JPS61251681A - Cyclopentenone ether derivative and production thereof - Google Patents

Abstract

NEW MATERIAL:The compound of formula I. EXAMPLE:( 1R,5S )-6,6-dimethyl-3-oxa-4( R )[1( R )-4-oxo-3-propargyl-2-cyclopenten yloxy]bicyclo[3,1,0]hexan-2-one. USE:Intermediate for pharmaceuticals and agricultural chemicals. PREPARATION:The objective cyclopentenone derivative of formula I can be produced by condensing 4-hydroxy-2-propargyl-2-cyclopentenone with the lactone of formula II (R is H or lower alkyl) in the presence of a dehydration catalyst (e.g. p-toluenesulfonic acid). The amount of the dehydration catalyst is usually 0.01-1 equivalent, preferably 0.05-0.4 equivalent per 1 equivalent of the lactone. The reaction is carried out usually at 20-150 deg.C, preferably at 30-130 deg.C.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a cyclobentenone derivative represented by formula [I] and a method for producing the same.

The above formula [! ] The cyclobentenone derivative represented by is a new compound synthesized for the first time by the present inventors,
It is useful as an intermediate for medicines or agricultural chemicals. For example, if a compound of formula CI) is (IK, 58)-6,6-dimethyl-3-oxa-4(R)-(IGR)-4-oxo-
In the case of 3-propargyl-2-cyclopentenyloxy]bicyclo(3,1,0)hexan-2-one, if this compound is hydrolyzed with, for example, a dioxane-water system, 4
A novel compound, (R)-hydroxy-2-propargyl-2-cyclopentenone, is provided which can be used as an intermediate for prostaglandin derivatives.

In addition, the ceremony [! ]As an analog of the compound, JP-A-57-15
No. 9777 describes a compound represented by the formula, and JP-A-58-41836 describes a compound represented by the formula, but there is no description at all of the compound of formula CI), which is the object compound of the present invention. Not only is there no such thing, but there is no mention of its possibility or usefulness at all.

The cyclobentenone derivative of the present invention represented by the above formula CI) has asymmetric carbon atoms in its molecule, but the present invention is directed to all optically active substances based on these asymmetric carbon atoms, or any proportion thereof. It includes a mixture.

Among these, (IR, 58)-6,6-dimethyl-3-oxa-4(R)-(14-4-oxa) is used as an intermediate for prostaglandin derivatives.

So-3-propargyl-2-'cyclopentenyloxy]bicyclo(3,1,0)hexan-2-one is also used as an intermediate for pyrethroid compounds (IR,55)-
6,6-dimethyl-3-oxa-4(R)-(1(S)
-4-oxo-3-propargyl-2-cyclopentenyloxy]bicyclo(3,1,0)hexan-2-one is preferred.

The cyclobentenone derivative represented by the formula CI) is
4-hydroxy-3-bronomargyl-2- represented by formula (II)
It can be produced by condensing cyclopentenone and lactones represented by the general formula (III) (in which the formula represents a hydrogen atom or a lower alkyl group) in the presence of a dehydration catalyst.

Here, 4-hydroxy-5,5 used as a raw material
-Dimethyl-2-cyclopentenone can be easily synthesized from furancarbinol by the method shown below.

For example, it can be synthesized by the known method described in Japanese Patent Publication No. 48-24695, and such lactones have asymmetric carbon atoms in their molecules. or a mixture of these in any proportion. Here, in the lactones of general formula (I[), a hydrogen atom or a lower alkyl group such as a methyl group, an ethyl group, a propyl group, a butyl group is shown as a substituent.

Among such lactones, (IR958)-6,
6-dimethyl-44-hydroxy-3-oxabicyclo(3,1,0)hexan-2-one and (Is, 5K
) -6,6-siftyl-4(S)-hydroxy-3-
Oxabicyclo(3,1,0)hexan-2-one is preferably used.

The reaction between 4-hydroxy-2-propargyl-2-cyclopentenone and the above-mentioned lactones is usually carried out by heating and condensation in the presence of a dehydration catalyst.

In this reaction, when a solvent is used, examples of the solvent include tetrahydrofuran, ethyl ether, acetone, methyl ethyl ketone, toluene, benzene, chlorobenzene, aliphatic or aromatic hydrocarbons such as chloroform, dimethylformamide, ether, Examples include solvents that are inert to the reaction of halogenated hydrocarbons, etc., alone or as a mixture, and the amount used is not particularly limited.

4-hydroxy-2-propargyl-2- used in the reaction
Cyclopentenone is required in an amount of 1 equivalent or more per equivalent of lactone (III), preferably in the range of 1.2 to 2 equivalents.

Examples of the dehydration catalyst used in the synthesis include para-toluenesulfonic acid, para-toluenesulfonyl chloride, methanesulfonic acid, camphor-1-sulfonic acid, sulfuric acid,
Examples include phosphoric acid, hydrochloric acid, chain acids, acidic ion exchange resins, and their pyridine salts.

The amount of such dehydration catalyst used is usually 0.01 to 1 equivalent per equivalent of lactone, preferably O, OS.

~0.4 equivalent.

In this reaction, if water is produced as a by-product, it is preferable to remove it from the system by azeotropy or to dehydrate it by coexisting magnesium sulfate, molecular sieves, etc.゛The reaction temperature is usually 20 to 150°C, preferably 30°C.
-130°C.

There is no particular restriction on the reaction time.

After the reaction is completed, the desired cyclobentenone ether derivative (I) can be isolated from the reaction mixture by conventional operations such as extraction, concentration, crystallization, and chromatography.

The lactones (III) include optically active lactones, such as (IK, 5S)-6,6-dimethyl-4-hydroxy-3-oxabicyclo(3,1,0)hexan-2-one or (18,5R )-5,6-dimetheru-4-hydrowaxy-3-oxabicyclo(3,1,0)
using hexan-2-one and di-4 as the other raw material.
-Hydroxy-2-propargyl-2-cyclopentenone, (IR,5S)-6,6-dimethyl-3-oxa-4(1)-(1(R1-4-oxo-3- propargyl-2-cyclopentenyl]bicyclo(3,1,0)hexan-2-one and (IR,55)-
6,6-dimethyl-3-oxa-4(he)-(1(S)
A mixture of diastereomers of -4-oxo-3-propargyl-2-cyclopentenyl]bicyclo(3,1,01hexan-2-one, or (IS, 5K)-6,
6-dimethyl-3-oxa-4(S)-(1(R)-4
-oxo-3-propargyl-2-cyclopentenyl]
Bicyclo(3,1゜0)hexan-2-one and (I S
, 5R)-6゜6-dimethyl-3-oxa-4(S)
-(1(S) -4-oxo-3-propargyl-2
A mixture of diastereomers of -cyclopentenyl]bicyclo(3,1,0)hexan-2-one is obtained.

4-Hydroxy-2-propargyl-2-cyclopentenone- and (IR,58)-6,6-dimethyl-4-hydroxy-3-oxabicyclo(3,1,0)hexane-
2-one or (Is, 5R) -6,6-dimethyl-4-hydroxy-3-oxabicyclo(3,1,0)
Lactones of hexane-2-one at a molar ratio of 1.5 to 2
:1, a reaction containing an excess amount of one of the optically active forms relative to its enantiomer by reacting with azeotropic dehydration in an azeotropic solvent in the presence of paratoluenesulfonic acid or benzenesulfonic acid. A mixture can be obtained.

Therefore, in the above reaction, it is extremely advantageous from an economical and purification standpoint to obtain an excess amount of either cyclobentenone ether by combining it with its enantiomer, and has great industrial significance.

The reaction mixture will be explained below.

Examples of raw material lactones include (IR,5S)-6,
6-dimethyl-4-hydroxy-3-oxabicyclo(
3,1,0) When using hexane-2-one, (IR,55)-6,6-dimethyl-3-oxa-4
(R)-(1 animal)-4-oxo-3-propargyl-2
-Cyclopentenyloxy]bicyclo(3,1,0)hexan-2-one (hereinafter referred to as [I-2]) is its enantiomer (IR, 5S) -6,6-di) k -3-oxa-4(R)-(1is) -4-oxo-3-propargyl-2-cyclopentenyloxy]
Bicyclo(3,1,03hexan-2-one (r
(1-a) and C
A mixture of I-b) is obtained.

In addition, as lactones (IS, 5R)-6゜6-
Dimethyl-4-hydroxy-3-oxabicyclo (3,
1,0) When hexan-2-one is used, an excess amount of (Is,5R)-6゜6-dimethyl-3-oxa-4
(S) -(1(S) -4-oxo-3-propargyl-2-cyclopentenyloxy]bicyclo[3,1,
CI-d) containing 01 hexan-2-one (hereinafter referred to as CI-d) and (IS, 51L)-6,6-Richleu-3-oxa-4(S)-(I(R1-4 -oxo-3-propargyl-2-cyclopentenyloxy]bicyclo(3,1,0)hexan-2-one (hereinafter CI-
A mixture of (referred to as C)) is obtained.

By separating each diastereomer from such a mixture, each optically active form of the compound of formula (I) with extremely high optical purity can be obtained.

As a method for separating such diastereomers, specifically, a recrystallization method, chromatography, etc. are used.

The present invention will be explained below with reference to Examples.

Example 1 4-Hydroxy-2-propargyl-2-
Cyclopentenone 21.76 Jr (0.16 mol)
, (IR,5S)-8,6-dimethyl-4-hydroxy-3-oxabicyclo(3,1,0)hexan-2-one 14.2, f (0.1 mol), benzenesulfonic acid 0. 31 and toluene 100- are charged and azeotropically dehydrated at 80 to 85°C under reduced pressure. The reaction time required 4 hours.

After the reaction is complete, 60% of water is added and the organic layer is separated. The organic layer is further washed with 50 g of 3 g heavy duty water and 60 g of water. The organic layer was concentrated under reduced pressure to give (IK, 58) -
6,6-dimethyl-3-oxa-44-(1(R)-4
-oxo-3-propargyl-2-cyclopentenyloxy]bicyclo(3,1,0)hexan-2-one[!
-2] and (IR,55)-6,6-dimethyl-3-oxa-4(R)-(1(S)-4-oxo-3-propargyl-2-cyclopentenyloxy)bicyclo(3,1
Mixture of ゜゛0〕hexane-2-one CI-b) 25.
74, obtained f.

[■-λ)/[I-b]-1,6 roughy (solvent dichloromethane: ethyl acetate-100:
2) - separated and purified with Cl-4) 15.22 F
and (I-b) 9.3II is obtained.

[■-mouse]

α) -77,1° (C-1, ethanol) n et al' 1.5206 CI-b) α) -126,4° (C-1, ethanol) Example 2 (IR, 58) -6,6 -Simethyl-4-hydroxy-3-oxabicyclo (a, i.

0] (Is, 5R)-8 in place of hexan-2-one,
6-dimethyl-4-hydroxy-3-oxabicyclo(
(15,5R)-
6,6-dimethyl-3-oxa-4(S)-(1(S)
-4-oxo-3-propargyl-2-cyclopentynyloxy]bicyclo(3,1°0]hexan-2-one CI-d) and (IS.

5R)-8,6-dimether-3-oxa-4(Sl-(
1(R)-4-oxo-3-propargyl-2-cyclopentenyloxy]bicyclo(3,1,0)hexane-
31.8 F of a mixture of 2-one CI-C) was obtained.

This mixture was separated and purified by column chromatography (rd) 1s, tay and CI-C) 9.4
2. Obtain F.

(I-d) α) +76.9° (C=1, ethanol) n”
1.5199 CI-C) α]Crystal' +125.5 (C-1, ethanol)
n" 1.5196 Example 3 Into the same apparatus as used in Example 1, 4-hydroxy-2
-propargyl-2-cyclopentene/ 17.681
(0,13%Jl/ ), (IR,55)-6,6-
Dimeter-4-hydroxy-3-oxabicyclo[3,
l, o] Hexan-2-one 14.2F (0.4 mol)
, toluenesulfonic acid pyridine salt 7I and benzene 8
oWJ is charged and azeotropically dehydrated under reflux. The reaction time requires 5 hours.

After the reaction is completed, 50 WJ of water is added and the organic layer is separated. The organic layer is further washed with 50 d of 3% sodium hydroxide solution and 50 d of water. The organic layer was concentrated under reduced pressure to give (1,55)-
6,6-dicyclo(3,1,0)hexan-2-one C
I-a) and (IK, 58) 6.6-di-thyl-3-
A mixture of 28.711 oxa-4-(1(S)-4-oxa-1)-(3,1,0)hexan-2-one [■-b) is obtained.

The above mixture was separated and purified by column chromatography (solvent dichloromethane:ethyl acetate = 100:2) to obtain CI-a) 12.74 tz and (1-b) 1
2. Obtain OJF.

[■-for]

α) −77,2° (C-1, ethanol) nD
l, 5210 CI-b) α) -124,9° (C-1, ethanol) n
” 1.5196

Claims (6)

[Claims] (1) Formula ▲Contains mathematical formulas, chemical formulas, tables, etc.▼ Cyclopentenone derivative represented by (2) The cyclopentenone derivative is (1R,5S)-6,
6-dimethyl-3-oxa-4(R)[1(R)-4-
The compound according to claim 1, which is oxo-3-propargyl-2-cyclopentenyloxy]bicyclo[3,1,0]hexan-2-one (3) The cyclopentenone derivative is (1S,5R)-6,
6-dimethyl-3-oxa-4(S)[1(R)-4-
The compound according to claim 1, which is oxo-3-propargyl-2-cyclopentenyloxy]bicyclo[3,1,0]hexan-2-one (4) The cyclopentenone derivative is (1R,5S)-6,
6-dimethyl-3-oxa-4(R)[1(S)-4-
The compound according to claim 1, which is oxo-3-propargyl-2-cyclopentenyloxy]bicyclo[3,1,0]hexan-2-one (5) The cyclopentenone derivative is (1S,5R)-6,
6-dimethyl-3-oxa-4(S)-[1(S)-4
-oxo-3-propargyl-2-cyclopentenyloxy]bicyclo[3,1,0]hexan-2-one, the compound according to claim 1 (6) 4-Hydroxy-2-propargyl-2-cyclopentenone and lactones represented by the general formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (In the formula, R represents a hydrogen atom or a lower alkyl group.) A method for producing a cyclopentenone derivative represented by the formula ▲There are mathematical formulas, chemical formulas, tables, etc.▼ characterized by condensation of and in the presence of a dehydration catalyst.