CN103068795A - Method for preparing diamine precursor compound - Google Patents
Method for preparing diamine precursor compound Download PDFInfo
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- CN103068795A CN103068795A CN2011800388702A CN201180038870A CN103068795A CN 103068795 A CN103068795 A CN 103068795A CN 2011800388702 A CN2011800388702 A CN 2011800388702A CN 201180038870 A CN201180038870 A CN 201180038870A CN 103068795 A CN103068795 A CN 103068795A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C269/06—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B61/00—Other general methods
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/20—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by nitrogen atoms not being part of nitro or nitroso groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Abstract
Provided is an inexpensive, simple, and efficient method for preparing, from a starting material, a nitro compound constituting a diamine precursor compound which is a starting material for producing a polyamic acid and/or polyimide. Compound (1) is reacted according to reaction formula (1) with di-tert-butyl dicarbonate ((Boc)2O) to produce compound (2) (1) (where R1 represents -CH2COOR or -CH2Ph(-Z)m (where Z is a substituent group for a phenyl group (Ph) and m ranges from 0 to 5), and R represents a lower alkyl group or alkali metal atom), compound (2) is then reacted according to reaction formula (2) with H-A-CH2-X to produce compound (3) (2) (where A represents -C=C- or -CH=CH-, and X represents a leaving substituent group), and compound (3) is then subjected to a coupling reaction according to reaction formula (3) with compound (4) to produce compound (5) (3); (where Y represents a leaving substituent group).
Description
Technical field
The present invention relates to easy by raw material cheaply and make efficiently precursor---the novel method of nitro-compound as the specific diamine compound of the manufacturing raw material of the polyimide that is used for liquid crystal aligning agent etc.
Background technology
Polyimide is widely used as the electronic material of protecting materials, insulating material, colored filter etc. in liquid crystal display device and the semi-conductor because of high mechanical strength, thermotolerance, insulativity, solvent resistance as its speciality.Particularly nearest, polyimide also is widely used as being formed for the liquid crystal aligning agent of the liquid crystal orientation film of the state of orientation of control liquid crystal in the liquid crystal display device used in LCD TV, liquid-crystal display etc.
Liquid crystal orientation film by with the liquid crystal aligning agent solution coat take the polyimide precursors such as polyamic acid or soluble polyimide as main component in the electrode base board of glass etc. and burn till, for the surface of the polyimide film of gained with the cloth of cotton, nylon, polyester etc. towards a direction friction, namely carry out friction treatment and form.
The friction treatment of polyimide film is being essential aspect the characteristic of performance liquid crystal orientation film, but finds gradually in this friction treatment to produce the variety of issue such as inhomogeneous in the face that impact because of damage, dust, mechanical force or the static on liquid crystal orientation film surface causes orientation process.Particularly nearest, based on to requirement of the high performance of liquid crystal display device, high-precision refinement, maximization etc., more and more strict for the reply of the problem that produces in the friction treatment.
On the other hand, for the friction treatment of polyimide liquid crystal orientation film, propose to have various acquisitions to control that damage produces or the method for the liquid crystal orientation film that film is peeled off.For example, propose to have the method (with reference to patent documentation 1, patent documentation 2) of the liquid crystal aligning agent that adopts the linking agents such as compound that in polyamic acid and/or polyimide, are added with the compound that contains epoxy group(ing), have epoxy group(ing) and the reactive group except epoxy group(ing).
As the also polyimide of easy damaged not in described friction treatment, the applicant proposes to use the polyimide liquid crystal aligning agent (with reference to patent documentation 3) of specific diamine compound in the early time.This liquid crystal aligning agent comprises the diamine compound that uses with the tert-butoxycarbonyl protection that breaks away from by heating, itself and tetracarboxylic dianhydride is reacted and the polyamic acid and/or the polyimide that get.In the situation of this liquid crystal aligning agent, in the sintering process of its manufacturing, tert-butoxycarbonyl breaks away from by heating, the fatty amine that formation reaction is high, this fatty amine become crosslink sites and the surface that makes film firmly, carry out the also liquid crystal orientation film of easy damaged not of friction treatment even can provide.
In the polyamic acid that discloses in the above-mentioned patent documentation 3 and/or the manufacturing of polyimide, as the diamine compound that contains tert.-butoxy (the following Boc yl that also claims), use with the diamine compound shown in the following formula 21.The starting raw material of this diamine compound is as follows, is propargylamine (the HC ≡ CCH of the high and difficult acquisition of price
2NH
2).And, in the purifying as the nitro-compound of the precursor compound of diamine compound, need to be not suitable for the column operation of the enforcement that industrialization makes.
[changing 1]
The prior art document
Patent documentation
Patent documentation 1: Japanese patent laid-open 9-146100 communique
Patent documentation 2: Japanese Patent Laid-Open 2007-11221 communique
Patent documentation 3: international open WO2010/050523 text
The summary of invention
Invent technical problem to be solved
The object of the present invention is to provide easy by raw material cheaply and make efficiently precursor---the novel method of nitro-compound as the diamine compound that contains tert-butoxycarbonyl (Boc yl) of the raw material of the polyamic acid that is used for liquid crystal aligning agent etc. and/or polyimide.
In addition, the present invention also provides the method that is contained the diamine compound of tert-butoxycarbonyl by the nitro-compound manufacturing as the precursor compound of diamine compound.
The technical scheme that the technical solution problem adopts
The present invention has carried out conscientiously research to achieve these goals, has finished the new manufacturing method with following technology contents.Described manufacture method comprises new compound in its process as described later.
1. make the method with the diamine precursor compound of formula 5 expressions, wherein, according to following reaction formula (1), make compound and tert-Butyl dicarbonate ((Boc) with formula 1 expression
2O) compound with formula 2 expressions is made in reaction, in the formula, and R
1For-CH
2COOR or-CH
2Ph (Z)
m, R is low alkyl group or alkali metal atom, and Ph is phenyl, and Z is the substituting group of phenyl (Ph), and m is 0～5;
According to following reaction formula (2), make gained with the compound of formula 2 expression under alkali and with H-A-CH
2The compound that-X represents reacts to make the compound with formula 3 expressions, in the formula, A is-C ≡ C-or-CH=CH-, X is the detachment substituting group;
Then, according to following reaction formula (3), make carrying out linked reaction with the compound of formula 3 expression and compound with formula 4 expressions and making diamine precursor compound with formula 5 expressions of gained, in the formula, Y is the detachment substituting group;
[changing 2]
2. as above-mentioned 1 described method, wherein, take the compound of formula 1 expression as tert-butyl glycinate or its salt or benzylamine or its salt.
3. such as above-mentioned 1 or 2 described methods, wherein, described linked reaction is carried out under the coexistence of metal complex, part and alkali.
As above-mentioned 1～3 in each described method, wherein, described linked reaction is containing tertiary phosphine or uncle's phosphorous acid ester (3
Off ォ ス ワ ァ ィ ト) carries out under the coexistence as the palladium complex of part.
5. as each the described method in above-mentioned 1～4, wherein, the Y in the compound of formula 4 expression is as Br, I or trifluoromethanesulfonic acid ester group.
As above-mentioned 1～5 in each described method, wherein, with H-A-CH
2X in the compound that-X represents is halogen or sulfonate group.
7. as above-mentioned 1 described method, wherein, with H-A-CH
2The compound that-X represents is propargylic halide or allyl halide.
8. make the method with the diamine compound of formula 6 expressions, wherein, according to following reaction formula (4), the compound with formula 5 expressions that will obtain by each the described method in above-mentioned 1～7 was also made the diamine compound with formula 6 expressions originally, in the formula, and R
2For hydrogen atom or-CH
2COOR, R are low alkyl group;
[changing 3]
9. the ester cpds that represents with following formula;
[changing 4]
10. the nitro-compound that represents with the arbitrary formula in following;
[changing 5]
The effect of invention
If employing the present invention then can provide easy by starting raw material cheaply and make efficiently precursor---the novel method of nitro-compound as the diamine compound that contains tert-butoxycarbonyl of the raw material of the polyamic acid that is used for liquid crystal aligning agent etc. and/or polyimide.
In addition, if adopt the present invention, then can provide the method that is contained the diamine compound of tert-butoxycarbonyl by the nitro-compound manufacturing as the precursor compound of the diamine compound of manufacturing.
In addition, if adopt the present invention, then can provide following new compound.
[changing 6]
The mode that carries out an invention
Below, the present invention will be described in more detail.
A. will be with the manufacturing with the compound of following formula 2 expressions as raw material of the compound of following formula 1 expression
Will be with the compound of formula 1 expression as raw material, make its with (Boc)
2O (tert-Butyl dicarbonate) reacts, thereby makes the compound that represents with formula 2 according to reaction formula (1).
In the formula 1, R
1For-CH
2COOR or-CH
2Ph (Z)
m, R is low alkyl group or alkali metal atom, and Ph is phenyl, and Z is the substituting group on the phenyl (Ph), and m is 0～5.
Here, low alkyl group refers to the alkyl of carbon number 1～6, better is the alkyl of carbon number 1～4, particularly preferably-and CH
2CO
2-tert-Bu (tertiary butyl).As basic metal, better be lithium, sodium or potassium, particularly preferably sodium or potassium.
Z is the substituting group on the phenyl, is fluorine atom, nitro, carboxyl, ester group, cyano group or C
1-4Alkoxy carbonyl better is methoxyl group or nitro.
M is 0～5, better is 0～2.
At R
1For-CH
2CO
2In the situation of-tert-Bu, take the compound of formula 1 expression as tert-butyl glycinate or its salt; At R
1For-CH
2In the situation of Ph, take the compound of formula 1 expression as benzylamine or its salt.These tert-butyl glycinates or its salt and benzylamine or its salt and propargylamine (HC ≡ CCH
2NH
2) etc. difference, easily obtain, cost is low.
[changing 7]
The reaction that obtains above-mentioned compound with formula 2 expressions better is to carry out in the presence of alkali.As alkali, can use the mineral alkalis such as sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium bicarbonate, saleratus, potassiumphosphate, yellow soda ash, salt of wormwood, Quilonum Retard, cesium carbonate, the amines such as Trimethylamine 99, triethylamine, tripropyl amine, tri-isopropyl amine, Tributylamine, diisopropylethylamine, pyridine, quinoline, trimethylpyridine, sodium hydride, potassium hydride KH, sodium tert-butoxide, potassium tert.-butoxide etc.
As the compound with formula 1 expression, use in the situation of free amine, even there is not alkali, reaction also can be carried out, but uses in the situation of alkali, considers the operability of the aftertreatment of reaction, better is to use amine.
As reaction solvent, so long as stable under the reaction conditions, inertia, do not hinder the solvent of goal response to get final product, can use arbitrarily solvent.For example, can use the non-proton property polar organic solvents such as dimethyl formamide, methyl-sulphoxide, dimethyl acetic acid ester, N-Methyl pyrrolidone, diethyl ether, isopropyl ether, THF (tetrahydrofuran (THF)), TBME (t-butyl methyl ether), CPME (cyclopentyl-methyl ether), two
The ethers such as alkane, the aliphatic hydrocarbons such as pentane, hexane, heptane, sherwood oil, the aromatic hydrocarbonss such as benzene,toluene,xylene, sym-trimethylbenzene, chlorobenzene, dichlorobenzene, oil of mirbane, tetraline, the halogen hydrocarbon such as chloroform, methylene dichloride, tetracol phenixin, ethylene dichloride, the low-grade fatty acid esters such as methyl acetate, ethyl acetate, butylacetate, methyl propionate, the nitriles such as acetonitrile, propionitrile, butyronitrile etc.
These solvents can consider that the easy generation of reacting etc. suitably selects, and can use separately to mix more than a kind or 2 kinds and use.Above-mentioned solvent is used as water-free solvent after also can using suitable dewatering agent or siccative.
Temperature of reaction can preferably be selected the temperature range till the boiling temperature of the reaction solvent that extremely uses more than-100 ℃, is more preferably-50～150 ℃, particularly preferably 0～60 ℃.Reaction times better is 0.1～1000 hour, is more preferably 0.5～50 hour.
By above-mentioned reaction formula (1) obtain can be by the purifying such as column chromatography of distillation, recrystallization or silica gel etc. with the compound of formula 2 expression, but also purifying and be directly used in subsequent processing not.
Make like this take the preferred example of the compound of formula 2 expressions as Boc-NHCH
2COO-tert-Bu or Boc-NHCH
2Ph (Z) m; Wherein, Z is the substituting group on the phenyl, is fluorine atom, nitro, carboxyl, ester group, cyano group or C
1-4Alkoxy carbonyl, m are 0～5.
B. by the manufacturing with the compound of following formula 3 expressions with the compound of following formula 2 expressions
By the compound with formula 2 expression that obtains by above-mentioned reaction formula (1), by make its in the presence of alkali with H-A-CH
2-X reacts, thereby makes the compound that represents with formula 3 according to following reaction formula (2); In the formula, A is-C ≡ C-or-CH=CH-, X is the substituting group that tool breaks away from ability.
[changing 8]
In the situation that A is-C ≡ C-above-mentioned H-A-CH
2-X is the propargylation agent; In the situation that A is-C=C-above-mentioned H-A-CH
2-X is the allylation agent.X is the substituting group that tool breaks away from ability, such as being the halogens such as F, Cl, Br, I, tosic acid ester group (OSO
2C
6H
4-p-CH
3), methylsulfonic acid ester group (OSO
2CH
3), trifluoromethanesulfonic acid ester group (OSO
2CF
3) etc. the sulphonate base class, acetate groups (OCOCH
3), (the organic acid ester group such as OCOPh) is with methoxycarbonyl oxygen base (OCO for the phenylformic acid ester group
2CH
3), ethoxy carbonyl oxygen base (OCO
2CH
2CH
3), isopropoxy carbonyl oxygen base (OCO
2CH (CH
3)
2), phenyloxycarbonyl oxygen base (OCO
2Ph) for the carboxylic acid ester groups of representative etc.Wherein, from reactive angle, better be halogen or sulfonate group.
As the alkali that is used for reaction, can use the mineral alkalis such as sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium bicarbonate, saleratus, potassiumphosphate, yellow soda ash, salt of wormwood, Quilonum Retard, cesium carbonate, the alkali such as sodium tert-butoxide, potassium tert.-butoxide, sodium hydride, potassium hydride KH, the amine such as Trimethylamine 99, triethylamine, tripropyl amine, tri-isopropyl amine, Tributylamine, diisopropylethylamine, pyridine, quinoline, trimethylpyridine.Wherein, better be sodium tert-butoxide, potassium tert.-butoxide, sodium hydride, potassium hydride KH etc.
As reaction solvent, so long as stable under the reaction conditions, inertia, do not hinder the solvent of goal response to get final product, can use arbitrarily solvent.For example, can use the non-proton property polar organic solvents such as dimethyl formamide, methyl-sulphoxide, dimethyl acetic acid ester, N-Methyl pyrrolidone, diethyl ether, isopropyl ether, THF, TBME, CPME, two
The ethers such as alkane, the aliphatic hydrocarbons such as pentane, hexane, heptane, sherwood oil, benzene,toluene,xylene, sym-trimethylbenzene, chlorobenzene, dichlorobenzene, oil of mirbane, tetraline etc. are aromatic hydrocarbon based, the halogen hydrocarbon such as chloroform, methylene dichloride, tetracol phenixin, ethylene dichloride, the low-grade fatty acid esters such as methyl acetate, ethyl acetate, butylacetate, methyl propionate, the nitriles such as acetonitrile, propionitrile, butyronitrile.
These solvents can consider that the easy generation of reacting etc. suitably selects, and can use separately to mix more than a kind or 2 kinds and use.In addition, according to circumstances, above-mentioned solvent is used as water-free solvent after also can using suitable dewatering agent or siccative.
In addition, carry out more efficiently in order to make above-mentioned reaction, also can add the iodide such as iodate tetra-n-butyl ammonium, sodium iodide, potassiumiodide.
Temperature of reaction can preferably be selected to be more preferably-50～150 ℃ from the temperature range till the boiling temperature of the reaction solvent that uses more than-100 ℃, particularly preferably-20～100 ℃.Reaction times better is 0.1～1000 hour, is more preferably 0.5～50 hour.
By above-mentioned reaction formula (2) obtain can be by the purifying such as column chromatography of distillation, recrystallization or silica gel etc. with the compound of formula 3 expression, but also purifying and be directly used in subsequent processing not.
Make like this take the preferred example of the compound of formula 3 expression as Boc-N (CH
2C ≡ CH) CH
2COOt-Bu, Boc-N (CH
2C ≡ CH) CH
2Ph (Z) m, Boc-N (CH
2CH=CH
2) CH
2COOt-Bu or Boc-N (CH
2CH=CH
2) CH
2Ph (Z) m.Here, Z is the substituting group on the phenyl, is fluorine atom, nitro, carboxyl, ester group, cyano group or C
1-4Alkoxy carbonyl, m are 0～5.
In the compound with formula 3 expressions, following ester cpds is new compound before the application.
[changing 9]
C. by the manufacturing with the compound of following formula 5 expressions with the compound of following formula 3 expressions
By the compound with formula 3 expressions that obtains by above-mentioned reaction formula (2), under the coexistence of metal complex, part and alkali, with the Hang Yuan head reaction of the compound Jin that represents with formula 4 (Japanese: Yuan Head
) or the linked reaction such as He Ke reaction, make the compound with formula 5 expressions.
[changing 10]
In the compound with formula 4 expressions, Y is the substituting group that tool breaks away from ability, such as being the halogens such as F, Cl, Br, I, tosic acid ester group (OSO
2C
6H
4-p-CH
3), methylsulfonic acid ester group (OSO
2CH
3), trifluoromethanesulfonic acid ester group (OSO
2CF
3) etc. sulfonate group etc.Wherein, from reactive angle, better be Br, I or trifluoromethanesulfonic acid ester group.
In this reaction, form the metal-complexing catalyzer with suitable metal complex and part and use.Usually, as metal complex, using palladium complex and nickel complex, according to the difference of reaction, better is that copper catalyst is coexisted as promotor sometimes.
As the metal-complexing catalyzer, can use the catalyzer of various structures, better be palladium complex or the nickel complex that uses so-called low valence, particularly preferably with tertiary phosphine or the uncle's phosphorous acid ester zero-valent metal coordination catalyst as part.In addition, also can use the suitable precursor that easily is converted into the zero-valent metal coordination catalyst in the reaction system.In addition, also can be in reaction system, mix as the metal complex of part with as tertiary phosphine or uncle's phosphorous acid ester of part not containing tertiary phosphine or uncle's phosphorous acid ester, generate tertiary phosphine or the uncle's phosphorous acid ester low valence metal-complexing catalyzer as part.
Tertiary phosphine or uncle's phosphorous acid ester as part can exemplify for example triphenyl phosphine, tri-o-tolyl phosphine, diphenyl methyl phosphine, phenyl dimethyl phosphine, 1, two (diphenylphosphino) ethane, 1 of 2-, two (diphenylphosphino) propane, 1 of 3-, two (diphenylphosphino) butane, 1,1 ' of 4--two (diphenylphosphino) ferrocene, trimethyl phosphite, triethyl-phosphite, triphenyl phosphite etc.Also can preferably use and mix the metal-complexing catalyzer more than 2 kinds that contains these parts.
As the metal-complexing catalyzer, also better be that the palladium complex that will not contain tertiary phosphine or uncle's phosphorous acid ester is used in combination with the metal complex that contains tertiary phosphine or uncle's phosphorous acid ester.In this situation, above-mentioned part capable of being combined also.As the palladium complex that does not contain tertiary phosphine or uncle's phosphorous acid ester, can exemplify two (benzylidene-acetone) palladiums, three (benzylidene-acetones), two palladiums, two (acetonitrile) dichloro palladium, two (benzonitrile) dichloro palladium, acid chloride, Palladous chloride, palladium-gac etc.In addition, be the palladium complex of part as containing tertiary phosphine or uncle's phosphorous acid ester, can exemplify (ethylidene) two (triphenyl phosphine) palladium, four (triphenyl phosphine) palladium, two (triphenyl phosphine) dichloro palladium etc.
The usage quantity of these palladium complexs is preferably so-called catalytic amount, better is below 20 % by mole, particularly preferably below 10 % by mole with respect to the compound that represents with formula 4.The copper catalyst that uses as promotor simultaneously better is the reagent of 1 valency, can exemplify such as cupric chloride (I), cupric bromide (I), cupric iodide (I), venus crystals (I) etc.
As alkali, can use the mineral alkalis such as sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium bicarbonate, saleratus, potassiumphosphate, yellow soda ash, salt of wormwood, Quilonum Retard, cesium carbonate, the amine such as methylamine, dimethylamine, Trimethylamine 99, ethamine, diethylamine, triethylamine, propylamine, dipropyl amine, tripropyl amine, Isopropylamine, Diisopropylamine, tri-isopropyl amine, butylamine, dibutylamine, Tributylamine, diisopropylethylamine, pyridine, imidazoles, quinoline, trimethylpyridine, tetramethyleneimine, piperidines, morpholine, N-methylmorpholine, sodium acetate, potassium acetate, lithium acetate etc.
In the situation as the terminal acetylide take the A of the compound of formula 3 expression as-C ≡ C-of raw material, also can use in advance organolithium, organic-magnesium, organic zinc etc. to make metallic acetylide (L as alkali
nM-C ≡ C-), again this metallic acetylide is used for reaction; In the formula, M is metal, and L is part, and n is nonzero integer.As M, can exemplify Li, Mg, Zn, Sn, B etc.As L, can exemplify F, Cl, Br, I, OH, C
1-6Alkoxyl group etc.
As reaction solvent, so long as stable under this reaction conditions, inertia, do not hinder the solvent of reaction to get final product, can use arbitrarily solvent.As reaction solvent, can make water, alcohols, amine, the non-proton property polar organic solvents such as dimethyl formamide (DMF), methyl-sulphoxide (DMSO), N,N-DIMETHYLACETAMIDE (DMAc), N-Methyl pyrrolidone (NMP), Et
2O, i-Pr
2O, TBME, CPME, THF, two
The ethers such as alkane, the aliphatic hydrocarbons such as pentane, hexane, heptane, sherwood oil, benzene,toluene,xylene, sym-trimethylbenzene, chlorobenzene, dichlorobenzene, oil of mirbane, tetraline etc. are aromatic hydrocarbon based, the halogen hydro carbons such as chloroform, methylene dichloride, tetracol phenixin, ethylene dichloride, the low-grade fatty acid ester classes such as methyl acetate, ethyl acetate, butylacetate, methyl propionate, the nitriles such as acetonitrile, propionitrile, butyronitrile etc.These solvents can consider that the easy generation of reacting etc. suitably selects, and can use separately to mix more than a kind or 2 kinds and use.In addition, according to circumstances, above-mentioned solvent is used as water-free solvent after also can using suitable dewatering agent or siccative.
Temperature of reaction can preferably be selected the temperature range till the boiling temperature of the reaction solvent that extremely uses more than-100 ℃, is more preferably-50～150 ℃, particularly preferably 20～150 ℃.Reaction times better is 0.1～1000 hour, is more preferably 0.5～100 hour.
Can be by the purifying such as column chromatography of distillation, recrystallization or silica gel etc. by the compound with formula 5 expressions that above-mentioned reaction formula (3) obtains.Recrystallization better is to carry out under alap temperature.
In the compound with formula 5 expressions of making like this, 3 kinds of following compounds are new compound before the application.
[changing 11]
D. by the manufacturing with the diamines of following formula 6 expressions with the compound of following formula 5 expressions
[changing 12]
By the compound with formula 5 expressions that obtains by above-mentioned reaction formula (3), the nitro that its phenyl ring has and the unsaturated link(age) of pendant moiety thereof are reduced, or benzyl is reduced in the certain structures, makes the diamines that represents with formula 6 according to above-mentioned reaction formula (4).In the compound with formula 6 expression, with the R of the compound of formula 5 expressions
1In the situation for benzyl, R
2Be hydrogen atom, R
1Be CH
2In the situation of COOR, R
2Also be CH
2COOR.R is low alkyl group, for the low alkyl group in this situation, and applicable and R
1The identical explanation of situation.
Method as the reduction of above-mentioned compound with formula 5 expression, use palladium-gac or platinum-gac etc. are arranged as the hydrogenation of catalyzer, the reduction reaction of under the coexistence of Fe, Sn, Zn or their salt and proton, carrying out, with the reduction reaction of formic acid as hydrogen source, with hydrazine as reaction of hydrogen source etc.In addition, also these reaction combinations can be implemented.
In the reduction reaction of above-mentioned example, being with the structure of the compound of formula 5 expression and the reactivity of reduction reaction if consider substrate, better is to use hydrogenation.
As the catalyzer that uses, the Activated Carbon Supported metal that has the commercially available product of can be used as to obtain, such as palladium-gac, platinum-gac, rhodium-gac etc.In addition, can be palladium hydroxide, platinum oxide, Raney nickel etc. also, might not be the metal catalyst of Activated Carbon Supported type.Even adopt the palladium-gac that generally is widely used, also can obtain good result.
As reaction solvent, so long as stable under the reaction conditions, inertia, do not hinder the solvent of goal response to get final product, can use arbitrarily solvent.For example, can use the non-proton property polar organic solvents such as dimethyl formamide, methyl-sulphoxide, dimethyl acetic acid ester, N-Methyl pyrrolidone, diethyl ether, isopropyl ether, THF, TBME, CPME, two
The ethers such as alkane, the aliphatic hydrocarbons such as pentane, hexane, heptane, sherwood oil, the aromatic hydrocarbonss such as benzene,toluene,xylene, sym-trimethylbenzene, chlorobenzene, dichlorobenzene, oil of mirbane, tetraline, the halogen hydrocarbon such as chloroform, methylene dichloride, tetracol phenixin, ethylene dichloride, the low-grade fatty acid esters such as methyl acetate, ethyl acetate, butylacetate, methyl propionate, the nitriles such as acetonitrile, propionitrile, butyronitrile.
These solvents can consider that the easy generation of reacting etc. suitably selects, and can use separately to mix more than a kind or 2 kinds and use.In addition, according to circumstances, above-mentioned solvent is used as water-free solvent after also can using suitable dewatering agent or siccative.
For above-mentioned reduction reaction is more effectively carried out, also can under the coexistence of gac, implement reaction.The amount of the gac that uses in this situation is not particularly limited, and as 1～20 % by weight, is more preferably 1～10 % by weight with respect to the compound that represents take formula 5
In addition, more effectively carry out in order to make reaction, also can implement reaction adding to depress.In this situation, for fear of the reduction of benzene nucleus, better be to implement reaction in the pressurization scope, the scope till being more preferably 10 normal atmosphere about 20 normal atmosphere (kgf).
Temperature of reaction can preferably be selected the temperature range till the boiling temperature of the reaction solvent that extremely uses more than-100 ℃, is more preferably-50～150 ℃, particularly preferably 0～80 ℃.Reaction times better is 0.1～1000 hour, is more preferably 1～200 hour.
Can be by the purifying such as column chromatography of distillation, recrystallization or silica gel etc. by the compound with formula 6 expressions that above-mentioned reaction formula (4) obtains.
The preferred example with the compound of formula 6 expression of making like this is R
2For hydrogen atom or with CH
2The compound that COOt-Bu represents.
Embodiment
Below, by embodiment the present invention is carried out more specific description, but explanation of the present invention is not subjected to the restriction of these embodiment.The analytical equipment and the analysis condition that adopt among the embodiment are as follows.
1H-NMR and
13C-NMR;
Device: 400 NB of Varian NMR system (400 MHz)
Measure solvent: CDCl
3, DMSO-d
6
Primary standard: tetramethylsilane (TMS) (the δ value of the 1H of TMS is made as 0.0 ppm)
CDCl
3(with CDCl
3 13The δ value of C is made as 77.0 ppm)
Embodiment 1 (example of reaction formula (1))
[changing 13]
Toluene (46.2 mL) suspension of glycine tert-butyl hydrochloride 9 (10.0 g, 59.7 mmol) is remained on 60 ℃, add triethylamine (6.51 g, 64.3 mmol), stirred 0.5 hour.Then, toluene (11.6 mL) solution of tert-Butyl dicarbonate (10.0 g, 45.9 mmol) is splashed into reaction mixture, make its reaction 6 hours.
Then, add entry (30 mL) after, separate organic layer.Then, heat up in a steamer desolventizing from organic layer, carry out recrystallization by normal hexane, obtain N-Boc-tert-butyl glycinate 10 (10.6 g, 45.9 mmol, 100% yields).The structure of resultant is passed through
1The H-NMR analysis confirmation.
1H-NMR?(CDCl
3):?δ?4.98?(b-s,?1H,?NH),?3.79?(d,?2H,?J=5.6?Hz,NCH
2CO
2-tert-Bu),?1.52-1.40?(m,?18H,?(tert-Bu)?×2).
Embodiment 2 (example of reaction formula (1))
[changing 14]
Toluene (10 L) suspension of glycine tert-butyl hydrochloride 9 (1.258 kg, 7.505 mol) is remained on 10 ℃, add triethylamine (0.9113 kg, 9.006 mol), stirred 1 hour.Then, tert-Butyl dicarbonate (1.474 kg, 6.754 mol) is splashed into reaction mixture, make its reaction 3 hours.
Then, after adding entry (5 L) reaction being stopped, separating organic layer.Then, heat up in a steamer desolventizing from organic layer, obtain the N-Boc-tert-butyl glycinate 10 (1.551 kg, 6.706 mol, 99% yield) as target.The N-Boc-tert-butyl glycinate 10 of gained is passed through
1H-NMR analyzes and confirms, the N-Boc-tert-butyl glycinate that obtains in result and the above embodiments 1
1H-NMR is in full accord.
Embodiment 3 (example of reaction formula (2))
[changing 15]
To N-Boc-tert-butyl glycinate 10 (150.0 g, 0.6485 at room temperature drip potassium tert.-butoxide (80.05 g in toluene mol) (550 mL) solution, 0.7134 THF mol) (550 mL) suspension at room temperature stirred this mixed solution 10 minutes.Then, the reaction mixture of gained is ice-cold, add successively toluene (200 mL) solution of iodate tetra-n-butyl ammonium (7.186 g, 0.01946 mol) and propargyl bromide (84.86 g, 0.7134 mol) in the reaction mixture.
After the reaction mixture of gained at room temperature stirred 3 hours, the aqueous ammonium chloride solution (500 mL) that adds 8 % by weight stopped reaction, separates organic layer.Then, heat up in a steamer desolventizing from organic layer, obtain the terminal acetylide 11 (153.4 g, 0.5695 mol, 88% yield) as target.
Structure as the terminal acetylide 11 of resultant is passed through
1The H-NMR analysis confirmation.
1H-NMR?(CDCl
3):?δ?4.20-4.10?(m,?2H,?HC≡CCH
2N),?4.00-3.90?(m,2H,?NCH
2CO
2-tert?-Bu),?2.23?(t,?1H,?J=2.6?Hz,?HC≡C),?1.50-1.40?(m,18H,?(tert-Bu)?×2).
Embodiment 4 (example of reaction formula (2))
[changing 16]
(55 % by weight Dormant oils disperse with sodium hydride, 0.8490 g, 19.46 mmol, hexane with 10 mL before using cleans, remove Dormant oils) DMF (6 mL) suspension ice-cold, slowly drip DMF (12 mL) solution of N-Boc-tert-butyl glycinate 10 (3.000 g, 12.97 mmol) in this solution.
After the reaction mixture of gained at room temperature stirred 1 hour, DMF (12 mL) solution with propargyl bromide (1.697 g, 14.27 mmol) under same temperature added reaction mixture.Reaction mixture is remained on room temperature, react after 18 hours, add entry (60 mL) under ice-cold reaction is stopped.Then, add hexane (50 mL), separatory also separates organic layer, and water layer is by hexane (50 mL) extraction 2 times.The organic layer that merges gained cleans with saturated aqueous common salt (50 mL), separates organic layer, uses dried over mgso.Leaching sal epsom, heat up in a steamer desolventizing from the organic layer of gained after, obtain the compound 11 (2.605g, 9.672 mmol, 75% yield) as target.
The structure of the compound of gained is passed through
1H-NMR analyzes and confirms, the compound 11 that use t-BuOK obtains in result and the above embodiments 3
1H-NMR is in full accord.
Embodiment 5 (example of reaction formula (3))
[changing 17]
To 2-iodo-4-N-methyl-p-nitroaniline 12 (111.7 g, 0.4231 mol), molybdenyl dichloride (triphenyl phosphine) palladium (2.970 g, 0.004231 mol) and cupric iodide (I) (1.611 g, 0.008461 at room temperature add successively diethylamine (37.13 g in THF mol) (500mL) suspension, 0.5077 mol) and THF (370 mL) solution of terminal acetylene 11 (152.9 g, 0.5680 mol).Then, reaction mixture is warming up to 40 ℃, stirred 24 hours.For reaction is stopped, after in the reaction mixture injected water (3850 mL), the target compound crystallization was stirred 3 hours under this state again.
From the reaction mixture leaching target compound of gained, make it dry and obtain thick product.The thick product of gained carries out recrystallization with toluene, obtains the nitro-body 13 (144.6 g, 0.3566 mol, 84% yield) as target.The structure of nitro-compound 13 is passed through
1The H-NMR analysis confirmation.
1H-NMR?(CDCl
3):?δ?8.16?(d,?1H,?J=2.4?Hz,?Ar-H),?7.99?(dd,?1H,J=9.2,?2.4?Hz,?Ar-H),?6.62?(d,?1H,?J=9.2?Hz,?Ar-H),?5.15?(s,?2H,?NH
2),4.45-4.32?(m.?2H,?C≡CCH
2N),?4.04-3.88?(m,?2H,?NCH
2CO
2tert-Bu),1.55-1.40?(m,?18H,?(tert-Bu)?×2).
Embodiment 6 (example of reaction formula (3))
[changing 18]
To 2-iodo-4-N-methyl-p-nitroaniline 12 (7.50 g, 28.4 mmol), molybdenyl dichloride (triphenyl phosphine) palladium (99.6mg, 0.142 mmol) and cupric iodide (I) (54.1 mg, 0.284 at room temperature add successively diethylamine (10.4 g in ethyl acetate mmol) (49.9 mL) suspension, 142 mmol) and toluene (28.9 mL) solution of terminal acetylene 11 (11.5g, 42.6 mmol).Then, reaction mixture is warming up to 50 ℃, stirred 6 hours.
In the reaction mixture of gained, add gac (0.750 g), remove by filter gac and reaction residues at 50 ℃, in filtrate, add entry (22.5 mL), separate organic phase.Then, the solvent of organic phase is heated up in a steamer in decompression, thick product to gained adds toluene (46.2 mL), gac (1.15 g), remove by filter gac being no more than under 80 ℃ the temperature, target compound is obtained nitro-body 13 (10.3 g from the filtrate recrystallization, 25.2 mmol, 89% yield).The structure of nitro-compound 13 is passed through
1H-NMR analyzes and confirms, the nitro-compound 13 that obtains in result and the above embodiments 5
1H-NMR is in full accord.
Embodiment 7 (example of reaction formula (3))
[changing 19]
To 2-iodo-4-N-methyl-p-nitroaniline 12 (8.03 g, 30.4 mmol), molybdenyl dichloride (triphenyl phosphine) palladium (213mg, 0.304mmol) and cupric iodide (I) (116 mg, 0.608 at room temperature add successively diethylamine (11.1 g in toluene mmol) (10.3 mL) suspension, 152 mmol) and toluene (34.2 mL) solution of terminal acetylene 11 (12.3 g, 45.6 mmol).Then, reaction mixture is warming up to 40 ℃, stirred 1 hour.
In the reaction mixture of gained, add ethyl acetate (53.4 mL) and gac (0.803 g), remove by filter gac and reaction residues at 50 ℃, in filtrate, add entry (24.1 mL), separate organic phase.Then, the solvent of organic phase is heated up in a steamer in decompression, to thick product adding toluene (35.6 mL), the gac (1.23 g) of gained, remove by filter gac at 100 ℃, target compound is obtained nitro-body 13 (10.2 g, 25.2 mmol, 83% yield) from the filtrate recrystallization.The structure of nitro-compound 13 is passed through
1H-NMR analyzes and confirms, the nitro-compound 13 that obtains in result and the above embodiments 5
1H-NMR is in full accord.
Embodiment 8 (example of reaction formula (3))
[changing 20]
To 2-iodo-4-N-methyl-p-nitroaniline 12 (5.00 g, 18.9 mmol), molybdenyl dichloride (triphenyl phosphine) palladium (133mg, 0.189 mmol) and cupric iodide (I) (72.0 mg, 0.378 at room temperature add successively di-n-butyl amine (2.93 g in toluene mmol) (7.6 mL) suspension, 22.7 mmol) and toluene (21.2 mL) solution of terminal acetylene 11 (7.65 g, 28.4 mmol).Then, reaction mixture is warming up to 40 ℃, stirred 27 hours.
In the reaction mixture of gained, add ethyl acetate (33.3 mL) and gac (0.500 g), remove by filter gac and reaction residues at 50 ℃, in filtrate, add entry (15.0 mL), separate organic phase.Then, the solvent of organic phase is heated up in a steamer in decompression, to thick product adding toluene (20.8 mL), the gac (0.766 g) of gained, remove by filter gac at 100 ℃, target compound is obtained nitro-body 13 (5.48 g, 13.5 mmol, 72% yield) from the filtrate recrystallization.The structure of nitro-compound 13 is passed through
1H-NMR analyzes and confirms, the nitro-compound 13 that obtains in result and the above embodiments 5
1H-NMR is in full accord.
Embodiment 9 (example of reaction formula (1～3))
[changing 21]
Toluene (46.2 mL) suspension of glycine tert-butyl hydrochloride 9 (10.02 g, 59.77 mmol) is remained on 20 ℃, add triethylamine (6.680 g, 66.01 mmol), stirred 1 hour.Then, toluene (11.6 mL) solution of tert-Butyl dicarbonate (10.01 g, 45.86 mmol) is splashed into reaction mixture, make its reaction 5 hours.Confirm that reaction finishes, add entry (40 mL) after, separate organic layer.Then, heat up in a steamer a part of solvent from organic layer, obtain to contain the toluene solution (43.47 g) as the N-Boc-tert-butyl glycinate 10 of target.
Then, at room temperature drip tetrahydrofuran (THF) (26.7 mL) suspension of potassium tert.-butoxide (5.490 g, 48.93 mol) in the toluene solution of the N-Boc-tert-butyl glycinate 10 that obtains in above-mentioned, this mixed solution was at room temperature stirred 10 minutes.This reaction mixture is ice-cold, add successively toluene (10.0 mL) solution of iodate tetra-n-butyl ammonium (0.4864 g, 13.17 mmol) and propargyl bromide (5.820 g, 48.95 mmol) in the reaction mixture.After reaction mixture at room temperature stirred 3 hours, the aqueous ammonium chloride solution (23.7 mL) that adds 13 % by weight stopped reaction, separates organic layer.Then, heat up in a steamer a part of solvent from organic layer, obtain to contain the toluene solution (32.71 g) as the terminal acetylide 11 of target.
To 2-iodo-4-N-methyl-p-nitroaniline 12 (6.84 g, 25.9 mmol), molybdenyl dichloride (triphenyl phosphine) palladium (90.0mg, 0.130 mmol) and cupric iodide (I) (49.3 mg, 0.25.9 at room temperature add successively in ethyl acetate mmol) (45.5 mL) suspension diethylamine (9.47 g, 129 mmol) and above-mentioned in the toluene solution of the terminal acetylene 11 that obtains.Then, reaction mixture is warming up to 50 ℃, stirred 6 hours.In this reaction mixture, add gac (0.68 g), remove by filter gac and reaction residues at 50 ℃, in filtrate, add entry (20.5 mL), separate organic phase.The solvent of organic phase is heated up in a steamer in decompression, thick product to gained adds toluene (42.5 mL), gac (1.05 g), remove by filter gac being no more than under 80 ℃ the temperature, target compound is obtained nitro-body 13 (7.86 g from the filtrate recrystallization, 19.4 mmol, 75% yield).The structure of nitro-compound 13 is passed through
1H-NMR analyzes and confirms, the nitro-compound 13 that obtains in result and the above embodiments 5
1H-NMR is in full accord.
Embodiment 10 (example of reaction formula (4))
[changing 22]
In toluene (1.500 L) suspension of nitro-compound 13 (144.0 g, 0.3552 mol), add 5% palladium-gac (14.40 g).After this reaction mixture placed nitrogen atmosphere, 50 ℃ of reactions 48 hours.Reaction removes by filter the catalyzer in the reaction mixture after finishing, and heats up in a steamer desolventizing from the filtrate of gained, obtains thick product.
Make the thick product of gained be dissolved in THF (0.7400 L), add gac (13.09 g), at room temperature stirred 1 hour.Then, remove by filter gac, heat up in a steamer desolventizing from filtrate and obtain the purifying product (129.8 g, 0.3420 mol, 96% yield) of diamines 14.The structure of diamines 14 is passed through
1H-NMR confirms.
1H-NMR?(DMSO-d
6):?δ?6.54-6.42?(m,?3H,?Ar-H),?3.51-3.45?(m,?2H,NCH
2CO
2tert-Bu),?3.38-3.30?(m,?2H,?CH
2CH
2N),?2.51-2.44?(m,?2H,?ArCH
2),1.84-1.76?(m,?2H,?CH
2CH
2CH
2),?1.48-1.44?(m,?18H,?(tert-Bu)?×2).
Embodiment 11 (example of reaction formula (4))
[changing 23]
In toluene (18.5 mL) suspension of nitro-compound 13 (2.002 g, 4.938 mmol), add gac (0.2006 g), 5% palladium-gac (0.2000 g).After this reaction mixture being placed the nitrogen atmosphere of 0.5MPa, 50 ℃ of reactions 10 minutes.Reaction removes by filter gac, catalyzer in the reaction mixture after finishing, and heats up in a steamer desolventizing from the filtrate of gained, obtains diamines 14 (1.790 g, 4.717mol, 97% yield).The structure of the diamine compound of gained is passed through
1H-NMR analyzes and confirms, the diamine compound 14 that obtains in result and the above embodiments 10
1H-NMR is in full accord.
Embodiment 12 (example of reaction formula (2))
[changing 24]
At room temperature drip toluene (200 mL) solution of N-Boc-tert-butyl glycinate 10 (50.00 g, 216.2 mmol) in toluene (100 mL) suspension of potassium tert.-butoxide (31.53 g, 281.0 mmol), stirred 30 minutes.Then, toluene (200 mL) solution that adds successively iodate tetra-n-butyl ammonium (7.985 g, 21.62 mmol) and allyl bromide 98 (28.77 g, 237.8 mmol) in the reaction mixture.
After the reaction mixture of gained at room temperature stirred 2 hours, add entry (300 mL) reaction is stopped, adding again toluene (100 mL) and water (200 mL) and separatory.The water layer that separates toluene (200 mL) extraction merges organic layer, cleans with saturated aqueous common salt (200 mL), behind the separation organic layer, uses dried over mgso.Then, behind the leaching sal epsom, heat up in a steamer the solvent of the organic layer of gained, obtain target compound 15 (57.62 g, 212.3 mmol, 98% yield).The structure of target compound 15 is passed through
1H-NMR confirms.
1H-NMR (CDCl
3): δ 5.84-5.73 (m, 1H ,-CH=CH
2), 5.20-5.08 (m, 2H ,-CH=CH
2), 3.95-3.71 (m, 4H ,-NCH
2CO
2Tert-Bu reaches-NCH
2CH=), 1.55-1.38 (m, 18H, (tert-Bu) * 2).
Embodiment 13 (example of reaction formula (3))
[changing 25]
Terminad olefin(e) compound 15 (5.000 g, 18.43 mmol) with 2-iodo-4-N-methyl-p-nitroaniline 12 (3.243 g, 12.28 N mmol), at room temperature add sodium acetate (2.015 g in the mixing solutions of N-N,N-DIMETHYLACETAMIDE DMAc (41 mL), 24.57 mmol) and acid chloride (0.02758 g, 0.1228mmol), in 110 ℃ of reactions 3 hours (He Ke reaction).
The reaction mixture diatomite filtration of gained adds ethyl acetate (60mL) and water (60 mL) and separatory in the filtrate of gained.The water layer that separates is used ethyl acetate (60 mL) extraction again, merges organic layer, after water (60 mL) cleans, separates organic layer.Then, heat up in a steamer the solvent of organic layer, obtain thick product.The thick product of gained carries out recrystallization with toluene, obtains the nitro-compound 16 (3.093 g, 7.591 mmol, 62% yield) as target.The structure of nitro-compound 16 is passed through
1The H-NMR analysis confirmation.
1H-NMR?(CDCl
3):?δ?8.10?(d,?1H,?J=2.4?Hz,?Ar-H),?7.96?(dd,?1H,J=8.8,?2.4?Hz,?Ar-H),?6.61?(d,?1H,?J=8.8?Hz,?Ar-H),?6.53?(d,?1H,?J=15.6Hz,?Ar-CH=C),?6.18?(dt,?1H,?J=15.6,?6.0?Hz,?C=CH-CH
2-),?4.72-4.60(m,?2H,?NH
2),?4.12-4.02?(m,?2H,?C=CHCH
2N),?3.94-3.88?(m,?2H,NCH
2CO
2tert-Bu?),?1.55-1.39?(m,?18H,(?tert-Bu)?×2).
Embodiment 14 (example of reaction formula (4))
[changing 26]
In toluene (37 mL) suspension of nitro-compound 16 (3.767 g, 9.245 mmol), add 5% palladium-gac (0.3767 g).After this reaction mixture placed nitrogen atmosphere, 50 ℃ of reactions 7 hours.After reaction finished, the catalyzer in the reaction mixture used diatomite filtration to remove, and heats up in a steamer desolventizing from the filtrate of gained, obtains thick product.
Make the thick product of gained be dissolved in THF (36 mL), add gac (0.35 g) and at room temperature stirred 30 minutes.Then, remove by filter gac, heat up in a steamer desolventizing from filtrate and obtain the purifying product (3.477 g, 9.162 mmol, 99% yield) of diamine compound 14.The structure of the diamine compound of gained is passed through
1H-NMR analyzes and confirms, the diamine compound 14 that obtains in result and the above embodiments 10
1H-NMR is in full accord.
Embodiment 15 (example of reaction formula (1))
[changing 27]
Toluene (780 mL) solution to benzylamine 17 (107.0 g, 0.9986 mol) at room temperature drips tert-Butyl dicarbonate (217.9 g, 0.9986 mol), makes its reaction 1 hour.Then, after adding entry (300mL) reaction being stopped, adding again toluene (60 mL) and separate organic layer, heat up in a steamer desolventizing and obtain the thick product of target compound.
Then, the thick product of gained is carried out recrystallization with hexane, obtain the N-Boc-benzylamine 18 (183.0 g, 0.8829 mol, 88% yield) as target.The structure of compound 18 is passed through
1The H-NMR analysis confirmation.
1H-NMR?(CDCl
3):?δ?7.35-7.23?(m,?5H,?-Ph),?4.88?(b-s,?1H,?NH),4.31?(d,?2H,?J=5.6?Hz,?NCH
2Ph),?1.46?(s,?9H,?tert-Bu).
Embodiment 16 (example of reaction formula (2))
[changing 28]
At room temperature drip toluene (40 mL) solution of N-Boc-benzylamine 18 (20.60 g, 99.39 mmol) in toluene (80 mL) suspension of potassium tert.-butoxide (14.50 g, 129.2 mmol), stirred 2 hours after being warming up to 60 ℃.Then, reaction mixture is cooled off in ice bath, add successively toluene (80 mL) solution of iodate tetra-n-butyl ammonium (1.836 g, 4.969 mmol) and propargyl bromide (13.01 g, 109.3mmol) in the reaction mixture.
Then, at room temperature stirred 4 hours, add entry (100 mL) stopped reaction.Then, organic layer is separated with water layer, water layer is used ethyl acetate (50 mL) extracting and separating again, merges organic layer, separates organic layer after cleaning with saturated aqueous common salt (30 mL).Heat up in a steamer desolventizing and obtain target compound 19 (22.86 g, 93.18 mmol, 94% yield).The structure of target compound 19 is passed through
1The H-NMR analysis confirmation.
1H-NMR?(CDCl
3):?δ?7.35-7.23?(m,?5H,?-Ph),?4.56?(s,?2H,?CH
2),4.10-3.82?(b-m,?2H,?CH
2),?2.21?(b-s,?1H,?H-C≡C),?1.58-1.39?(b-m,9H,?tert-Bu).
Embodiment 17 (example of reaction formula (3))
[changing 29]
To 2-iodo-4-N-methyl-p-nitroaniline 12 (1.499 g, 5.678 mmol), molybdenyl dichloride (triphenyl phosphine) palladium (0.03985 g, 0.05678 mmol) and cupric iodide (I) (0.02163 g, 0.1135 at room temperature add successively diethylamine (0.4983 g in THF mmol) (7mL) suspension, 6.813 mmol) and THF (2 mL) solution of terminal acetylide 19 (2.089 g, 8.516 mmol).Then, being warming up to 40 ℃ stirred 6 hours.
Add entry (10 mL) and ethyl acetate (10 mL) stops reaction to the reaction mixture of gained.Then, this reaction mixture diatomite filtration.Separate organic layer from the filtrate of gained, heat up in a steamer desolventizing and obtain thick product.Then, thick product carries out recrystallization with toluene and hexane, obtains target compound 20 (1.807 g, 4.737 mmol, 83% yield).The structure of target compound 20 is passed through
1The H-NMR analysis confirmation.
1H-NMR?(CDCl
3):?δ?8.11?(d,?1H,?J=2.4?Hz,?Ar-H),?8.00?(dd,?1H,J=9.2,?2.4?Hz,?Ar-H),?7.40-7.23?(m,?5H,?NCH
2Ph),?6.63?(d,?1H,?J=9.2Hz,?Ar-H),?5.10-4.67?(b-m,?2H,?NH
2),?4.59?(s,?2H,?CH
2),?4.25?(b-s,2H,?CH
2),?1.51?(s,?9H,?tert-Bu).
The possibility of utilizing on the industry
According to the present invention, can be by raw material cheaply easy and make efficiently the diamine compound of the raw material that can be used as liquid crystal aligning agent.In addition, manufacture method of the present invention can be implemented large-scale production, industrial useful.
Quote the full content of Japanese patent application 2010-182555 number specification sheets, claims and the specification digest of filing an application on August 17th, 2010 here as the announcement of specification sheets of the present invention.
Claims (10)
1. make the method with the diamine precursor compound of formula 5 expressions, it is characterized in that, according to following reaction formula (1), make compound and tert-Butyl dicarbonate ((Boc) with formula 1 expression
2O) compound with formula 2 expressions is made in reaction, in the formula, and R
1For-CH
2COOR or-CH
2Ph (Z)
m, R is low alkyl group or alkali metal atom, and Z is the substituting group of phenyl (Ph), and m is 0～5;
According to following reaction formula (2), make gained with the compound of formula 2 expression under alkali and with H-A-CH
2The compound that-X represents reacts to make the compound with formula 3 expressions, in the formula, A is-C ≡ C-or-CH=CH-, X is the detachment substituting group;
Then, according to following reaction formula (3), make carrying out linked reaction with the compound of formula 3 expression and compound with formula 4 expressions and making diamine precursor compound with formula 5 expressions of gained, in the formula, Y is the detachment substituting group;
[changing 1]
2. the method for claim 1 is characterized in that, take the compound of formula 1 expression as tert-butyl glycinate or its salt or benzylamine or its salt.
3. method as claimed in claim 1 or 2 is characterized in that, described linked reaction is carried out under the coexistence of metal complex, part and alkali.
4. such as each the described method in the claim 1～3, it is characterized in that, described linked reaction is carried out under as the coexistence of the palladium complex of part containing tertiary phosphine or uncle's phosphorous acid ester.
5. such as each the described method in the claim 1～4, it is characterized in that, the Y in the compound of formula 4 expression is as Br, I or trifluoromethanesulfonic acid ester group.
6. such as each the described method in the claim 1～5, it is characterized in that, with H-A-CH
2X in the compound that-X represents is halogen or sulfonate group.
7. the method for claim 1 is characterized in that, with H-A-CH
2The compound that-X represents is propargylic halide or allyl halide.
8. make the method with the diamine compound of formula 6 expressions, it is characterized in that, according to following reaction formula (4), the compound with formula 5 expressions that will obtain by each the described method in the claim 1～7 was also made the diamine compound with formula 6 expressions originally, in the formula, R
2For hydrogen atom or-CH
2COOR, R are low alkyl group;
[changing 2]
9. the ester cpds that represents with following formula;
[changing 3]
10. the nitro-compound that represents with the arbitrary formula in following;
[changing 4]
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| CN201410686834.2A CN104529826B (en) | 2010-08-17 | 2011-08-17 | Method for preparing diamine precursor compound |
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| CN201410686834.2A Active CN104529826B (en) | 2010-08-17 | 2011-08-17 | Method for preparing diamine precursor compound |
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| JP (1) | JP5737291B2 (en) |
| KR (1) | KR101832534B1 (en) |
| CN (2) | CN103068795B (en) |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105408272A (en) * | 2013-05-24 | 2016-03-16 | 康宁股份有限公司 | Double ion exchange process |
| CN105523958A (en) * | 2015-01-13 | 2016-04-27 | 北京海步医药科技股份有限公司 | Method for preparing key intermediate of diarylthiohydantoin derivative |
| CN106010582A (en) * | 2015-03-27 | 2016-10-12 | Jsr株式会社 | Liquid crystal aligning agent, liquid crystal alignment film, liquid crystal display element, phase difference film, a preparation method thereof, polymer and diamine |
| CN114479073A (en) * | 2021-12-20 | 2022-05-13 | 株洲时代新材料科技股份有限公司 | Polyamide acid resin composition, flexible AMOLED polyimide substrate and preparation method thereof |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6631077B2 (en) * | 2014-11-05 | 2020-01-15 | Jsr株式会社 | Liquid crystal alignment agent, liquid crystal alignment film and liquid crystal display device |
| JP6996509B2 (en) * | 2016-08-30 | 2022-01-17 | 日産化学株式会社 | Liquid crystal alignment agent, liquid crystal alignment film and liquid crystal display element using it |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1483056A (en) * | 2000-12-26 | 2004-03-17 | 日产化学工业株式会社 | Diamines, polyimide precursors and polyimides produced by using the diamines, and liquid crystal aligning agents |
| CN1720280A (en) * | 2002-12-11 | 2006-01-11 | 日产化学工业株式会社 | Novel diaminobenzene derivative, polyimide precursor and polyimide obtained therefrom, and aligning agent for liquid crystal |
| CN101608123A (en) * | 2008-06-17 | 2009-12-23 | Jsr株式会社 | Liquid crystal aligning agent, liquid crystal display device, polyamic acid, imide amination polymer and compound |
| WO2010050523A1 (en) * | 2008-10-29 | 2010-05-06 | 日産化学工業株式会社 | Diamine, polyimide, liquid crystal aligning agent, and liquid crystal alignment film |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102428121B (en) * | 2009-03-10 | 2014-05-28 | 日产化学工业株式会社 | Polyimide precursor, polyimide, and liquid crystal aligning agent |
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- 2011-08-17 JP JP2012529605A patent/JP5737291B2/en active Active
- 2011-08-17 CN CN201180038870.2A patent/CN103068795B/en active Active
- 2011-08-17 WO PCT/JP2011/068624 patent/WO2012023570A1/en active Application Filing
- 2011-08-17 KR KR1020137006720A patent/KR101832534B1/en active IP Right Grant
- 2011-08-17 CN CN201410686834.2A patent/CN104529826B/en active Active
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1483056A (en) * | 2000-12-26 | 2004-03-17 | 日产化学工业株式会社 | Diamines, polyimide precursors and polyimides produced by using the diamines, and liquid crystal aligning agents |
| CN1720280A (en) * | 2002-12-11 | 2006-01-11 | 日产化学工业株式会社 | Novel diaminobenzene derivative, polyimide precursor and polyimide obtained therefrom, and aligning agent for liquid crystal |
| CN101608123A (en) * | 2008-06-17 | 2009-12-23 | Jsr株式会社 | Liquid crystal aligning agent, liquid crystal display device, polyamic acid, imide amination polymer and compound |
| WO2010050523A1 (en) * | 2008-10-29 | 2010-05-06 | 日産化学工業株式会社 | Diamine, polyimide, liquid crystal aligning agent, and liquid crystal alignment film |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105408272A (en) * | 2013-05-24 | 2016-03-16 | 康宁股份有限公司 | Double ion exchange process |
| CN105408272B (en) * | 2013-05-24 | 2019-01-29 | 康宁股份有限公司 | Double ion exchange process |
| CN105523958A (en) * | 2015-01-13 | 2016-04-27 | 北京海步医药科技股份有限公司 | Method for preparing key intermediate of diarylthiohydantoin derivative |
| CN105523958B (en) * | 2015-01-13 | 2017-11-03 | 北京海步医药科技股份有限公司 | A kind of method for preparing Diarylthiohydantoin derivative key intermediate |
| CN106010582A (en) * | 2015-03-27 | 2016-10-12 | Jsr株式会社 | Liquid crystal aligning agent, liquid crystal alignment film, liquid crystal display element, phase difference film, a preparation method thereof, polymer and diamine |
| CN114479073A (en) * | 2021-12-20 | 2022-05-13 | 株洲时代新材料科技股份有限公司 | Polyamide acid resin composition, flexible AMOLED polyimide substrate and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JP5737291B2 (en) | 2015-06-17 |
| JPWO2012023570A1 (en) | 2013-10-28 |
| TWI547467B (en) | 2016-09-01 |
| CN103068795B (en) | 2016-02-24 |
| KR101832534B1 (en) | 2018-02-26 |
| WO2012023570A1 (en) | 2012-02-23 |
| CN104529826B (en) | 2017-04-12 |
| CN104529826A (en) | 2015-04-22 |
| KR20130098342A (en) | 2013-09-04 |
| TW201221503A (en) | 2012-06-01 |
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