Title of Invention	METHOD FOR PRODUCING 1,2-PHENYLETHANE COMPOUND USING ATOM TRANSFER RADICAL COUPLING REACTION
Abstract	An object of the present invention is to provide a method capable of producing a 1,2-phenylethane compound with extremely high yield in a short amount of tirae. Disclosed is a method for producing a 1,2-phenylethane compound, which comprises subjecting a compound represented by formula (I): wherein Ra represents a hydrogen atom or a substituted or unsubstitutsd phenyl group; Rb represents a hydrogen atom or a substituent; n represents an integer of 1 to 5 and when n is 2 or more, Rb may be the same or different, or may be combined with each other to form a ring; and X represents a halogen atom; to a coupling reaction in the presence of a transition metal complex to produce a compound represented by formula (II):

Title of Invention

METHOD FOR PRODUCING 1,2-PHENYLETHANE COMPOUND USING ATOM TRANSFER RADICAL COUPLING REACTION

Abstract

An object of the present invention is to provide a method capable of producing a 1,2-phenylethane compound with extremely high yield in a short amount of tirae. Disclosed is a method for producing a 1,2-phenylethane compound, which comprises subjecting a compound represented by formula (I): wherein Ra represents a hydrogen atom or a substituted or unsubstitutsd phenyl group; Rb represents a hydrogen atom or a substituent; n represents an integer of 1 to 5 and when n is 2 or more, Rb may be the same or different, or may be combined with each other to form a ring; and X represents a halogen atom; to a coupling reaction in the presence of a transition metal complex to produce a compound represented by formula (II):

Full Text	DESCRIPTION METHOD FOR PRODUCING 1,2-PHENYLETHANE COMPOUND U3IHC- ATOM TRANSFER RADICAL COUPLING REACTION TECHNICAL FIELD [0001] This application claims priority on Japanese Patent Application No. 2006-074463 filed on 17 March 2006, the disclosure of which is incorporated by reference herein. The present invention relates to a method for producing a 1,2-phenylethane compound, and particularly to a method for producing a 1,2-phenyIethane compound using a transition metal compound as a catalyst. BACKGROUND ART [0002] Tetrakis (hydroxyphenyl)alkane can be used as a host compound in polymolecular clathxate compounds. For example, 1, 1, 2, 2-tetrakis(4-hydroxyphenyl)ethane selectively forms clathrate compounds {compounds having an inclusion of guest molecule in a cavity formed by the host molecule} with various organic guest compounds and therefore i~'3 application is expected in technical fields such as selective separation, chemical stabilization, prevention of vaporization and pulverization. [0003] Up until the present, as a method for producing tetrakis(hydroxyphenyl)alkanes, a method of condensing phenol and glyoxal in acetic acid in a temperature range cf 2 to 10DC in the presence of sulfuric acid is known'for example, Non-Eatent Document 1}. [0004] In addition, there is a method for producing tetrakis(hydroxyphenyl)alkanes by condensing glyoxal and phenol in excess with respect to glyoxal in a temperature range of 100 to 1B0°C in the presence of hydrochlcric acid (for example, Patent Document 1) or a method characterize." by condensing phenol and a dialdehyde or derivatives thereof in the presence of sulfuric acid and phosphoric acid (for example, Patent Document 2). [0005] However as shown by the method disclosed in Parer.c Document 1, a reaction using a single sulfuric acid catalyst is difficult to control and tends to be associated with side reactions or runaway reactions. Furthermore although reactions at high temperatures using phenol in excess have characters such as no requirement of react:ien solvents, a short reaction time and a low cost, there is tendency for side reactions and high yields are net expected. Moreover there is the problem that it is extremely difficult to eliminate multiple produces resulting from such side reactions. [0006] As shown by the method disclosed in Patent Document 2, side reactions can be suppressed by condensation in the presence of a mixed acidic catalyst' comprising sulfuric acid and phosphoric acid resulting in highly efficient arc selective production of tetrakis(hydroxyphenyl)alkanes. However, the yield is on the order of 40 to 70% acid the reaction time requires from several to tens of hoars. [0007] As shown by the method disclosed in Patent a compound having a tetrakis phenyl backbone combining ester groups with phenyl groups can be produced by a coupling reaction using a zinc catalyst. However this method requires'a 24-hour reflux process, and has = lor:g reaction time and a low yield. [0008] Non-Patent Document 1: Monatshefte fur Chem I e., 82, 652 (1951) Patent Document 1: Japanese Unexamined Patent Application, Firsr Publication No. Sho-57-65716 Patent Document 2: Japanese Unexamined Patent Application, First Publication No. Hei-7-076538 Patent Document 3: WO 00/20372 DISCLOSURE OF THE INVENTION [0009] An object of the present invention is to provide £ method for producing a 1,2-phenylethane compound in = short reaction time and with an extremely high yield. [0010] The present inventors conducted diligent research into solving the above problems and completed the pr-aaenr invention based on the insight that it is possible to produce a 1,2-phenylethane compound using an atom transfer radical coupling reaction using a transition metal complex catalyst. As a result, it is possible to produce = 1.2-phenylethane compound in a extremely shorter reaction rime and higher yield in comparison to a coupling method using zinc or another conventional method. [0011] Namely, the present invention relates to the following: [1] A method for producing a 1,2-phenylethane compound, which comprises subjecting a compound represented by wherein Ra represents e hydrogen atom or a substituted or unsubstituted phenyl group; Rb represents a hydrogen --on: or a substituent; n represents an integer of 1 to 5 ar.d, when n is 2 or more, Rb may be the same or different, or may be combined with each other to form a ring; and X represents a halogen atom; to a coupling reaction in the presence of a transition metal complex to produce a compound represented by formula (II): [2] The method for producing a 1, 2-phenylethane compound according to the above-described [1], wherein Ra is substituted or unsubstituted phenyl group; and [3] The method for producing a 1, 2-phenylethane compound according to the above-describee. [1] or [2], wher^ir_ the substituent of the phenyl group represented by Ra or the substituent represented by Rb is COOR1, S02R2t 0RE. SR; :r N(R5)(R6), (R1 to R6 represent a hydrogen atom or an organic group). Furthermore, the present invention relates zo the following: [4] The method for producing a 1,2-phenylethane compound according to any one of the above-described [1] to .3", wherein the compound represented by formula (I) is a compound represented by formula (1-1): and the compound represented by formula (II) is a compound represented by formula (II-l): [5] The method for producing a 1,2-phenylethana compound according to the above-described [4], wherein Rb in formula (1-1) or (II-l) is OR3 or COOR1; and [6] The method for producing a 1,2-phenylethane compound according to any one of the above-described [1] to wherein the transition metal complex is a copper complex or an iron complex. [0013] The method according to the present invention allows production of a 1,2-phenylethane compound in an extremely short amount of time with a high yield. BEST MODE FOR CARRYING OUT THE INVENTION [0014] A method for producing a 1,2-phenylethane compound according to the present invention is not particularly limited as long as it is a method in which a compound represented by formula (I): [0015] [0016] is subjected to a coupling reaction in the preserce cf a transition metal complex to produce a compound rby formula (II): [0017] [001B] According to the present invention, it is possible to obtain the compound represented by formula (II) ir_ sr. extremely short amount of time with a high yield. One compound or more than one compound can be used as the compound represented by formula (I). The coupling reaction of the present invention can be homo-coupling or cross-coupling. [0019] Ra in formula (I) or (II) represents a hydroger. atom. or a substituted or unsubstituted phenyl group. Fror. the point of reactivity, a substituted or unsubstituted phenyl group is preferred. When there are two or more substituents in phenyl groups, the substituents same or different, or may be connected each other and form saturated rings, aromatic rings or heterocycles. Rb represents a hydrogen atom or a substituent. n represents an integer of 1 to 5 and, when n is 2 or more, Rb ~:a.y be the same or different, or may be combined with eazh other to form a saturated ring, an aromatic ring or a heterocycle. X represents a halogen atom and includes, for example, chlorine atoms, bromine atoms and iodine atoms. From the point of reactivity, bromine atoms are preferred. [0020] The substituent of the phenyl group represented by Ra or the substituent represented by Rb includes, for example, COOR1, S02R2, OR3, SR4 or N(R5)(R6;. COOR1 is preferred. R1 to R6 represent a hydrogen atom or an organic group. The organic group includes, for example, an alkyl group, a. silyl group, an acyl group, an aryl group, a phosphoryl group, a sulfonyl group, an alkylphosphoryl alkylsulfonyl group. Concretely, the substituent alkoxy groups such as a methoxy group or an ethcvv silyloxy group such as a trimethylsilyloxy group, dimethylsilyloxy group or a dimethylphenyl3ilyloxy an acyl group such as an acetyl group or a benzoyl or an aryloxy group such as a phenoxy group or a group. [0021] In particular, R3 can be a methyl group, a methoxymethyl group, a 2-inethoxyethaxymethyl group, a methylthiomethyl group, a tetrahydropyranyl group, = phenacyl group, a cyclopropylmethyl group, an al_yl an isopropyl group, a cyclohexyl group, a t-butyl a benzyl group, an ortho-nitrobenzyl group, a 9-antr.rylmetryi group, a 4-picolyl group, a trimethylsilyl group, a t-butyl-dimethylsilyl group, an acetyl group, a benzoyl a valeryl group, a 2,2,2-trichloroethylcarbonyl group, a vinylcarbonyl group, a benzylcarbonyl group, an aryl carbamoyl group, a methanesulfonyl group, and a toluenesulfonyl group. [0022] A preferred form of the compound is shown in [1]. [0023] [0024] The compound shown in formula [1] includes -he compound shown in formula [1-1]. [0025] A coupling reaction with the compound shown in formula [1-1] gives: [0026] [0027] The compound shown in formula (II-l) can be cb-ained by above-mentioned coupling reaction. [0028] The transition metal complex of the present includes, for example, a catalyst which can be used in a living radical polymerization method. In the method according to the present invention, the transition complex may be added directly to the system or a compound and a ligand compound therefof can be added system in order to form a transition metal complex system. [0029] The central metals forming the transition metal complex include elements from Groups 7 to 11 of Periodic Table such as manganese, rhenium, iron, rhodium, nickel or copper (using the periodic table disclosed :_n "Handbook of Chemistry Z, Basic, 4 th edition" (1993), edited by The Chemical Society Use cf copper and iron is preferred from among these with the use of copper being particularly preferred. [0030] Concretely, the copper complex includes copper conplexes having nitrogen-containing compounds as lig = r:ds, such as NH3, NO, NO2, N03, ethylenediamine, diethylenetriamine, tributylamine, 1,3-diisopropy--4,5-dimethylimidazol-2-ylidene, pyridine, phenanthroiine, diphenanthroline or substituted phenanthroiine, 2,2' : £' ,2"-terpyridine, pyridine imine, cross-linked aliphatic diamine, 4-4'-di(5-nonyl)-2,2'-bipyridine, thiocyanate, bipyridine coordinated with 0, S, Se or Te, iminodipyridine, alkylirainopyridine, alkylbipyridinylamine, alkyl-substituted tripyridine, di(alkylamino)alkyl pyridine, ethylenediamine dipyridine, tri (pyridinylmethyl; air.ine, N,N,N',N',N"-pentamethyl diethylene triaraine. Fur-hsrrr.ore, the copper complexes include copper complexes having nitrogen-containing compounds and/or halogen atom as ligands. Concretely, it includes acetyl-[4-4' -di(5-nonyl)-2,2'-bipyridine]copper, hexafluorophosphine-di[4-4'-di [0031] The iron complex includes di(triphenylphosphine.! iron dichioride, di(tributylamino) iron dichloride, triphenylphosphine iron trichloride, (1-bromo) triethoxyphosphine-iron dibromide, (1-bromo)ethylbenzene-triphenylphosphine-iron dibromide, (1-bromo) ethyloenzene-[4-4' -di(5-nonyl)-2,2'-bipyridine] iron dibromide, il-bromo)ethylbenzene-tri-n-butylamino-iron dibromice, 1-bromo)ethylbenzene-tri-n-butylphosphine-iron dibromide, tri-n-butylphosphine-iron dibromide, ;4-4'-di(5-nonyl)-2,2' -bipyridine\ iron dibromide, tetraalkylammonium iron (II) trihalide, dicarbonylcyclopentadienyl iron (Hi iodide, dicarbonylcyclopentadienyl iron(II) bromide, dicarbonylcyclopentadienyl iron(I") chloride, dicarbonylinder.yl iron(II) iodide, dicarbonylinder.yl iron (II) bromide, dicarbonylindenyl iron(II) chloride, dicarbonylfluorenyl iron(II) iodide, dicarbonylfiucrenyl iron(II) bromide, dicarbonylfluorenyl iron(II) chloride, 1, 3-diisopropyl-4,5-dimethylimidazol-2-ylidene iron chloride and 1, 3-diisopropyl-4, 5-dimethylimidazol-2-y_.i oene iron bromide. [0032] Other transition metal complexes include ru^neniurr. complexes such as dichlorotris(triphenylphosphine ruthenium, dichlorotris (tributylphosphine) ruthe-iur., dichloro(trialkylphosphine) p-cytnene ruthenium, dic'.iioro- di(tricymenephosphine)styryl ruthenium, dichloro (cyclooctadiene) ruthenium, dichlorobenzer_ ruthenium, dichloro p-cymene ruthenium, dichloro(norbornadiene) ruthenium, cis-dichloro-bis (2,2'- bipyridine) ruthenium, dichlorotris(1,lO-DhenanihroIine) ruthenium, carbonylchlorohydridetris (triphenylphcspninei ruthenium, chlorocyclopentadienylbis (triphenylphcsphiriei ruthenium, chloroindenylbis(triphenylphosphine) ruthenium, dihydrotetra(triphenylphosphine) ruthenium, dicarbonylcyclopentadienyl ruthenium(ii) iodine, di carbonylcyclopentadienyl ruthenium (H) bromide.. dicarbonylcyclopentadienyl ruthenium(II).chloride, dicarbonylindenyl ruthenium {II) iodine, dicarbor.yiir.ier.yl ruthenium(II) bromide, dicarbonylindenyl ruthenium ; chloride, dicarbonylfluorenyl ruthenium(II) iodide, dicarbonylfluorenyl ruthenium{II) bromide, dicarbonylfluorenyl ruthenium (II) chloride and iichlcra- di-2, 6-bis[(dimethylamino)-methyl] (u-N2) pyridine ruthenium(II). [0033] Nickel complexes include carbonylcyclopentadienyl nickel (II) iodine, carbonylcyclopentadienyl nickalilli btomide, carbonylcyclopentadienyl nickel(II) chloride, c^rbonylindenyl nickel(II) iodine, carbonylindenyl nickel (II) bromide, carbonylindenyl nickel[II) cileries, carbor.ylfluorenyl nickel(II) iodide, carbonylflucre^yl nickel{II) bromide, carbonylfluorenyl nickel{II. chloride, o,o'-ai(dimethylaminomethyl) phenyl nickel halide, di-triphenylphosphine nickel dibromide, di{tri-n-butyIamino; nickel dibromide, 1,3-diaminophenyl nickel bromide, diitri-n-butylphosphine) nickel dibromide and tetra (triphenylphosphine) nickel. [0034] Further complexes include molybdenum complexes including tricarbonylcyclopentadienyl molybdenura [II,- iodine, tricarbonylcyclopentadienyl molybdenum(II) bromide, tricarbonylcyclopentadienyl molybdenum (II) chloride, di-N-aryl-di (2-dimethylaminomethylphenyl) lithium molybdenum, di-N-aryl-(2-dimethylaminomethylphenyl)-methyl-Liihiur. molybdenum, di-N-aryl-(2-dimethylaminomethylphenyl}-trimethylsilylmethyl-lithium molybdenum, di-N-aryl-[2-dimetbylaminomethylphenyl)-p-tolyl lithium molybdenum; tungsten complexes including tricarbonylcyclopentadienyl tungsten(II) iodine, tricarbonylcyclopentadienyl tungsten (II) bromide, tricarbonylcyclopentadienyl tungsten(II) chloride; cobalt complexes including dicarbonylcyclopentadienyl cobalt(I); manganese complexes including tricarbonylcyclopentadienyl manganese':.;, tricarbonyl (nethylcyclopentadienyl) manganese (Ij ; rr.&niurp. complexes including tricarbonylcyclopentadienyl rnenium(I), dioxobis(triphenylphosphine) rhenium iodine; complexes including tri(triphenylphosphine) chloride; palladium complexes including triphenylrnos-r-ine diacetyl palladium. These transition metal complexes rr.sy be used singly or in combination. [0035] The amount of transition metal compound added depends on the type of compound. However it is generally preferable to add 0.1 to 5 equivalents to the compound acting as a raw material represented by formula {I) and more preferably to add 0.3 to 1 equivalents. [0036] In the method according to the present invg:. from the point of improving catalyst activity, it is preferable to perform the coupling reaction in the presence of a base. The base may be organic or inorganic. Organic bases include amines such as aliphatic amines or amines. Inorganic bases include alkali metal hydroxides or carbonates and alkaline earth metal oxides or carbonates. [0037] There is no particular limitation en the organic solvent used in the reaction and it includes aromatic hydrocarbons such as benzene, toluene and xylene; aliphatic hydrocarbons such as hexane, heptane and octane; hydrocarbons such as cyclopentane, cyclohexane ar.c cyclooctane; ketones such as acetone, methyl ethyl ketone and cyclohexanone; ethers such as tetrahydrofuran and dicxar.e; esters such as ethyl acetate and butyl scerate; amides such as N,N-dimethylformamid@ and N,N-dimethylacetamide; sulfoxides such as dimethylsulfoxide; alcohol such as methanol and ethanol; polyvalent alcohol derivates such as ethylene glycol monomethyl ethylene glycol monomethyl ether acetate. These solvents may be used singly or in combination. [0038] The reaction temperature is normally from room temperature to 150DC and preferably from 60 to 12 0iC. The reaction is normally performed under ordinary pressure or under pressurized conditions. Furthermore the reaction should proceed in an extremely short time and should reach completion in 3 to 90 minutes and preferably approximately 5 to 30 minutes. In this manner, the method cf production of the present invention can produce the target compound in an extremely efficient manner. The reaction can be terminated by lowering the reaction temperature. After terminating the reaction, the target compound can be isolated by normal isolation and purification methods such as recrystallization, column purification, depressrrizatrcr, purification and filtration. [0039] In the method of the present invention, when a produced compound represented by formula (II) substituents such as COOR1, S02R2, OR3, SR4 or the benzene ring, active hydrogen is produced by treatment and it is possible to convert the into COOH, S02E, OH, SH or NH2. Furthermore, after hydrolysis in the presence of a base, it is possible :c convert the substituents into OH or SH. Acids usee in an acid treatment include inorganic acids such as hydrochloric acid, bromic acid, sulfuric acid, nitric acid, bcric acid, methanesulfonic acid or organic acids such as The temperature during acid treatment is not particularly limited and may, for example, be in the range of ~1CCC -0 lSO^C. The base may be organic or inorganic. Organic bases include, for example, amines such as alipnatic amines and aromatic amines. Inorganic bases include alkali metal hydroxides or carbonates and alkaline earth metal oxidss and carbonates. [0040] The present invention will be described in further detail hereafter. However the scope of the invention is not limited to the examples. Example 1 [0041] [0042] 0.39 g (1 mmol} of PhCOOEt2-Br, 0.14 g (1 rrcnol) of CuBr, 0.25 g (4 mmol) of Cu(0) and 20 ml of toluene -,;ere charged into a 50 ml reaction flask. After degassing th_e solution, 0.35 g (2 mmol) of N,N,N',N',N"-pentaniethyldiethylenetriamine was added. The mixture "was stirred at 80°C for 0.5 h and cooled to room temperar.ar=. The insoluble matter was filtered and the reaction was washed with water until the coloring was removed completely from the water layer, and dried over sulfate. The solvent was removed under reduced pressure give 0.30g of a white powder solid, finally, (isolated yield 97%). Example 2 [0043] [0044] 1.15 g (5 mmol) of methyl 4-(bromomethyl)banzcaig, 0.72 g (5 raraol) of CuBr, 1.27 g (20 mmol) of Cu(0}, _.56 r (10 mmol) of bipyridine and 20 mL of toluene were charged into a 30 mL reaction flask. After degassing the solution, the mixture was stirred at 100°C for 1 h and cooled to room temperature. 10 mL of chloroform was added, and tr_e insoluble matter was filtered and the reaction nurture WHS washed with water and dried over magnesium sulfate. "The solvent was removed under reduced pressure and the crude product was recrystallized from ethyl acetate/hexans. The crystal thereby obtained was dried under reduced pressure to obtain 0.32 g of a faintly yellow crystal (isolates yield 43%). Example 3 [0045] 9.6 g (48 iranol) of bis(4-hydroxyphenyi)methane. 11.5 g (117 irimol) of triethylamine, 200 mL of tetrahy^rcf-irsr, were charged into a 200 mL reaction flask and cooled 14.9 g (106 nmol) of benzoyl chloride was added mixture was stirred at room temperature for 1 hour. Triethylamine hydrochloride was removed by the reaction mixture was evaporated. After the residue washed with water for three times, and dried over sulfate. After removal of solvent under reduced pressure, the crude product was recrystallized from hexane, ethyl acetate to give 16.8 g of a faintly yellow needle crystal A (isolated yield 86%;. 14.4 c (35 mmol) of the crystal A, 6.5 g (37 of N-bromosuccinimide, and 70 ml of benzene were charged into a 200 rnL reaction flask and refluxed for 1 hour. After cooling, the reaction mixture was concentrated under reduced pressure. The residue was dissolved in methylene chloride, washed with water for three times, and drisd over magnesium sulfate. After removal of solvent under reduced pressure, the crude product was recrystallized from etnyl acetate to give 11.7 g of a white floccular crystal 3 (isolated yield 68%). 4.9 g (10 mmol) of the crystal B, 0.7 g (5 CuBr, 1.3 g (20 mmol) of Cu, and 50 mL of toluene were charged into a 100 mL reaction flask. After deg£.sstng the solution and heating the solution to 80°C, 1.8 g ;i3 mmol; of N,N,N' ,W ,N"-per.taraethyl diethylene triaraine was added. The mixture was stirred at 80°C for 0.5 h and coded :: room temperature. The reaction mixture was filtered =nd the insoluble matter was washed with water for three times. 100 mL of chloroform was added to the insoluble matter, end refluxed for 10 minutes and filtered while still hct. After the concentration of the filtrate, the was washed with ethyl acetate to give 3.1 g of 2 floccular crystal C (isolated yield 76%). Then 2.6 g (3-2 miriol) of the crystal C, and of toluene were charged into 100 mL reaction flask, Hydrolysis products saponified in the presence of potassium. hydroxide and water were purified to give 1.1 g (2.8 mmol) powder of 1,1, 2, 2-tetrakis (4-hydroxyphenyl) ethane CLAIMS 1. A method for producing a 1,2-phenylethane compound which comprises subjecting a compound represented by formula (I): wherein Ra represents a hydrogen atom or a substituted or unsubstituted phenyl group; Rb represents a hydcoren atom or a subs tit uer.t; n represents an integer of 1 to 5 and when n is 2 or more, Kb may be the same or different, or may be combined with each other to form a ring; and X represents a halogen atom; to a coupling reaction in the presence of a transition metal complex to produce a compound represented by formula (II): 2. The method for producing a 1,2-phenylethane compcunc according to claim 1, wherein Ra is a substituted or unsubstituted phenyl group. 3. The method for producing a 1,2-phenylethane compound according to claim 1 or 2, wherein the substituer.t of -he phenyl graup represented by Ra cr the substituent represented by Rb is COOR1, S02R2, OR3, SR* or R1 to R6 represent a hydrogen atom or an organic -group. 4. The method for producing a 1,2-phenylethane ccmpcund according to claim 1 or 2, wherein the compound by formula (I) is a compound represented by formula 5. The method for producing a 1,2-phenylethans ccrapound according to claim 4, wherein Rb in formula (1-1) or (II-l) is OR3 or COOR1. 6. The method for producing a 1,2-phenylsthane compound according to claim 1 or 2, wherein the transit complex is a copper complex or an iron complex.

Full Text

DESCRIPTION
METHOD FOR PRODUCING 1,2-PHENYLETHANE COMPOUND U3IHC- ATOM TRANSFER RADICAL COUPLING REACTION
TECHNICAL FIELD [0001]
This application claims priority on Japanese Patent Application No. 2006-074463 filed on 17 March 2006, the disclosure of which is incorporated by reference herein.
The present invention relates to a method for producing a 1,2-phenylethane compound, and particularly to a method for producing a 1,2-phenyIethane compound using a transition metal compound as a catalyst.
BACKGROUND ART [0002]
Tetrakis (hydroxyphenyl)alkane can be used as a host compound in polymolecular clathxate compounds. For example, 1, 1, 2, 2-tetrakis(4-hydroxyphenyl)ethane selectively forms clathrate compounds {compounds having an inclusion of guest molecule in a cavity formed by the host molecule} with various organic guest compounds and therefore i~'3 application is expected in technical fields such as selective separation, chemical stabilization, prevention of

vaporization and pulverization.
[0003]
Up until the present, as a method for producing tetrakis(hydroxyphenyl)alkanes, a method of condensing phenol and glyoxal in acetic acid in a temperature range cf 2 to 10DC in the presence of sulfuric acid is known'for example, Non-Eatent Document 1}.
[0004]
In addition, there is a method for producing tetrakis(hydroxyphenyl)alkanes by condensing glyoxal and phenol in excess with respect to glyoxal in a temperature range of 100 to 1B0°C in the presence of hydrochlcric acid
(for example, Patent Document 1) or a method characterize." by condensing phenol and a dialdehyde or derivatives thereof in the presence of sulfuric acid and phosphoric acid (for example, Patent Document 2).
[0005]
However as shown by the method disclosed in Parer.c Document 1, a reaction using a single sulfuric acid catalyst is difficult to control and tends to be associated with side reactions or runaway reactions. Furthermore although reactions at high temperatures using phenol in excess have characters such as no requirement of react:ien solvents, a short reaction time and a low cost, there is tendency for side reactions and high yields are net

expected. Moreover there is the problem that it is extremely difficult to eliminate multiple produces resulting from such side reactions. [0006]
As shown by the method disclosed in Patent Document 2, side reactions can be suppressed by condensation in the presence of a mixed acidic catalyst' comprising sulfuric acid and phosphoric acid resulting in highly efficient arc selective production of tetrakis(hydroxyphenyl)alkanes. However, the yield is on the order of 40 to 70% acid the reaction time requires from several to tens of hoars. [0007]
As shown by the method disclosed in Patent a compound having a tetrakis phenyl backbone combining ester groups with phenyl groups can be produced by a coupling reaction using a zinc catalyst. However this method requires'a 24-hour reflux process, and has = lor:g reaction time and a low yield. [0008] Non-Patent Document 1:
Monatshefte fur Chem I e., 82, 652 (1951) Patent Document 1:
Japanese Unexamined Patent Application, Firsr Publication No. Sho-57-65716 Patent Document 2:

Japanese Unexamined Patent Application, First Publication No. Hei-7-076538 Patent Document 3:
WO 00/20372
DISCLOSURE OF THE INVENTION [0009]
An object of the present invention is to provide £ method for producing a 1,2-phenylethane compound in = short reaction time and with an extremely high yield. [0010]
The present inventors conducted diligent research into solving the above problems and completed the pr-aaenr invention based on the insight that it is possible to produce a 1,2-phenylethane compound using an atom transfer radical coupling reaction using a transition metal complex catalyst. As a result, it is possible to produce = 1.2-phenylethane compound in a extremely shorter reaction rime and higher yield in comparison to a coupling method using zinc or another conventional method. [0011]
Namely, the present invention relates to the following:
[1] A method for producing a 1,2-phenylethane compound, which comprises subjecting a compound represented by

wherein Ra represents e hydrogen atom or a substituted or unsubstituted phenyl group; Rb represents a hydrogen --on: or a substituent; n represents an integer of 1 to 5 ar.d, when n is 2 or more, Rb may be the same or different, or may be combined with each other to form a ring; and X represents a halogen atom; to a coupling reaction in the presence of a transition metal complex to produce a compound represented by formula (II):

[2] The method for producing a 1, 2-phenylethane compound according to the above-described [1], wherein Ra is substituted or unsubstituted phenyl group; and [3] The method for producing a 1, 2-phenylethane compound

according to the above-describee. [1] or [2], wher^ir_ the substituent of the phenyl group represented by Ra or the substituent represented by Rb is COOR1, S02R2t 0RE. SR; :r N(R5)(R6), (R1 to R6 represent a hydrogen atom or an organic group).
Furthermore, the present invention relates zo the following:
[4] The method for producing a 1,2-phenylethane compound according to any one of the above-described [1] to .3", wherein the compound represented by formula (I) is a compound represented by formula (1-1):

and the compound represented by formula (II) is a compound represented by formula (II-l):

[5] The method for producing a 1,2-phenylethana compound according to the above-described [4], wherein Rb in formula
(1-1) or (II-l) is OR3 or COOR1; and
[6] The method for producing a 1,2-phenylethane compound according to any one of the above-described [1] to wherein the transition metal complex is a copper complex or an iron complex.
[0013]
The method according to the present invention allows production of a 1,2-phenylethane compound in an extremely short amount of time with a high yield.
BEST MODE FOR CARRYING OUT THE INVENTION [0014]
A method for producing a 1,2-phenylethane compound according to the present invention is not particularly limited as long as it is a method in which a compound

represented by formula (I): [0015]

[0016]
is subjected to a coupling reaction in the preserce cf a transition metal complex to produce a compound rby formula (II):
[0017]

[001B]
According to the present invention, it is possible to obtain the compound represented by formula (II) ir_ sr. extremely short amount of time with a high yield. One compound or more than one compound can be used as the

compound represented by formula (I). The coupling reaction of the present invention can be homo-coupling or cross-coupling.
[0019]
Ra in formula (I) or (II) represents a hydroger. atom. or a substituted or unsubstituted phenyl group. Fror. the point of reactivity, a substituted or unsubstituted phenyl group is preferred. When there are two or more substituents in phenyl groups, the substituents same or different, or may be connected each other and form saturated rings, aromatic rings or heterocycles. Rb represents a hydrogen atom or a substituent. n represents an integer of 1 to 5 and, when n is 2 or more, Rb ~:a.y be the same or different, or may be combined with eazh other to form a saturated ring, an aromatic ring or a heterocycle. X represents a halogen atom and includes, for example, chlorine atoms, bromine atoms and iodine atoms. From the point of reactivity, bromine atoms are preferred.
[0020]
The substituent of the phenyl group represented by Ra or the substituent represented by Rb includes, for example, COOR1, S02R2, OR3, SR4 or N(R5)(R6;. COOR1 is preferred. R1 to R6 represent a hydrogen atom or an organic group. The organic group includes, for example, an alkyl group, a.
silyl group, an acyl group, an aryl group, a phosphoryl

group, a sulfonyl group, an alkylphosphoryl alkylsulfonyl group. Concretely, the substituent alkoxy groups such as a methoxy group or an ethcvv silyloxy group such as a trimethylsilyloxy group, dimethylsilyloxy group or a dimethylphenyl3ilyloxy an acyl group such as an acetyl group or a benzoyl or an aryloxy group such as a phenoxy group or a group. [0021]
In particular, R3 can be a methyl group, a methoxymethyl group, a 2-inethoxyethaxymethyl group, a methylthiomethyl group, a tetrahydropyranyl group, = phenacyl group, a cyclopropylmethyl group, an al_yl an isopropyl group, a cyclohexyl group, a t-butyl a benzyl group, an ortho-nitrobenzyl group, a 9-antr.rylmetryi group, a 4-picolyl group, a trimethylsilyl group, a t-butyl-dimethylsilyl group, an acetyl group, a benzoyl a valeryl group, a 2,2,2-trichloroethylcarbonyl group, a vinylcarbonyl group, a benzylcarbonyl group, an aryl carbamoyl group, a methanesulfonyl group, and a toluenesulfonyl group. [0022]
A preferred form of the compound is shown in [1]. [0023]

[0024]
The compound shown in formula [1] includes -he compound shown in formula [1-1]. [0025]
A coupling reaction with the compound shown in formula [1-1] gives: [0026]

[0027]
The compound shown in formula (II-l) can be cb-ained by above-mentioned coupling reaction. [0028]
The transition metal complex of the present includes, for example, a catalyst which can be used in a living radical polymerization method. In the method according to the present invention, the transition complex may be added directly to the system or a compound and a ligand compound therefof can be added system in order to form a transition metal complex system. [0029]
The central metals forming the transition metal complex include elements from Groups 7 to 11 of Periodic Table such as manganese, rhenium, iron, rhodium, nickel or copper (using the periodic table

disclosed :_n "Handbook of Chemistry Z, Basic, 4 th edition" (1993), edited by The Chemical Society Use cf copper and iron is preferred from among these with the use of copper being particularly preferred.
[0030]
Concretely, the copper complex includes copper conplexes having nitrogen-containing compounds as lig = r:ds, such as NH3, NO, NO2, N03, ethylenediamine, diethylenetriamine, tributylamine, 1,3-diisopropy--4,5-dimethylimidazol-2-ylidene, pyridine, phenanthroiine, diphenanthroline or substituted phenanthroiine, 2,2' : £' ,2"-terpyridine, pyridine imine, cross-linked aliphatic diamine, 4-4'-di(5-nonyl)-2,2'-bipyridine, thiocyanate, bipyridine coordinated with 0, S, Se or Te, iminodipyridine, alkylirainopyridine, alkylbipyridinylamine, alkyl-substituted tripyridine, di(alkylamino)alkyl pyridine, ethylenediamine dipyridine, tri (pyridinylmethyl; air.ine, N,N,N',N',N"-pentamethyl diethylene triaraine. Fur-hsrrr.ore, the copper complexes include copper complexes having nitrogen-containing compounds and/or halogen atom as ligands. Concretely, it includes acetyl-[4-4' -di(5-nonyl)-2,2'-bipyridine]copper, hexafluorophosphine-di[4-4'-di [0031]

The iron complex includes di(triphenylphosphine.! iron dichioride, di(tributylamino) iron dichloride, triphenylphosphine iron trichloride, (1-bromo) triethoxyphosphine-iron dibromide, (1-bromo)ethylbenzene-triphenylphosphine-iron dibromide, (1-bromo) ethyloenzene-[4-4' -di(5-nonyl)-2,2'-bipyridine] iron dibromide, il-bromo)ethylbenzene-tri-n-butylamino-iron dibromice, 1-bromo)ethylbenzene-tri-n-butylphosphine-iron dibromide, tri-n-butylphosphine-iron dibromide, ;4-4'-di(5-nonyl)-2,2' -bipyridine\ iron dibromide, tetraalkylammonium iron (II) trihalide, dicarbonylcyclopentadienyl iron (Hi iodide, dicarbonylcyclopentadienyl iron(II) bromide, dicarbonylcyclopentadienyl iron(I") chloride, dicarbonylinder.yl iron(II) iodide, dicarbonylinder.yl iron (II) bromide, dicarbonylindenyl iron(II) chloride, dicarbonylfluorenyl iron(II) iodide, dicarbonylfiucrenyl iron(II) bromide, dicarbonylfluorenyl iron(II) chloride, 1, 3-diisopropyl-4,5-dimethylimidazol-2-ylidene iron chloride and 1, 3-diisopropyl-4, 5-dimethylimidazol-2-y_.i oene iron bromide. [0032]
Other transition metal complexes include ru^neniurr. complexes such as dichlorotris(triphenylphosphine ruthenium, dichlorotris (tributylphosphine) ruthe-iur., dichloro(trialkylphosphine) p-cytnene ruthenium, dic'.iioro-

di(tricymenephosphine)styryl ruthenium,
dichloro (cyclooctadiene) ruthenium, dichlorobenzer_
ruthenium, dichloro p-cymene ruthenium,
dichloro(norbornadiene) ruthenium, cis-dichloro-bis (2,2'-
bipyridine) ruthenium, dichlorotris(1,lO-DhenanihroIine)
ruthenium, carbonylchlorohydridetris (triphenylphcspninei
ruthenium, chlorocyclopentadienylbis (triphenylphcsphiriei
ruthenium, chloroindenylbis(triphenylphosphine) ruthenium,
dihydrotetra(triphenylphosphine) ruthenium,
dicarbonylcyclopentadienyl ruthenium(ii) iodine,
di carbonylcyclopentadienyl ruthenium (H) bromide..
dicarbonylcyclopentadienyl ruthenium(II).chloride,
dicarbonylindenyl ruthenium {II) iodine, dicarbor.yiir.ier.yl
ruthenium(II) bromide, dicarbonylindenyl ruthenium ;
chloride, dicarbonylfluorenyl ruthenium(II) iodide,
dicarbonylfluorenyl ruthenium{II) bromide,
dicarbonylfluorenyl ruthenium (II) chloride and iichlcra-
di-2, 6-bis[(dimethylamino)-methyl] (u-N2) pyridine
ruthenium(II).
[0033]
Nickel complexes include carbonylcyclopentadienyl nickel (II) iodine, carbonylcyclopentadienyl nickalilli btomide, carbonylcyclopentadienyl nickel(II) chloride, c^rbonylindenyl nickel(II) iodine, carbonylindenyl nickel (II) bromide, carbonylindenyl nickel[II) cileries,

carbor.ylfluorenyl nickel(II) iodide, carbonylflucre^yl nickel{II) bromide, carbonylfluorenyl nickel{II. chloride, o,o'-ai(dimethylaminomethyl) phenyl nickel halide, di-triphenylphosphine nickel dibromide, di{tri-n-butyIamino; nickel dibromide, 1,3-diaminophenyl nickel bromide, diitri-n-butylphosphine) nickel dibromide and tetra (triphenylphosphine) nickel. [0034]
Further complexes include molybdenum complexes including tricarbonylcyclopentadienyl molybdenura [II,- iodine, tricarbonylcyclopentadienyl molybdenum(II) bromide, tricarbonylcyclopentadienyl molybdenum (II) chloride, di-N-aryl-di (2-dimethylaminomethylphenyl) lithium molybdenum, di-N-aryl-(2-dimethylaminomethylphenyl)-methyl-Liihiur. molybdenum, di-N-aryl-(2-dimethylaminomethylphenyl}-trimethylsilylmethyl-lithium molybdenum, di-N-aryl-[2-dimetbylaminomethylphenyl)-p-tolyl lithium molybdenum; tungsten complexes including tricarbonylcyclopentadienyl tungsten(II) iodine, tricarbonylcyclopentadienyl tungsten (II) bromide, tricarbonylcyclopentadienyl tungsten(II) chloride; cobalt complexes including dicarbonylcyclopentadienyl cobalt(I); manganese complexes including tricarbonylcyclopentadienyl manganese':.;, tricarbonyl (nethylcyclopentadienyl) manganese (Ij ; rr.&niurp. complexes including tricarbonylcyclopentadienyl rnenium(I),

dioxobis(triphenylphosphine) rhenium iodine; complexes including tri(triphenylphosphine) chloride; palladium complexes including triphenylrnos-r-ine diacetyl palladium. These transition metal complexes rr.sy be used singly or in combination. [0035]
The amount of transition metal compound added depends on the type of compound. However it is generally preferable to add 0.1 to 5 equivalents to the compound acting as a raw material represented by formula {I) and more preferably to add 0.3 to 1 equivalents. [0036]
In the method according to the present invg:. from the point of improving catalyst activity, it is preferable to perform the coupling reaction in the presence of a base. The base may be organic or inorganic. Organic bases include amines such as aliphatic amines or amines. Inorganic bases include alkali metal hydroxides or carbonates and alkaline earth metal oxides or carbonates. [0037]
There is no particular limitation en the organic solvent used in the reaction and it includes aromatic hydrocarbons such as benzene, toluene and xylene; aliphatic hydrocarbons such as hexane, heptane and octane; hydrocarbons such as cyclopentane, cyclohexane ar.c

cyclooctane; ketones such as acetone, methyl ethyl ketone and cyclohexanone; ethers such as tetrahydrofuran and dicxar.e; esters such as ethyl acetate and butyl scerate; amides such as N,N-dimethylformamid@ and N,N-dimethylacetamide; sulfoxides such as dimethylsulfoxide; alcohol such as methanol and ethanol; polyvalent alcohol derivates such as ethylene glycol monomethyl ethylene glycol monomethyl ether acetate. These solvents may be used singly or in combination. [0038]
The reaction temperature is normally from room temperature to 150DC and preferably from 60 to 12 0iC. The reaction is normally performed under ordinary pressure or under pressurized conditions. Furthermore the reaction should proceed in an extremely short time and should reach completion in 3 to 90 minutes and preferably approximately 5 to 30 minutes. In this manner, the method cf production of the present invention can produce the target compound in an extremely efficient manner. The reaction can be terminated by lowering the reaction temperature. After terminating the reaction, the target compound can be isolated by normal isolation and purification methods such as recrystallization, column purification, depressrrizatrcr, purification and filtration. [0039]

In the method of the present invention, when a produced compound represented by formula (II) substituents such as COOR1, S02R2, OR3, SR4 or the benzene ring, active hydrogen is produced by treatment and it is possible to convert the into COOH, S02E, OH, SH or NH2. Furthermore, after hydrolysis in the presence of a base, it is possible :c convert the substituents into OH or SH. Acids usee in an acid treatment include inorganic acids such as hydrochloric acid, bromic acid, sulfuric acid, nitric acid, bcric acid, methanesulfonic acid or organic acids such as The temperature during acid treatment is not particularly limited and may, for example, be in the range of ~1CCC -0 lSO^C. The base may be organic or inorganic. Organic bases include, for example, amines such as alipnatic amines and aromatic amines. Inorganic bases include alkali metal hydroxides or carbonates and alkaline earth metal oxidss and carbonates.
[0040]
The present invention will be described in further detail hereafter. However the scope of the invention is not limited to the examples. Example 1
[0041]

[0042]
0.39 g (1 mmol} of PhCOOEt2-Br, 0.14 g (1 rrcnol) of CuBr, 0.25 g (4 mmol) of Cu(0) and 20 ml of toluene -,;ere charged into a 50 ml reaction flask. After degassing th_e solution, 0.35 g (2 mmol) of N,N,N',N',N"-pentaniethyldiethylenetriamine was added. The mixture "was stirred at 80°C for 0.5 h and cooled to room temperar.ar=. The insoluble matter was filtered and the reaction was washed with water until the coloring was removed completely from the water layer, and dried over sulfate. The solvent was removed under reduced pressure give 0.30g of a white powder solid, finally,
(isolated yield 97%). Example 2
[0043]

[0044]
1.15 g (5 mmol) of methyl 4-(bromomethyl)banzcaig, 0.72 g (5 raraol) of CuBr, 1.27 g (20 mmol) of Cu(0}, _.56 r (10 mmol) of bipyridine and 20 mL of toluene were charged into a 30 mL reaction flask. After degassing the solution, the mixture was stirred at 100°C for 1 h and cooled to room temperature. 10 mL of chloroform was added, and tr_e insoluble matter was filtered and the reaction nurture WHS washed with water and dried over magnesium sulfate. "The solvent was removed under reduced pressure and the crude product was recrystallized from ethyl acetate/hexans. The crystal thereby obtained was dried under reduced pressure to obtain 0.32 g of a faintly yellow crystal (isolates yield 43%). Example 3 [0045]

9.6 g (48 iranol) of bis(4-hydroxyphenyi)methane. 11.5 g (117 irimol) of triethylamine, 200 mL of tetrahy^rcf-irsr, were charged into a 200 mL reaction flask and cooled 14.9 g (106 nmol) of benzoyl chloride was added mixture was stirred at room temperature for 1 hour. Triethylamine hydrochloride was removed by the reaction mixture was evaporated. After the residue

washed with water for three times, and dried over sulfate. After removal of solvent under reduced pressure, the crude product was recrystallized from hexane, ethyl acetate to give 16.8 g of a faintly yellow needle crystal A (isolated yield 86%;.
14.4 c (35 mmol) of the crystal A, 6.5 g (37 of N-bromosuccinimide, and 70 ml of benzene were charged into a 200 rnL reaction flask and refluxed for 1 hour. After cooling, the reaction mixture was concentrated under reduced pressure. The residue was dissolved in methylene chloride, washed with water for three times, and drisd over magnesium sulfate. After removal of solvent under reduced pressure, the crude product was recrystallized from etnyl acetate to give 11.7 g of a white floccular crystal 3 (isolated yield 68%).
4.9 g (10 mmol) of the crystal B, 0.7 g (5 CuBr, 1.3 g (20 mmol) of Cu, and 50 mL of toluene were charged into a 100 mL reaction flask. After deg£.sstng the solution and heating the solution to 80°C, 1.8 g ;i3 mmol; of N,N,N' ,W ,N"-per.taraethyl diethylene triaraine was added. The mixture was stirred at 80°C for 0.5 h and coded :: room temperature. The reaction mixture was filtered =nd the insoluble matter was washed with water for three times. 100 mL of chloroform was added to the insoluble matter, end refluxed for 10 minutes and filtered while still hct.

After the concentration of the filtrate, the was washed with ethyl acetate to give 3.1 g of 2 floccular crystal C (isolated yield 76%).
Then 2.6 g (3-2 miriol) of the crystal C, and of toluene were charged into 100 mL reaction flask, Hydrolysis products saponified in the presence of potassium. hydroxide and water were purified to give 1.1 g (2.8 mmol) powder of 1,1, 2, 2-tetrakis (4-hydroxyphenyl) ethane

CLAIMS
1. A method for producing a 1,2-phenylethane compound which comprises subjecting a compound represented by formula (I):

wherein Ra represents a hydrogen atom or a substituted or unsubstituted phenyl group; Rb represents a hydcoren atom or a subs tit uer.t; n represents an integer of 1 to 5 and when n is 2 or more, Kb may be the same or different, or may be combined with each other to form a ring; and X represents a halogen atom; to a coupling reaction in the presence of a transition metal complex to produce a compound represented by formula (II):

2. The method for producing a 1,2-phenylethane compcunc according to claim 1, wherein Ra is a substituted or unsubstituted phenyl group.
3. The method for producing a 1,2-phenylethane compound according to claim 1 or 2, wherein the substituer.t of -he phenyl graup represented by Ra cr the substituent represented by Rb is COOR1, S02R2, OR3, SR* or R1 to R6 represent a hydrogen atom or an organic -group.
4. The method for producing a 1,2-phenylethane ccmpcund according to claim 1 or 2, wherein the compound by formula (I) is a compound represented by formula

5. The method for producing a 1,2-phenylethans ccrapound
according to claim 4, wherein Rb in formula (1-1) or (II-l)
is OR3 or COOR1.
6. The method for producing a 1,2-phenylsthane compound
according to claim 1 or 2, wherein the transit
complex is a copper complex or an iron complex.

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Patent Number

260497

Indian Patent Application Number

4892/CHENP/2008

PG Journal Number

18/2014

Publication Date

02-May-2014

Grant Date

01-May-2014

Date of Filing

15-Sep-2008

Name of Patentee

NIPPON SODA CO., LTD.

Applicant Address

2-1, OHTEMACHI 2-CHOME, CHIYODA-KU, TOKYO,1008165

Inventors:

#	Inventor's Name	Inventor's Address
1	NIITANI, TAKESHI ,	C/O NIPPON SODA CO., LTD. T&D LABORATORY FOR HIGH-PERFOMANCE MATERIALS, 12-54, GOINMINAMIKAIGAN, ICHIHARA-SHI, CHIBA-KEN,

PCT International Classification Number

C07C67/343

PCT International Application Number

PCT/JP07/55393

PCT International Filing date

2007-03-16

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	2006-074463	2006-03-17	Japan