CN103641776A - Manufacturing method of N-methylene substituted methylamine polymer and triazine derivative - Google Patents
Manufacturing method of N-methylene substituted methylamine polymer and triazine derivative Download PDFInfo
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- CN103641776A CN103641776A CN201310561782.1A CN201310561782A CN103641776A CN 103641776 A CN103641776 A CN 103641776A CN 201310561782 A CN201310561782 A CN 201310561782A CN 103641776 A CN103641776 A CN 103641776A
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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
- C07D213/61—Halogen atoms or nitro radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G73/00—Macromolecular compounds obtained by reactions forming a linkage containing nitrogen with or without oxygen or carbon in the main chain of the macromolecule, not provided for in groups C08G12/00 - C08G71/00
- C08G73/02—Polyamines
- C08G73/0206—Polyalkylene(poly)amines
- C08G73/0213—Preparatory process
Abstract
The invention relates to a manufacturing method of one of or a mixture of more than two of N-methylene substituted methylamine polymer as shown in the following formula (II), which is characterized in that one of or a mixture of more than two of N-methylene substituted methylamine polymer as shown in the formula (II) are obtained by reacting hexamethylene tetramine compounds shown in formula (I) with alkali. In the formula (I), A represents any organic group of an alkyl or heterocyclic group, or the organic group with a substituent group; R represents a hydrogen atom, or any organic group of an alkyl or heterocyclic group, or the organic group with a substituent group; L represents a halogen atom, an alkyl sulfonyl oxy group with a carbon atom number of 1-20, a halogenated alkyl sulfonyl oxy group with a carbon atom number of 1-20, or substituted or unsubstituted aryl sulfonyl oxy group. In the formula (II), A and R represent the same as the above, and n represents an integer of 2-20.
Description
(the application is to be dividing an application of April 24, application number in 2007 are 200780052685.2, denomination of invention is " manufacture method of substituted methylamine compound and pyrrolotriazine derivatives " patent application the applying date.）
Technical field
The present invention relates to easy and high yield, manufacture as the useful substituted methylamine compound of manufacture intermediate of agricultural chemicals and the medicine method of pyridyl methylamine compound for example at low cost, and manufacture N-methylene radical-substituted methylamine polymer of intermediate as it.
Background technology
Substituted methylamine compound is as agricultural chemicals and the medical useful compound of manufacture intermediate such as pyridyl methylamine compounds such as the chloro-5-pyridyl of 2-methylamines.
All the time, manufacture method as pyridyl methylamine compound, the known CCMP that makes reacts with potassium phthalimide, obtains N-(the chloro-5-pyridylmethyl of 2-) phthalic imidine, then makes the method (patent documentation 1) of this material and hydrazine reaction; With the chloro-5-of 2-(chloromethyl) pyridine is reacted with vulkacit H, obtain the chloro-5-pyridylmethyl of 2-hexa-methylene four ammonium muriates, the method being then hydrolyzed (patent documentation 2) under the existence of lower alcohol and mineral acid; Utilize water or buck to make the four ammonium muriate hydrolysis of the chloro-5-pyridylmethyl of 2-hexa-methylene, generate and emanate as the chloro-5-pyridyl of N-methylene radical-2-methylamine, further utilize the sour method (patent documentation 3) being hydrolyzed etc.
But these manufacture method may not can be described as industrial effective means.That is, in the first method, because raw material need to be used more expensive potassium phthalimide, so can not say preferred method at economic aspect.In addition, because need to remove the operation of phthalazines from the reaction solution with hydrazine, so post-processing operation is numerous and diverse.In the second method, the consumption of the solvent using in reaction is many, and the more expensive vulkacit H of a large amount of uses, so can not say preferred method at economic aspect.And in the method, the chloro-5-pyridylmethyl of the 2-hexa-methylene four ammonium muriates that temporary transient segregation generates, are then hydrolyzed, so there is the miscellaneous problem of operation.Third method exists that the chloro-5-pyridyl of the N-methylene radical-2-methylamine emanated is unstable, the problem of difficult treatment.
Patent documentation 1: No. 3727126 communiques of Deutsches Reichs-Patent
Patent documentation 2: Japanese kokai publication hei 3-271273 communique
Patent documentation 3: Japanese kokai publication hei 8-295670 communique
Summary of the invention
The present invention completes in view of the practical situation of above-mentioned prior art, its object is to provide a kind of easy and high yield, manufactures as the useful substituted methylamine compound of the manufacture intermediate of agricultural chemicals and medicine, the preferred method of pyridyl methylamine compound at low cost, and manufactures intermediate.
In order to address the above problem, the present inventor furthers investigate, found that: by making hexa-methylene four ammonium salt compounds and alkali reaction, can obtain with high yield the one kind or two or more mixture of the N-methylene radical substituted methylamine polymer shown in following formula II.Then, by making this mixture be hydrolyzed under sour existence, can obtain with high yield as the substituted methylamine compound shown in the following formula III of object product, thereby complete the present invention.
As mentioned above, according to the first viewpoint of the present invention, the manufacture method of the substituted methylamine compound shown in a kind of following formula III is provided, it is characterized in that, comprise: by making hexa-methylene four ammonium salt compounds and the alkali reaction shown in following formula I, obtain the operation of the one kind or two or more mixture of the N-methylene radical substituted methylamine polymer shown in following formula II; With under sour existence, make the operation of the one kind or two or more mixture hydrolysis of the N-methylene radical substituted methylamine polymer shown in described formula II, wherein,
(in formula, A represents any one organic radical of alkyl or heterocyclic radical or has substituent described organic radical, R represents any one organic radical of hydrogen atom or alkyl or heterocyclic radical or has substituent described organic radical, L represents the alkylsulfonyloxy that halogen atom, carbonatoms are 1～20, haloalkyl sulfonyloxy or replacement or the unsubstituted aryl-sulfonyl oxygen that carbonatoms is 1～20)
(in formula, A and R represent implication same as described above, and n represents 2～20 arbitrary integers),
(in formula, A and R represent implication same as described above).
Preferred above-mentioned A represents be selected from any one organic radical of phenyl, pyridyl, thiazolyl, two thienyl (ジ チ ア ニ Le) or tetrahydrofuran base or have any group in substituent described organic radical.
More preferably above-mentioned A represents to be selected from any group in following formula IV～(X),
(in formula, X represents hydrogen atom, halogen atom or replaces or substituted alkyl not).
Further preferred above-mentioned A represents 2-chloropyridine-5-base.
In addition, preferred above-mentioned R represents hydrogen atom or replacement or does not replace low alkyl group, more preferably represents that hydrogen atom or carbonatoms are 1～5 alkyl.
In the manufacture method of substituted methylamine compound of the present invention, preferably under the condition of pH9～12, carry out reacting of hexa-methylene four ammonium salt compounds shown in above-mentioned formula I and alkali.
According to a second aspect of the invention, the manufacture method of the substituted methylamine compound shown in a kind of following formula III is provided, it is characterized in that, comprise: by making the substituent methyl compound shown in following formula (X I) and vulkacit H or ammonia or ammonium salt and formaldehyde or formaldehyde equivalent and alkali reaction, obtain the operation of the one kind or two or more mixture of the N-methylene radical substituted methylamine polymer shown in following formula II; With under sour existence, make the operation of the one kind or two or more mixture hydrolysis of the substituted methylamine polymer shown in described formula II, wherein,
(in formula, A represents any one organic radical of alkyl or heterocyclic radical or has substituent described organic radical, R represents any one organic radical of hydrogen atom or alkyl or heterocyclic radical or has substituent described organic radical, L represents the alkylsulfonyloxy that halogen atom, carbonatoms are 1～20, haloalkyl sulfonyloxy or replacement or the unsubstituting aromatic yl sulfonyloxy that carbonatoms is 1～20)
(in formula, A and R represent implication same as described above, and n represents 2～20 arbitrary integer),
(in formula, A and R represent implication same as described above).
Preferred above-mentioned A represents to be selected from any one organic radical of phenyl, pyridyl, thiazolyl, two thienyl or tetrahydrofuran base or has any group in substituent described organic radical.
More preferably above-mentioned A represents to be selected from any group in following formula IV～(X),
(in formula, X represents hydrogen atom, halogen atom or replaces or substituted alkyl not).
Further preferred above-mentioned A is 2-chloropyridine-5-base.
Preferred above-mentioned R represents hydrogen atom or replacement or does not replace low alkyl group, more preferably represents that hydrogen atom or carbonatoms are 1～5 alkyl.
In manufacture method of the present invention, preferably under the condition of pH9～12, carry out reacting of the substituent methyl compound shown in above-mentioned formula (X I) and vulkacit H or ammonia or ammonium salt and formaldehyde or formaldehyde equivalent and alkali.
In addition, in manufacture method of the present invention, preferably make the substituent methyl compound shown in above-mentioned formula (X I) and vulkacit H or ammonia or ammonium salt and formaldehyde or formaldehyde equivalent and alkali reaction, from the reaction solution that obtains, reclaim vulkacit H or ammonia and formaldehyde, then by gained material for the reacting of the substituent methyl compound shown in above-mentioned formula (X I).
According to a third aspect of the invention we, provide the polymer of the N-methylene radical-pyridyl methylamine shown in a kind of following formula (II '),
(in formula, X represents hydrogen atom, halogen atom or replaces or substituted alkyl not, and n represents 2～20 arbitrary integer).
This polymer is useful as the manufacture intermediate of the substituted methylamine compound shown in above-mentioned formula III.Wherein, the trimerical pyrrolotriazine derivatives as N-methylene radical substituted methylamine shown in the following formula (II ') of preferred illustration n=3.
(in formula, X represents implication same as described above).
Invention effect
Manufacturing method according to the invention, can be advantageously industrial, can be easy and high yield, manufacture the substituted methylamine compound shown in above-mentioned formula III at low cost.
N-methylene radical substituted methylamine polymer of the present invention, useful as the manufacture intermediate of the substituted methylamine compound shown in above-mentioned formula III.
Embodiment
Below, describe the present invention in detail.
Substituted methylamine compound shown in formula III of the present invention is (following, be sometimes referred to as " amine compound (III) ") manufacture method be characterised in that, comprise: by making substituent methyl hexa-methylene four ammonium salt compounds shown in above-mentioned formula I (following, be sometimes referred to as " ammonium salt compound (I) ") and alkali reaction, obtain the operation (hereinafter referred to as " operation (1) ") of the one kind or two or more mixture of the N-methylene radical-substituted methylamine polymer shown in formula II (following, to be sometimes referred to as " N-benzylidene amino polymer (II) "); With under sour existence, make the operation (hereinafter referred to as " operation (2) ") of the one kind or two or more mixture hydrolysis of above-mentioned N-benzylidene amino polymer (II).
Operation (1)
Operation (1) is by making ammonium salt compound (I) and alkali reaction, obtains the operation of the one kind or two or more mixture of N-benzylidene amino polymer (II).
In above-mentioned formula I, A represents any one organic group of alkyl or heterocyclic radical or has substituent above-mentioned organic group.
As above-mentioned alkyl, specifically can illustration phenyl, the aromatic hydrocarbyl such as naphthyl, indenyl, pyrenyl, acenaphthenyl, anthryl, phenanthryl, the aliphatic alkyls such as methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, sec-butyl, the tertiary butyl, n-hexyl, n-octyl, vinyl, allyl group, ethynyl, propargyl, the alicyclic alkyls such as cyclopropyl, cyclohexyl, two ring ［ 3.2.1 ］ octyl groups.As above-mentioned heterocyclic radical, specifically can illustration contain 1～5 Sauerstoffatom, sulphur atom, heteroatomic 5～7 rings such as nitrogen-atoms or its condensed ring, more specifically, can illustration furans-2-base, furans-3-base, thiophene-2-base, thiene-3-yl-, pyrroles-2-base, pyrroles-3-base, oxazole-2-base, oxazole-4-base, oxazole-5-base, thiazol-2-yl, thiazole-4-yl, thiazole-5-base, isoxazole-3-base, isoxazole-4-base, isoxazole-5-base, isothiazole-3-base, isothiazole-4-base, isothiazole-5-base, imidazoles-2-base, imidazol-4 yl, imidazoles-5-base, pyrazole-3-yl, pyrazoles-4-base, pyrazoles-5-base, 1,3,4-oxadiazole-2-base, 1,3,4-thiadiazoles-2-base, 1,2,3-triazoles-4-base, 1,2,4-triazole-3-base, 1,2,4-triazole-5-base, 5-phenyl-5-trifluoromethyl-isoxazolines-3-base, 2-furfuryl group methyl, 3-thianthrene methyl, unsaturated 5 yuan of heterocyclic radicals such as 1-methyl-3-pyrazolyl methyl, pyridine-2-base, pyridin-3-yl, pyridin-4-yl, pyridazine-3-base, pyridazine-4-base, pyrazine-2-base, pyrimidine-2-base, pyrimidine-4-yl, pyrimidine-5-base, 1,3,5-triazines-2-base, 1,2,4-triazine-3-base, 2-pyridylmethyl, 3-pyridylmethyl, 6-chloro-3-pyridyl ylmethyl, unsaturated 6 yuan of heterocyclic radicals such as 2-Pyrimidylmethyl, tetrahydrofuran (THF)-2-base, tetrahydrofuran (THF)-4-base, piperidines-3-base, pyrrolidin-2-yl, morpholinyl, piperidyl, N methyl piperazine base, two thienyl, 2-tetrahydrofuran (THF) ylmethyl, 3-piperazinyl methyl, N-methyl-3-pyrrolidyl methyl, the saturated heterocyclyls such as morpholino methyl etc.Wherein, above-mentioned A is preferably phenyl, pyridyl, thiazolyl, two thienyl or tetrahydrofuran base.
In addition, above-mentioned alkyl or heterocyclic radical, also in the scope that does not affect reaction, can be substituted, as its substituting group, specifically can illustration hydroxyl, thio group, the halogen atoms such as fluorine atom, chlorine atom, bromine atoms, iodine atom, cyano group, nitro, formyl radical, amino, methylamino, benzylamino, phenylamino, dimethylamino, diethylamino, phenylethyl amino etc. do not replace or substituted-amino, the alkyl such as methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, sec-butyl, isobutyl-, the tertiary butyl, n-pentyl, n-hexyl (preferred C
1-6alkyl), the alkenyls such as vinyl, allyl group, 2-methoxyl group-vinyl, the alkynyls such as ethynyl, 1-proyl, 2-phenylene-ethynylene, propargyl, the alkynyls such as ethynyl, 1-proyl, 2-phenylene-ethynylene, propargyl, the alkoxyl groups such as methoxyl group, oxyethyl group, propoxy-, isopropoxy, n-butoxy, sec-butoxy, isobutoxy, tert.-butoxy (preferred C
1-6alkoxyl group), the alkenyloxy such as vinyloxy group, allyloxy, the alkynyloxy groups such as second alkynyloxy group, alkynes propoxy-, the aryloxy such as phenoxy group, benzyloxy, 2-pyridyloxy, the haloalkyls such as chloromethyl, methyl fluoride, brooethyl, dichloromethyl, difluoromethyl, two brooethyls, trichloromethyl, trifluoromethyl, bromine difluoro methyl, trifluoroethyl, 1-chloroethyl, 2-chloroethyl, 1-bromotrifluoromethane, 2-bromotrifluoromethane, pentafluoroethyl group (preferred C
1-6haloalkyl), the halogenated alkoxy such as fluorine methoxyl group, chlorine methoxyl group, bromine methoxyl group, difluoro-methoxy, dichloro methoxyl group, dibromo methoxyl group, trifluoromethoxy, trichlorine methoxyl group, tribromo methoxyl group, trifluoro ethoxy, five fluorine oxyethyl groups, seven fluorine propoxy-(preferred C
1-6halogenated alkoxy), the alkyl thiocarbonyl such as methyl thiocarbonyl, ethylenebis dithiocarbamate carbonyl, propyl dithiocarbamate carbonyl, isopropylthio carbonyl, butyl thiocarbonyl, isobutyl-thiocarbonyl, sec-butyl thiocarbonyl, t-butylthio carbonyl (preferred C
1-6alkyl thiocarbonyl), amino (the preferred C of the alkyl sulfonyl such as sulfonyloxy methyl amino, ethyl sulfonamido, sulfonyl propyl amino, sec.-propyl sulfonamido, butyl sulfonamido, tertiary butyl sulfonamido
1-6alkyl sulfonyl is amino), the Arenesulfonyl aminos such as phenyl sulfonamido, piperazinyl sulfonamido (preferred C
6-12arenesulfonyl amino), the alkyl-carbonyl-amino such as methyl carbonylamino, ethyl carbonylamino, propyl group carbonylamino, sec.-propyl carbonylamino (preferred C
1-6the alkoxycarbonyl aminos such as alkyl-carbonyl-amino), methoxycarbonyl is amino, ethoxy carbonyl is amino, propoxycarbonyl is amino, isopropoxy carbonyl is amino (preferred C
1-6alkoxycarbonyl amino), the haloalkyl sulfonamido such as methyl fluoride sulfonamido, chloromethyl sulfonamido, brooethyl sulfonamido, difluoromethyl sulfonamido, dichloromethyl sulfonamido, difluoromethyl sulfonamido, trimethyl fluoride sulfonyl amino, trifluoroethyl sulfonamido, pentafluoroethyl group sulfonamido (preferred C
1-6haloalkyl sulfonamido), two (methyl sulphonyl) is amino, two (ethylsulfonyl) amino, (methyl sulphonyl) (ethylsulfonyl) is amino, two (sulfonyl propyl base) is amino, two (sec.-propyl alkylsulfonyl) is amino, two (butyl alkylsulfonyl) is amino, two (tertiary butyl alkylsulfonyl) amino two (alkyl sulphonyl) amino (preferred two (C that wait
1-6alkyl sulphonyl) amino), two (methyl fluoride alkylsulfonyl) is amino, two (chloromethyl alkylsulfonyl) amino, two (brooethyl alkylsulfonyl) is amino, two (difluoromethyl alkylsulfonyl) is amino, two (dichloromethyl alkylsulfonyl) is amino, two (difluoromethyl alkylsulfonyl) is amino, two (trifluoromethyl sulfonyl) is amino, two (trifluoroethyl alkylsulfonyl) is amino, two (pentafluoroethyl group alkylsulfonyl) amino two (halogenated alkyl sulfonyl) amino (preferred two (C that wait
1-6halogenated alkyl sulfonyl) amino), diazanyl, N'-phenyl diazanyl, N'-methoxycarbonyl diazanyl etc. do not replace or replace diazanyl, the alkoxy carbonyls such as methoxycarbonyl, ethoxy carbonyl, propoxycarbonyl, isopropoxy carbonyl, butoxy carbonyl, tert-butoxycarbonyl (preferred C
1-6alkoxy carbonyl), the aryl such as phenyl, 1-naphthyl, 2-naphthyl (preferred C
6-12aryl), furans-2-base, furans-3-base, thiophene-2-base, thiene-3-yl-, pyrroles-2-base, pyrroles-3-base, oxazole-2-base, oxazole-4-base, oxazole-5-base, thiazol-2-yl, thiazole-4-yl, thiazole-5-base, isoxazole-3-base, isoxazole-4-base, isoxazole-5-base, isothiazole-3-base, isothiazole-4-base, isothiazole-5-base, imidazoles-2-base, imidazol-4 yl, imidazoles-5-base, pyrazole-3-yl, pyrazoles-4-base, pyrazoles-5-base, 1,3,4-oxadiazole-2-base, 1,3,4-thiadiazoles-2-base, 1,2,3-triazoles-4-base, 1,2,4-triazole-3-base, 1,2,4-triazole-5-base, 5-phenyl-5-trifluoromethyl-isoxazolines-3-base, 2-furfuryl group methyl, 3-thienyl methyl, unsaturated 5 yuan of heterocyclic radicals such as 1-methyl-3-pyrazolyl methyl, pyridine-2-base, pyridin-3-yl, pyridin-4-yl, pyridazine-3-base, pyridazine-4-base, pyrazine-2-base, pyrimidine-2-base, pyrimidine-4-yl, pyrimidine-5-base, 1,3,5-triazines-2-base, 1,2,4-triazine-3-base, 2-pyridylmethyl, 3-pyridylmethyl, 6-chloro-3-pyridyl ylmethyl, unsaturated 6 yuan of heterocyclic radicals such as 2-Pyrimidylmethyl, tetrahydrofuran (THF)-2-base, tetrahydrofuran (THF)-4-base, piperidines-3-base, pyrrolidin-2-yl, morpholinyl, piperidyl, N methyl piperazine base, 2-tetrahydrofuran (THF) ylmethyl, 3-piperazinyl methyl, N-methyl-3-pyrrolidyl methyl, the saturated heterocyclyls such as morpholino methyl, N-dimethylamino iminomethyl, 1-N-phenylimino ethyl, N-oxyimino methyl, the N such as N-methoxyimino methyl do not replace or N substituted imido alkyl, N'-methyl diazanyl carbonyl, N'-phenyl diazanyl carbonyl, the N such as diazanyl carbonyl do not replace or N replaces diazanyl carbonyl, aminocarboxyl, dimethylamino carbonyl, the N such as N-phenyl-N-methylamino carbonyl do not replace or N substituted aminocarbonyl, diazanyl, N'-ethanoyl diazanyl, N'-methyl diazanyl, N'-phenyl diazanyl, the N such as N'-methoxycarbonyl diazanyl do not replace or N replaces diazanyl, methylthio group, ethylmercapto group, the alkylthios such as tertiary butylthio, ethene sulfenyl, the alkenyl thios such as allyl sulfenyl, acetylene sulfenyl, the alkynes sulfenyls such as alkynes rosickyite base, thiophenyl, 4-chlorobenzene sulfenyl, benzylthio-, benzene ethylmercapto group, the arylthios such as 2-pyridine thio, methyl sulphonyl, ethylsulfonyl, the alkyl sulphonyls such as tertiary butyl alkylsulfonyl, the alkenyl alkylsulfonyls such as allyl group alkylsulfonyl, the alkynyl alkylsulfonyls such as propargyl alkylsulfonyl, phenyl sulfonyl, benzyl alkylsulfonyl, the aryl sulfonyls such as 2-pyridyl sulfonyl etc.These substituting groups can replace another one substituting group on a substituting group, two or more substituting group is merged and form new substituting group.
More specifically, preferred above-mentioned A represents to be selected from any group in formula IV～(X), more preferably 2-chloropyridine-5-base.As the X in formula IV～(X), specifically can illustration hydrogen atom, the halogen atom such as fluorine atom, bromine atoms, chlorine atom or iodine atom, the alkyl such as methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, sec-butyl, the tertiary butyl, n-hexyl, n-octyl.Alkyl can have substituting group on suitable carbon atom, as this substituting group, can illustration and above-mentioned A in the same substituting group of illustrative substituting group.Substituting group in above-mentioned A, can with alkali reaction before with the protection of suitable protecting group.
In formula I, as R, specifically can illustration and the same group of A.
L as formula I, specifically can illustration hydrogen atom, the halogen atom such as fluorine atom, chlorine atom or bromine atoms, the alkylsulfonyloxy that the carbonatomss such as sulfonyloxy methyl oxygen base, ethyl sulfonyloxy, n-propyl sulfonyloxy are 1～20, trimethyl fluoride sulfonyl oxygen base, trichloromethyl sulfonyloxy, 2,2, the haloalkyl sulfonyloxy that the carbonatomss such as 2-trifluoroethyl sulfonyloxy, perfluor ethyl sulfonyloxy are 1～20, the aryl-sulfonyl oxygens such as phenyl sulfonyloxy, naphthyl sulfonyloxy, anthryl sulfonyloxy, phenanthryl sulfonyloxy.Aryl-sulfonyl oxygen can have substituting group in position, as this substituting group, can illustration and above-mentioned A in the same substituting group of illustrative substituting group.The halogen atom such as illustration fluorine atom, chlorine atom, bromine atoms particularly preferably, the alkyl such as methyl, ethyl, the alkoxyl groups such as methoxyl group, oxyethyl group, the haloalkyls such as trifluoromethyl, nitro etc.
The manufacture method of ammonium salt compound (I) is not particularly limited, and particularly preferably illustration makes the method for the substituent methyl compound shown in formula (X I) (be sometimes referred to as below " substituent methyl compound (X I)) and the mixture reaction of vulkacit H or ammonia or ammonium salt and formaldehyde or formaldehyde equivalent.
Substituent methyl compound (X I) can adopt known method manufacture, the compound that the A of take is halogen atom as formula IV, X is example, can adopt the method for 2-halo-5-picoline halogenation and the manufactures such as method that under alkali exists, 2-halo-5-4-hydroxymethylpiperidine reacted with heteroaryl-alkylsulfonyl halides or aryl sulfonyl halide.
As the compound shown in formula (X I), specifically can illustration 3-(methyl fluoride) pyridine, 3-(chloromethyl) pyridine, 3-(brooethyl) pyridine, ［ (pyridin-3-yl) methyl ］ methanesulfonate ester, ［ (pyridin-3-yl) methyl ］ ethylsulfonic acid ester, ［ (pyridin-3-yl) methyl ］ n-propyl sulphonate, ［ (pyridin-3-yl) methyl ］ phenylbenzimidazole sulfonic acid ester, the fluoro-5-of 2-(methyl fluoride) pyridine, 5-chloromethyl-2-fluorine pyridine, 5-brooethyl-2-fluorine pyridine, ［ (2-fluorine pyridine-5-yl) methyl ］ methanesulfonate ester, ［ (2-fluorine pyridine-5-yl) methyl ］ ethylsulfonic acid ester, (2-fluorine pyridine-5-yl) n-propyl sulphonate, ［ (2-fluorine pyridine-5-yl) methyl ］ phenylbenzimidazole sulfonic acid ester, the chloro-5-of 2-(methyl fluoride) pyridine, the chloro-5-of 2-(chloromethyl) pyridine, 5-brooethyl-2-chloropyridine, ［ (2-chloropyridine-5-yl) methyl ］ methanesulfonate ester, ［ (2-chloropyridine-5-yl) methyl ］ ethylsulfonic acid ester, [(2-chloropyridine-5-yl) methyl] n-propyl sulphonate, ［ (2-chloropyridine-5-yl) methyl ］ phenylbenzimidazole sulfonic acid ester, the bromo-5-of 2-(methyl fluoride) pyridine, the bromo-5-of 2-(chloromethyl) pyridine, the bromo-5-of 2-(brooethyl) pyridine, ［ (2-bromopyridine-5-yl) methyl ］ methanesulfonate ester, ［ (2-bromopyridine-5-yl) methyl ］ ethylsulfonic acid ester, ［ (2-bromopyridine-5-yl) methyl ］ n-propyl sulphonate, ［ (2-bromopyridine-5-yl) methyl ］ phenylbenzimidazole sulfonic acid ester etc., the particularly preferably chloro-5-of 2-(chloromethyl) pyridine.
As the alkali with using in the reacting of the ammonium salt compound shown in formula I, be not particularly limited, specifically can illustration sodium hydroxide, the alkali metal hydroxide such as potassium hydroxide, the alkaline earth metal hydroxides such as magnesium hydroxide, calcium hydroxide, the carbonate such as sodium carbonate, salt of wormwood, magnesiumcarbonate, calcium carbonate, the metal alkoxides such as sodium methylate, sodium ethylate, magnesium methylate, triethylamine, diisopropylethylamine, pyridine, 1,4-diazabicylo ［ 2.2.2 ］ octane, 1,8-diazabicylo ［ 5.4.0 ］-organic basess such as 7-undecylene etc.Wherein, from manufacturing cost and can obtain the viewpoint of object with high yield, preferred alkali metal hydroxide, sodium hydroxide particularly preferably wherein.
PH while making ammonium salt compound (I) with alkali reaction is controlled at 9～12 conventionally, is preferably controlled at 9.5～11.5, is more preferably controlled at 10～11.By the pH of reaction system is controlled in above-mentioned scope, can obtain N-benzylidene amino polymer (II) with high yield.
Ammonium salt compound (I) carries out in solvent with reacting conventionally of alkali.Solvent as using, so long as be inactive solvent for reaction, is not particularly limited.For example, can make water, the alcoholic solvents such as methyl alcohol, ethanol, n-propyl alcohol, the aliphatic hydrocarbon kind solvents such as Skellysolve A, normal hexane, normal heptane, octane, the clicyclic hydrocarbon such as pentamethylene, hexanaphthene kind solvent, the aromatic hydrocarbon solvent such as benzene,toluene,xylene, chlorobenzene, the ketones solvents such as acetone, methylethylketone, diethyl ketone, methyl isopropyl Ketone, methyl iso-butyl ketone (MIBK), pimelinketone, diethyl ether, tetrahydrofuran (THF), diox, 1, the ether solvents such as 2-glycol dimethyl ether, or the mixed solvent that two or more forms by these.Wherein, preferably make the mixed solvent of water and aromatic hydrocarbon solvent, particularly preferably make the mixed solvent of water and toluene.
The temperature of reaction of ammonium salt compound (I) and alkali is the temperature range from room temperature to solvent boiling point normally, is preferably 40～70 ℃.Reaction times, conventionally from several minutes to a few days, is preferably 1～10 hour.
The end of reaction for example can, by reaction solution is sampled, utilize the known analysis means such as thin-layer chromatography, gas-chromatography, high-speed liquid chromatography to confirm.
In addition, in the present invention, also can, by making substituent methyl compound (XI), vulkacit H and alkali reaction, obtain once N-benzylidene amino polymer (II).
Now, the pH of reaction solution is controlled at 9～12 conventionally, is preferably controlled at 9.5～11.5, is more preferably controlled at 10～11 scope.By the pH of reaction system is controlled in above-mentioned scope, can obtain N-benzylidene amino polymer (II) with high yield.
With respect to 1 mole of substituent methyl compound (XI), the consumption of vulkacit H is generally the scope of 0.1～10 mole, is preferably the scope of 0.25～2 mole.
And, in the present invention, by making substituent methyl compound (X I) and ammonia or ammonium salt and formaldehyde or formaldehyde equivalent and alkali reaction, also can obtain once N-benzylidene amino polymer (II).
Now, the pH of reaction solution is controlled at 9～12 conventionally, is preferably controlled at 9.5～11.5, is more preferably controlled at 10～11 scope.By the pH of reaction system is controlled to above-mentioned scope, can obtain N-benzylidene amino polymer (II) with high yield.
Because being used as the ammonia of cheap industrial raw material or ammonium salt and formaldehyde or formaldehyde equivalent, the method replaces vulkacit H, so, highly beneficial when producing in a large number with technical scale.
The ammonia using is not particularly limited, and can use the form arbitrarily such as gas, the aqueous solution, alcoholic solution.While using ammonia soln, its concentration is generally 5～25%, is preferably 10～25%.In addition, also can use ammonium salt to replace ammonia.As ammonium salt, such as enumerating ammonium acetate, ammonium nitrate, ammonium sulfate, ammonium chloride etc.
With respect to 1 mole of substituent methyl compound (XI), the consumption of ammonia is generally 1～40 mole, is preferably 1～8 mole.
The formaldehyde using is not particularly limited, and can use the form arbitrarily such as the aqueous solution, alcoholic solution.In addition, also can use formaldehyde equivalent to replace formaldehyde.As formaldehyde equivalent, for example, can enumerate the paraformaldehyde as the polymkeric substance of formaldehyde.This material is at room temperature white powder, by dissolving or be heated in the organic solvent using, generates formaldehyde.
With respect to 1 moles of ammonia, the consumption of formaldehyde is generally 0.1～20 mole, is preferably 1～2 mole.
In addition, in these cases, substituent methyl compound (X I) and vulkacit H or ammonia etc. and formaldehyde etc. are reacted, from the reaction solution obtaining, reclaim vulkacit H or ammonia and formaldehyde, can by they again for the reacting of substituent methyl compound (X I).By reclaiming vulkacit H or ammonia and formaldehyde, by they again for the reacting of substituent methyl compound (X I), can reduce the whole consumption of vulkacit H or ammonia and formaldehyde, can manufacture N-benzylidene amino polymer (II) with lower cost.
In addition, when continuously using the solution that contains ammonia and formaldehyde reclaiming, can directly use, but ammonia in this solution and formaldehyde containing proportional with for continuing to react necessary ratio when different, must supplementary ammonia and aldehyde in insufficient section.That is,, when ammonia is not enough, add ammonia or ammonium salt; When formaldehyde is not enough, add formaldehyde or formaldehyde equivalent, the ratio of ammonia and formaldehyde is adjusted to optimum proportion.This optimum proportion is according to reaction conditions etc. and different, and with respect to 1 moles of ammonia, the amount of formaldehyde is generally 0.1～20 mole, is preferably 1～2 mole.
When the mixture that uses substituent methyl compound (X I), vulkacit H or ammonia etc. and formaldehyde etc. replaces ammonium salt compound (I), the alkali of use and solvent species, temperature of reaction etc. are identical when using ammonium salt compound (I).
In any case, by common aftertreatment, can emanate as the one kind or two or more mixture of the N-benzylidene amino polymer (II) of object product.
The structure example of the N-benzylidene amino polymer (II) obtaining is as passed through
1h-NMR,
13the known analysis means such as C-NMR, IR spectrum, mass spectrum, ultimate analysis is confirmed.
The structure of N-benzylidene amino polymer (II) can be that the arbitrary structures that has structure is mixed in chain-like structure, ring texture or their, as particularly preferred object lesson, and the ring compound shown in can illustration formula (II ').In formula (II '), X represents implication same as described above, can the same substituting group of illustration.In formula II or in formula (II '), n represents 2～20 arbitrary integer, the wherein preferably scope of illustration 2～10, the more preferably scope of illustration 2～5.The structure of N-benzylidene amino polymer (II) can be estimated as following structure by various spectrum.
The pyrrolotriazine derivatives shown in illustration formula (II ') particularly preferably.
The one kind or two or more mixture of the N-benzylidene amino polymer (II) that the above operation obtains, useful as the manufacture intermediate of amine compound (III).
In addition, in the present invention, after reaction finishes, can be not from the one kind or two or more mixture of reaction soln segregation amine compound (II), by it directly for operation (2) below.
That is, N-benzylidene amino polymer (II) is alkaline matter, has the character of dissolving in sour water.Therefore, for example the mixed solvent being formed by water and toluene such in the mixed solvent of water and the organic solvent that do not mix with water, carry out reacting of ammonium salt compound (I) and alkali, from the reaction solution separation obtaining, obtain organic layer, the organic layer of obtaining from separation with sour water, extract, can access thus the aqueous solution as the salt of the one kind or two or more mixture of the N-benzylidene amino polymer (II) of object product.This aqueous solution can be directly for operation (2) below.
Operation (2)
Operation (2) is under sour existence, makes the one kind or two or more mixture hydrolysis of N-benzylidene amino polymer (II), thereby obtains the operation of amine compound (III).
The acid of using in reaction is not particularly limited, specifically can illustration sulfuric acid, the mineral acid such as hydrochloric acid, phosphoric acid, the organic carboxyl acid such as acetic acid, trifluoracetic acid, the organic sulfonic acids such as tosic acid, methylsulfonic acid, trifluoromethanesulfonic acid, the Lewis acids such as boron trifluoride, titanium tetrachloride, aluminum chloride etc.
With respect to 1 molar ammonium salt compound (I) or substituent methyl compound (XI), the consumption of acid is generally 1～100 mole, is preferably 2～20 moles, more preferably 3～10 moles.By sour consumption is set within the scope of this, the high yield of can usining obtains the substituted methylamine compound (III) as object product.
Under sour existence, make the reaction of the one kind or two or more mixture hydrolysis of N-benzylidene amino polymer (II), conventionally with solvent cut, carry out.The solvent using can be set forth in the solvent phase that uses in the reacting of mixture of substituent methyl compound (XI) and vulkacit H or ammonia etc. and formaldehyde etc. solvent together.Wherein, the mixed solvent of preferably water and alcohol, the particularly preferably mixed solvent of water and methyl alcohol.
Temperature of reaction while making the one kind or two or more mixture hydrolysis of N-benzylidene amino polymer (II) under sour existence, conventionally from room temperature to 90 ℃, is preferably 50～90 ℃.Reaction times is generally several minutes to a few days, is preferably 1～10 hour.The end of reaction for example can, by reaction solution is sampled, utilize the known analysis means such as thin-layer chromatography, gas-chromatography, high-speed liquid chromatography to confirm.
After reaction finishes, carry out common post-processing operation, by known refining means such as distillation, column chromatographys, can access the amine compound (III) as object product.
According to the present invention, can be easy and high yield, manufacture amine compound (III), the pyridyl methylamine compound shown in preferred formula (III ') at low cost.
(in formula, X represents implication same as described above)
The amine compound being obtained by manufacture method of the present invention (III), as the manufacture intermediate of agricultural chemicals, medicine, very useful such as the manufacture intermediate of the activeconstituents as chloro nicotinoids salt, garderning pesticides such as Provado, Ti304, acetamiprids.
In addition, manufacturing method according to the invention, by making formula (XII):
Hexa-methylene four ammonium salt compounds and alkali reaction shown in (in formula, B represents phenyl, pyridyl, thiazolyl, two thienyl or tetrahydrofuran base, two thienyl particularly preferably, L represents implication same as described above), can access formula (X III):
(in formula, B represents implication same as described above, n and m represent respectively 2～20 arbitrary integer independently) shown in the one kind or two or more mixture of N-benzylidene amino polymer, and under acid exists, make the one kind or two or more mixture of the N-benzylidene amino polymer shown in above-mentioned formula (X III) be hydrolyzed, can manufacture formula (X IV):
H
2N-H
2C-B-CH
2-NH
2 (XIV)
Substituted methylamine compound shown in (in formula, B represents implication same as described above).
In addition, manufacturing method according to the invention, by making formula (X V):
L-H
2C-B-CH
2-L (XV)
(in formula, B and L represent implication same as described above) shown in substituent methyl compound and vulkacit H or ammonia or ammonium salt and formaldehyde or formaldehyde equivalent and alkali reaction, can access the one kind or two or more mixture of the N-benzylidene amino polymer shown in above-mentioned formula (X III), and in sour existence, the one kind or two or more mixture of the N-benzylidene amino polymer shown in above-mentioned formula (X III) is hydrolyzed, also can manufacture the substituted methylamine compound shown in above-mentioned formula (X IV).
As mentioned above, manufacturing method according to the invention, can be easy and high yield, manufacture the compound that can not manufacture in the prior art at low cost.
Embodiment
Below, enumerate embodiment and describe the present invention in detail, but the present invention is not limited to these embodiment.
Wherein, the analysis of resultant of reaction is used Liquid Chromatograph (HPLC, LC-10 type, Shimadzu Scisakusho Ltd produces) and gas chromatograph (GC, GC-14B type, Shimadzu Scisakusho Ltd produces) to carry out.
The manufacture (1) of (embodiment 1) (2-chloropyridine-5-yl) methylamine
At 3.02g(10mmol) add 5ml water and 5ml toluene in (2-chloropyridine-5-yl) hexa-methylene four ammonium muriates (I-1), with 28% aqueous sodium hydroxide solution, by pH regulator, be 10～11, at 60 ℃, stir 7 hours simultaneously.
In reaction solution, add 4ml toluene, separation obtains toluene layer.In toluene layer, add 7g concentrated hydrochloric acid, separation obtains water layer, contains the one kind or two or more mixture of the hydrochloride of N-methylene radical-2-chloro-3-pyridyl base methylamine polymer (II-1) in this water layer.
In the water layer of obtaining in separation, add 3.2g methyl alcohol, at 60 ℃, process 3 hours, as the aqueous solution, obtain the hydrochloride of (2-chloropyridine-5-yl) methylamine (III-1).The result of being analyzed by HPLC, growing amount is 1.21g(yield 85%).
The manufacture (2) of (embodiment 2) (2-chloropyridine-5-yl) methylamine
At 1.62g(10mmol) the chloro-5-of 2-(chloromethyl) pyridine (XI-1) and 1.48g(10mmol) add 5ml water and 1ml toluene in vulkacit H, with 28% aqueous sodium hydroxide solution, by pH regulator, be 10～11, at 60 ℃, stir 7 hours simultaneously.
In reaction solution, add 4ml toluene, separation obtains toluene layer.In toluene layer, add 7g concentrated hydrochloric acid, separation obtains water layer, contains the one kind or two or more mixture of the hydrochloride of N-methylene radical-2-chloro-3-pyridyl base methylamine polymer (II-1) in this water layer.
In the water layer of obtaining in separation, add 3.2g methyl alcohol, at 60 ℃, process 3 hours, as the aqueous solution, obtain the hydrochloride of (2-chloropyridine-5-yl) methylamine (III-1).The result of being analyzed by HPLC, growing amount is 1.28g(yield 90%).
The manufacture (3) of (embodiment 3) (2-chloropyridine-5-yl) methylamine
At 1.62g(10mmol) CCMP (XI-1) and 0.7g(5mmol) add 5ml water and 1ml toluene in vulkacit H, with 28% aqueous sodium hydroxide solution, by pH regulator, be 10～11, at 60 ℃, stir 7 hours simultaneously.
In reaction solution, add 4ml toluene, separation obtains toluene layer.In toluene layer, add 7g concentrated hydrochloric acid, separation obtains water layer, contains the one kind or two or more mixture of the hydrochloride of pyridylmethyl group with imine moiety (II-3) in this water layer.
In the water layer of obtaining in separation, add 3.2g methyl alcohol, at 60 ℃, process 3 hours, as the aqueous solution, obtain the hydrochloride of (2-chloropyridine-5-yl) methylamine (III-1).The result of being analyzed by HPLC, growing amount is 1.26g(yield 89%).
Known as mentioned above, compare with embodiment 2, even if reduce the consumption of vulkacit H, on the receipts amount of object, can not produce any impact yet.
(embodiment 4) 1,3,5-tri-［ (2-chloropyridine-5-yl) methyl ］-1,3, the manufacture of 5-perhydro triazine
In the mixed solution of 10ml methyl alcohol and 10ml water, add successively 2.72g(40mmol) 25% ammonia soln, 1.21g(40mmol) paraformaldehyde and 3.24g(20mmol) the chloro-5-of 2-(chloromethyl) pyridine (XI-1), with 28% aqueous sodium hydroxide solution, by pH regulator, be 10～11, at 50 ℃, stir 2.5 hours simultaneously.With chloroform extraction reaction solution and concentrated, obtain 1,3 of 2.50g, 5-tri-(2-chloropyridine-5-yl) methyl isophthalic acid, 3,5-perhydro triazine (II-4) (yield 81%).
1H-NMR（CDCl
3，δppm）：3.37（bs，6H），3.62（s，6H），7.26（d，3H），7.61（d，3H），8.33（s，3H）
m/s462
The manufacture (4) of (embodiment 5) (2-chloropyridine-5-yl) methylamine
At 0.77g(1.66mmol) 1,3,5-tri-［ (2-chloropyridine-5-yl) methyl ］-1,3, adds 0.40g methyl alcohol and 1.83g concentrated hydrochloric acid successively in 5-perhydro triazine (II-4), at 75～80 ℃, stir 6 hours.Use chloroform dilute reaction solution, add 28% aqueous sodium hydroxide solution to be adjusted to alkalescence, then separation obtains chloroform layer, is concentrated, and obtains 0.68g (2-chloropyridine-5-yl) methylamine (III-1) (yield 95%).
The manufacture (5) of (embodiment 6) (2-chloropyridine-5-yl) methylamine
At 1.62g(10mmol) the chloro-5-of 2-(chloromethyl) pyridine (XI-1) and 1.48g(10mmol) add 5ml water and 1ml toluene in vulkacit H, with 28% aqueous sodium hydroxide solution, by pH regulator, be 10～11, at 60 ℃, stir 7 hours simultaneously.In reaction solution, add 4ml toluene, separation obtains water layer, reclaims thus vulkacit H.The result of being analyzed by GC, its rate of recovery is 73%.
In addition, by processing similarly to Example 2 toluene layer, can access (2-chloropyridine-5-yl) methylamine (III-1).
In the aqueous solution of the vulkacit H that contains above-mentioned recovery, add 1.62g(10mmol) the chloro-5-of 2-(chloromethyl) pyridine (XI-1), 0.52g(3.5mmol) vulkacit H, 0.18g ammonium chloride and 1ml toluene, with 28% aqueous sodium hydroxide solution, by pH regulator, be 10～11, simultaneously 60 ℃ of heating 7 hours.In this reaction solution, add 4ml toluene, obtain respectively toluene layer and water layer.From water layer, reclaim vulkacit H, its rate of recovery is 69%.
On the other hand, add 7g concentrated hydrochloric acid in toluene layer, separation obtains water layer, contains the one kind or two or more mixture of the hydrochloride of N-methylene radical-(2-chloropyridine-5-yl) methylamine polymer (II-5) in this water layer.In the water layer of obtaining in separation, add 3.2g methyl alcohol, at 60 ℃, process 3 hours, as the aqueous solution, obtain the hydrochloride of (2-chloropyridine-5-yl) methylamine.The result of being analyzed by HPLC, the growing amount of (2-chloropyridine-5-yl) methylamine is 1.28g(yield 90%).
As mentioned above, in the present embodiment, can reclaim approximately 70% vulkacit H, by supplementing the vulkacit H of insufficient section, can maintain same scale and proceed reaction.
Claims (15)
1. a manufacture method for the one kind or two or more mixture of the N-methylene radical substituted methylamine polymer shown in following formula II, is characterized in that,
By making hexa-methylene four ammonium salt compounds and the alkali reaction shown in following formula I, obtain the one kind or two or more mixture of the N-methylene radical substituted methylamine polymer shown in following formula II,
In formula I, A represents any one organic radical of alkyl or heterocyclic radical or has substituent described organic radical, R represents any one organic radical of hydrogen atom or alkyl or heterocyclic radical or has substituent described organic radical, L represents the alkylsulfonyloxy that halogen atom, carbonatoms are 1～20, haloalkyl sulfonyloxy or replacement or the unsubstituted aryl-sulfonyl oxygen that carbonatoms is 1～20
In formula II, A and R represent implication same as described above, and n represents 2～20 integer.
2. the manufacture method of the one kind or two or more mixture of N-methylene radical substituted methylamine polymer as claimed in claim 1, is characterized in that:
Described A represents to be selected from any one organic radical of phenyl, pyridyl, thiazolyl, two thienyl or tetrahydrofuran base or has any group in substituent described organic radical.
3. the manufacture method of the one kind or two or more mixture of N-methylene radical substituted methylamine polymer as claimed in claim 2, is characterized in that:
Described A represents to be selected from any group in following formula IV～(X),
In formula, X represents hydrogen atom, halogen atom or replaces or substituted alkyl not.
4. the manufacture method of the one kind or two or more mixture of N-methylene radical substituted methylamine polymer as claimed in claim 3, is characterized in that:
Described A is 2-chloropyridine-5-base.
5. the manufacture method of the one kind or two or more mixture of the N-methylene radical substituted methylamine polymer as described in any one in claim 1～4, is characterized in that:
Described R represents the alkyl that hydrogen atom or carbonatoms are 1～5.
6. the manufacture method of the one kind or two or more mixture of the N-methylene radical substituted methylamine polymer as described in any one in claim 1～4, is characterized in that:
Under the condition of pH9～12, carry out reacting of hexa-methylene four ammonium salt compounds shown in above-mentioned formula I and alkali.
7. a manufacture method for the one kind or two or more mixture of the N-methylene radical substituted methylamine polymer shown in following formula II, is characterized in that, comprising:
By making substituent methyl compound and vulkacit H and the alkali reaction shown in following formula (X I), or by making the substituent methyl compound shown in following formula (X I) and ammonia or ammonium salt and formaldehyde or formaldehyde equivalent and alkali reaction, obtain the one kind or two or more mixture of the N-methylene radical substituted methylamine polymer shown in following formula II, wherein
In formula (X I), A represents any one organic radical of alkyl or heterocyclic radical or has substituent described organic radical, R represents any one organic radical of hydrogen atom or alkyl or heterocyclic radical or has substituent described organic radical, L represents the alkylsulfonyloxy that halogen atom, carbonatoms are 1～20, haloalkyl sulfonyloxy or replacement or the unsubstituting aromatic yl sulfonyloxy that carbonatoms is 1～20
In formula II, A and R represent implication same as described above, and n represents 2～20 arbitrary integer.
8. the manufacture method of the one kind or two or more mixture of N-methylene radical substituted methylamine polymer as claimed in claim 7, is characterized in that:
Described A represents to be selected from any one organic radical of phenyl, pyridyl, thiazolyl, two thienyl or tetrahydrofuran base or has any group in substituent described organic radical.
9. the manufacture method of the one kind or two or more mixture of N-methylene radical substituted methylamine polymer as claimed in claim 8, is characterized in that:
Described A represents to be selected from any group in following formula IV～(X),
In formula, X represents hydrogen atom, halogen atom or replaces or substituted alkyl not.
10. the manufacture method of the one kind or two or more mixture of N-methylene radical substituted methylamine polymer as claimed in claim 9, is characterized in that:
Described A is 2-chloropyridine-5-base.
The manufacture method of the one kind or two or more mixture of 11. N-methylene radical substituted methylamine polymers as described in any one in claim 7～10, is characterized in that:
Described R represents the alkyl that hydrogen atom or carbonatoms are 1～5.
The manufacture method of the one kind or two or more mixture of 12. N-methylene radical substituted methylamine polymers as described in any one in claim 7～10, is characterized in that:
Under the condition of pH9～12, carry out reacting of the substituent methyl compound shown in described formula (X I) and vulkacit H and alkali, or,
Under the condition of pH9～12, carry out reacting of the substituent methyl compound shown in described formula (X I) and ammonia or ammonium salt and formaldehyde or formaldehyde equivalent and alkali.
The manufacture method of the one kind or two or more mixture of 13. N-methylene radical substituted methylamine polymers as described in any one in claim 7～10, is characterized in that:
Substituent methyl compound shown in described formula (X I) is reacted with vulkacit H, or the substituent methyl compound shown in described formula (X I) and ammonia or ammonium salt and formaldehyde or formaldehyde equivalent are reacted, from the reaction solution that obtains, reclaim vulkacit H or ammonia and formaldehyde, then by gained material for the reacting of the substituent methyl compound shown in described formula (X I).
14. 1 kinds of N-methylene radical-pyridyl methylamine polymers, is characterized in that:
By following formula (II '), represented,
In formula, X represents hydrogen atom, halogen atom or replaces or substituted alkyl not, and n represents 2～20 arbitrary integer.
15. 1 kinds of pyrrolotriazine derivatives, is characterized in that:
By following formula (II '), represented,
In formula, X represents hydrogen atom, halogen atom or replaces or substituted alkyl not.
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|---|---|---|---|---|
| CN105837500A (en) * | 2016-03-31 | 2016-08-10 | 常州大学 | Synthetic method for N-(2-(3-(trifluoromethyl)phenoxy)-4-pyridyl)methylenimine |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1471213A (en) * | 1922-11-27 | 1923-10-16 | Naugatuck Chem Co | Manufacture of formaldehyde condensation products of aliphatic amines and products obtained thereby |
| US4002564A (en) * | 1974-07-24 | 1977-01-11 | Diamond Shamrock Corporation | Cation-exchange resins having cross-linked vinyl aromatic polymer matrix with attached amino alkylene phosphonic acid groups, their use, and preparation |
| DE3727126A1 (en) * | 1987-08-14 | 1989-02-23 | Bayer Ag | N-(2-chloro-pyridin-5-ylmethyl)phthalimide, process for its preparation, and its processing to give 2-chloro-5-aminomethylpyridine |
| JPH03271273A (en) * | 1990-03-20 | 1991-12-03 | Nippon Soda Co Ltd | Production of 2-chloro-5-(aminomethyl)pyridine |
| JPH05230026A (en) * | 1992-02-20 | 1993-09-07 | Nippon Soda Co Ltd | Production of 2-chloro-5-methylpyridine derivative |
| JPH08295670A (en) * | 1995-02-28 | 1996-11-12 | Koei Chem Co Ltd | 2-chloropyridine derivative and its production thereof |
| CN1338924A (en) * | 1999-01-08 | 2002-03-06 | 艾米斯菲尔技术有限公司 | Polymeric delivery agents and delivery agent compounds |
| CN1714079A (en) * | 2002-11-25 | 2005-12-28 | 弗·哈夫曼-拉罗切有限公司 | Mandelic acid derivatives |
| WO2006109811A1 (en) * | 2005-04-07 | 2006-10-19 | Sumitomo Chemical Company, Limited | Process for producing an aminomethyl thiazole compound |
-
2007
- 2007-04-24 CN CN201310561782.1A patent/CN103641776A/en active Pending
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1471213A (en) * | 1922-11-27 | 1923-10-16 | Naugatuck Chem Co | Manufacture of formaldehyde condensation products of aliphatic amines and products obtained thereby |
| US4002564A (en) * | 1974-07-24 | 1977-01-11 | Diamond Shamrock Corporation | Cation-exchange resins having cross-linked vinyl aromatic polymer matrix with attached amino alkylene phosphonic acid groups, their use, and preparation |
| DE3727126A1 (en) * | 1987-08-14 | 1989-02-23 | Bayer Ag | N-(2-chloro-pyridin-5-ylmethyl)phthalimide, process for its preparation, and its processing to give 2-chloro-5-aminomethylpyridine |
| JPH03271273A (en) * | 1990-03-20 | 1991-12-03 | Nippon Soda Co Ltd | Production of 2-chloro-5-(aminomethyl)pyridine |
| JPH05230026A (en) * | 1992-02-20 | 1993-09-07 | Nippon Soda Co Ltd | Production of 2-chloro-5-methylpyridine derivative |
| JPH08295670A (en) * | 1995-02-28 | 1996-11-12 | Koei Chem Co Ltd | 2-chloropyridine derivative and its production thereof |
| CN1338924A (en) * | 1999-01-08 | 2002-03-06 | 艾米斯菲尔技术有限公司 | Polymeric delivery agents and delivery agent compounds |
| CN1714079A (en) * | 2002-11-25 | 2005-12-28 | 弗·哈夫曼-拉罗切有限公司 | Mandelic acid derivatives |
| WO2006109811A1 (en) * | 2005-04-07 | 2006-10-19 | Sumitomo Chemical Company, Limited | Process for producing an aminomethyl thiazole compound |
Non-Patent Citations (1)
| Title |
|---|
| 贾怀锋,等: "六亚甲基四胺法合成芳甲基胺", 《合成化学》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105837500A (en) * | 2016-03-31 | 2016-08-10 | 常州大学 | Synthetic method for N-(2-(3-(trifluoromethyl)phenoxy)-4-pyridyl)methylenimine |
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