CN108586369B - Process for producing phenyltriazine compound and process for producing phenylpyridine compound - Google Patents

Process for producing phenyltriazine compound and process for producing phenylpyridine compound Download PDF

Info

Publication number
CN108586369B
CN108586369B CN201810571784.1A CN201810571784A CN108586369B CN 108586369 B CN108586369 B CN 108586369B CN 201810571784 A CN201810571784 A CN 201810571784A CN 108586369 B CN108586369 B CN 108586369B
Authority
CN
China
Prior art keywords
carbon atoms
formula
compound
phenyl
structure shown
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.)
Active
Application number
CN201810571784.1A
Other languages
Chinese (zh)
Other versions
CN108586369A (en
Inventor
郭海泉
马平川
杨正慧
陈文慧
宋玉春
高连勋
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Changchun Institute of Applied Chemistry of CAS
Original Assignee
Changchun Institute of Applied Chemistry of CAS
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Changchun Institute of Applied Chemistry of CAS filed Critical Changchun Institute of Applied Chemistry of CAS
Priority to CN201810571784.1A priority Critical patent/CN108586369B/en
Publication of CN108586369A publication Critical patent/CN108586369A/en
Application granted granted Critical
Publication of CN108586369B publication Critical patent/CN108586369B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D253/00—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00
    • C07D253/02—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00 not condensed with other rings
    • C07D253/06—1,2,4-Triazines
    • C07D253/065—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members
    • 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
    • C07D213/06—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 containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
    • C07D213/08—Preparation by ring-closure
    • 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
    • C07D213/06—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 containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
    • C07D213/16—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 containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing only one pyridine ring
    • 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
    • C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/26—Radicals substituted by halogen atoms or nitro radicals
    • 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
    • C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/30—Oxygen atoms
    • 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
    • C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/55—Acids; Esters
    • 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
    • C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/56—Amides
    • 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
    • C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/57—Nitriles

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

The invention relates to the technical field of compound synthesis, in particular to a preparation method of a phenyl triazine compound and a preparation method of a phenylpyridine compound. Then, the phenyl triazine compound with the structure shown in the formula (III), the norbornadiene and a second organic solvent which are prepared by the method are subjected to inverse Diels-Alder reaction to obtain the phenyl pyridine compound with the structure shown in the formula (VI), a noble metal catalyst is not needed in the reaction, and the reaction yield and the purity are high. In addition, the preparation method provided by the invention has the advantages of simple route, good process controllability, low cost and easy industrial production.

Description

Process for producing phenyltriazine compound and process for producing phenylpyridine compound
Technical Field
The invention relates to the technical field of compound synthesis, in particular to a preparation method of a phenyl triazine compound and a preparation method of a phenylpyridine compound.
Background
The phenylpyridine and the derivatives thereof are not only important intermediates for chemical and pharmaceutical synthesis, but also can be used as ligands of metal catalysts due to unique chelation, and are applied to photosensitizers and indicators for detecting metal ions, so that the research on the synthesis method of the phenylpyridine attracts wide attention.
At present, cross-coupling reaction, such as Suzuki coupling reaction of phenylboronic acid, is mainly adopted for synthesizing phenylpyridine, but the coupling reaction needs noble metal as a catalyst, and particularly, when the coupling reaction is carried out on two substituents simultaneously on diphenyl substituted pyridine, satisfactory yield cannot be obtained.
In 2007, kappa et al (Advanced Synthesis and Catalysis, 2007, 349: 448-452) reported the Synthesis of 2, 5-diphenylpyridine by Suzuki coupling reaction of 2-bromo-5-mercaptopyridine with phenylboronic acid using tetrakis (triphenylphosphine) palladium as a catalyst. In 2013, the Suzuki coupling reaction of 2, 5-dibromopyridine and phenylboronic acid is reported to be synthesized into 2, 5-diphenylpyridine by Zhou et al (Tetrahedron, 2013, 51: 10996-11003). The reaction uses expensive palladium acetate as catalyst, the yield is only 73%, and the single coupling product reaches 25%. In 2013, Wang et al (European journal of Organic Chemistry, 2013, 31: 7175-7183) reported the Suzuki coupling reaction of 2-bromo-5-hydroxypyridine p-toluenesulfonate with phenylboronic acid to synthesize 2, 5-diphenylpyridine. Expensive palladium acetate catalysts are also used. In 2015, Frost et al (chemical communications, 2015, 51: 12807-12810) reported the synthesis of 2-p-nitrophenylpyridine from 2-bromopyridine and p-nitrobenzoic acid. The reaction uses tetrakis (triphenylphosphine) palladium as a catalyst, and the yield is only 68 percent after the reaction is carried out for 15 hours at 100 ℃.
It was found that these cross-coupling reactions not only require the use of expensive palladium catalysts, but also give low yields.
Disclosure of Invention
In view of this, the technical problem to be solved by the present invention is to provide a preparation method of phenyl triazine compound and a preparation method of phenyl pyridine compound, wherein the phenyl triazine compound prepared by the preparation method of the present invention has a high yield; the phenyl pyridine compound prepared by the preparation method has high yield.
The invention provides a preparation method of a phenyl triazine compound, which comprises the following steps:
mixing a compound with a structure shown in a formula (I), a compound with a structure shown in a formula (II), an organic protonic acid, an ammonium salt and a first organic solvent, and reacting at 50-200 ℃ for 2-48 h to obtain a phenyl triazine compound with a structure shown in a formula (III);
Figure BDA0001678531200000021
wherein, X is selected from one of halogen;
R1and R2Independently selected from phenyl or phenyl containing substituent, wherein the substituent is selected from one or more of alkyl, alkoxy, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, amino, amido, carboxyl, ester group and acyl.
Preferably, the first and second liquid crystal materials are,
x is selected from chlorine or bromine;
the R is1And R2The aryl group is independently selected from phenyl or phenyl containing substituent groups, wherein the substituent groups are selected from one or more of alkyl with 1-5 carbon atoms, alkoxy with 1-5 carbon atoms, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, amino, acylamino with 1-5 carbon atoms, carboxyl with 1-5 carbon atoms, ester with 1-5 carbon atoms and acyl with 1-5 carbon atoms.
Preferably, said R is1Has a structure shown in a formula (IV):
Figure BDA0001678531200000022
wherein R is3One or more selected from hydrogen, alkyl with 1-5 carbon atoms, alkoxy with 1-5 carbon atoms, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, amino, acylamino with 1-5 carbon atoms, carboxyl with 1-5 carbon atoms, ester with 1-5 carbon atoms and acyl with 1-5 carbon atoms;
the R is2Has a structure represented by formula (V):
Figure BDA0001678531200000023
wherein R is4One or more selected from hydrogen, alkyl with 1-5 carbon atoms, alkoxy with 1-5 carbon atoms, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, amino, acylamino with 1-5 carbon atoms, carboxyl with 1-5 carbon atoms, ester with 1-5 carbon atoms and acyl with 1-5 carbon atoms.
Preferably, the molar ratio of the compound having the structure shown in the formula (I) to the compound having the structure shown in the formula (II) to the organic protonic acid to the ammonium salt is 1: 0.92-1.05: 3.0-10.0: 3.0 to 10.0;
the organic protonic acid is selected from formic acid, acetic acid or propionic acid;
the ammonium salt is selected from ammonium formate, ammonium acetate or ammonium propionate.
Preferably, the first organic solvent is selected from one or more of methanol, ethanol, propanol, isopropanol, tert-butanol, tetrahydrofuran, dioxane, ethylene glycol methyl ether, ethylene glycol ethyl ether, ethylene glycol butyl ether, methyl tert-butyl ether, dimethylformamide, dimethylacetamide, methylpyrrolidone and dimethyl sulfoxide;
the dosage ratio of the first organic solvent to the compound with the structure shown in the formula (I) is 500 mL: 10-125 g.
The invention also provides a preparation method of the phenylpyridine compound, which comprises the following steps:
mixing a phenyl triazine compound with a structure shown in a formula (III), norbornadiene and a second organic solvent, and reacting at 100-200 ℃ for 2-48 hours to obtain a phenylpyridine compound with a structure shown in a formula (VI);
Figure BDA0001678531200000031
wherein,R1and R2Independently selected from phenyl or phenyl containing substituent, wherein the substituent is selected from one or more of alkyl, alkoxy, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, amino, amido, carboxyl, ester group and acyl;
the phenyl triazine compound having the structure represented by the formula (III) is prepared according to the preparation method described above.
Preferably, said R is1And R2The aryl group is independently selected from phenyl or phenyl containing substituent groups, wherein the substituent groups are selected from one or more of alkyl with 1-5 carbon atoms, alkoxy with 1-5 carbon atoms, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, amino, acylamino with 1-5 carbon atoms, carboxyl with 1-5 carbon atoms, ester with 1-5 carbon atoms and acyl with 1-5 carbon atoms.
Preferably, said R is1Has a structure shown in a formula (IV):
Figure BDA0001678531200000032
wherein R is3One or more selected from hydrogen, alkyl with 1-5 carbon atoms, alkoxy with 1-5 carbon atoms, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, amino, acylamino with 1-5 carbon atoms, carboxyl with 1-5 carbon atoms, ester with 1-5 carbon atoms and acyl with 1-5 carbon atoms;
the R is2Has a structure represented by formula (V):
Figure BDA0001678531200000041
wherein R is4One or more selected from hydrogen, alkyl with 1-5 carbon atoms, alkoxy with 1-5 carbon atoms, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, amino, acylamino with 1-5 carbon atoms, carboxyl with 1-5 carbon atoms, ester with 1-5 carbon atoms and acyl with 1-5 carbon atoms.
Preferably, the molar ratio of the phenyl triazine compound with the structure shown in the formula (III) to the norbornadiene is 0.09-0.1: 0.2 to 0.9.
Preferably, the second organic solvent is selected from one or more of toluene, xylene, trimethylbenzene, chlorobenzene and dichlorobenzene;
the dosage ratio of the second organic solvent to the phenyl triazine compound with the structure shown in the formula (III) is 200 mL: 4-50 g.
The invention provides a preparation method of a phenyl triazine compound, which comprises the following steps:
mixing a compound with a structure shown in a formula (I), a compound with a structure shown in a formula (II), an organic protonic acid, an ammonium salt and a first organic solvent, and reacting at 50-200 ℃ for 2-48 h to obtain a phenyl triazine compound with a structure shown in a formula (III);
Figure BDA0001678531200000042
wherein, X is selected from one of halogen;
R1and R2Independently selected from phenyl or phenyl containing substituent, wherein the substituent is selected from one or more of alkyl, alkoxy, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, amino, amido, carboxyl, ester group and acyl.
According to the invention, the compound with the structure shown in the formula (I), the compound with the structure shown in the formula (II), the organic protonic acid, the ammonium salt and the first organic solvent are subjected to nucleophilic addition reaction and cyclization reaction to prepare the phenyl triazine compound with the structure shown in the formula (III), a noble metal catalyst is not required to be used in the reaction, and the obtained phenyl triazine compound with the structure shown in the formula (III) has high yield and purity. Then, the phenyl triazine compound with the structure shown in the formula (III), the norbornadiene and a second organic solvent which are prepared by the method are subjected to inverse Diels-Alder reaction to obtain the phenylpyridine compound with the structure shown in the formula (VI), and a noble metal catalyst is not needed in the reaction, so that the yield and the purity of the obtained phenylpyridine compound with the structure shown in the formula (VI) are high. In addition, the preparation method provided by the invention has the advantages of simple route, good process controllability, low cost and easy industrial production.
Experimental results show that when the phenyl triazine compound with the structure shown in the formula (III) is prepared by the preparation method disclosed by the invention, the obtained yield is not lower than 91%, even 96% can be achieved, and the purity (HPLC) > 99.0%; the phenyl pyridine compound with the structure shown in the formula (VI) is prepared by the preparation method, the obtained yield is not lower than 92 percent, even can reach 97 percent, and the purity (HPLC) is more than 99.0 percent.
Detailed Description
The technical solutions of the present invention will be described clearly and completely with reference to the following embodiments of the present invention, 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 invention provides a preparation method of a phenyl triazine compound, which comprises the following steps:
mixing a compound with a structure shown in a formula (I), a compound with a structure shown in a formula (II), an organic protonic acid, an ammonium salt and a first organic solvent, and reacting at 50-200 ℃ for 2-48 h to obtain a phenyl triazine compound with a structure shown in a formula (III);
Figure BDA0001678531200000051
wherein, X is selected from one of halogen;
R1and R2Independently selected from phenyl or phenyl containing substituent, wherein the substituent is selected from one or more of alkyl, alkoxy, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, amino, amido, carboxyl, ester group and acyl.
In the present invention, X is preferably chlorine or bromine;
the R is1Preferably phenyl or phenyl containing substituent, wherein the substituent is selected from one or more of alkyl with 1-5 carbon atoms, alkoxy with 1-5 carbon atoms, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, amino, acylamino with 1-5 carbon atoms, carboxyl with 1-5 carbon atoms, ester with 1-5 carbon atoms and acyl with 1-5 carbon atoms; the substituent is preferably one or more of alkoxy with 1-5 carbon atoms, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, acylamino with 1-5 carbon atoms and ester with 1-5 carbon atoms; the substituent is more preferably one or more of methoxy, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, acetamido and acetoxy.
More preferably, R is1Has a structure shown in a formula (IV):
Figure BDA0001678531200000061
wherein R is3One or more selected from hydrogen, alkyl with 1-5 carbon atoms, alkoxy with 1-5 carbon atoms, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, amino, acylamino with 1-5 carbon atoms, carboxyl with 1-5 carbon atoms, ester with 1-5 carbon atoms and acyl with 1-5 carbon atoms; preferably one or more of alkoxy with 1-5 carbon atoms, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, acylamino with 1-5 carbon atoms and ester with 1-5 carbon atoms; more preferably one or more of methoxy, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, acetamido and acetoxy.
In certain embodiments of the invention, the compound having the structure shown in formula (I) is α -bromoacetophenone, α -chloro-4-methoxyacetophenone, α -bromo-4-nitroacetophenone, α -chloro-4-bromoacetophenone, α -chloro-4-cyanoacetophenone, α -chloro-4-hydroxyacetophenone, α -bromo-4-acetamidoacetophenone or α -bromo-4-formylacetophenone.
The R is2Preferably phenyl or phenyl containing substituents; the substituent is selected from one or more of alkyl with 1-5 carbon atoms, alkoxy with 1-5 carbon atoms, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, amino, acylamino with 1-5 carbon atoms, carboxyl with 1-5 carbon atoms, ester with 1-5 carbon atoms and acyl with 1-5 carbon atoms. More preferably, R is2Has a structure represented by formula (V):
Figure BDA0001678531200000062
wherein R is4One or more selected from hydrogen, alkyl with 1-5 carbon atoms, alkoxy with 1-5 carbon atoms, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, amino, acylamino with 1-5 carbon atoms, carboxyl with 1-5 carbon atoms, ester with 1-5 carbon atoms and acyl with 1-5 carbon atoms; preferably one or more of alkoxy with 1-5 carbon atoms, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, acylamino with 1-5 carbon atoms and ester with 1-5 carbon atoms; more preferably one or more of methoxy, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, acetamido and acetoxy.
In certain embodiments of the present invention, the compound having the structure of formula (II) is phenylhydrazide, 4-methoxybenzenehydrazide, 4-nitrobenzenehydrazide, 4-fluorobenzenehydrazide, 4-hydroxybenzenehydrazide, 4-ethoxyacylphenylhydrazide or 4-acetamidophenylhydrazide.
The organic protic acid is preferably formic acid, acetic acid or propionic acid. The ammonium salt is preferably ammonium formate, ammonium acetate or ammonium propionate.
In the present invention, the molar ratio of the compound having the structure represented by formula (I), the compound having the structure represented by formula (ii), the organic protonic acid, and the ammonium salt is preferably 1: 0.92-1.05: 3.0-10.0: 3.0 to 10.0; more preferably 1: 1: 5.0-8.0: 5.0 to 8.0. In certain embodiments of the present invention, the compound having the structure of formula (I), the compound having the structure of formula (ii), the organic protic acid, and the ammonium salt are present in a molar ratio of 1: 1: 6: 6. 1: 1: 4: 4. 1: 0.92: 10: 10. 1: 1: 8: 8. 1: 1: 9: 9 or 1: 1: 5: 5.
the first organic solvent is preferably one or more of methanol, ethanol, propanol, isopropanol, tert-butanol, tetrahydrofuran, dioxane, ethylene glycol methyl ether, ethylene glycol ethyl ether, ethylene glycol butyl ether, methyl tert-butyl ether, dimethylformamide, dimethylacetamide, methylpyrrolidone and dimethylsulfoxide, and more preferably one or more of ethylene glycol, ethylene glycol ethyl ether, ethylene glycol butyl ether, dimethylacetamide, methylpyrrolidone and dimethylsulfoxide.
The dosage ratio of the first organic solvent to the compound with the structure shown in the formula (I) is 500 mL: 10-125 g. In certain embodiments of the present invention, the amount ratio of the first organic solvent to the compound having the structure represented by formula (I) is 500 mL: 19.9g, 500 mL: 18.4g, 500 mL: 22.9g, 500 mL: 23.3g, 500 mL: 18.6g, 500 mL: 17.0g, 500 mL: 25.6g, 500 mL: 22.7g or 500 mL: 27.1 g.
Mixing a compound with a structure shown in a formula (I), a compound with a structure shown in a formula (II), an organic protonic acid, an ammonium salt and a first organic solvent, and reacting for 2-48 h at 50-200 ℃ to obtain the phenyl triazine compound with a structure shown in a formula (III).
In the invention, the reaction temperature is 50-200 ℃; preferably 80 to 160 ℃. In certain embodiments of the invention, the temperature of the reaction is 140 ℃, 150 ℃, 190 ℃, 130 ℃, 160 ℃ or 170 ℃. The reaction time is 2-48 h; preferably 5-24 h. In certain embodiments of the invention, the reaction time is 15h, 16h, 18h, 20h, 30h, or 36 h.
After the reaction, it is preferable to further include: and (3) filtering and drying the precipitate obtained by the reaction to obtain the phenyl triazine compound with the structure shown in the formula (III). The precipitated product was separated from the reaction system through a filtration process.
The method of filtration is not particularly limited in the present invention, and a filtration method known to those skilled in the art may be used. The solvent adsorbed on the surface of the filtered product is removed through a drying process to obtain a solvent-free product. The method and parameters for drying are not particularly limited in the present invention, and those known to those skilled in the art can be used.
In certain embodiments of the invention, the phenyltriazine compound having the structure shown in formula (III) is 3, 6-diphenyl-1, 2, 4-triazine, 3, 6-bis (4-methoxyphenyl) -1,2, 4-triazine, 3, 6-bis (4-nitrophenyl) -1,2, 4-triazine, 3- (4-fluorophenyl) -6- (4-bromophenyl) -1,2, 4-triazine, 3- (4-hydroxyphenyl) -6- (4-cyanophenyl) -1,2, 4-triazine, 3- (4-methoxyphenyl) -6- (4-hydroxyphenyl) -1,2, 4-triazine, 3- (4-ethoxyacylphenyl) -6- (4-acetamidophenyl) -1,2, 4-triazine, 3- (4-methoxyphenyl) -6- (4-formylphenyl) -1,2, 4-triazine or 3- (4-acetylaminophenyl) -6- (4-nitrophenyl) -1,2, 4-triazine.
According to the invention, the compound with the structure shown in the formula (I), the compound with the structure shown in the formula (II), the organic protonic acid, the ammonium salt and the first organic solvent are subjected to nucleophilic addition reaction and cyclization reaction to prepare the phenyl triazine compound with the structure shown in the formula (III), a noble metal catalyst is not required to be used in the reaction, and the obtained phenyl triazine compound with the structure shown in the formula (III) has high yield and purity. In addition, the preparation method provided by the invention has the advantages of simple route, good process controllability, low cost and easy industrial production.
The invention also provides a preparation method of the phenylpyridine compound, which comprises the following steps:
mixing a phenyl triazine compound with a structure shown in a formula (III), norbornadiene and a second organic solvent, and reacting at 100-200 ℃ for 2-48 hours to obtain a phenylpyridine compound with a structure shown in a formula (VI);
Figure BDA0001678531200000081
wherein R is1And R2Independently selected from phenyl or phenyl containing substituent selected fromOne or more of alkyl, alkoxy, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, amino, acylamino, carboxyl, ester group and acyl;
the phenyl triazine compound having the structure represented by the formula (III) is prepared according to the preparation method described above.
In the present invention, said R1Preferably phenyl or phenyl containing substituent, wherein the substituent is selected from one or more of alkyl with 1-5 carbon atoms, alkoxy with 1-5 carbon atoms, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, amino, acylamino with 1-5 carbon atoms, carboxyl with 1-5 carbon atoms, ester with 1-5 carbon atoms and acyl with 1-5 carbon atoms; the substituent is preferably one or more of alkoxy with 1-5 carbon atoms, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, acylamino with 1-5 carbon atoms and ester with 1-5 carbon atoms; the substituent is more preferably one or more of methoxy, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, acetamido and acetoxy.
More preferably, R is1Has a structure shown in a formula (IV):
Figure BDA0001678531200000091
wherein R is3One or more selected from hydrogen, alkyl with 1-5 carbon atoms, alkoxy with 1-5 carbon atoms, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, amino, acylamino with 1-5 carbon atoms, carboxyl with 1-5 carbon atoms, ester with 1-5 carbon atoms and acyl with 1-5 carbon atoms; preferably one or more of alkoxy with 1-5 carbon atoms, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, acylamino with 1-5 carbon atoms and ester with 1-5 carbon atoms; more preferably one or more of methoxy, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, acetamido and acetoxy.
The R is2Preferably phenyl or phenyl containing substituents; the takingThe substituent is one or more selected from alkyl with 1-5 carbon atoms, alkoxy with 1-5 carbon atoms, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, amino, acylamino with 1-5 carbon atoms, carboxyl with 1-5 carbon atoms, ester with 1-5 carbon atoms and acyl with 1-5 carbon atoms. More preferably, R is2Has a structure represented by formula (V):
Figure BDA0001678531200000092
wherein R is4One or more selected from hydrogen, alkyl with 1-5 carbon atoms, alkoxy with 1-5 carbon atoms, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, amino, acylamino with 1-5 carbon atoms, carboxyl with 1-5 carbon atoms, ester with 1-5 carbon atoms and acyl with 1-5 carbon atoms; preferably one or more of alkoxy with 1-5 carbon atoms, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, acylamino with 1-5 carbon atoms and ester with 1-5 carbon atoms; more preferably one or more of methoxy, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, acetamido and acetoxy.
In certain embodiments of the invention, the phenyltriazine compound having the structure shown in formula (III) is 3, 6-diphenyl-1, 2, 4-triazine, 3, 6-bis (4-methoxyphenyl) -1,2, 4-triazine, 3, 6-bis (4-nitrophenyl) -1,2, 4-triazine, 3- (4-fluorophenyl) -6- (4-bromophenyl) -1,2, 4-triazine, 3- (4-hydroxyphenyl) -6- (4-cyanophenyl) -1,2, 4-triazine, 3- (4-methoxyphenyl) -6- (4-hydroxyphenyl) -1,2, 4-triazine, 3- (4-ethoxyacylphenyl) -6- (4-acetamidophenyl) -1,2, 4-triazine, 3- (4-methoxyphenyl) -6- (4-formylphenyl) -1,2, 4-triazine or 3- (4-acetylaminophenyl) -6- (4-nitrophenyl) -1,2, 4-triazine.
The second organic solvent is preferably one or more of toluene, xylene, trimethylbenzene, chlorobenzene and dichlorobenzene.
The molar ratio of the phenyl triazine compound with the structure shown in the formula (III) to the norbornadiene is preferably 0.09-0.1: 0.2 to 0.9. In certain embodiments of the present invention, the molar ratio of the phenyl triazine compound having the structure represented by formula (iii) to norbornadiene is 0.095: 0.3, 0.094: 0.5, 0.092: 0.4, 0.092: 0.5, 0.091: 0.3, 0.096: 0.4 or 0.093: 0.2.
200mL of the second organic solvent and the phenyl triazine compound having the structure represented by formula (III): 4-50 g. In certain embodiments of the present invention, the mass ratio of the second organic solvent to the phenyl triazine compound having the structure represented by formula (iii) is 200 mL: 22.2g, 200 mL: 27.5g, 200 mL: 31.0g, 200 mL: 31.4g, 200 mL: 25.5g, 200 mL: 25.7g, 200 mL: 33.3g, 200 mL: 27.4g or 200 mL: 33.0 g.
The phenyl triazine compound with the structure shown in the formula (III), norbornadiene and a second organic solvent are mixed and react for 2-48 hours at the temperature of 100-200 ℃, and then the phenyl pyridine compound with the structure shown in the formula (VI) is obtained.
The reaction temperature is 100-200 ℃; preferably 120 to 180 ℃. In certain embodiments of the invention, the temperature of the reaction is 160 ℃. The reaction time is 2-48 h. In certain embodiments of the invention, the reaction time is 15 hours.
After the reaction, it is preferable to further include: cooling and filtering. The cooling method is not particularly limited in the present invention, and a cooling method known to those skilled in the art may be used. The temperature of the cooling is preferably room temperature. The product can be separated from the solvent and excess norbornadiene via a simple filtration process to obtain the pure target product. The method of filtration is not particularly limited in the present invention, and a filtration method known to those skilled in the art may be used.
The phenyl triazine compound with the structure shown in the formula (III), the norbornadiene and the second organic solvent which are prepared by the method are subjected to inverse Diels-Alder reaction to obtain the phenyl pyridine compound with the structure shown in the formula (VI), a noble metal catalyst is not needed in the reaction, and the yield and the purity of the obtained phenyl pyridine compound with the structure shown in the formula (VI) are high. In addition, the preparation method provided by the invention has the advantages of simple route, good process controllability, low cost and easy industrial production.
The source of the raw material components used in the present invention is not particularly limited, and may be generally commercially available.
The invention provides a preparation method of a phenyl triazine compound, which comprises the following steps:
mixing a compound with a structure shown in a formula (I), a compound with a structure shown in a formula (II), an organic protonic acid, an ammonium salt and a first organic solvent, and reacting at 50-200 ℃ for 2-48 h to obtain a phenyl triazine compound with a structure shown in a formula (III);
Figure BDA0001678531200000111
wherein, X is selected from one of halogen;
R1and R2Independently selected from phenyl or phenyl containing substituent, wherein the substituent is selected from one or more of alkyl, alkoxy, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, amino, amido, carboxyl, ester group and acyl.
According to the invention, the compound with the structure shown in the formula (I), the compound with the structure shown in the formula (II), the organic protonic acid, the ammonium salt and the first organic solvent are subjected to nucleophilic addition reaction and cyclization reaction to prepare the phenyl triazine compound with the structure shown in the formula (III), a noble metal catalyst is not required to be used in the reaction, and the obtained phenyl triazine compound with the structure shown in the formula (III) has high yield and purity. Then, the phenyl triazine compound with the structure shown in the formula (III), the norbornadiene and a second organic solvent which are prepared by the method are subjected to inverse Diels-Alder reaction to obtain the phenylpyridine compound with the structure shown in the formula (VI), and a noble metal catalyst is not needed in the reaction, so that the yield and the purity of the obtained phenylpyridine compound with the structure shown in the formula (VI) are high. In addition, the preparation method provided by the invention has the advantages of simple route, good process controllability, low cost and easy industrial production.
Experimental results show that when the phenyl triazine compound with the structure shown in the formula (III) is prepared by the preparation method disclosed by the invention, the obtained yield is not lower than 91%, even 96% can be achieved, and the purity (HPLC) > 99.0%; the phenyl pyridine compound with the structure shown in the formula (VI) is prepared by the preparation method, the obtained yield is not lower than 92 percent, even can reach 97 percent, and the purity (HPLC) is more than 99.0 percent.
In order to further illustrate the present invention, the following examples are provided to describe the preparation method of phenyl triazine compound and the preparation method of phenyl pyridine compound in detail, but should not be construed as limiting the scope of the present invention.
The reagents used in the following examples are all commercially available.
Example 1
Alpha-bromoacetophenone (19.9g,0.1mol), phenylhydrazide (13.6g,0.1mol), acetic acid (36g,0.6mol), ammonium acetate (46.2g,0.6mol) and dimethyl sulfoxide (500ml) are added into a reactor, the reaction mixture is heated to 150 ℃ for reaction for 15h, and the product is precipitated, filtered and dried to obtain 3, 6-diphenyl-1, 2, 4-triazine (22.2g, yield 95%, purity (HPLC) > 99.0%) which is directly used for the next reaction.
3, 6-diphenyl-1, 2, 4-triazine (22.2g, 0.095mol), norbornadiene (27.6g,0.3mol) and trimethylbenzene (200ml) obtained in the above reaction are added into a reactor, heated to 160 ℃ and reacted for 15 hours. After the reaction, the reaction mixture was cooled to room temperature and filtered to obtain 21.3g of 2, 5-diphenylpyridine (yield 97%, purity (HPLC) > 99.0%). 1HNMR (300MHz, DMSO). delta.8.94 (s, 1H), 8.05(d, 2H), 7.95(d, 1H), 7.81(d, 1H), 7.64(d, 2H), 7.50(t, 4H), 7.42(dd, 2H).
Example 2
Alpha-chloro-4-methoxyacetophenone (18.4g,0.1mol), 4-methoxybenzophenone hydrazide (16.6g,0.1mol), propionic acid (29.6g,0.4mol), ammonium propionate (36.4g,0.4mol) and methylpyrrolidone (500ml) were charged to a reactor, and the reaction mixture was heated to 190 ℃ for 36h to precipitate the product, which was filtered and dried to obtain 3, 6-bis (4-methoxyphenyl) -1,2, 4-triazine (27.5g, yield 94%, purity (HPLC) > 99.0%) which was used directly in the next reaction.
3, 6-bis (4-methoxyphenyl) -1,2, 4-triazine (27.5g, 0.094mol) obtained in the above reaction, norbornadiene (46.1g,0.5mol) and xylene (200ml) were added to a reactor, heated to 130 ℃ and reacted for 18 hours. After the reaction was completed, it was cooled to room temperature and filtered to obtain 25.2g of 2, 5-bis (4-methoxyphenyl) pyridine (yield 92%, purity (HPLC) > 99.0%). 1H NMR (300MHz, CDCl3) Δ 8.88(d, 1H), 8.0(d, 2H), 7.92(d, 1H), 7.73(d, 1H), 7.52(d, 2H), 7.29(d, 2H), 7.01(d, 2H), 3.87(s, 6H).
Example 3
Alpha-bromo-4-nitroacetophenone (22.9g,0.1mol), 4-nitrobenzophenone hydrazide (16.6g,0.092mol), acetic acid (60g,1.0mol), ammonium acetate (77g,1.0mol) and ethylene glycol ethyl ether (500ml) were charged to a reactor, the reaction mixture was heated to 130 ℃ and reacted for 20h to precipitate the product, which was filtered and dried to give 3, 6-bis (4-nitrophenyl) -1,2, 4-triazine (31.0g, yield 96%, purity (HPLC) > 99.0%) which was used directly in the next reaction.
3, 6-bis (4-nitrophenyl) -1,2, 4-triazine (31.0g, 0.096mol) obtained in the above reaction, norbornadiene (31.0g,0.4mol) and dichlorobenzene (200ml) were added to a reactor, and the mixture was heated to 180 ℃ to react for 15 hours. After the reaction was completed, it was cooled to room temperature and filtered to obtain 29.0g of 2, 5-bis (4-nitrophenyl) pyridine (31.2g, yield 94%, purity (HPLC) > 99.0%). 1HNMR (300MHz, DMSO). delta.9.18 (s, 1H), 8.46-8.31(dt, 8H), 8.15-8.12(d, 2H).
Example 4
Alpha-chloro-4-bromoacetophenone (23.3g,0.1mol), 4-fluorobenzene hydrazide (15.4g,0.1mol), acetic acid (36g,0.6mol), ammonium acetate (46.2g,0.6mol) and ethylene glycol butyl ether (500ml) were added to a reactor, and the reaction mixture was heated to 150 ℃ to react for 18 hours, and the product was precipitated, filtered and dried to obtain 3- (4-fluorophenyl) -6- (4-bromophenyl) -1,2, 4-triazine (31.4g, yield 95%, purity (HPLC) > 99.0%) which was used directly in the next reaction.
3- (4-fluorophenyl) -6- (4-bromophenyl) -1,2, 4-triazine (31.4g, 0.095mol), norbornadiene (27.6g,0.3mol) and dichlorobenzene (200ml) obtained in the above reaction were added to a reactor, and the mixture was heated to 180 ℃ to react for 27 hours. After the reaction is complete, it is cooled to room temperature and filtered, yielding 29.5g of 2- (4-fluorophenyl) -5- (4-bromophenyl) -pyridine (95% yield, 99.0% purity (HPLC)). 1HNMR (400MHz, CDCl3) delta 8.94(s, 1H), 8.15(d, 2H), 7.99(d, 1H), 7.81(d, 1H), 7.56(t, 4H), 7.34(dd, 2H).
Example 5
Alpha-chloro-4-cyanoacetophenone (18.6g,0.1mol), 4-hydroxybenzohydrazide (15.2g,0.1mol), propionic acid (59.2g,0.8mol), ammonium propionate (72.8g,0.8mol) and ethylene glycol butyl ether (500ml) were charged into a reactor, and the reaction mixture was heated to 170 ℃ to react for 18 hours, and the product was precipitated, filtered and dried to obtain 3- (4-hydroxyphenyl) -6- (4-cyanophenyl) -1,2, 4-triazine (25.5g, yield 93%, purity (HPLC) > 99.0%) which was used directly in the next reaction.
3- (4-hydroxyphenyl) -6- (4-cyanophenyl) -1,2, 4-triazine (25.5g, 0.093mol), norbornadiene (18.4g,0.2mol) and chlorobenzene (200ml) obtained in the above reaction were added to a reactor, heated to 130 ℃ and reacted for 38 hours. After the reaction, the reaction mixture was cooled to room temperature and filtered to obtain 23.8g of 2- (4-hydroxyphenyl) -5- (4-cyanophenyl) pyridine (yield 94%, purity (HPLC) > 99.0%). 1HNMR (500MHz, DMSO). delta.9.67 (s, 1H), 8.90(d, 1H), 7.92(d, 1H), 7.89(d, 1H), 7.68(d, 4H), 7.59(d, 2H), 6.78(d, 2H).
Example 6
Alpha-chloro-4-hydroxyacetophenone (17.0g,0.1mol), 4-methoxybenzophenozide (16.6g,0.1mol), propionic acid (66.6g,0.9mol), ammonium propionate (81.9g,0.9mol) and ethylene glycol (500ml) were charged to a reactor, and the reaction mixture was heated to 190 ℃ to react for 30 hours, and the product was precipitated, filtered and dried to obtain 3- (4-methoxyphenyl) -6- (4-hydroxyphenyl) -1,2, 4-triazine (25.7g, yield 92%, purity (HPLC) > 99.0%) which was used directly in the next reaction.
3- (4-methoxyphenyl) -6- (4-hydroxyphenyl) -1,2, 4-triazine (25.7g, 0.092mol), norbornadiene (36.9g,0.4mol) and trimethylbenzene (200ml) obtained in the above reaction were added to a reactor, and the mixture was heated to 160 ℃ to react for 22 hours. After the reaction, the reaction mixture was cooled to room temperature and filtered to obtain 23.9g of 2- (4-methoxyphenyl) -5- (4-hydroxyphenyl) pyridine (yield 94%, purity (HPLC) > 99.0%). 1HNMR (300MHz, CDCl3) delta 9.50(s, 1H), 8.79(d, 1H), 8.02(d, 2H), 7.82(d, 1H), 7.70(d, 1H), 7.50(d, 2H), 7.22(d, 2H), 6.96(d, 2H), 3.87(s, 3H).
Example 7
Alpha-bromo-4-acetamidoacetophenone (25.6g,0.1mol), 4-ethoxyacylphenylhydrazide (20.8g,0.1mol), acetic acid (36g,0.6mol), ammonium acetate (46.2g,0.6mol) and dimethyl sulfoxide (500ml) were charged into a reactor, and the reaction mixture was heated to 150 ℃ to react for 15h, and the product precipitated, filtered and dried to obtain 3- (4-ethoxyacylphenyl) -6- (4-acetamidophenyl) -1,2, 4-triazine (33.3g, yield 92%, purity (HPLC) > 99.0%) which was used directly in the next step.
3- (4-Ethoxyacylphenyl) -6- (4-acetamidophenyl) -1,2, 4-triazine (33.3g, 0.092mol), norbornadiene (46.1g,0.5mol) and dichlorobenzene (200ml) obtained in the above reaction were added to the reactor, heated to 180 ℃ and reacted for 15 hours. After the reaction, it was cooled to room temperature and filtered to obtain 31.0g of 2- (4-ethoxyacylphenyl) -5- (4-acetamidophenyl) pyridine (yield 94%, purity (HPLC) > 99.0%). 1HNMR (300MHz, DMSO),. delta.9.22 (s, 1H), 8.85(d, 1H), 8.10(d, 1H), 7.91(d, 2H), 7.84(m, 3H), 7.60(d, 2H), 7.12(dd, 2H), 2.3(s, 3H), 2.02(s, 3H).
Example 8
Alpha-bromo-4-formylacetophenone (22.7g,0.1mol), 4-methoxybenzoyl hydrazide (16.6g,0.1mol), acetic acid (30g,0.5mol), ammonium acetate (33.5g,0.5mol) and ethylene glycol ethyl ether (500ml) were charged into a reactor, and the reaction mixture was heated to 140 ℃ for reaction for 16 hours to precipitate a product, which was then filtered and dried to obtain 3- (4-methoxyphenyl) -6- (4-formylphenyl) -1,2, 4-triazine (27.4g, yield 95%, purity (HPLC) > 99.0%) for the next reaction.
3- (4-methoxyphenyl) -6- (4-formylphenyl) -1,2, 4-triazine (27.4g, 0.095mol) obtained in the above reaction, norbornadiene (27.6g,0.3mol) and xylene (200ml) were added to the reactor, and the mixture was heated to 150 ℃ to react for 30 hours. After the reaction, the reaction mixture was cooled to room temperature and filtered to obtain 25.1g of 2- (4-methoxyphenyl) -5- (4-formylphenyl) pyridine (yield 93%, purity (HPLC) > 99.0%). 1H NMR (300MHz, DMSO),. delta.9.52 (s, 1H), 8.91(d, 1H), 8.20(d, 2H), 8.01(d, 2H), 7.94(d, 1H), 7.80(m, 3H), 7.02(dd, 2H), 3.86(s, 3H).
Example 9
Alpha-bromo-4-nitroacetophenone (27.1g,0.1mol), 4-acetamidophenylhydrazide (19.3g,0.1mol), acetic acid (30.0g,0.5mol), ammonium acetate (33.5g,0.5mol) and dimethyl sulfoxide (500ml) were added to a reactor, and the reaction mixture was heated to 150 ℃ to react for 20h, and the product precipitated, filtered and dried to obtain 3- (4-acetamidophenyl) -6- (4-nitrophenyl) -1,2, 4-triazine (33.0g, yield 91%, purity (HPLC) > 99.0%) which was used directly in the next reaction.
3- (4-acetamidophenyl) -6- (4-ethoxyacylphenyl) -1,2, 4-triazine (33.0g, 0.091mol), norbornadiene (27.6g,0.3mol) and xylene (200ml) obtained in the above reaction were added into a reactor, heated to 140 ℃ and reacted for 24 hours. After the reaction, the reaction mixture was cooled to room temperature and filtered to obtain 30.8g of 2- (4-acetamidophenyl) -5- (4-nitrophenyl) pyridine (yield 94%, purity (HPLC) > 99.0%). 1HNMR (300MHz, DMSO). delta.9.44 (s, 1H), 8.90(d, 1H), 8.23(m, 4H), 8.01(d, 1H), 7.81(m, 5H), 2.02(s, 3H).
The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims (10)

1. A process for the preparation of a phenyl triazine compound comprising the steps of:
mixing a compound with a structure shown in a formula (I), a compound with a structure shown in a formula (II), an organic protonic acid, an ammonium salt and a first organic solvent, and reacting at 50-200 ℃ for 2-48 h to obtain a phenyl triazine compound with a structure shown in a formula (III);
Figure DEST_PATH_IMAGE002
（I）；
Figure DEST_PATH_IMAGE004
（Ⅱ）；
Figure DEST_PATH_IMAGE006
（Ⅲ）；
wherein, X is selected from one of halogen;
R1and R2Independently selected from phenyl or phenyl containing substituent, wherein the substituent is selected from one or more of alkyl, alkoxy, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, amino, amido, carboxyl, ester group and acyl;
the molar ratio of the compound with the structure shown in the formula (I) to the compound with the structure shown in the formula (II) to the organic protonic acid to the ammonium salt is 1: 0.92-1.05: 3.0-10.0: 3.0 to 10.0.
2. The production method according to claim 1,
x is selected from chlorine or bromine;
the R is1And R2The aryl group is independently selected from phenyl or phenyl containing substituent groups, wherein the substituent groups are selected from one or more of alkyl with 1-5 carbon atoms, alkoxy with 1-5 carbon atoms, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, amino, acylamino with 1-5 carbon atoms, ester with 1-5 carbon atoms and acyl with 1-5 carbon atoms.
3. The method of claim 2, wherein R is1Has a structure shown in a formula (IV):
Figure DEST_PATH_IMAGE008
（Ⅳ）；
wherein R is3One or more selected from hydrogen base, alkyl with 1-5 carbon atoms, alkoxy with 1-5 carbon atoms, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, amino, acylamino with 1-5 carbon atoms, ester with 1-5 carbon atoms and acyl with 1-5 carbon atoms;
the R is2Has a structure represented by formula (V):
Figure DEST_PATH_IMAGE010
（Ⅴ）；
wherein R is4One or more selected from hydrogen base, alkyl with 1-5 carbon atoms, alkoxy with 1-5 carbon atoms, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, amino, acylamino with 1-5 carbon atoms, ester with 1-5 carbon atoms and acyl with 1-5 carbon atoms.
4. The method according to claim 1, wherein the organic protic acid is selected from formic acid, acetic acid, and propionic acid;
the ammonium salt is selected from ammonium formate, ammonium acetate or ammonium propionate.
5. The preparation method according to claim 1, wherein the first organic solvent is selected from one or more of methanol, ethanol, propanol, tert-butanol, tetrahydrofuran, dioxane, ethylene glycol methyl ether, ethylene glycol ethyl ether, ethylene glycol butyl ether, methyl tert-butyl ether, dimethylformamide, dimethylacetamide, N-methylpyrrolidone, and dimethylsulfoxide;
the dosage ratio of the first organic solvent to the compound with the structure shown in the formula (I) is 500 mL: 10-125 g.
6. A process for preparing a phenylpyridine compound comprising the steps of:
preparing a phenyl triazine compound having a structure represented by formula (iii) according to the method of claim 1;
mixing the phenyl triazine compound with the structure shown in the formula (III), norbornadiene and a second organic solvent, and reacting at 100-200 ℃ for 2-48 hours to obtain a phenylpyridine compound with the structure shown in the formula (VI);
Figure DEST_PATH_IMAGE011
（Ⅲ）；
Figure DEST_PATH_IMAGE013
（Ⅵ）；
wherein R is1And R2Independently selected from phenyl or phenyl containing substituent, wherein the substituent is selected from one or more of alkyl, alkoxy, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, amino, amido, carboxyl, ester group and acyl.
7. The method of claim 6, wherein R is1And R2The aryl group is independently selected from phenyl or phenyl containing substituent groups, wherein the substituent groups are selected from one or more of alkyl with 1-5 carbon atoms, alkoxy with 1-5 carbon atoms, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, amino, acylamino with 1-5 carbon atoms, ester with 1-5 carbon atoms and acyl with 1-5 carbon atoms.
8. The method of claim 6, wherein R is1Has a structure shown in a formula (IV):
Figure 428433DEST_PATH_IMAGE008
（Ⅳ）；
wherein R is3One selected from the group consisting of a hydrogen group, an alkyl group having 1 to 5 carbon atoms, an alkoxy group having 1 to 5 carbon atoms, fluorine, chlorine, bromine, a hydroxyl group, a nitro group, a cyano group, an amino group, an acylamino group having 1 to 5 carbon atoms, an ester group having 1 to 5 carbon atoms and an acyl group having 1 to 5 carbon atomsOr a plurality of the components;
the R is2Has a structure represented by formula (V):
Figure 79994DEST_PATH_IMAGE010
（Ⅴ）；
wherein R is4One or more selected from hydrogen base, alkyl with 1-5 carbon atoms, alkoxy with 1-5 carbon atoms, fluorine, chlorine, bromine, hydroxyl, nitro, cyano, amino, acylamino with 1-5 carbon atoms, ester with 1-5 carbon atoms and acyl with 1-5 carbon atoms.
9. The method according to claim 6, wherein the molar ratio of the phenyltriazine compound having the structure represented by formula (III) to norbornadiene is 0.09 to 0.1: 0.2 to 0.9.
10. The preparation method according to claim 6, wherein the second organic solvent is one or more selected from toluene, xylene, trimethylbenzene, chlorobenzene and dichlorobenzene;
the dosage ratio of the second organic solvent to the phenyl triazine compound with the structure shown in the formula (III) is 200 mL: 4-50 g.
CN201810571784.1A 2018-05-30 2018-05-30 Process for producing phenyltriazine compound and process for producing phenylpyridine compound Active CN108586369B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201810571784.1A CN108586369B (en) 2018-05-30 2018-05-30 Process for producing phenyltriazine compound and process for producing phenylpyridine compound

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201810571784.1A CN108586369B (en) 2018-05-30 2018-05-30 Process for producing phenyltriazine compound and process for producing phenylpyridine compound

Publications (2)

Publication Number Publication Date
CN108586369A CN108586369A (en) 2018-09-28
CN108586369B true CN108586369B (en) 2021-08-17

Family

ID=63630924

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201810571784.1A Active CN108586369B (en) 2018-05-30 2018-05-30 Process for producing phenyltriazine compound and process for producing phenylpyridine compound

Country Status (1)

Country Link
CN (1) CN108586369B (en)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1349514A (en) * 1999-05-04 2002-05-15 辛根塔参与股份公司 Pesticidal triazine derivatives
WO2010112799A1 (en) * 2009-02-26 2010-10-07 University Of York Luminophores comprising platinum-ligand complexes

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1349514A (en) * 1999-05-04 2002-05-15 辛根塔参与股份公司 Pesticidal triazine derivatives
WO2010112799A1 (en) * 2009-02-26 2010-10-07 University Of York Luminophores comprising platinum-ligand complexes

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
A Novel Synthesis of 1,2,4-Triazines;Saraswathi, T. V., et al;《Tetrahedron Letters》;19711231(第25期);第2315-2316页，第2315页第1段、Scheme1 *

Also Published As

Publication number Publication date
CN108586369A (en) 2018-09-28

Similar Documents

Publication Publication Date Title
WO2010123806A1 (en) Synthesis of pyrazines including 2,6-diaminopyrazine-1-oxide (dapo) and 2,6-diamino-3,5-dinitropyrazine-1-oxide (llm-105)
CN114957125B (en) Synthesis method of 4-nitro-5-nitroaminopyrazole
Vériot et al. Synthesis of C3-cyclotriveratrylene ligands for iron (II) and iron (III) coordination
CN113072436A (en) Preparation method of benzyl aryl ether
CN108586369B (en) Process for producing phenyltriazine compound and process for producing phenylpyridine compound
US5498711A (en) Synthesis of 4,10-dinitro-2,6,8,12-tetraoxa-4,10-diazatetracyclo[5.5.0.05,903,11]dodecane
CN109651271B (en) Synthetic method of 3-tert-butyl-N-methylquinoxaline-2 (1H) -ketone compound
CN114213424B (en) Synthesis method of furan [3,2-b ] pyridine derivative
KR0141482B1 (en) Process for the preparation of o-carboxypyridyl and o-carboxyquinolylimidazolinones
CN107382898B (en) Energetic material based on ANPZ energetic parent structure and synthetic method thereof
JPS60208963A (en) Manufacture of diaminopyridine derivative
CN116813525B (en) Synthesis method of polyacetyl substituted oxindole compound
CN113201015B (en) Preparation method of allyl organophosphorus compound
CN111320579B (en) Preparation method of 8-amide-5-halogenated quinoline derivative
CA2401546C (en) Preparation of derivatives of 3-sulfonamido-4-phenylaminopyridine
KR102292794B1 (en) Preparation method of 2-substituted 1,2,3,4-tetrahydroquinoline compound
CN113045491B (en) Preparation method of lenvatinib and intermediate
JP2564141B2 (en) Method for producing alkylbenzothiazoles
JPH01316352A (en) Production of 3-cyano-4-arylpyrrole
US20050159596A1 (en) Cyclic compounds and their use as complex ligands
JPS6261032B2 (en)
CN110551114A (en) Preparation method of raltitrexed
WO2019029507A1 (en) Preparation method for imidazoisoindole derivatives
CN116554081A (en) Synthesis method of 3-phenyl-1-propyl-1H-isoindolecarboxylic acid
CN111333528A (en) Synthesis method of multi-configuration O-phenyl-serine compound

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
GR01 Patent grant
GR01 Patent grant