JP2995206B2 - Optical resolution method - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for optically resolving polyfunctional compounds.

[0002]

2. Description of the Related Art Aliphatic diols, dihydroxybiaryls, hydroxyoximes and the like generally show only neutral or weak acidity, and therefore do not normally interact with the resolving agent as they are, and have a plurality of functional groups. Is a compound that is extremely difficult to resolve. The few conventional optical resolution methods are methods of resolving after conversion to derivatives such as esters, and are not practical because resolving agents are difficult to obtain.

[0003] 1,1'-Bi-2-naphthol (for example, J. Am. Chem. Soc., 106 , 6) which is an optically active compound extremely effective in a wide range of asymmetric reactions.
709 (1984)), a phosphoric ester obtained by allowing phosphorus oxychloride to act on racemic 1,1'-bi-2-naphthol is treated with cinchonine,
Or division with cinchonidine (Org. Synth., 6
7, 1 (1988)) or resolution with optically active 2-aminobutanol (Synthesis, 222 (199)
0)), and then reduced with lithium aluminum hydride (O
rg. Synth. , 67, 13 (1988)) to obtain optically active 1,1'-bi-2-naphthol. However, these methods require a complicated operation of once leading 1,1'-bi-2-naphthol to a phosphate ester, optically resolving this, and then reductively removing the phosphate moiety. There is a problem that phosphine, which is a poison gas, is generated in the process.

[0004]

That is, an object of the present invention is to solve the above-mentioned problems, and it is an object of the present invention to provide a dihydroxybiary which is a racemic or partially resolved compound.
, Aliphatic diols and hydroxy oximes
An object of the present invention is to provide an effective optical resolution method for a polyfunctional compound containing no carboxyl group selected from the group . Another object of the present invention is to provide a method for optically resolving the polyfunctional compound which is easy to operate, industrially safe, and practical.

[0005]

Means for Solving the Problems The present inventors have developed an aliphatic geo
Lumpur, dihydroxybiaryl, at least two hydro containing no carboxyl group, such as hydroxy oxime
It has been found that effective optical resolution can be achieved by using a bifunctional diamino compound as a resolving agent for a compound having a xyl group, and the optical resolution method of the present invention has been completed.

The present invention has the following configuration. Dihydroxybiali , a racemic or partially resolved compound
Alcohols, aliphatic diols and hydroxy oximes.
Polyfunctional compound containing no carboxyl group selected from the group that optical (hereinafter, polyfunctional compounds may be referred to)
Complexes formed by hydrogen bonding by the action of a bifunctional resolving agent comprising an active diamino compound (hereinafter sometimes referred to as a resolving agent)
The optical resolution method of the polyfunctional compound, characterized by forming

[0007]

[0008]

In the optical resolution method of the present invention, the polyfunctional compound and the optically active bifunctional compound are preferably similar in structural symmetry, and most preferably the same.

The polyfunctional compounds of the optical resolution method of the present invention include 1,2-butanediol, 1,3-butanediol, 2,3-butanediol, 3,4-hexanediol, and 4,5-octanediol. 5,6-decanediol, 1,2-cyclopentanediol, 1,2-cyclohexanediol, 1,2-cyclooctanediol,
1,2-diphenyl-1,2-ethanediol, 1,2
-Dihydro-1,2-dihydroxybenzene, 2,2 '
-Dihydroxy-1,1'-binaphthyl, 6,6'-dibromo-2,2'-dihydroxy-1,1'-binaphthyl, 6,6'-dimethyl-2,2'-dihydroxy-
1,1'-biphenyl, 2-hydroxy-3-hydroxyiminobutan, 3-hydroxy-4-hydroxyiminohexane, 4-hydroxy-5-hydroxyiminooctane, 5-hydroxy-6-hydroxyiminodecane, 1,2 -Diphenyl-1-hydroxy-2-hydroxyiminoethane, and 1,2-bis (4-methoxy
Phenyl) -1-hydroxy-2-hydroxyiminoe
A compound in which a part of a rayami body or a racemate selected from the group consisting of tan is resolved.

On the other hand, bifunctional compounds used as resolving agents include 1,2-diaminopropane, 2,3-diaminobutane, 1,2-diaminocyclohexane, 1,2-diamino-1,2-diphenylethane, And optically active compounds such as 2,2'-diamino-1,1'-binaphthyl. The solvent used in the resolution method of the present invention is usually benzene,
Aromatic hydrocarbons such as toluene and xylene; ethers such as diethyl ether, tetrahydrofuran and dioxane; aliphatic hydrocarbons such as pentane and hexane ;
Tolyl or these solvents with methanol, ethanol
Alcohols selected from the group of solvents consisting of
However, a mixed solvent that does not use a polyester as a main solvent can be used.

The amount of the resolving agent used is usually 0.5 to 1.5 equivalents to the polyfunctional compound, but preferably 1 equivalent. If it is less than 0.5 equivalent or more than 1.5 equivalent, it may affect the chemical yield and the optical purity.

2 formed from a resolving agent and a polyfunctional compound
Species diastereomeric compounds differ in crystallinity and solubility and can be easily separated from diastereomers by filtration, chromatography and the like. The purity of a crystalline compound can be increased by recrystallization.

The complex formed and separated from the resolving agent and the polyfunctional compound is decomposed by a mineral acid such as hydrochloric acid or sulfuric acid, an organic acid such as acetic acid, or silica gel, and separated into the resolving agent and the polyfunctional compound. can do.

The dividing method of the present invention is specifically the following method.

A polyfunctional compound, which is a racemic or partially resolved compound, and 0.5 to 1.5 equivalents of an optically active bifunctional resolving agent are added to a solvent such as benzene and reacted to form a precipitated crystal. The solid compound is subjected to solid-liquid separation. The obtained crystalline compound is purified by recrystallization using a solvent such as benzene if necessary. By repeating recrystallization, high optical purity can be obtained. Then, this is treated with a mineral acid or the like, and the released optically active polyfunctional compound is separated by filtration or extracted with an organic solvent, washed with water, and dried.
Alternatively, an optically active compound is obtained by eluting with an organic solvent through silica gel column chromatography.

Further, by treating the easily soluble complex obtained by concentrating the filtrate from which the crystalline compound has been removed with a mineral acid,
An enantiomer of the optically active polyfunctional compound obtained from the crystalline compound is obtained. This is further reacted with an enantiomer of the resolving agent used first to lead to a crystalline compound, and the same treatment can be performed to increase the optical purity.

The resulting compound is treated with an acid, and the resolving agent present in the filtrate from which the polyfunctional compound has been removed is treated with an alkali .
As a result, a high yield can be obtained without lowering the optical purity.

Furthermore, by switching the roles of the polyfunctional compound and the resolving agent in the present invention, an optically active compound can be obtained. For example, a racemic diamino compound can be optically resolved with an optically active diol compound to obtain an optically active diamino compound.

The polyfunctional compound is represented by the formula

Embedded image Using 1,1'-bi-2-naphthol represented by the following formula, as an optically active bifunctional resolving agent,

Embedded image The optical resolution method of the present invention using the optically active 1,2-diphenylethylenediamine represented by formula (1) will be specifically described. One is the 1,1'-bi-2 represented by the formula (I).
-Formula for naphthol

Embedded image (R, R)-(+)-1,2-diphenylethylenediamine to form a poorly soluble complex,
Treating the complex with a mineral acid and formula

Embedded image (R)-(+)-1,1'-bi-2-naphthol represented by the following formula:

The other one is represented by the formula (I)
1′-B-2-naphthol has the formula

Embedded image Is reacted with (S, S)-(-)-1,2-diphenylethylenediamine to form a poorly soluble complex, and the complex is treated with a mineral acid;

Embedded image To obtain (S)-(-)-1,1'-bi-2-naphthol.

The optically active 1,2-diphenylethylenediamine of the formula [II] can be obtained by converting the (R, R)-(+) of the formula (II _R )
-1,2-diphenylethylenediamine and a compound of the formula (I
( _Is ) is (S, S)-(-)-1,2-diphenylethylenediamine which is an optically active threo-1,2-diphenylethylenediamine. Use any of these depending on the purpose.

The amount of the optically active 1,2-diphenylethylenediamine used is 0.5 to 1.0 equivalent relative to racemic 1,1'-bi-2-naphthol. When the amount is less than 0.5 equivalent, the yield decreases, and when the amount is 1.0 equivalent or more, the yield and the optical purity are not affected, but it is uneconomical. The action of optically active 1,2-diphenylethylenediamine on racemic 1,1'-bi-2-naphthol is to form a poorly soluble complex after dissolving in a solvent.

Hydrochloric acid, sulfuric acid or the like is used as a mineral acid, the amount of which is equal to or more than the optically active 1,2-diphenylethylenediamine used.
It is used as an alcohol mixed solution, and its concentration is not limited, but 0.1-1M is preferable. When an alcoholic aqueous solution is used, the content of alcohol is desirably 50% or less to facilitate the precipitation of 1,1'-bi-2-naphthol.

As the solvent, an aromatic hydrocarbon such as benzene or toluene, or a mixed solvent thereof with an aliphatic hydrocarbon such as hexane can be used. Poorly soluble
The temperature of the treatment of the complex with the mineral acid is usually 0 ° C to 30 ° C, preferably 0 ° C to 15 ° C.

The specific method described above is as follows. Racemic 1,1'-bi-2-naphthol and 0.5 to 1.5 equivalents of optically active 1,2-diphenylethylenediamine are added to a solvent such as benzene, dissolved by heating, and then cooled to obtain a supersaturated solution. The precipitated hardly soluble complex is separated by solid-liquid separation, or a benzene solution of racemic 1,1'-bi-2-naphthol is added with 0.5 to 1.5 equivalents of optically active 1,
A benzene solution of 2-diphenylethylenediamine is added, and the precipitated hardly soluble complex is subjected to solid-liquid separation.

The obtained complex is purified by recrystallization using a solvent such as benzene if necessary. The resulting poorly soluble complex
The body is treated with a mineral acid to release the optically active 1,1'-bi-2-naphthol as a white solid. This is collected by filtration, washed with water and dried to obtain an optically active (R)-(+)-.
1,1'-bi-2-naphthol or (S)-(-)
-1,1'-bi-2-naphthol is obtained.

Further, poorly soluble by treating the readily soluble complex obtained by concentrating the filtrate obtained by removing insoluble complex with a mineral acid
Optically active 1,1'-bi-2- having a configuration opposite to that of optically active 1,1'-bi-2-naphthol obtained from the complex
Naphthol is obtained. This leads to a poorly soluble complex ,
The optical purity can be increased by performing the same treatment.

On the other hand, the optically active 1,2-diphenylethylenediamine present as a mineral salt in an aqueous solution is recovered in a high yield by alkali treatment without a decrease in optical purity, and can be reused as a resolving agent. .

The poorly soluble complex formed is (R)-(+)
-1,1'-bi-2-naphthol. (R, R)-(+)
-1,2-diphenylethylenediamine complex or (S)-(-)-1,1'-bi-2-naphthol.
(S, S)-(-)-1,2-diphenylethylenediamine complex . These poorly soluble complexes are hydrolyzed by treatment with a mineral acid to give (R)-(+)-1,1'-
Bi-2-naphthol or (S)-(-)-1,1 '
-Bi-2-naphthol is liberated.

The optically active 1,2-diphenylethylenediamine of the formula (II) is

Embedded image The optically active 1,2-diaminocyclohexane represented by the formula (I _R ) or (I _s )
The optically active 1,1'-bi-2-naphthol represented by the following formula can be obtained.

One of them is the one represented by the formula (I).
Formula for 1'-bi-2-naphthol

Embedded image (IR, 2R)-(-)-1,2-diaminocyclohexane represented by the formula (1) to form a poorly soluble complex, the complex is treated with a mineral acid, and the ( _R ) represented by the formula (IR) −
(+)-1,1'-Bi-2-naphthol is obtained.

The other one is represented by the formula (I)
1′-B-2-naphthol has the formula

Embedded image Is reacted with (IS, 2S)-(+)-1,2-diaminocyclohexane to form a poorly soluble complex, and the complex is treated with a mineral acid to give (S) represented by the formula (I _s ). −
(-)-1,1'-Bi-2-naphthol is obtained. The detailed procedure is the same as described above.

According to the above method, the poorly soluble complex formed from the solvent containing the aromatic hydrocarbon is (R)-(+)-
1,1'-binaphthol. (IR, 2R)-(-)-
1,2-diaminocyclohexane / aromatic hydrocarbon (1: 1: n) complex or (S)-(−)-1,1 ′
-Bi-2-naphthol.・ (IS, 2S)-(+)-
It is a 1,2-diaminocyclohexane / aromatic hydrocarbon (1: 1: n) complex. Here, n is n when the aromatic hydrocarbon is benzene, toluene, or xylene.
= 2, n = 1, and n = 1. These complexes emit aromatic hydrocarbons when heated to a temperature higher than the boiling point of the aromatic hydrocarbons contained in the complexes, and (R)-(+)-1,1'-bi-2-naphthol. (1R, 2R )-(-)-1,2-
Diaminocyclohexane (1: 1) complex or (S)
-(-)-1,1'-bi-2-naphthol. (1S, 2
S)-(+)-1,2-diaminocyclohexane (1:
1) It becomes a complex. The complex formed from a solvent containing no aromatic hydrocarbon is (R)-(+)-1,1'-bi-2.
-Naphthol. (1R, 2R)-(-) 1,2-diaminocyclohexane (1: 1) complex or (S)-
(-)-1,1'-bi-2-naphthol. (1S, 2
S)-(+)-1,2-diaminocyclohexane (1:
1) It is a complex.

Each of these poorly soluble complexes is hydrolyzed by treatment with a mineral acid to give (R)-(+)-1,
1'-bi-2-naphthol or (S)-(-)-
Releases 1,1'-bi-2-naphthol.

The optical resolution method of the present invention is a method in which a polyfunctional compound serving as a compound to be resolved and an optically active bifunctional resolving agent are used.
It is characterized by causing interaction at several places. The interaction is a hydrogen bond between the respective functional groups of the polyfunctional compound and the optically active difunctional resolving agent. For example, a bond generated between a hydroxyl group, a hydroxyimino group, and an amino group . Specifically, ( a) a hydroxyl group
Bond between amino acid and amino group and (b) hydroxyimino
Hydrogen bond between the amino group and the amino group .

Embedded image That is, two types of hydrogen bonds form two types of compounds that are in a diastereomeric relationship and have significantly different three-dimensional structures, and that the two types of compounds have significantly different physical properties such as solubility. Can be divided very effectively.

[0037]

Next, the present invention will be described more specifically with reference to examples, but the scope of the present invention is not limited thereby. (Example 1) [α] _D ²⁰ -36.7 ° (c 4.
1.28 g (11.2 mmol) of (1R, 2R)-(−)-1,2-diaminocyclohexane of ( 14 , H ₂ O)
And dl-threo-2,3-butanediol 1.
After adding 00 g (11.1 mmol) and stirring with heating,
After cooling to room temperature, the precipitated crystals were
By recrystallization twice, (1R, 2R)-(-)-
1,2-diaminocyclohexane. (2R, 3R)-
1.00 g of (-)-2,3-butanediol was obtained. The physical properties are as follows. m. p. 128-138 ° C, ¹ H-NMR (CDCl ₃ ) δ: 1.2 (d) 6H),
2.3 (s, 6H), 0.8-2.7 (m, 10H),
3.3-4.0 (m, 2H) Dissolve 1.00 g (4.89 mmol) of these crystals in ethanol, pass through a silica gel short column, concentrate, and concentrate on (2R, 3R)-(-)-2, 0.428 g (4.75 mmol) of 3-butanediol was obtained. Yield 86
%, [Α] D ²⁰ -4.8 ° (c 0.3, EtOH)
Met.

Example 2 [α] _D ²⁰ -36.7 ° (c 4.
1.00 g (8.76 mmol) of (1R, 2R)-(−)-1,2-diaminocyclohexane of (14, H ₂ O)
And dl-trans-1,2-cyclohexanediol 1.02 g (8.78 mmol) were added, and the mixture was heated and stirred, and then cooled to room temperature.
By recrystallizing twice from l, (1R, 2R)-
(-)-1,2-diaminocyclohexane. (1R, 2
R)-(-)-1,2-cyclohexanediol 0.4
85 g were obtained. The physical properties are as follows. m. p. 73-76 ° C, IR (cm ^-1 , KBr disk): 3450,34
_{^{00,3350,3600-2400,1070 1 H-NMR (CDCl 3}} ) δ: 0.7-2.7 (m)
18H), 2.5 (brs, 6H), 3.1-3.6.
(M, 2H) 0.485 g (2.11 mmol) of these crystals was dissolved in ethanol, passed through a silica gel short column, and concentrated, and 0.245 g of (1R, 2R)-(−)-1,2-cyclohexanediol ( 2.11 mmol). Yield 48%, optical purity 96%, m.p. p. 98-10
0 ° C., [α] _D ²⁴ -44.6 ° (c0.02, H
₂ O).

Example 3 [α] _D ²⁰ -36.7 ° (c)
_{4.14, H} 2 O) of (1R, 2R) - (- ) - 1,2
0.268 g of diaminocyclohexane (2.35 mm
ol) and 0.502 g of dl-threo-1,2-dihydroxy-1,2-diphenylethane (2.34 m
mol), and the mixture was heated and stirred, cooled to room temperature, and the precipitated crystals were recrystallized twice from 5 ml of toluene to give (1R, 2R)-(-)-1,2-diaminocyclohexane. (1S, 0.30 g of 2S)-(-)-1,2-dihydroxy-1,2-diphenylethane was obtained. The physical properties are as follows. m. p. 95-98 ° C, IR (cm ⁻¹ , KBr disk): 3540, 34
_{^{40,3300-2500,1050 1 H-NMR (CDCl 3}} ) δ: 0.8-2.7 (m,
10H), 2.6 (s, 6H), 4.6 (s, 2H),
7.1 (s, 10H) 0.300 g (0.913 mmol) of these crystals was added with 1 ml of methanol and 10 ml of 1M hydrochloric acid under ice-cooling, followed by stirring for 30 minutes. After extraction with methylene chloride, washing with water, drying over anhydrous sodium sulfate, and concentration, (S, S)-(-)-
1,2-dihydroxy-1,2-diphenylethane
193 g (0.901 mmol) were obtained. 77% yield,
The optical purity is 98%, and [α] _D ²⁴ −88.3 ° (c
1.25, EtOH).

Example 4 [α] _D ²⁰ -36.7 ° (c 4.
_{14, H} 2 O) of (1R, 2R) - (- ) - 1,2- diaminocyclohexane 0.826g (7.23mmo
l) and 1.04 g (7.21 mmol) of dl-trans-1,2-cyclooctanediol were added, and the mixture was stirred with heating, cooled to room temperature, and the precipitated crystals were recrystallized twice from 2 ml of toluene ( 1R, 2R)
-(-)-1,2-diaminocyclohexane. (1R,
2R)-(-)-1,2-cyclooctanediol
735 g were obtained. The physical properties are as follows. m. p. 59-63 ° C, IR (cm ^-1 , KBr disk): 3450,36
00-2400, 1040 ¹ H-NMR (CDCl ₃ ) δ: 0.7-2.7 (m,
22H), 2.2 (brs, 6H), 3.4-3.7
(M, 2H) 0.735 g (2.84 mmol) of these crystals was dissolved in ethanol, passed through a silica gel short column, and concentrated, and 0.390 g of (1R, 2R)-(−)-1,2-cyclooctanediol was obtained. (2.70 mmol) was obtained. Yield 75%, [α] _D ²⁴ -16.4 ° (c 0.32
EtOH).

Example 5 [α] _D ²⁰ −35 ° (c 4.0) was added to 10 ml of benzene.
_{0, H} 2 O) of (1R, 2R) - (- ) - 1,2- diaminocyclohexane 1.00 g (8.76 mmol) and dl-1,1'-bi-2-naphthol 2.51g
(8.77 mmol), heated and stirred, cooled to room temperature, and the precipitated crystals were collected by filtration to give (R)-
(+)-1,1'-bi-2-naphthol. (1R, 2
2.05 g (3.68 mmol) of R)-(-)-1,2-diaminocyclohexane-benzene (1: 1: 2) complex
1) was obtained. The yield was 84% (based on half the amount of dl-1,1'-bi-2-naphthol), and the physical properties were as follows. m. p. 144-1478 ° C, [α] _D ²⁴ -16.3 ° (c 1.02, CHC
l ₃ ) IR (cm ⁻¹ , KBr disk): 3450, 33
80, 3300, 3060 2950, 2860, 162
0,1600,1515,1460,1380,136
0, 1230, 1210, 960, 820, 745, 6
95 ¹ H-NMR (CDCl ₃ ) δ: 0.3-2.0 (m,
10H), 3.6 (s, 6H), 7.1-8.3 (m,
12H), 7.4 (s, 12H)

Example 6 (R)-(+)-1,1'- obtained in the same manner as in Example 5.
Bi-2-naphthol ・ (1R, 2R)-(−)-1,2
Under cooling, 5 ml of methanol and 50 ml of 0.1 M hydrochloric acid were added to 2.55 g (4.58 mmol) of -diaminocyclohexane-benzene (1: 1; 2) complex, and the mixture was stirred for 30 minutes. The precipitated white solid was washed with water and dried under reduced pressure to obtain 1.29 g (4.51 mmol) of (R)-(+)-1,1'-bi-2-naphthol. 98% yield,
Optical purity 81%, m.p. p. 202-203 ° C, [α] _D ²⁴ + 29.7 ° (c 0.539, THF)
Met.

(Example 7) (R)-(+)-1,1'- obtained in the same manner as in Example 5.
Bi-2-naphthol ・ (1R, 2R)-(−)-1,2
1.79 g (3.22 mmol) of a diaminocyclohexane-benzene (1: 1; 2) complex was treated with 50 m of benzene.
recrystallized from 1.50 g of unemployed transparent needle-like crystals (2.
69 mmol). The complex was decomposed in the same manner as in Example 6 to obtain 0.764 g (2.67 mmol) of (R)-(+)-1,1'-bi-2-naphthol. 83% yield, 96% optical purity, m.p. p. 202-20
4 ° C., [α] _D ²⁴ + 35.0 ° (c 0.500, T
HF).

Example 8 Instead of (1R, 2R)-(−)-1,2-diaminocyclohexane used in Example 5, [α] _D ²⁴ + 35 ° was used.
(C _{4.00, H} 2 O) of the (1S, 2S) - (+ ) -
Example 5 using 1,2-diaminocyclohexane
And by performing the same operation as in Example 7,
(S)-(-)-1,1'-Bi-2-naphthol was obtained. 75% yield (based on half the amount of dl-1,1'bi-2-naphthol), 96% optical purity, m.p. p. 20
2-204 ° C, [α] _D ²⁴ -35.1 ° (c 0.5
04, THF).

Example 9 [α] _D was added to 5 ml of benzene.
²⁴ + 103 ° (c 1.00, MEOH) at (R,
R)-(+)-1,2-diphenylethylenediamine 1
0.0 g (47.1 mmol) and dl-1,1'-
13.5 g (47.1 mmol) of bi-2-naphthol was added, dissolved by heating, cooled to room temperature, and the precipitated crystals were collected by filtration to obtain a poorly soluble complex. This complex is purified by recrystallizing it four times from 20 ml of benzene.
(R)-(+)-1,1'-bi-2-naphthol.
(R, R)-(+) 1,2-diphenylethylenedia
7.97 g of the min complex were obtained. Yield 68% (dl-1.
1'-bi-2-naphthol), and the physical properties are as follows. m. p. 55-57 ° C, [α] _D ²⁴ + 14.8 °
(C 0.500, benzene) IR (cm ^-1 , KBr
disk): 3520, 3420, 3390, 330
0,3600-2000,1615,1590,150
_{^{5 1 H-NMR (CDCl 3}} ) δ: 3.20 (s, 6
H), 3.78 (s, 2H), 6.8-8.1 (m, 1
2H), 7.33 (s, 10H)

(Example 10) (R)-(+)-1,1'-bi-2-naphthol. (R, R)-(+) 1,2-diphenylethylenediamine complex 2 obtained in Example 9 .12 g (4.25 mmol)
Under ice cooling, 150 ml of 0.1 M hydrochloric acid was added, and the mixture was stirred for 30 minutes. After washing precipitated white solid with water, and dried in vacuo, (R) - to obtain a 1,1'-bi-2-naphthol 1.19g (4.16mmol) - (+) . 66% yield
(Relative to half of dl-1.1'-bi-2-naphthol), m.p. p. 202-203 ° C, [α] _D ²⁴
+ 30.1 ° (c 0.500, THF).

(Example 11) (R,
[Α] _D ²⁴ −103 ° (c 1.00, Me) instead of R)-(+)-1,2-diphenylethylenediamine
Using (S, S)-(-)-1,2-diphenylethylenediamine of (OH), the same operation as in Example 9 (however, purification of the complex by recrystallization is omitted) and Example 10 is performed. In this way, (S)-(-)-1,1'-
2-Naphthol was obtained. Yield 123% (dl-1,1 '
-Bi-2-naphthol), m.p.
p. 202-204 ° C, [α] _D ²⁴ -20.8 ° (c
0.504, THF).

Example 12 [α] _D ²⁰ + 103 ° (c 1.0
1.00 g of (1R, 2R)-(+)-1,2-diamino-1,2-diphenylethane of (0, MeOH).
mmol) and dl-6,6'-dibromo-2,2 '
-Dihydroxy-1,1'-binaphthyl 2.09 g
(4.71 mmol) was added, and the mixture was heated and stirred, cooled to room temperature, and the precipitated crystals were recrystallized once from 3 ml of ether to give (1R, 2R) -1,2-diamino-1,2-diphenyl. Ethane ・ (R)-(-)-6
6'-dibromo-2,2'-dihydroxy-1,1'-
0.836 g of binaphthyl was obtained. The physical properties are as follows. m. p. 101-104 ° C, IR (cm ⁻¹ , KBr disk): 3460, 34
00, 3320, 3600-2400, 1610, 15
90, 1500, 820, 700 ¹ H-NMR (CD ₃ SOCD ₃ ) δ: 3.4 (br
s, 6H), 3.7 (s, 2H), 6.7-8.0.
(M, 20H) To 0.00.836 g (1.27 mmol) of the crystals were added 3 ml of ethanol and 10 ml of 1M hydrochloric acid under ice-cooling to give 30 ml.
Stirred for minutes. The precipitated crystals are collected by filtration, dried in vacuum,
0.410 g of (R)-(-)-6,6'-dibromo-2,2'-dihydroxy-1,1'-binaphthyl (0.9
23 mmol). Yield 39%, m.p. p. 109-
114 ° C., [α] ₅₇₈ ²⁴ -131.7 ° (c 0.
501, CH ₂ Cl ₂ ). (Literature value: [α]
₅₇₈ ²⁴ -129 ° (c 1.0, CH ₂ Cl ₂ ))
Met.

Example 13 [α] _D ²⁰ -36.7 ° (c) was added to 10 ml of benzene.
_{4.14, H} 2 O) of (1R, 2R) - (- ) - 1,2
2.00 g of diaminocyclohexane (17.5 mmol
l) and dl-1-hydroxy-2-hydroxyimino-1,2-diphenylethane 4.00 g (17.6 m
mol)), and the mixture was heated and stirred, cooled to room temperature, and the precipitated crystals were recrystallized twice from 30 ml of benzene to give (1R, 2R)-(-)-1,2-diaminocyclohexane. (R 2.) g of)-(-)-(E) -1-hydroxy-2-hydroxyimino-1,2-diphenylethane were obtained. The physical properties are as follows.
m. p. 85-100 ° C, IR (cm ⁻¹ , KBr disk): 3500,34
00, 3360, 3330, 3300, 3250, 36
00-2400,960,710 ¹ H- NMR (CDCl ₃ -CD ₃ SOCD ₃ ) δ:
0.7-2.7 (m, 10H), 2.7-4.6 (br
s, 6H), 5.6 (s, 1H), 7.2 (s, 10
H) 2 ml of ethanol and 10 ml of 1M hydrochloric acid were added to 1.00 g (2.93 mmol) of the crystals under ice cooling, and the mixture was stirred for 30 minutes. The precipitated crystals are collected by filtration, dried in vacuum,
0.483 g of (R)-(E) -1-hydroxy-2-hydroxyimino-1,2-diphenylethane (2.13
mmol). Yield 56%, [α] _D ²⁴ -5.1
2 ° (c 0.508, CHCl ₃ ), (literature value:
[Α] _D ²⁴ -3.2 (c 0.5, CHCl ₃ ))
Met. ¹ H-NMR (CD ₃ COCD ₃ -CD ₃ S
OCD ₃ ) δ: 4.8 (s, 1H), 5.6 (s, 1
H), 7.2 (s, 10H) and 10.0 (s, 1H).

Example 14 [α] _D ²⁰ -103.1 ° (c) was added to 3 ml of benzene.
1.00, MeOH) of (1S, 2S)-(-)-1,
0.934 g of 2-diamino-1,2-diphenylethane
(4.40 mmol) and dl-1-hydroxy-2
-Hydroxyimino-1,2-diphenylethane 1.0
After adding 0 g (4.40 mmol) and stirring with heating, the mixture was cooled to room temperature, and the precipitated crystals were recrystallized once from 2 ml of benzene to give (1S, 2S)-(-)-.
1,2-diamino-1,2-diphenylethane-1
0.250 g of -hydroxy-2-hydroxyimino-1,2-diphenylethane were obtained. The physical properties are as follows. m. p. 152-155 ° C, [α] _D ²⁴ −
8.98 ° (c 1.00, CHCl ₃ ) ¹ H-NMR (CDCl ₃ ) δ: 4.2 (s, 2H),
5.6 (s, 1H), 7.3 (s, 20H) To 0.250 g (0.569 mmol) of these crystals were added 2 ml of ethanol and 20 ml of 1M hydrochloric acid under ice-cooling, followed by stirring for 30 minutes. The precipitated crystals are collected by filtration, dried in vacuum,
0.129 g (0.5) of (S)-(+)-1-hydroxy-2-hydroxyimino-1,2-diphenylethane
69 mmol). Yield 26%, [α] _D ²⁴ +
7.95 ° (c 1.01, CHCl ₃ ), ¹ H-NM
R (CD ₃ SOCD ₃ ) δ: 3.3 (s, 1.5H),
5.5 (s, 0.5H), 5.9 (brs, 0.5
H), 7.20 (s, 5H), 7.25 (s, 5H),
10.7 (s, 0.5H).

Example 15 [α] _D ²⁰ −35 ° (c 4.0) was added to 25 ml of toluene.
_{0, H} 2 O) of (1R, 2R) - (- ) - 1,2- diaminocyclohexane 1.00 g (8.76 mmol) and dl-1,1'-bi-2-naphthol 2.51g
(8.77 mmol), heated and stirred, cooled to room temperature, and the precipitated crystals were collected by filtration to give (R)-
(+)-1,1'-bi-2-naphthol. ( 1R, 2
R )-(-)-1,2-diaminocyclohexane / toluene (1: 1: 1) complex, 2.15 g (4.36 mmol)
1) was obtained. Yield 100% (dl-1,1'-bi-2-
Naphthol), and the physical properties are as follows. m. p. 150-155 ° C, [α] _D ²⁴ -16.3 ° (c 1.02, CHC
l ₃ ) IR (cm ⁻¹ , KBr disk): 3450, 33
80, 3300, 3060, 1620, 1600, 15
15,820,745 ¹ H-NMR (CDCl ₃ ) δ: 0.3-2.0 (m,
10H), 2.3 (s, 3H), 3.7 (s, 6H),
7.1-8.0 (m, 12H), 7.3 (s, 5H) 5 ml of methanol and 50 m of 1M hydrochloric acid were added to this complex under ice-cooling.
was added and stirred for 10 minutes. The precipitated white solid was washed with water and dried under reduced pressure to give (R)-(+)-1,1'-
1.23 g (4.30 mmol) of bi-2-naphthol was obtained. Yield 98% (based on half of dl-1,1'bi-2-naphthol), Optical yield 100% ee (HPLC,
CHIRALPAK OP, manufactured by Daicel Chemical Industries, Ltd.
(MEOH, 0.5 ml / min).

(Example 16) [α] _D ²⁰ -35 ° (c) was added to 25 ml of m-xylene.
_{4.00, H} 2 O) of (1R, 2R) - (- ) - 1,2
1.00 g of diaminocyclohexane (8.76 mmol
l) and dl-1,1'-bi-2-naphthol 2.5
1 g (8.77 mmol) was added, and the mixture was heated and stirred, cooled to room temperature, and the precipitated crystals were collected by filtration.
(R)-(+)-1,1'-bi-2-naphthol. (1
2.20 g of (R, 2R)-(-)-1,2-diaminocyclohexane.m-xylene (1: 1: 1) complex (4.
34 mmol). Yield 99% (dl-1,1'-
Bi-2-naphthol), and the physical properties are as follows. m. p. 150-155 ° C, IR (cm ⁻¹ , KBr disk): 3450, 33
80, 3300, 3060, 1620, 1600, 15
15,820,745 ¹ H-NMR (CDCl ₃ ) δ: 0.3-2.0 (m,
10H), 2.3 (s, 6H), 3.7 (s, 6H),
7.1-8.0 (m, 12H), 7.3 (s, 4H) 5 ml of methanol and 50 m of 1M hydrochloric acid were added to this complex under ice cooling.
was added and stirred for 10 minutes. The precipitated white solid was washed with water and dried under reduced pressure to give (R)-(+)-1,1'-
1.20 g (4.19 mmol) of bi-2-naphthol were obtained. 96% yield (based on half of dl-1,1'bi-2-naphthol), 100% ee optical yield (HPLC,
CHIRALPAK OP manufactured by Dial Chemical Industry Co., Ltd.
(MEOH, 0.5 ml / min) .

[0053]

EFFECT OF THE INVENTION The resolution method of the present invention provides an optically active diamination
By using consists compound bifunctional resolving agent, racemate
Dihydroxy, a dimeric or partially resolved compound
Biaryls, aliphatic diols and hydroxyoximes
And a polyfunctional compound containing no carboxyl group selected from the group consisting of: In other words, it is a practical optical resolution method that can easily resolve a compound that has been difficult to resolve directly until it can be resolved without conversion to a derivative. In addition, the operation is simple, industrially safe and practical.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code FI C07C 35/06 C07C 35/06 35/14 35/14 35/20 35/20 39/14 39/14 39/38 39/38 249/14 249/14 251/40 251/40 251/48 251/48

Claims (4)

(57) [Claims] 1. A racemic or partially resolved compound, dihydroxybiaryl, an aliphatic diol and
Carboxy selected from the group consisting of hydroxyoximes
Optically active diamino compounds to polyfunctional compounds containing no
Complex by hydrogen bonding by the action of bifunctional resolving agent consisting of object
A method for optical resolution of the polyfunctional compound, which comprises forming a body . 2. A solvent containing no alcohol as a main solvent.
In which the bifunctional resolving agent acts on the polyfunctional compound.
2. The optical splitting method according to claim 1, comprising: 3. The dihydroxybiaryl, aliphatic di
Selected from the group consisting of all and hydroxy oxime
Polyfunctional compound containing no carboxyl group
Tandiol, 1,3-butanediol, 2,3-buta
Diol, 3,4-hexanediol, 4,5-octane
Tandiol, 5,6-decanediol, 12-cyclo
Pentanediol, 1,2-cyclohexanediol,
1,2-silooctanediol, 1,2-diphenyl-
1,2-ethanediol, 1,2-dihydro-1,2-
Dihydroxybenzene, 2,2'-dihydroxy-1,
1'-binaphthyl, 6,6'-dibromo-2,2'-di
Hydroxy-1,1′-binaphthyl, 6,6′-dimethyl
Ru-2,2'-dihydroxy-1,1'-biphenyl,
2-hydroxy-3-hydroxyiminobutane, 3-hi
Droxy-4-hydroxyiminohexane, 4-hydro
Xy-5-hydroxyiminooctane, 5-hydroxy
-6-hydroxyiminodecane, 1,2-diphenyl-
1-hydroxy-2-hydroxyiminoethane, and
1,2-bis (4-methoxyphenyl) -1-hydroxy
Selected from the group consisting of c-2-hydroxyiminoethane
Racemic or partially racemic compound
And a bifunctional compound comprising the optically active diamino compound.
The resolving agent is 1,2-diaminopropane, 2,3-diamino
Butane, 1,2-diaminocyclohexane, 1,2-di
Amino-, 2-diphenylethane, 2,2'-diamino
-1,1'-binaphthyl
Item 1. The optical resolution method according to item 1 or 2. 4. The dihydroxybiaryl, aliphatic di
Carboki selected from all and hydroxy oxime
Polyfunctional compound containing no sill group, 2,3-Bed Tanji
All, 1,2-cyclohexanediol, 1,2-di
Phenyl-, 2-ethanediol, 1,2-cyclooctane
Tandiol, 2,2'-dihydroxy-11'-bina
Futyl, 6,6'-dibromo-2,2'-dihydroxy
-1,1'-binaphthyl or 1,2-diphenyl-1
-Hydroxy-2-hydroxyiminoethane racemate
Or a compound in which a part of the racemate is resolved,
A bifunctional resolving agent comprising the optically active diamino compound
1,2-diaminocyclohexane or 1,2-diamido
3. The compound according to claim 1, which is no-, 2-diphenylethane.
Optical resolution method described above.