CN112939800B - Synthesis method of vanilloylamine - Google Patents

Synthesis method of vanilloylamine Download PDF

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CN112939800B
CN112939800B CN202110178733.4A CN202110178733A CN112939800B CN 112939800 B CN112939800 B CN 112939800B CN 202110178733 A CN202110178733 A CN 202110178733A CN 112939800 B CN112939800 B CN 112939800B
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ferric
indium
vanillylamide
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CN112939800A (en
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陆军
李梦倩
田光进
于锡东
刘辉
左美娟
胡宇航
刘明荣
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Suzhou Huadao Biological Pharmacy Co ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/10—Preparation of carboxylic acid amides from compounds not provided for in groups C07C231/02 - C07C231/08
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Abstract

The invention discloses a synthesis method of vanillylamide, which takes alcohol and vanillylamide as raw materials, or takes aldehyde and vanillylamide as raw materials, takes inorganic ferric salt and inorganic indium salt as composite catalysts, takes oxygen as an oxidant, and generates the vanillylamide by a one-pot reaction in an organic solvent. The synthesis method has the advantages of wide sources of the adopted synthesis raw materials, avoidance of generation of a large amount of chemical reaction wastes in the whole reaction process, cleanness, environmental friendliness, mild and controllable reaction conditions, simplicity in operation, convenience in product separation and purification, high product yield, wide universality of reaction substrates and the like, and is suitable for industrial production.

Description

Synthesis method of vanilloylamine
Technical Field
The invention belongs to the technical field of chemical production, and particularly relates to a synthetic method of vanilloylamine.
Background
Natural capsaicin is an amide compound, mainly present in capsicum; the capsaicinoids can promote adrenal secretion of catecholamine, have antibacterial, anti-tumor, analgesic and anti-inflammatory effects, and can be used as stomachic, to promote gastric secretion, stimulate appetite, promote blood circulation, improve disease resistance of organism, and improve digestion. Most capsaicin substances have the physiological effects of relieving pain, resisting cancer, regulating blood fat, resisting bacteria and inflammation, losing weight, resisting fatigue, relieving pain, relieving itching, resisting inflammation, resisting oxidation, protecting cardiac muscle, regulating blood pressure and the like, can also dilate skin blood vessels and improve microcirculation, and the pungent taste of the capsaicin substances can generate a series of physiological reactions and repelling effects on people and animals; at present, the compounds are widely applied to a plurality of fields such as medical treatment, cosmetology, biological control, food additives, military affairs and the like to realize a plurality of effects; such as:
1) Biochemical pesticide: the capsaicinoids are sprayed on stems, leaves, flowers and fruits of plants, so that aphids, spiders, leaf eating insects, fleas and the like can be effectively driven, and the capsaicinoids are environment-friendly and can meet the requirement of food safety;
2) The clinical analgesic effect is as follows: the capsaicin can effectively treat postherpetic neuralgia, diabetic neuralgia, facial neuralgia, rheumatoid arthritis, skin diseases, etc.;
3) Appetizing and tonifying spleen: the capsaicin has stimulating effect on oral cavity and stomach and intestine, and has effects of enhancing gastrointestinal peristalsis, promoting digestive juice secretion, improving appetite, inhibiting intestinal abnormal fermentation, and eliminating gas accumulated in digestive tract;
4) Health care and beauty treatment: the capsaicinoids can promote fat metabolism, and thus can be used for weight reduction;
5) Functional coating: the capsaicinoids are coated on the hull of the ship to prevent the attachment of seaweed and marine organisms; the coating on the surface of the cable and the wood can prevent mice from gnawing;
6) Military supplies: capsaicinoids are used as starting materials for the manufacture of repellent repellents for tear-gas guns and defense weapons.
The natural capsaicin compounds extracted from the peppers are homologs which have a common structural mother nucleus (shown as a formula (I)), and belong to vanillic amide compounds, and the difference is only that R groups in molecules are different;
Figure BDA0002941525070000021
the natural capsaicin homologous substances extracted from Capsici fructus are more than fourteen kinds, and mainly comprise capsaicin, dihydrocapsaicin, nordihydrocapsaicin, high dihydrocapsaicin, and high capsaicin, wherein the content of capsaicin and dihydrocapsaicin accounts for more than 90% of the total content of the extracted capsaicin. The natural capsaicin extracted from capsicum is a mixture, and each high-purity capsaicin compound is difficult to obtain, and the low-content components are often impossible to obtain through purification. Therefore, each high purity capsaicin compound must be chemically synthesized to meet the needs of research.
The existing chemical synthesis method of capsaicin compounds adopts corresponding carboxylic acid to prepare acyl chloride, and the acyl chloride reacts with vanillyl amine to generate vanillyl amine under the action of an organic or inorganic acid-binding agent;
Figure BDA0002941525070000022
in the synthesis process, the adopted carboxylic acid needs to react with thionyl chloride, phosphorus oxychloride, phosphorus trichloride, phosphorus pentachloride and the like to prepare acyl chloride; this step produces a large amount of acid gas and acid waste water; and also in the amidation reaction, a large amount of waste water and other wastes are generated. Therefore, there is a need for further improved synthetic methods for producing capsaicin compounds.
Disclosure of Invention
In order to solve the technical problems, the invention aims to provide a synthetic method of vanillylamide, which has the advantages of wide sources of adopted synthetic raw materials, avoidance of generation of a large amount of chemical reaction wastes in the whole reaction process, cleanness, environmental friendliness, mild and controllable reaction conditions, simplicity in operation, convenience in product separation and purification, high product yield, wide universality of reaction substrates and the like, and is suitable for industrial production.
In order to achieve the technical purpose and achieve the technical effect, the invention is realized by the following technical scheme:
a method for synthesizing vanillyl amine takes alcohol and vanillyl amine as raw materials, or aldehyde and vanillyl amine as raw materials, inorganic ferric salt and inorganic indium salt as composite catalysts, oxygen as an oxidant, and the vanillyl amine is generated by a one-pot reaction in an organic solvent;
specifically, alcohol or aldehyde and vanillylamine can be selectively oxidized and amidated to generate vanillylamine, and the reaction process of one pot is as follows:
Figure BDA0002941525070000031
in oxygen atmosphere and under the action of iron-indium catalyst, alcohol can be oxidized to generate aldehyde, and the aldehyde and vanillyl amine are subjected to addition reaction to obtain semi-amine acetal intermediate A, and the latter is further subjected to oxidation reaction to generate amide.
Furthermore, the reaction temperature of the synthesis method is 20-80 ℃.
Preferably, the inorganic ferric salt is at least one of ferric chloride, ferric nitrate, ferric sulfate, ferric phosphate, ferric bromide, ferric fluoride, ferric trifluoromethanesulfonate, ferric p-toluenesulfonate and ferric tetrafluoroborate.
Preferably, the inorganic indium salt is at least one of indium trichloride, indium trifluoride, indium tribromide, indium nitrate, indium trifluoromethanesulfonate, indium perchlorate and indium acetate.
Preferably, the organic solvent is at least one of toluene, trifluoromethyl benzene, fluorobenzene, chloroform, dichloromethane, 1, 2-dichloroethane, acetonitrile, nitromethane, tetrahydrofuran and ethylene glycol dimethyl ether.
Further, the alcohol or aldehyde is used in an amount of 100 to 500mol% based on the amount of vanillylamine.
Furthermore, the dosage of the inorganic iron salt is 1 to 10mol percent based on the dosage of the vanillylamine.
Furthermore, the amount of the inorganic indium salt is 1 to 10mol% based on the amount of vanillylamine.
Furthermore, the dosage of the organic solvent is 1-10 mL/mmol based on the dosage of the vanillyl amine.
And further, after the reaction is finished, carrying out suction filtration and washing on the reacted materials, combining organic phases, concentrating to obtain a crude product, and purifying the crude product by column chromatography to obtain a purified vanillic amide product.
The invention has the beneficial effects that:
the invention takes inorganic ferric salt and inorganic indium salt as composite catalysts and oxygen as an oxidant, and the 'one-pot method' generates vanillylamide by the selective catalytic oxidation and amidation of alcohol or aldehyde and vanillylamide. The synthesis method is a one-pot reaction, the reaction conditions are extremely mild, and the reaction can be smoothly carried out at room temperature and in the oxygen atmosphere at normal pressure; the whole reaction process of the invention basically does not generate wastes harmful to the environment, and is a green and environment-friendly chemical synthesis method;
the synthesis method has the advantages of wide sources of the adopted synthesis raw materials, simple operation, convenient product separation and purification, high product yield and wide reaction substrate universality, and can greatly reduce the production and manufacturing cost.
Drawings
FIG. 1 is a NMR spectrum of vanillyl N-9-decanoate (homodihydrocapsaicin) obtained in example 10.
Detailed Description
The technical solutions in the present invention will be described clearly and completely with reference to specific embodiments, and it should be understood that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The synthetic method of vanillyl amide provided by the invention takes alcohol and vanillyl amide as raw materials, or takes aldehyde and vanillyl amide as raw materials, takes inorganic iron salt and inorganic indium salt as composite catalysts, takes oxygen as an oxidant, and generates vanillyl amide in an organic solvent by a one-pot reaction;
specifically, alcohol or aldehyde and vanillylamine can be selectively oxidized and amidated to generate vanillylamine, and the reaction process of one pot is as follows:
Figure BDA0002941525070000051
in oxygen atmosphere and under the action of iron-indium catalyst, alcohol can be oxidized to generate aldehyde, and the aldehyde and vanillyl amine are subjected to addition reaction to obtain semi-amine acetal intermediate A, and the latter is further subjected to oxidation reaction to generate amide.
The reaction temperature of the synthesis method is 20-80 ℃.
In the synthesis method, the inorganic ferric salt is at least one of ferric chloride, ferric nitrate, ferric sulfate, ferric phosphate, ferric bromide, ferric fluoride, ferric trifluoromethanesulfonate, ferric p-toluenesulfonate and ferric tetrafluoroborate.
In the synthesis method, the inorganic indium salt is at least one of indium trichloride, indium trifluoride, indium tribromide, indium nitrate, indium trifluoromethanesulfonate, indium perchlorate and indium acetate.
In the synthesis method, the organic solvent is at least one of toluene, trifluoromethyl benzene, fluorobenzene, chloroform, dichloromethane, 1, 2-dichloroethane, acetonitrile, nitromethane, tetrahydrofuran and ethylene glycol dimethyl ether.
In the synthesis method, the alcohol is one of ethanol, n-propanol, n-butanol, n-pentanol, hexanol, n-heptanol, n-octanol, n-nonanol, 8-methylnonanol, 9-methyldecanol and benzyl alcohol, and the aldehyde is one of propionaldehyde, n-butyraldehyde, n-hexanal, n-heptaldehyde, n-octaldehyde, n-nonanal and benzaldehyde.
In the synthesis method, the dosage of the alcohol or the aldehyde is 100 to 500mol percent based on the dosage of the vanillyl amine.
In the synthesis method, the dosage of the inorganic ferric salt is 1-10 mol% based on the dosage of the vanillylamine.
In the synthesis method, the dosage of the inorganic indium salt is 1-10 mol% based on the dosage of the vanillylamine.
In the synthesis method, the dosage of the organic solvent is 1-10 mL/mm ol based on the dosage of the vanillylamine.
After the reaction of the synthesis method is finished, the reacted materials are subjected to suction filtration and washing, organic phases are combined and concentrated to obtain a crude product, and the crude product is purified by column chromatography to obtain a purified vanilloylamine product.
Example 1: synthesis of vanillyl N-acetate
Figure BDA0002941525070000061
0.24g of ferric nitrate (1 mmol), 0.22g of indium trichloride (1 mmol) and 50mL of trifluoromethylbenzene were added to a Schlenk reaction tube and stirred for 30 minutes; adding 0.69g of ethanol (15 mmol) and 1.53g of vanillylamine (10 mmol), inserting a pure oxygen bag, vacuumizing for 3 times, placing the reaction tube in a constant-temperature oil bath at 30 ℃, and stirring for reaction.
Detecting by TLC until the reaction is completed, performing suction filtration on the reaction liquid through a sand core funnel filled with silica gel, washing with ethyl acetate, combining organic phases, concentrating to obtain a crude product, and purifying the crude product by silica gel column chromatography (eluent is ethyl acetate: petroleum ether = 15); melting point: 82-83 ℃; 1 H NMR(400MHz,CDCl 3 ):δ6.86(d,J＝8.0Hz,1H)，6.81(s,1H)，6.75(d,J＝8.0Hz,1H)，5.66(brs,2H)，4.36(d,J＝5.6Hz,2H)，3.88(s,3H)，2.01(s,3H)。
example 2: n-propionic acid vanillimide
Figure BDA0002941525070000071
The experimental operation is the same as that of example 1, the molar amounts of the reaction raw materials, the catalyst and the organic solvent are the same as those of example 1,the differences are that: the alcohol used in example 2 was n-propanol; the obtained crude product was purified by silica gel column chromatography (ethyl acetate: petroleum ether = 15); melting point: 106 to 108 ℃; 1 H NMR(400MHz,CDCl 3 ):δ6.84(d,J＝8Hz,1H),6.79(d,J＝1.8Hz,1H),6.78(dd,J＝8.1,1.8Hz,1H),5.70(br s,1H),5.55(br s,1H),4.33(d,J＝5.6Hz,2H),3.86(s,3H),2.22(t,J＝7.6Hz,2H),1.16(t,J＝7.6Hz,3H)。
example 3: N-N-Butanoic acid vanillylamide
Figure BDA0002941525070000072
The experimental operation is the same as that of example 1, and the molar amounts of the reaction raw materials, the catalyst and the organic solvent are the same as those of example 1, except that: the alcohol used in example 3 was n-butanol; the obtained crude product was purified by silica gel column chromatography (ethyl acetate: petroleum ether = 15); melting point: 74-76 ℃; 1 H NMR(400MHz,CDCl 3 ):δ6.88(d,J＝8.5Hz,1H),6.81(d,J＝1.5Hz,1H),6.78(dd,J＝8.5,1.6Hz,1H),5.63(s,1H),5.61(s,1H),4.36(d,J＝6Hz,2H),3.88(s,3H),2.18(t,J＝7.5Hz,2H),1.68(q,J＝7.5Hz,2H),0.96(d,J＝7.5Hz,3H)。
example 4: N-N-pentanoic acid vanillic amide
Figure BDA0002941525070000081
The experimental operation is the same as that of example 1, and the molar amounts of the reaction raw materials, the catalyst and the organic solvent are the same as those of example 1, except that: the alcohol used in example 4 was n-pentanol; the obtained crude product was purified by silica gel column chromatography (ethyl acetate: petroleum ether = 20); melting point: 54-55 ℃; 1 H NMR(400MHz,CDCl 3 ):δ6.76(d,J＝8Hz,1H),6.69(d,J＝1.8Hz,1H),6.6.2(dd,J＝8,1.6Hz,1H),6.51(s,1H),6.01(s,1H),4.24(d,J＝5.6Hz,2H),3.81(s,3H),2.13(t,J＝7.6Hz,2H),1.55(m,2H),1.25(m,2H),0.86(d,J＝7.4Hz,3H)。
example 5: n-hexanoic acid vanillylamide
Figure BDA0002941525070000082
The experimental operation is the same as that of example 1, and the molar amounts of the reaction raw materials, the catalyst and the organic solvent are the same as those of example 1, except that: the alcohol used in example 5 was hexanol; the obtained crude product was purified by silica gel column chromatography (ethyl acetate: petroleum ether = 20); melting point: 58 to 60 ℃; 1 H NMR(400MHz,CDCl 3 ):δ6.86(d,J＝8Hz,1H),6.81(d,J＝2Hz,1H),6.76(dd,J＝8.0,1.6Hz,1H),5.64(s,1H),5.61(s,1H),4.35(d,J＝5.5Hz,2H),3.88(s,3H),2.19(t,J＝7.5Hz,2H),1.65(m,2H),1.32(m,4H),0.88(d,J＝7.0Hz,3H)。
example 6: N-N-heptanoic acid vanillylamide
Figure BDA0002941525070000083
The experimental operation is the same as that of example 1, and the molar amounts of the reaction raw materials, the catalyst and the organic solvent are the same as those of example 1, except that: the alcohol used in example 6 was n-heptanol; the obtained crude product was purified by silica gel column chromatography (ethyl acetate: petroleum ether = 20); melting point: 58 to 59 ℃; 1 H NMR(400MHz,CDCl 3 ):δ6.74(d,J＝7.9Hz,1H),6.71(d,J＝2Hz,1H),6.61(dd,J＝7.9,2Hz,1H),5.65(s,1H),5.58(s,1H),4.22(d,J＝5.5Hz,2H),3.78(s,3H),2.24(t,J＝7.4Hz,2H),1.58(m,2H),1.48-1.18(m,6H),0.86(d,J＝7.0Hz,3H)。
example 7: n-octanoic acid vanillic amide
Figure BDA0002941525070000091
Experimental procedure is the same as in example 1The molar amounts of the reaction raw materials, the catalyst and the organic solvent are the same as those in example 1 except that: the alcohol used in example 7 was n-octanol; the obtained crude product is purified by silica gel column chromatography (ethyl acetate: petroleum ether = 12); melting point: 42-44 ℃; 1 H NMR(400MHz,CDCl 3 ):δ6.86(d,J＝8Hz,1H),6.81(d,J＝2Hz,1H),6.76(dd,J＝8.0,2.0Hz,1H),5.64(s,1H),5.62(s,1H),4.35(d,J＝5.8Hz,2H),3.88(s,3H),2.19(t,J＝7.5Hz,2H),1.65(m,2H),1.31-1.26(m,8H),0.87(d,J＝6.8Hz,3H)。
example 8: n-nonanoic acid vanillylamide
Figure BDA0002941525070000092
The experimental operation is the same as that of example 1, and the molar amounts of the reaction raw materials, the catalyst and the organic solvent are the same as those of example 1, except that: the alcohol used in example 8 was n-nonanol; the obtained crude product is purified by silica gel column chromatography (ethyl acetate: petroleum ether = 12); melting point: 57-58 ℃; 1 H NMR(400MHz,CDCl 3 ):δ6.86(d,J＝8.0Hz,lH),6.81(s,lH),6.76(d,J＝8.2Hz,lH),5.73(brs,2H),4.34(d,J＝5.7Hz,2H),3.86(s,3H),2.19(t,J＝7.6Hz,2H),1.68-1.59(m,2H),1.38-1.18(m,10H),0.87(t,J＝7.0Hz,3H)。
example 9: N-8-Methylnonanoic vanillylamide (dihydrocapsaicin)
Figure BDA0002941525070000101
The experimental operation is the same as that of example 1, and the molar amounts of the reaction raw materials, the catalyst and the organic solvent are the same as those of example 1, except that: the alcohol used in example 9 was 8-methylnonanol; the obtained crude product is purified by silica gel column chromatography (ethyl acetate: petroleum ether = 10); melting point: 62-64 ℃; 1 H NMR(400MHz,CDCl 3 ):δ6.86(d,J＝8.0H z,lH),6.81(s,lH),6.76(d,J＝8.2Hz,lH),5.64(s,1H),5.60(s,1H),4.35(d,J＝5.8Hz,2H),3.86(s,3H),2.19(t,J＝7.6Hz,2H),1.65(m,2H),1.50(m,1H),1.32-1.15(m,8H),0.86(t,J＝6.5Hz,3H)。
example 10: N-9-Methyldecanoic acid vanillylamide (high dihydrocapsaicin)
Figure BDA0002941525070000102
The experimental operation is the same as that of example 1, and the molar amounts of the reaction raw materials, the catalyst and the organic solvent are the same as those of example 1, except that: the alcohol used in example 10 was 9-methyldecanol; the obtained crude product was purified by silica gel column chromatography (ethyl acetate: petroleum ether = 16); the nuclear magnetic detection map is shown in figure 1; the melting point is 68-69 ℃; 1 H NMR(400MH z,CDCl 3 ):δ6.88(d,J＝8Hz,1H),6.81(d,J＝2Hz,1H),6.78(dd,J＝1.6,1.6Hz,1H),5.65(brs,2H),4.36(d,J＝5.6Hz,2H),3.88(s,3H),2.20(t,J＝7.6Hz,2H),1.65(m,2H),1.52-1.48(m,1H),1.30-1.25(m,8H),1.16-1.13(m,2H),0.86(d,J＝6.4Hz,6H)。
example 11: n-benzoic acid vanillimide
Figure BDA0002941525070000111
The experimental operation is the same as that of example 1, and the molar amounts of the reaction raw materials, the catalyst and the organic solvent are the same as those of example 1, except that: the alcohol used in example 11 was benzyl alcohol; the obtained crude product was purified by silica gel column chromatography (ethyl acetate: petroleum ether = 16); the melting point is 68-69 ℃; 1 H NMR(400MHz,CDCl 3 ):δ7.76(d,J＝7.5Hz,2H),7.48(t,J＝7.1Hz,1H),7.44–7.46(m,2H),6.91–6.82(m,3H),6.32(brs,1H),5.62(s,1H),4.58(d,J＝5.6Hz,2H),3.88(s,3H)。
example 12: n-propionic acid vanillimide
Figure BDA0002941525070000112
0.12g of ferric nitrate (0.5 mmol), 0.11g of indium trichloride (0.5 mmol) and 50mL of trifluoromethylbenzene were put into a Schlenk reaction tube and stirred for 30 minutes; adding 0.87g of propionaldehyde (15 mmol) and 1.53g of vanillylamine (10 mmol), plugging a pure oxygen bag, vacuumizing for 3 times, placing the reaction tube in a constant-temperature oil bath at 30 ℃, and stirring for reaction.
Detecting by TLC until the reaction is complete, performing suction filtration on the reaction solution through a sand core funnel filled with silica gel, washing with ethyl acetate, combining organic phases, concentrating to obtain a crude product, and purifying the crude product by silica gel column chromatography (ethyl acetate: petroleum ether = 15) to obtain 2g of corresponding N-N-propionic acid vanillylamide with the yield of 96%; melting point: 106 to 108 ℃; 1 H NMR(400MHz,CDCl 3 ):δ6.84(d,J＝8Hz,1H),6.79(d,J＝1.8Hz,1H),6.78(dd,J＝8.1,1.8Hz,1H),5.70(br s,1H),5.55(br s,1H),4.33(d,J＝5.6Hz,2H),3.86(s,3H),2.22(t,J＝7.6Hz,2H),1.16(t,J＝7.6Hz,3H)。
example 13: n-butyric acid vanillimide
Figure BDA0002941525070000121
The experimental operation is the same as example 12, and the molar amounts of the reaction raw materials, the catalyst and the organic solvent are the same as example 12, except that: the aldehyde used in example 13 was n-butyraldehyde; the obtained crude product was purified by silica gel column chromatography (ethyl acetate: petroleum ether = 15); melting point: 74-76 ℃; 1 H NMR(400MHz,CDCl 3 ):δ6.88(d,J＝8.5H z,1H),6.81(d,J＝1.5Hz,1H),6.78(dd,J＝8.5,1.6Hz,1H),5.63(s,1H),5.61(s,1H),4.36(d,J＝6Hz,2H),3.88(s,3H),2.18(t,J＝7.5Hz,2H),1.68(q,J＝7.5Hz,2H),0.96(d,J＝7.5Hz,3H)。
example 14: n-hexanoic acid vanillylamide
Figure BDA0002941525070000122
The experimental procedure was as in example 12, and the molar amounts of the reaction materials, the catalyst and the organic solvent were as in example 14, except that: the aldehyde used in example 14 was n-hexanal; the obtained crude product was purified by silica gel column chromatography (ethyl acetate: petroleum ether = 20); melting point: 58-60 deg.C; 1 H NMR(400MHz,CDCl 3 ):δ6.86(d,J＝8Hz,1H),6.81(d,J＝2Hz,1H),6.76(dd,J＝8.0,1.6Hz,1H),5.64(s,1H),5.61(s,1H),4.35(d,J＝5.5Hz,2H),3.88(s,3H),2.19(t,J＝7.5Hz,2H),1.65(m,2H),1.32(m,4H),0.88(d,J＝7.0Hz,3H)。
example 15: N-N-heptanoic acid vanillimide
Figure BDA0002941525070000131
The experimental operation was the same as example 12, and the molar amounts of the reaction raw materials, the catalyst and the organic solvent were the same as example 15, except that: the aldehyde used in example 15 was n-heptanal; the obtained crude product was purified by silica gel column chromatography (ethyl acetate: petroleum ether = 20); melting point: 58 to 59 ℃; 1 H NMR(400MHz,CDCl 3 ):δ6.74(d,J＝7.9Hz,1H),6.71(d,J＝2Hz,1H),6.61(dd,J＝7.9,2Hz,1H),5.65(s,1H),5.58(s,1H),4.22(d,J＝5.5Hz,2H),3.78(s,3H),2.24(t,J＝7.4Hz,2H),1.58(m,2H),1.48-1.18(m,6H),0.86(d,J＝7.0Hz,3H)。
example 16: n-octanoic acid vanillic amide
Figure BDA0002941525070000132
The experimental operation was the same as example 12, and the molar amounts of the reaction raw materials, the catalyst and the organic solvent were the same as example 16, except that: the aldehyde used in example 16 was n-octanal; the obtained crude product was purified by silica gel column chromatography (ethyl acetate: petroleum ether = 12); melting point: 42-44℃； 1 H NMR(400MHz,CDCl 3 ):δ6.86(d,J＝8Hz,1H),6.81(d,J＝2Hz,1H),6.76(dd,J＝8.0,2.0Hz,1H),5.64(s,1H),5.62(s,1H),4.35(d,J＝5.8Hz,2H),3.88(s,3H),2.19(t,J＝7.5Hz,2H),1.65(m,2H),1.31-1.26(m,8H),0.87(d,J＝6.8Hz,3H)。
Example 17: n-nonanoic acid vanillylamide
Figure BDA0002941525070000141
The experimental operation was the same as example 12, and the molar amounts of the reaction raw materials, the catalyst and the organic solvent were the same as example 17, except that: the aldehyde used in example 17 was n-nonanal; the obtained crude product was purified by silica gel column chromatography (ethyl acetate: petroleum ether = 12); melting point: 57-58 ℃; 1 H NMR(400MHz,CDCl 3 ):δ6.86(d,J＝8.0Hz,lH),6.81(s,lH),6.76(d,J＝8.2Hz,lH),5.73(brs,2H),4.34(d,J＝5.7Hz,2H),3.86(s,3H),2.19(t,J＝7.6Hz,2H),1.68-1.59(m,2H),1.38-1.18(m,10H),0.87(t,J＝7.0Hz,3H)。
example 18: n-benzoic acid vanillimide
Figure BDA0002941525070000142
The experimental procedure was as in example 12, and the molar amounts of the reaction materials, the catalyst and the organic solvent were as in example 18, except that: the aldehyde used in example 18 was benzaldehyde; the obtained crude product was purified by silica gel column chromatography (ethyl acetate: petroleum ether = 16); melting point is 68-69 ℃; 1 H NMR(400MHz,CDCl 3 ):δ7.76(d,J＝7.5Hz,2H),7.48(t,J＝7.1Hz,1H),7.44–7.46(m,2H),6.91–6.82(m,3H),6.32(brs,1H),5.62(s,1H),4.58(d,J＝5.6Hz,2H),3.88(s,3H)。
the above description is only an embodiment of the present invention, and not intended to limit the scope of the present invention, and all modifications and equivalents made by the contents of the present invention or directly or indirectly applied to other related technical fields are included in the scope of the present invention.

Claims (8)

1. The synthetic method of vanillyl amide is characterized in that alcohol and vanillyl amide are used as raw materials, or aldehyde and vanillyl amide are used as raw materials, inorganic iron salt and inorganic indium salt are used as composite catalysts, oxygen is used as an oxidizing agent, and the reaction is carried out in an organic solvent by a one-pot method to generate the vanillyl amide; the alcohol is one of ethanol, n-propanol, n-butanol, n-pentanol, hexanol, n-heptanol, n-octanol, n-nonanol, 8-methylnonanol, 9-methyldecanol and benzyl alcohol; the aldehyde is one of propionaldehyde, n-butyraldehyde, n-hexanal, n-heptaldehyde, n-octaldehyde, n-nonanal and benzaldehyde; the inorganic ferric salt is at least one of ferric chloride, ferric nitrate, ferric sulfate, ferric phosphate, ferric bromide, ferric fluoride, ferric trifluoromethanesulfonate, ferric p-toluenesulfonate and ferric tetrafluoroborate; the inorganic indium salt is at least one of indium trichloride, indium trifluoride, indium tribromide, indium nitrate, indium trifluoromethanesulfonate, indium perchlorate and indium acetate.
2. The method for synthesizing vanilloylamine according to claim 1, characterized in that the reaction temperature of the synthesis method is 20-80 ℃.
3. The method for synthesizing vanilloylamine as claimed in claim 1, wherein the organic solvent is at least one of toluene, trifluoromethyl benzene, fluorobenzene, chloroform, dichloromethane, 1, 2-dichloroethane, acetonitrile, nitromethane, tetrahydrofuran and ethylene glycol dimethyl ether.
4. The method for synthesizing vanillylamide according to claim 1, wherein the amount of alcohol or aldehyde is 100 to 500mol% based on the amount of vanillylamide.
5. The method for synthesizing vanillylamide according to claim 1, wherein the amount of the inorganic iron salt is 1 to 10mol% based on the amount of vanillylamine.
6. The method as claimed in claim 1, wherein the amount of the inorganic indium salt is 1 to 10mol% based on the amount of vanillylamine.
7. The method for synthesizing vanilloylamine as claimed in claim 1, wherein the amount of the organic solvent is 1 to 10ml/mmol based on the amount of vanillylamine.
8. The method for synthesizing vanillylamide according to claim 1, wherein after the reaction is finished, the reacted materials are subjected to suction filtration and washing, organic phases are combined and concentrated to obtain a crude product, and the crude product is purified by column chromatography to obtain a purified vanillylamide product.
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