JPH09268178A - Optically active 4,5-diphenyl-2-imidazolidinone derivative - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an optically active 4, 5-dipheny1-2-imidazolidinone derivative useful as a reagent for analyzing an optical purity, especially the optical purity of amines havnig asymmetric carbons. SOLUTION: This optically active 4,5-diphenyl-2-imidazolidinone derivative is represented by formula I [R<1> is an alkyl; R<2> is an alkylene; (1) is 0 or 1; (*) represents a position of an asymmetric carbon] and obtained by reacting a compound represented by formula II (X<3> is a halogen) with a metal thiocyanate represented by the formula MSCN (M is an alkali metal). Optical purities of amines having asymmetric carbons are accurately analyzed and determined by a simple method of condensing the amines and the compound of formula I, forming into thiourea derivatives as diastereomers and analyzinz the resultant thiourea derivatives by a nuclear electromagnetic resonance spectrography.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a compound useful as a reagent for optical purity analysis, particularly as a reagent for optical purity analysis of amines having asymmetric carbon atoms, and an optical purity analysis method using the same.

[0002]

2. Description of the Related Art Enantiomers (enantiomers) exist in organic compounds having an asymmetric carbon. And in flavors and food additives, the odors and tastes differ depending on both enantiomers, and in pharmaceuticals, the drug efficacy and toxicity differ greatly depending on both isomers, as is clearly shown in the example of thalidomide. Further, a ferroelectric liquid crystal is required to have a pure chiral molecular structure, and a decrease in purity is said to cause a remarkable decrease in function. For these reasons, in the industrial fields such as medicine, agricultural chemicals, fragrances, food additives, and electronics,
Optically active compounds with high optical purity are required, and at the same time, accurate methods for determining optical purity are becoming important.

Conventionally known methods for determining optical purity include a method by measuring optical rotation, a method using NMR, a method using chromatography and the like. Particularly, in the method using NMR, the setting of measurement conditions is easy. It is widely used because of its wide application range. Then, for example, in the case of determining the optical purity of optically active amines by a method by NMR, each separated by adding an optically active shift reagent or a chiral solvating reagent, or by introducing the amines into diastereomers. This is done by comparing the integrated values of the isomer signals.

[0004]

However, an optical activity shift reagent represented by tris [3-heptafluorobutanoyl-d-camphorato] europium (III) [Eu (hfc) ₃ ] is expensive and OH is high. In some cases, the signal of the enantiomer of the sample, which is likely to be coordinated to the impurities having a group or NH group and has poor optical purity, is not separated. As a method of adding a chiral solvating reagent, a reagent of Pirkle,
(R)-(-) 2,2,2-trifluoro-1- (9-
Although anthryl) ethanol and the like are known, the expected shift effect may not be obtained in some cases. Further, as a method for introducing an amine into a diastereomer and measuring a diastereomer ratio, a method using an acid chloride of α-methoxy-α-trifluorophenylacetic acid (MTPA) is known, but a commercially available acid chloride is used. There was a drawback that the reagent could not be stored for a long period of time because the acid chloride was unstable and the acid chloride was unstable.

Therefore, it is an object of the present invention to provide an inexpensive reagent and an optical purity analysis method capable of easily determining the optical purity of amines.

[0006]

Under such circumstances, the present inventors have conducted earnest research to develop a new method for determining the optical purity of amines, and as a result, a novel compound represented by the following general formula (1) A thiourea derivative obtained as a diastereomer by condensing an optically active 4,5-diphenyl-2-imidazolidinone derivative with an amine is
The inventors have found that signals can be separated by MR measurement, and that the optical purity of the amines can be easily determined by measuring the diastereomer ratio, and completed the present invention.

That is, the present invention has the general formula (1)

[0008]

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[Wherein R ¹ represents an alkyl group, R ² represents an alkylene group, l represents a number of 0 or 1, and * represents a position of an asymmetric carbon]. The present invention provides a 4,5-diphenyl-2-imidazolidinone derivative.

The present invention also contains a 4,5-diphenyl-2-imidazolidinone derivative represented by the general formula (1), characterized in that it contains an asymmetric carbon-containing amine for optical purity analysis. Is provided.

Furthermore, the present invention is a thiourea derivative obtained by reacting an optically active 4,5-diphenyl-2-imidazolidinone derivative represented by the general formula (1) with an amine having an asymmetric carbon. Nuclear magnetic resonance spectrum analysis (N
The present invention provides an optical purity analysis method for amines having an asymmetric carbon, which is characterized by being subjected to MR).

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION The 4,5-diphenyl-2 of the present invention
The imidazolidinone derivative is represented by the general formula (1), and the alkyl group represented by R ¹ in the formula includes a linear or branched alkyl group having 1 to 20 carbon atoms. In particular, a linear or branched alkyl group having 1 to 6 carbon atoms is preferable. As a specific example of the R ^1, a methyl group,
Examples thereof include ethyl group, n-propyl group, isopropyl group, n-butyl group and tert-butyl group. Examples of the alkylene group represented by R ² include linear or branched alkylene groups having 1 to 8 carbon atoms, particularly 1 to 4 carbon atoms.
The linear alkylene group of is preferable.

The compound (1) of the present invention can be produced, for example, according to the following reaction (a) or reaction (b).

[0014]

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(In the formula, R ³ represents an alkyl group, and X ¹ ,
X ² , X ³ and X ⁴ each represent a halogen atom, and M
Represents an alkali metal atom, and R ¹ and R ² are the same as above)

That is, 1,2-diphenyl-1,2-
Reaction of ethanediamine (2) with urea (3) 4,5
-Diphenyl-2-imidazolidinone (4) was obtained (step 1), and this was reacted with an acyl halide (5) to give a 1-acyl compound (6) (step 2), which was alkylated to 1-. No acyl-3-alkyl derivative (8) (step 3),
This is hydrolyzed to eliminate the acyl group (step 4), and this is reacted with a halogenocarboxylic acid halogenide (10) to give a halogenoacyl-4,5-diphenyl-2-.
A thiocyanatoacyl derivative (1a) is produced by obtaining an imidazolidinone derivative (11) (step 5) and then reacting this with a metal thiocyanate (12) (step 6).

The above reaction will be described below step by step. (1) Step 1 Optically active 1,2-diphenyl-1,2-ethanediamine (2) is cyclized with urea (3) and water to give 4,5-diphenyl-2-imidazolidinone (4). )
Is obtained. Optically active 1,2-used as raw material
As diphenyl-1,2-ethanediamine (2),
(1R, 2R) -1,2-diphenyl-1,2-ethanediamine, (1S, 2S) -1,2-diphenyl-1,
2-ethanediamine etc. are mentioned. This reaction is carried out by heating while distilling off water.

(2) Step 2 1-acyl-4,5-diphenyl-2 by reacting 4,5-diphenyl-2-imidazolidinone (4) with fatty acid halogenide (5) represented by propionyl chloride. -Imidazolidinone (7) is obtained. This reaction is carried out in the presence of a base such as sodium hydride.

(3) Step 3 3-acyl-1-alkyl-4,5- by reacting 1-acyl-4,5-diphenyl-2-imidazolidinone (7) with alkyl halide (8). Diphenyl-2-imidazolidinone (9) is obtained. Specific examples of the alkyl halide (8) include methyl iodide, ethyl iodide, ethyl bromide, n-propyl iodide, and n-bromide.
Propyl, n-propyl chloride, i-propyl iodide, i-propyl bromide, n-butyl iodide, n-butyl bromide,
Examples thereof include i-butyl iodide, i-butyl bromide and t-butyl chloride. This reaction is carried out in the presence of a base such as sodium hydride.

(4) Step 4 3-Acyl-1-alkyl-4,5-diphenyl-2-
Hydrolysis of imidazolidinone (9) yields 1-alkyl-4,5-diphenyl-2-imidazolidinone (10)
Is obtained. This reaction is carried out under the condition that only an acyl group is eliminated in the presence of a base such as sodium methoxide.

(5) Step 5 1-Alkyl-4,5-diphenyl-2-imidazolidinone (10) is converted to halogenocarboxylic acid halogenide (11).
The halogenoacyl-4,5-diphenyl-2-imidazolidinone derivative (12) is obtained by reacting Specific examples of the halogenocarboxylic acid halogenide include:
Examples thereof include chloroacetyl chloride and bromoacetyl chloride. This reaction is carried out by dimethylformamide,
A metal salt of compound (10) is prepared using an organometallic compound such as n-butyllithium or lithium diisopropylamide or sodium hydride or lithium hydride in an inert solvent such as tetrahydrofuran or diethyl ether, and then cooled to room temperature or cooled. It is carried out by dropping a solution of the metal salt of the compound (10) into the solution of the halogenocarboxylic acid halogenide (11) below.

(6) Step 6 The compound (1a) of the present invention is obtained by reacting the halogenoacyl-4,5-diphenyl-2-imidazolidinone derivative (12) with the metal thiocyanate (13). Specific examples of the metal thiocyanate (13) include potassium thiocyanate, sodium thiocyanate, lithium thiocyanate and the like. In this reaction, the compound (12) and the metal thiocyanate (13) are treated with ethanol,
Dissolved in a solvent such as methanol or dimethylformamide,
It is performed by heating.

[0023]

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(In the formula, X ⁵ represents a halogen atom, and R ¹
And R ² is the same as above)

That is, 1-alkyl-4,5-diphenyl-2-imidazolidinone (9) is reacted with N-halogenoalkylphthalimide (13) to give compound (14).
Was obtained (step 7), and this was reacted with hydrazine hydrate to give compound (15) (step 8), and then this was reacted with carbon disulfide (step 9) to give the thiocyanatoalkyl compound (1b). ) Is manufactured.

The above reaction will be described below step by step. (1) Step 7 1-Alkyl-4,5-diphenyl-2-imidazolidinone (9) was added to N-halogenoalkylphthalimide (1
By reacting 3), phthalimidoalkyl-
4,5-Diphenyl-2-imidazolidinone derivative (1
4) is obtained. Specific examples of the N-halogenoalkyl phthalimide (13) include N-butyl iodide phthalimide, N-butyl bromide phthalimide, N-butyl chloride phthalimide, N-propyl bromide phthalimide, N-ethyl bromide phthalimide, N- Examples include methyl bromide bromide and the like. This reaction is carried out in an inert solvent such as dimethylformamide, tetrahydrofuran, diethyl ether,
n-butyllithium, lithium diisopropylamide,
It is carried out in the presence of a base such as sodium hydride.

(2) Step 8 Aminoalkyl-4,5-diphenyl- by reacting the phthalimidoalkyl-4,5-diphenyl-2-imidazolidinone derivative (14) with hydrazine hydrate.
A 2-imidazolidinone derivative (15) is obtained. This reaction is carried out by dissolving the compound (14) and hydrazine hydrate in a solvent such as ethanol, methanol or tetrahydrofuran and heating.

(3) Step 9 The aminoalkyl-4,5-diphenyl-2-imidazolidinone derivative (15) is reacted with carbon disulfide in the presence of a base, and then 2-chloro-1,3-dimethylimidazoli. The thiocyanatoalkyl-4,5-diphenyl-2-imidazolidinone (1b) is obtained by reacting with a nickel chloride. Examples of the base used include organic bases such as triethylamine, pyridine and N, N-dimethylaniline, and inorganic bases such as potassium carbonate, sodium hydroxide and sodium hydrogen carbonate. The reaction is carried out in an inert solvent such as methylene chloride, dimethylformamide and acetonitrile at room temperature or under cooling.

In order to analyze the optical purity of amines having an asymmetric carbon by using the compound (1) of the present invention thus obtained, the compound (1) of the present invention is reacted with an amine as a test substance to obtain the compound. The obtained thiourea derivative may be measured by NMR and the integrated values of the signal peaks of the diastereomers may be compared. This reaction is represented by the following reaction formula.

[0030]

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(In the formula, at least one of R ⁴ and R ⁵ represents an organic group having an asymmetric carbon, and R ¹ , R ² and l are the same as above)

This reaction is carried out at room temperature to reflux temperature in an inert solvent such as toluene, methylene chloride, tetrahydrofuran or acetonitrile. Further, the NMR measurement can be carried out as it is after isolating the product or concentrating the reaction solution.

[0033]

EXAMPLES Hereinafter, the present invention will be described in more detail by way of examples, but the present invention is not limited thereto.

Production Example 1 Production of (4S, 5S) -4,5-diphenyl-2-imidazolidinone: (1S, 2S)
-1,2-diphenyl-1,2-ethanediamine 20.
A mixture of 0 g (94 mmol), 6.0 g of urea (100 mmol) and 1 ml of water was heated at 200 ° C. for 3 hours while distilling off water. After standing to cool, the mixture was dissolved in methylene chloride, and the solution was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain a white crystalline residue. The residue was washed with acetonitrile to obtain 19.6 g (yield 87%) of the title compound.

IR (ν ^KBr _max cm ⁻¹ ): 3200, 3060, 1700, 695 ¹ H-NMR (CDCl ₃ ) δ: 4.60 (2H, s), 4.93 (2H, s), 7.19 to 7.3
8 (10H, m)

Preparation Example 2 Preparation of (4S, 5S) -4,5-diphenyl-1-propionyl-2-imidazolidinone: (4S, 5 in 180 ml of anhydrous dimethylformamide.
S) -4,5-Diphenyl-2-imidazolidinone 1
7.6 g (74 mmol) and 6.5 g of sodium hydride
(55% 148 mmol) was added, and the mixture was stirred at room temperature for 1.5 hours. The reaction solution was cooled with ice and propionyl chloride 6.8.
g (74 mmol) was slowly added dropwise, and after completion, stirring was continued at room temperature for 1 hour. The reaction solution was added to dilute aqueous hydrochloric acid solution and extracted with methylene chloride. The extract solution was washed successively with water and saturated aqueous sodium hydrogen carbonate solution, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to give 25.9 g of residue. Got The residue was purified by silica gel chromatography (solvent: chloroform) to give 18.3 g of the title compound (yield 84
%)Obtained.

¹ H-NMR (CDCl ₃ ) δ: 1.07 (3H, t, J = 7.5Hz),
2.91 ~ 3.00 (2H, m), 4.50 (1H, d, J = 3.3Hz), 5.11 (1H, d, J =
3.3Hz), 5.61 (1H, bs), 7.24 ~ 7.41 (10H, m)

Preparation Example 3 Preparation of (4S, 5S) -4,5-diphenyl-1-propionyl-3-propyl-2-imidazolidinone: In 50 ml of dimethylformamide,
(4S, 5S) -4,5-diphenyl-1-propionyl-2-imidazolidinone 5.26 g (17.9 mmol)
And sodium hydride 0.94g (55% 21.5mm
ol) was added and the mixture was stirred at room temperature for 1 hour to prepare a sodium salt. Next, 2.42 g of propyl bromide (1
(9.7 mmol) was slowly added dropwise, and stirring was continued for another 17 hours after the completion. The reaction solution was added to dilute aqueous hydrochloric acid solution and extracted with methylene chloride. The extract solution was washed with water and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain an oily residue.
The residue was purified by silica gel chromatography (solvent: chloroform) to obtain 4.93 g (yield 82%) of the title compound as a viscous oil.

IR (ν ^neat _max cm ^-1 ): 1725, 1690 ¹ H-NMR (CDCl ₃ ) δ: 0.85 (3H, t, J = 7.5Hz), 1.13 (3H, t, J =
7.3Hz), 1.44 to 1.49 (2H, m), 2.69 to 2.77 (1H, m), 3.06 (2
H, t, J = 7.3Hz), 3.58 ~ 3.63 (1H, m), 4.34 (1H, d, J = 2.9Hz),
5.06 (1H, d, J = 2.9Hz), 7.17〜7.43 (10H, m)

Production Example 4 Production of (4S, 5S) -4,5-diphenyl-1-propyl-2-imidazolidinone:
In 30 ml of methanol was dissolved 4.93 g (14.7 mmol) of (4S, 5S) -4,5-diphenyl-1-propionyl-3-propyl-2-imidazolidinone, and 28% sodium methoxide methanol was added thereto. Solution 5.70
g (29.4 mmol) was added, and the mixture was stirred at room temperature for 20 minutes. A diluted hydrochloric acid aqueous solution was added to the reaction solution, followed by extraction with methylene chloride. The extract was washed with a saturated sodium hydrogen carbonate aqueous solution and water in that order, and dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure to obtain 3.57 of the title compound as white crystals.
g (yield 87%) was obtained.

IR (ν ^KBr _max cm ⁻¹ ): 3200, 1700 ¹ H-NMR (CDCl ₃ ) δ: 0.81 (3H, t, J = 7.6Hz), 1.36 to 1.43 (2
H, m), 2.66 ~ 2.75 (1H, m), 3.41 ~ 3.51 (1H, m), 4.36 (1H,
d, J = 8.8Hz), 4.51 (1H, d, J = 8.8Hz), 4.97 (1H, bs), 7.21〜
7.25 (4H, m), 7.26-7.42 (6H, m)

Preparation 5 Preparation of (4S, 5S) -1-Bromoacetyl-4,5-diphenyl-3-propyl-2-imidazolidinone: (4S, 5S) -4,5- in 30 ml of dimethylformamide. Diphenyl-1-propyl-
3.57 g (12.8 mmol) of 2-imidazolidinone and 0.61 g (55% 14.0 mmol) of sodium hydride
Was added and stirred at room temperature for 2.5 hours to prepare a sodium salt. This sodium salt was added to bromoacetyl chloride 2.
81 g (17.9 mmol) of dimethylformamide 30 ml
The solution was slowly added dropwise to the solution under ice cooling, and after completion, the mixture was further stirred at room temperature for 1 hour. Then, the reaction solution was added to a dilute hydrochloric acid aqueous solution and extracted with methylene chloride. The extract was washed successively with saturated sodium hydrogen carbonate and water, and dried over anhydrous magnesium sulfate. The red oily residue obtained by distilling off the solvent under reduced pressure was subjected to silica gel chromatography (solvent: chloroform).
And purified by 2.74 g of the title compound as a viscous oil.
(Yield 54%) was obtained.

IR (ν ^neat _max cm ^-1 ): 1720 ¹ H-NMR (CDCl ₃ ) δ: 0.86 (3H, t, J = 7.5Hz), 1.46 to 1.51 (2
H, m), 2.64 ~ 2.77 (1H, m), 3.48 ~ 3.58 (1H, m), 4.41 (1H,
d, J = 3.1Hz), 4.78 (1H, d, J = 15.2Hz), 4.92 (1H, d, J = 15.2H
z), 5.06 (1H, d, J = 3.1Hz), 7.17 ~ 7.27 (4H, m), 7.33 ~ 7.4
3 (6H, m)

Example 1 (4S, 5S) -4,5-diphenyl-1-propyl-3-thiocyanatoacetyl-2
-Preparation of imidazolidinone: (4
S, 5S) -1-Bromoacetyl-4,5-diphenyl-3-propyl-2-imidazolidinone 2.74 (6.
8 mmol) and 0.80 g of potassium thiocyanate (8.2
mmol) was added and the mixture was heated under reflux for 2 hours. After cooling, water was added to the reaction solution and extracted with methylene chloride. The extract was washed with water and dried over anhydrous magnesium sulfate. Next, 2.71 g of a brown viscous oily substance obtained by distilling off the solvent under reduced pressure was purified by silica gel chromatography (solvent n-hexane / ethyl acetate) to obtain 2.27 g of the title compound (yield 88%). )Obtained.

Light yellow oil [α] ^27.5 _D = −69.10 ° (c = 1.00, CHCl ₃ ) UV (λ ^MeOH _max nm): 208.4 (ε 24200) IR (ν ^neat _max cm ⁻¹ ): 2150, 1715 , 1685 ¹ H-NMR (CDCl ₃ ) δ: 0.87 (3H, t, J = 7.3Hz), 1.46-1.51 (2H,
m), 2.73 to 2.81 (1H, m), 3.57 to 3.62 (1H, m), 4.43 (1H, d, J
= 3.3Hz), 4.50 (1H, d, J = 15.4Hz), 4.57 (1H, d, J = 15.4Hz),
5.04 (1H, d, J = 3.3Hz), 7.16 ~ 7.26 (4H, m), 7.35 ~ 7.46 (6
H, m) ¹³ C-NMR (CDCl ₃ ) δ: 11.14, 20.32, 38.27, 43.48, 63.7
3, 65.56, 111.57, 125.27, 126.15, 128.67, 129.30, 1
29.35, 129.61, 138.08, 139.58,154.17, 164.99

Preparation Example 6 Preparation of (4S, 5S) -1-bromoacetyl-4,5-diphenyl-3-methyl-2-imidazolidinone: Obtained in the same manner as in Preparation Examples 1 to 4 in 20 ml of dimethylformamide. (4S, 5S) -4,
5-Diphenyl-1-methyl-2-imidazolidinone 5.90 g (23.4 mmol) and sodium hydride 1.
12 g (55% 25.7 mmol) was added and the mixture was stirred at room temperature for 2.5 hours to prepare a sodium salt. 5.53 g (35.1 mmol) of this sodium salt was added to bromoacetyl chloride.
Was slowly added dropwise to a 20 ml solution of dimethylformamide under ice-cooling, and after completion, the mixture was further stirred at room temperature for 3 hours. Less than,
The same operation as in Production Example 5 was carried out to obtain 5.04 g of the title compound.
(Yield 58%) was obtained.

Example 2 (4S, 5S) -4,5-diphenyl-1-methyl-3-thiocyanatoacetyl-2-
Preparation of imidazolidinone: In 50 ml of methanol (4
S, 5S) -1-Bromoacetyl-4,5-diphenyl-3-methyl-2-imidazolidinone 4.52 g (1
2.1 mmol) and 1.31 g of potassium thiocyanate (1
(3.5 mmol) was added and the mixture was heated under reflux for 4 hours. Thereafter, the same operation as in Example 1 was carried out to obtain 3.89 g of the title compound (yield: 9
2%).

Mp 77.8 to 78.6 ° C [α] ^23.7 _D = -60.5 ° (c = 1.00, CHCl ₃ ) UV (λ ^MeOH _max nm): 209.6 (ε 23300) IR (ν ^KBr _max cm ^-1 ): 2150, 1715, 1685 ¹ H-NMR (CDCl ₃ ) δ: 2.82 (3H, s), 4.37 (1H, d, J = 3.7Hz), 4.
49 (1H, d, J = 15.4Hz), 4.57 (1H, d, J = 15.4Hz), 5.04 (1H, d,
J = 3.7Hz), 7.16 to 7.26 (4H, m), 7.35 to 7.46 (6H, m) ¹³ C-NMR (CDCl ₃ ) δ: 29.09, 38.22, 63.67, 67.72, 111.
61, 125.38, 126.12, 128.60, 129.23, 129.28, 129.58,
137.57, 139.25, 154.15,164.96

Production Example 7 (4S, 5S) -4,5-diphenyl-1-methyl-3- (4-phthalimidobutyl)
Preparation of 2-imidazolidinone: 0.28 g (55%) of sodium hydride in 10 ml of N, N-dimethylformamide.
% 6.48 mmol) and (4S, 5S) -4,5-diphenyl-1-methyl-2-imidazolidinone 1.36 g
(5.40 mmol) was added and the mixture was stirred at room temperature for 20 minutes to prepare a sodium salt. Then, 1.52 g (5.40 mmol) of N- (4-bromobutyl) phthalimide was added to the reaction solution, and the mixture was stirred at room temperature for 16 hours. The reaction solution was added to a dilute aqueous hydrochloric acid solution and extracted with methylene chloride. The extract solution was washed with water and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain an oily residue. This residue was purified by silica gel chromatography (solvent: chloroform) to give 1.
76 g (yield 72%) was obtained.

IR (ν ^neat _max cm ^-1 ): 1750, 1705 ¹ H-NMR (CDCl ₃ ) δ: 1.36 to 1.39 (2H, m), 1.59 to 1.66 (2H,
m), 2.66 (3H, s), 2.86 ~ 2.88 (1H, m), 3.43 ~ 3.48 (1H, m),
3.58 (2H, t, J = 7.3Hz), 4.09 (1H, d, J = 8.0Hz), 4.19 (1H, d,
J = 8.0Hz), 7.09 ~ 7.36 (10H, m), 7.66 ~ 7.69 (2H, m), 7.78
~ 7.81 (2H, m)

Production Example 8 (4S, 5S) -1- (4-aminobutyl) -4,5-diphenyl-3-methyl-2-
Preparation of imidazolidinone: In 100 ml of ethanol (4
S, 5S) -4,5-Diphenyl-1-methyl-3-
(4-phthalimidobutyl) -2-imidazolidinone 1.76 g (3.89 mmol) and hydrazine hydrate 5.0
g (99.8 mmol) was added, and the mixture was heated under reflux for 3 hours. After cooling, the precipitated crystals were separated by filtration, an aqueous sodium hydroxide solution was added to the filtrate, and the mixture was extracted with methylene chloride. The extract was washed with water and dried over anhydrous sodium sulfate. Then, the solvent was distilled off under reduced pressure to obtain 1.20 g (yield 100%) of the title compound.

IR (ν ^neat _max cm ^-1 ): 1700 ¹ H-NMR (CDCl ₃ ) δ: 1.26 to 1.42 (6H, m), 2.60 to 2.65 (2H,
m), 2.68 (3H, s), 2.74 ~ 2.81 (1H, m), 3.44 ~ 3.50 (1H, m),
4.09 (1H, d, J = 8.3Hz), 4.21 (1H, d, J = 8.3Hz), 7.08 ~ 7.36
(10H, m)

Example 3 (4S, 5S) -4,5-diphenyl-1-methyl-3- (4-thiocyanatobutyl)
Preparation of 2-imidazolidinone: (4S, 5S) -1- (4-aminobutyl) -4, in 20 ml of methylene chloride
1.21 g (3.92 mmol) of 5-diphenyl-3-methyl-2-imidazolidinone, 0.33 g of carbon disulfide
(4.31 mmol) and 1.38 g of triethylamine (1
(3.71 mmol) was added and the mixture was stirred at room temperature for 2.5 hours. Then, 0.79 g (4.70 mmol) of 2-chloro-1,3-dimethylimidazolinium chloride was added to the reaction solution, and the mixture was stirred at room temperature for 16 hours. Water was added to the reaction solution, which was extracted with methylene chloride. The extract was washed with water and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to give an oily residue. The residue was purified by silica gel chromatography (solvent n-hexane / ethyl acetate) to give 1.29 g of the title compound.
(Yield 90%) was obtained.

IR (ν ^neat _max cm ^-1 ): 2090, 1695 ¹ H-NMR (CDCl ₃ ) δ: 1.42 to 1.67 (4H, m), 2.69 (3H, s), 2.8
7 to 2.94 (1H, m), 3.40 to 3.47 (3H, m), 4.13 (1H, d, J = 8.0H
z), 4.19 (1H, d, J = 8.0Hz), 7.08〜7.37 (10H, m)

EXAMPLE 4 Optical isomer analysis of 1,2-diphenylethylamine: (4S, 5S) in 5 ml of toluene.
145 mg of 4,5-diphenyl-1-methyl-3- (4-thiocyanatobutyl) -2-imidazolidinone (0.
39 mmol) and 1,2-diphenylethylamine 77 mg
(0.39 mmol) was added and the mixture was stirred at room temperature for 24 hours. Then, the residue obtained by distilling off the solvent under reduced pressure was purified by silica gel chromatography (solvent: toluene / ethyl acetate) to obtain an equal mixture of diastereomers (4S, 5).
S) -4,5-diphenyl-1- [4- (3- (1,2
-Diphenylethyl) thioureido] butyl] -3-methyl-2-imidazolidinone (IR (ν ^neat _max cm ^-1 ): 33
00, 1670). When this mixture was analyzed by nuclear magnetic resonance spectroscopy (300MHz, CDCl ₃ ), peaks (equal amounts) of the methyl groups of S, S, S and S, S, R were detected at 2.64ppm and 2.68ppm. Admitted.

Example 5 Analysis of optical isomers of 1- (1-naphthyl) ethylamine (4S, 5S) -4,5-diphenyl-1-methyl-3- (4-thiocyanatobutyl) -in 10 ml of benzene. Two
-Imidazolidinone 310 mg (0.85 mmol) and 1-
(1-Naphthyl) ethylamine 145 mg (0.85 mmo
l) was added and the mixture was stirred at room temperature for 24 hours. Then, the solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel chromatography (solvent: toluene / ethyl acetate) to obtain an equivalent mixture of diastereomers (4S, 5S) -4,5.
-Diphenyl-1- [4- [3- [1- (1-naphthyl) ethyl] thioureido] butyl] -3-methyl-2
-Imidazolidinone (IR (ν ^neat _max cm ^-1 ): 3310, 167
0). This mixture was analyzed by nuclear magnetic resonance spectroscopy (3
00MHz, CDCl ₃ ) 2.46ppm and 2.50pp
At m, peaks (equal amounts) of S, S, S isomer and S, S, R isomer, respectively, were observed.

[0057]

By using the compound (1) of the present invention, the optical purity of amines having an asymmetric carbon can be accurately analyzed and determined by a simple operation.

Claims (3)

[Claims] 1. The following general formula (1): [Wherein R ¹ represents an alkyl group, R ² represents an alkylene group, l represents a number of 0 or 1, and * represents a position of an asymmetric carbon]. -Diphenyl-2
-Imidazolidinone derivatives. 2. The 4,5-diphenyl-2 according to claim 1,
-A reagent for optical purity analysis of amines having an asymmetric carbon, characterized by containing an imidazolidinone derivative. 3. The optically active 4,5-diphenyl-2-imidazolidinone derivative according to claim 1 is reacted with an amine having an asymmetric carbon, and the resulting thiourea derivative is subjected to nuclear magnetic resonance spectrum analysis. An optical purity analysis method for amines having an asymmetric carbon, characterized in that