CN117886717A - Method for preparing 3, 4-dihydroxybenzonitrile - Google Patents
Method for preparing 3, 4-dihydroxybenzonitrile Download PDFInfo
- Publication number
- CN117886717A CN117886717A CN202311838182.5A CN202311838182A CN117886717A CN 117886717 A CN117886717 A CN 117886717A CN 202311838182 A CN202311838182 A CN 202311838182A CN 117886717 A CN117886717 A CN 117886717A
- Authority
- CN
- China
- Prior art keywords
- aprotic solvent
- dihydroxybenzonitrile
- mass ratio
- reaction
- vanillin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 52
- NUWHYWYSMAPBHK-UHFFFAOYSA-N 3,4-dihydroxybenzonitrile Chemical compound OC1=CC=C(C#N)C=C1O NUWHYWYSMAPBHK-UHFFFAOYSA-N 0.000 title claims abstract description 36
- IBGBGRVKPALMCQ-UHFFFAOYSA-N 3,4-dihydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1O IBGBGRVKPALMCQ-UHFFFAOYSA-N 0.000 claims abstract description 52
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims abstract description 28
- 229960003371 protocatechualdehyde Drugs 0.000 claims abstract description 26
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 claims abstract description 26
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 claims abstract description 26
- 235000012141 vanillin Nutrition 0.000 claims abstract description 26
- 239000000010 aprotic solvent Substances 0.000 claims abstract description 22
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 8
- 230000001335 demethylating effect Effects 0.000 claims abstract description 8
- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- 238000006243 chemical reaction Methods 0.000 claims description 33
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 12
- 239000012074 organic phase Substances 0.000 claims description 12
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical group Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 11
- 230000008569 process Effects 0.000 claims description 9
- 239000012649 demethylating agent Substances 0.000 claims description 8
- 239000003960 organic solvent Substances 0.000 claims description 8
- 239000011780 sodium chloride Substances 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 4
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 238000010791 quenching Methods 0.000 claims description 4
- 230000000171 quenching effect Effects 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 4
- 239000000706 filtrate Substances 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 239000011592 zinc chloride Substances 0.000 claims description 2
- 235000005074 zinc chloride Nutrition 0.000 claims description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 abstract description 14
- 239000002994 raw material Substances 0.000 abstract description 14
- 239000003814 drug Substances 0.000 abstract description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 abstract description 7
- 230000009286 beneficial effect Effects 0.000 abstract description 6
- 239000000543 intermediate Substances 0.000 abstract description 6
- 229940079593 drug Drugs 0.000 abstract description 4
- 238000009776 industrial production Methods 0.000 abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 238000011112 process operation Methods 0.000 abstract description 2
- 231100000331 toxic Toxicity 0.000 abstract description 2
- 230000002588 toxic effect Effects 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 9
- 239000007858 starting material Substances 0.000 description 6
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 4
- 239000007810 chemical reaction solvent Substances 0.000 description 4
- SATCULPHIDQDRE-UHFFFAOYSA-N piperonal Chemical compound O=CC1=CC=C2OCOC2=C1 SATCULPHIDQDRE-UHFFFAOYSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 229910018516 Al—O Inorganic materials 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 150000008359 benzonitriles Chemical class 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000005265 energy consumption Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 229940081310 piperonal Drugs 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical group N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
- -1 3, 4-methylene benzonitrile Chemical compound 0.000 description 1
- GNWREYFHYLIYJE-UHFFFAOYSA-N 3,4-dihydroxybenzamide Chemical compound NC(=O)C1=CC=C(O)C(O)=C1 GNWREYFHYLIYJE-UHFFFAOYSA-N 0.000 description 1
- OSEQIDSFSBWXRE-UHFFFAOYSA-N 3,4-dimethoxybenzonitrile Chemical compound COC1=CC=C(C#N)C=C1OC OSEQIDSFSBWXRE-UHFFFAOYSA-N 0.000 description 1
- QIWQJGMBIABGRX-UHFFFAOYSA-N 4-oxocyclohexane-1-carbonitrile Chemical compound O=C1CCC(C#N)CC1 QIWQJGMBIABGRX-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- DQPBABKTKYNPMH-UHFFFAOYSA-N amino hydrogen sulfate Chemical compound NOS(O)(=O)=O DQPBABKTKYNPMH-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000017858 demethylation Effects 0.000 description 1
- 238000010520 demethylation reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- SQDFHQJTAWCFIB-UHFFFAOYSA-N n-methylidenehydroxylamine Chemical compound ON=C SQDFHQJTAWCFIB-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
Landscapes
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a method for preparing 3, 4-dihydroxybenzonitrile, and belongs to the field of drug synthesis. The method comprises the following steps: (1) Reacting vanillin with a demethylating reagent in an aprotic solvent to obtain protocatechuic aldehyde; (2) Protocatechuic aldehyde and hydroxylamine hydrochloride react in an aprotic solvent to obtain 3, 4-dihydroxybenzonitrile. Compared with the method for preparing 3, 4-dihydroxybenzonitrile in the prior art, the method for preparing 3, 4-dihydroxybenzonitrile has the following beneficial effects: (1) The invention solves the problem that the raw materials or intermediates are supervision products and highly toxic products; (2) The raw materials adopted by the invention are wide in sources, cheap and easy to obtain, so that the use of raw materials with expensive pyridine equivalent grids is avoided, and the production cost is reduced; (3) The method has simple and convenient process operation and controllable cost, and is more suitable for industrial production.
Description
Technical Field
The invention belongs to the field of medicine synthesis, and in particular relates to a method for preparing 3, 4-dihydroxybenzonitrile by taking vanillin as a starting material.
Background
The 3, 4-dihydroxybenzonitrile is an important intermediate of medicines and pesticides, and is widely applied to industries such as pesticides, medicines, dyes and the like. The 3, 4-dihydroxybenzonitrile is mainly used for synthesizing medicaments containing thiazole, 2-oxazoline, imidazole, triazole and benzopyrimidine structures, such as quinazoline medicaments for resisting cancer. In addition, in recent years, 3, 4-dihydroxybenzonitrile has also been used for the synthesis of photosensitive materials.
At present, the method for synthesizing 3, 4-dihydroxybenzonitrile mainly comprises the following steps:
(1) Vanillin or 3, 4-dimethoxy benzonitrile is used as a starting material, and reacts with hydroxylamine hydrochloride to form oxime in one step, the oxime is dehydrated at a high temperature to obtain substituted benzonitrile, and the substituted benzonitrile is subjected to lithium bromide demethylation to obtain a target product. The method has higher reaction temperature and longer reaction time, and is not beneficial to industrialization.
(2) Piperonal is used as a starting material or an intermediate, and reacts with hydroxylamine hydrochloride to obtain 3, 4-methylene benzonitrile, and then methylene protection is carried out by aluminum trichloride or hydrochloric acid to obtain a target product. However, the piperonal as the raw material belongs to a first type of chemicals easy to poison, and is not beneficial to industrialization.
(3) The 3, 4-dihydroxybenzonitrile is synthesized by one step by taking 4-oxo-cyclohexane carbonitrile as a starting material and elemental iodine as an oxidant. The method has higher yield, but the price of the initial material and the simple substance iodine is expensive, which is not beneficial to industrialization.
(4) 3, 4-Dihydroxybenzamide is taken as a starting material, and a target product is obtained through dehydration reaction with thionyl chloride. The method has mature process conditions, is relatively suitable for industrialization, but has high raw material price and is not beneficial to the industrialization.
(5) Literature (reaction research of synthesizing protocatechuic aldehyde and 3, 4-dihydroxybenzonitrile by vanillin, zhou Huahua and the like, university of Hebei industry, 2011) also reports that under the action of AlCl 3 and pyridine, alCl 3 firstly attacks phenolic hydroxyl groups in vanillin and forms an Al-O coordination bond with the phenolic hydroxyl groups, pyridine attacks-OCH 3 and forms a five-membered ring coordination bond with Al-O on the ortho position of a benzene ring, so that the strength of the O-CH 3 bond is weakened, H + can attack O-CH 3 to remove-CH 3, and protocatechuic aldehyde is prepared by hydrolysis; then the protocatechuic aldehyde reacts with hydroxylamine-O-sulfonic acid to prepare the 3, 4-dihydroxybenzonitrile. The method shortens the reaction time, improves the production efficiency and reduces the energy consumption. However, the method adopts pyridine with the equivalent weight of 3.2-10 times when preparing protocatechuic aldehyde, the pyridine is expensive, the production cost is increased, and the industrialization is not facilitated.
It can be seen that the method for preparing 3, 4-dihydroxybenzonitrile in the prior art has the problems of difficult raw material source, high price, complex process and the like due to the use of supervision products and drastic drugs as raw materials or intermediates, and is not suitable for industrial production.
Disclosure of Invention
In order to overcome the above problems of the prior art, the present invention aims to provide a novel process for preparing 3, 4-dihydroxybenzonitrile.
The invention provides a method for preparing 3, 4-dihydroxybenzonitrile, which comprises the following steps:
(1) Reacting vanillin with a demethylating reagent in an aprotic solvent to obtain protocatechuic aldehyde;
(2) Protocatechuic aldehyde and hydroxylamine hydrochloride react in an aprotic solvent to obtain 3, 4-dihydroxybenzonitrile.
Further, in the step (1), the aprotic solvent is dichloromethane, dichloroethane, N-dimethylformamide, N-dimethylacetamide or acetonitrile, and the mass ratio of vanillin to aprotic solvent is 1: (1-5) g/mL; in the step (2), the aprotic solvent is dichloromethane, dichloroethane, N-dimethylformamide, N-dimethylacetamide or acetonitrile, and the mass ratio of protocatechuic aldehyde to aprotic solvent is 1: (1-5) g/mL.
Further, in the step (1), the aprotic solvent is N, N-dimethylacetamide, and the mass ratio of vanillin to aprotic solvent is 1:3g/mL; in the step (2), the aprotic solvent is N, N-dimethylacetamide, and the mass ratio of protocatechuic aldehyde to the aprotic solvent is 1:3g/mL.
Further, in step (1), the demethylating agent is aluminum trichloride, zinc chloride, or hydrobromic acid; the mass ratio of the demethylating reagent to the vanillin is 1: (0.8-2.5).
Further, in the step (1), the demethylating agent is aluminum trichloride; the mass ratio of the demethylating reagent to the vanillin is 1: (1.2-1.4).
Further, in the step (1), the temperature of the reaction is 80-140 ℃ and the time is 4-12 hours; in the step (2), the temperature of the reaction is 80-140 ℃ and the time is 7-15 hours.
Further, in the step (1), the temperature of the reaction is 100 ℃ and the time is 6 hours; in the step (2), the temperature of the reaction is 100 ℃ and the time is 9 hours.
Further, in the step (2), the mass ratio of the hydroxylamine hydrochloride to the protocatechuic aldehyde is (0.5-0.8): 1.
Further, in the step (2), the mass ratio of the hydroxylamine hydrochloride to the protocatechuic aldehyde is 0.6:1.
Further, in the step (1), after the reaction is finished, the method further comprises the following post-treatment steps: quenching with dilute hydrochloric acid, extracting with organic solvent, washing the organic phase with sodium chloride aqueous solution, collecting the organic phase, and concentrating; the organic solvent is preferably ethyl acetate;
In the step (2), after the reaction is finished, the method further comprises the following post-treatment steps: quenching with water, extracting with organic solvent, washing the organic phase with sodium chloride aqueous solution, collecting the organic phase, decolorizing with active carbon, filtering, collecting filtrate, and drying; the organic solvent is preferably ethyl acetate.
Compared with the method for preparing 3, 4-dihydroxybenzonitrile in the prior art, the method for preparing 3, 4-dihydroxybenzonitrile has the following beneficial effects:
(1) The invention solves the problem that the raw materials or intermediates are supervision products and highly toxic products.
(2) According to the invention, under the action of aluminum trichloride and N, N-dimethylacetamide, even if pyridine is not adopted, high-yield high-purity protocatechualdehyde can be prepared, and high-yield high-purity 3, 4-dihydroxybenzonitrile can be prepared. The raw materials adopted by the invention are wide in sources, cheap and easy to obtain, so that the use of raw materials with expensive pyridine equivalent grids is avoided, and the production cost is reduced.
(3) The method has simple and convenient process operation and controllable cost, and is more suitable for industrial production.
It should be apparent that, in light of the foregoing, various modifications, substitutions and alterations can be made herein without departing from the spirit and scope of the invention as defined by the appended claims.
The above-described aspects of the present invention will be described in further detail below by way of specific embodiments of the present invention. It should not be construed that the scope of the above subject matter of the present invention is limited to the following examples. All techniques implemented based on the above description of the invention are within the scope of the invention.
Drawings
FIG. 1 is a high performance liquid chromatography of protocatechuic aldehyde obtained in the step (1) of example 1.
FIG. 2 is a high performance liquid chromatography of 3, 4-dihydroxybenzonitrile obtained in step (2) of example 2.
FIG. 3 is a nuclear magnetic resonance spectrum of 3, 4-dihydroxybenzonitrile obtained in step (2) of example 2.
Detailed Description
The raw materials and equipment used in the invention are all known products and are obtained by purchasing commercial products.
The synthetic route of the 3, 4-dihydroxybenzonitrile in the embodiment of the invention is shown as follows:
Example 1 method for preparing 3, 4-dihydroxybenzonitrile
(1) 30G of N, N-dimethylacetamide is added into a 100mL three-neck flask provided with a stirrer and a condensation reflux device at 25+/-10 ℃,12 g of aluminum trichloride solid is slowly added in batches, and stirring is carried out for 5min; 10g of vanillin is slowly added in batches, and the system gradually changes from light yellow suspension to dark purple clear solution; the system was heated to 100 ℃ and stirred for 6h, and tlc detected the starting material was essentially complete and stopped. After cooling to 25 ℃ ± 10 ℃, the system was quenched by pouring into 6% dilute hydrochloric acid, extracted with ethyl acetate (25 g×2), and the organic phase was washed with 50mL aqueous sodium chloride; the organic phase was collected and concentrated to give protocatechuic aldehyde 8.1g in 89% yield and 99% purity. The characterization map is shown in figure 1.
(2) 24G of N, N-dimethylacetamide and 8.1g of protocatechuic aldehyde are added into a 100mL three-neck flask equipped with a stirrer and a condensation reflux device at 25+/-10 ℃, after stirring for 5min, 4.9g of hydroxylamine hydrochloride is added, the temperature is raised to 100 ℃, the stirring reaction is carried out for 9h, the TLC detection raw materials are basically unchanged, and the reaction is stopped. After cooling to 25 ℃ ± 10 ℃, the system was quenched by pouring into 3-fold weight of water, extracted with ethyl acetate (25 g×2), and the organic phase was washed with 50mL of aqueous sodium chloride; collecting organic phase solution, adding 2% of active carbon by mass, heating at 70+/-5 ℃, stirring and decoloring for 1h; the active carbon is filtered while the active carbon is hot, the filtrate is concentrated and dried to obtain 7.05g of white solid (namely 3, 4-dihydroxybenzonitrile), the yield is 89%, and the purity is 99%. The characterization map is shown in figures 2-3.
HNMR(400M,DMSO-d6):δ9.87(s,2H),7.06(dd,J＝8.2,2.1Hz,1H),7.02(d,J＝2.0Hz,1H),6.82(d,J＝8.2Hz,1H).
Examples 2 to 5, methods for preparing 3, 4-dihydroxybenzonitrile
The procedure of example 1 was referred to, except that the reaction solvent of step (1) was changed as in Table 1, and the conversion of vanillin and the yield and purity of protocatechuic aldehyde obtained in step (1) under each process were as shown in Table 1.
TABLE 1 influence of the reaction solvent on the conversion and yield of the vanillin preparation of raw dicarbaldehyde
Note that: in the table "/" indicates poor control and no further treatment was performed to calculate yield or purity.
According to the results of Table 1, the cost and yield of the reaction solvent were combined, and N, N-dimethylacetamide was selected as the optimal reaction solvent.
Examples 6 to 8, methods for preparing 3, 4-dihydroxybenzonitrile
The procedure of example 1 was followed except that the demethylating agent of step (1) was changed as shown in Table 2, and the conversion of vanillin and the yield and purity of protocatechuic aldehyde obtained in step (1) under each process were as shown in Table 2.
TABLE 2 influence of demethylating reagent species on conversion and yield of Vanillin to give raw dicarbaldehyde
Note that: in the table "/" indicates poor centering effect and no further treatment was performed to calculate yield or purity.
According to the results of table 2, the cost and yield of the demethylating agent are combined and aluminum trichloride is selected as the optimal demethylating agent.
Examples 9 to 11, methods for preparing 3, 4-dihydroxybenzonitrile
The procedure of example 1 was referred to, except that the amount of aluminum trichloride used in the step (1) was changed as shown in Table 3, and the conversion of vanillin in the step (1) and the yield and purity of protocatechuic aldehyde obtained in each process were as shown in Table 3.
TABLE 3 influence of the amount of aluminum trichloride on the conversion and yield of the Vanillin preparation to give raw dicarbaldehyde
According to the results of table 3, the cost of the amount of demethylating agent and the yield were combined and aluminum trichloride/vanillin=1.2 w/w was selected as the optimum ratio.
Examples 12 to 14, method for preparing 3, 4-dihydroxybenzonitrile
The procedure of example 1 was referred to, except that the reaction temperature of step (1) was changed as shown in Table 4, and the conversion of vanillin and the yield and purity of protocatechuic aldehyde obtained in step (1) under each process were as shown in Table 4.
TABLE 4 influence of reaction temperature on conversion and yield of Vanillin to give raw dicarbaldehyde
Note that: in the table "/" indicates poor centering effect and no further treatment was performed to calculate yield or purity.
According to the results of Table 4, the reaction temperature energy consumption and conversion were combined, and 100℃was selected as the optimal reaction temperature.
Examples 15 to 17, methods for preparing 3, 4-dihydroxybenzonitrile
The procedure of example 1 was followed except that the amount of hydroxylamine hydrochloride used in step (2) was changed as shown in Table 5, and the conversion of raw dicarbaldehyde in step (2) and the yield and purity of the resulting 3, 4-dihydroxybenzonitrile in each process were as shown in Table 5.
TABLE 5 influence of hydroxylamine hydrochloride consumption on conversion and yield of the reaction of raw Dithealdehyde to 3, 4-dihydroxybenzonitrile
Note that: in the table "/" indicates poor centering effect and no further treatment was performed to calculate yield or purity.
Based on the results of Table 5, the cost and reaction yield were combined and 0.6w/w hydroxylamine hydrochloride/orthodicarbaldehyde was selected as the optimum ratio.
The invention takes vanillin as a raw material, and develops a method for generating 3, 4-dihydroxybenzonitrile by removing methyl and then reacting with hydroxylamine hydrochloride to convert aldehyde groups into cyano groups. The method avoids using or generating raw materials or intermediates of high toxicity and supervision products, and has the advantages of simplicity, convenience, high efficiency, controllable cost and suitability for industrial production to a certain extent.
Claims (10)
1. A process for preparing 3, 4-dihydroxybenzonitrile, comprising the steps of:
(1) Reacting vanillin with a demethylating reagent in an aprotic solvent to obtain protocatechuic aldehyde;
(2) Protocatechuic aldehyde and hydroxylamine hydrochloride react in an aprotic solvent to obtain 3, 4-dihydroxybenzonitrile.
2. The method according to claim 1, wherein in the step (1), the aprotic solvent is dichloromethane, dichloroethane, N-dimethylformamide, N-dimethylacetamide or acetonitrile, and the mass ratio of vanillin to aprotic solvent is 1: (1-5) g/mL; in the step (2), the aprotic solvent is dichloromethane, dichloroethane, N-dimethylformamide, N-dimethylacetamide or acetonitrile, and the mass ratio of protocatechuic aldehyde to aprotic solvent is 1: (1-5) g/mL.
3. The method according to claim 2, wherein in the step (1), the aprotic solvent is N, N-dimethylacetamide, and the mass ratio of vanillin to aprotic solvent is 1:3g/mL; in the step (2), the aprotic solvent is N, N-dimethylacetamide, and the mass ratio of protocatechuic aldehyde to the aprotic solvent is 1:3g/mL.
4. The process of claim 1, wherein in step (1), the demethylating agent is aluminum trichloride, zinc chloride, or hydrobromic acid; the mass ratio of the demethylating reagent to the vanillin is 1: (0.8-2.5).
5. The method of claim 4, wherein in step (1), the demethylating agent is aluminum trichloride; the mass ratio of the demethylating reagent to the vanillin is 1: (1.2-1.4).
6. The process of claim 1, wherein in step (1), the reaction is carried out at a temperature of 80-140 ℃ for a period of 4-12 hours; in the step (2), the temperature of the reaction is 80-140 ℃ and the time is 7-15 hours.
7. The method according to claim 6, wherein in step (1), the temperature of the reaction is 100 ℃ for 6 hours; in the step (2), the temperature of the reaction is 100 ℃ and the time is 9 hours.
8. The method according to claim 1, wherein in the step (2), the mass ratio of hydroxylamine hydrochloride to protocatechuic aldehyde is (0.5 to 0.8): 1.
9. The method according to claim 1, wherein in the step (2), the mass ratio of hydroxylamine hydrochloride to protocatechuic aldehyde is 0.6:1.
10. The method according to any one of claims 1 to 9, wherein in step (1), after the reaction is completed, further comprising the following post-treatment steps: quenching with dilute hydrochloric acid, extracting with organic solvent, washing the organic phase with sodium chloride aqueous solution, collecting the organic phase, and concentrating; the organic solvent is preferably ethyl acetate;
In the step (2), after the reaction is finished, the method further comprises the following post-treatment steps: quenching with water, extracting with organic solvent, washing the organic phase with sodium chloride aqueous solution, collecting the organic phase, decolorizing with active carbon, filtering, collecting filtrate, and drying; the organic solvent is preferably ethyl acetate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311838182.5A CN117886717A (en) | 2023-12-28 | 2023-12-28 | Method for preparing 3, 4-dihydroxybenzonitrile |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311838182.5A CN117886717A (en) | 2023-12-28 | 2023-12-28 | Method for preparing 3, 4-dihydroxybenzonitrile |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117886717A true CN117886717A (en) | 2024-04-16 |
Family
ID=90640686
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311838182.5A Pending CN117886717A (en) | 2023-12-28 | 2023-12-28 | Method for preparing 3, 4-dihydroxybenzonitrile |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117886717A (en) |
-
2023
- 2023-12-28 CN CN202311838182.5A patent/CN117886717A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109053625B (en) | Preparation method of substituted benzothiazole C2 alkylated derivative | |
| CN106632073B (en) | The synthetic method of ionic liquid constant temperature catalyzing 3,4- dihydropyrimidine-2-keto class compound | |
| CN114292231A (en) | 2-methyl-8-substituent-quinoline and preparation method thereof | |
| CN107235891B (en) | Preparation method of 4-bromocarbazole | |
| CN117886717A (en) | Method for preparing 3, 4-dihydroxybenzonitrile | |
| CN109320468B (en) | Method for mild preparation of benzo [ a ] phenazine compound | |
| CN117003727A (en) | Preparation method of 4, 5-dibromo-3-chlorothiophene-2-formic acid | |
| CN114940763B (en) | Metal organic framework material with reversible structure conversion, and preparation method and application thereof | |
| CN110256451B (en) | Synthetic method of benzofuro [2,3-b ] quinoline derivative | |
| CN111905825B (en) | Zinc coordination polymer catalytic material and preparation method and application thereof | |
| CN102050702B (en) | Method for promoting synthesis of resveratrol by micro waves | |
| CN103804187B (en) | Synthesis method of diethylstilbestrol compound pigeon pea ketonic acid A | |
| CN108675999A (en) | A kind of acetic acid copper catalysis preparation 8-（9- sulfoxide group -10- dihydro phenanthrenes）The method of quinoline | |
| CN105713028B (en) | A kind of solid-state phase transfer catalyst, preparation method and application based on Cd MOF | |
| CN113444061A (en) | Synthetic method of mono-substituted or di-substituted furan derivative | |
| CN116813525B (en) | Synthesis method of polyacetyl substituted oxindole compound | |
| CN101148402A (en) | Process for preparing 2-bromofluorenone | |
| CN103012087A (en) | Green synthetic method of alpha, alpha'-double benzylidene cycloalkanone compound | |
| CN103145692A (en) | Preparation method of 4, 5-dihydro-6H-cyclopenta[b]thiophene-6-ketone | |
| CN115322109B (en) | Preparation method of dobutamine hydrochloride suitable for industrial production | |
| CN109824576B (en) | Synthetic method of organic photoelectric material intermediate dimethylindenocarbazole | |
| CN111943939B (en) | Synthesis method of chromanone compound and agricultural biological activity thereof | |
| CN110845511B (en) | Preparation method of 3-benzimidazole-4-arylpyranocoumarin derivative | |
| CN116332889B (en) | Preparation method of 3,3',4' -benzophenone tetracarboxylic dianhydride | |
| CN115286568B (en) | Preparation method of 2-hydroxy-4-trifluoromethyl pyridine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |