Geranic acid derivatives

Details Geranic acid derivatives Geranic acid derivatives

2001-06-21

2002-05-07

Killos, Paul J. (Department: 1623)

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C554S121000, C554S132000, C554S161000, C562S510000, C560S126000

Reexamination Certificate

active

06384242

ABSTRACT:

This application is a 371 national stage application of International Application PCT/IB99/01463, filed on Aug. 24, 1999, which has benefit of European Patent Application 98116634.1, filed on Sep. 3, 1998.
BACKGROUND OF THE INVENTION
Field of the Invention
The invention relates to 4-methyl-4-(methylpent-3-en-1-yl)-2-oxetanone of the formula:
as a new intermediate product for the preparation of various geranic acid derivatives.
The invention also relates to a process for the preparation of 3-hydroxycitronellic acid derivatives of the general formula:
where R
2
is hydrogen or an alkyl group, a process for the preparation of cyclogeranic derivatives of the general formula:
where R
1
is hydrogen or an alkyl group, a process for the preparation of geranic acid derivatives of the formula:
and a process for the preparation of 2,6-dimethyl-hepta-1,5-diene.
4-Methyl-4-(4-methylpent-3-en-1-yl)-2-oxetanone and the aforementioned compounds prepared therefrom according to the invention are important synthetic building blocks in the preparation of perfumes and fragrances.
BROAD DESCRIPTION OF THE INVENTION
The object of the invention is to provide simple, commercially feasible access to the aforementioned synthetic building blocks.
The object is achievable by the provision of the intermediate product 4-methyl-4-(4-methylpent-3-en-1-yl)-2-oxetanone of the formula:
4-Methyl-4-(4-methylpent-3-en-1-yl)-2-oxetanone of the formula I is prepared according to the invention by conversion of 6-methyl-5-hepten-2-one with ketene in the presence of a catalyst.
DETAILED DESCRIPTION OF THE INVENTION
6-Methyl-5-hepten-2-one is a commercially available compound. Ketene is obtained in a known manner, usually directly by cracking diketene, at temperatures of over 300° C.
Lewis acids are suitable as catalysts. The conventional Lewis acids known to those skilled in the art can be used, e.g., zinc chloride, titanium tetrachloride, aluminum chloride, boron trifluoride or boron trifluoride etherate. Good results are obtained with boron trifluoride etherate.
The Lewis acids are advantageously used in an amount of 0.1 mol percent to 5 mol percent relative to the 6-methyl-5-hepten-2-one used.
It is possible to carry out conversion in the absence of a solvent, but an inert solvent is advantageously used; for example, halogenated hydrocarbons such as methylene chloride or carbon tetrachloride have proved successful.
Usually, the ketene is added, and the reaction takes place at a temperature of −30° C. to 40° C., preferably −30° C. to 0° C.
Depending on the temperature gradient of the ketene addition, the 4-methyl-4-(4-methylpent-3-en-1-yl)-2-oxetanone can. form an oligomer of the formula:
where n is usually a number ≧1. At low temperatures of −30° C. to 0° C., 4-methyl-4-(4-methylpent-3-en-1-yl)-2-oxetanone of the formula I is generally formed, whereas temperatures of 0° C. to 40° C. generally give rise to the oligomer of the formula V.
The desired lactone can be isolated in pure form by methods conventional to the skilled worker, e.g. by removing the ketene and the excess solvent and finally by distillation, e.g. in a thin-film evaporator.
To prepare the 3-hydroxycitronellic acid derivatives of the general formula
where R
2
is hydrogen or an alkyl group, the 4-methyl-4-(4-methylpent-3-en-1-yl)-2-oxetanone of the formula
is esterified with an alcohol of the formula
R
2
OH  IV
where R
2
has the aforesaid meaning, or hydrolysed with a base to form the acid.
In the following, alkyl group is taken to mean a straight-chain or branched alkyl group with 1 to 6 C atoms, which can optionally contain one or more substituents from the series C
1-4
alkyl or phenyl. Preferably, R
2
stands for methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl or benzyl.
Esterification is carried out with an alcohol of the formula
R
2
OH  IV
where R
2
has the aforesaid meaning, advantageously in the presence of an alkali alcoholate.
In the alkali alcoholate, the alcoholate part advantageously corresponds to the R
2
OH alcohol used.
Preferably, the sodium or potassium alcoholates of the R
2
OH alcohols in question are used.
Conversion is usually carried out at a temperature of 0° C. to 30° C. The alcohol, used in excess, acts as a solvent.
The resulting esters can be isolated by methods conventional to the skilled worker and obtained in pure form, e.g. by distillation.
Hydrolysis is carried out with a base to form the acid.
The selection of the base is in itself not critical and the conventional base hydrolysis methods can be used. Suitable bases are aqueous solutions of alkali or alkaline-earth hydroxides; an aqueous sodium hydroxide solution is particularly suitable.
Addition of a catalyst is not necessary for hydrolysis, but can be advantageous in accelerating the reaction.
In this case, the conventional phase-transfer catalysts known to those skilled in the art are suitable, e.g. quaternary ammonium compounds. Good results can be obtained using tributylbenzylammonium chloride, for example.
Base hydrolysis is advantageously carried out at a temperature in the range from 20° C. to 80° C. The 3-hydroxycitronellic acid can be isolated from the reaction mixture e.g. by extraction of the acidified aqueous phase using a suitable organic solvent, e.g. diethyl ether.
To prepare the cyclogeranic acid derivatives of the general formula
where R
1
is hydrogen or an alkyl group, the 4-methyl-4-(4-methylpent-3-en-1-yl)-2-oxetanone of the formula I is converted in the presence of a strong acid at a temperature of 20° C. to 100° C.
The broken line in formula II is intended to show that the double bond can either be in the &agr;-position or &bgr;-position relative to the carboxyl group or in the exo-position, and that a mixture of the compounds
where R
1
has the aforesaid meaning, is usually produced as a reaction product.
The starting product for the ring closure can either be the 4-methyl-4-(4-methylpent-3-en-1-yl)-2-oxetanone of the formula I or the polymer of the formula V.
According to the invention, cyclisation takes place in the presence of a strong acid.
Sulfuric acid or a mixture of the aforementioned acid with formic acid or acetic acid can be used as a strong acid.
The reaction temperature is advantageously selected in a range from 20° C. to 100° C.
The cyclogeranic acid derivatives of the general formula II can be isolated from the reaction mixture by methods conventionally used by skilled workers and optionally further purified by distillation.
If the conversion of the 4-methyl-4-(4-methylpent-3-en-1-yl)-2-oxetanone of the formula I is carried out under comparatively less acid conditions, the geranic acid derivatives of the following formula are produced:
The broken line is intended to show that various isomers of the geranic acid can be produced as a reaction product. The wavy line indicates that the geranic acid can be present as either an E-isomer or a Z-isomer. The preferred geranic acid derivative is the (E)- or (Z)-geranic acid of the formula
However, it has been shown that the acidity and temperature of the reaction mixture are the decisive factors in determining whether cyclogeranic acid derivatives of the formula II are produced or whether the reaction stops at the preliminary stage of the geranic acid derivatives of the formula VIII.
To promote the production of the geranic acid derivatives of the formula VIII, it has proved advantageous to use a mineral acid such as sulfuric acid in the presence of an organic solvent.
Good results can be obtained using protonated N,N-dimethyl formamide. Conversion can advantageously be carried out at a temperature of 0° C. to 60° C. This conversion generally results in a mixture of isomers which, however, can be substantially converted into the (E)- and/or (Z)-geranic acid of the formula VIIIa using p-toluenesulfonyl chloride/pyridine by the method used by Fujisawa et al in Bull. Soc. Chem. Jpn. 55 (1982) 3555-3559.
According to a further embodiment of the invention, the 4-methyl-4-(4-methylpent-3-en-1-yl)-2-oxetanone of the formula

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