Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
1998-06-23
2001-04-24
Dentz, Bernard (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
active
06222049
ABSTRACT:
TECHNICAL FIELD
The present invention relates to a method for producing 2-(&ohgr;)-alkoxycarbonyl alkanoyl)-4-butanolide and a long-chain &ohgr;-hydroxycarboxylic acid
BACKGROUND OF THE INVENTION
A macrocyclic lactone can be derived from a long-chain &ohgr;-hydroxycarboxylic acid through intramolecular cyclization. Such macrocyclic lactones as cyclopentadecanolide and cyclohexadecanolide are important materials for preparing musk odor. It is known that 2-(&ohgr;-alkoxycarbonyl alkanoyl)-4-butanolide can be converted into a long-chain &ohgr;-hydroxycarboxylic acid through hydrolysis, decarboxylation, and subsequent reduction of the carbonyl group. The present invention relates to a method for producing a long-chain &ohgr;-hydroxycarboxylic acid, which is an intermediate to macrocyclic lactones, and 2-(&ohgr;-alkoxycarbonyl alkanoyl)-4-butanolide, which is an intermediate to said acid.
Conventionally, there have been many known methods to synthesize long-chain &ohgr;-hydroxycarboxylic acids such as 15-hydroxypentadecanoic acid and 16-hydroxyhexadecanoic. An example is the method disclosed in Dutch Patent 67, 458 (1951) [Polak and Schwarz] C. A. 45 9076 (1951). This method, however, needs as many as ten steps to produce a long-chain &ohgr;-bromoxylic acid, which is hydrolyzed into a long-chain &ohgr;-hydroxycarboxylic acid. This cannot provide a satisfactory industrial process because of the need for many steps for synthesis, relatively low availability of material substances, and hence, unsuitability for industrial mass-production.
Another known method is disclosed in Japanese Patent Laid-Open (Kokai) HEI 5-86013, which uses a &ohgr;-cyano fatty ester and &ggr;-butyrolactone as starting materials. Specifically, 11-methyl cyanoundecanoate reacts with &ggr;-butyrolactone in the presense of an alkali metal alcoholate to produce &agr;-(11-cyanoundecanoyl)-&ggr;-butyrolactone, which is then hydrolyzed into 15-hydroxy-12-ketopentadecanonitrile, followed by isolation, secondary hydrolysis, and reduction to provide 15-hydroxypentadecanoic acid.
This method, though being a good one, is still not sufficiently satisfactory because many of the starting materials are not readily available and also because 11-methyl cyanoundecanoate, which is relatively high in price, has to be used as a material. Another problem, though not very serious, is that the nitrile group at the &ohgr;-position has to be converted finally into a carboxyl group.
SUMMARY OF THE INVENTION
The objective of the invention is to provide an industrially advantageous method for producing 2-(&ohgr;-alkoxycarbonyl alkanoyl)-4-butanolide, which eventually makes it possible to produce a long-chain &ohgr;-hydroxycarboxylic acid through a short process and from highly available materials. Another objective is to provide an industrially advantageous method for producing a long-chain &ohgr;-hydroxycarboxylic acid.
The present inventors have reached the invention after earnest studies which show that 2-(&ohgr;-alkoxycarbonyl alkanoyl)-4-butanolide can be produced unexpectedly with a high selectivity and yield through condensation reacting of &ggr;-butyrolactone with a readily available, lo&ohgr;-price dicarboxylate as represented by the following general formula: ROOC(CH
2
)
n
COOR (where n denotes an integer of 7 to 13, and R denotes an alkyl or an alkenyl group). The present inventors have established an industrially advantageous method for producing a long-chain &ohgr;-hydroxycarboxylic acid after finding that a long-chain &ohgr;-hydroxycarboxylic acid is produced by subjecting 2-(&ohgr;-alkoxycarbonyl alkanoyl)-4-butanolide to hydrolysis and decarboxylation and reducing the carbonyl groups in the resultant product into methylene groups.
The molecule of a typical long-chain dicarboxylate as used for the present invention contains two functional ester groups connected through a long methylene chain. Therefore, long-chain dicarboxylate is largely different from such compounds as oxalates that contain two functional ester groups located close to each other, which easily undergo such side reactions as self-condensation and intramolecular crosslinking (Dieckmann condensation; J. P. Schaefer, Organic Reactions, Vol.15, p.1, John Wisely & Sons, 1967).
It is expected therefore that only a poorly-practical, lo&ohgr;-selectivity method can be formed if an attempt is to be made to obtain a specific condensate through condensation of different esters such as long-chain dicarboxylate and monocarboxylate (including lactone, which is an intramolecular ester). The inventors have found that the same results are generated from reactions of &ggr;-butyrolactone with adipate, a dicarboxylate that consists of a relatively small number of carbon atoms. They also found, however, that when &ggr;-butyrolactone and a dicarboxylate with 9-15 atoms are used as monocarboxylate and dicarboxylate, respectively, selective condensation takes place on one of the esters in the long-chain dicarboxylate at the &agr;-position of &ggr;-lactone to form 2-(&ohgr;)-alkoxycarbonyl alkanoyl)-4-butanolide with a high yield, contrary to the above expectation.
As widely known, long-chain dicarboxylic acid is low in price and widely available as a material for high-quality nylons such as nylon 612 and nylon 610, and therefore long-chain dicarboxylates can also be obtained easily at low cost.
Most Preferred Embodiments of the Invention
For the present invention, condensation of the &ggr;-lactone should be performed in the presense of a condensation agent consisting of a base. Such condensation agents as used herein are those generally used for Claisen condensation and Dieckmann condensation of esters, including alkali metals such as lithium, sodium, and potassium; alkali metal hydrides such as lithium hydride, sodium hydride, and potassium hydride; alkali metal salts of ammonium such as lithium amide, sodium amide, and potassium amide; alkali metal amides of amines such as lithium di-isopropyl amide, sodium di-isopropyl amide, lithium N-methylanilide, and sodium N-methylanilide; magnesium salts of amines such as di-isopropylaminomagnesium chloride and N-methylanilinomagnesium chloride; alkali metal alcoholates of alcohols such as sodium methoxide, sodium ethoxide, sodium n-propoxide, sodium iso-propoxide, sodium n-butoxide, and potassium t-butoxide; and organic alkali metal compounds such as sodium naphthalene and triphenylmethylsodium. Preferred condensation agents for the present invention are alkali metal alcoholates as represented by the general formula ROM where R and M denote an alkyl group with 1-4 carbons and an alkali metal, respectively). There are no specific limitations on the amount of a condensation agent to be used for the invention, but the preferred range is 0.1-5 equivalents, more preferably 0.5-3 equivalents, relative to 1 mole of &ggr;-butyrolactone.
There are no specific limitations on the temperature of the condensation reaction, such as the Claisen condensation, but the preferred range is 0-200° C., more preferably 50-150° C. to produce the alkali metal salt of 2-(&ohgr;-alkoxycarbonyl)-4-butanolide.
A dicarboxylate as used for the present invention should be used in an amount that is excessive in moles relative to &ggr;-butyrolactone, preferably two times its amount in moles. The use of a two-fold amount in moles is very effective to increase the selectivity. Recovery of unreacted dicarboxylate from the reaction product and its recycling for the condensation are preferred for increased reaction efficiency. Such recovery of unreacted dicarboxylate from the reaction product can be achieved easily by simple distillation. The use of dicarboxylate in an excessive amount in moles, coupled with its recycling, serves to further increase the reaction efficiency.
It is not essential to use a solvent, but a solvent widely used in ester condensation may be employed in the reaction as long as said solvent does not reduce the activity of the condensation agent. Group R contained in an ester of the general formula ROOC(CH
2
)
n
COOR as used for the present inve
Etoh Takeaki
Hata Go
Ito Nobuhiko
Katou Tetsuya
Dentz Bernard
Miller Austin R.
Toray Industries
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