JP6277470B2 - Method for producing trans-1,2-diaminocyclohexane - Google Patents

Description

  In the present invention, high-purity trans-1,2-diaminocyclohexane can be obtained with high yield from a 1,2-diaminocyclohexane isomer mixture composed of cis-1,2-diaminocyclohexane and trans-1,2-diaminocyclohexane. The present invention relates to a method for producing trans-1,2-diaminocyclohexane.

  In recent years, high-purity trans-1,2-diaminocyclohexane has been used as a raw material for polymer materials such as polyimide and polyamide, and is useful for film applications and electronic material applications (see Patent Document 1).

  As a method for producing trans-1,2-diaminocyclohexane, for example, 1,2-diacetyldiaminocyclohexane is synthesized from acetic anhydride from an isomer mixture of trans-1,2-diaminocyclohexane and cis-1,2-diaminocyclohexane, A method of obtaining trans-1,2-diaminocyclohexane by obtaining trans-1,2-diacetyldiaminocyclohexane by recrystallization, carrying out a deacetylation reaction with hydrochloric acid, is known (see Patent Document 2).

  In this method, chloroform is used as a halogen-based solvent at the time of acetylation reaction or extraction, or crude 1,2-diacetyldiaminocyclohexane is synthesized, concentrated to dryness, and then isolated by recrystallization. This is a method for purifying -1,2-diacetyldiaminocyclohexane, which involves many unit operations and is complicated.

  After reacting isomers of trans-1,2-diaminocyclohexane and cis-1,2-diaminocyclohexane with phosgene to synthesize N, N′-cyclohexyleneurea, it reacts with an inorganic acid at high temperature, A method of obtaining trans-1,2-diaminocyclohexane by contacting with a base (see Patent Document 3) is known.

  In this method, the toxicity of phosgene as a reactant is high, and the reaction selectivity at the time of synthesis of N, N′-cyclohexylene urea is low.

  After reacting an isomer mixture of trans-1,2-diaminocyclohexane and cis-1,2-diaminocyclohexane with benzyl to synthesize trans-hexahydro-2,3-diphenylquinoxaline, it reacts with an acid at high temperature. Thereafter, a method of obtaining trans-1,2-diaminocyclohexane by contacting with a base (see Patent Document 4) is known.

  This method has a low crystallization yield per time and requires a dehydration operation during the reaction, and the above three methods are industrially disadvantageous.

  In addition, a mixture of trans-1,2-diaminocyclohexane and cis-1,2-diaminocyclohexane was added to an aqueous solvent in an equivalent amount of sulfuric acid to take out as trans-1,2-diaminocyclohexane sulfate, In addition, a method for obtaining trans-1,2-diaminocyclohexane (see Patent Document 5) is known.

  This method obtains high-purity trans-1,2-diaminocyclohexane because there is almost no difference in water solubility between trans-1,2-diaminocyclohexane sulfate and cis-1,2-diaminocyclohexane sulfate. In this case, it is necessary to repeat recrystallization, resulting in a low yield.

  A mixture of trans-1,2-diaminocyclohexane and cis-1,2-diaminocyclohexane was taken out as trans-1,2-diaminocyclohexane adipate by adding an equivalent amount of adipic acid in an alcohol solvent, In addition, a method for obtaining trans-1,2-diaminocyclohexane (see Patent Document 6) is known.

  This method attempts to remove trans-1,2-diaminocyclohexane adipate by adding an equivalent amount of adipic acid to a mixture of trans-1,2-diaminocyclohexane and cis-1,2-diaminocyclohexane in an isopropanol solvent. Then, since cis-1,2-diaminocyclohexane adipate precipitates together, trans-1,2-diaminocyclohexane cannot be efficiently produced.

  Thus, the known method is not a method capable of industrially producing trans-1,2-diaminocyclohexane efficiently.

JP 2013-23597 A JP 61-9725 A US Pat. No. 3,167,587 U.S. Pat. No. 3,163,675 U.S. Pat. No. 3,187,045 Japanese Patent Laid-Open No. 45-29655

  The present invention provides a production method capable of industrially obtaining trans-1,2-diaminocyclohexane from an isomer mixture of trans-1,2-diaminocyclohexane and cis-1,2-diaminocyclohexane. is there.

reacting a mixture of isomers of 1,2-diaminocyclohexane including cis-1,2-diaminocyclohexane and trans-1,2-diaminocyclohexane with a protecting agent that reacts with an amino group, thereby protecting the two amino groups with protecting groups Tran-1 which improves the trans / cis ratio of the isomer mixture of 1,2-diaminocyclohexane by neutralizing the acid generated from the protecting agent using a base and crystallization after neutralizing the base , 2-diaminocyclohexane.

In the present invention, an isomer mixture of 1,2-diaminocyclohexane including cis-1,2-diaminocyclohexane and trans-1,2-diaminocyclohexane is reacted with a protecting agent that reacts with an amino group to give two amino acids. Trans which improves the trans / cis ratio of the isomer mixture of 1,2-diaminocyclohexane by protecting the group with a protecting group and neutralizing the acid generated from the protecting agent with a base , followed by crystallization By the method for producing -1,2-diaminocyclohexane, high-purity trans-1,2-diaminocyclohexane can be efficiently obtained from an inexpensive raw material by a method that can be industrially produced.

  Hereinafter, the present invention will be described in detail.

  The present invention is a production method capable of industrially obtaining trans-1,2-diaminocyclohexane from an isomer mixture of trans-1,2-diaminocyclohexane and cis-1,2-diaminocyclohexane.

  In the method for producing trans-1,2-diaminocyclohexane according to the present invention, a mixture of trans-1,2-diaminocyclohexane and cis-1,2-diaminocyclohexane is produced, for example, by the following method. In the production process of 1,6-diaminohexane, which is a raw material for nylon-6,6, 1,4-dicyanobutane is reduced to produce 1,6-diaminohexane as a by-product, trans-1,2- A mixture of diaminocyclohexane and cis-1,2-diaminocyclohexane is obtained.

  In the present invention, the mixture of trans-1,2-diaminocyclohexane and cis-1,2-diaminocyclohexane contains two isomers, but if the proportion of trans-1,2-diaminocyclohexane is small, trans-1, The production efficiency of 2-diaminocyclohexane tends to be low. Therefore, the ratio of the cis body to the trans body is preferably cis body: trans body = 1: 20 to 10: 6, and more preferably, cis body: trans body = 1: 20 to 10: 8. In industrial products, cis isomer: trans isomer = 1.2: 2 is generally available.

  Further, the mixture of trans-1,2-diaminocyclohexane and cis-1,2-diaminocyclohexane is mixed with amines other than 1,2-diaminocyclohexane, such as 1,6-diaminohexane, It can be used. Preferably, amines other than 1,2-diaminocyclohexane are less than or equal to 1,2-diaminocyclohexane. If the amount of amines other than 1,2-diaminocyclohexane increases, production efficiency may decrease.

  In the process for producing trans-1,2-diaminocyclohexane according to the present invention, a 1,2-diaminocyclohexane isomer mixture containing cis-1,2-diaminocyclohexane and trans-1,2-diaminocyclohexane is reacted with an amino group. React with a protecting agent to protect the two amino groups with a protecting group.

  Examples of the protecting group obtained by protecting the amino group include methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group, n-butoxycarbonyl group, tert-butoxycarbonyl group, 9-fluorenylmethoxycarbonyl group, 9- (2,7 -Dibromo) fluorenylmethoxycarbonyl group, 2-chloro-3-indenylmethoxycarbonyl group, 2,2,2-trichloroethoxycarbonyl group, 2-trimethylsilylethoxycarbonyl group, 2-phenylethoxycarbonyl group, 2- Chloroethoxycarbonyl group, 1,1-dimethyl-2-chloroethoxycarbonyl group, 1,1-dimethyl-2,2-dibromoethoxycarbonyl group, 1,1-dimethyl-2,2,2-trichloroethoxycarbonyl group, 1-adamantyloxycarbonyl group, 2- Damantyloxycarbonyl group, vinyloxycarbonyl group, allyloxycarbonyl group, 1-isopropylallyloxycarbonyl group, cinnamyloxycarbonyl group, N-hydroxypiperidinyloxycarbonyl group, benzyloxycarbonyl group, p-methoxybenzyl Urethane type protecting groups such as oxycarbonyl group, p-chlorobenzyloxycarbonyl group, p-bromobenzyloxycarbonyl group, 4-methylsulfinylbenzyloxycarbonyl group, biphenylmethoxycarbonyl group, formyl group, acetyl group, chloroacetyl group Amide-type protecting groups such as tolchloroacetyl group, trifluoroacetyl group, 3-phenylpropionyl group, 3-phenylpropanamide group, picolinoyl group, nicotinoyl group and benzoyl group, N-alkyl type protective groups such as benzyl group, ethyl group, propyl group, n-butyl group, tert-butyl group, allyl group, N-cyanomethyl group, and the like. It is done. The protecting group is preferably a urethane-type protecting group or an amide-type protecting group.

  The protecting group obtained by protecting the amino group is more preferably a formyl group, an acetyl group, a methoxycarbonyl group, an ethoxycarbonyl group, a tert-butoxycarbonyl group, a benzoyl group, or a benzyloxycarbonyl group.

  The protecting agent that reacts with the amino group varies depending on the type of protecting group.For example, when the amino group is protected with an acetyl group to form an acetamide group, the protecting agent used is acetic anhydride, acetyl chloride, methyl acetate, Examples include ethyl acetate. For example, when the amino group is protected with a tert-butoxycarbonyl group to form a tert-butyl carbamate group, examples of the protective agent used include di-tert-butyl dicarbonate and tertbutyl chlorocarbonate.

  The amount of the protective agent added depends on the type of the protective agent used, but is preferably 1.5 to 5.0 moles, more preferably 1.9, with respect to the 1,2-diaminocyclohexane isomer mixture. It is -3.0 mol times.

  It is preferable to use a solvent for the reaction with the protecting agent that reacts with the amino group. Examples of the solvent include aromatic hydrocarbons such as benzene, toluene, ethylbenzene, o-xylene, m-xylene, p-xylene, styrene, chlorobenzene, and naphthalene, pentane, hexane, heptane, octane, nonane, decane, dodecane, and the like. Aliphatic hydrocarbons, halogenated solvents such as carbon tetrachloride, dichloromethane, chloroform, 1,2-dichloroethane, methanol, ethanol, propanol, isopropanol, butanol, isobutanol, sec-butanol, tert-butanol, pentanol, Alcohols such as 2-pentanol, hexanol, heptanol, octanol, allyl acetate, isobutyl acetate, isopropyl acetate, isopentyl acetate, ethyl acetate, vinyl acetate, phenyl acetate, butyl acetate, acetate acetate Pill, benzyl acetate, methyl acetate, isobutyl formate, butyl formate, methyl propionate, ethyl propionate, methyl butyrate, ethyl butyrate, propyl butyrate, isopropyl butyrate, butyl butyrate, isobutyl butyrate, pentyl butyrate, isopentyl butyrate, ethyl isobutyrate, Aliphatic esters such as methyl isovalerate and ethyl isovalerate, aromatic esters such as methyl benzoate and ethyl benzoate, tetrahydrofuran, cyclopentyl methyl ether, diethyl ether, diisopropyl ether, dibutyl ether, anisole, diphenyl ether, etc. Ethers, acetone, acetylacetone, ethyl methyl ketone, cyclopentanone, cyclohexanone, 3-heptanone, 4-heptanone, ketones such as 2-pentanone, 3-pentanone, Nitriles such as cetonitrile and the like, preferably toluene, ethylbenzene, o-xylene, m-xylene, p-xylene, isopropanol, butanol, isobutanol, sec-butanol, tert-butanol, tetrahydrofuran, cyclopentyl methyl ether, Diethyl ether, diisopropyl ether, ethyl methyl ketone, more preferably toluene, ethyl benzene, o-xylene, m-xylene, p-xylene, tetrahydrofuran, and cyclopentyl methyl ether. Preferably, water, methanol, ethanol, 1-propanol, isopropanol, 1-butanol, isobutanol, sec-butanol, tert-butanol and other alcohols, acetone, ethyl methyl ketone, more preferably water, methanol, ethanol, 1-propanol, isopropanol, acetone, ethyl methyl ketone. The solvent may be a single solvent or a mixed solvent of two or more.

  The amount of the solvent to be used depends on the type of the solvent, but for example, in the case of water, it is preferably 1.0 times by weight or more, more preferably 1.0 to 10 times with respect to the 1,2-diaminocyclohexane isomer mixture. 0 times by weight. For example, in the case of acetone, 0.1 times by weight or more is preferable with respect to the 1,2-diaminocyclohexane isomer mixture, and more preferably 0.5 to 5.0 times by weight.

In the present invention, two amino groups of an isomer mixture of 1,2-diaminocyclohexane including cis-1,2-diaminocyclohexane and trans-1,2-diaminocyclohexane are protected with a protecting group, and a base is used. Crystallization occurs after neutralizing the acid produced from the protective agent .

  The base is preferably lithium hydroxide, sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium methoxide, sodium ethoxide, magnesium ethoxy. And sodium isopropoxide, lithium tert-butoxide, ammonia, methylamine, diisopropylamine, trimethylamine, and triethylamine, more preferably sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, and trimethylamine. If the base is not added, the amount of 1,2-diaminocyclohexane derivative with the amino group protected is less than that when the base is added, and the production efficiency is lowered.

  The base is preferably used in an amount of 0.9 to 4.0 moles with respect to an isomer mixture of 1,2-diaminocyclohexane including cis-1,2-diaminocyclohexane and trans-1,2-diaminocyclohexane, More preferably, it is used 1.0 to 3.0 mole times.

In the present invention, preferably, the number of crystallization after neutralizing the acid produced from the protecting agent using a base is one.

  In the present invention, the trans / cis ratio is preferably 1.3 times or more, more preferably, compared to the trans / cis ratio of the isomer mixture of 1,2-diaminocyclohexane before crystallization in one crystallization. 3 times or more.

  In the present invention, it is preferably obtained by solid-liquid separation of an isomer mixture of 1,2-diaminocyclohexane having an amino group protected.

  In the present invention, preferably, an isomer mixture of 1,2-diaminocyclohexane in which an amino group is protected is obtained as crystals.

  In the present invention, preferably, the obtained isomer mixture of 1,2-diaminocyclohexane in which the amino group is protected is deprotected to give trans-1,2-diaminocyclohexane.

  In the present invention, more preferably, the obtained amino group-protected 1,2-diaminocyclohexane isomer mixture is deprotected by contact with, for example, a mineral acid, or contacted with hydrogen in the presence of a metal catalyst. Deprotect, then isolate and purify.

  The purity of trans-1,2-diaminocyclohexane obtained in the present invention is preferably 75-100 when the total of cis-1,2-diaminocyclohexane and trans-1,2-diaminocyclohexane is 100%. %, More preferably 80 to 100%.

  Hereinafter, a method for producing trans-1,2-diaminocyclohexane using di-tert-butyl dicarbonate as a protecting agent that reacts with an amino group and methanol as a solvent will be exemplified.

  The amount of methanol charged is preferably 1.0 times or more, more preferably 2.5 to 3.5 times the weight of the 1,2-diaminocyclohexane isomer mixture. After the methanol charge, 1,2-diaminocyclohexane isomer mixture and triethylamine as base are added. The amount of triethylamine charged at this time is preferably 1.0 mol times or more, more preferably 1.9 to 2.5 mol times based on the 1,2-diaminocyclohexane isomer mixture.

  The temperature of the reaction solution after the addition is preferably 0 ° C. or higher, more preferably 10 to 50 ° C. Next, di-tert-butyl dicarbonate is added dropwise. The amount of di-tert-butyl dicarbonate charged is preferably 1.5 mol times or more, more preferably 1.9 to 2.5 mol times based on the 1,2-diaminocyclohexane isomer mixture. The dropwise addition time of di-tert-butyl dicarbonate is preferably 0.5 hours or longer, more preferably 1.0 hour or longer. After completion of dropping, the reaction solution is cooled. The cooling temperature is preferably 30 ° C. or lower, more preferably 15 ° C. or lower.

  After cooling, solid-liquid separation is performed to obtain trans-1,2-di-tert-butoxycarbonyldiaminocyclohexane. The obtained trans-1,2-di-tert-butoxycarbonyldiaminocyclohexane is deprotected, isolated and purified to obtain trans-1,2-diaminocyclohexane.

  Hereinafter, the present invention will be described in more detail with reference to examples. In addition, the chemical purity of trans-1,2-diaminocyclohexane was measured by the method shown below.

<Chemical purity analysis method>
About 0.1 g of trans-1,2-diaminocyclohexane was collected in a 10 ml volumetric flask and diluted with methanol to the marked line. The prepared solution was analyzed by gas chromatography, and the purity was obtained by area percentage.

Gas chromatographic analysis conditions Column Inert Cap1 (GL Science)
ID 0.4mm, Film 0.25μm, Length 60m
Helium flow rate 50 ml / min
Column temperature 100 ° C. (10 min) → 15 ° C./min (10 min) → 200 ° C. (10 min)
Inlet temperature 230 ° C
Detector temperature 250 ° C
Detector F ID
Injection volume 1.0 μl
Split ratio 13
Retention time trans-1,2-diaminocyclohexane 8.6 minutes
cis-1,2-diaminocyclohexane 9.0 min.

Example 1
228.4 g of water was charged into a 2000 ml four-necked flask equipped with a thermometer, a dropping funnel and a stirrer. Subsequently, 228.4 g (2.0 mol) of a 1,2-diaminocyclohexane isomer mixture in which the ratio of cis-1,2-diaminocyclohexane to trans-1,2-diaminocyclohexane is 1.2: 2 is stirred. Added. The reaction solution was heated to 65 ° C., and 449.2 g (4.4 mol) of acetic anhydride was added dropwise from the dropping funnel in 2.5 hours. After completion of the dropwise addition, the mixture was further heated and stirred at 70 to 80 ° C. for 1 hour, and then 342.6 g of water was added while maintaining the reaction temperature. It cooled to 55-60 degreeC over 2 hours, and diluted by adding 228.4g of acetone. Thereafter, while maintaining the temperature at 55 to 60 ° C., seed crystals were added to precipitate crystals. It cooled to 40 degrees C or less over 1 hour or more, and 366.7 g (4.4 mol) of 48% sodium hydroxide aqueous solution was added keeping 20-40 degreeC. After stirring at 25-35 ° C. for 1 hour or longer, solid-liquid separation was performed with a centrifugal dehydrator, rinsed with water, and dried to obtain 220.9 g (1.1 mol) of trans-1,2-diacetyldiaminocyclohexane. . The yield was 89% with respect to trans-1,2-diaminocyclohexane, and the ratio of the cis form to the trans form was 1: 200.

  A 1000 ml four-necked flask equipped with a thermometer, a vacuum stirrer, and a condenser was charged with 390.2 g of water and the total amount of trans-1,2-diacetyldiaminocyclohexane obtained. Then 215.7 g (2.2 mol) of sulfuric acid was added. After adding sulfuric acid, the reaction solution was heated to reflux for about 8 hours. After cooling to 25 ° C. over 5 hours and stirring at 20-30 ° C. for 1 hour or more, it was separated into solid and liquid with a Kiriyama funnel and dried to 193.8 g (0.9 mol) of trans-1,2- Diaminocyclohexane sulfate was obtained. In a yield of 83%, the chemical purity of trans-1,2-diaminocyclohexane was 99.9% or higher, and no cis form was detected.

  The total amount of the obtained trans-1,2-diaminocyclohexane sulfate and 327.5 g of water were charged, and the mixture was stirred at 20 to 30 ° C. There, 155.4g (1.9 mol) of 48% sodium hydroxide aqueous solution was dripped, keeping 20-40 degreeC. After stirring and aging at 20 to 30 ° C. for 0.5 hour, the reaction solution was divided into two layers. Therefore, stirring was stopped and liquid separation was performed, and an upper layer which was an oil layer was collected. 416.6 g of 1-butanol was added to the lower layer which is an aqueous layer, and the mixture was aged and stirred at 20 to 30 ° C. for 0.5 hour, and then stirred to separate the liquid, and the upper layer which was an oil layer was collected. The two oil layers collected were separated and the collected oil layer was mixed. The solution was concentrated under reduced pressure to distill off 1-butanol and water, and then the residue was distilled under reduced pressure to obtain trans-1,2-diaminocyclohexane 64. 0.6 g (0.6 mol) was obtained. The yield was 62% with respect to the trans-1,2-diaminocyclohexane sulfate, and the chemical purity of trans-1,2-diaminocyclohexane was 99.9% or more, and no cis form was detected.

(Comparative Example 1)
1000.0 g of water was charged into a 5000 ml four-necked flask equipped with a thermometer, a dropping funnel and a stirrer. Then, with stirring, 400.0 g (3.5 mol) of a 1,2-diaminocyclohexane isomer mixture in which the ratio of cis-1,2-diaminocyclohexane to trans-1,2-diaminocyclohexane is 1.2: 2 is added. Added. The reaction solution was heated to 65 ° C., and 858.3 g (8.4 mol) of acetic anhydride was added dropwise from the dropping funnel in 2.5 hours. After completion of dropping, the mixture was further heated and stirred at 70 to 80 ° C. for 1 hour, then cooled to 40 ° C. over 3 hours, and diluted by adding 400.0 g of acetone. After cooling to 25 ° C over 1 hour and stirring at 20-30 ° C for 1 hour or more, solid-liquid separation with a centrifugal dehydrator, rinsing with water, drying and 151.1 g (0.8 mol) -1,2-Diacetyldiaminocyclohexane was obtained. The yield was 35% with respect to trans-1,2-diaminocyclohexane, the chemical purity of trans-1,2-1,2-diacetyldiaminocyclohexane was 99.9% or more, and no cis form was detected.

(Comparative Example 2)
A 5000 ml four-necked flask equipped with a thermometer, a dropping funnel and a stirrer was charged with 2000 ml of chloroform. Subsequently, 114.2 g (1.0 mol) of a 1,2-diaminocyclohexane isomer mixture in which the ratio of cis-1,2-diaminocyclohexane to trans-1,2-diaminocyclohexane is 1.2: 2 is stirred. Added and dissolved. Acetic anhydride 245.0 g (2.4 mol) was added dropwise over 30 minutes while stirring at room temperature. After dropping, the mixture was further stirred at room temperature for 1 hour, and then the reaction solution was washed with 1000 ml of 20% aqueous sodium hydroxide solution. After separation, the chloroform layer was concentrated to dryness under reduced pressure to obtain 199 g of crude 1,2-diacetyldiaminocyclohexane. The ratio of cis form to trans form remained 1.2: 2. The whole amount of crude 1,2-diacetyldiaminocyclohexane was dissolved in 730 g of water by heating, and then gradually cooled to room temperature to precipitate crystals. The crystals were filtered and dried to obtain 98 g (0.5 mol) of trans-1,2-diacetyldiaminocyclohexane. The yield was 80% based on trans-1,2-diaminocyclohexane, and the ratio of cis form to trans form was 1:32. 75.9 g (0.38 mol) of the obtained trans-1,2-diacetyldiaminocyclohexane was dissolved in 600 ml of 2N hydrochloric acid aqueous solution and heated to reflux for 9 hours. The mixture was allowed to cool, then washed with chloroform, and concentrated under reduced pressure. To the residue, 200 g of 25% aqueous sodium hydroxide solution was added while keeping the temperature at room temperature. After the addition, trans-1,2-diaminocyclohexane produced with chloroform was extracted. The chloroform layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure, and further distilled under reduced pressure to obtain 36 g (0.32 mol) of trans-1,2-diaminocyclohexane. The yield was 83% based on trans-1,2-diacetyldiaminocyclohexane, and the ratio of cis form to trans form remained at 1:32.

(Example 2)
228.4 g of water was charged into a 2000 ml four-necked flask equipped with a thermometer, a dropping funnel and a stirrer. Subsequently, 228.4 g (2.0 mol) of a 1,2-diaminocyclohexane isomer mixture in which the ratio of cis-1,2-diaminocyclohexane to trans-1,2-diaminocyclohexane is 1.2: 2 is stirred. Added. The reaction solution was heated to 65 ° C., and 387.5 g (4.4 mol) of formic acid-acetic acid mixed acid anhydride was added dropwise from the dropping funnel over 2.5 hours. After completion of the dropwise addition, the mixture was further heated and stirred at 70 to 80 ° C. for 1 hour, and then 342.6 g of water was added while maintaining the reaction temperature. It cooled to 55-60 degreeC over 2 hours, and diluted by adding 228.4g of acetone. Thereafter, while maintaining the temperature at 55 to 60 ° C., seed crystals were added to precipitate crystals. It cooled to 40 degrees C or less over 1 hour or more, and 366.7 g (4.4 mol) of 48% sodium hydroxide aqueous solution was added keeping 20-40 degreeC. After stirring for 1 hour or more at 25 to 35 ° C., solid-liquid separation with a centrifugal dehydrator, rinsing with water, and drying to obtain 180.8 g (1.1 mol) of trans-1,2-diformyldiaminocyclohexane It was. The yield was 85% with respect to trans-1,2-diaminocyclohexane, and the ratio of cis form to trans form was 1:32.

  A 1000 ml four-necked flask equipped with a thermometer, a vacuum stirrer, and a condenser was charged with 390.2 g of water and the total amount of trans-1,2-diacetyldiaminocyclohexane obtained. Then, 208.4 g (2.1 mol) of sulfuric acid was added. After the addition of sulfuric acid, the reaction solution was heated to 50 to 55 ° C. and stirred for about 5 hours. Then, after cooling to 25 ° C. over 5 hours and stirring at 20-30 ° C. for 1 hour or more, solid-liquid separation with a Kiriyama funnel, drying and 180.4 g (0.9 mol) of trans-1, A sulfate of 2-diaminocyclohexane was obtained. In a yield of 80%, trans-1,2-diaminocyclohexane had a chemical purity of 99.9% or more, and no cis form was detected.

  The total amount of the obtained trans-1,2-diaminocyclohexane sulfate and 304.9 g of water were charged, and the mixture was stirred at 20 to 30 ° C. Thereto, 149.4 g (1.79 mol) of a 48% aqueous sodium hydroxide solution was added dropwise while maintaining the temperature at 20 to 40 ° C. After stirring and aging at 20 to 30 ° C. for 0.5 hour, the reaction solution was divided into two layers. Therefore, stirring was stopped and liquid separation was performed, and an upper layer which was an oil layer was collected. 17.9-Butanol 387.9g was added to the lower layer which is an aqueous layer, and after stirring and aging at 20-30 degreeC for 0.5 hour, stirring was stopped and liquid-separated and the upper layer which is an oil layer was extract | collected. The two oil layers collected were separated and the collected oil layer was mixed. The solution was concentrated under reduced pressure to distill off 1-butanol and water, and then the residue was distilled under reduced pressure to obtain trans-1,2-diaminocyclohexane 61. 0.1 g (0.5 mol) was obtained. The yield was 63% with respect to the trans-1,2-diaminocyclohexane sulfate, and the chemical purity of trans-1,2-diaminocyclohexane was 99.9% or more, and no cis form was detected.

(Comparative Example 3)
228 g of methanol was charged into a 2000 ml four-necked flask equipped with a thermometer, a dropping funnel and a stirrer. Subsequently, 114.2 g (1.0 mol) of a 1,2-diaminocyclohexane isomer mixture in which the ratio of cis-1,2-diaminocyclohexane to trans-1,2-diaminocyclohexane is 1.2: 2 is stirred. Added. The reaction solution was added dropwise at 20 to 30 ° C. with 132.1 g (2.2 mol) of methyl formate in about 1 hour from a dropping funnel. After completion of dropping, the mixture is aged at 20 to 30 ° C. for 1 hour, cooled to 10 ° C. or less over 1 hour, stirred at 0 to 10 ° C. for 1 hour or more, then solid-liquid separated with a centrifugal dehydrator and dried. 31.4 g (0.2 mol) of trans-1,2-diformyldiaminocyclohexane was obtained. The yield was 27.3% with respect to trans-1,2-diaminocyclohexane, and the ratio of cis form to trans form was 7.5: 92.5.

  A 500 ml four-necked flask equipped with a thermometer, a vacuum stirrer, and a condenser was charged with 55.6 g of water and the total amount of trans-1,2-diformyldiaminocyclohexane obtained. Then 36.2 g (0.4 mol) of sulfuric acid was added. After adding sulfuric acid, the reaction solution was heated to reflux for about 8 hours. After cooling to 25 ° C. over 5 hours and stirring at 20-30 ° C. for 1 hour or more, solid-liquid separation with a Kiriyama funnel, drying and 29.0 g (0.1 mol) of trans-1,2- Diaminocyclohexane sulfate was obtained. In a yield of 80%, trans-1,2-diaminocyclohexane had a chemical purity of 99.9% or more, and no cis form was detected.

  The total amount of the obtained trans-1,2-diaminocyclohexane sulfate and 49.0 g of water were charged and stirred at 20 to 30 ° C. Thereto, 24.0 g (0.3 mol) of a 48% aqueous sodium hydroxide solution was added dropwise while maintaining the temperature at 20 to 40 ° C. After stirring and aging at 20 to 30 ° C. for 0.5 hour, the reaction solution was divided into two layers. Therefore, stirring was stopped and liquid separation was performed, and an upper layer which was an oil layer was collected. 62.4 g of 1-butanol was added to the lower layer, which is an aqueous layer, and the mixture was aged and stirred at 20 to 30 ° C. for 0.5 hour. The two oil layers collected were separated, and the collected two oil layers were mixed. The solution was concentrated under reduced pressure to distill off 1-butanol and water, and then the residue was distilled under reduced pressure to obtain trans-1,2-diaminocyclohexane 10 0.0 g (0.1 mol) was obtained. The yield was 64% with respect to trans-1,2-diaminocyclohexane sulfate, and the chemical purity of trans-1,2-diaminocyclohexane was 99.9% or more, and no cis form was detected.

(Example 3)
228 g of methanol was charged into a 2000 ml four-necked flask equipped with a thermometer, a dropping funnel and a stirrer. Then, with stirring, 114.2 g (1.0 mol) of a 1,2-diaminocyclohexane isomer mixture in which the ratio of cis-1,2-diaminocyclohexane to trans-1,2-diaminocyclohexane is 1.2: 2. 222.6 g (2.2 mol) of triethylamine was added. At 30 ° C., 207.9 g (2.2 mol) of methyl chloroformate was added dropwise from the dropping funnel in about 1 hour. After ripening at 20-30 ° C. for about 1 hour after completion of dropping, 228 g of water was added, then cooled to 10 ° C. over 1 hour and stirred at 0-10 ° C. for 1 hour or more, then centrifugal dehydrator The solid was separated into solid and liquid and dried to obtain 120.4 g (0.5 mol) of trans-1,2-dimethoxycarbonyldiaminocyclohexane. The yield was 78.4% based on trans-1,2-diaminocyclohexane, and the ratio of the cis form to the trans form was 6.3: 93.7.

  A 1000 ml four-necked flask equipped with a thermometer, a vacuum stirrer and a condenser was charged with 212.4 g of water and the total amount of trans-1,2-dimethoxycarbonyldiaminocyclohexane obtained. Subsequently, 102.6 g (1.0 mol) of sulfuric acid was added. After adding sulfuric acid, the reaction solution was heated to reflux for about 8 hours. After cooling to 25 ° C. over 5 hours and stirring at 20-30 ° C. for 1 hour or more, it was solid-liquid separated with a Kiriyama funnel and dried to 83.2 g (0.4 mol) of trans-1,2- Diaminocyclohexane sulfate was obtained. In a yield of 80%, trans-1,2-diaminocyclohexane had a chemical purity of 99.9% or more, and no cis form was detected.

  The total amount of trans-1,2-diaminocyclohexane sulfate obtained and 140.6 g of water were charged, and the mixture was stirred at 20 to 30 ° C. Thereto, 68.9 g (0.8 mol) of a 48% aqueous sodium hydroxide solution was added dropwise while maintaining the temperature at 20 to 40 ° C. After stirring and aging at 20 to 30 ° C. for 0.5 hour, the reaction solution was divided into two layers. Therefore, stirring was stopped and liquid separation was performed, and an upper layer which was an oil layer was collected. 178.9 g of 1-butanol was added to the lower layer, which is an aqueous layer, and the mixture was aged and stirred at 20 to 30 ° C. for 0.5 hour. The stirring was stopped and liquid separation was performed, and the upper layer that was an oil layer was collected. The two oil layers collected were separated, and the collected two oil layers were mixed. The solution was concentrated under reduced pressure to distill off 1-butanol and water, and then the residue was distilled under reduced pressure to obtain trans-1,2-diaminocyclohexane 29. 0.1 g (0.3 mol) was obtained. The yield was 65% with respect to the trans-1,2-diaminocyclohexane sulfate, and the chemical purity of trans-1,2-diaminocyclohexane was 99.9% or more, and no cis form was detected.

Example 4
343 g of methanol was charged into a 2000 ml four-necked flask equipped with a thermometer, a dropping funnel and a stirrer. Then, with stirring, 114.2 g (1.0 mol) of a 1,2-diaminocyclohexane isomer mixture in which the ratio of cis-1,2-diaminocyclohexane to trans-1,2-diaminocyclohexane is 1.2: 2. 222.6 g (2.2 mol) of triethylamine was added. The reaction solution was added at a temperature of 30 to 50 ° C., and 480.2 g (2.2 mol) of di-tert-butyl dicarbonate was added dropwise from the dropping funnel over 1 hour. After completion of dropping, the mixture is aged at 20 to 30 ° C. for 1 hour, cooled to 10 ° C. or less over 1 hour, stirred at 0 to 10 ° C. for 1 hour or more, then solid-liquid separated with a centrifugal dehydrator and dried. 167.6 g (0.5 mol) of trans-1,2-di-tert-butoxycarbonyldiaminocyclohexane was obtained. The yield was 71.5% with respect to trans-1,2-diaminocyclohexane, and the ratio of the cis form to the trans form was 16.1: 83.9.

  A 1000 ml four-necked flask equipped with a thermometer, a vacuum stirrer, and a condenser was charged with 335.2 g of water and the total amount of trans-1,2-di-tert-butoxycarbonyldiaminocyclohexane obtained. Then, 104.6 g (1.1 mol) of sulfuric acid was added. After adding sulfuric acid, the reaction solution was heated to reflux for about 8 hours. After cooling to 25 ° C. over 5 hours and stirring at 20-30 ° C. for 1 hour or more, solid-liquid separation with a Kiriyama funnel and drying were performed 66.4 g (0.3 mol) of trans-1,2- Diaminocyclohexane sulfate was obtained. In a yield of 70%, the chemical purity of trans-1,2-diaminocyclohexane was 99.9% or higher, and no cis form was detected.

  The total amount of the obtained trans-1,2-diaminocyclohexane sulfate and 112.2 g of water were charged, and the mixture was stirred at 20 to 30 ° C. Thereto, 55.0 g (0.7 mol) of a 48% aqueous sodium hydroxide solution was added dropwise while maintaining the temperature at 20 to 40 ° C. After stirring and aging at 20 to 30 ° C. for 0.5 hour, the reaction solution was divided into two layers. Therefore, stirring was stopped and liquid separation was performed, and an upper layer which was an oil layer was collected. 142.8 g of 1-butanol was added to the lower layer, which was an aqueous layer, and the mixture was aged and stirred at 20-30 ° C. for 0.5 hour. The two oil layers collected were separated and the collected oil layer was mixed. The solution was concentrated under reduced pressure to distill off 1-butanol and water, and then the residue was distilled under reduced pressure to obtain trans-1,2-diaminocyclohexane 23. 0.2 g (0.2 mol) was obtained. The yield was 65% with respect to the trans-1,2-diaminocyclohexane sulfate, and the chemical purity of trans-1,2-diaminocyclohexane was 99.9% or more, and no cis form was detected.

(Example 5)
To a 3000 ml four-necked flask equipped with a thermometer, a dropping funnel and a stirrer, 1311 g of methanol was charged. Then, with stirring, 114.2 g (1.0 mol) of a 1,2-diaminocyclohexane isomer mixture in which the ratio of cis-1,2-diaminocyclohexane to trans-1,2-diaminocyclohexane is 1.2: 2. 222.6 g (2.2 mol) of triethylamine was added. At 30 ° C., 375.3 g (2.2 mol) of benzyl chloroformate was added dropwise from the dropping funnel over 2 hours at 30 ° C. After completion of dropping, the mixture was aged at 25 to 35 ° C. for 2 hours, then solid-liquid separated with a centrifugal dehydrator and dried to obtain 157.3 g (0.4 mol) of trans-1,2-dibenzyloxycarbonyldiaminocyclohexane. It was. The yield was 65.8% with respect to trans-1,2-diaminocyclohexane, the ratio of cis form to trans form was 0: 100, and no cis form was detected.

  A 2000 ml SUS autoclave was charged with 629.2 g of methanol and the total amount of trans-1,2-dibenzyloxycarbonyldiaminocyclohexane obtained and 15.7 g of 5% Pd / C. The reaction was carried out at a hydrogen pressure of 0.05 MPa and a reaction temperature of 20-40 ° C. for about 10 hours. After the reaction, the mixture was cooled to room temperature, and Pd / C was removed with a membrane filter. There is no trans-1,2-dibenzyloxycarbonyldiaminocyclohexane in the filtrate from which Pd / C has been removed, and the chemical purity of trans-1,2-diaminocyclohexane excluding the solvent is 99.9% or more. , Cis bodies were not detected.

  The obtained filtrate was concentrated under reduced pressure to distill off methanol and water, and then the residue was distilled under reduced pressure to obtain 37.6 g (0.3 mol) of trans-1,2-diaminocyclohexane. The yield was 80% with respect to trans-1,2-dibenzyloxycarbonyldiaminocyclohexane, the chemical purity of trans-1,2-diaminocyclohexane was 99.9% or more, and no cis form was detected.

(Comparative Example 4)
1,2-diaminocyclohexane in which a ratio of cis-1,2-diaminocyclohexane to trans-1,2-diaminocyclohexane is 1.2: 2 in a 500 ml four-necked flask equipped with a thermometer, a dropping funnel and a stirrer 11.4 g (0.1 mol) of the isomer mixture and 100 g of 2-propanol were charged and dissolved. A solution prepared by dissolving 14.6 g (0.1 mol) of adipic acid in 100 g of 2-propanol was added to the dropping funnel and dropped into the reaction solution. The precipitated crystals were separated into solid and liquid by a centrifugal dehydrator and dried to obtain 25.0 g (1.0 mol) of 1,2-diaminocyclohexane adipate. The yield is 96% with respect to trans-1,2-diaminocyclohexane, and the ratio of the cis form to the trans form is 1.2: 2.0. The body ratio did not change.

  Table 1 lists the 1,2-diaminocyclohexane isomer mixture of the raw materials in Examples and Comparative Examples, and 1,2-diaminocyclohexane derivatives in which the amino group is protected with a protecting group and the amino group is protected once. The trans / cis isomer ratio and the crystallization yield of one time of the crystals obtained in (1) were summarized.

Claims (6)

reacting a mixture of isomers of 1,2-diaminocyclohexane including cis-1,2-diaminocyclohexane and trans-1,2-diaminocyclohexane with a protecting agent that reacts with an amino group, thereby protecting the two amino groups with protecting groups The trans / cis ratio of the isomer mixture of 1,2-diaminocyclohexane is improved by neutralizing the acid generated from the protecting agent with a base and then crystallization , and then trans-1,2 -Production method of diaminocyclohexane. The method for producing trans-1,2-diaminocyclohexane according to claim 1, wherein the protecting group is a urethane-type protecting group or an amide-type protecting group. The trans-1,2- of claim 1 or 2, wherein a mixture of isomers of 1,2-diaminocyclohexane in which two amino groups are protected with a protecting group is obtained as a crystal by crystallization and then deprotected. A method for producing diaminocyclohexane. The trans-1, 2-amino group according to any one of claims 1 to 3, wherein the protecting group is a formyl group, an acetyl group, a methoxycarbonyl group, an ethoxycarbonyl group, a tert-butoxycarbonyl group, a benzoyl group, or a benzyloxycarbonyl group. A method for producing 2-diaminocyclohexane. The increase ratio of trans-1,2-diaminocyclohexane is 3 times or more in one crystallization as compared with the isomer mixture of 1,2-diaminocyclohexane before crystallization. A method for producing trans-1,2-diaminocyclohexane according to any one of the above. The method for producing trans-1,2-diaminocyclohexane according to any one of claims 1 to 5, wherein the number of crystallizations after neutralizing the acid produced from the protecting agent using a base is one.