Organic compounds -- part of the class 532-570 series – Organic compounds – Fatty compounds having an acid moiety which contains the...
Reexamination Certificate
2001-05-03
2003-02-04
Carr, Deborah D. (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Fatty compounds having an acid moiety which contains the...
C554S162000, C554S163000, C568S412000
Reexamination Certificate
active
06515154
ABSTRACT:
Acetoacetic acid derivatives, process for their preparation and their use
The present invention relates to acetoacetic acid derivatives of the formula Ia or Ib, to processes for their preparation and to their use for the preparation of 2,15-hexadecanedione. The invention further relates to the use of the compounds of the formula Ia or Ib as intermediate for the preparation of muscone (3-methylcyclopentadecanone).
Muscone(3-methylcyclopentadecanone) of the formula III
is one of the most important ingredients of the natural musk extracts which are very highly sought after in perfumery. Because of the extremely high cost of natural extracts, the synthetic preparation of III is of great interest, particularly since III is far superior to all other known musk fragrances, such as tetralin or nitro musk compounds.
The preparation methods used hitherto are based mainly on ring enlargement reactions, starting from cyclododecanone (cf. for example Helv. Chim. Acta 71 (1988), pp. 1704-1718, and literature cited in loc. Cit.). All of these methods have a multistage process step, which is sometimes extremely involved, and they are therefore unattractive for commercial exploitation.
All known synthesis methods involve intramolecular condensation reactions, such as aldol, Dieckmann or acyloin condensation (see here Houben-Weyl, Methoden der organischen Chemie [Methods of organic chemistry], Vol. 4/2, pp. 729-815). All of these methods have the major disadvantage that relatively good yields of macrocycles are only obtained in very high dilution.
Helv. Chim. Acta, 62 (1979), pages 2673-2680, presents a new type of synthesis process for muscone based on 4,8-dodecadienediol. The key step here is the acid-catalyzed intramolecular cyclization of an open-chain hydroxyacetal to give bicyclic dihydropyran, where, however, because of the required dilution principle, large amounts of solvent are required, as a result of which this process can only be sensibly used for the synthesis of laboratory amounts.
One possibility, which is in itself very good, for preparing II seems to the aldol condensation starting from hexadecane-2,15-dione first described by Stoll (cf. Helv. Chim. Acta, 30 (1974), pages 2019-2023).
However, this process was burdened with considerable disadvantages:
1) The preparation possibilities for the 2,15-diketone required as starting material were hitherto unsatisfactory.
2) The yields achievable in the aldol condensation are relatively low despite working in heavily diluted solutions (according to loc. cit. 17%).
A particular disadvantage of this synthesis is the use of the costly and also toxicologically unacceptable 1,10-dibromodecane.
In addition, the synthesis below starting from 2,2′,5′,2″-terthienyl was presented in J. Am. Chem. Soc. 82 (1960), pages 1447-1450.
However, this synthesis is unsuitable for the synthesis of relatively large amounts of diketone due to the poor accessibility of the starting material.
Two further processes for the preparation of the diketone, each starting from butadiene, have been described by Tsuji et al.:
a) in Chem. Lett. 1976, pages 773-774 and
b) in Bull. Chem. Soc. Japan, 51 (1978), page 1915.
Both processes use expensive palladium catalysts, as a result of which these syntheses too become unattractive for industrial use.
Furthermore, Bull. Chem. Soc. Japan, 56 (1983), pages 345-346, discloses a process for the preparation of IIa starting from &agr;,&ohgr;-tetradecanedicarboxylic acid. A disadvantage of this process is the poor accessibility of the starting compound.
Moreover, J. Organomet. Chem. 264 (1984), pages 229-237, discloses a process for the preparation of IIa starting from (CH
3
)
3
Si—CH
2
—CH═CH—CH
2
—CH
2
—C(CH
3
)═CH—CH
2
—Si(CH
3
)
3
. In addition to the poor accessibility of the starting compound, a disadvantage of this process is the need to use problematical reagents, such as readily flammable potassium hydride.
Also known is the preparation, disclosed in EP-B 0400509 but very complex, of 2,15-hexadecanedione which, inter alia, includes steps such as an oxidation of a diol using sodium hypochlorite to give the dialdehyde and either a Wittig reaction or a Grignard reaction.
It is an object of the present invention to find a simple and economical method for the preparation of 2,15-hexadecanedione and thus also for the preparation of muscone, without the disadvantages specified in the prior art.
We have found that this object is achieved according to the invention by a process for the preparation of compounds of the formula Ia or Ib
where R is an optionally substituted straight-chain or branched C
1
-C
6
-alkyl, C
1
-C
6
-alkoxyalkyl or phenyl radical, which comprises adding an acetoacetic ester of the formula II
to 1,9-decadiene by a free-radical means, and hydrolyzing and carboxylating the compounds of the formula Ia or Ib thus synthesized (scheme 1)
In the process, two molecules of an ester of acetoacetic acid are firstly added, in a free-radical reaction, to the 1,9-decadiene which can be prepared very easily and cost-effectively by metathesis of cyclooctene with ethylene.
The resulting addition products are the corresponding esters of 2,13-bisacetyl-1,14-tetradecanedioic acid (Ia). In addition, the corresponding ester of 2-acetyl-14-oxopentadecanoic acid (Ib) may also be formed as early as during the free-radical addition. This compound is formed by decarboxylation of an ester group of the primary product.
Said compounds can be decarboxylated in the manner customary for keto esters to give 2,15-hexadecanedione.
From the beta-keto esters it is also possible to prepare the corresponding beta-keto acids or salts of the acids, which can both arise as intermediates during cleaving-off of the ester groups. However, the beta-keto acids are not stable compounds since they very readily decarboxylate upon heating to give 1,15-hexadecanedione. They are therefore preferably isolated in the form of their metal salts.
Alkyl in the case of the radical R means, unless stated otherwise, alone or in combination with alkoxy, a straight-chain, branched, saturated or unsaturated radical having 1 to 6 carbon atoms, such as, for example, the methyl, ethyl, propyl, isopropyl, tert-butyl, tert-pentyl, allyl or propynyl radicals.
Alkyl is preferably the methyl, ethyl, propyl, tert-butyl or tert-pentyl radicals.
Alkoxy groups mean a combination of an alkyl group according to the above definition with an oxygen atom, e.g. methoxy, ethoxy, propoxy, butoxy or pentoxy groups. Particular preference is given to the 2-methoxyethyl radical.
A simple two-stage process for the preparation of 2,15-hexadecanedione thus results, which signifies significant progress over the prior art.
Since the 2,15-diketones of the formula Ia or Ib can be prepared by the process described above in a technically simple manner, an industrially simple and advantageous synthesis route to the sought-after musk fragrance muscone is obtained.
One method of the subsequent intramolecular aldol condensation of the 2,15-hexadecanedione prepared according to the invention to give muscone is disclosed, for example, in EP-B 0400509.
The examples below serve to illustrate the invention in more detail without, however, limiting it thereto.
REFERENCES:
patent: 5120880 (1992-06-01), Huellmann et al.
patent: 5247122 (1993-09-01), Witzemann et al.
patent: 400 509 (1990-12-01), None
patent: WO 00/01648 (2000-01-01), None
Allen et al. “Synthetic Aspects of Free-Radical Addition. Part I. Radical-alkylation of Malonic Ester and Related Compounds” J. Chem Soc. vol. 11 (1962) pp. 4468-4475.
Sakurai et al. “Chemistry of Organosilicon Compounds” J. Organometallic Chemistry Bol. 264 (1984) pp. 229-237.
Fujisawa et al. “One-step Synthesis of Long-chain Aliphatic &agr;, &ohgr;-Dicarboxylic Acids Utilizing the Copper-catalyzed Reaction of &bgr;-Priopiolactone with &agr;,&ohgr;-Di-Grignard Reagents” Bull. Chem. Soc. of Japan vol. 56 (1983) pp. 345-346.
Matsumoto et al. “Conversion of Disilanes of Functional Monosilanes IV.1)Synthesis of Methyldchlorosilane and Dlmethylc
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Carr Deborah D.
Keil & Weinkauf
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