.34g of 4-hydroxy-3-methoxy-5-methyl mandelate) synthesized in example 9 and 6.2g of CuO as a catalyst were charged into a 1 liter autoclave, and then an appropriate amount of sulfuric acid was added to adjust the pH of the reaction system to 12.0. Stirring is started to 400rmp, the air in the kettle is replaced by nitrogen, then the nitrogen is replaced by oxygen, the oxygen pressure is maintained at 0.15MPa, and the reaction is carried out for 6h at the temperature of 75 ℃. After the reaction is finished, filtering out the catalyst, acidifying the reaction solution by using 50% sulfuric acid water solution until the pH value is 3-4, and extracting by using chloroform; chloroform was recovered and distilled to obtain 56.7g (content: 99.5%) of 5-methyl vanillin with a yield of 86.1%.
Example 23:
361.4g of the reaction mixture (containing 77.34g of 4-hydroxy-3-methoxy-5-methyl mandelate) synthesized in example 9 and 6.2g of CuO as a catalyst were charged into a 1 liter autoclave, and then an appropriate amount of sulfuric acid was added to adjust the pH of the reaction system to 12.0. Stirring is started to 400rmp, the air in the kettle is replaced by nitrogen, then the nitrogen is replaced by oxygen, the oxygen pressure is maintained at 0.15MPa, and the reaction is carried out for 6h at 85 ℃. After the reaction is finished, filtering out the catalyst, acidifying the reaction solution by using 50% sulfuric acid water solution until the pH value is 3-4, and extracting by using chloroform; chloroform was recovered and distilled to obtain 57.0g (content: 99.5%) of 5-methyl vanillin with a yield of 86.5%.
Example 24:
361.4g of the reaction mixture (containing 77.34g of 4-hydroxy-3-methoxy-5-methyl mandelate) synthesized in example 9 and 6.2g of CoO as a catalyst were charged into a 1 liter autoclave, and then an appropriate sulfuric acid was added to adjust the pH of the reaction system to 12.0. Stirring is started to 400rmp, the air in the kettle is replaced by nitrogen, then the nitrogen is replaced by oxygen, the oxygen pressure is maintained at 0.15MPa, and the reaction is carried out for 6h at the temperature of 80 ℃. After the reaction is finished, filtering out the catalyst, acidifying the reaction solution by using 50% sulfuric acid water solution until the pH value is 3-4, and extracting by using chloroform; chloroform was recovered and distilled to obtain 53.1g (content: 99.5%) of 5-methyl vanillin with a yield of 80.6%.
Example 25:
361.4g of the reaction mixture (containing 77.34g of 4-hydroxy-3-methoxy-5-methyl mandelate) synthesized in example 9 and 6.2g of CuO as a catalyst were charged into a 1 liter autoclave, and then an appropriate amount of sulfuric acid was added to adjust the pH of the reaction system to 12.0. Stirring is started to 400rmp, the air in the kettle is replaced by nitrogen, then the nitrogen is replaced by oxygen, the oxygen pressure is maintained at 0.15MPa, and the reaction is carried out for 6h at the temperature of 80 ℃. After the reaction is finished, filtering out the catalyst, acidifying the reaction solution by using 50% sulfuric acid water solution until the pH value is 3-4, and extracting by using chloroform; the chloroform was recovered and distilled to obtain 60.3g (content: 99.5%) of 5-methyl vanillin with a yield of 91.5%.
In the above embodiments, each reaction parameter may be adjusted according to actual conditions, for example:
in step 1), the hydrogenation catalyst comprises Pd/C catalyst, Rh/C catalyst, Ru/C catalyst or PtO2One kind of catalyst. In the hydrogenation reduction reaction process, the hydrogen pressure is 1.0-4.0 MPa (such as 2MPa and 3MPa), the reaction temperature is 100.0-180.0 ℃ (such as 130 ℃ and 150 ℃), and the reaction time is longIs 5.0 to 10.0 hours (e.g., 7 hours, 9 hours). The mass ratio of the o-vanillin to the hydrogenation catalyst is 100.0 (1.0-8.0) (e.g. 100:3, 100: 6).
In the step 2), alkaline conditions are obtained by adding alkali, wherein the alkali comprises one of sodium hydroxide or potassium hydroxide; the pH value is 10.0-14.0 (for example, 11, 12) under alkaline conditions. In the condensation reaction process, the reaction temperature is 15.0-50.0 ℃ (for example, 25 ℃, 35 ℃) and the reaction time is 10.0-20.0 h (for example, 13h, 18 h). The molar ratio of 6-methyl guaiacol to glyoxylic acid is 1.0 (1.0-1.2) (e.g., 1: 1.1).
In step 3), the oxidation catalyst comprises one of a CuO catalyst, a NiO catalyst, or a CoO catalyst. In the oxidation reaction process, the reaction temperature is 70.0-100.0 ℃ (for example, 75 ℃, 85 ℃), the reaction time is 4.0-8.0 h (for example, 5h, 7h), the oxygen pressure is 0.10-0.20 MPa (for example, 0.12MPa, 0.18MPa), the pH value of the reaction system is 10.0-14.0 (for example, 12, 13), and the mass ratio of the oxidation catalyst to the 4-hydroxy-3-methoxy-5-methyl mandelate (4.0-12.0) is 100.0 (for example, 6:100, 9: 100). And after the oxidation reaction, acidifying until the pH value is 3-4.
The embodiments described above are described to facilitate an understanding and use of the invention by those skilled in the art. It will be readily apparent to those skilled in the art that various modifications to these embodiments may be made, and the generic principles described herein may be applied to other embodiments without the use of the inventive faculty. Therefore, the present invention is not limited to the above embodiments, and those skilled in the art should make improvements and modifications within the scope of the present invention based on the disclosure of the present invention.
Claims (10)
1. A preparation method of 5-methyl vanillin is characterized by comprising the following steps:
1) taking ortho-vanillin as a raw material, and carrying out hydrogenation reduction reaction under the action of a hydrogenation catalyst to obtain 6-methyl guaiacol;
2) carrying out condensation reaction on 6-methyl guaiacol and glyoxylic acid under an alkaline condition to obtain 4-hydroxy-3-methoxy-5-methyl mandelate;
3) 4-hydroxy-3-methoxy-5-methyl mandelate is subjected to oxidation reaction under the action of an oxidation catalyst, and then the 5-methyl vanillin is obtained after acidification.
2. The method as claimed in claim 1, wherein the hydrogenation catalyst in step 1) comprises Pd/C catalyst, Rh/C catalyst, Ru/C catalyst or PtO2One kind of catalyst.
3. The preparation method of 5-methyl vanillin according to claim 1, wherein in the step 1), the hydrogen pressure is 1.0-4.0 MPa, the reaction temperature is 100.0-180.0 ℃, and the reaction time is 5.0-10.0 h in the hydrogenation reduction process.
4. The preparation method of 5-methyl vanillin according to claim 1, wherein in the step 1), the mass ratio of the ortho-vanillin to the hydrogenation catalyst is 100.0 (1.0-8.0).
5. The method for preparing 5-methyl vanillin of claim 1, wherein in the step 2), the alkaline condition is obtained by adding an alkali, wherein the alkali comprises one of sodium hydroxide or potassium hydroxide; in the alkaline condition, the pH value is 10.0-14.0.
6. The preparation method of 5-methyl vanillin according to claim 1, wherein in the step 2), the reaction temperature is 15.0-50.0 ℃ and the reaction time is 10.0-20.0 h in the condensation reaction process.
7. The method for preparing 5-methyl vanillin according to claim 1, wherein in the step 2), the molar ratio of the 6-methyl guaiacol to the glyoxylic acid is 1.0 (1.0-1.2).
8. The method as claimed in claim 1, wherein the oxidation catalyst in step 3) comprises one of a CuO catalyst, a NiO catalyst or a CoO catalyst.
9. The preparation method of 5-methyl vanillin of claim 1, wherein in the step 3), in the oxidation reaction process, the reaction temperature is 70.0-100.0 ℃, the reaction time is 4.0-8.0 h, the oxygen pressure is 0.10-0.20 MPa, the pH value of the reaction system is 10.0-14.0, and the mass ratio of the oxidation catalyst to the 4-hydroxy-3-methoxy-5-methyl mandelate (4.0-12.0): 100.0.
10. The method for preparing 5-methyl vanillin according to claim 1, wherein in the step 3), the solution is acidified to a pH value of 3-4 after the oxidation reaction.
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| CN104447254A (en) * | 2014-10-14 | 2015-03-25 | 上海应用技术学院 | Method for preparing 3-methoxy-4-hydroxybenzaldehyde |
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| CN104447254A (en) * | 2014-10-14 | 2015-03-25 | 上海应用技术学院 | Method for preparing 3-methoxy-4-hydroxybenzaldehyde |
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