Title of Invention	"A PROCESS FOR PRODUCING AN N-METHYLIDENE-SUBSTITUTED METHYLAMINE OLIGOMER"
Abstract	The present invention provides a process that enables a substituted methylamine compound which is useful as an intermediate for the production of agricultural chemicals and medicines, to be produced easily, with good yield, and at low cost, and also provides a production intermediate thereof. The process comprises a step of reacting a hexamethylenetetraammonium salt compound represented by a formula (I) with a base to obtain an N-methylidene-substituted methylamine oligomer represented by a formula (II) or a mixture of two or more of the oligomers, and a step of hydrolyzing the N-methylidene-substituted methylamine oligomer represented by formula (II) or the mixture of two or more of the oligomers in the presence of an acid. [Chemical Formula I] (wherein A represents an organic group that is either a hydrocarbon group or a heterocyclic group, or said organic group that has a substituent, R represents a hydrogen atom, an organic group that is either a hydrocarbon group or a heterocyclic group, or said organic group that has a substituent, L represents a halogen atom and the like, and n represents an integer of 2 to 20)

Title of Invention

"A PROCESS FOR PRODUCING AN N-METHYLIDENE-SUBSTITUTED METHYLAMINE OLIGOMER"

Abstract

The present invention provides a process that enables a substituted methylamine compound which is useful as an intermediate for the production of agricultural chemicals and medicines, to be produced easily, with good yield, and at low cost, and also provides a production intermediate thereof. The process comprises a step of reacting a hexamethylenetetraammonium salt compound represented by a formula (I) with a base to obtain an N-methylidene-substituted methylamine oligomer represented by a formula (II) or a mixture of two or more of the oligomers, and a step of hydrolyzing the N-methylidene-substituted methylamine oligomer represented by formula (II) or the mixture of two or more of the oligomers in the presence of an acid. [Chemical Formula I] (wherein A represents an organic group that is either a hydrocarbon group or a heterocyclic group, or said organic group that has a substituent, R represents a hydrogen atom, an organic group that is either a hydrocarbon group or a heterocyclic group, or said organic group that has a substituent, L represents a halogen atom and the like, and n represents an integer of 2 to 20)

Full Text	PROCESS FOR PRODUCING SUBSTITUTED METHYLAMINE COMPOUND AND TRIAZINE DERI VATIVE TECHNICAL FIELD [0001] The present invention relates to a process that enables a substituted methylamine compound, such as a pyridylmethylamine compound, which is useful as an intermediate for the production of agricultural chemicals and medicines and the like, to be produced easily, with good yield, and at low cost, and also relates to an N-methylidene-substituted methylaniine oligomer that acts as a production intermediate. BACKGROUND ART [0002] Substituted methylaniine compounds, including pyridymethylamine compounds such as 2-chloro-5-pyridylmeithylamine are useful as intermediates for the production of agricultural chemicals and medicines. Conventionally, known processes for producing pyridylmethylamine compounds include a process in which 2-chlQro-5-chloromethylpyridine is reacted with potassium phthaiimide to obtain N-(2-chloro 5-pyridylmethyl)phthalimide, which is subsequently reacted v,'ith hydrazine (see Patent Document 1), a process in which 2-chloro-S-(chloromethyl)pyridine is reacted with hexamethylenetetramine to obtain 2-chloro-'5-pyridylmethylhexamethylenetetraammonium chloride, and a hydrolysis is subsequently performed in the presence of a lower alcohol and a mineral acid (see Patent Document 2), and a process in which 2-chloro-5-pyridylmethylhexamethylenetetrammonium chloride is hydrolyzed using water or alkaline water to generate N-methylidene-2-chlpro'5-pyridylmethylamine, which is subsequently isolated and then hydrolyzed in an acid (see Patent Document 3). [0003] However, none of these production processes can be claimed to be entirely satisfactory- from an industrial perspective. Namely, the first process requires the use of the comparatively expensive potassium phthalimide as a raw material, meaning the process is undesirable from an economic perspective. Further, because an operation is required to remove phthalazine from the hydrazine reaction mixture, the post-processing operation tends to be complex. In the case of the second process, the amount of solvent used in the reaction is large, and a large amount of comparatively expensive hexamethylenetetramine must also be used, and therefore the process is undesirable from an economic perspective. Further, in this process, because the generated 2-chloro-5-pyridylmethylhexamethylenetetraammonium chloride must be first isolated, before being subjected to hydrolysis, a problem arises in that the operation is overly complex, In the third process a problem arises in that the isolated N-uitthy'iuciiC--^ vchloro! • pyridinemethylamine is unstable and difficult to handle- [0004] [Patent Document 1] (West) German Pat No, 3.727,126 [Petent Document 2] .Japanese Unexamined Patent Apphcation, First Publication No. Hei 3-271273 [Patent Document 3] .Japanese Unexamined Patent Application, First PubUcation No. Hei 8-295670 DISCLOSURE OF THE INVENTION PROBLEMS TO BE SOLVED BY THE INVENTION [0005] The present invention has been developed in light of the issues associated with the prior arts described above, and has an object of providing a process that enables a substituted methylamine compound, preferably a pyridylmethylamine compound, that is useful as an intermediate for the production of agricultural chemicals and medicines to be produced easily, with good yield, and at low cost, and the production intermediate thereof, MEANS TO SOLVE THE, PROBLEMS [0006] As a result of intensive research aimed at achieving the above object, the inventorsof the present invention discovered that by reacting a hexamethylenetetraammonium salt compound with a base, an N-methylidene-substituted rnethylamine oligomer represented by formula (IT) below, or a mixture of two or more 'such oligomers. could be obtained with good yield. Further, the inventors also discovered that by hydrolyzing this mixture in the presence of an acid, a substituted methyiamine compound represented by formula (10) below, which represents the target product, could be obtained with good yield, and they were therefore able to complete the present invention. [0007] Accordingly, a fust aspect of the present invention provides a process for producing a substituted methylamine compound, the process comprising: reacting a hexamethylenetetraammonium salt; compound represented by formula (D shown below: [0008] [Chemical Formula 1] (wherein A represents an organic group that is either a hydrocarbon group or a heterocyclic group, or said organic group that has a substituent, R represents a hydrogen atom, an organic group that is either a hydrocarbon group or a heterocyclic group, or said organic group that has a substituent, and L represents a halogen atom, an alkylsulfonyloxy group of 1 to 20 carbon atoms, a haloalkylsulfonyloxy group of 1 to 20 carbon atoms, or a substituted or unsubstituted arylsuifonyloxy group) with a base to obtain an N-methylidcne-substituted methylamine oligomer represented by formula (11) shown below: [0010] [Chemical Fomiula 2] (wherein, A and R are as defined above, and n represents an integer of 2 to 20), or a mixture of two or more of the oligomers. and hydrolyzing the N-methylidene-substituted methylamine oligomer represented by formula (tl) or the mixture of two or more of the oligomers in the presence of an acid, thereby producing a substituted methylamine compound represented by a formula (III) shown below, [0012] [Chemical Formula 3] [0013] (wherein A und R are as defined above), [0014] The abovementioned A preferably represents one group selected from the group . consisting of organic groups including a phenyl group, a pyridyl group, a thiazolyl group, a diiiuaiiyi gioup and a lelrauydrolm-auyl group, and said, organic groups having a Rub.stituent, [0015] More preferably, A represents one group selected from the group consisting of groups represented by formulas (IV) to (X) shown below: [Chemical Formula 4] (wherein X represents a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl group). [0016] The group A is still more preferably a 2-chloropyridin-5-yl group. Furthermore, the abovementioned R preferably represents a hydrogen atom, or a substituted or unsubstituted lower alkyl group, and more preferably represents a hydrogen tom or a n lkyl group of 1 to 5crbon toms [0017] In the process for producing a substituted methylamine compound of the present invention, the reaction between the hexamethylenetetraammonium salt compound represented by formula (I) and the base is preferably conducted at apH of 9 to 12. [0018] A second aspect of the present invention provides a process for producing a substituted methylamine compound, the process compring: reacting a substituted methyl Compound represented by formula (XI) shov,T\ below: [0019] [Chemical Formula 5] [0020] (wherein A represents an organic group that is either a hydrocarbon group or a heterocyclic group, or said organic group that has a substituent, R represents a hydrogen atom, an organic group that is either a hydrocarbon group or a heterocyclic group, or said organic group that has a substituent, and L represents a halogen atom, an alkylsulfonyloxy group of 1 to 20 carbon atoms, a haloalkylsulfonyloxy group of 1 to 20 carbon atoms, or a substituted or unsubstituted arylsnlfonyloxy group) with hextanethylenetetramine, or ammonia or an ammonium salt and formaldehyde or a formaldehyde equivalent, and a base to obtain an N-methylidene-substituted methylamine oligomer represented by formula (11) shown below: [0021] [Chemical Formula 6] [0022] (wherein Alifras defined above, and n represents an integer of 2 to 20), or a mixture of two or more of the oligomers, and hydrolyzing the substituted methylamine oligomer represented by formula (11) or the mixture of two or more of the oligomers in the presence of an acid, thereby producing a substituted methyl amine compound represented by a formula (01) shown below: [0023] [Chemical Formula 7] [0024J (wherein Alj* as defined above). i [0025] The above mentioned A preferably represents one group selected from the group consisting of organic groups including a phenyl group, a pyridyl group, a thiazolyl group, a dithianyl group and a tetrahydrofuranyl group, and said organic groups having a substituent. More preferably, A represents one group selected from the group consisting of groups represented by formulas (TV) to (X) shown below: [0026] [Chemical Formula 8] [0027] (wherein X represents a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl group). [0028] The group A is still more preferably a 2-chloropyridin-5-yl group. Furthermore, the above mentioaed R preferably represents a hydrogen atom, or a substituted or unsubstituted lower alkyl group, and more preferably represents a hydrogen atom or an alkyl group of 1 to 5 carbon atoms. [0029] In the production process of the present invention, the reaction between the substituted methyl compound represented by formula (XI), the hexamethylenetetramine, or the ammonia or ammonium salt and the formaldehyde or formaldehyde equivalent, and the base is preferably conducted at a pH of 9 to ) 2. [0030] Further,, in the production process of the present invention, it is preferable that the hexamethylenetetramine, or the ammonia and formaldehyde, are recovered from the reaction mixture obtained following the reaction of the substituted methyl compound represented by formula (XI) with the hexamethylenetetramine, or the ammonia or ammonium salt and the formaldehyde or formaldehyde equivalent and the base, and are subsequently reused in reaction with the substituted methyl compound represented by formula. (XI). [0031J A third aspect of the present invention provides an N-methylidene-pyridylmethylamine oligomer represented by formula (11') shown below: [0032] [Chemical Formula 9] (wherein X represents a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl group, and n represents an integer of 2 to 20). This oligomer is useful as an intermediate for the production of a substituted methylamine compound represented by formula (TIT). Of the various oligomers, an N-methylidene-substituted methylamine trimer m which n=3, which is a triazine derivative represented by formula (11") shown below, is preferred. [Chemical Formula 10] (wherein X is as defined above.) EFFECT OF THE INVENTION [0033] According to the present invention, a substituted jaethylarmne compound represented by formula (HI) can be produced in an industrially favorable manner, namely, easily, with good yield, and at low cost An N-methylidene -substituted methylamine oligomer of the present invention is useful as an intermediate for producing a substituted methylamine compound represented by formula (JIT). BEST MODE FOR CARRYING OUT THE INVENTION [0034] A more detailed description of the present invention is presented below. A process for producing a substituted methylamine compound represented by formula (III) (hereafter also refen-ed to as '"the amine compound (III)") comprises a step (hereafter referred to as "step (])") of reacting a substituted methylhexamethylenetetraammonium salt compound represented by formula (I) shown above (hereafter also referred to as "the ammouium salt compound (1)") with a base to obtain an N-methylidene-substituted metbylamine oligomer represented by formula (H) (hereafter also referred to as "the N-methylideneamine oligomer (11)") or a mixture of two or more such oligomers, and a step (hereafter referred to as "step (2)") of hydrolyzing the N-methylideneamine oligomer (II) or the mixture of two ot more N-melhylideneamine oligomers (IT) in the presence of an acid. [0035] Step (1) In step (l), the ammonium salt compound (I) is reacted with a base, yielding the N-methylideneamine oligomer (0) or a mixture of two or more such oligomers, In formula (T), A represents an organic group that is either a hydrocarbon group or a helerocyclic group, or said organic group that has a substituent. [0036] Specific examples of the hydrocarbon group include aromatic hydrocarbon group such s a phenyl group, naphthyl group, indenyl group, pyrenyl group, acenaphthenyl group, anthryl group or phenanthxyl group, aliphatic hydrocarbon groups such as a methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, s-butyl group, t-butyl group, n-hexyl group, n-octyl group. Vinyl group, allyl group, ethynyl group or propargyl group, and alicyclic hydrocarbon, groups such as a cyclopropyl group, cyclohexyl group or bic.yclof3.2.1]octyl group. Examples of the heterocyclic group include 5- to 7-membered rings containing 1 to 5 hetero atoms such as an oxygen atom, sulfur atom or nitrogen atom, and condensed rings thereof, and more specific examples include unsaturated 5-membered heterocyclic groups such as a furan- 2-yl proup, furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, pyn:ol-2-yl group, pyrrol-3-y] group, oxazol-2-yl group, oxa2ol-4-yl group, oxaznl-5-y] group, tthiazol-2-yl group, thiazol 4-yl group, thiazol-5-yI group, isoxazoI-3-yl group, isooxazol-4-yl group, isooxazol-5-yl group, isothiazol-j-yl group, isothiazol-4-yl group, isothiazol-5-yl group, imidazol-2-yl group, itiiidazol-4-yl group, imidazol-5-yl group, pyrazol-3-yl group, pyrazol-4-yl group, pyrazol-5-yl group, l,3,4-oxadiazol-2-yl group, l,3,4-thiadiazol-2-yl group, 1,2,3 triazol-4-yl group, l,2,4-tria2ol-3-yl group, 1,2,4-triazol-S-yl group, 5-phenyl--5-trifluoromethyl-isooxazolin-3~yl group, 2-furfurylmetbyl group, 3-thienyljnetbyl group, or l-methyl-S-pyiazolomethyl group; unsaturated 6-meTObered heterocyclic groups such as a pyridin-2-yl group, pyridm-3-yl group, pyridin-4-yl group, pyTidazin-3-yl group, pyridazin-4-yl group, pyrazin-2-yl group, pyrimidin-2 yl group, pyrimidin-4-yl group, pyrimidin-5-yl group, l,3,5-triaziQ-2-yl group, l,2,4-triazm-3-yl group, 2-pridylmetliyl group, S-pyndylmethyl gi-oup, 6-cWoro-3-pyTidyteiethyl group or 2-pyrimidyknethyl group; and saturated heterocyclic groups such as a tetrahydrofuraii-2-yl group, iditi niJiydi'flp')jiau-4-yI group, piperidin-3-yl group, pyrrolidm-2-yl group, moipholitio group, pipeiidino group, N-metiiylpipcrazinyl group, dithianyl gi-oup, 2-r.f'Triiiiijrrliru mwuyirnoLbyl group, 3 pnnmianii) iiiuwii'_'i'l' ffloup, N-methyl S-pyrrolidyhrietliyl group, or morpholinomethyl group. Of these, A is preferably a phenyl group, pyridyl group, tluazolyl group, dithianyl group or tetrahydrofiiranyl group. The hydrocarbon group or heterocydic group may be substituted, provided the substitution has uo effect on the reaction, and specific examples of the substituent include a hydroxyl group; a thiol group; halogen atoms such as a fluorine atom, chlorine atom, bromine atom or iodiae atom; a cyano group; a nitro group; a formyl group; unsubstituted or substituted amino groups such as an amino group, methylamino group, betrzylaraino group, aniliao group, diniethylamino group, diethylamino group or phenylethykroino group; alkyl groups (and preferably C1to C6 aJkyl groups) such as a methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group, isobutyl group, t-butyl group, n-pentyl group or n-hexyl group;alkenyl groups sucb as a vinyl group, allyl group or 2-mp.thoxyetlienyl group; alkynyl groups such as an ethjiiyl group, 1-propynyl group, 2-phenylethynyl group orpropargyl group; allcoxy groups (and preferably Ci to C6 alkoxy groups) such as a methoxy group, ethoxy group, propoxy group, isoptopoxy group, n-butoxy group, sec-butoxy group, isobutoxy group or t-butoxy group; alkynyloxy groups such as a vinyloxy group or allyloxy group; alkynyloxy groups such as an ethynyloxy group or propargyloxy group; aryloxy groups such as a phenoxy group, benzyloxy group or 2-pyridyloxy group; haloalkyl groups (and preferably C1 to C6 haloalkyl groups) such as a chloromethyl group, fluoromethyl group, bromomethyl group, dichloromethyl group, difluoromethyl group, dibromomethyl group, trichloromethyl group, trifluoromethyl group, bromodifluoromethyl group, trifluoroethyl group, 1-chloroethyl group, 2-chloroethyl group, 1-bromoetbyl group, 2-bromoethyl group pentafluoroethyl g^Mf; haloalkoxy groups (and preferably C1 to C6 haloalkoxy groups) such as a fluoromethoxy group, chloromethoxy group, bromometboxy group, diflnriioiiiethox^,' group, dichloroinctho^c}' group, dibroiarjuietliox}" fei'Jtip, triiluoromethoxy group, trichloromethoxy group, tiibromomcthoxy group, trifluovoethoxy group, peutalluorocthoxy group or pentajfluoropropoxy group; alkylthiocarbonyl groups (and preferably C1 to C6 alkylthiocarbouyl groups) such as a methylthiocarbonyl group, ethylthiocaibonyl group, propylthiocarbouyl group, isopropylthiocarbonyl group, butylthiocarbonyl group, isobutylthiocarbouyl group,^ec-hutjfUhiiiM^oiiyj- group or t butylthiocarbonyl group; alkylsulfonylamino groups (and preferably C, to Ce alkylsulfonylamino groups) such as a methylsulfonylamino group, ethylsulfonylamino group, propylsulfonylamino group, isopropylsulfonylamirjo group. butylsulfonylamino group or t-butylsulfonylamino group; arylsulfonylamino groups (and preferably C6 to C12 arylsulfonylamino groups) such as a pheoylsulfonylamino group or piperazmysullfonyl,amino group; alkylcarbonylamino groups (and preferably C1 to C6 alkylcarbonylamino groups) such as a methylcarboaylammo group, ethylcarbonylamino group, propylcarbonylamino group or isopropylcarboaylamino group; alkoxycaxbonylamino groups (and preferably C1 to C6 alkoxycarbonylamino groups) such as a methoxycarbonylamino group, ethoxycaxbonylamino group, propoxycarbonylamino group or isopropoxycarbonylamino group; haloalkylsulfonylamino groups (and preferably C1 to C6 haloalkylsulfonylamino groups) such as a fluoromethylsulfonylamia, group, chloromethylsulfonylamino group, bromomethylsulfonylamino group, difluoToraethylsulfonylaraino group, dichloromethylsulfonylammo group, difluoromethylsulfonylamino group, trifluorometliylsulfonylamiuo group, trifluoroethylsulfonylamino group or pentafluoroethylsulfonylanibo group; bis(alkylsu]fonyi)amino groups (and preferably bis(Ci to Cft alkylsulfonyl)amino groups) such ai! a bis(methylsulfonyl)ammo group, bis(ethylsulfony1)amino gioup, (methylsulfonyl)(ethylsulfonyl)anuno group, bis(propylsuIfonvDamino group. bT!3(isnprnpy]sii1tVirtyl)fltr!mo f^oirp, bi3(butylsxilfonyl)ammo group or bis(t-butylsulfonyl)amino group; bis(haloalkylsulfonyl)animo groups (and preferably tais(Ci to Cg haloalkylsulfoByl)ainino groups) such as a bis(fluoromethylsulfony))amino group. bis(chloromethylsulfonyl)amitio group, bis(bii,omomethylsulfonyl)ammo group, bis(difluoroinethylsulfonyl)arDino group, bis(dichloromethylsulfonyl)atnino gi'oup, bis(drl:luororoethylsulfonyl)amino group, bis(irifluorometliylsu]fonyl)an)ino group, bis(trifluoroethylsulfonyl)amino group or bi$(pentafluoroethyl3ulfonyl)amino gjoup; ansubstituied or substituted hydrazinotDatboiiyawh oay^ groups such as a hydraxino group, N'-phenylhydiazino group orN'-methoxycarbonyHiydrazino group; alkoxycarbonyl groups (and prefeiably Ci to Ce alkoxycarbonyl groups) such as a methoxyciirbonyl group, ethoxycaj-bonyl group, propox7caibonyl group, isopropoxycaibonyl gioup, butoxycarbonyl group or i-butoxycarbonyl group; aryl groups (and preferably Cs to Cu arj'l groups) such as a phenyl group, 1-naphthyl group or 2-napbtliyl group; unsatmated S-membered heterocyclic groups such as a furan-2-yl group, futaji-S-yl group, thiophen-2-yl group, tMopheu-3-yl group, pytrol-2-yl group, pyrrol-3-yl group, oxaz;ol-2-yl group, oxazol-4-yl group, oxazol-5-yl group, thia2Ql-2-yl group, Lhia2;ol^l-yl group, thiazol-5-yl group, isooxazol-3-yl group, isooxazol-4-yl group, isooxa2:ol-5-yl group, isothiazol-3-yl group, isothiazol-4-yl group, isothiazol-5-yl group, briida2:ol-2-yl group, imidazol-4-yl group, imidazol-5-yl group, pyrazol-3-yl group, p>Tazol-4-yl group, pyra2ol-5-yl group, l,3,4-oxadiazol-2-yl group, l,3,4-tliiadiazol-2-yl gioup, l,2,3-tria2;ol-4-yl gi-oup, 1,2,4-tria2ol-3-yl group, l,2,4-tiiazol-5-yl group, 5-phenyl-5-ti-itlnorom.ethyl-isooxazolin-3-yl group, 2-furfarylmethy\ group, 3-thienylmethyl group or 1 -methyl-S-pyrazolomethyl group; unsaturated 6-menibered heterocyclic groups such as a pyTidin-2-yl group, pytidin-3-yl group, pyridiii-4-yl group, p\TidaziQ-3-vl eroiip. r>yriria7in-4-yl grnup m;rfl5dt hydroxyiminomethyl group or N-methoxyiminomethyl group; N-unsubstituted or N-substituted hydrazinocarbonyl groups such as an N'-methylhydrainocarhonyl group, N'-phenylhydrazinocarbonyl group or hydrazinocarbonyl group; N-unsubstituted or N-substituted aminocarbonyl groups such as an aminocarbonyll group, dimethylaminocarbonyl group orN-phenyl-N-methylaminocarbonyl group; N-unsubstituted or N-substituted hydramino groups such as a hydra2ino group, N'-acetylhydrazino group, N'-mcthylhydraziTio group, N'-phenyhydrazino group or N'-raethoxycarbonylhydrazino group; alkylthio groups such as a methylthio group, etliyltbio gioup or t-butyltliio gi'oiip; aJJcenylthio groups such a$ a vinyltMo group or allylthio gj oup; alkynylthio groups such as an etbynylthio group or propargyltluo group; ar>1tMo groups such as a phenylthio group, 4-cMoroph.enyIthio group, benzylthio group, phenethylthio group or 2-pyTidylthio group; alkylsulfonyl groups such as a luethylsulfonyl group, ethylsulfonyl group or t-butylsulfonyl group; alkenylsuJfonyl groups such as an allylsulfonyl group; alliiDa)4»ulfoiiyl groups such as a propaigylsulfonyl group; and arylsulfonyl groups such as a phenylsutfonyl group, beuzylsolfonyl group or 2-pyridylsulfonyl group. Other novel substituents generated by 3uhil3ti:ticg one Gubstituent Vvitb another 3ub:^tinicnt, dieroby combining P.vo or more substituents, may also be used. More specifically, A is preferably one group selected fi:om the group consisting of groups represented by fonnulas (TV) to (X), and is most preferably a 2-chloropyridin-5-yl group. Specific exatnples of X within formulas (IV) to (X) include a hydrogen atom, halogen atoms such as a fluorine atom, bromine atom, chlorine atom or iodine atom, arid alkyl groups such as a methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, s-butyl group, t-butyl group, n-hexyl group or n-octyl group. Tlie alkyl group may include a substihient on an appropriate carbon atom, and examples of the substituent include the same substituents as those exemplified above for A. The substituent within A may be protected with an appropriate protective group prior to conducting the reaction with the base. In formula (I), specific examples of R include the same groups as those exemplified above for A. [0037] Specific examples of L m formula (T) include a hydrogen atom, halogen, atoms such as a fluorine atom, chlorine atom or bromine atom, alkyisulfonyloxy groups of 1 to 20 carbon atoms such as a methylsulfonyloxy group, ethylsulfonyloxy group or n-propylsulfonyloxy group, haloalkylsuLfonyloxy groups of 1 to 20 carbon atoms such as a trifluoromethylsulfonyloxy group, trichloromethylsulfbnyloxy group, 2,2,2-trifluoroethylsulfonyloxy group or perfluoroethylsulfonyloxy gfottp, and arylsulfonyloxy groups such as a phenylsiilfonyloxy group, napbthylsulfonyloxy group, anthrylsulfonyloxy group or phenanthr>4sulfonyloxy group. The arylsnlfonyloxy groups may include a substituent at an appropriate position, and examples of the substituent include the same substitueuts as those exemplified above for A. Examples of preferred .vuu^ui.u«jiiis. iiitludti halogen aioiiis iuui a^ u, iiuuriuc uloiu, cliioiinv; atom oi bivujjJiic atom, alkyl groups such as a methyl group or ethyl group, alkoxy groups such as a methoxy group or ethoxy group, haloalkyl groups such as a trifluoromethyl gioup, and a nitro group. [0038] Although there are no particular restrictions on the process used for producing the aiamonimn salt compound (I), one example of a preferred process involves reacting a substituted methyl compomid represented by foim.ula (XI) (hereafter also referred to as "the substituted methyl compoxmd (XT)"), -with either hexamethylenetetramine, or a mixture of ammonia or an ammonium salt and formaldehyde or a formaldehyde equivalent. [0039] The substituted methyl compound (XT) can be produced using conventional methods, and n the case of a compound where A is represented by formula (IV) and X is a halogen atom, can be produced by a process that iitvolves halogenating a 2-halogeno-5-methylpyridine, or a process that involves reacting a 2-halogeno-5-hydxoxyraethylpyridine with an alkylsulfonyl halide or arylsulfonyl halide in the presence of a base, [0040] Specific examples of the compound represented by formula (XI) include 3-(fluoromethyl)pyridine, 3-(chloromethyl)pyridine, 3-(bromomethyl)pyridine, [(pyridine-S-yl)methyllmethyl sulfonate, [(pyridin 3 -yl)ethyl]ethyl sulfonate, [(pyridin-3-yl)methyl]-D-propyl sulfonate, [(pyridin-3-yl)mediyl]phenyl sulfonate, 2-fluoro-5-(fluoromethyljpyridine, 5-chloromethyl-2-fluoropyfidme, 5-bromomethyl-2-fluoropyridiue, [(2-fluoTop>Tidm-5-yl)methyl]metbyl sulfonate, [(2-fluoropyridm-5- .^ jyiULUj-j iJv^igQji :iuinjuaic, v_i.-liuuii;ljjinuii.i-,'-^ij-u-piup}] ^^uUOuaLCj [i_^'jJ.uuj,vjj^viiiMk4li-^ yl)methyl]plieiiyl sulfonate, 2-chloro-5-(fluoromethyl)pyriditie, 2-chloro-5-(chloroniethyl)pyridme, 5-bromomethyl-2-chloropyridine, [(2-cliloropyridin-5-yl)metliyl]melh.yl sulfonate, [(2-chloropyridin-5-yl)mcthyl]etliyl sulfonate, [(2-chloropyridin-5-yl)methyl]-n-propyIsidfonate, [(2-chloropyridia-5-yl)methyl]phenyl sulfonate, 2-bromo-5-(fluoromethyl)pyridJne, 2-bi'Orao-5-(chloromethyl)pyridine, 2-bromo-5-(bromomethyI)pyridine, [(2-bromopyridin-5-yl)methyl]methyl sulfonate, [(2-bromopyridin-5-yl)taethyl]ethyl sulfonate, [(2-bromopyridin-5-yl)methyl]"n-propyl sulfonate and [(2-bromopyriclin-5-yl)methyl\|phenyl sulfonate- Of these, 2-chJoTo-5-(chloromethyl)pyridme is particularly desirable. [0041] There are no particular restrictions on the base used in the reaction with the ammorauTtt salt compound represented by formula (1), and specific examples include alkali metal hydroxides such as soditim hydroxide or potassium hydroxide, alkalme earth metal hydroxides such as magnesium hydro3dde or calcium hydroxide, carbonates such 05 sodium carbonate, potassium carbonate, magnesinm carbonate or calcium carbonate, metal alkoxides such as sodium methoxide, soditim ethoxide or magnesiiun, methoxide, and organic bases such as triethylamine, dnsopropylethylamine, pyridine, 1,4-dia2abicyclo[2.2.2]octane or l,8-diazabicyclo[5.4.0]-7-undecene. Of these, from the viewpoints of production costs and maximizing the yield of the target product, alkali metal hydroxides are preferred, and sodium hydroxide is particularly desirable, [0042] Tlie pH during the reaction of the ammonium salt compound (T) with the base is tvpically within a range from 9 to 12, and is preferably controlled withtin a range from 9.5 to 11.5. and more preferably fi-om 10 to 1 ] Py ("nntroLHrig the pH of tbf refaction ^yst?!:;^, within this range, the N-methylideneamiue oUgomer (II) can be produced with good yield. [0043] The reaction between the ammonium salt compound (I) and the base is typically conducted withm a solvent. There are no particular restrictions on the solvent used, provided it is inert with respect to the reaction. Examples of solvents that may be used include water; alcohol-based solvents such as metlaanol, ethanol or n-propanol; ahphatic hydrocarbon-based solvents such as n-pentane, n-hexane, n-heptane or n-octane; alicyclic hychrocarbon-based solvents such as cyclopentane or cyclohexane; aromatic hydrocarbon- based solvents such iis beiizene, toluene, xylene or cblorobenzene; ketone-based solvents 3uch as acetone, tnethyl ethyl ketone, diethyl ketone, methyl isopropyl ketone, methyl bobutyl ketone or cyclohexanotie; ether-based solvents such as diethyl ether, tetrahydrofuraix, dioxane or 1,2-dimethoxyethane, nad nuxtiires of two or more of the above solvents. Of the above po$sibilities, the use of a mixed solvent of water iind an aromatic hydrocarbon-based solvent is preferred, and the use of a mixed solvent of water and tohiene is particularly desirable. [004^1] Tlie reaction temperature for the reaction betw^een the ammonium salt compound (I) and the base is typically within a range from room temperature to the boiling point of the solvent, and is preferably within a range from 40 to 70°C. The reaction time is typically within a range from several minutes to several days, and is preferably within a range tVom 1 to 10 hours. Following completion of the reaction, tl^e reaction liquid may be sampled, and the completion of the reaction can be confirmed using conventional analytical techniques such as thin layer cluomatography, gas chromatography or high-performance liquid chromatocraphv. [0045] Further, in the present invention, the N-metliylideneamine oligomer (11) may also be obtained in a suigle step by reacting the substituted methyl compound (XI) with hexametliyleuetetramine and a base. In this case also, the pH of the reaction liquid is typically vrithin a range from 9 to 12, and is preferably controlled withm a range from 9.5 to 11.5, and more preferably from 10 to 11. By controlling the pH of the reaction system within this range, the N-methylideneamine oligomer (II) can be obtained with good yield. [0046] The amount of hexamethylenetetramine used is U-pically within a range from 0 1 to 10 mol, and preferably from 0,25 to 2 mol, per 1 mol of the substituted methyl compound (XI). [0047] Moreover, ui the present invention^ the N-metliylideneanune oligomer (11) may also be obtained m a single step by reacting the substituted tnefhyl compound (XT) with finmionia or an anunonitUB salt, formaldehyde or a formaldehyde equivalent, and a base. In this case also, the pH of the reaction liquid is typically within a range from 9 to 12, and is preferably controlled within a range from 9.5 to 11.5, and more preferably from 10 to 11. By controlling the pH of the reaction system within this range, the N-metbylideneaniine oligomer (Tf) can be obtained with good yield. [0048] Becau.se this process replaces hexamethylenetetramine with ammonia or an ammonium salt and formaldehyde or a formaldehyde equivalent, all of which are low-cost industrial raw materials, it is particularly advantageous in the case of mass [0049] There are no particular restrictions on tlie ammonia used, and gaseous ammonia or an aqueous solution or alcohol solution or the like of aranioma may be used. In tjiose cases where an ammonia aqueous solution is used, the concentration of the solution is typically within a range from 5 to 25%, and is preferably from 10 to 25%. Further, an anxuionium salt may be used in.'jtead of the ammonia. Examples of ammoniiun salts that may be used include ammonium acetate, ammonium nitrate, ammonium stilfate or ammonium chloride. rhe amoimt ':)f ammoiua used is t^'pically within a raage from 1 to 40 mol and preferably from 1 to 8 mol, per 1 mol of tlie substituted methyl compound (XT). [0050J There me no particular restrictions on the foritialdehyde used, and an aqueous solution or alcohol solution or the like of formaldehyde may be used. Ftutheraiore, a fonnaldehyde equivalent may also be used instead of foimaldebyde. An. example of the formaldehyde equivalent is paraformaldehyde, which is a polymer of formaldehyde. Paraformaldehyde is a white powder at room temperature, and can be used to generate fonnaldehyde by dissolution in the organic solvent and subsequent heating. The amount of formaldehyde used is typically vvithia a range from 0.1 to 20 mol, and preferably from 1 to 2 mol, per 1 mol of ammonia. [0051] In the cases described above, the substituted methyl compotmd (Xl) is reacted with the hexamethyleiietetnimine, or witli the aramonia or the like and formaldehyde or the like, and the hexametliylenetetramine or the ammonia and the formaldehyde can be recovered from the obtained reaction mixture and subsequently reused in reaction with th^ [0052] Furthermore, in those cases where the solution containing the recovered anamonia and fonnaldehyde is used in a continuotis process, the solution may be used as is, although m those cases where the ratio of ammonia and formaldehyde within the recovered Solution differs from the ratio required to en.'jure continuvty of the inaction, a supplementan' amount of the component among the auimonia and the aldehyde that is lacking must be added to the solution. In other words, if the amount of ammonia is insufficient, then amtnonia or an ammonium salt is added, whereas if the amount of the formaldehyde is insufficient, fonnaldehyde or a fonnaldehyde equivalent is added, thereby adjusting the ratio between the aumionia and the formaldehyde to the optimum ratio. This optimum ratio varies depending on factors such as the reaction conditions, but the amount of the formaldehyde is typically within a i^mge from 0.1 to 20 mol, and preferably fiom 1 to 2 mol, per 1 mol of the ammonia. [0053] In those cases where a mixture of the substituted raethyl compound (XI) with either hexamethylenetetramine, or ammonia or the like and formaldehyde or the like is used instead of the axnmonium salt compound (I), the base and solvent used, and other factors such as the reaction temperatoe and the like may aU be the same as those described above for the reaction that uses the ammonium salt compo^md (I). [0054] Tn 'hither ca,-.c, the N-mcthylidcucamhic oligomer (11) or u'liivlure of t^Mj i;i HWIM such oligomers that represents the target product can be isolated using typical post¬processing operations. [0055] The stnicture of fhe obtained N-methylideneamine oligomer (II) can be confumed using conventional analytical techniques such as 'H-NMR, '^C-NMR, IR spectroscopy, mass spectrometry and elemental analysis. [0056] Tlie structure of die N-melhyHdeneamme oligomer (11) may be a chain-like stnictare,, a cyclic stnicuire, oi a structure contaimng botii chain-like and cyclic portions, althougti a cyclic compound represented by fonaula (TI') is particularly desirable Lu formula (H'), X is as defined above, and examples thereof ijiclude the same substituents as those exemplified above. In either Ibmaula (11) or fonniHa (IP), n represents an integer of 2 to 20, and is preferably witliin a range from 2 to 10, and more preferably from 2 to 5. Based on the various spectra mentioned above, the N-methylideneamine oligomer (II) is thouglit to have a structure s-uch as those shown below. [0057] [Chemical FoiTQula+4t- 14--3^1 [0059] [Chemical Fomai;Ia 16] [0060] Tnazme derivatives represented by formula (IV) aie particularly desirable. The N-methylideneamine oligomer (11) or the mixture of two or moie such oligomers obtained in the maimer described above is useful as an intermediate for the prodiiction of the amine compound (HI). [0061] In the present iaventioo, following completion of the reaction, the imine compound (IT) or the mixture of tw^o or more such compounds need not necessarily be isolated from the reaction solution, and the reaction solution may be supplied, as is, to the subsequent step (2). [0062] In other words, the N-methylidsneamine oligomer (II) is a basic substance, and has the property of being soluble in acidic water. Accordingly, by conducting the reaction berweeu the animoaium salt compound (\) and the base in a mixed solvent mediLin:! containiag water and an organic solvent that is tonmscible with water, such as a mixed solvent medium composed of water and toluene, subsequently separating the organic layer fi:om the obtained reaction mixture, and then extracting the separated organic layer with acidic water, a salt of the N-methyhdeneauiine oligomer (iri or roixture of two or more such oligomers that represents the target product caij be obtained as an aqueous solution. This aqueous solution may be supplied, as is, to the subsequent step (2). [0063] Step (2) Step (2) involves hydrplyzing the N-methyUdeneamine oKgomer (II) or the mi}fture of two or more such oligomers in the presence of an acid to obtain the amine compound (IIT). [0064] Tliere are no particular restrictions on the acid used in the reaction, and specific examples include inorganic acids stich as sulfuric acid, hydrochloric acid or phosphoric acid, organic carboxylic acids such as acetic acid or triJQuoroacetic acid, oreanic sulfonic acids such as p-tohienesulfonic acid, methanesulfonic acid or trifluororuethanesulfonic acid, and Lewis acids such as boron tritluoride, titanium tetrachloride or aluminum chloride. [0065] The amount of acid used is typically within a range from 1 to 100 mol, preferably from 2 to 20 mol, and more preferably fi-om 3 to 10 mol, per 1 mol of the ammonium salt compound (I) or the substituted methyl compound (XI). By setting the amount of acid 1 used TO a value within this range, the tai'geted substituted methylajiii"ne compound (III) can be obiaiued with, good yield. [0066] The hydrolysis reaction of tiie N-methylideueamine oligomer (ID or miximve of two or mors such ohgomers in tlie presence of an acid is typically conducted with the reactauts diluted vvith a solvent. Exaroples of tluii solvent include the same solveQt.s as those exempliiied above for use within the reaction of the substituted methyl compound (XI) \vitli hexamethylenetetramine, or the tmxture of ammonia or the like and formaldehyde or the like. Of these solvents, a mixed solvent containing water and an alcohol is preferred, and a mixed solvent containing water and methanol is particularly desirable. [0067] The reaction temperature during the hydrolysis of the N-methylideneamine oligomer (11) or mixti-ire of two or more such oligomers in the presence of an acid is typically within a range fi-oni room temperature to 90'C, and is preferably from 50 to 90C. The reaction time is tjfpically within a range from several minutes to several days, ?)ii(l is nrpferably vvithin a range from 1 to !0 hour's. FcUo-vrlng completion of the reaction, the reaction liquid may be sampled, and the completion of the reaction can be confirmed using convfcntional analytical techniques such as thin layer chromatography, gas chromatography or high-performance liquid chromatography. [0068] Following completion of the reaction, the target amine compound (TH) can be obtained by conducting typical post-processing operations, and then using conventional purification techniques such as distillation and column chromatography. Accordmg to the present iiwentinn, the mixine compound (III), and preferably a pvTidylmethylamiiie compoimd represented by fomiula (lH')' [0069] [Chemical Fonnula 17] [0070] (wherein X is as defined above) can be produced easily, with good yield, and al low cost, [0071] The aroine compound (III) obtained using the production process of the present invention is asefiil as an intermediate in the production of agiicultitral chemicals and medicines and the like, such as an intermediate in the production of the active component cVlororMcotinyl, in obtorr:iniiii#Hh4--based agricultural and horticultuial insecticides such as Imidacloprid, A Nitenpyxam and Acetaxniprid. [0072] Furthermore, according to the production process of the present iavention, by reacting a hexamethylenetetraammonium salt compound represented by fomiula (XII): [Chemical Fonuula 18] (wherein B represents a phenyl group, pjTidyl group, tliiazolyl group, dithirinyl group oi tettahydrofuranyl group, ajid mo.st, preferably represents a dithianyl group, and L is as defined above) with a base, an N-methylideneaniine oligomer represented by formula (XITI); [0074] [Chemical Formula 19] [0075] (wherein B is as dctmed above, and n and m each independently represents an integer of 2 to 20) ox a mixture of two or more such oligomers can be obtained, and by subsequently bydrolyzing the N-methylideneamine oligomer repre$ented by formula (XHI) or the mixture of two or more such oligomers in the presence of an acid, a substituted methylanrine compound represented by formula (XIV) can be produced. [0076] [Chemical Formula 20] [0077] (wlierein B is as defined above.) [0078] Fui'tlieimore, according to the prnduction process of the present invention, by reacting a substituted metlij'l compound represented by fomiula (XY): [0079] [Cheniical Formula 21] [0080] (wherein B and L are as defined above) Mth hexaraetbylenetetramine, or ammonia or an ammooiiim salt and formaldehyde or a formaldehyde equivaJant and a base, an N-meLhylideneamine oligomer represented by formula (XHI) or a mLxtuie of two or more such oligomers can be obtained, and by subsequently hydrotyzmg the N-methylideneamine oligomer represented by foimula (XlII) or the mixture of two or more such oligomers in the presence of an acid, a substituted methylamine compound represented by formula (XIV) can be produced. [0081] In this manner, the production proce.ss of the present invention enables even compovmds that have proven impossible to produce -mth conventional processes to be produced easily, with good >ield, and at low cost. EXAMPLES fOOS2] The present invention is described in fuither detail below using a series of examples, although the present invention is in no way limited by tliese examples. ./Analysis of the reaction, products was performed using liiglv-perforraaiice liquid cliromatogi-aphy (HPLC, model LC-10, roanufacrLired by Shimadzii C;oTporation) and gas chromatography (GC, model GC:-14B, mauufaciured by Shiniadzu Corporation) (Example 1) Production of (2-chlofopyridin-5-yl)methyktiune(l) To 3.02 g (10 mmol) of (2-cliloi-opT/Tidin-5-yr)hexamethy!enetetraattmionimn chloride (1-1) were added 5 ml of water and 5 ru) of toluene, and the restilting mixture was stirred for 7 Jiours at 60'C while a 28% aqueous solution of sodium hydroxide was used to maintam the pH of the reaction mixture wthin a range from 10 to 11. An additional 4 ml of toluene was added to the reaction mixture, and the toluene layer was separated. 7 g of concentrated hydrochloric acid was added to the toluene layer, and the water layer containing the hydrochloride salt of anN-methylidene-2-eliloro-3-p>Tidylmethylaraine oUgomer (II-l) or a mixture of two or more such salts was separated, 3.2 g of methanol Avas added to the separated water layer, and the resulting mixture was treated for 3 hours at 60C, yielding an aqueous solution of the hydrochloride salt of (2-chIoropyridin-5-yl)methylamiQe (lll-l). Analysis by IIPLC rf^^.'.-glp [0083] (Example 2) Production of (2-cMoropyridin-5-yl)methylan3iae (2) To 1,62 g (10 mmol) of 2-chloro-5-(chloromethyl)pyridine (XI-1) and 1.48 g (10 nunol) of hexametliyleoetetramine were added 5 ml of water and 1 ml of toluene, and the resulting mixture was stirred for 7 hours at 60°C while a 28% aqueoits solution of sodium hydroxide was used to maintain the pH of the reaction mixture within a range fi-omlOtoU. All additional 4 ml of toluene was added to tlie reaction mixture, and the toluene layer \vf\^ separated. 7 g of concentrated hydrochlonc acid was added to the toluene layer, and tiie water layer contmiiiig the hydrochloride salt of anN-methylideiie-2-clJoro-3-pyiidyhnetliylaEnine oligomer (Il-l) or a inixtme of t^vo or more such salts was separated, 3.2 g of merlianol was added to the separated water layer, and fhe resulting roLxture was treated for 3 hours at 60°C, yielding an aqueous solution of the hydrochloride salt of (2-chloropyridiii-5-yr)inethylmnine (III-1). Analysis by HPLC revealed a product amouat of 1.28 g (yield: 90%). [00S4] (Example 3) Production of (2-chlotopyTidin-5-yl)melhylamiDe (3) [0085] To 1.62 g (10 rrnnol) of 2"diloro-5'diloromethylpyridine (XI-1) and 0.7 g (5 rnmol) of hexamethylenetetramine were added 5 ml of water and 1 ml of toluene, and the resulting mixture was stirred for 7 hours at 60'C while a 28% aqueous solution of sodium hydroxide was used to maintahi the pH of the reaction mixture within a range Liutu iO Lu 11. An additional 4 nil of toluene was added to the reaction mixture, and the toluene layer was separated. 7 g of concentrated hydrocWoric acid was added to the toluene layer, and die water layer containing the hydrocUoride salt of a pyridyhnethyliitiine compound (11-3) or a mixture of t\\'o or more such salts was separated. 3.2 g of methanol was added to the separated water layer, and the resulting mixture was treated for 3 hours at 60°C, yielding an aqueous solution of the hydrochloride salt of (2-chloropyTidin-5-yr)metl.iylainirie (III-l). Analysis by HPLC revealed a product amount of 1,26 g (yield: 89%). Comparison mih exm^ph 2 above confirmed that even if the amotint of hexamethyleuetetiamine was reduced, tJieie was no substimtial effect on the \ield of the target product. [0086] (Example 4) Production of 1,3,5'tris[(2-chloropyridiflo-yl)methyl]-1,3,5-perhydrotriazine [0087] 10 a mixed solution containing 10 ml of methanol and 10 nal of water were sequentially added2.72 g (40 mjaiol) of a25% aqueous solutioaof ammoma, 1.21 g (40 mmol) of paiaformaldehyde, and 3.24 g (20 mmoY) of 2-chloro-5-(chloromethyl)pyridjjie (XI-1), and tlie resulting mixture was stirred for 2.5 hours at 50°C while a 28% aqtieous solution of sodium hydroxide was used to maintain the pH of the reaction iriixture within a rduge fi-om 10 to 11. The reaction auxture was then extracted wtli chloroform, and the chloroform layer was separated and concentrated, yielding 2.50 g (yield: Sl%) of 1,3,5-(ri"s(2-':hlorop:.T-:din ;> v!.)raethyM,3,5 pcrlrydrotr;a7,uu; (u-i). ^H-NMR (CDCI3,5 ppra): 3.37 (bs, 6H), 3.62 (s, 6H), 7.26 (d, 3.H), 7.61 (d, 3H), 8.33 (s, 3H) m/s: 462 (0088] (Example 5) Production of (2<.hloropyridin-5-yl> To 0.77 g (1.66 mol) of l,3,5-tris[(2-chloropyridio-5-yl)methyl]-l,3,5-perhydxotriazLne (n-4) were sequentially added 0.40 g of methanol and I.S3 g of ("■■oncentrateJ hydrocMoric acid, and the resulring mixture was stirred at 75 to 80°C for 6 hours ITie reaction mixture was then diluted with chloroforai, and following conversion of the mixture to an alkalme state by adding a 28% aqueous solution of sodium liydfo,vdde, the chlorofotm layer was separated and concentrated, yielding 0-68 g (yield: 95'?/o) of (2-chloTOp5Tidin-5-yl)methylamine (1114). [0089] (Example 6) Production of (2-chloropyridin-5-yl)methylaiiune (5) To 1.62 g (10 mmol) of 2-chloro-5-(cWofomethyl)pyTidine (Xl-1) and 1.48 g (10 mmol) of heKamethylenetctraitiiae were added 5 nd of water and 1 ml of toluene, and tlie resulting mixture was stirred for 7 hours at 60°C vvhile a 28% aqueous solution of sodium hydroxide was used to maintain the pH of the reaction mixture \sithin a range from 10 to 11. An additional 4 ml of toluene was then added to the reaction mixture, and the water layer was separated to recover the hexamethylenetetramine, Analysis by GC revealed a recovei7 rate of 75%. The toluene layer was treated in die same manner as eJcample 2, yielding (2-chloropyridin-5-yl)metliylaniiDe(ni-l). rnnQOi To the aqueous solution containing hexamethylenetetramine recovered in the manner described above were added 1.62 g (10 mmol) of 2-chloro-5-(cbloromethyl)pyridine (XH), 0.52 g (3.5 mmol) of hexamethyleoetetrainine, 0.18 g of aimnoruum chloride and 1 ml of toluene, and the resulting nuxture was heated for 7 hours at 60C while a 28?^ aqueou.s solution of sodium hydroxide was used to maintain thft pH of the reaction niixture within a range iiom 10 to 11. An additional 4 ml of toluene was then added to the reaction mij^ture, and the toluene layer and water layer were each separated. The hexamethylenctetTajiiine was recovered from the water layer-arid the recovery rate was 69" o, . [0091] Orx the other hand, 7 g of concentrated hydrochloric acid was added to the toluene layer, and tlie resulting water layer containing the hydrochloride salt of an N-methyUdene-(2-cMoro-pyridin-5-yl)methylarDine oligomer (11-5) or a mixture of two or more such salts was separated. 3.2 g of methanol was added to the separated water layer, and the resulting mixture was treated for 3 hours at 60^0, yielding an aqueous solution of the hydrochloride salt of (2.chloropyridin-5-yl)methylamine. Analysis by HPLC revealed an amount of the (2-chloropyridin-5-yl)methylamiae of 1.28 g (yield: 90%). [0092] As described above, in the examples, approximately 70?/o of the hexarnetliylenetetramine was able to be recovered, and by simply supplementing the reaction with the required amount of additional hexamethylenetetramine!, the reaction was able to be continued at the same scale. 1. A process for producing a substituted methylamine compound, said process comprising: reacting a hexamethylenetetraammonum salt compound represented by a formula (I) shown below: [Chemical Formula 1] (wherein A represent; an organic group that is either a hydrocarbon group or a heterocyclic group, or said organic group that has a substituent, R represents a hydrogen atom, an organic group that is either a hydrocarbon group or a heterocyclic group, or said organic group that has a substituent, and L represents a halogen atom, an alkylsulfonyloxy group of 1 to 20 carbon atoms, a haloalkylsulfonyloxy group of 1 to 20 carbon atoms, or a substituted or unsnbstitnted arylsulfonybxy group) with a base to obtaan an N-methylidene-substituted methylamine oligomer represented by a formula (n) shown below: [Chemical Formula 2] (wherein A and R are as defined above, and n represents an integer of 2 l,o 20) or a mixture of two or more of the oligomers, and hydrolyzing the N-methylidene-substituted methylamine oligomer represented by formula (II) or the mixture of two or more of the oligomers in the presence of an acid, thereby producing a substituted methyl amine compound represented by a formula (III) shown below: IChemical Formula 3] (wherein A aod R are as defined above). 2. The process for producing a substituted methylamine compound according to claim 1, wherein said A represents one group selected from the group consisting of organic groups including a phenyl group, a pyridyl group, a thiazolyl group, a dithianyl group and atetrahydfofbranyl group, and said organic groups having a substitiient, 3. The process for producing a substituted methylamine compound according to claim 2, wherein said A represents one group selected from the group consisting of groups represented by formulas (IV) to (X) shown below. [Chemical Formula 4] .' (wherein X represents a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl group). 4, The process for producing a substituted methylamine compound according to claim 3, wherein said A is a 2-chloropyridin-5-yl group. 5, The process for producing a substituted methylainine compound according to any one of claims 1 to 4, wherein said R represents a hydrogen atom or an alkyl group of 1 to 5 carbon atoms. 6, The process for producing a substituted methylamine compound according to any one of claims 1 to 5, wherein reaction between said hexamethylenetetraammonium salt compound represented by said formula (I) and said base is conducted al a pH of 9 to 12. 7. A process for producing a substituted methylamine compound, said process comprising; reacting a substituted methyl compound represented by a formula (XI) shown below: [Chemical Formula 5] (wherein A represents an organic group that is either a hydrocarbon group or a heterocyclic group, or said organic group that has a substituent, R represents a hydrogen atom, an organic group that is either a hydrocarbon gronp or a heterocyclic group, or said organic group that has a substituent, and L represents a halogen atom, an alkylsultonyloxy group of 1 to 20 carbon atoms, a haloalkylsulfonyloxy group of 1 to 20 carbon atoms, or a substituted or unsubstituted arylsulfonyloxy group) with hexamethylenetetramine, or ammonia or an ammonium salt and fonnaldehyde or a formaldehyde equivalent, and a base to obtain an N-methyiidene-substituted methylamine oligomer represented by a formula (IT) shown below: [Chemical Formula 6] (wherein A and R are as defined above, and n represents an integer of 2 to 20), or a mixture of two or more of the oligomers, and hydrolyzing the N-methylidene-substituted methylamine oligomer representcd by formula (U) or the mixture of two or more of the oligomers in the presence of an acid, thereby produciug a substituted methylamine compound represented by a formula. (Ill) shown below; [Chemical Formula 7] \ (wherein A is as defined above). 8^ The process for producing a substituted methylamine compound according to claim 7, wherein said A represents one group selected from the group consisting of organic groups including u phenyl group, a pyridyl group, a thiazolyl group, a dithianyl group and a tetrahydrofuranyl group, and said organic groups having a substituent. 9. The process for producing a substituted methylamine compound according to claim 8, wherein, said A represents one group selected from the group consisting of groups represented by formulas (IV) to (X) shown below: [Chemical Fonnula 8) (wherein X represents a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl group). 10. The process for producing a substituted methylamine compound according to claim 9, wherein said A is a 2-cbloropyridin-'5-yl group. 11. The process for producing a substituted methylamine compound according to any one of claims 7 to 10, wherein said R represents a hydrogen atom or an alkyl group of 1 to 5 carbon atoms. 12. The process for producing a substituted methylanxine compound according to any one of claims 7 to 11, wherein reaction of said substituted methyl compound represented by said formula (XI) with bexamethylenetetramine, or ammonia or an ammonium salt and formaldehyde or a formaldehyde equivalent, and a base is conducted at a pH of 9 to 12. 13. The process for producing a substituted methylamine compound according to any one of claims 7 to 12, wherein hexametliyleiietetramine, or ammonia and fomialdehyde^ are recovered from a reaction mixture obtained following reaction of said substituted methyl compound represented by Said formula. (XI) with hexamethylenetetramine, or ammonia or an ammonium salt and formaldehyde or a formaldehyde equivalent, and are subsequently reused in reaction "with said substituted methyl compound represented by said formula QiX). 14. An N-methylidene-pyridylnethylamine oligomer represented by a formula (II') shown below: [Chemical Formula 9] (wherein X represents a hydrogen atom, a halogen atom, or a substituted or unsubstituted alley] group, and n represents an integer of 2 to 20). 15. A triazine derivative represented by a formula (I?') shown below: [Chemical Formula 10] (wherein X represents a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl group).

Full Text

PROCESS FOR PRODUCING SUBSTITUTED METHYLAMINE COMPOUND AND
TRIAZINE DERI VATIVE
TECHNICAL FIELD
[0001]
The present invention relates to a process that enables a substituted methylamine compound, such as a pyridylmethylamine compound, which is useful as an intermediate for the production of agricultural chemicals and medicines and the like, to be produced easily, with good yield, and at low cost, and also relates to an N-methylidene-substituted methylaniine oligomer that acts as a production intermediate.
BACKGROUND ART
[0002]
Substituted methylaniine compounds, including pyridymethylamine compounds such as 2-chloro-5-pyridylmeithylamine are useful as intermediates for the production of agricultural chemicals and medicines.
Conventionally, known processes for producing pyridylmethylamine compounds include a process in which 2-chlQro-5-chloromethylpyridine is reacted with potassium phthaiimide to obtain N-(2-chloro 5-pyridylmethyl)phthalimide, which is subsequently reacted v,'ith hydrazine (see Patent Document 1), a process in which 2-chloro-S-(chloromethyl)pyridine is reacted with hexamethylenetetramine to obtain 2-chloro-'5-pyridylmethylhexamethylenetetraammonium chloride, and a hydrolysis is subsequently performed in the presence of a lower alcohol and a mineral acid (see Patent Document 2),

and a process in which 2-chloro-5-pyridylmethylhexamethylenetetrammonium chloride is hydrolyzed using water or alkaline water to generate N-methylidene-2-chlpro'5-pyridylmethylamine, which is subsequently isolated and then hydrolyzed in an acid (see Patent Document 3).
[0003]
However, none of these production processes can be claimed to be entirely satisfactory- from an industrial perspective. Namely, the first process requires the use of the comparatively expensive potassium phthalimide as a raw material, meaning the process is undesirable from an economic perspective. Further, because an operation is required to remove phthalazine from the hydrazine reaction mixture, the post-processing operation tends to be complex. In the case of the second process, the amount of solvent used in the reaction is large, and a large amount of comparatively expensive hexamethylenetetramine must also be used, and therefore the process is undesirable from an economic perspective. Further, in this process, because the generated 2-chloro-5-pyridylmethylhexamethylenetetraammonium chloride must be first isolated, before being subjected to hydrolysis, a problem arises in that the operation is overly complex, In the third process a problem arises in that the isolated N-uitthy'iuciiC--^ vchloro! • pyridinemethylamine is unstable and difficult to handle-
[0004]
[Patent Document 1]
(West) German Pat No, 3.727,126
[Petent Document 2]
.Japanese Unexamined Patent Apphcation, First Publication No. Hei 3-271273
[Patent Document 3]
.Japanese Unexamined Patent Application, First PubUcation No. Hei 8-295670

DISCLOSURE OF THE INVENTION
PROBLEMS TO BE SOLVED BY THE INVENTION
[0005]
The present invention has been developed in light of the issues associated with the prior arts described above, and has an object of providing a process that enables a substituted methylamine compound, preferably a pyridylmethylamine compound, that is useful as an intermediate for the production of agricultural chemicals and medicines to be produced easily, with good yield, and at low cost, and the production intermediate thereof,
MEANS TO SOLVE THE, PROBLEMS
[0006]
As a result of intensive research aimed at achieving the above object, the inventorsof the present invention discovered that by reacting a hexamethylenetetraammonium salt compound with a base, an N-methylidene-substituted rnethylamine oligomer represented by formula (IT) below, or a mixture of two or more 'such oligomers. could be obtained with good yield. Further, the inventors also discovered that by hydrolyzing this mixture in the presence of an acid, a substituted methyiamine compound represented by formula (10) below, which represents the target product, could be obtained with good yield, and they were therefore able to complete the present invention.
[0007]
Accordingly, a fust aspect of the present invention provides a process for producing a substituted methylamine compound, the process comprising:

reacting a hexamethylenetetraammonium salt; compound represented by formula (D shown below: [0008] [Chemical Formula 1]

(wherein A represents an organic group that is either a hydrocarbon group or a heterocyclic group, or said organic group that has a substituent, R represents a hydrogen atom, an organic group that is either a hydrocarbon group or a heterocyclic group, or said organic group that has a substituent, and L represents a halogen atom, an alkylsulfonyloxy group of 1 to 20 carbon atoms, a haloalkylsulfonyloxy group of 1 to 20 carbon atoms, or a substituted or unsubstituted arylsuifonyloxy group) with a base to obtain an N-methylidcne-substituted methylamine oligomer represented by formula (11) shown below:
[0010]
[Chemical Fomiula 2]

(wherein, A and R are as defined above, and n represents an integer of 2 to 20), or a mixture of two or more of the oligomers. and
hydrolyzing the N-methylidene-substituted methylamine oligomer represented by formula (tl) or the mixture of two or more of the oligomers in the presence of an acid, thereby producing a substituted methylamine compound represented by a formula (III) shown below,
[0012]
[Chemical Formula 3]

[0013] (wherein A und R are as defined above),
[0014]
The abovementioned A preferably represents one group selected from the group . consisting of organic groups including a phenyl group, a pyridyl group, a thiazolyl group, a diiiuaiiyi gioup and a lelrauydrolm-auyl group, and said, organic groups having a Rub.stituent,
[0015]
More preferably, A represents one group selected from the group consisting of groups represented by formulas (IV) to (X) shown below:
[Chemical Formula 4]

(wherein X represents a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl group).
[0016]
The group A is still more preferably a 2-chloropyridin-5-yl group.
Furthermore, the abovementioned R preferably represents a hydrogen atom, or a substituted or unsubstituted lower alkyl group, and more preferably represents a
hydrogen tom or a n lkyl group of 1 to 5crbon toms
[0017]
In the process for producing a substituted methylamine compound of the present invention, the reaction between the hexamethylenetetraammonium salt compound represented by formula (I) and the base is preferably conducted at apH of 9 to 12.
[0018]
A second aspect of the present invention provides a process for producing a substituted methylamine compound, the process compring:

reacting a substituted methyl Compound represented by formula (XI) shov,T\ below:
[0019]
[Chemical Formula 5]

[0020] (wherein A represents an organic group that is either a hydrocarbon group or a heterocyclic group, or said organic group that has a substituent, R represents a hydrogen atom, an organic group that is either a hydrocarbon group or a heterocyclic group, or said organic group that has a substituent, and L represents a halogen atom, an alkylsulfonyloxy group of 1 to 20 carbon atoms, a haloalkylsulfonyloxy group of 1 to 20 carbon atoms, or a substituted or unsubstituted arylsnlfonyloxy group) with hextanethylenetetramine, or ammonia or an ammonium salt and formaldehyde or a formaldehyde equivalent, and a base to obtain an N-methylidene-substituted methylamine oligomer represented by formula (11) shown below:
[0021]
[Chemical Formula 6]

[0022]

(wherein Alifras defined above, and n represents an integer of 2 to 20), or a mixture of two or more of the oligomers, and
hydrolyzing the substituted methylamine oligomer represented by formula (11) or the mixture of two or more of the oligomers in the presence of an acid, thereby producing a substituted methyl amine compound represented by a formula (01) shown below:
[0023]
[Chemical Formula 7]

[0024J
(wherein Alj* as defined above). i
[0025]
The above mentioned A preferably represents one group selected from the group consisting of organic groups including a phenyl group, a pyridyl group, a thiazolyl group, a dithianyl group and a tetrahydrofuranyl group, and said organic groups having a substituent.
More preferably, A represents one group selected from the group consisting of groups represented by formulas (TV) to (X) shown below:
[0026]
[Chemical Formula 8]

[0027] (wherein X represents a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl group).
[0028]
The group A is still more preferably a 2-chloropyridin-5-yl group.
Furthermore, the above mentioaed R preferably represents a hydrogen atom, or a substituted or unsubstituted lower alkyl group, and more preferably represents a hydrogen atom or an alkyl group of 1 to 5 carbon atoms.
[0029]
In the production process of the present invention, the reaction between the substituted methyl compound represented by formula (XI), the hexamethylenetetramine, or the ammonia or ammonium salt and the formaldehyde or formaldehyde equivalent, and the base is preferably conducted at a pH of 9 to ) 2.
[0030]

Further,, in the production process of the present invention, it is preferable that the hexamethylenetetramine, or the ammonia and formaldehyde, are recovered from the reaction mixture obtained following the reaction of the substituted methyl compound represented by formula (XI) with the hexamethylenetetramine, or the ammonia or ammonium salt and the formaldehyde or formaldehyde equivalent and the base, and are subsequently reused in reaction with the substituted methyl compound represented by formula. (XI).
[0031J
A third aspect of the present invention provides an N-methylidene-pyridylmethylamine oligomer represented by formula (11') shown below:
[0032]
[Chemical Formula 9]

(wherein X represents a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl group, and n represents an integer of 2 to 20).
This oligomer is useful as an intermediate for the production of a substituted methylamine compound represented by formula (TIT). Of the various oligomers, an N-methylidene-substituted methylamine trimer m which n=3, which is a triazine derivative represented by formula (11") shown below, is preferred.

[Chemical Formula 10]

(wherein X is as defined above.)
EFFECT OF THE INVENTION
[0033]
According to the present invention, a substituted jaethylarmne compound represented by formula (HI) can be produced in an industrially favorable manner, namely, easily, with good yield, and at low cost
An N-methylidene -substituted methylamine oligomer of the present invention is useful as an intermediate for producing a substituted methylamine compound represented by formula (JIT).
BEST MODE FOR CARRYING OUT THE INVENTION [0034]
A more detailed description of the present invention is presented below. A process for producing a substituted methylamine compound represented by formula (III) (hereafter also refen-ed to as '"the amine compound (III)") comprises a step

(hereafter referred to as "step (])") of reacting a substituted
methylhexamethylenetetraammonium salt compound represented by formula (I) shown above (hereafter also referred to as "the ammouium salt compound (1)") with a base to obtain an N-methylidene-substituted metbylamine oligomer represented by formula (H) (hereafter also referred to as "the N-methylideneamine oligomer (11)") or a mixture of two or more such oligomers, and a step (hereafter referred to as "step (2)") of hydrolyzing the N-methylideneamine oligomer (II) or the mixture of two ot more N-melhylideneamine oligomers (IT) in the presence of an acid.
[0035] Step (1)
In step (l), the ammonium salt compound (I) is reacted with a base, yielding the N-methylideneamine oligomer (0) or a mixture of two or more such oligomers,
In formula (T), A represents an organic group that is either a hydrocarbon group or a helerocyclic group, or said organic group that has a substituent. [0036]
Specific examples of the hydrocarbon group include aromatic hydrocarbon group such s a phenyl group, naphthyl group, indenyl group, pyrenyl group, acenaphthenyl group, anthryl group or phenanthxyl group, aliphatic hydrocarbon groups such as a methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, s-butyl group, t-butyl group, n-hexyl group, n-octyl group. Vinyl group, allyl group, ethynyl group or propargyl group, and alicyclic hydrocarbon, groups such as a cyclopropyl group, cyclohexyl group or bic.yclof3.2.1]octyl group. Examples of the heterocyclic group include 5- to 7-membered rings containing 1 to 5 hetero atoms such as an oxygen atom, sulfur atom or nitrogen atom, and condensed rings thereof, and more specific examples include unsaturated 5-membered heterocyclic groups such as a furan-

2-yl proup, furan-3-yl group, thiophen-2-yl group, thiophen-3-yl group, pyn:ol-2-yl group, pyrrol-3-y] group, oxazol-2-yl group, oxa2ol-4-yl group, oxaznl-5-y] group, tthiazol-2-yl group, thiazol 4-yl group, thiazol-5-yI group, isoxazoI-3-yl group, isooxazol-4-yl group, isooxazol-5-yl group, isothiazol-j-yl group, isothiazol-4-yl group, isothiazol-5-yl group, imidazol-2-yl group, itiiidazol-4-yl group, imidazol-5-yl group, pyrazol-3-yl group, pyrazol-4-yl group, pyrazol-5-yl group, l,3,4-oxadiazol-2-yl group, l,3,4-thiadiazol-2-yl group, 1,2,3 triazol-4-yl group, l,2,4-tria2ol-3-yl group, 1,2,4-triazol-S-yl group, 5-phenyl--5-trifluoromethyl-isooxazolin-3~yl group, 2-furfurylmetbyl group, 3-thienyljnetbyl group, or l-methyl-S-pyiazolomethyl group; unsaturated 6-meTObered heterocyclic groups such as a pyridin-2-yl group, pyridm-3-yl group, pyridin-4-yl group, pyTidazin-3-yl group, pyridazin-4-yl group, pyrazin-2-yl group, pyrimidin-2 yl group, pyrimidin-4-yl group, pyrimidin-5-yl group, l,3,5-triaziQ-2-yl group, l,2,4-triazm-3-yl group, 2-pridylmetliyl group, S-pyndylmethyl gi-oup, 6-cWoro-3-pyTidyteiethyl group or 2-pyrimidyknethyl group; and saturated heterocyclic groups such as a tetrahydrofuraii-2-yl group, iditi niJiydi'flp')jiau-4-yI group, piperidin-3-yl group, pyrrolidm-2-yl group, moipholitio group, pipeiidino group, N-metiiylpipcrazinyl group, dithianyl gi-oup, 2-r.f'Triiiiijrrliru mwuyirnoLbyl group, 3 pnnmianii) iiiuwii'_'i'l' ffloup, N-methyl S-pyrrolidyhrietliyl group, or morpholinomethyl group. Of these, A is preferably a phenyl group, pyridyl group, tluazolyl group, dithianyl group or tetrahydrofiiranyl group.
The hydrocarbon group or heterocydic group may be substituted, provided the substitution has uo effect on the reaction, and specific examples of the substituent include a hydroxyl group; a thiol group; halogen atoms such as a fluorine atom, chlorine atom, bromine atom or iodiae atom; a cyano group; a nitro group; a formyl group; unsubstituted or substituted amino groups such as an amino group, methylamino group, betrzylaraino group, aniliao group, diniethylamino group, diethylamino group or

phenylethykroino group; alkyl groups (and preferably C1to C6 aJkyl groups) such as a methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group, isobutyl group, t-butyl group, n-pentyl group or n-hexyl group;alkenyl groups sucb as a vinyl group, allyl group or 2-mp.thoxyetlienyl group; alkynyl groups such as an ethjiiyl group, 1-propynyl group, 2-phenylethynyl group orpropargyl group; allcoxy groups (and preferably Ci to C6 alkoxy groups) such as a methoxy group, ethoxy group, propoxy group, isoptopoxy group, n-butoxy group, sec-butoxy group, isobutoxy group or t-butoxy group; alkynyloxy groups such as a vinyloxy group or allyloxy group; alkynyloxy groups such as an ethynyloxy group or propargyloxy group; aryloxy groups such as a phenoxy group, benzyloxy group or 2-pyridyloxy group; haloalkyl groups (and preferably C1 to C6 haloalkyl groups) such as a chloromethyl group, fluoromethyl group, bromomethyl group, dichloromethyl group, difluoromethyl group, dibromomethyl group, trichloromethyl group, trifluoromethyl group, bromodifluoromethyl group, trifluoroethyl group, 1-chloroethyl group, 2-chloroethyl group, 1-bromoetbyl group, 2-bromoethyl group pentafluoroethyl g^Mf; haloalkoxy groups (and preferably C1 to C6 haloalkoxy groups) such as a fluoromethoxy group, chloromethoxy group, bromometboxy group, diflnriioiiiethox^,' group, dichloroinctho^c}' group, dibroiarjuietliox}" fei'Jtip, triiluoromethoxy group, trichloromethoxy group, tiibromomcthoxy group, trifluovoethoxy group, peutalluorocthoxy group or pentajfluoropropoxy group; alkylthiocarbonyl groups (and preferably C1 to C6 alkylthiocarbouyl groups) such as a methylthiocarbonyl group, ethylthiocaibonyl group, propylthiocarbouyl group, isopropylthiocarbonyl group, butylthiocarbonyl group, isobutylthiocarbouyl group,^ec-hutjfUhiiiM^oiiyj- group or t butylthiocarbonyl group; alkylsulfonylamino groups (and preferably C, to Ce alkylsulfonylamino groups) such as a methylsulfonylamino group, ethylsulfonylamino group, propylsulfonylamino group, isopropylsulfonylamirjo group.

butylsulfonylamino group or t-butylsulfonylamino group; arylsulfonylamino groups (and preferably C6 to C12 arylsulfonylamino groups) such as a pheoylsulfonylamino group or piperazmysullfonyl,amino group; alkylcarbonylamino groups (and preferably C1 to C6 alkylcarbonylamino groups) such as a methylcarboaylammo group, ethylcarbonylamino group, propylcarbonylamino group or isopropylcarboaylamino group; alkoxycaxbonylamino groups (and preferably C1 to C6 alkoxycarbonylamino groups) such as a methoxycarbonylamino group, ethoxycaxbonylamino group, propoxycarbonylamino group or isopropoxycarbonylamino group; haloalkylsulfonylamino groups (and preferably C1 to C6 haloalkylsulfonylamino groups) such as a fluoromethylsulfonylamia, group, chloromethylsulfonylamino group, bromomethylsulfonylamino group, difluoToraethylsulfonylaraino group, dichloromethylsulfonylammo group, difluoromethylsulfonylamino group, trifluorometliylsulfonylamiuo group, trifluoroethylsulfonylamino group or pentafluoroethylsulfonylanibo group; bis(alkylsu]fonyi)amino groups (and preferably bis(Ci to Cft alkylsulfonyl)amino groups) such ai! a bis(methylsulfonyl)ammo group, bis(ethylsulfony1)amino gioup, (methylsulfonyl)(ethylsulfonyl)anuno group, bis(propylsuIfonvDamino group. bT!3(isnprnpy]sii1tVirtyl)fltr!mo f^oirp, bi3(butylsxilfonyl)ammo group or bis(t-butylsulfonyl)amino group; bis(haloalkylsulfonyl)animo groups (and preferably tais(Ci to Cg haloalkylsulfoByl)ainino groups) such as a bis(fluoromethylsulfony))amino group. bis(chloromethylsulfonyl)amitio group, bis(bii,omomethylsulfonyl)ammo group, bis(difluoroinethylsulfonyl)arDino group, bis(dichloromethylsulfonyl)atnino gi'oup, bis(drl:luororoethylsulfonyl)amino group, bis(irifluorometliylsu]fonyl)an)ino group, bis(trifluoroethylsulfonyl)amino group or bi$(pentafluoroethyl3ulfonyl)amino gjoup; ansubstituied or substituted hydrazinotDatboiiyawh oay^ groups such as a hydraxino

group, N'-phenylhydiazino group orN'-methoxycarbonyHiydrazino group; alkoxycarbonyl groups (and prefeiably Ci to Ce alkoxycarbonyl groups) such as a methoxyciirbonyl group, ethoxycaj-bonyl group, propox7caibonyl group, isopropoxycaibonyl gioup, butoxycarbonyl group or i-butoxycarbonyl group; aryl groups (and preferably Cs to Cu arj'l groups) such as a phenyl group, 1-naphthyl group or 2-napbtliyl group; unsatmated S-membered heterocyclic groups such as a furan-2-yl group, futaji-S-yl group, thiophen-2-yl group, tMopheu-3-yl group, pytrol-2-yl group, pyrrol-3-yl group, oxaz;ol-2-yl group, oxazol-4-yl group, oxazol-5-yl group, thia2Ql-2-yl group, Lhia2;ol^l-yl group, thiazol-5-yl group, isooxazol-3-yl group, isooxazol-4-yl group, isooxa2:ol-5-yl group, isothiazol-3-yl group, isothiazol-4-yl group, isothiazol-5-yl group, briida2:ol-2-yl group, imidazol-4-yl group, imidazol-5-yl group, pyrazol-3-yl group, p>Tazol-4-yl group, pyra2ol-5-yl group, l,3,4-oxadiazol-2-yl group, l,3,4-tliiadiazol-2-yl gioup, l,2,3-tria2;ol-4-yl gi-oup, 1,2,4-tria2ol-3-yl group, l,2,4-tiiazol-5-yl group, 5-phenyl-5-ti-itlnorom.ethyl-isooxazolin-3-yl group, 2-furfarylmethy\ group, 3-thienylmethyl group or 1 -methyl-S-pyrazolomethyl group; unsaturated 6-menibered heterocyclic groups such as a pyTidin-2-yl group, pytidin-3-yl group, pyridiii-4-yl group, p\TidaziQ-3-vl eroiip. r>yriria7in-4-yl grnup m;rfl5dt
hydroxyiminomethyl group or N-methoxyiminomethyl group; N-unsubstituted or N-substituted hydrazinocarbonyl groups such as an N'-methylhydrainocarhonyl group, N'-phenylhydrazinocarbonyl group or hydrazinocarbonyl group; N-unsubstituted or N-substituted aminocarbonyl groups such as an aminocarbonyll group, dimethylaminocarbonyl group orN-phenyl-N-methylaminocarbonyl group; N-unsubstituted or N-substituted hydramino groups such as a hydra2ino group, N'-acetylhydrazino group, N'-mcthylhydraziTio group, N'-phenyhydrazino group or N'-raethoxycarbonylhydrazino group; alkylthio groups such as a methylthio group, etliyltbio gioup or t-butyltliio gi'oiip; aJJcenylthio groups such a$ a vinyltMo group or allylthio gj oup; alkynylthio groups such as an etbynylthio group or propargyltluo group; ar>1tMo groups such as a phenylthio group, 4-cMoroph.enyIthio group, benzylthio group, phenethylthio group or 2-pyTidylthio group; alkylsulfonyl groups such as a luethylsulfonyl group, ethylsulfonyl group or t-butylsulfonyl group; alkenylsuJfonyl groups such as an allylsulfonyl group; alliiDa)4»ulfoiiyl groups such as a propaigylsulfonyl group; and arylsulfonyl groups such as a phenylsutfonyl group, beuzylsolfonyl group or 2-pyridylsulfonyl group. Other novel substituents generated by 3uhil3ti:ticg one Gubstituent Vvitb another 3ub:^tinicnt, dieroby combining P.vo or more substituents, may also be used.
More specifically, A is preferably one group selected fi:om the group consisting of groups represented by fonnulas (TV) to (X), and is most preferably a 2-chloropyridin-5-yl group. Specific exatnples of X within formulas (IV) to (X) include a hydrogen atom, halogen atoms such as a fluorine atom, bromine atom, chlorine atom or iodine atom, arid alkyl groups such as a methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, s-butyl group, t-butyl group, n-hexyl group or n-octyl group. Tlie alkyl group may include a substihient on an appropriate carbon atom, and examples

of the substituent include the same substituents as those exemplified above for A. The substituent within A may be protected with an appropriate protective group prior to conducting the reaction with the base.
In formula (I), specific examples of R include the same groups as those exemplified above for A.
[0037]
Specific examples of L m formula (T) include a hydrogen atom, halogen, atoms such as a fluorine atom, chlorine atom or bromine atom, alkyisulfonyloxy groups of 1 to 20 carbon atoms such as a methylsulfonyloxy group, ethylsulfonyloxy group or n-propylsulfonyloxy group, haloalkylsuLfonyloxy groups of 1 to 20 carbon atoms such as a trifluoromethylsulfonyloxy group, trichloromethylsulfbnyloxy group, 2,2,2-trifluoroethylsulfonyloxy group or perfluoroethylsulfonyloxy gfottp, and arylsulfonyloxy groups such as a phenylsiilfonyloxy group, napbthylsulfonyloxy group, anthrylsulfonyloxy group or phenanthr>4sulfonyloxy group. The arylsnlfonyloxy groups may include a substituent at an appropriate position, and examples of the substituent include the same substitueuts as those exemplified above for A. Examples of preferred .vuu^ui.u«jiiis. iiitludti halogen aioiiis iuui a^ u, iiuuriuc uloiu, cliioiinv; atom oi bivujjJiic atom, alkyl groups such as a methyl group or ethyl group, alkoxy groups such as a methoxy group or ethoxy group, haloalkyl groups such as a trifluoromethyl gioup, and a nitro group. [0038]
Although there are no particular restrictions on the process used for producing the aiamonimn salt compound (I), one example of a preferred process involves reacting a substituted methyl compomid represented by foim.ula (XI) (hereafter also referred to as "the substituted methyl compoxmd (XT)"), -with either hexamethylenetetramine, or a

mixture of ammonia or an ammonium salt and formaldehyde or a formaldehyde equivalent.
[0039]
The substituted methyl compound (XT) can be produced using conventional methods, and n the case of a compound where A is represented by formula (IV) and X is a halogen atom, can be produced by a process that iitvolves halogenating a 2-halogeno-5-methylpyridine, or a process that involves reacting a 2-halogeno-5-hydxoxyraethylpyridine with an alkylsulfonyl halide or arylsulfonyl halide in the presence of a base,
[0040]
Specific examples of the compound represented by formula (XI) include 3-(fluoromethyl)pyridine, 3-(chloromethyl)pyridine, 3-(bromomethyl)pyridine, [(pyridine-S-yl)methyllmethyl sulfonate, [(pyridin 3 -yl)ethyl]ethyl sulfonate, [(pyridin-3-yl)methyl]-D-propyl sulfonate, [(pyridin-3-yl)mediyl]phenyl sulfonate, 2-fluoro-5-(fluoromethyljpyridine, 5-chloromethyl-2-fluoropyfidme, 5-bromomethyl-2-fluoropyridiue, [(2-fluoTop>Tidm-5-yl)methyl]metbyl sulfonate, [(2-fluoropyridm-5-
.^
j*yiULUj-j iJv^igQji :iuinjuaic, v_i.-liuuii;ljjinuii.i-,'-^ij-u-piup}] ^^uUOuaLCj [i_^'jJ.uuj,vjj^viiiMk4li-^
yl)methyl]plieiiyl sulfonate, 2-chloro-5-(fluoromethyl)pyriditie, 2-chloro-5-(chloroniethyl)pyridme, 5-bromomethyl-2-chloropyridine, [(2-cliloropyridin-5-yl)metliyl]melh.yl sulfonate, [(2-chloropyridin-5-yl)mcthyl]etliyl sulfonate, [(2-chloropyridin-5-yl)methyl]-n-propyIsidfonate, [(2-chloropyridia-5-yl)methyl]phenyl sulfonate, 2-bromo-5-(fluoromethyl)pyridJne, 2-bi'Orao-5-(chloromethyl)pyridine, 2-bromo-5-(bromomethyI)pyridine, [(2-bromopyridin-5-yl)methyl]methyl sulfonate, [(2-bromopyridin-5-yl)taethyl]ethyl sulfonate, [(2-bromopyridin-5-yl)methyl]"n-propyl

sulfonate and [(2-bromopyriclin-5-yl)methyl|phenyl sulfonate- Of these, 2-chJoTo-5-(chloromethyl)pyridme is particularly desirable. [0041]
There are no particular restrictions on the base used in the reaction with the ammorauTtt salt compound represented by formula (1), and specific examples include alkali metal hydroxides such as soditim hydroxide or potassium hydroxide, alkalme earth metal hydroxides such as magnesium hydro3dde or calcium hydroxide, carbonates such 05 sodium carbonate, potassium carbonate, magnesinm carbonate or calcium carbonate, metal alkoxides such as sodium methoxide, soditim ethoxide or magnesiiun, methoxide, and organic bases such as triethylamine, dnsopropylethylamine, pyridine, 1,4-dia2abicyclo[2.2.2]octane or l,8-diazabicyclo[5.4.0]-7-undecene. Of these, from the viewpoints of production costs and maximizing the yield of the target product, alkali metal hydroxides are preferred, and sodium hydroxide is particularly desirable,
[0042]
Tlie pH during the reaction of the ammonium salt compound (T) with the base is tvpically within a range from 9 to 12, and is preferably controlled withtin a range from 9.5 to 11.5. and more preferably fi-om 10 to 1 ] Py ("nntroLHrig the pH of tbf refaction ^yst?!:;^, within this range, the N-methylideneamiue oUgomer (II) can be produced with good yield.
[0043]
The reaction between the ammonium salt compound (I) and the base is typically conducted withm a solvent. There are no particular restrictions on the solvent used, provided it is inert with respect to the reaction. Examples of solvents that may be used include water; alcohol-based solvents such as metlaanol, ethanol or n-propanol; ahphatic hydrocarbon-based solvents such as n-pentane, n-hexane, n-heptane or n-octane; alicyclic hychrocarbon-based solvents such as cyclopentane or cyclohexane; aromatic hydrocarbon-

based solvents such iis beiizene, toluene, xylene or cblorobenzene; ketone-based solvents 3uch as acetone, tnethyl ethyl ketone, diethyl ketone, methyl isopropyl ketone, methyl bobutyl ketone or cyclohexanotie; ether-based solvents such as diethyl ether, tetrahydrofuraix, dioxane or 1,2-dimethoxyethane, nad nuxtiires of two or more of the above solvents. Of the above po$sibilities, the use of a mixed solvent of water iind an aromatic hydrocarbon-based solvent is preferred, and the use of a mixed solvent of water and tohiene is particularly desirable. [004^1]
Tlie reaction temperature for the reaction betw^een the ammonium salt compound (I) and the base is typically within a range from room temperature to the boiling point of the solvent, and is preferably within a range from 40 to 70°C. The reaction time is typically within a range from several minutes to several days, and is preferably within a range tVom 1 to 10 hours.
Following completion of the reaction, tl^e reaction liquid may be sampled, and the completion of the reaction can be confirmed using conventional analytical techniques such as thin layer cluomatography, gas chromatography or high-performance liquid chromatocraphv. [0045]
Further, in the present invention, the N-metliylideneamine oligomer (11) may also be obtained in a suigle step by reacting the substituted methyl compound (XI) with hexametliyleuetetramine and a base.
In this case also, the pH of the reaction liquid is typically vrithin a range from 9 to 12, and is preferably controlled withm a range from 9.5 to 11.5, and more preferably from 10 to 11. By controlling the pH of the reaction system within this range, the N-methylideneamine oligomer (II) can be obtained with good yield.

[0046]
The amount of hexamethylenetetramine used is U-pically within a range from 0 1 to 10 mol, and preferably from 0,25 to 2 mol, per 1 mol of the substituted methyl compound (XI).
[0047]
Moreover, ui the present invention^ the N-metliylideneanune oligomer (11) may also be obtained m a single step by reacting the substituted tnefhyl compound (XT) with finmionia or an anunonitUB salt, formaldehyde or a formaldehyde equivalent, and a base.
In this case also, the pH of the reaction liquid is typically within a range from 9 to 12, and is preferably controlled within a range from 9.5 to 11.5, and more preferably from 10 to 11. By controlling the pH of the reaction system within this range, the N-metbylideneaniine oligomer (Tf) can be obtained with good yield.
[0048]
Becau.se this process replaces hexamethylenetetramine with ammonia or an ammonium salt and formaldehyde or a formaldehyde equivalent, all of which are low-cost industrial raw materials, it is particularly advantageous in the case of mass
[0049]
There are no particular restrictions on tlie ammonia used, and gaseous ammonia or an aqueous solution or alcohol solution or the like of aranioma may be used. In tjiose cases where an ammonia aqueous solution is used, the concentration of the solution is typically within a range from 5 to 25%, and is preferably from 10 to 25%. Further, an anxuionium salt may be used in.'jtead of the ammonia. Examples of ammoniiun salts that may be used include ammonium acetate, ammonium nitrate, ammonium stilfate or ammonium chloride.

rhe amoimt ':)f ammoiua used is t^'pically within a raage from 1 to 40 mol and preferably from 1 to 8 mol, per 1 mol of tlie substituted methyl compound (XT).
[0050J
There me no particular restrictions on the foritialdehyde used, and an aqueous solution or alcohol solution or the like of formaldehyde may be used. Ftutheraiore, a fonnaldehyde equivalent may also be used instead of foimaldebyde. An. example of the formaldehyde equivalent is paraformaldehyde, which is a polymer of formaldehyde. Paraformaldehyde is a white powder at room temperature, and can be used to generate fonnaldehyde by dissolution in the organic solvent and subsequent heating.
The amount of formaldehyde used is typically vvithia a range from 0.1 to 20 mol, and preferably from 1 to 2 mol, per 1 mol of ammonia.
[0051]
In the cases described above, the substituted methyl compotmd (Xl) is reacted with the hexamethyleiietetnimine, or witli the aramonia or the like and formaldehyde or the like, and the hexametliylenetetramine or the ammonia and the formaldehyde can be recovered from the obtained reaction mixture and subsequently reused in reaction with th^ [0052]
Furthermore, in those cases where the solution containing the recovered anamonia and fonnaldehyde is used in a continuotis process, the solution may be used as is, although m those cases where the ratio of ammonia and formaldehyde within the

recovered Solution differs from the ratio required to en.'jure continuvty of the inaction, a supplementan' amount of the component among the auimonia and the aldehyde that is lacking must be added to the solution. In other words, if the amount of ammonia is insufficient, then amtnonia or an ammonium salt is added, whereas if the amount of the formaldehyde is insufficient, fonnaldehyde or a fonnaldehyde equivalent is added, thereby adjusting the ratio between the aumionia and the formaldehyde to the optimum ratio. This optimum ratio varies depending on factors such as the reaction conditions, but the amount of the formaldehyde is typically within a i^mge from 0.1 to 20 mol, and preferably fiom 1 to 2 mol, per 1 mol of the ammonia. [0053]
In those cases where a mixture of the substituted raethyl compound (XI) with either hexamethylenetetramine, or ammonia or the like and formaldehyde or the like is used instead of the axnmonium salt compound (I), the base and solvent used, and other factors such as the reaction temperatoe and the like may aU be the same as those described above for the reaction that uses the ammonium salt compo^md (I). [0054]
Tn 'hither ca,-.c, the N-mcthylidcucamhic oligomer (11) or u'liivlure of t^Mj i;i HWIM such oligomers that represents the target product can be isolated using typical post¬processing operations. [0055]
The stnicture of fhe obtained N-methylideneamine oligomer (II) can be confumed using conventional analytical techniques such as 'H-NMR, '^C-NMR, IR spectroscopy, mass spectrometry and elemental analysis. [0056]

Tlie structure of die N-melhyHdeneamme oligomer (11) may be a chain-like stnictare,, a cyclic stnicuire, oi a structure contaimng botii chain-like and cyclic portions, althougti a cyclic compound represented by fonaula (TI') is particularly desirable Lu formula (H'), X is as defined above, and examples thereof ijiclude the same substituents as those exemplified above. In either Ibmaula (11) or fonniHa (IP), n represents an integer of 2 to 20, and is preferably witliin a range from 2 to 10, and more preferably from 2 to 5. Based on the various spectra mentioned above, the N-methylideneamine oligomer (II) is thouglit to have a structure s-uch as those shown below.
[0057]
[Chemical FoiTQula+4t- 14--3^1

[0059]
[Chemical Fomai;Ia 16]

[0060]
Tnazme derivatives represented by formula (IV) aie particularly desirable.
The N-methylideneamine oligomer (11) or the mixture of two or moie such oligomers obtained in the maimer described above is useful as an intermediate for the prodiiction of the amine compound (HI).
[0061]
In the present iaventioo, following completion of the reaction, the imine compound (IT) or the mixture of tw^o or more such compounds need not necessarily be isolated from the reaction solution, and the reaction solution may be supplied, as is, to the subsequent step (2).
[0062]
In other words, the N-methylidsneamine oligomer (II) is a basic substance, and has the property of being soluble in acidic water. Accordingly, by conducting the

reaction berweeu the animoaium salt compound (\) and the base in a mixed solvent mediLin:! containiag water and an organic solvent that is tonmscible with water, such as a mixed solvent medium composed of water and toluene, subsequently separating the organic layer fi:om the obtained reaction mixture, and then extracting the separated organic layer with acidic water, a salt of the N-methyhdeneauiine oligomer (iri or roixture of two or more such oligomers that represents the target product caij be obtained as an aqueous solution. This aqueous solution may be supplied, as is, to the subsequent step (2).
[0063] Step (2)
Step (2) involves hydrplyzing the N-methyUdeneamine oKgomer (II) or the mi}fture of two or more such oligomers in the presence of an acid to obtain the amine compound (IIT). [0064]
Tliere are no particular restrictions on the acid used in the reaction, and specific examples include inorganic acids stich as sulfuric acid, hydrochloric acid or phosphoric acid, organic carboxylic acids such as acetic acid or triJQuoroacetic acid, oreanic sulfonic acids such as p-tohienesulfonic acid, methanesulfonic acid or trifluororuethanesulfonic acid, and Lewis acids such as boron tritluoride, titanium tetrachloride or aluminum chloride.
[0065]
The amount of acid used is typically within a range from 1 to 100 mol, preferably from 2 to 20 mol, and more preferably fi-om 3 to 10 mol, per 1 mol of the ammonium salt compound (I) or the substituted methyl compound (XI). By setting the amount of acid
1

used TO a value within this range, the tai'geted substituted methylajiii"ne compound (III) can be obiaiued with, good yield.
[0066]
The hydrolysis reaction of tiie N-methylideueamine oligomer (ID or miximve of two or mors such ohgomers in tlie presence of an acid is typically conducted with the reactauts diluted vvith a solvent. Exaroples of tluii solvent include the same solveQt.s as those exempliiied above for use within the reaction of the substituted methyl compound (XI) \vitli hexamethylenetetramine, or the tmxture of ammonia or the like and formaldehyde or the like. Of these solvents, a mixed solvent containing water and an alcohol is preferred, and a mixed solvent containing water and methanol is particularly desirable.
[0067]
The reaction temperature during the hydrolysis of the N-methylideneamine oligomer (11) or mixti-ire of two or more such oligomers in the presence of an acid is typically within a range fi-oni room temperature to 90'C, and is preferably from 50 to 90*C. The reaction time is tjfpically within a range from several minutes to several days, ?)ii(l is nrpferably vvithin a range from 1 to !0 hour's. FcUo-vrlng completion of the reaction, the reaction liquid may be sampled, and the completion of the reaction can be confirmed using convfcntional analytical techniques such as thin layer chromatography, gas chromatography or high-performance liquid chromatography.
[0068]
Following completion of the reaction, the target amine compound (TH) can be obtained by conducting typical post-processing operations, and then using conventional purification techniques such as distillation and column chromatography.

Accordmg to the present iiwentinn, the mixine compound (III), and preferably a pvTidylmethylamiiie compoimd represented by fomiula (lH')' [0069] [Chemical Fonnula 17]

[0070] (wherein X is as defined above) can be produced easily, with good yield, and al low cost,
[0071]
The aroine compound (III) obtained using the production process of the present
invention is asefiil as an intermediate in the production of agiicultitral chemicals and
medicines and the like, such as an intermediate in the production of the active component cVlororMcotinyl,
in obtorr:iniiii#Hh4--based agricultural and horticultuial insecticides such as Imidacloprid,
A
Nitenpyxam and Acetaxniprid.
[0072]
Furthermore, according to the production process of the present iavention, by reacting a hexamethylenetetraammonium salt compound represented by fomiula (XII):
[Chemical Fonuula 18]

(wherein B represents a phenyl group, pjTidyl group, tliiazolyl group, dithirinyl group oi tettahydrofuranyl group, ajid mo.st, preferably represents a dithianyl group, and L is as defined above) with a base, an N-methylideneaniine oligomer represented by formula (XITI);
[0074]
[Chemical Formula 19]

[0075] (wherein B is as dctmed above, and n and m each independently represents an integer of 2 to 20) ox a mixture of two or more such oligomers can be obtained, and by subsequently bydrolyzing the N-methylideneamine oligomer repre$ented by formula (XHI) or the mixture of two or more such oligomers in the presence of an acid, a substituted methylanrine compound represented by formula (XIV) can be produced.
[0076]
[Chemical Formula 20]

[0077] (wlierein B is as defined above.) [0078]

Fui'tlieimore, according to the prnduction process of the present invention, by reacting a substituted metlij'l compound represented by fomiula (XY): [0079] [Cheniical Formula 21]

[0080] (wherein B and L are as defined above)
Mth hexaraetbylenetetramine, or ammonia or an ammooiiim salt and formaldehyde or a formaldehyde equivaJant and a base, an N-meLhylideneamine oligomer represented by formula (XHI) or a mLxtuie of two or more such oligomers can be obtained, and by subsequently hydrotyzmg the N-methylideneamine oligomer represented by foimula (XlII) or the mixture of two or more such oligomers in the presence of an acid, a substituted methylamine compound represented by formula (XIV) can be produced.
[0081]
In this manner, the production proce.ss of the present invention enables even compovmds that have proven impossible to produce -mth conventional processes to be produced easily, with good >ield, and at low cost.
EXAMPLES fOOS2]
The present invention is described in fuither detail below using a series of examples, although the present invention is in no way limited by tliese examples.

./Analysis of the reaction, products was performed using liiglv-perforraaiice liquid cliromatogi-aphy (HPLC, model LC-10, roanufacrLired by Shimadzii C;oTporation) and gas chromatography (GC, model GC:-14B, mauufaciured by Shiniadzu Corporation) (Example 1) Production of (2-chlofopyridin-5-yl)methyktiune(l)
To 3.02 g (10 mmol) of (2-cliloi-opT/Tidin-5-yr)hexamethy!enetetraattmionimn chloride (1-1) were added 5 ml of water and 5 ru) of toluene, and the restilting mixture was stirred for 7 Jiours at 60'C while a 28% aqueous solution of sodium hydroxide was used to maintam the pH of the reaction mixture wthin a range from 10 to 11.
An additional 4 ml of toluene was added to the reaction mixture, and the toluene layer was separated. 7 g of concentrated hydrochloric acid was added to the toluene layer, and the water layer containing the hydrochloride salt of anN-methylidene-2-eliloro-3-p>Tidylmethylaraine oUgomer (II-l) or a mixture of two or more such salts was separated,
3.2 g of methanol Avas added to the separated water layer, and the resulting mixture was treated for 3 hours at 60*C, yielding an aqueous solution of the hydrochloride salt of (2-chIoropyridin-5-yl)methylamiQe (lll-l). Analysis by IIPLC rf^^.'.-glp [0083] (Example 2) Production of (2-cMoropyridin-5-yl)methylan3iae (2)
To 1,62 g (10 mmol) of 2-chloro-5-(chloromethyl)pyridine (XI-1) and 1.48 g (10 nunol) of hexametliyleoetetramine were added 5 ml of water and 1 ml of toluene, and the resulting mixture was stirred for 7 hours at 60°C while a 28% aqueoits solution of sodium hydroxide was used to maintain the pH of the reaction mixture within a range fi-omlOtoU.

All additional 4 ml of toluene was added to tlie reaction mixture, and the toluene layer \vf\^ separated. 7 g of concentrated hydrochlonc acid was added to the toluene layer, and tiie water layer contmiiiig the hydrochloride salt of anN-methylideiie-2-clJoro-3-pyiidyhnetliylaEnine oligomer (Il-l) or a inixtme of t^vo or more such salts was separated,
3.2 g of merlianol was added to the separated water layer, and fhe resulting roLxture was treated for 3 hours at 60°C, yielding an aqueous solution of the hydrochloride salt of (2-chloropyridiii-5-yr)inethylmnine (III-1). Analysis by HPLC revealed a product amouat of 1.28 g (yield: 90%).
[00S4] (Example 3) Production of (2-chlotopyTidin-5-yl)melhylamiDe (3)
[0085]
To 1.62 g (10 rrnnol) of 2"diloro-5'diloromethylpyridine (XI-1) and 0.7 g (5 rnmol) of hexamethylenetetramine were added 5 ml of water and 1 ml of toluene, and the resulting mixture was stirred for 7 hours at 60'C while a 28% aqueous solution of sodium hydroxide was used to maintahi the pH of the reaction mixture within a range Liutu iO Lu 11.
An additional 4 nil of toluene was added to the reaction mixture, and the toluene layer was separated. 7 g of concentrated hydrocWoric acid was added to the toluene layer, and die water layer containing the hydrocUoride salt of a pyridyhnethyliitiine compound (11-3) or a mixture of t\\'o or more such salts was separated.
3.2 g of methanol was added to the separated water layer, and the resulting mixture was treated for 3 hours at 60°C, yielding an aqueous solution of the

hydrochloride salt of (2-chloropyTidin-5-yr)metl.iylainirie (III-l). Analysis by HPLC revealed a product amount of 1,26 g (yield: 89%).
Comparison mih exm^ph 2 above confirmed that even if the amotint of hexamethyleuetetiamine was reduced, tJieie was no substimtial effect on the \ield of the target product. [0086] (Example 4) Production of 1,3,5'tris[(2-chloropyridiflo-yl)methyl]-1,3,5-perhydrotriazine [0087]
10 a mixed solution containing 10 ml of methanol and 10 nal of water were sequentially added2.72 g (40 mjaiol) of a25% aqueous solutioaof ammoma, 1.21 g (40 mmol) of paiaformaldehyde, and 3.24 g (20 mmoY) of 2-chloro-5-(chloromethyl)pyridjjie (XI-1), and tlie resulting mixture was stirred for 2.5 hours at 50°C while a 28% aqtieous solution of sodium hydroxide was used to maintain the pH of the reaction iriixture within a rduge fi-om 10 to 11. The reaction auxture was then extracted wtli chloroform, and the chloroform layer was separated and concentrated, yielding 2.50 g (yield: Sl%) of 1,3,5-(ri"s(2-':hlorop:.T-:din ;> v!.)raethyM,3,5 pcrlrydrotr;a7,uu; (u-i).
^H-NMR (CDCI3,5 ppra): 3.37 (bs, 6H), 3.62 (s, 6H), 7.26 (d, 3.H), 7.61 (d, 3H), 8.33 (s, 3H)
m/s: 462 (0088] (Example 5) Production of (2<.hloropyridin-5-yl> To 0.77 g (1.66 mol) of l,3,5-tris[(2-chloropyridio-5-yl)methyl]-l,3,5-perhydxotriazLne (n-4) were sequentially added 0.40 g of methanol and I.S3 g of

("■■oncentrateJ hydrocMoric acid, and the resulring mixture was stirred at 75 to 80°C for 6 hours ITie reaction mixture was then diluted with chloroforai, and following conversion of the mixture to an alkalme state by adding a 28% aqueous solution of sodium liydfo,vdde, the chlorofotm layer was separated and concentrated, yielding 0-68 g (yield: 95'?/o) of (2-chloTOp5Tidin-5-yl)methylamine (1114).
[0089] (Example 6) Production of (2-chloropyridin-5-yl)methylaiiune (5)
To 1.62 g (10 mmol) of 2-chloro-5-(cWofomethyl)pyTidine (Xl-1) and 1.48 g (10 mmol) of heKamethylenetctraitiiae were added 5 nd of water and 1 ml of toluene, and tlie resulting mixture was stirred for 7 hours at 60°C vvhile a 28% aqueous solution of sodium hydroxide was used to maintain the pH of the reaction mixture \sithin a range from 10 to 11. An additional 4 ml of toluene was then added to the reaction mixture, and the water layer was separated to recover the hexamethylenetetramine, Analysis by GC revealed a recovei7 rate of 75%.
The toluene layer was treated in die same manner as eJcample 2, yielding (2-chloropyridin-5-yl)metliylaniiDe(ni-l).
rnnQOi
To the aqueous solution containing hexamethylenetetramine recovered in the manner described above were added 1.62 g (10 mmol) of 2-chloro-5-(cbloromethyl)pyridine (XH), 0.52 g (3.5 mmol) of hexamethyleoetetrainine, 0.18 g of aimnoruum chloride and 1 ml of toluene, and the resulting nuxture was heated for 7 hours at 60*C while a 28?^ aqueou.s solution of sodium hydroxide was used to maintain thft pH of the reaction niixture within a range iiom 10 to 11. An additional 4 ml of toluene was then added to the reaction mij^ture, and the toluene layer and water layer

were each separated. The hexamethylenctetTajiiine was recovered from the water layer-arid the recovery rate was 69" o, .
[0091]
Orx the other hand, 7 g of concentrated hydrochloric acid was added to the toluene layer, and tlie resulting water layer containing the hydrochloride salt of an N-methyUdene-(2-cMoro-pyridin-5-yl)methylarDine oligomer (11-5) or a mixture of two or more such salts was separated. 3.2 g of methanol was added to the separated water layer, and the resulting mixture was treated for 3 hours at 60^*0, yielding an aqueous solution of the hydrochloride salt of (2.chloropyridin-5-yl)methylamine. Analysis by HPLC revealed an amount of the (2-chloropyridin-5-yl)methylamiae of 1.28 g (yield: 90%).
[0092]
As described above, in the examples, approximately 70?/o of the hexarnetliylenetetramine was able to be recovered, and by simply supplementing the reaction with the required amount of additional hexamethylenetetramine!, the reaction was able to be continued at the same scale.

1. A process for producing a substituted methylamine compound, said process comprising:
reacting a hexamethylenetetraammonum salt compound represented by a formula (I) shown below:
[Chemical Formula 1]

(wherein A represent*; an organic group that is either a hydrocarbon group or a heterocyclic group, or said organic group that has a substituent, R represents a hydrogen atom, an organic group that is either a hydrocarbon group or a heterocyclic group, or said organic group that has a substituent, and L represents a halogen atom, an alkylsulfonyloxy group of 1 to 20 carbon atoms, a haloalkylsulfonyloxy group of 1 to 20 carbon atoms, or a substituted or unsnbstitnted arylsulfonybxy group) with a base to obtaan an N-methylidene-substituted methylamine oligomer represented by a formula (n) shown below: [Chemical Formula 2]

(wherein A and R are as defined above, and n represents an integer of 2 l,o 20) or a mixture of two or more of the oligomers, and
hydrolyzing the N-methylidene-substituted methylamine oligomer represented by formula (II) or the mixture of two or more of the oligomers in the presence of an acid, thereby producing a substituted methyl amine compound represented by a formula (III) shown below:
IChemical Formula 3]

(wherein A aod R are as defined above).
2. The process for producing a substituted methylamine compound according to
claim 1, wherein said A represents one group selected from the group consisting of
organic groups including a phenyl group, a pyridyl group, a thiazolyl group, a dithianyl
group and atetrahydfofbranyl group, and said organic groups having a substitiient,
3. The process for producing a substituted methylamine compound according to
claim 2, wherein said A represents one group selected from the group consisting of
groups represented by formulas (IV) to (X) shown below.
[Chemical Formula 4]

.'

(wherein X represents a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl group).
4, The process for producing a substituted methylamine compound according to
claim 3, wherein said A is a 2-chloropyridin-5-yl group.
5, The process for producing a substituted methylainine compound according to any
one of claims 1 to 4, wherein said R represents a hydrogen atom or an alkyl group of 1 to
5 carbon atoms.
6, The process for producing a substituted methylamine compound according to any
one of claims 1 to 5, wherein reaction between said hexamethylenetetraammonium salt
compound represented by said formula (I) and said base is conducted al a pH of 9 to 12.

7. A process for producing a substituted methylamine compound, said process comprising;
reacting a substituted methyl compound represented by a formula (XI) shown below:
[Chemical Formula 5]

(wherein A represents an organic group that is either a hydrocarbon group or a heterocyclic group, or said organic group that has a substituent, R represents a hydrogen atom, an organic group that is either a hydrocarbon gronp or a heterocyclic group, or said organic group that has a substituent, and L represents a halogen atom, an alkylsultonyloxy group of 1 to 20 carbon atoms, a haloalkylsulfonyloxy group of 1 to 20 carbon atoms, or a substituted or unsubstituted arylsulfonyloxy group) with hexamethylenetetramine, or ammonia or an ammonium salt and fonnaldehyde or a formaldehyde equivalent, and a base to obtain an N-methyiidene-substituted methylamine oligomer represented by a formula (IT) shown below: [Chemical Formula 6]

(wherein A and R are as defined above, and n represents an integer of 2 to 20), or a mixture of two or more of the oligomers, and

hydrolyzing the N-methylidene-substituted methylamine oligomer representcd by formula (U) or the mixture of two or more of the oligomers in the presence of an acid, thereby produciug a substituted methylamine compound represented by a formula. (Ill) shown below;
[Chemical Formula 7]

\ (wherein A is as defined above).
8^ The process for producing a substituted methylamine compound according to claim 7, wherein said A represents one group selected from the group consisting of organic groups including u phenyl group, a pyridyl group, a thiazolyl group, a dithianyl group and a tetrahydrofuranyl group, and said organic groups having a substituent.
9. The process for producing a substituted methylamine compound according to claim 8, wherein, said A represents one group selected from the group consisting of groups represented by formulas (IV) to (X) shown below: [Chemical Fonnula 8)

(wherein X represents a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl group).
10. The process for producing a substituted methylamine compound according to
claim 9, wherein said A is a 2-cbloropyridin-'5-yl group.
11. The process for producing a substituted methylamine compound according to any
one of claims 7 to 10, wherein said R represents a hydrogen atom or an alkyl group of 1
to 5 carbon atoms.
12. The process for producing a substituted methylanxine compound according to any
one of claims 7 to 11, wherein reaction of said substituted methyl compound represented
by said formula (XI) with bexamethylenetetramine, or ammonia or an ammonium salt
and formaldehyde or a formaldehyde equivalent, and a base is conducted at a pH of 9 to
12.

13. The process for producing a substituted methylamine compound according to any
one of claims 7 to 12, wherein hexametliyleiietetramine, or ammonia and fomialdehyde^
are recovered from a reaction mixture obtained following reaction of said substituted
methyl compound represented by Said formula. (XI) with hexamethylenetetramine, or
ammonia or an ammonium salt and formaldehyde or a formaldehyde equivalent, and are
subsequently reused in reaction "with said substituted methyl compound represented by
said formula QiX).
14. An N-methylidene-pyridylnethylamine oligomer represented by a formula (II')
shown below:
[Chemical Formula 9]

(wherein X represents a hydrogen atom, a halogen atom, or a substituted or unsubstituted alley] group, and n represents an integer of 2 to 20).
15. A triazine derivative represented by a formula (I?') shown below: [Chemical Formula 10]

(wherein X represents a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl group).

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Patent Number

271097

Indian Patent Application Number

6258/CHENP/2009

PG Journal Number

06/2016

Publication Date

05-Feb-2016

Grant Date

02-Feb-2016

Date of Filing

22-Oct-2009

Name of Patentee

NIPPON SODA CO.,LTD

Applicant Address

2-1, OHTEMACHI 2-CHOME, CHIYODA-KU, TOKYO 100-8165

Inventors:

#	Inventor's Name	Inventor's Address
1	IMAGAWA, TSUTOMU	C/O NIPPON SODA CO.,LTD., TAKAOKA PLANT, 300, MUKAINOHONMACHI, TAKAOKA-SHI, TOYAMA 933-8507
2	SHIBATA, YASUSHI	C/O NIPPON SODA CO.,LTD., TAKAOKA PLANT, 300, MUKAINOHONMACHI, TAKAOKA-SHI, TOYAMA 933-8507

PCT International Classification Number

C07D213/61

PCT International Application Number

PCT/JP07/58842

PCT International Filing date

2007-04-24

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA