Organic compounds -- part of the class 532-570 series – Organic compounds – Oxygen containing
Reexamination Certificate
2001-12-11
2003-05-20
Shippen, Michael L. (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Oxygen containing
C512S019000
Reexamination Certificate
active
06566562
ABSTRACT:
FIELD OF THE INVENTION
The invention relates to the preparation of the compounds isolongifolanol (IUPAC name: 2,2,7,7-tetramethyltricyclo[6.2.1.0
1,6
]undecan-6-ol) and isolongifolenol (1,3,4,5,6,8a-hexahydro-1,1,5,5-tetramethyl-2,4a-methanonaphthalen-8a (2H)-ol; IUPAC name: 2,2,7,7-tetramethyltricyclo[6.2.1.0
1,6
]undec-4-en-6-ol), and to the use thereof as fragrances or aroma substances in functional perfumery and in fine perfumery.
BACKGROUND OF THE INVENTION
There is a constant need for new fragrances with interesting scent notes, particularly for those having an additional use. This need arises from the need to adapt to changing trends and fashions and the associated need to supplement the existing palette of natural fragrances. Furthermore, there is, in general, a constant need for synthetic fragrances which can be prepared favorably and with uniform quality. These substances should have odor profiles which are as pleasant and as natural as possible.
Because of the highly fluctuating prices and qualities of natural patchouli oils there is an urgent need for synthetic compounds with patchouli character and woody-earthy notes which can be prepared in an efficient synthesis from cost-effective starting materials and, moreover, broaden the composition possibilities of the perfumer with their original scent properties.
Isolongifolanol (4) is known from JP 58/022450 B4 and JP 60/010007 B4. However, the compound is obtained in the process described therein only with a content of 5% by hydrogenation of the isolongifolene oxide (2) in a multicomponent mixture.
J. Agric. Food. Chem. 1994, 42, 138-142 describes the reaction of isolongifolene oxide (2) with lithium aluminum hydride. In this way, small amounts (<100 mg) of the isolongifolanol (4) were obtained with a yield of 76%. Disadvantages of this process are the price of the reducing agent and the safety problems associated with the handling of lithium aluminum hydride.
SUMMARY OF THE INVENTION
It was, therefore, also the object to prepare compound 4 in an efficient, reliable synthesis which can be realized on an industrial scale, from cost-effective starting materials.
The invention therefore provides a process for the preparation of isolongifolanol (4), characterized by the following process steps:
a) epoxidation of isolongifolene (1) to give isolongifolene oxide (2),
b) rearrangement of isolongifolene oxide (2) in the presence of a base to give isolongifolenol (3) and
c) reduction of isolongifolenol (3) to give isolongifolanol (4).
DETAILED DESCRIPTION OF THE INVENTION
The following equation can illustrate the invention:
In the first stage, isolongifolene (1) can be reacted in a known manner, for example with peracetic acid, to give isolongifolene oxide (2) (Tetrahedron Lett. 1964, 8, 417; J. Org. Chem. 1970, 35, 1172).
In the second step, the epoxide 2 can be rearranged in thermally and chemically inert solvents in the presence of a strong base to give isolongifolenol (3).
Conditions under which the rearrangement can be carried out favorably are given, for example, in Helv. Chim. Acta 1967, 50, 153; Synthesis 1972,194 and also Tetrahedron 1983, 39, 2323. An overview is given in Larock, Comprehensive Organic Transformations, VCH, 1989, 117-118.
Strong bases are typically alkali metal, alkaline earth metal and light metal alkoxides or alkali metal, alkaline earth metal and light metal amides.
For the purposes of this invention, light metals are, in particular, aluminum, titanium and beryllium.
It is particularly surprising that the rearrangement with unbranched metal alkoxides such as methoxides and ethoxides leads to the isolongifolenol with very high selectivity. Using these bases, epoxides typically produce the corresponding vicinal hydroxyalkyl ethers (Chem. Rev.1959, 737).
Examples of bases which may be mentioned are lithium diethylamide, lithium n-dipropylamide, lithium diisopropylamide, lithium n-dibutylamide, lithium ethylenediamide, trilithium phosphate, sodium hydride, potassium hydride, diethylaluminum 2,2,6,6-tetramethylpiperidide, potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide, sodium ethoxide, potassium ethoxide, lithium ethoxide, sodium methoxide, potassium methoxide, lithium methoxide, sodium isopropoxide, potassium isopropoxide, lithium isopropoxide, magnesium ethoxide, magnesium methoxide, calcium ethoxide and calcium methoxide.
Preferred bases are the alkoxides of lithium, sodium and potassium having 1 to 6 carbon atoms.
More preference is given to sodium methoxide, sodium ethoxide, sodium isopropoxide, sodium tert-butoxide, potassium methoxide, potassium ethoxide, potassium isopropoxide, potassium tert-butoxide, lithium methoxide, lithium ethoxide, lithium isopropoxide and lithium tert-butoxide.
0.3 to 2.5 molar equivalents of the base, preferably 0.6 to 1.8 equivalents and more preferably 0.8 to 1.4 equivalents are used. The equivalents here are based on the content of epoxide 2.
The reaction can be carried out in a large number of solvents. Suitable are, in general, nonpolar or aprotically polar solvents.
Solvents which may be mentioned are open-chain or cyclic dialkyl or alkyl aryl ethers, such as, for example: diethyl ether, tetrahydrofuran, anisole, aliphatic or aromatic hydrocarbons having 6 to 10 carbon atoms, such as cyclohexane, n-heptane, isooctane, toluene, ethylbenzene, xylenes, open-chain or cyclic N,N-di-lower alkyl carboxamides, such as, for example, N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidinone or sulphoxides, such as, for example, dimethyl sulphoxide and diethyl sulphoxide.
Preferred solvents are aromatic hydrocarbons having 7 to 9 carbon atoms, N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidinone, N-ethylpyrrolidinone, N-methylvalerolactam, N-methylcaprolactam, dimethyl sulphoxide, xylenes and anisole.
More preferred solvents are N,N-dimethylformamide, N-methyl-2-pyrrolidinone, dimethyl sulphoxide, xylenes and anisole.
The rearrangement can be carried out in the temperature range from 0 to 250° C., preferably in the range from 50 to 220° C., more preferably in the range from 80 to 190° C.
The reaction can be carried out at 0 to 200 bar, preferred pressures are in the range 1 to 50 bar.
The reduction of 3 to 4 in the third step advantageously takes place over hydrogenation catalysts in a hydrogen atmosphere. Suitable hydrogenation catalysts are, for example, elements of transition group 8 of the Periodic Table of the Elements. Particularly advantageous here are the elements nickel, palladium, platinum, rhodium, iridium, ruthenium and mixtures, compounds and alloys thereof. These catalysts can be used, for example, in finely divided form, applied to carriers or together with other metals or compounds thereof.
Advantageous carrier materials which may be mentioned are activated carbon, aluminum oxides, metal oxides, silica gels, zeolites, clays, clay granules, amorphous aluminum silicates, or other inorganic or polymeric carriers.
The hydrogen pressure during the hydrogenation reaction is in the range from 1 to 200 bar, preferably in the range from 1 to 100 bar, more preferably in the range from 5 to 50 bar.
The isolongifolanol (4) can be purified by customary methods, e.g. by distillation or crystallization.
The compound 4 prepared by the process according to the present invention is a fragrance and has complex odor properties. In addition to patchouli and wood notes, it has camphoraceous, ambergris and green notes. The incorporation into woody and spicy compositions is advantageous, and also an excellent recreation of natural patchouli oils is possible with 4.
A further part of the present invention relates to isolongifolenol of the structural formula:
The compound according to the present invention, isolongifolenol (3), has notable and complex odor properties. In addition to the specifically requested patchouli and wood notes, it also has powerful earthy-camphoraceous and mossy-acrid aspects. The substance is distinguished by originality and natural character and by a very high intensity combined w
Nienhaus Jürgen
Wöhrle Ingo
Haarmann & Reimer GmbH
Pendorf & Cutliff
Shippen Michael L.
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