Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acids and salts thereof
Reexamination Certificate
2001-11-29
2003-07-29
Killos, Paul J. (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acids and salts thereof
C568S410000
Reexamination Certificate
active
06600070
ABSTRACT:
TECHNICAL FIELD
The present invention relates to methods for making 2-(&ohgr;-alkoxycarbonylalkanoyl)-4-butanolide and derivatives thereof, novel esters of &ohgr;-hydroxy-(&ohgr;-3)-ketoaliphatic acid and derivatives thereof, which are useful as a variety of synthetic raw materials and intermediates, and are prepared as intermediates in the production step of &ohgr;-hydroxyaliphatic acid being important intermediates of large cyclic lactone-based perfumes in the perfume industry.
The present invention also relates to a method for separating and purifying an alkaline metal salt of 2-(&ohgr;-alkoxycarbonylalkanoyl)-4-butanolide and derivatives thereof, and unreacted dicarboxylic ester, in the production of &ohgr;-hydroxyaliphatic acid, being an important intermediate of the large cyclic lactone-based perfume.
Furthermore, the present invention relates to a method for separating and recovering &ohgr;-hydroxy-(&ohgr;-3)-ketoaliphatic acid and salts thereof, dicarboxylic acid and salts thereof, and &agr;,&ohgr;-dihydroxy-&dgr;,(&ohgr;-3)-alkanedione, in the production of &ohgr;-hydroxyaliphatic acid, being an important intermediate of the large cyclic lactone-based perfume.
BACKGROUND ART
Alkaline metal salts of &ohgr;-hydroxy-(&ohgr;-3)-ketoaliphatic acid represented by the general formula (5):
(wherein n is an integer of 7 to 13, and M indicates an alkaline metal), and &ohgr;-hydroxy-(&ohgr;-3)-ketoaliphatic acids represented by the general formula (10):
(wherein n is an integer of 7 to 13) are useful as a variety of synthetic raw materials and intermediates and are particularly important intermediates for macro cyclic lactone-based perfumes in the perfume industry.
2-(&ohgr;-Alkoxycarbonylalkanoyl)-4-butanolide is useful as a variety of synthetic raw materials and intermediates and is effectively used as an intermediate in the production of the above-mentioned &ohgr;-hydroxyaliphatic acid, which is a particularly important intermediate for large cyclic lactone-based perfumes, such as cyclopentadecanolide and cyclohexadecanolide, in the perfume industry.
Among conventional synthesizing processes for &ohgr;-hydroxyaliphatic acid, a method using &ohgr;-cyanoundecanoate ester and &ggr;-butyrolactone as starting materials is disclosed in Japanese Patent Application Laid-Open No. Hei 5-86013.
In this method, however, raw materials are generally difficult to prepare, and relatively expensive methyl 11-cyanoundecanoate is used as a raw material. Furthermore, ammonia formed in the final carboxylation step of the nitrile group at the &ohgr;-position requires a complicated procedure and adversely affects the scent of the final product; hence this method is still industrially unsatisfactory.
Other synthesizing methods for &ohgr;-hydroxyaliphatic acid using &agr;-(&ohgr;-cyanoalkanoyl)-&ggr;-butyrolactone as a starting material are disclosed in Japanese Patent Application Laid-Open Nos. 3-11036 and 5-86013. As an advantage of these methods, the intermediate, &ohgr;-hydroxyketonitrile, which is prepared by hydrolysis and decarboxylation of &agr;-(&ohgr;-cyanoalkanoyl)-&ggr;-butyrolactone in the presence of an alkaline metal hydroxide, is oil-soluble; hence a large amount of water used and alkaline metal carbonate formed as a byproduct are easily separable.
Starting materials for &agr;-(&ohgr;-cyanoalkanoyl)-&ggr;-butyrolactone, however, are difficult to obtain. When relatively expensive a &ohgr;-cyanoundecanoate ester is used as a raw material or when the nitrile group at the &ohgr;-position is finally carboxylated, ammonia forms. Thus, a complicated process is required and ammonia adversely affects the scent of the final product; hence, this method is still industrially unsatisfactory.
PCT Patent Application Laid-Open No. WO97-06156 discloses a method using a significantly readily obtainable and inexpensive dicarboxylate ester represented by the general formula ROOC(CH
2
)
n
COOR, wherein n is an integer of 7 to 13 and R is an alkyl group, and &ggr;-butyrolactone as starting materials. In this method, an excess of dicarboxylate ester is mixed with &ggr;-butyrolactone in the presence of a basic condensing agent at room temperature and is heated and stirred under normal pressure while removing methanol formed in the reaction to prepare 2-(&ohgr;-alkoxycarbonylalkanoyl)-4-butanolide. This method is also excellent.
The selectivity and yield, however, is still unsatisfactory. Furthermore, a large excess of aqueous alkaline solution must be added during hydrolysis and decarboxylation of the intermediate, 2-(&ohgr;-alkoxycarbonylalkanoyl)-4-butanolide. Thus, a disadvantage of the method is removal of the large amount of water by distillation before the subsequent Wolff-Kishner reduction step.
In this method, an excess of dicarboxylate ester which is two times or more the fed amount of &ggr;-butyrolactone is used to increase the selectivity on the basis of the dicarboxylate ester raw material represented by the above-mentioned general formula, and unreacted dicarboxylate ester is recovered from the reaction mixture to reuse in the next reaction.
In the separation of the unreacted dicarboxylate ester and 2-(&ohgr;-alkoxycarbonylalkanoyl)-4-butanolide after the reaction, after acidification of the condensation solution, extraction with a solvent such as ethyl acetate, washing, and recovery of the solvent, the reaction mixture is subjected to simple distillation so that the unreacted dicarboxylate ester in the distilled section is separated from the condensation product, 2-(&ohgr;-alkoxycarbonylalkanoyl)-4-butanolide, in the distillation residue.
This method, however, requires a complicated process including many steps, such as extraction and simple distillation, and has a problem of decomposition of 2-(&ohgr;-alkoxycarbonylalkanoyl)-4-butanolide in the distillation. Furthermore, in the subsequent alkaline hydrolysis, decarboxylation, and Wolff-Kishner reduction, the method requires a complicated step in which alkaline is readded to 2-(&ohgr;-alkoxycarbonylalkanoyl)-4-butanolide obtained by the acidification.
Japanese Patent Application Laid-Open No. Hei 4-134047 discloses a method for separating three types of mixtures, that is, &ohgr;-hydroxyaliphatic acid or its ester, &agr;-&ohgr;-diol, and dicarboxylic acid or its ester, but does not suggest a compound having a carbonyl group in the molecule.
DISCLOSURE OF THE INVENTION
The present inventors have intensively researched solutions to the problems in the method disclosed in the PCT Patent Application Laid-Open No. WO97-06156, that is, the use of a large amount of aqueous alkaline solution and a large amount of heat, and the laborious steps for separating water, and have discovered that these problems may be solved by using a novel compound, an ester of &ohgr;-hydroxy-(&ohgr;-3)-ketoaliphatic acid, as an intermediate in the production of &ohgr;-hydroxyaliphatic acid, and have thereby completed the present invention.
It is an object of the present invention to provide methods, with high yield, improved selectively, and industrial advantages, for making 2-(&ohgr;-alkoxycarbonylalkanoyl)-4-butanolide and its derivatives, such as an alkaline metal salt, using readily obtainable and inexpensive dicarboxylate ester.
The present inventors have also discovered a method for effectively separating the condensation products, alkaline metal of 2-(&ohgr;-alkoxycarbonylalkanoyl)-4-butanolide and its derivative from the unreacted ester by extraction using an inactive solvent with water or an aqueous alkaline solution or by solid-liquid separation using an inactive solvent in the separation of the reaction product and the unreacted dicarboxylate ester from the condensation solution which is prepared from &ggr;-butyrolactone and an excess of dicarboxylate ester in the presence of a base, and have completed the present invention.
It is another object of the present invention to provide a novel compound, ester of &ohgr;-hydroxy-(&ohgr;-3)-ketoaliphatic acid, which is advantageously used as an intermediate in the industrial production of &ohgr;-hydroxyaliphatic acid b
Hasebe Akio
Imamura Shinzo
Ito Nobuhiko
Muraoka Hideo
Takaoka Hideaki
Killos Paul J.
Piper Rudnick LLP
Soda Aromatic Co., Ltd.
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