CN109096294A - The preparation method of pyridine compounds - Google Patents
The preparation method of pyridine compounds Download PDFInfo
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- CN109096294A CN109096294A CN201811021055.5A CN201811021055A CN109096294A CN 109096294 A CN109096294 A CN 109096294A CN 201811021055 A CN201811021055 A CN 201811021055A CN 109096294 A CN109096294 A CN 109096294A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
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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
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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
- C07D213/803—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
- C07D213/89—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 with hetero atoms directly attached to the ring nitrogen atom
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- Pyridine Compounds (AREA)
Abstract
The present invention relates to a kind of productions 2, the method of bis- substitution -5- alkoxy methyl pyridine (I) of 3- is reacted using at least one of formula (I-a) compound represented, formula (II) compound represented and formula (II') compound represented compound and formula (III) compound represented as raw material；
Description
Technical field
The present invention relates to a kind of manufacturing methods of pyridine compounds.
Background technique
5- (methoxy) -2,3- pyridinedicarboxylic acid dimethyl ester (or ethyl ester) is a weight of herbicide imazamox
Want intermediate.
Common synthetic method method, as patent EP0322616, EP-0747360, EP-0933362, CN102245576B,
The synthetic method of the reports such as CN103613535, CN104447527 has big synthesis difficulty, reaction risk factor height, yield low,
The disadvantages of three wastes are big.It is not easy to be mass produced.
Method of the invention has many advantages, such as that simple reaction, high income, the three wastes are small, is suitble to large-scale production.
Summary of the invention
Technical scheme is as follows:
1, a kind of pyridine compounds, as shown in logical formula (I):
In Formulas I:
R1And R2Can be identical or different, it is respectively selected from OR1、NR1R2, or R when considered together1R2It can be with are as follows:-O- ,-
S- or NR3；
R3Indicate C1-C12Alkyl, halogenated C1-C12Alkyl, C3-C6Naphthenic base or C2-C6Alkenyl；
R1And R2It is independently selected from: hydrogen, K, Na, Ca, C1-C6Alkyl, halogenated C1-C6Alkyl, C3-C6Naphthenic base, C2-
C6Alkenyl, C2-C6Alkynyl group, (by 1-3 C1-C6Alkyl, C1-C6Alkoxy or halogen atom) replace C5-C12Aryl is miscellaneous
Aryl；
R3Selected from hydrogen, C1-C6Alkyl, halogenated C1-C6Alkyl, C3-C6Naphthenic base；
N is selected from 0 or 1；
2, a kind of preparation method as led to pyridine compounds shown in formula (I), is, with (I-a) compound represented, formula
(II) at least one of compound represented and formula (II') compound represented compound and formula (III) compound represented
It is synthesized for raw material, reaction process are as follows:
Wherein raw material II, II', III are respectively selected from following structural compounds:
In Formula II, X1And X2Separately indicate chlorine atom, bromine atom or iodine atom, R4、R5、R6And R7Independently
Indicate halogen atom, C1-C6Alkyl, halogenated C1-C6Alkyl, C2-C6Alkenyl, C1-C6Alkoxy, C2-C6Alkoxy carbonyl, hydrogen
Atom or cyano, wherein X1、X2、R4、R5、R6And R7And it is not all identical, in addition, R5And R7Can bond together and with their institutes
The carbon atom of bonding is formed together ring；
In formula (II'), X3、X4、X5Indicate halogen atom, R8Indicate hydrogen atom, nitro, halogen atom, C1-C6Alkyl, halogen
For C1-C6Alkyl, C1-C6Alkoxy or by (1-3 C1-C6Alkyl, C1-C6Alkoxy or halogen atom) replace C5-C12Aryl or
Heteroaryl；
R3-OM(III)
In formula (III), R3Indicate C1-C12Alkyl, halogenated C1-C12Alkyl, C3-C6Naphthenic base or C2-C6Alkenyl, M indicate alkali
Metallic atom；
In reaction equation, R1、R2And n has meaning same as described above.
3. the manufacturing method of the pyridine compounds according to 2, is, with formula (I-a) compound represented, formula (II)
Compound represented and formula (III) compound represented are that raw material is synthesized.
4. a kind of preparation method of pyridine compounds as indicated with 1, which is characterized in that with formula (IV) compound represented,
Formula (V) compound represented, formula (I-a) compound represented and shown in formula (II) compound represented and the formula (II')
At least one of compound compound is that raw material is synthesized, reaction process are as follows:
Wherein raw material IV, V is respectively selected from following compound:
R3-OH (IV)
In formula (IV), R3Indicate C1-C12Alkyl, C3-C6Naphthenic base or C2-C6Alkenyl；
M-OH (V)
In formula (V), M indicates alkali metal atom；
In reaction equation, R1、R2、R3, II, II' and n have meaning same as described above.
5. the manufacturing method of the pyridine compounds according to 4 is with formula (IV) compound represented, formula (V) institute
Compound, formula (I-a) compound represented and (II) compound represented shown are that raw material is synthesized.
6. the manufacturing method according to 2, X1With X2It is identical.
7. the manufacturing method according to 2, formula (II) compound represented is preferably 1,2- bis- bromo- 1,1,2,2- tetra- chloroethene
Alkane or the bromo- 1,1,2,2- tetrafluoroethane of 1,2- bis-.
8. the manufacturing method of the pyridine compounds according to 2, is, with formula (I-a) compound represented, formula
(II') compound represented and formula (III) compound represented are that raw material is synthesized.
9. the manufacturing method of the pyridine compounds according to 4, is, with formula (IV) compound represented, formula (V) institute
Compound, formula (I-a) compound represented and (II') compound represented shown are that raw material is synthesized.
10. being according to the manufacturing method of pyridine compounds described in 8 or 9, R8For halogen atom.
11. being according to the manufacturing method of pyridine compounds described in 9 or 10, formula (II') compound represented is preferably
Tetrabromomethane or bromine chloroform.
12. a kind of pyridine compounds, as shown in logical formula (VI)::
In formula (VI), R1And R2Can be identical or different, it is respectively selected from OR1、NR1R2, or R when considered together1R2It can be with
Are as follows:-O- ,-S- or NR3；
R1And R2It is independently selected from: hydrogen, K, Na, Ca, C1-C6Alkyl, halogenated C1-C6Alkyl, C3-C6Naphthenic base；
R3Selected from hydrogen, C1-C6Alkyl, halogenated C1-C6Alkyl, C3-C6Naphthenic base；N is selected from 0 or 1；
13. the pyridine compounds according to 12, are, R1With R2It is identical, it is C1-C6Alkoxy or R1R2Are as follows:-O-, n choosing
From 0 or 1.
14. the pyridine compounds according to 12, are, R1With R2It is identical, preferably methoxyl group, ethyoxyl or R1R2
Are as follows:-O-, n are selected from 0 or 1.
Specific embodiment
Firstly, being illustrated to the manufacturing method of pyridine compounds shown in formula (I).
Formula (I-a) compound represented:
In formula (I-a),
R1And R2Can be identical or different, it is respectively selected from OR1、NR1R2, or R when considered together1R2It can be with are as follows:-O- ,-
S- or NR3；
R1And R2It is independently selected from: hydrogen, K, Na, Ca, C1-C6Alkyl, halogenated C1-C6Alkyl, C3-C6Naphthenic base, C2-
C6Alkenyl, C2-C6Alkynyl group, (by 1-3 C1-C6Alkyl, C1-C6Alkoxy or halogen atom) replace C5-C12Aryl is miscellaneous
Aryl；
R3Selected from hydrogen, C1-C6Alkyl, halogenated C1-C6Alkyl, C3-C6Naphthenic base；
N is selected from 0 or 1；
Halogen atom can be selected from fluorine atom, chlorine atom, bromine atom and iodine atom.
As R1、R2And R3In C1-C6Alkyl can enumerate methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tertiary fourth
Base, amyl and hexyl.It is preferred that methyl, ethyl, propyl, isopropyl.
As R1、R2And R3In halogenated C1-C6Alkyl can enumerate trifluoromethyl, difluoromethyl, perfluoro-ethyl, 1,1,1-
Trifluoroethyl, 1,1- bis-fluoro ethyls, perfluoro propyl, perfluoroisopropyl, perfluoro butyl, perfluor sec-butyl, perfluoro-t-butyl, perfluor
Amyl, perfluoro hexyl, trichloromethyl, 1,1,1- trichloroethyl, 1,1,1- three bromomethyl, trisbromomethyl and three iodomethyls etc..
It is preferred that trifluoromethyl, difluoromethyl, 1,1,1- trifluoroethyl, 1,1- bis-fluoro ethyls.
As R1、R2And R3In C3-C6Naphthenic base can enumerate cyclopropyl, cyclobutyl, cyclopenta and cyclohexyl.It is preferred that
Cyclopropyl and cyclobutyl.
As R1、R2In the C being related to1-C6Alkoxy can enumerate methoxyl group, ethyoxyl, propoxyl group, isopropoxy, fourth
Oxygroup, amoxy and hexyloxy.Preferably methoxyl group, ethyoxyl, propoxyl group, isopropoxy.
As R1、R2In C2-C6Alkenyl can enumerate vinyl, allyl, 2- cyclobutenyl, 3- cyclobutenyl.
As R1、R2In C2-C6Alkynyl group can enumerate acetenyl, propargyl, 2- butynyl, 3- butynyl.
As R1、R2In C5-C12Aryl or heteroaryl, can enumerate phenyl, naphthalene, tolyl, pyrazolyl, isoxazolyl,
Pyrimidine radicals, pyridazinyl, pyrazinyl, pyridyl group, furyl, thienyl, pyrrole radicals, triazine radical, thiazolyl etc., preferably phenyl, first
Phenyl.
R1And R2It preferably is selected from OR1、OR2, further preferably from methoxyl group, ethyoxyl.
Formula (II) compound represented:
In formula (II), X1、X2Expression chlorine atom, bromine atom or iodine atom independently, R4、R5、R6And R7Independently
Expression halogen atom, C1-C6Alkyl, halogenated C1-C6Alkyl, C2-C6Alkenyl, C1-C6Alkoxy, C2-C6Alkoxy carbonyl,
Hydrogen atom or cyano, wherein X1、X2、R4、R5、R6And R7And it is not all identical, in addition, R5And R7Can bond together and and they
The carbon atom being bonded is formed together the ring of cyclopropane ring, cyclobutane ring, pentamethylene ring, cyclohexane ring etc..In the feelings for forming ring
Under condition, it is preferably formed as pentamethylene ring or cyclohexane ring.
As R4、R5、R6And R7In halogen atom, C1-C6Alkyl, halogenated C1-C6Alkyl, C1-C6Alkoxy can be enumerated
Group same as described above.
As R4、R5、R6And R7In C2-C6Alkenyl can enumerate vinyl, allyl, 1- acrylic and 1- methyl -2- third
Alkenyl.Preferably vinyl, allyl and 1- acrylic.
As R4、R5、R6And R7In C2-C6Alkoxy carbonyl can enumerate methoxycarbonyl, ethoxy carbonyl, propoxyl group
Carbonyl, isopropoxy carbonyl and butoxy carbonyl.Preferably methoxycarbonyl, ethoxy carbonyl, propoxycarbonyl and isopropyl oxygen
Base carbonyl.
R4、R5、R6And R7Preferably halogen atom, the halogen atom are more preferably chlorine atom.
R4、R5、R6And R7It is preferred that all identical.
X1、X2Separately indicate chlorine atom, bromine atom or iodine atom, X1、X2It is preferred that identical.
X1、X2Both preferably bromine atom.
In X1、X2Identical and R4、R5、R6And R7In the case where halogen atom, R4、R5、R6And R7Preferably and X1、X2It is different
Halogen atom.
Formula (II) concrete example is 1,2- bis- bromo- 1, and 1,2,2- tetrachloroethanes and 1,2- bis- bromo- 1,1,2,2- tetrafluoroethane is excellent
Selecting example is the bromo- 1,1,2,2- tetrachloroethanes of 1,2- bis-.
Formula (II') compound represented:
X in formula (II')3、X4、X5Indicate halogen atom, R8Indicate hydrogen atom, nitro, halogen atom, C1-C6It is alkyl, halogenated
C1-C6Alkyl, C1-C6Alkoxy or by (1-3 C1-C6Alkyl, C1-C6Alkoxy or halogen atom) replace C5-C12Aryl is miscellaneous
Aryl；
X3、X4、X5Indicate halogen atom.Fluorine atom, chlorine atom, bromine atom and iodine atom can be enumerated as halogen atom.It is excellent
Choosing makes X3、X4、X5In it is at least two mutually the same, more preferably make X3、X4、X5It is all identical.
R8Indicate hydrogen atom, nitro, halogen atom, C1-C6Alkyl, halogenated C1-C6Alkyl, C1-C6Alkoxy or by (1-3
A C1-C6Alkyl, C1-C6Alkoxy or halogen atom) replace C5-C12Aryl or heteroaryl.As R8In halogen atom, can arrange
Lift fluorine atom, chlorine atom, bromine atom and iodine atom.As R8In C1-C6Alkyl, halogenated C1-C6Alkyl can enumerate methyl, second
Base, propyl, isopropyl, butyl, sec-butyl, tert-butyl, amyl, hexyl, trifluoromethyl, difluoromethyl, perfluoro-ethyl, perfluor third
Base, perfluoroisopropyl, perfluoro butyl, perfluor sec-butyl, perfluoro-t-butyl, perfluoropentyl, perfluoro hexyl, trichloromethyl, tribromo
Methyl and three iodomethyls, preferably C1-C3Alkyl, trifluoromethyl and difluoromethyl.As R8In C1-C6Alkoxy can be enumerated
Methoxyl group, ethyoxyl, propoxyl group, isopropoxy, butoxy, amoxy and hexyloxy, preferably C1-C3Alkoxy.As R8In
C5-C12Aryl, heteroaryl, phenyl, naphthalene, pyrazolyl, oxazolyl, pyridyl group and tolyl, preferably C can be enumerated6-C8Virtue
Base, heteroaryl.
R8Preferably nitro or halogen atom, more preferably halogen atom, particularly preferably and X3、X4、X5Different halogens
Atom.
As formula (II'), can enumerate tetrachloromethane, tetrabromomethane, bromine chloroform, three bromoiodomethanes, bromotrifluoro-methane,
Bromochlorodifluoromethane and bromopicrin.Preferably tetrabromomethane, bromine chloroform, three bromoiodomethanes, bromotrifluoro-methane and
Bromochlorodifluoromethane, more preferably tetrabromomethane and bromine chloroform.
In addition both compound (II) and compound (II') can be used, also can be used alone compound (II) or change
It closes object (II').
Relative to 1 mole of compound (I-a), it is selected from least one of compound (II) and compound (II') compound
Usage amount be usually 0.2~10 mole of ratio, preferably 0.5~5 mole of ratio, more preferably 1~5 mole of ratio
Example, further preferably 1~4 mole of ratio.
Formula (III) compound represented
R3-OM (III)
In formula (III), R3Indicate C1-C12Alkyl, halogenated C1-C12Alkyl, C3-C6Naphthenic base or C2-C6Alkenyl, M indicate alkali
Metallic atom；
As R3In C1-C12Alkyl can enumerate methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, penta
Base, hexyl, nonyl, decyl, undecyl and dodecyl.Preferably C1-C6Alkyl.
As R3In C3-C6Naphthenic base can enumerate cyclopropyl, cyclobutyl, cyclopenta and cyclohexyl.Preferably C3-C5Ring
Alkyl.
As R3In C2-C6Alkenyl can enumerate vinyl, allyl, 1- acrylic and 1- methyl -2- acrylic.It is preferred that
For C2-C3Alkenyl.
R3Preferably C1-C6Alkyl, further preferably methyl or ethyl.
It is sodium methoxide, sodium ethoxide, sodium isopropylate, sodium propoxide, sodium tert-butoxide, potassium methoxide, ethyl alcohol as compound (III)
Potassium, potassium isopropoxide, potassium propoxide, potassium tert-butoxide, lithium methoxide, lithium ethoxide, isopropyl lithium alkoxide, lithium propoxide and tert-butyl alcohol lithium.Preferably first
Sodium alkoxide, potassium methoxide, sodium ethoxide.
As alkali metal hydroxide, (V) compound represented can be enumerated.
M-OH (V)
In formula (V), M indicates alkali metal atom；
As the alkali metal in M, sodium atom, potassium atom and lithium atom can be enumerated.Preferably sodium atom and potassium atom.
Sodium hydroxide, potassium hydroxide and lithium hydroxide can be enumerated as compound (V).Preferably sodium hydroxide and hydroxide
Potassium.
As alkali metal hydride, lithium hydride, sodium hydride and hydrofining can be enumerated.
As alkali metal, lithium atom, sodium atom and potassium atom can be enumerated.
As corresponding alcohol, formula (IV) compound represented can be enumerated.
R3-OH (IV)
In formula (IV), R3Indicate C1-C12Alkyl, C3-C6Naphthenic base or C2-C6Alkenyl；
As compound (IV), methanol, ethyl alcohol, propyl alcohol, isopropanol, the tert-butyl alcohol, cyclopropyl alcohol, cyclohexanol and 2- third can be enumerated
Alkene -1- alcohol, preferably methanol or ethyl alcohol.
Relative to 1 mole of compound (I-a), the usage amount of compound (III) is usually 1~100 mole, preferably 1~
10 moles of ratio.
Pyridine compounds (I) can be by making compound (III), compound (I-a) and selected from compound (II) and chemical combination
The compound reaction of at least one of both objects (II') is to manufacture.In reaction, these compounds are mixed in any order it is
It can.For example, can be mixed selected from least one of compound (II) and compound (II') compound and compound (I-a)
It closes in object and adds compound (III), addition can also be selected from chemical combination in the mixture of compound (I-a) and compound (III)
At least one of object (II) and compound (II') compound.In addition it can the parallel additionization simultaneously in compound (I-a)
It closes object (III) and is selected from least one of compound (II) and compound (II') compound.
Compound (I-a) once can be mixed all, can also be mixed with piecemeal.
Compound (II) and compound (II') once can also be mixed all, can also be mixed with piecemeal.
Reaction can carry out in a nitrogen atmosphere.
Reaction temperature be usually -20 DEG C~150 DEG C in the range of, in the range of preferably 0~100 DEG C.Reaction time is logical
It is often 0.1~72 hour, preferably 1~24 hour.
The reaction of compound (III), compound (I-a) and compound (II) and compound (II') can in a solvent into
Row, as solvent, can enumerate methanol, ethyl alcohol, propyl alcohol, isopropanol and the tert-butyl alcohol.
Pyridine compounds (I) can be by making compound (IV), compound (V), compound (I-a) and being selected from compound
(II) and the compound reaction of at least one of both compound (II') is to manufacture.In reaction, by these compounds according to any
Sequence mixes.For example, can be in compound (I-a), compound (IV) and in compound (II) and compound (II')
At least one compound mixture in add compound (V), at this point it is possible to by a part and compound of compound (IV)
(V) parallel addition simultaneously.Can also compound (I-a), compound (IV), compound (V) mixture in addition selected from change
Close at least one of object (II) and compound (II') compound.Furthermore it is also possible to add parallel simultaneously in compound (I-a)
Add compound (IV), compound (V) and selected from least one of compound (II) and compound (II') compound.
It once can also all be added selected from least one of compound (II) and compound (II') compound, it can also
It is added with piecemeal, compound (V) once can also be added all, can also be added with piecemeal.Into
And compound (IV) once can also be added all, it can also a part of addition of a part.
Relative to 1 mole of compound (I-a), the usage amount of compound (IV) is usually 1~100 mole, preferably 1~10
Mole ratio.
Relative to 1 mole of compound (I-a), the usage amount of compound (V) is usually 1~100 mole, preferably 1~10
Mole ratio.
Reaction can carry out in a nitrogen atmosphere.
Reaction temperature be usually -20 DEG C~150 DEG C in the range of, in the range of preferably 0~100 DEG C.Reaction time is logical
It is often 0.1~72 hour, preferably 1~24 hour.
The by-product generated with reaction can be removed to side and implement to react outside reaction system.
After reaction, resulting reaction mixture is concentrated, it is possible thereby to take out pyridine compounds (I).It can also
Acid or ammonium chloride are added in resulting reaction mixture as needed.
As acid, hydrogen chloride and sulfuric acid can be enumerated.
Resulting pyridine compounds (I) can use the common means of purification such as cleaning, distillation, column chromatography and be purified.
In the pyridine compounds shown in formula (I), preferred formula (VI) compound represented.
R in formula (VI)1And R2It preferably is selected from methoxyl group, ethyoxyl, propoxyl group, isopropoxy, n-butoxy, sec-butoxy, uncle
Butoxy.Further preferred methoxyl group, ethyoxyl.
Unless otherwise indicated, remaining is market purchase gained to required raw material in reaction.
Embodiment
Embodiment 1
In a nitrogen atmosphere, by 20.9 grams of 5- methyl -2,3- pyridinedicarboxylic acid dimethyl ester, 1,2- bis- bromo- 1,1,2,2- tetra-
60 grams of chloroethanes.And 40 grams of 20% sodium methoxide-methanol solution mixing.Resulting mixture is stirred at room temperature 20 hours.Reaction
It finishes, is acidified with hydrochloric acid.It is extracted with 200ml ethyl acetate.Resulting organic layer is successively used into water and saturated common salt
Water is cleaned, and is dried with anhydrous sodium sulfate, later, is concentrated under reduced pressure.Obtain 5- (methoxy) -2,3- pyridine
25.1 grams of dicarboxylic acid dimethyl ester.Content 85.2%.
Embodiment 2
In a nitrogen atmosphere, by 23.7 grams of 5- methyl -2,3- diethyl pyridinedicarboxylate, 1,2- bis- bromo- 1,1,2,2- tetra-
60 grams of chloroethanes and 100 grams of methanol mixing, are heated to 65 DEG C.32 grams of potassium hydroxide of the addition into resulting reaction mixture, then
1,2- bis- bromo- 1 is added, 1,2,2- 10 grams of tetrachloroethanes and 8 grams of potassium hydroxide stir 2 hours.Resulting reaction mixture is cold
But to after room temperature, saturated aqueous ammonium chloride is added, is concentrated under reduced pressure.Liquid separation is carried out after residue with ethyl acetate is diluted,
Obtain organic layer and water layer.Resulting aqueous layer with ethyl acetate is extracted, ethyl acetate layer is obtained.By ethyl acetate layer with
The organic layer previously obtained merges.It is dry, it is concentrated under reduced pressure.Obtain 5- (methoxy) -2,3- diethyl pyridinedicarboxylate
30.2 grams, content 86%.
Embodiment 3
In a nitrogen atmosphere, 42 grams of 5- methyl -2,3- pyridinedicarboxylic acid dimethyl esters and 3 grams of phosphotungstic acid catalysts are mixed,
Stirring, is slowly added to 90 grams of hydrogen peroxide of 30%, 70 DEG C insulation reaction 5 hours, be cooled to room temperature, filter, isolate catalysis
Agent, the filtrate of concentration obtain 45 grams of finished product of pyridinedicarboxylic acid dimethyl ester nitrogen oxides of 5- methyl -2,3-, yield 97.6%.
In a nitrogen atmosphere, to 45 grams of 5- methyl -2,3- pyridinedicarboxylic acid dimethyl ester nitrogen oxides and bromine three at 70 DEG C
In the mixture that 105 grams of chloromethanes, with 230 grams of sodium methoxide-methanol solution of dropwise addition 28% in 8 hours.Resulting mixture is existed
Continue stirring 3 hours at this temperature.Resulting reaction mixture is concentrated, water is added to residue, is extracted with toluene.
Resulting organic layer is concentrated under reduced pressure, is obtained comprising 5- (methoxy) -2,3- pyridinedicarboxylic acid dimethyl ester nitrogen
46 grams of oxide.Yield 90.2%.
Embodiment 4
In a nitrogen atmosphere, by 23.7 grams of 5- methyl -2,3- diethyl pyridinedicarboxylate, 60 grams of ethyl alcohol and 28% second
120 grams of alcohol-alcohol sodium solution mixing, are added dropwise 60 grams of bromine chloroform, stir 12 hours at 50 DEG C.Acidification, removed under reduced pressure ethyl alcohol,
Water layer is extracted with ethyl acetate, removes water layer, organic layer is concentrated under reduced pressure.Obtain 5- (ethoxyl methyl) -2,3- pyridinedicarboxylic acid
19.6 grams of diethylester, yield 70%.
Under nitrogen atmosphere, by 19.6 grams of 5- (ethoxyl methyl) -2,3- diethyl pyridinedicarboxylates of above-mentioned gained, 100
The acetic acid solution of gram 20% hydrogen bromide, is warming up to 65 DEG C and is stirred to react 5 hours.End of reaction, decompression abjection reaction dissolvent, obtains 5-
21.5 grams of (bromomethyl) -2,3- diethyl pyridinedicarboxylate, yield 97.7%.
Above-mentioned resulting 21.5 grams of 5- (bromomethyl) -2,3- diethyl pyridinedicarboxylate is mixed with 80 grams of methanol at room temperature
It closes, 13 gram 30% of sodium methoxide-methanol solution is added dropwise.It is stirred to react 3 hours, prolapse solvent obtains product 5- (methoxy)-
2,3- 17.5 grams of diethyl pyridinedicarboxylates, yield 96.7%.
Embodiment 5
In a nitrogen atmosphere, by 20.9 grams of 5- methyl -2,3- pyridinedicarboxylic acid dimethyl ester, 50 grams of tetrabromomethane and 30% first
40 grams of sodium alkoxide-methanol solution mixing.Resulting mixture is stirred at room temperature 15 hours.End of reaction, acidification.With 200ml second
Acetoacetic ester extracts it.Resulting organic layer is successively cleaned with water and saturated salt solution, and uses anhydrous sodium sulfate
It is dried, later, is concentrated under reduced pressure.Obtain 18 grams of dimethyl ester of 5- (methoxy) -2,3- pyridinedicarboxylic acid.Content
75.2%.
Embodiment 6
In a nitrogen atmosphere, it was added dropwise simultaneously with 8 hours at 70 DEG C into 16.3 grams of 5- methyl -2,3- pyridinedicarboxylic acid acid anhydrides
45 grams of bromine chloroform and 160 grams of sodium hydroxide-methanol solution of 20%, continue stirring 3 hours at such a temperature.To resulting
Reaction mixture is concentrated, and to residue plus water, is extracted with toluene.Organic layer concentration, obtains 5- methoxy -2,3-
16.2 grams of pyridinedicarboxylic acid acid anhydride, yield 84%.
Claims (14)
1. a kind of pyridine compounds, it is characterised in that:
In Formulas I:
R1And R2Can be identical or different, it is respectively selected from OR1、NR1R2, or R when considered together1R2Can be with are as follows:-O- ,-S- or
NR3；
R3Indicate C1-C12Alkyl, halogenated C1-C12Alkyl, C3-C6Naphthenic base or C2-C6Alkenyl；
R1And R2It is independently selected from: hydrogen, K, Na, Ca, C1-C6Alkyl, halogenated C1-C6Alkyl, C3-C6Naphthenic base, C2-C6Alkene
Base, C2-C6Alkynyl group, (by 1-3 C1-C6Alkyl, C1-C6Alkoxy or halogen atom) replace C5-C12Aryl or heteroaryl；
R3Selected from hydrogen, C1-C6Alkyl, halogenated C1-C6Alkyl, C3-C6Naphthenic base；
N is selected from 0 or 1.
2. a kind of preparation method of pyridine compounds as shown in claim 1, which is characterized in that with chemical combination shown in (I-a)
Change shown at least one of object, formula (II) compound represented and formula (II') compound represented compound and formula (III)
Closing object is that raw material is synthesized, reaction process are as follows:
Wherein raw material II, II', III are respectively selected from following structural compounds:
In Formula II, X1And X2Separately indicate chlorine atom, bromine atom or iodine atom, R4、R5、R6And R7Expression independently
Halogen atom, C1-C6Alkyl, halogenated C1-C6Alkyl, C2-C6Alkenyl, C1-C6Alkoxy, C2-C6Alkoxy carbonyl, hydrogen atom
Or cyano, wherein X1、X2、R4、R5、R6And R7And it is not all identical, in addition, R5And R7It can bond together and be bonded with them
Carbon atom be formed together ring；
In formula (II'), X3、X4、X5Indicate halogen atom, R8Indicate hydrogen atom, nitro, halogen atom, C1-C6Alkyl, halogenated C1-
C6Alkyl, C1-C6Alkoxy or by (1-3 C1-C6Alkyl, C1-C6Alkoxy or halogen atom) replace C5-C12Aryl or heteroaryl
Base；
R3-OM (III)
In formula (III), R3Indicate C1-C12Alkyl, halogenated C1-C12Alkyl, C3-C6Naphthenic base or C2-C6Alkenyl, M indicate alkali metal
Atom；
In reaction equation, R1、R2And n has meaning same as described above.
3. the manufacturing method of pyridine compounds according to claim 2, which is characterized in that with chemical combination shown in formula (I-a)
Object, formula (II) compound represented and formula (III) compound represented are that raw material is synthesized.
4. a kind of preparation method of pyridine compounds as shown in claim 1, which is characterized in that with chemical combination shown in formula (IV)
Object, formula (V) compound represented, formula (I-a) compound represented and selected from shown in formula (II) compound represented and formula (II')
At least one of compound compound be that raw material is synthesized, reaction process are as follows:
Wherein raw material IV, V is respectively selected from following compound:
R3-OH (IV)
In formula (IV), R3Indicate C1-C12Alkyl, C3-C6Naphthenic base or C2-C6Alkenyl；
M-OH (V)
In formula (V), M indicates alkali metal atom；
In reaction equation, R1、R2、R3, II, II' and n have meaning same as described above.
5. the manufacturing method of pyridine compounds according to claim 4, it is characterised in that with formula (IV) compound represented,
Formula (V) compound represented, formula (I-a) compound represented and (II) compound represented are that raw material is synthesized.
6. manufacturing method according to claim 2, which is characterized in that X1With X2It is identical.
7. manufacturing method according to claim 2, which is characterized in that formula (II) compound represented is preferably 1,2- bis-
Bromo- 1,1,2,2- tetrachloroethanes or the bromo- 1,1,2,2- tetrafluoroethane of 1,2- bis-.
8. the manufacturing method of pyridine compounds according to claim 2, which is characterized in that with chemical combination shown in formula (I-a)
Object, formula (II') compound represented and formula (III) compound represented are that raw material is synthesized.
9. the manufacturing method of pyridine compounds according to claim 4, which is characterized in that with chemical combination shown in formula (IV)
Object, formula (V) compound represented, formula (I-a) compound represented and (II') compound represented are that raw material is synthesized.
10. the manufacturing method of pyridine compounds according to claim 8 or claim 9, which is characterized in that R8For halogen atom.
11. the manufacturing method of pyridine compounds according to claim 9 or 10, which is characterized in that change shown in formula (II')
Closing object is preferably tetrabromomethane or bromine chloroform.
12. a kind of pyridine compounds, it is characterised in that:
In formula (VI), R1And R2Can be identical or different, it is respectively selected from OR1、NR1R2, or R when considered together1R2It can be with are as follows:-
O- ,-S- or NR3；
R1And R2It is independently selected from: hydrogen, K, Na, Ca, C1-C6Alkyl, halogenated C1-C6Alkyl, C3-C6Naphthenic base；
R3Selected from hydrogen, C1-C6Alkyl, halogenated C1-C6Alkyl, C3-C6Naphthenic base；N is selected from 0 or 1.
13. pyridine compounds according to claim 12, which is characterized in that R1With R2It is identical, it is C1-C6Alkoxy or R1R2
Are as follows:-O-, n are selected from 0 or 1.
14. pyridine compounds according to claim 12, which is characterized in that R1With R2It is identical, preferably methoxyl group, ethoxy
Base or R1R2Are as follows:-O-, n are selected from 0 or 1.
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| CN114904474A (en) * | 2022-05-26 | 2022-08-16 | 内蒙古新农基科技有限公司 | 5-bromomethylpyridine-2, 3-dicarboxylic acid diethyl ester reaction device and method |
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| CN114904474B (en) * | 2022-05-26 | 2024-02-09 | 内蒙古新农基科技有限公司 | Device and method for reacting diethyl 5-bromomethylpyridine-2, 3-dicarboxylic acid |
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