JPS61291535A - Optical resolution of 1,1'-bi-2-naphthol derivative - Google Patents

Abstract

PURPOSE:To carry out the crystallization resolution of the titled compound, by using racemic 1,1'-bi-2-naphthol derivative or a mixture containing one of the optically active isomer in excess as a raw material, dissolving the material in a solvent, cooling the solution to a supersaturated state and adding the crystal of an optically active isomer to the solution. CONSTITUTION:Racemic compound of formula (R<1> and R<2> are alkyl) or a mixture of the compound containing one of the optically active isomer in excess is dissolved in a solvent (e.g. hexane, benzene, etc.), cooled to supersaturated state, and added with the crystal of an optically active compound as a seed crystal to the solution in an amount of 1-20wt% based on the racemic compound or the mixture to effect the crystallizing resolution of the compound. EFFECT:The process can be carried out extremely economically without necessitating expensive or hardly available optical resolution agent.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing an optically active 1,1'-bi-2-naphthol derivative represented by formula (1) (wherein R1 and R2 represent an alkyl group). be.

Furthermore, the optically active form of the above compound (1) can be converted into the optically active form of 1,1'-bi-2-naphthol represented by the formula (2) by steric dealkylation. Therefore, the method of the present invention is suitable for optically active 1,1'-
It is useful in the production of intermediates for B2-S7 toll construction.

Furthermore, the compound represented by Formula 1 (2) has uses such as optically active ligands and phase transfer catalysts.

The optically active 1,1'-bi-2-naphthol represented by the formula (2) is an optically active compound characterized by its axial chirality, and is used as a ligand for asymmetric reduction of ketones, or as an optical compound for amino acids, etc. It is a compound useful as a raw material for optically active kracune ether having resolution ability, or as a chemical resolution agent for asymmetric sulfoxides as it is.

BACKGROUND ART Conventionally, as a method for obtaining optically active 1,1'-bi-2-naphthol, the following method of optically resolving two semiforms of #1t''-bi-2-naphthol has been known. .

(1) A method in which the phosphoric ester is cleaved after optical resolution as cinchonidine salt via the phosphoric ester (T
e-ronhi bn TJBtt,, 1 q 71461 y
).

(2) A method using optically active methyl m-)lyl sulfoxide as a resolving agent (Tetrahairon Le
tt,, f? 84492? ).

Problems to be Solved Conventional techniques have a common problem that the racemic form of 1,1'-bi-2-naphthol is sparingly soluble in water; There is a problem in that racemic synthesis is not easy. Also,
The above method (1) has the problems of using relatively expensive cinchonidine and requiring multiple steps, and (2)
Although this method is quite simple, it has the problem of using a difficult-to-obtain resolving agent, which is an optically active form of methyl m-)lyl sulfoxide.

Means for Solving the Problems The present inventors have developed optically active 1.1 that does not pass through the racemic form of 1,1-bi-2-naphthol and does not use an expensive and/or difficult-to-obtain optical resolving agent. '-B-2-naphthol production method was studied intensively.

(1) First, the manufacturing method for which the present inventors have already applied (Patent No. 11)
1360-15065) directly from 2-alkoxynaphthalene without passing through the poorly soluble 1,1'-bi-2-naphthol, or as necessary, the general formula (2)
A 1,1'-bi-2-naphthol derivative represented by the general formula (1) is obtained by alkylating the 2 semiforms of 1,1'- and -2-7tol represented by; (
2) Next, optically resolve this 1.1'-bi-2-naphthol derivative by a so-called preferential crystallization method and use it as it is; or (3) further improve the optical activity of this 1.1'-bi-2-naphthol derivative. We have completed a process for obtaining optically active 1,1'-be-2-7-toll by dealkylating the body in a steric-retentive manner.

The method of the present invention will be explained in more detail. The general formula (1
) or a mixture in which one optically active form is present in excess over the other optically active form,
First, the mixture is dissolved in an organic solvent.

The solvent used is preferably one in which the solubility of the racemate is greater than the solubility of the optically active substance. For example, hydrocarbons such as hexane, benzene, and toluene; ethers such as ethyl ether and inglovir ether; halogenated hydrocarbons such as chloroform and dichloromethane; methanol, ethanol, and impropanol. , alcohols such as t-butanol; acetone, methyl ethyl ketone, methyl acetate, DM80.
Aprotic polar solvents such as DMIF and mixtures thereof can be used.

Next, it is cooled to supersaturation. However, the smaller the degree of supersaturation, the higher the optical purity of the obtained crystal.

The amount you can get at one time will be smaller. Usually, supersaturation is achieved so that 10 to 100% of the solubility of the racemate at that temperature is precipitated. However, in the case of a mixture in which one optically active substance is present in excess of the other optically active substance, this excess must be taken into consideration in advance.

Next, inoculate. If the optically active substance to be inoculated is a racemate or a mixture close to a racemate, then! body, S
Any of the optically active forms may be used, but when one optically active form is present in excess compared to the other optically active form, the optically active form in the excess is desirable.

There are no particular restrictions on the amount and particle size of seed crystals added.

Usually, it is appropriate to use a powder obtained by crushing crystals in an amount of about 1 to 20% by weight based on the racemate or partially separated mixture in the solution.

The crystallization can be carried out by cooling, by distilling off the solvent, by dropping a solvent with low solubility, etc. In addition to the batch method, it is also possible to introduce a continuous crystallizer. Adjustment of crystallization rate is important.

When the crystallization rate is slowed down, the optical purity of the precipitated crystals tends to increase.

The optically active form of the compound (1) thus obtained was dealkylated in a steric retention manner, and 1.1- and -2-7
Methods for obtaining toll include heating with hydrogen halide and a hydrous organic carboxylic acid (e.g., hydroiodic acid-acetic acid or hydrobromic acid-acetic acid), and treatment with boron tribromide at low temperature [e.g. J, Amer,
Chew, soc.

104.881 (1982)).

Effects of the invention: No expensive or difficult-to-obtain optical resolving agents are required;
This method is industrially advantageous because it requires only a small amount of one of the seed crystals to be prepared first, and the resulting crystals are used as the next seed crystals.

In addition, the 1,1'-bi-2-naphthol derivative represented by the formula (already expressed) used as a raw material is the formula (
The 1,1-bi-2-naphthol derivative represented by 2) is much easier to synthesize.

Example 1μ An example will be shown below and will be explained in more detail. Note that the second invention is not limited to these Examples.

Reference example 1゜1.58 f of 2-methoxynaphthalene to 1 methylene chloride
00- and stirred and cooled on a -10 to -15C bath. Add ferric chloride 1261 little by little to this and stir.
After the addition was completed, the mixture was stirred for an additional 30 minutes, and then 50 d of water was added little by little. After adding water, the mixture was thoroughly stirred and the color of the dark brown liquid changed to pale yellow, after which the temperature was gradually returned to room temperature. The separated organic layer was concentrated and further distilled to obtain racemic t1at of 1,1'- and -2-methoxynaphthalene as a colorless oil. This stuff solidified quickly. Yield: 75 cm. The physical property values were as follows.

mp 199-202.50 (benzene) NMR (C
DO12) δ174(s, 6H), 7.15-11
20 (m, 12H) MS (m/e) 314 (M+
, 100), 268 (10) The physical properties were consistent with those of a standard product obtained by methylating commercially available 1,1'-bi-2-naphthol with methyl iodide and sodium hydride in dimethylformamide.

Example 1゜The racemic body 201.511p of 1,17- and -2-methoxynaphthalene obtained in Reference Example t was dissolved in benzene LOf, cooled to 24C, and powdered optically active substance 6.
T4! n9((r)'; -44,0°(c=1,
0, CHCl5), 85.3% e,e,)
was inoculated. It was slowly cooled for 14 hours with stirring (from J+2-IC to 9C) and filtered.
62.5IIg [a] 25-17.5° (559%a
e,), when the liquid part is concentrated, it becomes 97.511g [α]0+λ3G(
It was 4.5% e, e,). 1 body, d body is 5~5II#
This means that the number has increased by 9.

Example 2 1.1'-B-2-methoxynaphthalene racemate 51
5 Da to chloroform 12. Optically active substance 24.6■ ([α formula +5
1.1° (c=1.0.CHCLs).

99.0% e, e, ) was inoculated. 1 at 19-21C
Stir for an hour and filter. The crystal part is 1248119 [f
f], +1 &7° (32-4% e, e,), P
When the liquid part is concentrated, it becomes 4241n9 [α]2:, Z
so (4.8% e, e,). d body, one body is 17
~211n9 increased.

Example 5 11'-B-2-methoxynaphthalene 2-semiconductor 164
4In9 and d-isomer 451ng ((α)o+51.6°(c
A mixture of =LD, 0FiC1,), no%e, e,) was dissolved in chloroform 3&Of, cooled to 20C, and powdered optically active substance 3L6Fng ((α]o+5
7.80, 75.5% e, e, ) were inoculated. 20C
The mixture was stirred for 1 hour and filtered. The crystal part is 273F! For Ig, (a) H+ 2 Noo (44.6% e, e,). This means that 4 bodies have grown by 99 da.

From this F solution part, 1. After distilling off,
Redissolved and cooled to 20C.

Powdered optically active substance 390 da ([α] Amase 44.0°
.

8a5%e, e,) was inoculated, stirred at 20C for 1 hour, and filtered. The crystal part is 349 da [α) D-sin.

(69.8% e, e,), which means that one body has increased by 2101v. This material was heated and dissolved in 4.3 f of chloroform to the reflux temperature, further cooled slowly to 20 C, and then heated in an oven to obtain 185 v of colorless crystals. (α:+:-
51,5° (9y, 4% e, e,). mp232-23
The 4.5C (benzene) NMR and MS values were the same as those of the 2 semiform of Example t.

Reference example 2 Reference example 1. 1.72°1 of 2-ethoxynaphthalene was used instead of 1.58f of 2-methoxynaphthalene in Reference Example 1. The mixture was reacted and treated in the same manner as above to obtain racemic Q, 86f of 1.1-bi-2-ethoxynaphthalene as a colorless oil. This stuff solidified quickly. The yield was 50%.The physical properties were as follows.

mp 1G & 5~107.5C (7 setons) NMR (
CD01B) δi, 01(t, 6H), 198(
q, 4H).

70~a1 (m, 12H) Me (Ve) 342 (M”, 100), 286
(26), 26B (15) The physical properties of commercially available 1,
They were consistent with those of the standard obtained by ethylating 1-bi-2-naphthol with ethyl iodide and sodium hydride in dimethylformamide. The melting point of the standard optically active substance obtained by this ethylation was 137 to 140C (hexane).

The racemic form of 1,1'-bi-2-ethoxynaphthalene obtained in Reference Example 2 (770 da) was dissolved in acetone 1α2t, cooled to 20 C, and powdered □ body 355# (( a
)”, '+67.0' (c=to, 0HOts).

100% e, e, ) were inoculated. The mixture was cooled to 19C, stirred for 1 hour, and then filtered. The crystal part is 127.3W [α
Formula +2y, s° (41,0% e, e,), concentrating the fp liquid part gives 692■ [α par 1.8° (2-7% e,
, e, ). This means that 1 out of 4 patients had an increase in 1911Ig.

Claims (2)

[Claims] (1) Formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) 1,1'-bi-2- represented by (In the formula, R^1 and R^2 represent an alkyl group) A racemic naphthol derivative or a mixture in which one optically active form is present in excess of the other is dissolved in a solvent, cooled to supersaturation, and then either one of the optically active forms is inoculated. ,
A method for optical resolution of optically active 1,1'-bi-2-naphthol derivatives, characterized by crystallization resolution. (2) The optical resolution method according to claim (1), wherein R^1 and R^2 in formula (I) are the same and are lower alkyl groups.