Isomerization of 2,6,6-trimethylcyclohex-1 or 2-ENYL ketones or esters catalyzed by strong base

Abstract

The present invention relates to a of isomerization process of a compound of the formula (I-A) or of the formula (I-B) into a mixture of a compound of the formula (I-A) and (I-B). Using this isomerization process, depending on the desire, either selectively the compound of formula (I-A) or of the formula (I-B), respectively, can be obtained in high isomeric purity from the undesired isomer or a mixture of the desired and undesired isomer of formula (I-A) and (I-B).

Description

[0001] ISOMERIZATION OF 2,6,6-TRIMETHYLCYCLOHEX-1 OR 2-ENYL KETONES OR ESTERS CATALYZED BY STRONG BASE

[0002] Technical Field

[0003] The present invention relates to field of 2,6,6-trimethylcyclohex-1 or 2-enyl ketones or esters and to the field of perfumery ingredients and intermediates, particularly to a-damascone or [3-damascone and its intermediates.

[0004] Background of the invention

[0005] Damascenes are a series of closely related chemical compounds that are components of a variety of essential oils. The damascenes belong to a family of chemicals known as rose ketones and used as fruity floral fragrant materials. Particularly, a-damascone and [3-damascone are highly valued ingredients. Particularly, [3-damascone is very attractive. However, its price is particularly high.

[0006] Preferred synthetic pathways to a-damascone or [3-damascone, respectively, are based on 2,6,6-trimethyl-2-cyclohexenyl methyl ketone (= 1- (2,6,6-trimethylcyclohex-2-en-1 -yl)ethan-1 -one) of formula (I-A1 ) as shown below), or 2,6, 6-trimethyl-1 -cyclohexenyl methyl ketone (=1 -(2,6,6-trimethylcyclohex-1-en- 1 -yl)ethan-1-one of formula (I-B1 ) as shown below), respectively.

[0007] EP 1 162 190 A2 discloses the isomerization of a different isomer, i.e. of 2,6,6-trimethyl-3-cyclohexenyl methyl ketone (= 1 -(2,6,6-trimethylcyclohex-3-en-1- yl)ethan-1 -one) in the presence of an acid or base as catalyst.

[0008] However, this isomerization leads to a mixture, in which not only the isomers (I-A1 ) and (I-B1 ) but also significant amounts of different isomers or decomposition products are formed. When a pure end product using this intermediate is needed a separation of the isomers is needed. The separation of this great number of isomers, however, is difficult, and therefore very costly, to achieve. Finally, the undesired isomer could not be used for the desired end- product.

[0009] As the synthesis in a pure form of particularly 2,6,6-trimethyl-1 - cyclohexenyl methyl ketone, is very difficult and costly, an efficient pathway would be highly appreciated in the market.

[0010] Summary of the invention Therefore, the problem to be solved by the present invention is to offer a new pathway to compounds of the formula (l-A) and / or (l-B) at particularly high yields.

[0011] Surprisingly, it has been found that the process according to claim 1 offers a solution to this problem.

[0012] This isomerization avoids the formation of a wild mixture of isomers as found in the prior art. This advantage leads to the possibility of easily separate the desired isomer, i.e. the compound of the formula (I) or (l-B).

[0013] The combining of this isomerisation process with a reactive distillation, resp. inverse reactive distillation, allows to convert the starting isomer completely into the desired isomer, either from the pure form of the undesired isomer or an isomer mixture of the desired and undesired isomer.

[0014] Further aspects of the invention are subject of further independent claims. Particularly preferred embodiments are subject of dependent claims.

[0015] Detailed description of the invention

[0016] In a first aspect the present invention relates to a process of isomerization of a compound of the formula (l-A) or of the formula (l-B) into a mixture of a compound of the formula (l-A) and (l-B) whereas R1represents either a methyl group or O-C1-10 alkyl group, particularly 0- CH3, characterized in that that the isomerization is performed in the presence of a strong base.

[0017] For sake of clarity, some terms used in the present document are defined as follows: In the present document, a “Cx-y-alkyl” group is an alkyl group comprising x to y carbon atoms, i.e. , for example, a Ci-3-alkyl group is an alkyl group comprising 1 to 3 carbon atoms. The alkyl group can be linear or branched. For example -CH(CH3)-CH2-CH3 is considered as a C4-alkyl group.

[0018] In case identical labels for symbols or groups are present in several formulae, in the present document, the definition of said group or symbol made in the context of one specific formula applies also to other formulae which comprises the same said label.

[0019] The term “independently from each other” in this document means, in the context of substituents, moieties, or groups, that identically designated substituents, moieties, or groups can occur simultaneously with a different meaning in the same molecule.

[0020] Any single dotted line in any formulae represents the bond by which said substituent is bound to the rest of a molecule.

[0021] The term "stereoisomer" is a general term used for all isomers of individual compounds that differ only in the orientation of their atoms in space, not in the connectivity of the atoms Thus, the term stereoisomer includes mirror image isomers (enantiomers), geometric (cis / trans or E / Z) isomers, and diastereoisomers. For precise definitions of the terms, see G. Helmchen:"Vocabulary and Nomenclature of Organic Stereochemistry", in Houben-Weyl E21a, Stereoselective Synthesis G. Helmchen, R.W. Hoffmann, J. Mulzer, E. Schaumann (Hrsg.), 1995, 1 -74. The possible isomers can be present either in pure isomeric form or as mixtures (i.e. racemates, cis / trans-mixtures or mixtures of diasteroisomers).

[0022] The term “strong base” in this document means that the base has a pkb of less than 5, particularly of less than 3.75, more particularly less than 0. As the person skilled in the art the pkb is related to the pkaof the respective conjugated acid by the relation pkb = 14-pka. In one of the embodiments, a compound of the formula (l-A) is isomerized

[0023] In another embodiment, a compound of the formula (l-B) is isomerized In a further embodiment, a mixture of the compounds of the formula (l-A) and (l-B) is isomerized.

[0024] In any of these embodiments, after isomerization a mixture of the compounds of the formula (l-A) and (l-B) is obtained. Said resulting mixture of compounds of the formula (l-A) and (l-B) reaches an isomeric equilibrium, in which the compound of the formula (l-A) is in excess over (l-B). Typically this isomeric mixture has a isomer ratio of (l-A) : (l-B) of between 75 : 25 and 60 : 40, particularly between 70:30 and 67 : 33. It has been observed that the isomerization can be performed using any of stereoisomers of the compound of the formula (l-A) and / or (l-B).

[0025] The most preferred compounds of the formula (l-A) and / or (l-B) are the compounds of the formula (I-A1 ) (= 1-(2,6,6-trimethylcyclohex-2-en-1-yl)ethan-1- one) and / or (I-B1 ) (=1-(2,6,6-trimethylcyclohex-1-en-1-yl)ethan-1-one)

[0026] (I-A1 )

[0027]

[0028] The above process of isomerization is performed in the presence of a strong base. The strong base is a base having a pkb of less than 5, particularly of less than 3.75, more particularly less than 0.

[0029] Preferably the strong base is selected from the group consisting of alkali metal alcoholates, particularly alkali metal ethanolates or alkali metal methanolates, preferably sodium or potassium methanolate, more preferably potassium methanolate; or ammonium hydroxide; or hydroxides of metals, particularly alkali metal hydroxides. Preferably the strong base is selected from the group consisting of alkali metal alcoholates, particularly alkali metal ethanolates or alkali metal methanolates, preferably sodium or potassium methanolate, more preferably potassium methanolate, or hydroxides of metals, particularly alkali metal hydroxides

[0030] More preferably the strong base is an alkali metal methanolate or an alkali metal hydroxide. Preferred strong bases are MeONa, MeOK, NaOH and KOH., more preferably the strong base is MeONa or MeOK.

[0031] It is preferred that the strong base is present in an amount of between 0.1 % and 20%, preferably between 0.5 % and 10%, relative to the weight of the compound the formula (l-A) or of the formula (l-B) prior to the isomerization.

[0032] The isomerization is performed preferably at a temperature of between 90°C and 260°C, preferably between 110°C and 200°C.

[0033] It is further preferred, that the isomerization is performed in the presence of at least one solvent with a boiling point of above 150°C, preferably above 200°C, more preferably above 300°C, at ambient pressure.

[0034] Said solvent has preferably a boiling point at ambient pressure (1013 hPa) which is above the temperature at which the isomerization is performed. In one of the embodiments, the solvent is either N-methyl-2-pyrrolidone (NMP) or 2-pyrrolidone or dimethylformamide (DMF).

[0035] In another embodiment, said the solvent is preferably selected from the group consisting of polyethers, polyols, ethers of polyols, and polyether polyols. More preferably the solvent is a polyol, particularly a polyether polyol, or an ether of polyol, the polyol being particularly selected from the group consisting of the polyether polyols polyethylene glycol (PEG), polypropylene glycol (PPG) and polytetrahydofuran (PTHF), more preferably polyethylene glycol (PEG).

[0036] Most preferred solvent is a polyethylene glycol.

[0037] In an ether of a said polyols at least one of the hydroxy group of the polyol is etherified forming an ether alcohol. For example, tripropyleneglycol monomethylether, is an example of a polyol which is partially etherified.

[0038] It is further preferred, that isomerization is performed at an absolute pressure of between 10 and 5’000 hPa, preferable between 100 and 2’000 hPa, most preferably between 100 and 1300 hPa.

[0039] It is more preferred to perform the isomerization at reduced pressure at an absolute pressure of between 10 and 1000 hPa, particularly between 100 and 1000 hPa, or even more preferred at ambient pressure.

[0040] The compound of the formula (l-A), particular (I-A1 ), has a lower boiling point than the corresponding compound of the formula (l-B), particular the corresponding compound of the formula (I-B1 ).

[0041] The process of isomerization is particularly useful for optimizing the yield of production of compound of the for formula (l-A) or formula (l-B), particularly in a process which either yields in a first instance a mixture of the compounds (l-A) and (l-B) or only the undesired isomer (l-A) resp. (l-B).

[0042] As pointed out in above, depending on the situation either the isomer of the formula(l-A) or of the formula (l-B) is the isomer which is needed for further reaction steps yielding a targeted end product. However, it is important to have the respective isomer in a high purity to avoid undesired side products. Therefore, depending on the situation, either the compound of the formula (l-A) or the compound of the formula (l-B) is the desired product.

[0043] For example, when the compound of the formula (l-A) is the desired compound, the above process of isomerization allows to convert the undesired isomer, i.e. compound of the formula (l-B) either in pure form or in a mixture to the desired isomer, i.e. the compound of the formula (l-A) using a specific process.

[0044] Hence, in a further aspect, the invention relates to a process of preparing the compound of the formula (l-A) comprising the steps ia) isomerizing a compound of the formula (l-B) by a process of isomerization as described above in great details to yield a mixture of the formula (l-A) and (I- B); iia) isolating the compound of the formula (l-A) from said mixture by reactive distillation whereas R1represents either a methyl group or group or O-C1-10 alkyl group, particularly O-CH3. The reactive distillation allows separating the desired isomer, i.e. compound of the formula (l-A), from the reaction mixture and collecting it in pure form. In the absence of any isomerization catalyst the compound of the formula (l-A) is stable and does not isomerize anymore.

[0045] As the compound of the formula (l-A) is removed from the reaction mixture which still comprises the strong base as isomerization catalyst, the undesired isomer, i.e. the compound of the formula (l-B) is isomerized to the compound of the formula (l-A) in such an amount as to reach the equilibrium of compound of the formula (l-A) and (l-B) according to the principle of Le Chatelier (see figure 1a). When the reactive distillation is performed in a continuous manner, i.e. the compound of the formula (l-A) is constantly removed, essential all the undesired compound of the formula (l-B) is converted by this method to the desired isomer of the formula (l-A).

[0046] Therefore, it is preferred that this process is a continuous process.

[0047] For a quantitative separation, the person skilled in the art will use a respective distillation column(s).

[0048] Figure 2a shows a schematic set-up of an equipment for reactive distillation 1 for such a process. Material flows are indicated by grey arrows.

[0049] The compound of formula (l-B) is placed in a reaction vessel 2 together with a strong base. By the presence of the strong base the compound of formula (l-B) isomerizes to a mixture of compounds of formula (l-A) and (l-B). By heating the reaction mixture of the reaction vessel, the gas phase formed is directed and separated by a distillation column 3. Said distillation column is chosen in such a manner that it separates the compounds of formula (l-A) and (l-B) in a sufficient manner that quantitative separation is enabled. It has been shown that particularly fractional distillation columns of the type BX, sold by Sulzer, Switzerland, are especially suited for the separation of the compound of the formula (l-A) and (l-B). The gas phase leaves the distillation column 1 through an outlet 4 at the top or in the area near the top-end of the column. In a condenser 5 the gas phase is condensed. The flow of condensate can be directed by a valve 6 to be reintroduced into the distillation column at an inlet 8 at upper part of distillation column or to a cooler 7. For optimizing the separation of compound of the formula (l-A) and (l-B) the position of the valves 6 is used in such a manner that the flow of condensate is split between distillation column 3 and cooler 7, respectively the collection vessel(s) 9, in a suitable flow ratio. The quality of separation can be assessed by analytical determination of the quantities of compound of the formula (l-A) and (l-B) leaving the distillation column or before the entry into the cooler 7. As the use of cooler is primarily for reducing injuries of the operators working at the equipment 1 . Therefore, the cooler 7 is principally not a mandatory feature of the equipment 1 . The condensate consists essentially of the compound of the formula (l-A), preferably of pure compound of the formula (l-A).

[0050] The embodiment as represented in figure 2a, shows a series of different collection vessels, such as drums. The direction of flow to the individual collection vessel can be directed by using a valve 6, or several valves 6, to fill a specific collection vessel 9. It is obvious to the person skilled in the art, that the compound of the formula (l-A) can also be performed in an arrangement which has only one collection vessel 9.

[0051] By the removal of the compound of the formula (l-A) from the reaction mixture in the reaction vessel 2, compound of the formula (l-B) isomerizes to compound of the formula (l-A) forming isomeric mixture of compound of the formula (l-A) and (l-B) in equilibrium as schematically shown in figure 1a. It is important to realize that the isomerization does only take place in the presence of a strong base, i.e. only in reaction vessel 2. In other words, in any part of the equipment 1 where the isomers are not in contact with the strong base, isomerization does not take place.

[0052] The reactive distillation step iia) is preferably performed at a temperature of between 90°C and 260°C, preferably between 110°C and 200°C.

[0053] It is further preferred that the reactive distillation step iia) is performed at reduced pressure, preferably at an absolute pressure of 1 - TOGO hPa, preferably 20 - 50 hPa.

[0054] When the compound of the formula (l-B), however, is the desired compound, the above process of isomerization allows to convert the undesired isomer, i.e. compound of the formula (l-A) either in pure form, or in a mixture to the desired isomer, i.e. the compound of the formula (l-B) using a specific process. Hence, in a further aspect, the invention relates to a process of preparing the compound of the formula (l-B) comprising the steps ib) isomerizing a compound of the formula (l-A) by a process of isomerization as described above in great details to yield a mixture of the formula (l-A) and (I- B); iib) isolating the compound of the formula (l-B) from said mixture by inverse reactive distillation. s either a methyl group or O-C1-10 alkyl group, particularly O-CH3.

[0055] The inverse reactive distillation allows separating the desired isomer, i.e. compound of the formula (l-B), from the reaction mixture and collecting it in pure form. In the absence of any isomerization catalyst the compound of the formula (l-B) is stable and does not isomerize anymore.

[0056] As the compound of the formula (l-B) is removed from the reaction mixture which still comprises the strong base as isomerization catalyst, the undesired isomer, i.e. the compound of the formula (l-A) is isomerized to the compound of the formula (l-B) in such an amount as to reach the equilibrium of compound of the formula (l-A) and (l-B) according to the principle of Le Chatelier (see figure 1 b). When the inverse reactive distillation is performed in a continuous manner, i.e. the compound of the formula (l-B) is constantly removed, essential all the undesired compound of the formula (l-A) is converted by this method to the desired isomer of the formula (l-B).

[0057] Therefore, it is preferred that this process is a continuous process.

[0058] For a quantitative separation, the person skilled in the art will use a respective distillation column(s).

[0059] Figure 2b shows a schematic set-up of an equipment for reactive distillation T for such a process. Material flows are indicated by grey arrows.

[0060] The compound of formula (l-A) is placed in a reaction vessel 2 together with a strong base. By the presence of the strong base the compound of formula (l-A) isomerizes to a mixture of compounds of formula (l-A) and (l-B). In embodiment shown in figure 2b, the strong base is a solid. A part of the liquid phase of the reaction mixture in reaction vessel 2 is directed to the heater 10 assuring, for example by means of a filter or mesh, (not shown in figure 2b) that the strong base remains in the rection vessel. The heated mixture of compound of the formula (l-A) and (l-b) is introduced into the distillation column, preferably at an inlet 8 at upper part of distillation column.

[0061] In a different embodiment, the strong base is not solid. In this case the reaction mixture can be heated, preferably in the reaction vessel 2, to form a gas phase consisting of compounds of the formula (l-A) and (l-B). It is then preferred to cool the separated gas phase to such an extent that it condenses at least partially, before introducing said mixture of compound of formula (l-A) and (l-B) to the distillation column, preferably at an inlet 8 at upper part of distillation column.

[0062] The distillation column is chosen in such a manner that it separates the compounds of formula (l-A) and (l-B) in a sufficient manner that quantitative separation is enabled. It has been shown that particularly fractional distillation columns of the type BX, sold by Sulzer, Switzerland, are especially suited for the separation of the compound of the formula (l-A) and (l-B).

[0063] At the outlet 11 at bottom of distillation column essentially pure compound of the formula (l-B) can be taken out of the distillation column and transferred to a reboiler 12, by which the gas phase which comprises some residual compound of the formula (l-A) is formed and re-introduced in the distillation column, particularly by an inlet 13 at the lower part of distillation column. The quality of separation of compound of formula (l-A) and (l-B) by the reboiler 12 can be influenced by the process parameters, particularly by the choice of temperature within the reboiler. The liquid phase in the reboiler 12 is then transfer through an outlet for liquids 14 of the reboiler to the collection vessel(s) 9.

[0064] This liquid phase can optionally be cooled by means of a cooler (not shown in figure 2b) and consists essentially of the compound of the formula (l-B), preferably of pure compound of the formula (l-B). Said liquid phase is then directed to the collection vessel 9 by selecting a different position of the valve 6. The embodiment as represented in figure 2b, shows a series of different collection vessels 9, such as drums. The direction of flow to the individual collection vessel can be directed by using a valve 6, or several valves 6, to for filling of a specific collection vessel 9. It is obvious to the person skilled in the art, that the compound of the formula (l-B) can also be performed in an arrangement which has only one collection vessel 9.

[0065] The quality of separation can be assessed by analytical determination of the quantities of compound of the formula (l-A) and (l-B) leaving the distillation column at the outlet 11 , or the outlet 14 of the reboiler 12, respectively.

[0066] The gas phase formed in the distillation column 1 , leaves the distillation column 1 through an outlet 4 at the top or in the area near the top-end of the column. In a condenser 5 the gas phase is then condensed. The condensate, which is highly enriched in compound of the formula (l-A), is then transferred to the reaction vessel 2.

[0067] By the removal of the compound of the formula (l-B) from the reaction mixture in the reaction vessel 2, compound of the formula (l-A) isomerizes to compound of the formula (l-A) forming isomeric mixture of compound of the formula (l-A) and (l-B) in equilibrium as schematically shown in figure 1b. It is important to realize that the isomerization does only take place in the presence of a strong base, i.e. only in reaction vessel 2. In other words, in any part of the equipment T where the isomers are not in contact with the strong base, isomerization does not take place.

[0068] The inverse reactive distillation step iib) is preferably performed at a temperature of between 90°C and 260°C, preferably between 110°C and 200°C. It is further preferred that the inverse reactive distillation iib) is performed at reduced pressure, preferably at an absolute pressure of 1 - TOGO hPa, preferably 20 - 50 hPa. It has been shown that by using the above processes either the compound of the formula (l-A) or of the formula (l-B) can be obtained in a quantitative manner and at high purity.

[0069] The compound of the formula (l-A) or formula (l-B) exhibits a high isomeric purity, typically of more than 95% (i.e. [(l-A)] I ([(l-A)]+[(l-B)] ) respectively [(l-B)] I ( [(l-A)]+[(l-B)] ).

[0070] It offers the flexibility to use the undesired isomer either in pure form or in a mixture of the desired and undesired isomers and have the undesired isomer converted essentially completely into other desired isomer.

[0071] As discussed above in great detail, the composition comprising a compound of the formula (l-A) and / (or of the formula (l-B) and at least one strong base, preferably a strong base selected from the group of alkali metal alcoholates, particularly alkali metal ethanolates or alkali metal methanolates, preferably sodium or potassium methanolate, more preferably potassium methanolate or ammonium hydroxide or hydroxides of metals, particularly alkali metal hydroxides; is suitable to be used for the isomerization of a compound of the formula (l-A) or of the formula (l-B) into a mixture of a compound of the formula (l-A) and (l-B) or a process of preparing the compound of the formula (l-A) or a process of preparing the compound of the formula (l-B) as discussed above.

[0072] Hence, in a further aspect the invention relates to a composition comprising at least a compound of the formula (l-A) and / or of the formula (l-B) whereas R1represents either a methyl group or an O-C1-10 alkyl group, particularly O-CH3; and at least one strong base, preferably a strong base selected from the group of alkali metal alcoholates, particularly alkali metal ethanolates or alkali metal methanolates, preferably sodium or potassium methanolate, more preferably potassium methanolate or ammonium hydroxide or hydroxides of metals, particularly alkali metal hydroxides.

[0073] As pointed out above, it is preferred that said composition further comprises at least one solvent with a boiling point of above 150°C, preferably above 200°C, more preferably above 300°C, at ambient pressure.

[0074] The details and preferred embodiments are those as discussed above in great detail for the processes.

[0075] The compounds of the formula (l-A) and / or (l-B) are important intermediates in the field of perfumes, flavours and fragrances.

[0076] Particularly, 2,6,6-trimethyl-2-cyclohexenyl methyl ketone (= 1 -(2,6,6- trimethylcyclohex-2-en-1-yl)ethan-1-one) of formula (I-A1 ) is very useful intermediate in the synthesis of a-damascone.

[0077] Furthermore, 2, 6, 6-trimethyl-1 -cyclohexenyl methyl ketone (=1 -(2,6,6- trimethylcyclohex-1-en-1-yl)ethan-1-one of formula (I-B1 ) is very useful intermediate in the synthesis of [3-damascone.

[0078] Using 2,6,6-trimethyl-2-cyclohexenyl methyl ketone or 2,6,6-trimethyl-1- cyclohexenyl methyl ketone, respectively, as prepared by the processes of this invention, a highly pure a-damascone or [3-damascone, respectively, can be achieved. This is particularly important, as a-damascone or [3-damascone in high purity, particularly in highly isomeric purity, are highly valued in the field of of perfumes, flavours and fragrances.

[0079] Therefore, the invention relates in a further aspect to a perfume composition comprising a-damascone or [3-damascone, respectively, in a high isomeric purity which is manufactured from the compound of the formula (I-A1 ) or formula (I-B1 ), respectively, obtained by a process of the present invention as described above in great detail.

[0080] List of reference signs

[0081] 1 Equipment for reactive distillation 1 ’ Equipment for inverse reverse distillation

[0082] 2 Reaction vessel

[0083] 3 Distillation column

[0084] 4 Outlet at the top of distillation column

[0085] 5 Condenser

[0086] 6 Valve

[0087] 7 Cooler

[0088] 8 Inlet at upper part of distillation column

[0089] 9 Collection vessel

[0090] 10 Heater

[0091] 11 Outlet at bottom of distillation column

[0092] 12 Reboiler

[0093] 13 Inlet at the lower part of distillation column

[0094] 14 Outlet for liquids of the reboiler

[0095] Examples

[0096] The following examples are provided to further illustrate the compositions and effects of the present invention. These examples are illustrative only and are not intended to limit the scope of the invention in any way.

[0097] Experimental series 1 : Isomerization of pure ( l-A) or ( l-B)

[0098] In a dried reactor (1 L) equipped with a mechanical stirrer, a reflux condenser and a Dean Stark apparatus are loaded 750 g of pure compound of the compound (“starting compound”), optionally the solvent polyethylene glycol (PEG)(Tetraethyleneglycol; molecular weight = 194.23 g / mol, boiling point = 327 °C), as well as the strong base in an amount as given in table 1 . The resulting mixture is stirred over 1-2h at the reaction temperature (TR) until reaching the isomeric equilibrium to a mixture of isomers (l-A) and (l-B). During the reaction time, methyl alcohol is collected in the Dean Stark apparatus. The amounts of isomers (l-A) and (l-B) in equilibrium have been quantified by gas chromatography (GC) and shown in table 1 .

[0099]

[0100] Table 1 . somerization of pure isomers of mixture of formula (l-A) and (l-B). determined from the collected amounts of (l-A) and (l-B) determined by GC

[0101] These results show that the isomers of formula (l-A) or (l-B) can be isomerized quantitatively to a mixture of isomers of the formula (l-A) and (l-B).

[0102] Particularly, no 2,6,6-trimethyl-3-cyclohexenyl methyl ketone or 2,6,6-trimethyl-4- cyclohexenyl methyl ketone have been found. Experimental series 2: Comparison isomerization of isomers 2,6,6-trimethyl-3- cyclohexenyl methyl ketone (EP 1 162 190 A2)

[0103] For comparison’s sake the compound of the formula (Ref.l-C) was submitted to the isomerization process as given in experimental series 1 and using 32 wt.-% MeOK in MeOH and PEG stirring over 6h at the reaction temperature of 168°C until reaching the isomeric equilibrium.

[0104] The following isomers have been found and quantified: This experiment shows that the isomerization of 2,6,6-trimethyl-3-cyclo- hexenyl methyl ketone leads to a very complex mixture of isomers having the carbon-carbon double bond at either position 1 , 2, 3, 4 or in the exo position. Finally, an isomer reduced to the alcohol has been observed in an amount of 0.8%.

[0105] Experimental series 3: Isomerization using a reactive distillation

[0106] The isomerization of (I-A1 ) I (I-B1 ) according to the first series was performed with a fractional distillation column 9m BX Sulzer attached to the reaction vessel in accordance to figure 2a. The pure isomer of the formula (I-A1 ) could be collected continuously from the top of the column, whereas it could be monitored that the isomer of the formula (I-B1 ) was continuously isomerized to the compound of the formula (I-A1 ) to maintain the equilibrium ratio of mixture (I-A1 ) I (I-B1 ) of constantly about 66 I 34.

[0107] Experimental series 4: Isomerization using an inverse reactive distillation

[0108] The isomerization of (I-A1 ) I (I-B1 ) according to the first series was performed with an inverted fractional distillation column 9m BX Sulzer attached to the reaction vessel in accordance to figure 2b. In such columns, the reaction vessel is placed above the column rather than underneath it. The pure isomer of the formula (I-B1 ) could be collected continuously from the bottom of the column, whereas it could be monitored that the isomer of the formula (I-A1 ) was continuously isomerized to the compound of the formula (I-B1 ) to maintain the equilibrium ratio of mixture (I-A1 ) / (I-B1 ) of constantly about 66 / 34.

Claims

Claims1 . A process of isomerization of a compound of the formula (l-A) or of the formula (l-B) into a mixture of a compound of the formula (l-A) and (l-B)whereas R1represents either a methyl group or O-C1-10 alkyl group, particularly O-CH3, characterized in that that the isomerization is performed in the presence of a strong base.

2. The process according to claim 1 , characterized in that the strong base is selected from the group of alkali metal alcoholates, particularly alkali metal ethanolates or alkali metal methanolates, preferably sodium or potassium methanolate, or hydroxides of metals, particularly alkali metal hydroxides.

3. The process according to claim 1 or 2, characterized in that the isomerization is performed at a temperature of between 90°C and 260°C, preferably between 110°C and 200°C.

4. The process according to any of the preceding claims characterized in that the isomerization is performed in the presence of at least one solvent with a boiling point of above 150°C, preferably above 200°C, more preferably above 300°C, at ambient pressure.

5. The process according to claim 4, characterized in that that the solvent has a boiling point at ambient pressure which is above the temperature at which the isomerization is performed.

6. The process according to claim 4 or 5, characterized in that that the solvent is selected from the group consisting of polyethers, polyols, ethers of polyols, and polyether polyols, preferably polyols selected from the group consisting of polyethylene glycol (PEG), polypropylene glycol (PPG) and polytetrahydofuran (PTHF), more preferably polyethylene glycol (PEG).

7. The process according to any of the preceding claims characterized in that the strong base is present in an amount of between 0.1 % and 20%, preferably between 0.5 % and 10%, relative to the weight of the compound the formula (l-A) or of the formula (l-B) prior to the isomerization.

8. The process according to any of the preceding claims characterized in that the isomerization is performed at an absolute pressure of between 10 and 5’000 hPa, preferable between 100 and 2’000 hPa, most preferably between 100 and 1300 hPa.

9. A process of preparing the compound of the formula (l-A) comprising the steps ia) isomerizing a compound of the formula (l-B) by a process according to anyone of the claims 1 -8 to yield a mixture of the formula (l-A) and (I- B); iia) isolating the compound of the formula (l-A) from said mixture by reactive distillationwhereas R1represents either a methyl group or group or O-C1-10 alkyl group, particularly O-CH3.

10. A process of preparing the compound of the formula (l-B) comprising the stepsib) isomerizing a compound of the formula (l-A) by a process according to anyone of the claims 1 -8 to yield a mixture of the formula (l-A) and (I- B); iib) isolating the compound of the formula (l-B) from said mixture by inversewhereas R1represents either a methyl group or O-C1-10 alkyl group, particularly O-CH3.11 . The process according to claim 9 or 10, characterized in that the reactive distillation of step iia) or inverse reactive distillation iib) is performed at a temperature of between 90°C and 260°C, preferably between 110°C and 200°C.

12. The process according to claim 9 or 10 or 11 , characterized in that the reactive distillation of step iia) or inverse reactive distillation iib) is performed at reduced pressure, preferably at an absolute pressure of 1 - 1’000 hPa, preferably 20 - 50 hPa.

13. The process according to claim 9 or 10 or 11 or 12, characterized in that the process is a continuous process.

14. A composition comprising at least a compound of the formula (l-A) and / or of the formula (l-B)whereas R1represents either a methyl group or an O-C1-10 alkyl group, particularly O-CH3; and at least one strong base, preferably a strong base selected from the group of alkali metal alcoholates, particularly alkali metal ethanolates or alkali metal methanolates, preferably sodium or potassium methanolate, or hydroxides of metals, particularly alkali metal hydroxides.

15. The composition according to claim 14 characterized in that the composition further comprises at least one solvent with a boiling point of above 150°C, preferably above 200°C, more preferably above 300°C, at ambient pressure.

16. Perfume composition comprising a-damascone or [3-damascone in high isomeric purity, which is manufactured from the compound of the formula (I- A) or formula (l-B), respectively, obtained by a process according to claim 9- 13, characterized in that that R1represents a methyl group.

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