CN106349157B - A kind of method of hydro-thermal method synthesis 2- halogenated nicotinate and the halogenated niacin of 2- - Google Patents
A kind of method of hydro-thermal method synthesis 2- halogenated nicotinate and the halogenated niacin of 2- Download PDFInfo
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- CN106349157B CN106349157B CN201610736034.6A CN201610736034A CN106349157B CN 106349157 B CN106349157 B CN 106349157B CN 201610736034 A CN201610736034 A CN 201610736034A CN 106349157 B CN106349157 B CN 106349157B
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/803—Processes of preparation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
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Abstract
The invention discloses a kind of methods of hydro-thermal method synthesis 2- halogenated nicotinate and the halogenated niacin of 2-, are related to the field of chemical synthesis.This method is raw material by substituted-amino methacrylaldehyde, catalyst, catalyst promoter, water, cyan-acetic ester, using the halogenated nicotinate of hydro-thermal method method synthesis 2- and the halogenated niacin of 2-.Compared with prior art, synthetic method of the invention have it is environmentally protective, be easily isolated, the features such as product yield is high, high-quality, more conducively realization large-scale industrial production.
Description
Technical field
The present invention relates to the field of chemical synthesis, specifically a kind of hydro-thermal method synthesizes the halogenated nicotinate of 2- and 2- is halogenated
The method of niacin.
Background technique
2- chlorine apellagrin is a kind of important drug and pesticide intermediate, mainly for the preparation of high efficiency anti-inflammatory antalgesic Buddhist nun's fluorine
Fenamic acid, pranoprofen, hiv reverse transcriptase inhibitor nevirapine and highy potent herbicide nicosulfuron etc., can be by the halogenated niacin of 2-
Ester hydrolysis is made.
It is disclosed the preparation method of the halogenated niacin of a variety of 2- in the prior art, such as cyan-acetic ester chloridising, niacin nitrogen
Oxidation-chloride-hydrolysis etc., although the halogenated niacin of 2- can be obtained, generally existing " three wastes " are mostly and be difficult to handle is stranded
It is difficult.
The patent document of Publication No. CN10500115A be disclosed " a kind of halogenated nicotinate of ionic liquid method synthesis 2- and its
The method of intermediate ", this method is using ionic liquid as solvent and catalyst, although above-mentioned the deficiencies in the prior art can be overcome,
The problems such as there are still product yields generally, the reaction time is longer.
Summary of the invention
Technical assignment of the invention is in view of the above shortcomings of the prior art, to provide low a kind of reaction condition, high income, anti-
High-efficient hydro-thermal method is answered to synthesize the halogenated nicotinate of 2-.
The further technical assignment of the present invention is to provide a kind of method of hydro-thermal method synthesis halogenated niacin of 2-.
Technical assignment of the invention is realized in the following manner: a kind of method of the hydro-thermal method synthesis halogenated nicotinate of 2-,
Include:
A, 5- (N, N- dialkyl) amino -2- cyano -2,4- pentadiene acid esters shown in preparation formula (I)；
In formula (I), R1And R2Respectively stand alone as H, C1-C18Alkyl, phenyl or benzyl；R3For C1-C18Alkyl；
B, the halogenated nicotinate of 2- shown in preparation formula (II),
In formula (II), X F, Cl, Br or I；R3Indicate C1-C18Alkyl,
It is characterized by:
Step a: hydrothermal reactor is added in substituted-amino methacrylaldehyde, catalyst, catalyst promoter, water, cyan-acetic ester
In, hydro-thermal reaction is carried out under certain temperature, nitrogen pressurization, is extracted, is obtained containing shown in formula (I) with organic solvent after the reaction was completed
The organic phase of compound；
Step b: it is passed through dry hydrogen halide into organic phase, is reacted in hydrothermal reactor, reaction terminates
Afterwards, lye adjusting pH value is added and obtains the halogenated nicotinate of 2- as shown in formula (II) by refinement treatment to neutrality,
Reaction equation is as follows:
In step a, the catalyst can be vanadium, manganese, iron, copper, zinc, titanium, chromium, cobalt, nickel, lead, silver, platinum, mercury or zirconium member
Element or its oxide or its complex.Oxide such as V2O5、MnO2Or TiO2Deng；Complex such as Ni (CO)4、SnCl2·
H2PtCl6Or HCo (CO)4Deng, but in order to reach optimal reaction effect, the catalyst is preferably Cu, CuO, V2O5、TiO2、
Ni(CO)4Or HCo (CO)4, with weight ratio meter, the dosage of catalyst is 0.001-0.5 times of substituted-amino methacrylaldehyde, preferably
0.001-0.3 times.
The catalyst promoter is quaternary ammonium base or quaternary ammonium salt, preferably trimethyl benzyl ammonia chloride, triethylbenzyl chlorination
Ammonium, trimethyldodecane ammonium chloride, tetraethyl ammonium hydroxide or tetrabutylammonium hydroxide, the dosage of catalyst promoter are to replace
0.001-0.5 times of amino methacrylaldehyde (weight ratio), preferably 0.001-0.3 times.
Polar solvent common in the art, preferably n-hexane, normal heptane, hexamethylene can be selected in the organic solvent
Alkane, dimethylbenzene, dichloro-benzenes, methyl tertiary butyl ether(MTBE) or isopropyl ether, the weight of organic solvent are the 1- of compound by weight shown in formula (I)
6 times, preferably 1-4 times.
Through many experiments it is found that when the reaction temperature of hydro-thermal reaction is 50-200 DEG C, when reaction pressure is 0.1-30MPa,
Hydro-thermal reaction of the present invention energy is efficient, high quality is completed, but working as reaction temperature is 80-110 DEG C, reaction pressure 0.2-
When 5MPa, the reaction time be can be shortened to 0.2-0.5 hours.
Lye described in step b is preferably monomethyl amine, dimethylamine, trimethylamine or ammonium bicarbonate soln, lye mass concentration
For 30%-40%.
The refinement treatment can be used commonly uses method of purification in the prior art, as decompression steams solvent, residue after liquid separation
Rectification under vacuum again；It is washed after liquid separation, is dry, filtering, then the processing methods such as solvent are sloughed in decompression.
The halogenated nicotinate of 2- made from the above method passes through hydrolysis, can be prepared by the halogenated niacin of 2-, reaction equation is as follows:
Compared with prior art, preparation method of the invention have it is following prominent ground the utility model has the advantages that
(1) hydro-thermal reaction is completed in water phase, does not have to organic solvent, environmentally protective, the influence very little to environment；
(2) with specific catalyst, catalyst aid, under specific temperature, pressure, the halogenated nicotinate of 2- contains in product
Amount can reach 99.0% or more, and yield can reach 95% or more, and the reaction time can be shortened to 0.2-0.5 hours, more suitable for
Industrialized production.
Specific embodiment
With method of the specific embodiment to the halogenated nicotinate of hydro-thermal method synthesis 2- of the invention and the halogenated niacin of 2- make with
Under explain in detail.
Embodiment one (synthesis of 2- chlorine apellagrin methyl esters):
Respectively by N, N- dibutyl amino methacrylaldehyde 69mL (0.5mol), TiO20.3g, tetrabutylammonium hydroxide 10.0g and
Deionized water 50mL is added in hydrothermal reactor, malonic methyl ester nitrile 65mL (0.6mol) mixing is added, in 90 DEG C, nitrogen
Hydro-thermal method reacts 0.25h under 0.3MPa, filters after reaction, and n-hexane dosage 90g extraction, organic phase is passed through dry again
HCl gas reaction, TLC (ethyl acetate is unfolded, and observes under ultraviolet lamp) tracking reaction terminate until reacting, and matter is added in reaction solution
It measures 30% trimethylamine aqueous solution of content and adjusts pH value to neutrality, liquid separation obtains organic phase, and decompression steams solvent (recovery), remaining
110-115 DEG C/1mmHg fraction is collected in object rectification under vacuum, and 2- chloro-nicotinic acid methyl esters colourless liquid is made, and 2- chlorine apellagrin methyl esters contains
Amount 99.6%, yield 96.5%.
The MS and NMR of product are characterized as below:
ESI-MS:m/z Calcd for C7H6NClO2 172.5887[M+H]+, found 172.5879 [M+H]+。
1HNMR(300MHz,CDCl3-d6)δ(ppm):3.19(s,CH3), 7.33 (t, J=6Hz, 1H, CH), 8.15 (d, J
=6Hz, 1H.CH), 8.49 (d, J=6Hz, 1H, CH)
13CNMR(75MHz,CDCl3-d6)δ(ppm):61.07(OCH3), 122.09 (CH=*CH=CH), 127.27 (* C-
COOCH3), 140.16 (* CH=C), 149.98 (Cl-*C=N), 151.39 (N-*CH=CH), 164.55 (* C=O).
Embodiment two (synthesis of 2- bromo-nicotinic acid methyl esters):
It by 3- lignocaine methacrylaldehyde 61mL (0.5mol), copper powder 6.5g, triethyl benzyl ammonia chloride 10.0g and goes respectively
Ionized water 50mL is added in hydrothermal reactor, malonic methyl ester nitrile 65mL (0.6mol) mixing is added, in 100 DEG C, nitrogen
Hydro-thermal method reacts 0.5h under 3MPa, filters after reaction, and hexamethylene 120g extraction, organic phase is passed through dry HBr gas again
Reaction, TLC (ethyl acetate is unfolded, and observes under ultraviolet lamp) tracking reaction terminate until reacting, and mass content is added in reaction solution
40% dimethylamine lye adjusts pH value to neutrality, and liquid separation obtains organic phase, and washing, anhydrous sodium sulfate dry, filter, and decompression is sloughed molten
Agent (recovery) obtains 2- bromo-nicotinic acid methyl esters, light brown liquid, 2- bromo-nicotinic acid methyl ester content 99.8%, yield 95.3%.
The MS of product is characterized as below:
ESI-MS:m/z Calcd for C7H6NBrO2 217.0400[M+H]+, found 217.0391 [M+H]+。
Embodiment three (synthesis of 2- chlorine apellagrin ethyl ester):
Respectively by N, N- dibutyl amino methacrylaldehyde 69mL (0.5mol), CuO 6.5g, trimethyldodecane base ammonium bromide
10.0g and deionized water 50mL is added in hydrothermal reactor, cyan-acetic ester 65mL (0.6mol) mixing is added, 110
DEG C, hydro-thermal method reacts 0.3h under nitrogen 0.25MPa, filters after reaction, dimethylbenzene 220g extraction, organic phase is passed through drying again
HCl gas reaction, TLC (ethyl acetate expansion, observe under ultraviolet lamp) tracking reaction terminates until reaction, is added in reaction solution
40% ammonium hydrogen carbonate of mass content adjusts pH value to neutrality, and liquid separation obtains organic phase, and decompression steams solvent (recovery), residue
110-115 DEG C/1mmHg fraction is collected in rectification under vacuum, and 2- chloro-nicotinic acid ethyl ester colourless liquid, 2- chlorine apellagrin ethyl ester content is made
99.4%, yield 97.5%.
The MS and NMR of product are characterized as below:
ESI-MS:m/z Calcd for C8H8NClO2 186.0316[M+H]+, found 186.0310 [M+H]+。
1HNMR(300MHz,CDCl3-d6) δ (ppm): 1.39 (t, J=6Hz, CH3), 4.39 (q, J=6Hz, CH2),7.31
(t, J=6Hz, 1H, CH), 8.13 (d, J=6Hz, 1H.CH), 8.48 (d, J=6Hz, 1H, CH)
13CNMR(75MHz,CDCl3-d6)δ(ppm):14.09(*CH3),62.07(*CH2CH3), 122.04 (CH=*CH
=CH), 127.22 (* C-COOCH2CH3), 140.11 (* CH=C-COO), 149.92 (Cl-*C=N), 151.33 (N-*CH=
), CH 164.51 (* C=O)
Example IV (synthesis of 2- bromo-nicotinic acid ethyl ester):
Respectively by 3- lignocaine methacrylaldehyde 61mL (0.5mol), CuO 6.5g, tetraethyl ammonium hydroxide 12.0g and go from
Sub- water 50mL is added in hydrothermal reactor, cyan-acetic ester 65mL (0.6mol) mixing is added, in 100 DEG C, nitrogen
Hydro-thermal method reacts 0.4h under 0.3MPa, filters after reaction, and dichloro-benzenes 181g extraction, organic phase is passed through dry HBr gas again
Precursor reactant, TLC (ethyl acetate is unfolded, and observes under ultraviolet lamp) tracking reaction is until reaction terminates, and addition quality contains in reaction solution
It measures 40% monomethyl amine and adjusts pH value to neutrality, liquid separation obtains organic phase, and washing, anhydrous sodium sulfate dry, filter, and solvent is sloughed in decompression
(recovery) obtains 2- bromo-nicotinic acid ethyl ester, light brown liquid, 2- bromo-nicotinic acid ethyl ester content 99.0%, yield 95.7%.
The MS and NMR of product are characterized as below:
ESI-MS:m/z Calcd for C8H8NBrO2 231.0666[M+H]+, found 231.0658 [M+H]+。
1HNMR(300MHz,CDCl3-d6) δ (ppm): 1.38 (t, J=6Hz, CH3), 4.37 (q, J=6Hz, CH2),7.30
(t, J=6Hz, 1H, CH), 8.11 (d, J=6Hz, 1H.CH), 8.47 (d, J=6Hz, 1H, CH)
Embodiment five (synthesis of 2- iodine ethyl nicotinate):
Respectively by 3- lignocaine methacrylaldehyde 61mL (0.5mol), TiO26.5g, triethylbenzyl ammonium hydroxide 10.0g
It is added in hydrothermal reactor with deionized water 50mL, cyan-acetic ester 65mL (0.6mol) mixing is added, in 106 DEG C, nitrogen
Hydro-thermal method reacts 0.4h under gas 0.5MPa, filters after reaction, and isopropyl ether 153g extraction, organic phase is passed through dry HI gas again
Precursor reactant, TLC (ethyl acetate is unfolded, and observes under ultraviolet lamp) tracking reaction terminate until reacting, and 40% 1 is added in reaction solution
Methylamine adjusts pH value to neutrality, and liquid separation obtains organic phase, and washing, anhydrous sodium sulfate dry, filter, and solvent (recovery set is sloughed in decompression
With), 2- iodine ethyl nicotinate is obtained, light brown liquid, 2- iodine ethyl nicotinate content 99.3%, yield 96.4% are obtained.
The MS and NMR of product are characterized as below:
ESI-MS:m/z Calcd for C8H8NIO2 278.0671[M+H]+, found 278.0664 [M+H]+。
1HNMR(300MHz,CDCl3-d6) δ (ppm): 1.37 (t, J=6Hz, CH3), 4.37 (q, J=6Hz, CH2),7.31
(t, J=6Hz, 1H, CH), 8.10 (d, J=6Hz, 1H.CH), 8.46 (d, J=6Hz, 1H, CH).
Embodiment six (synthesis of 2- fluorine nicotinic acid ethyl ester)
Respectively by N, N- dibutyl amino methacrylaldehyde 69mL (0.5mol), HCo (CO)48.5g, trimethyldodecane bromide
Ammonium 12.5g and deionized water 50mL is added in hydrothermal reactor, adds cyan-acetic ester 65mL (0.6mol) mixing,
106 DEG C, hydro-thermal method reacts 0.4h under nitrogen 0.6MPa, filters after reaction, methyl tertiary butyl ether(MTBE) 140g extraction, organic phase is again
It is passed through dry HF gas reaction, TLC (ethyl acetate is unfolded, and observes under ultraviolet lamp) tracking reaction terminates until reacting, reacts
30% ammonium bicarbonate soln of mass content is added in liquid and adjusts pH value to neutrality, liquid separation obtains organic phase, and decompression steams solvent (recycling
Apply), 110-115 DEG C/1mmHg fraction is collected in residue rectification under vacuum, and 2- fluoro ethyl nicotinate is made, obtains light brown liquid,
2- fluorine nicotinic acid ethyl ester content 99.0%, yield 95.0%.
The MS of product is characterized as below:
ESI-MS:m/z Calcd for C8H8NFO2 170.1610[M+H]+, found 170.1614 [M+H]+。
Embodiment seven (synthesis of the positive 12 carbon ester of 2- chlorine apellagrin)
Respectively by 3- lignocaine methacrylaldehyde 61mL (0.5mol), V2O56.0g, triethylbenzyl ammonium hydroxide 10.0g and
Deionized water 50mL is added in hydrothermal reactor, adds the positive 12 carbon ester 73mL (0.6mol) of cyanoacetic acid and mixes, 100
DEG C, hydro-thermal method reacts 0.3h under nitrogen 1.6MPa, filters after reaction, dimethylbenzene 200g extraction, organic phase is passed through drying again
HCl gas reaction, TLC (ethyl acetate expansion, observe under ultraviolet lamp) tracking reaction terminates until reaction, is added in reaction solution
40% dimethylamine solution of mass content adjusts pH value to neutrality, and liquid separation obtains organic phase, and washing, anhydrous sodium sulfate dry, filter, subtract
Solvent (recovery) alkane is removed in pressure-off, obtains 2- iodine ethyl nicotinate, obtains colourless liquid, the positive 12 carbon ester content of 2- chlorine apellagrin
99.1%, yield 96.5%.
The MS of product is characterized as below:
ESI-MS:m/z Calcd for C18H28NClO2 326.8811[M+H]+, found 326.8807 [M+H]+。
Embodiment eight (synthesis of 2- chlorine apellagrin)
Respectively by N, N- dibutyl amino methacrylaldehyde 69mL (0.5mol), CuO 6.5g, triethyl benzyl ammonia chloride 10.0g and
Deionized water 50mL is added in hydrothermal reactor, cyan-acetic ester 65mL (0.6mol) mixing is added, in 90 DEG C, nitrogen
Hydro-thermal method reacts 0.4h under 2MPa, filters after reaction, and dichloro-benzenes 100g extraction, organic phase is passed through dry HCl gas again
Reaction, TLC (ethyl acetate is unfolded, and observes under ultraviolet lamp) tracking reaction terminate until reacting, and 40% diformazan is added in reaction solution
Amine aqueous solution adjusts pH value to neutrality, and liquid separation obtains organic phase, and decompression steams (recovery), and 110- is collected in residue rectification under vacuum
2- chloro-nicotinic acid ethyl ester colourless liquid is made in 115 DEG C/1mmHg fraction, is added in 100mL40% trimethylamine solution and mixes, and 60 DEG C
Lower heat preservation 2h, is cooled to room temperature, and 3%HCl is neutralized to pH=5-6,3 DEG C of crystallization 4h, filtering, and white crystals are made in crystallizing and drying
2- chloro-nicotinic acid, 2- chlorine apellagrin content 99.2%, yield 95.1%.
The MS of product is characterized as below:
ESI-MS:m/z Calcd for C6H4O2NCl 158.5621[M+H]+, found 158.5617 [M+H]+。
Claims (6)
1. a kind of method of the hydro-thermal method synthesis halogenated nicotinate of 2-, comprising:
A, 5- (N, N- dialkyl) amino -2- cyano -2,4- pentadiene acid esters shown in preparation formula (I)；
In formula (I), R1And R2Respectively stand alone as C1-C18Alkyl；R3For C1-C18Alkyl；
B, the halogenated nicotinate of 2- shown in preparation formula (II),
In formula (II), X F, Cl, Br or I；R3Indicate C1-C18Alkyl,
It is characterized by:
Step a: substituted-amino methacrylaldehyde, catalyst, catalyst promoter, water, cyan-acetic ester are added in hydrothermal reactor,
Certain temperature, the lower progress hydro-thermal reaction of nitrogen pressurization, are extracted with organic solvent after the reaction was completed, are obtained containing chemical combination shown in formula (I)
The organic phase of object,
The catalyst is Cu, CuO, V2O5、TiO2、Ni(CO)4Or HCo (CO)4,
The catalyst promoter is trimethyl benzyl ammonia chloride, triethyl benzyl ammonia chloride, trimethyldodecane ammonium chloride, four
Ethyl ammonium hydroxide or tetrabutylammonium hydroxide,
The reaction temperature of hydro-thermal reaction is 50-200 DEG C, reaction pressure 0.1-30MPa；
Step b: being passed through dry hydrogen halide into organic phase, reacted in hydrothermal reactor, after reaction, adds
Enter lye adjusting pH value and obtains the halogenated nicotinate of 2- as shown in formula (II) by refinement treatment to neutrality.
2. the method for the hydro-thermal method synthesis halogenated nicotinate of 2- according to claim 1, which is characterized in that in step a, with
Weight ratio meter, the dosage of catalyst are 0.001-0.5 times of substituted-amino methacrylaldehyde.
3. the method for the hydro-thermal method synthesis halogenated nicotinate of 2- according to claim 2, which is characterized in that in step a, with
Weight ratio meter, the dosage of catalyst promoter are 0.001-0.5 times of substituted-amino methacrylaldehyde.
4. the method for the hydro-thermal method synthesis halogenated nicotinate of 2- according to claim 1 or 2, which is characterized in that in step a
The organic solvent be n-hexane, normal heptane, hexamethylene, dimethylbenzene, dichloro-benzenes, methyl tertiary butyl ether(MTBE) or isopropyl ether, it is organic
The weight of solvent is 1-6 times of compound by weight shown in formula (I).
5. the method for the hydro-thermal method synthesis halogenated nicotinate of 2- according to claim 1 or 2, which is characterized in that in step b
The lye is monomethyl amine, dimethylamine, trimethylamine or ammonium bicarbonate soln.
6. a kind of method of the hydro-thermal method synthesis halogenated niacin of 2-, it is characterised in that: the halogenated nicotinate of 2- passes through hydrolysis,
The halogenated niacin of 2- is made, the synthetic method of the halogenated nicotinate of 2- includes:
A, 5- (N, N- dialkyl) amino -2- cyano -2,4- pentadiene acid esters shown in preparation formula (I)；
In formula (I), R1And R2Respectively stand alone as C1-C18Alkyl；R3For C1-C18Alkyl；
B, the halogenated nicotinate of 2- shown in preparation formula (II),
In formula (II), X F, Cl, Br or I；R3Indicate C1-C18Alkyl,
It is characterized by:
Step a: substituted-amino methacrylaldehyde, catalyst, catalyst promoter, water, cyan-acetic ester are added in hydrothermal reactor,
Certain temperature, the lower progress hydro-thermal reaction of nitrogen pressurization, are extracted with organic solvent after the reaction was completed, are obtained containing chemical combination shown in formula (I)
The organic phase of object,
The catalyst is Cu, CuO, V2O5、TiO2、Ni(CO)4Or HCo (CO)4,
The catalyst promoter is trimethyl benzyl ammonia chloride, triethyl benzyl ammonia chloride, trimethyldodecane ammonium chloride, four
Ethyl ammonium hydroxide or tetrabutylammonium hydroxide,
The reaction temperature of hydro-thermal reaction is 50-200 DEG C, reaction pressure 0.1-30MPa；
Step b: being passed through dry hydrogen halide into organic phase, reacted in hydrothermal reactor, after reaction, adds
Enter lye adjusting pH value and obtains the halogenated nicotinate of 2- as shown in formula (II) by refinement treatment to neutrality.
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