JP3072150B2 - Method for producing optically active [3] (1,1 ') ferrocenophanes - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a process for producing optically active [3] (1,1 ') ferrocenophanes represented by the general formulas (II) and (III). It is known that optically active ferrocenes are used for modifying an asymmetric reduced metal complex catalyst. (T.Hayashi, et.al., Bu
Chem. Soc. Jpn., 53, 1138 (1980).) Optical activity [3]
(1,1 ′) ferrocenophanes are also expected to have similar fields of use as modifiers for organometallic complex catalysts.

[0002]

2. Description of the Related Art Optically active [3] (1,1 ') ferrocenophanes are known as 5- and 6-hydroxymethyl forms, 5- and 6-carboxy forms, 5- and 6-carboxy forms. Such as formyl form, all of which are optically active 5-
And 6-carboxy [3] (1,1 ′) ferrocenophane, which was chemically synthesized as a raw material, wherein (H. Falk,
O. Hofer, K. Schoegl, Monatsch. Chem., 100, 624 (196
9).) The production method by fermentation using lipase, esterase, etc. is not yet known.

[0003]

SUMMARY OF THE INVENTION Conventional optical activity [3]
The method for producing (1,1 ′) ferrocenophanes has been produced by a complicated method of optical resolution of a racemate, but the present invention relates to 5- and 6-alkoxycarbonyl [3] (1,1 ′). Disclosed is a method for producing optically active 5- and 6- [3] (1,1 ′) ferrocenophanes by a simple method by asymmetric hydrolysis reaction of ferrocenophan with lipase or esterase. .

[0004]

That is, the present invention provides an optically active carboxy [3] (1,1 ') characterized by hydrolyzing a compound represented by the general formula (I) in the presence of an esterase or a lipase. Ferrocenophanes (II)
And an optically active alkoxycarbonyl [3] (1,
1 ′) A method for producing ferrocenophanes (III).

Embedded image (I) (wherein, R represents an alkyl group having 1 to 24 carbon atoms)

Embedded image (II)

Embedded image (III) (wherein, R represents an alkyl group having 1 to 24 carbon atoms)

The [3] (1,1 ') ferrocenophanes that can be produced by the present invention are specifically exemplified by (+)-5-
Carboxy [3] (1,1 ′) ferrosenophane,
(-)-5-Alkoxycarbonyl [3] (1,1 ')
Ferrocenophane, (-)-5-carboxy [3]
(1,1 ′) ferrocenophane, (+)-5-alkoxycarbonyl [3] (1,1 ′) ferrocenophane,
(+)-6-carboxy [3] (1,1 ′) ferrocenophane, (−)-6-alkoxycarbonyl [3]
(1,1 ′) ferrocenophane, (−)-6-carboxy [3] (1,1 ′) ferrocenophane, (+)-6-
Alkoxycarbonyl [3] (1,1 ′) ferrocenophane and the like.

The racemic 5- or 6-alkoxycarbonyl [3] of the general formula (I) as a starting material of the present invention
(1,1 ′) ferrocenophanes can be produced by a known method. (H.Falk, O.Hofer, K.Schoegl, Monatsc
h. Chem., 100, 624 (1969).) That is, [3] (1,
1 ') Ferrocenophane is reacted with N, N-diphenylcarbamyl chloride by Friedel-Crafts reaction to give 5- and 6-carboke [3] (1,1') ferrocenophane and further ester 5 and 6
—Alkoxycarbonyl [3] (1,1 ′) ferrocenophane.

[0007] The lipase used in the present invention includes commercially available lipase PS, porcine pancreatic lipase, lipase MY of Candida cylindrasse, lipase M10, and lipase O.
Any of F, lipase P679, and cellulase can be used, and immobilized lipase immobilized on a polymer such as lipozyme can also be used.

[0008] In addition, animals, plants and esterases can be used. Specific examples of these esterases include steabsin, pancreatin, pig pancreatic esterase, and wheat malt esterase.

The asymmetric hydrolysis reaction is usually carried out by vigorously stirring a mixture of the starting ester (I) and the above enzyme or microorganism in a buffer. As the buffer, a commonly used buffer of an inorganic acid salt such as sodium phosphate or potassium phosphate, or a buffer of an organic acid salt such as sodium acetate or sodium citrate is used. The pH is preferably 8 to 11 for bacterial cultures and alkaline esterases, and 5 to 8 for non-alkaliphilic esterases. The concentration is usually 0.05-2 molar, preferably 0.05-0.
The range is 5 molar. The reaction temperature is usually 10 to 60
° C and the reaction time is generally 10 to 70 hours, but is not limited thereto.

[0010] By such an ester hydrolysis reaction, one of the optically active isomers of the racemic ester (I) as a raw material is hydrolyzed to give an optically active carboxylic acid (I).
I) is produced as a hydrolysis product, and the other optically active ester (III) of the raw material compound remains as a hydrolysis residue, and as a result, the hydrolysis product and the hydrolysis residue The above two optically active compounds are simultaneously obtained. When the ester (III) as the hydrolysis residue is hydrolyzed with an alkali,
It is possible to easily obtain an optically active carboxylic acid having a configuration opposite to that of the optically active carboxylic acid (II) which is a hydrolysis product obtained earlier. In addition, at the time of this asymmetric hydrolysis reaction, an organic solvent which is inert to the reaction, such as toluene, chloroform, methyl isobutyl ketone, and dichloromethane, can be used in addition to the buffer solution. Decomposition can be performed advantageously.

After the completion of the asymmetric hydrolysis reaction, the reaction solution is extracted with a solvent such as toluene, methyl isobutyl ketone, ethyl acetate, ethyl ether, chloroform or dichloromethane, and the solvent is distilled off from the organic layer. The filtrate residue can be separated into optically active carboxylic acids and esters by a method such as column chromatography.

Hereinafter, the present invention will be described in more detail with reference to examples.

EXAMPLE 6-Methoxycarbonyl [3] (1,1 ′)
61.6-Methoxycarbonyl [3] (1,1 ′) ferrocenophane, a raw material for asymmetric hydrolysis of ferrocenophane, 81.6.
The mg was stirred vigorously with 40 ml of phosphate buffer (pH 7.2), 5 ml of hexane, 0.8 g of polyvinyl alcohol and 200 units (0.03 ml) of pig liver esterase at 20 ° C. for 4 days. After completion of the reaction, the reaction mixture was extracted with 300 ml of chloroform. The organic layer was washed with a saturated aqueous solution of sodium hydrogen carbonate and separated into an organic layer and an aqueous layer. The aqueous layer was neutralized with dilute hydrochloric acid, extracted with chloroform, the chloroform layer was washed with saturated saline, dried,
The solvent was concentrated under reduced pressure, and the residue was recrystallized from benzene-hexane to give (+)-(4S, 6R) -6-carboxy [3] (1,1 ') ferrocenophane mp172-1
76 ° C., [α] _D ²⁰ + 107 ° (c 0.1 in E
tOH) (literature value [α] _D ²⁰ + 155 °), ee69
% And a yield of 28%}. The organic layer separated from the aqueous layer was washed with saturated saline, dried, and the solvent was concentrated under reduced pressure. The residue was purified by column chromatography using a mixed solvent of chloroform-ethyl acetate (10: 1) as an eluent ( +)
-(4R, 6S) -6-methoxycarbonyl [3]
(1,1 ′) ferrocenophane mp 52-57 ° C.
[Α] _D ²⁰ -284 ° (c 0.11 in EtO
H), yield 22% ２２.

According to the present invention, optically active [3] (1,1 ') ferrocenophanes expected as a modifier for an organometallic complex catalyst can be produced by a simple method. Patent applicant Kawaken Fine Chemical Co., Ltd.

────────────────────────────────────────────────── ─── Continued on the front page (58) Field surveyed (Int. Cl. ⁷ , DB name) C12P 41/00 BIOSIS (DIALOG) CA (STN)

Claims (1)

(57) [Claims] 1. A racemic 5- and 6-alkoxycarbonyl [3] (1, 1) represented by the following general formula (I)
1 ′) A process for producing optically active [3] (1,1 ′) ferrocenophanes (II) and (III), which comprises hydrolyzing ferrocenophanes in the presence of esterase or lipase. Embedded image (I) (In the formula, R represents an alkyl group having 1 to 24 carbon atoms.) (II) (III) (wherein, R represents an alkyl group having 1 to 24 carbon atoms)