Method for producing jasmonate derivatives and intermediates...

Organic compounds -- part of the class 532-570 series – Organic compounds – Oxygen containing

Reexamination Certificate

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C568S343000, C568S347000, C568S348000, C568S355000, C568S356000, C560S122000

Reexamination Certificate

active

06500990

ABSTRACT:

TECHNICAL FIELD OF THE INVENTION
The present invention relates to a method for producing a 2-alkyl-2-cyclopentenone useful as a synthetic intermediate of a biologically active substance or a perfume as well as a method for producing a jasmonate derivative useful as a perfume material or a biologically active substance by using the same.
PRIOR ART
As a method for producing a 2-alkyl-2-cyclopentenone, for instance, there is a method which comprises obtaining a 2-alkylidene cyclopentanone by dehydrating reaction of a 2-(1-hydroxyalkyl)-cyclopentanone and then isomerizing this 2-alkylidene cyclopentanone. Among such a method, there is known a method for producing a 2-alkyl-2-cyclopentenone by bringing a hydrogen halide into contact with a 2-alkylidene cyclopentanone and there are also investigated variable improvements thereof (JP-A 59-80625 etc.).
In this method, however, it is impossible to obtain the product in a high yield without low concentration condition so that further improvements have been desired for industrial production. As this improved method therefor, there is also known a method using a hydrogen halide salt of an amine in place of the above-mentioned hydrogen halide (JP-A 6-80606). Even in this method, however, no sufficiently satisfactory yield can be obtained without adding a solvent in excess.
Further, those methods wherein a 2-(1-hydroxyalkyl)-cyclopentanone is dehydrated and isomerized at one stage are also known (JP-A 56-147740 and JP-A.5-92934). However, these methods have drawbacks such as longer reaction time, poor yield, much solvent and poor productivity.
JP-A 51-23240 discloses a method for producing a 2-alkyl-2-cyclopentenone with a hydrogen halide or sulfonic acid.
DISCLOSURE OF THE INVENTION
The object of the present invention is to provide a method for efficiently producing a 2-alkyl-2-cyclopentenone as well as a method for producing a jasmonate derivative by using the same.
The present invention relates to a method for producing a 2-alkyl-2-cyclopentenone represented by the formula (2) (referred to hereinafter as the compound (2)):
wherein each of R
1
and R
2
represents a hydrogen atom or a linear or branched alkyl group having 1 to 8 carbon atoms, or R
1
and R
2
may be formed into a cyclopentane or cyclohexane ring together with a bonded carbon atom, which comprises reacting an amine and a hydrogen halide with a 2-alkylidene cyclopentanone represented by the formula (1) (referred to hereinafter as the compound (1)) at a molar ratio of the amine/the hydrogen halide of from 1.1/1 to 5/1 to carry out isomerization reaction:
wherein R
1
and R
2
have the same meanings as defined above, as well as it relates to a method for producing the compound (2), which comprises reacting a catalyst comprising an amine and a hydrogen halide with a 2-(1-hydroxyalkyl)-cyclopentanone represented by the formula (3) (referred to hereinafter as the compound (3)) to carry out dehydration-isomerization reaction:
wherein R
1
and R
2
have the same meanings as defined above.
Further, the present invention relates to a method for producing a jasmonate derivative represented by the formula (5) (referred to hereinafter as the compound (5)):
wherein R
1
and R
2
have the same meanings as defined above, R
3
represents a linear or branched alkyl group having 1 to 3 carbon atoms, which comprises reacting the compound (2) obtained in the method described above with a malonic acid diester represented by the formula (4) (referred to hereinafter as the compound (4)):
wherein R
1
, R
2
and R
3
have the same meanings as defined above, and the two R
3
groups may be the same or different, and then reacting water therewith.
Furthermore, the present invention also provides use of the 2-alkyl-2-cyclopentenone obtained by the method described above as an intermediate for a jasmonate derivative.
MODE FOR CARRYING OUT THE INVENTION
[Method 1: The Method for Producing the Compound (2) Obtained from the Compound (1)]
The compound (1) used in the present invention can be produced by a publicly known method in the conventional art. For example, it can be easily synthesized by a method for condensing an enamine of cyclopentanone with an aldehyde and then decomposing the dehydrated-condensed product with an acid; a method of dehydrating the compound (3); or the like.
The compound (1) includes 2-butylidene cyclopentanone, 2-(2′-methylbutylidene) cyclopentanone, 2-pentylidene cyclopentanone, 2-hexylidene cyclopentanone, 2-cyclopentylidene cyclopentanone, 2-cyclohexylidene cyclopentanone and 2-(1′-methylbutylidene)-cyclopentanone.
The amine and hydrogen halide used in the present method at are reacted at a molar ratio of the amine/the hydrogen halide of from 1.1/1 to 5/1, preferably 1.2/1 to 3/1 and more preferably 1.5/1 to 3/1 in order to obtain the compound (2) in a high yield even in a small amount of a solvent.
The amine used in the present method is preferably a weakly basic aromatic amine or heterocyclic aromatic amine. Specifically, there may be exemplified aniline, diphenylamine, pyridine, picoline, quinoline and polyvinyl pyridine. Pyridine, picoline or quinoline is particularly preferable. The hydrogen halide may be hydrogen chloride, hydrogen bromide or hydrogen iodide. Hydrogen chloride or hydrogen bromide is particularly preferable.
The amine and hydrogen halide may be previously mixed at the ratio described above having the excess amine in order to use the mixture. On the other hand, the amine and hydrogen halide may be added to a reaction vessel at the ratio described above. The amount of the hydrogen halide used is preferably 1 to 50 mol-% and particularly preferably 2 to 20 mol-% as compared with the compound (1).
The reaction is preferably carried out in an alcohol solvent or under no solvents. As the alcohol solvent, e.g. C
1-8
lower alcohols, diols or triols are used. C
1-8
lower alcohols are particularly preferable. Specially, examples thereof include methanol, ethanol, 1-propanol, 2-propanol, butanol, pentanol, hexanol, 2-ethylhexanol, cyclohexanol, ethyleneglycol, 1,8-octanediol, glycerol and polyethyleneglycol. The amount of the solvent used is preferably 0.5 to 5 times and economically more preferably 0.5 to 2 times the weight of the compound (1). The reaction solvent is suitably selected depending on the physical properties of the compound (1) to be used. If the boiling point of the selected solvent is the reaction temperature or less, the reaction may be carried out under pressurization.
The reaction temperature is preferably 80 to 200° C. and particularly preferably 100 to 180° C., and the reaction is carried out for a suitable time and, after the reaction is finished, a work-up is carried out according to a usual manner, whereby the compound (2) can be obtained.
The compound (1), the solvent, the amine and the hydrogen halide can be simultaneously introduced and reacted, but the reaction procedure is preferably that, when the reaction temperature is reached, the compound (1) is brought into contact with the catalyst. This procedure includes a method which comprises introducing the compound (1) and the solvent, then adding dropwise a mixed solution of the amine and the hydrogen halide thereto at a predetermined temperature and reacting them and a method which comprises previously introducing the solvent, the amine and the hydrogen halide and then adding dropwise the compound (1) thereto at a predetermined temperature. Any method thereof may be adopted.
[Method 2: The Method for Producing the Compound (2) Obtained from the Compound (3)]
In the compound (3) used as the starting material in the present method, the alkyl group constituting 1-hydroxyalkyl group includes e.g. methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, amyl group, isoamyl group, hexyl group and heptyl group.
This compound (3) can be produced by a publicly known method in the conventional art. For example, it can be obtained by reacting cyclopentanone with an aldehyde or ketone represented by the formula (6):
wherein R
1

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