TECHNICAL FIELD
The present invention relates to a novel method for producing a diamine
compound which is useful as a raw material for a polyimide polymer for producing a
liquid crystal alignment film, etc. and a novel method for producing an intermediate
thereof.
10
BACKGROUND ART
At present, a polyimide film is used as a liquid crystal alignment film to be used in
a liquid crystal display device in many cases, and the liquid crystal alignment film made
of the polyimide film is produced by a method of coating a substrate with a solution of a
15 polyamic acid which is a precursor of a polyimide or a solution of a polyimide which is
soluble in a solvent, followed by baking and subjecting an obtained film to alignment
treatment such as rubbing treatment (Patent Documents 1 and 2).
Such a polyamic acid and polyimide are usually produced by a condensation
polymerization reaction of a diamine and a tetracarboxylic acid derivative such as
20 tetracarboxylic acid dihydrate.
The diamine which is a raw material for the polyamic acid, the polyimide, etc. is
important, since properties of a liquid crystal alignment film to be obtained from the
diamine, namely properties of the liquid crystal display device are influenced. Various
diamine compounds have been conventionally used and proposed.
25
PRIOR ART DOCUMENTS
PATENT DOCUMENTS
Patent Document 1: JP-A-7-120769
Patent Document 2: JP-A-9-146100
30
DISCLOSURE OF INVENTION
TECHNICAL PROBLEM
2
The present inventors have found a diamine represented by the following formula
(A) as a diamine compound which is a raw material for a polyamic acid and a polyimide
to obtain a liquid crystal alignment film having a high voltage retention, excellent
alignment property of a liquid crystal and low residual electric charge accumulated by
5 DC voltage even though treated by a rubbing method or an alignment treatment by a
photo-alignment method:
As a method for producing the above-mentioned diamine compound, the present
inventors have studied and carried out a method of reacting p-fluoronitrobenzene and 4-
10 (aminomethyl)piperidine to prepare a dinitro compound and subjecting the dinitro
compound to tertiary butoxycarbonylation, followed by reduction.
However, at the time of carrying out such a production method, in a case where
intermediates of the diamine compound are formed and isolated in respective previous
steps, the yield deteriorates due to the isolation. Further, in a case where as a solvent
15 under the presence of potassium carbonate which is an ordinal condition of the reaction,
an ordinal solvent such as DMF(N,N-dimethylformamide) is used at the time of reacting
p-fluoronitrobenzene and 4-(aminomethyl)piperidine, a fluorine atom is substituted by a
dimethylamino group derived from DMF, p-nitro-N,N-dimethylaniline is by produced, and
thereby the yield further deteriorates, such being problematic.
20 It is an object of the present invention to provide a method for producing a diamine
compound represented by the formula (A) and a method for producing an intermediate
thereof, whereby the above problem can be overcome, while the reaction rate is high,
the volume efficiency is high, by-products are few, the purity is high, it is not necessary
to isolate an intermediate, and the efficiency is high.
25
SOLUTION TO PROBLEM
In view of the above circumstance, the present inventors have conducted
extensive studies to achieve the above object and as a result, have found the method
3
for producing the diamine compound represented by the formula (A) and the method for
producing an intermediate thereof. Thus, they have accomplished the present
invention.
That is, the present invention has the following features.
5 1. A method for producing 4-(p-nitrophenylaminomethyl)-N-(p-nitrophenyl)piperidine
(C), which comprises reacting p-fluoronitobenzene and 4-(aminomethyl)piperidine in at
least one solvent selected from the group consisting of dimethylacetamide, 1,3-
dimethyl-2-imidazolidinone, dimethyl sulfoxide and N-methylpyrrolidone:
10 2. The method according to the above 1, wherein the reaction is carried out in the
presence of a base.
3. The method according to the above 1 or 2, wherein from 2 to 10 moles of pfluoronitobenzene
is reacted per 1 mole of 4-(aminomethyl)piperidine.
4. The method according to any one of the above 1 to 3, wherein the solvent is N-
15 methylpyrrolidone.
5. A method for producing 4-(N-p-nitrophenyl-N-tertiary-butoxycarbonylamino)methylN-(p-nitrophenyl)piperidine
(B) which comprises subjecting 4-(pnitrophenylaminomethyl)-N-(p-nitrophenyl)piperidine
(C) obtained in any one of the
above 1 to 3 to tertiary butyloxycarbonylation:
20
6. The method according to the above 5, wherein the tertiary butyloxycarbonylation is
carried out in the presence of a base.
7. The method according to the above 5 or 6, wherein the amount of the tertiary
butyloxycarbonylation agent to be used is from 1 to 5 moles per 1 mole of the
25 compound represented by the formula (C).
8. The method according to any one of the above 5 to 7, wherein the tertiary
4
butyloxycarbonylation is carried out in tetrahydrofuran.
9. A method for producing 4-(N-p-aminophenyl-N-tertiarybutoxycarbonylamino)methyl-N-(p-aminophenyl)piperidine
(A), which comprises
reducing 4-(N-p-nitrophenyl-N-tertiary-butoxycarbonylamino)methyl-N-(p-
5 nitrophenyl)piperidine (B) obtained by the tertiary butyloxycarbonylation in any one of
the above 5 to 8:
10. The method according to the above 9, wherein the reduction is carried out by a
hydrogenation reaction in the presence of a catalyst.
10 11. The method according to the above 9 or 10, wherein the reduction is carried out in
the presence of an activated carbon-supported catalyst.
ADVANTAGEOUS EFFECTS OF INVENTION
According to the present invention, the method for producing the diamine
15 compound represented by the formula (A) which is useful as a raw material for
producing a polyimide precursor or a polyimide and the method for producing an
intermediate thereof, wherein the reaction rate is high, the volume efficiency is high, byproducts
are few, the purity is high, it is not necessary to isolate an intermediate, and
the yield is high, are provided.
20
DESCRIPTION OF EMBODIMENTS
Now, the present invention will be described in detail.
In the present invention, p-fluoronitrobenzene (D) and 4-(aminomethyl)piperidine
(E) are reacted to obtain 4-(p-nitrophenylaminomethyl)-N-(p-nitrophenyl)piperidine (C):
25
In the above reaction, as the proportion of 4-(aminomethyl)piperidine (E) and pfluoronitrobenzene
(D) to be used, the latter is preferably from 2 to 10 mol per one mol
5
of the former, and the latter is more preferably from 2.0 to 2.2 mol, from the viewpoint of
suppressing residual intermediates and the formation of excess reactants.
In the above reaction, p-fluoronitrobenzene and 4-(aminomethyl)piperidine to be
used as starting materials can be available as commercial products. Further, in the
5 present invention, the benzene ring in p-fluoronitrobenzene may have one or plural
substituents such as a methyl group.
The reaction system may be either rotating (batch) system or flow system,
however, from the viewpoint of the handling efficiency, the batch system is preferred.
The reaction is preferably carried out in the presence of a base. As the base, for
10 example, an alkali metal hydroxide such as sodium hydroxide or potassium hydroxide,
an alkali metal carbonate such as sodium carbonate or potassium carbonate, an alkali
metal dicarbonate such as sodium hydrogencarbonate or potassium hydrogencarbonate
or an organic base such as potassium phosphate or 1,8-diazabicyclo[5,4,0]-7-undecene
may be used.
15 Among them, the alkali metal carbonate such as sodium carbonate or potassium
carbonate is preferred. Particularly, a fine powder of potassium carbonate is preferably
used, since the reactivity improves. As a commercially available fine powder of
potassium carbonate, FG-F20 (tradename, manufactured by Asahi Glass Company,
Limited), etc. may be mentioned.
20 As the amount of the base to be used, from 1 to 4 equivalent amount, preferably
from 1.0 to 1.5 equivalent amount may be used per 4-(aminomethyl)piperidine (E).
As the reaction solvent, at least one type selected from the group consisting of
dimethylacetamide (DMAc), 1,3-dimethyl-2-imidazolidinone (DMI), dimethylsulfoxide
(DMSO) and N-methylpyrrolidone (NMP) is used. Among them, N-methylpyrrolidone is
25 particularly preferred.
When such a solvent is used, after the termination of the reaction, the reaction
solution may be used as it is in the subsequent Boc step, such being also advantageous
in the production.
The amount of the solvent to be used is not particularly restricted, however, from 1
30 to 10 parts by mass of the solvent is preferably used per 1 part by mass of the
compound represented by the formula (C). The amount of the solvent is more
preferably from 3 to 5 parts by mass, further preferably from 3.1 to 3.3 parts by mass.
6
The reaction temperature is for example, from -10 to 200°C, preferably form 40 to
100°C. In the case of the batch treatment, the reaction time is from 0.5 to 20 hours,
preferably from 1 to 15 hours.
In the present invention, the reaction solution containing 4-(p-
5 nitrophenylaminomethyl)-N-(p-nitrophenyl)piperidine (C) obtained by the above reaction
is subjected to tertiary butyloxycarbonylation to obtain 4-(N-p-nitrophenyl-N-tertiarybutoxycarbonylamino)methyl-N-(p-nitrophenyl)piperidine
(B). In the present invention,
without isolating 4-(p-nitrophenylaminomethyl)-N-(p-nitrophenyl)piperidine, a reaction
solution containing it may be used as it is in the subsequent step. Thus, the present
10 invention has advantages such as the improvement of the reaction efficiency and the
improvement of the yield.
In the above reaction, from 1 to 5 moles, preferably from 1.3 to 2.5 moles of a
tertiary butyloxycarbonylation agent such as di-tert-butyl dicarbonate (Boc2 O) is used
15 per 1 mole of the compound (C). When the above amount is used, it is possible to
control the number of introduction of di-tert-butyl dicarbonate (also referred to as "Boc
group").
The tertiary butyloxycarbonylation agent may, for example, be N-tertbutoxycarbonylimidazole,
tert-butylphenyl carbonate, tert-butyl carbazate, tert-butyl
20 chloroformate or di-tert-butyl dicarbonate. Di-tert-butyl dicarbonate is particularly
preferred.
In the above reaction, the presence of the base is not always necessary.
However, in a case where the base is used, an inorganic base such as sodium
hydroxide, potassium hydroxide, lithium hydroxide, sodium hydrogencarbonate,
25 potassium hydrogencarbonate, potassium phosphate, sodium carbonate, potassium
carbonate, lithium carbonate or cesium carbonate; an amine such as trimethylamine,
triethylamine, tripropylamine, triisopropylamine, tributylamine, diisopropylethylamine,
pyridine, N,N-dimethyl-4-aminopyridine, imidazole, quinoline or collidine; a base such as
sodium hydride, potassium hydride, tert-butoxysodium or tert-butoxypotassium may, for
7
example, be used. Among them, N,N-dimethyl-4-aminopyridine (DMAP) is preferred.
The amount of the base to be used is preferably from 0.01 to 5.0 equivalent
amount, more preferably from 0.01 to 0.10 equivalent amount, per the compound
represented by the formula (C).
5 As the solvent at the time of reacting 4-(p-nitrophenylaminomethyl)-N-(pnitrophenyl)piperidine
with the tertiary butyloxycarbonylation agent, any solvent may be
used, so long as the solvent will not react with the respective materials.
For example, an aprotic polar organic solvent (such as dimethylformamide (DMF),
DMSO, DMAc or NMP); an ether (such as diethyl ether (Et2 O), diisopropyl ether (i-
10 Pr2 O), tertiary butylmethyl ether (TBME), cyclopentylmethyl ether (CPME),
tetrahydrofuran (THF) or dioxane); an aliphatic hydrocarbon (such as pentane, hexane,
heptane or petroleum ether); an aromatic hydrocarbon (such as benzene, toluene,
xylene, mesitylene, chlorobenzene, dichlorobenzene, nitrobenzene or tetralin); a
halogenated hydrocarbon (such as chloroform, dichloromethane, carbon tetrachloride or
15 dichloroethane); a lower fatty acid ester (such as methyl acetate, ethyl acetate, butyl
acetate or methyl propionate); or a nitrile (such as acetonitrile, propionitrile or
butyronitrile) may, for example, be used. Such a solvent may be appropriately selected
in consideration of the occurrence of the reaction, etc. One type may be solely used,
or two or more types may be used in combination. As the case requires, a solvent is
20 dried with an appropriate dehydrating agent or drying agent, and the solvent may be
used as the non-aqueous solvent.
As the solvent, the ether is preferred, and THF is particularly preferred. In a case
where THF is used, by adding water for liquid separation after the termination of the
reaction, the desired compound represented by the formula (B) can be obtained in a
25 state being contained in the THF solution.
THF and water are usually mixed each other to be a uniform solution. However,
in the production method of the present invention, potassium fluoride by produced in a
condensation step is dissolved in a water phase, whereby the salt concentration in the
water phase is high, and the desired compound represented by the formula (B) is poorly
30 soluble in water. Thus, THF and water are satisfactorily separated. Here, the
proportion of THF and water is preferably from 0.1 to 0.5 parts by mass of water, more
preferably from 0.3 to 0.4 parts by mass of water, per 1 part by mass of THF.
8
The amount of the solvent to be used is not particularly restricted, however, from
0.1 to 100 parts by mass of the solvent is preferably used, per 1 part by mass of the
dinitro compound represented by the formula (C). The amount of the solvent to be
used is more preferably from 0.5 to 30 parts by mass, further preferably from 1 to 10
5 parts by mass.
The reaction temperature is not particularly restricted, however, the reaction
temperature is within the range of from -100°C to the boiling point of the solvent to be
used, preferably from -50 to 150°C.
The reaction time is usually from 0.05 to 200 hours, preferably from 0.5 to 100
10 hours.
After the termination of the reaction, as described above, water is added for liquid
separation, whereby a THF solution containing the compound represented by the
formula (B) is obtained.
Next, in the present invention, the above obtained 4-(N-p-nitrophenyl-N-tertiary-
15 butoxycarbonylamino)methyl-N-(p-nitrophenyl)piperidine (B) is reduced to obtain 4-(N-paminophenyl-N-tertiary-butoxycarbonylamino)methyl-N-(p-aminophenyl)piperidine
(A).
In the present invention, without isolating the nitro compound of the formula (B), a
solution containing the nitro compound represented by the formula (B) can be supplied
to a subsequent reduction reaction as it is, such being preferred on the improvement of
20 the reaction efficiency, the improvement of the yield, etc.
The reduction method may, for example, be a hydrogenation reaction in the
presence of a catalyst, a reduction reaction carried out under the coexistence with
protons, a reduction with formic acid as a hydrogen source or a reduction reaction with
25 hydrazine as a hydrogen source, and some of such reduction reactions may be
combined. Considering the structure and the reactivity of the dinitro compound of the
formula (B), as the reduction method, the hydrogenation reaction in the presence of a
catalyst is preferred.
The catalyst to be used for the hydrogenation reaction is preferably a
9
commercially available activated carbon-supported metal and may, for example, be
palladium-activated carbon, platinum-activated carbon or rhodium-activated carbon.
Further, palladium hydroxide, platinum oxide, Raney nickel, etc. are not necessarily
activated carbon-supported type metal catalyst. Palladium-activated carbon which is
5 widely used in general is preferred, since good results are obtained such that waste is
not generated after the reaction, and side reactions hardly occur.
The amount of the catalyst to be used is not particularly restricted, however, from
the viewpoint of the reactivity, the amount of the catalyst to be used is preferably from
0.0001 to 0.1 mol, more preferably from 0.001 to 0.01 mol, per 1 mol of the compound
10 represented by the formula (B).
The hydrogenation reaction may be carried out under the coexistence with further
activated carbon, in order to let the reaction further effectively proceed. In such a
case, the amount of the activated carbon to be used is not particularly restricted,
however, the amount of activated carbon to be used is preferably from 1 to 20 mass%,
15 more preferably from 5 to 10 mass%, per 100 mass% of the dinitro compound of the
formula (B).
The reaction may be carried out under pressurized hydrogen to further accelerate
the reaction. In such a case, in order to avoid the reduction of the benzene nucleus,
the reaction is carried out within the range of the pressure of at most 20 atm. The
20 reaction is preferably carried out within the range of at most 10 atm.
The solvent may be used without any restriction, so long as the solvent will not
react with respective starting materials.
For example, an aprotic polar organic solvent (such as DMF, DMSO, DMAc or
NMP); an ether (such as Et2 O, i-Pr2 O, TBME, CPME, THF or dioxane); an aliphatic
25 hydrocarbon (such as pentane, hexane, heptane or petroleum ether); an aromatic
hydrocarbon (such as benzene, toluene, xylene, mesitylene, chlorobenzene,
dichlorobenzene, nitrobenzene or tetralin); a halogenated hydrocarbon (such as
chloroform, dichloromethane, carbon tetrachloride or dichloroethane); a lower fatty acid
ester (such as methyl acetate, ethyl acetate, butyl acetate or methyl propionate); a
30 nitrile (such as acetonitrile, propanenitrile or butyronitrile); or the like may be used.
Among them, THF, dioxane and ethyl acetate are preferred.
Such a solvent may be appropriately selected, considering the easiness of the
10
initiation of the reaction. Further, one type of a solvent may be used alone, or two or
more types may be used in combination. As the case requires, a solvent may be dried
with a suitable dehydrating agent or drying agent, and the solvent may be used as the
non-aqueous solvent.
5 The amount of the solvent (reaction concentration) is not particularly restricted,
however, the amount of the solvent to be used is from 0.1 to 100 parts by mass, per 1
part by mass of the dinitro compound of the formula (B). The amount of the solvent to
be used is preferably from 0.5 to 30 parts by mass, further preferably from 0.1 to 10
parts by mass.
10 The reaction temperature is not particularly restricted and within the range of from
-100°C to a boiling point of a solvent to be used, preferably from -50 to 150°C. The
reaction time is usually from 0.05 to 350 hours, preferably from 0.5 to 100 hours.
EXAMPLES
15 Now, the present invention will be described in further detail with reference to
Examples. However, it should be understood that the present invention is by no
means restricted thereto. Further, analyzers and analysis conditions in Examples are
mentioned below.
(
1 H-NMR measurement)
20 Apparatus: Varian NMR system 400NB (400 MHz) (manufactured by Varian,
Inc.) and JMTC-500/54/SS (500 MHz) (manufactured by JEOL Ltd.)
Measuring solvent: CDCl3 (deuterated chloroform), DMSO-d6 (deuterated
dimethylsulfoxide)
Standard substance: TMS (tetramethylsilane) (δ: 0.0 ppm, 1 H) and CDCl3 (δ:
77.0 ppm, 25 1 3 C)
(HPLC (high performance liquid chromatography) measurement)
Apparatus: LC-20AD (manufactured by Shimadzu Corporation)
Column: X Bridge BEHC18 5 μm, 4.6×250 mm Column (Waters)
Detector: SPD-M20A (manufactured by Shimadzu Corporation) (detection
30 wavelength: 254 nm)
Eluent: MeOH/0.2% AcOH, 0.8% Et3N aq.=70/30 [vol/vol]

4-(aminomethyl)piperidine (15.0 g,131.4 mmol), potassium carbonate (21.8 g,
5 157.7 mmol) and N-methylpyrrolidone (40.5 g) were charged in a 1 L (liter)-four necked
flask, and the temperature was raised to 75°C under stirring with blades. Then, pfluoronitrobenzene
(38.9 g, 275.9 mmol) and N-methylpyrrolidone (7.5 g) were dropwise
added over 2 hours, followed by stirring for 6 hours at 75°C. The termination of the
reaction was confirmed by HPLC, and then the reaction solution was used as it is in a
10 subsequent step.

Tetrahydrofuran (270.0 g) and DMAP (N,N-dimethyl-4-aminopyridine) (0.80 g, 6.57
mmol) were charged in the reaction solution obtained by the above step, and Boc2 O (ditert-butyl
dicarbonate) (57.3 g, 262.5 mmol) were dropwise added thereto over 30
15 minutes, followed by stirring for 1 hour. The termination of the reaction was confirmed
by HPLC, and then, tetrahydrofuran (15.0 g) and water (90.0 g) were added, followed by
stirring (1 hour). Then, the water layer was removed by liquid separation, and the THF
solution was used as it is in a subsequent step.

20 A 5 mass% Pd/C (50 mass% hydrous type) (3.0 g) and activated carbon
(Shirasagi WP-H (6.0 g)) were charged in the above THF solution. Then, the hydrogen
substitution was carried out, and the temperature was raised to 50°C, followed by
stirring for 5 hours. The termination of the reaction was confirmed by HPLC, and then
12
the filtration with a membrane filter was carried out to remove Pd/C, etc. Then, the
filtrate was concentrated until the amount of contents became 210.0 g. Then, 2-
propanol (420.0 g) was dropwise added thereto, followed by cooling to 5°C and stirring
for 1 hour. The precipitated crystals were filtrated under reduced pressure, washed
5 with 2-propanol (27.0 g) and dried to obtain 4-(N-p-aminophenyl-N-tertiarybutoxycarbonylamino)methyl-N-(p-aminophenyl)piperidine
as a powder crystal
(obtained amount: 44.3 g, yield: 85.0%).
1 H-NMR(DMSO-d6 ):δ=6.83(d,2H, J=8.0), 6.65(d,2H J=8.4), 6.50(d,2H, J=8.4),
6.45(d,2H, J=8.4), 5.05(br, 2H), 4.54(br,2H), 3.41(d,2H, J=6.8), 3.29(d,2H,J=12.4),
10 2.36(t,2H, J=10.8), 1.64(d,2H, J=11.6), 1.42-1.19(br,12H).
INDUSTRIAL APPLICABILITY
4-(N-p-aminophenyl-N-tertiary-butoxycarbonylamino)methyl-N-(paminophenyl)piperidine
to be obtained by the present invention is useful as a raw
15 material for a polyimide precursor or a polyimide to be used for a liquid crystal alignment
film, etc.
The entire disclosure of Japanese Patent Application No. 2015-045862 filed on
March 9, 2015 including specification, claims and summary is incorporated herein by
20 reference in its entirety.

CLAIMS
1. A method for producing 4-(p-nitrophenylaminomethyl)-N-(p-nitrophenyl)piperidine
(C), which comprises reacting p-fluoronitobenzene and 4-(aminomethyl)piperidine in at
least one solvent selected from the group consisting of dimethylacetamide, 1,3-
5 dimethyl-2-imidazolidinone, dimethyl sulfoxide and N-methylpyrrolidone:
2. The method according to Claim 1, wherein the reaction is carried out in the
presence of a base.
3. The method according to Claim 1 or 2, wherein from 2 to 10 moles of p-
10 fluoronitobenzene is reacted per 1 mole of 4-(aminomethyl)piperidine.
4. The method according to any one of Claims 1 to 3, wherein the solvent is Nmethylpyrrolidone.
5. A method for producing 4-(N-p-nitrophenyl-N-tertiary-butoxycarbonylamino)methylN-(p-nitrophenyl)piperidine
(B) which comprises subjecting 4-(p-
15 nitrophenylaminomethyl)-N-(p-nitrophenyl)piperidine (C) obtained in any one of Claims
1 to 3 to tertiary butyloxycarbonylation:
6. The method according to Claim 5, wherein the tertiary butyloxycarbonylation is
carried out in the presence of a base.
20 7. The method according to Claim 5 or 6, wherein the amount of the tertiary
butyloxycarbonylation agent to be used is from 1 to 5 moles per 1 mole of the
compound represented by the formula (C).
8. The method according to any one of Claims 5 to 7, wherein the tertiary
butyloxycarbonylation is carried out in tetrahydrofuran.
25 9. A method for producing 4-(N-p-aminophenyl-N-tertiarybutoxycarbonylamino)methyl-N-(p-aminophenyl)piperidine
(A), which comprises