Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters
Reexamination Certificate
2002-05-06
2003-07-01
Rotman, Alan L. (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acid esters
C560S128000, C549S546000
Reexamination Certificate
active
06586620
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to the field of organic synthesis. It relates, more particularly, to a process for the preparation of alkyl 3-oxo-2-pentyl-1-cylopentene-1-acetates of the general formula
in which R
1
is a C
3
-C
7
alkyl group and R
2
is a C
1
to C
4
, linear or branched, alkyl radical, more preferably a methyl group. The present invention is also drawn to useful intermediate products in the synthesis of the above molecules of formula (I).
BACKGROUND OF THE INVENTION
The cyclopentene derivates (I) are important compounds for the preparation of the alkyl 3-oxo-2-alkyl-1-cyclopentaneacetates (II) which form a class of highly appreciated perfuming ingredients. There should be cited, in particular, the methyl 3-oxo-2-pentyl-1-cyclopentaneacetate, or methyl dihydrojasmonate, which is present in practically every perfume and which is, for example, on sale under the name Hedione® (origin: Firmenich SA, Geneva, Switzerland). There exist a large number of syntheses for the named methyl dihydrojasmonate and its homologues. A possible synthesis is the hydrogenation of the above cyclopentenyl derivatives (I), in order to transform the starting molecule into the compounds of formula (H), having a saturated C
5
-ring.
From the above formula (II) it is clear that these compounds can exist in the form of several stereoisomers, due to the presence of 2 asymmetric carbon atoms. The hydrogenation processes described in the prior art give specific products, according to the conditions employed.
It is known that the catalytic hydrogenation of methyl 3-oxo-2-pentyl-1-cyclopentene-1-acetate, for example, in the presence of aluminum methoxide (see DE-OS 2 162 820) gives racemic cis-methyl-dihydrojasmonate the floral odor note of which is particularly appreciated by perfumers. Another hydrogenation process which makes use of chiral metal complexes is described in EP-B-810 903 (applicant: Firmenich SA). There is obtained the (IR)-cis-methyl dihydrojasmonate, which is the enantiomer showing the best olfactive qualities of all optical isomers.
There is hence a need for a process which can provide industrial amounts of the compounds of formula (1), in particular those in which R
1
is n-pentyl and R
2
is methyl, in order to have starting products for the synthesis of the above-mentioned qualities of the cyclopentyl compounds of formula (II).
The prior art reports a variety of syntheses of methyl 3-oxo-2-pentyl-1-cyclopenteneacetate. Among them, only one utilizes an acyclic derivative in its last step (see Jap. Pat. 58 118,536; Chem. Abstracts 1983, 99 175481 d), whereas the others have as key-intermediates cyclic compounds. According to the nature of these latters, the known processes can be classified in 5 different categories:
a. via a gamma-lactone by rearrangement in the presence of polyphosphoric acid (Dutch Pat. 69 18,228; Chem Abstracts 1971, 75, 109953 d);
b. via methyl dihydrojasmonate by bromination and dehydrobromination (Dutch Pat. 70 02,279; Chem. Abstracts 1972, 76, 3462 g) or by anodic oxidation of its enol-acetate (J. Am. Chem. Soc., 1975, 97, 6144);
c. via 2-pentyl-1,3-cyclopentanedione by reaction with dimethyl malonate (see e.g. DE-OS 2,008,833; Chem. Abstracts, 1970, 73, 109363 d);
d. via 2-pentyl-2-cyclopentene-1-one by radical addition of methyl dihydroxyacetate followed by dehydration (Parf. Cosm. Sav. France 1972, 2(8), 356); by reaction with methyl diazoacetate (Perf. Essent. Oil Rec. 1969, 267; JP 70 00862), or by addition of methyl bromoacetate (J. Org. Chem. 1974, 39, 2637) or of methyl lithioacetate followed by oxidation with chromic acid;
e. via isomerisation of certain epoxy-esters, namely alkyl 2,3-epoxy-2-pentyl-1-cyclopentylidene acetates, in the presence of an acidic isomerisation agent like mineral or organic protic acids or Lewis type acids (U.S. Pat. No. 5,302,745).
All those cited processes, however, do not allow an economic production of the desired cyclopentenyl derivatives of formula (I) on an industrial scale. The problem underlying the present invention was the finding of a process which does not show the disadvantages of those known in the prior art.
SUMMARY OF THE INVENTION
This problem is solved by a process for the preparation of a compound according to formula
wherein R
1
is a C
3
-C
7
alkyl group and R
2
is a methyl or ethyl group, characterized in that said process comprises the isomerisation of an epoxide of formula
wherein R
1
and R
2
have the meaning given in formula (I), in the presence of an isomerisation agent, such as a Lewis or protic acid, a thermal treatment or a combination thereof.
This process is an important feature of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Typical isomerisation agents which can be used in the context of the present invention are known to a person skilled in the art and include mineral acids, organic protic acids and Lewis type acids. Specific examples of those acids are hydrochloric acid, sulfuric acid, phosphoric acid, p-toluenesulfonic acid, methanesulfonic acid, BF
3
, SnCl
4
, TiCl
4
and acidic ion exchange resins.
Additionally, a thermal treatment can be used as an isomerization agent. Preferably, a prolonged thermal treatment conducted at a temperature of between 140 and 220° C. for a time of between 1 and 10 hours is suitable. The thermal treatment can be used along with the acidic isomerization agent for optimum results.
The reaction takes place in the usual solvents. There can be cited here, as non-limiting examples, alcohols (e.g. methanol, ethanol and isopropanol), aromatic solvents (e.g. toluene and xylene), and ethers (e.g. diethyl ether).
Advantageous results could be obtained when methanol was used as solvent. Preferred acids include methanesulfonic acid, phosphoric acid and sulfuric acid. As methyl dihydrojasmonates are the preferred perfuming ingredients which can be prepared according to the process of the present invention, R
1
preferably is a n-pentyl group and R
2
is a methyl group.
The epoxides according to formula (III) can be prepared by the epoxidation of an enol acetate according to the formula (IV) below, in which R
1
and R
2
have the meaning given above for formula (I), with an epoxidising agent.
For the epoxidation reaction, the usual reagents can be used. Non-limiting examples include peracids such as peracetic, performic and perpropionic acid, perbenzoic acid, m-chloroperbenzoic acid and MMPP (magnesium mono perphthalic acid). Hydroperoxides such as t-butylhydroperoxide and hydrogen peroxide can also be used.
It is preferred to use peracetic acid, most preferably peracetic acid in acetic acid.
The epoxides of formula (III) are novel compounds and form an object of the present invention, as well as the above-described process which leads to their formation.
In what concerns the enol acetates of formula (IV), these are known compounds. They can be obtained according to the method as described in J. Am. Chem. Soc. 97, p. 6144-6147 (1975).
It was observed that, depending on the conditions which were chosen when the epoxides of formula (III) are prepared or purified, two other products could be isolated, resulting also from a rearrangement reaction. These compounds can also be formed when the epoxides are submitted to the rearrangement reaction as described above.
One of these products is the cyclic ketone of formula (V)
in which R
1
is a C
3
-C
7
alkyl group and R
2
is a methyl or ethyl group. The ketones (V) are, for example, formed when the epoxides of formula (III) are submitted to a thermal treatment. Often, even at room temperature a certain degree of conversion occurs, whereas a complete conversion is often observed, for example, when the ketones are distilled. It has to be noted here that the synthesis of the cyclopentenyl compounds according to formula (I) is not hampered by the fact that the compounds (V) may be present. These compounds form the desired cyclopentenyl compound (I) under practically the same reaction conditions as do the epoxides, i.e. in presence of an appropriate acidic agent or
Crawford Khushrav
Rautenstrauch Valentin
Uijttewaal Arnoldus
Firmenich SA
Reyes Hector M.
Rotman Alan L.
Winston & Strawn
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