WO2004092099A1

WO2004092099A1 - Method for producing cyclic enols

Info

Publication number: WO2004092099A1
Application number: PCT/EP2004/003957
Authority: WO
Inventors: Marko Friedrich; Klaus Ebel; Norbert Götz; Ulrich Müller
Original assignee: Basf Aktiengesellschaft
Priority date: 2003-04-17
Filing date: 2004-04-14
Publication date: 2004-10-28
Also published as: DE10318043A1

Abstract

The invention relates to an improved method for carrying out cyclising ene reactions of unsaturated aldehydes to form cyclic enols, whereby the cyclisation is carried out in the presence of small quantities of solvent of up to 10 wt. %, in relation to the quantity of aldehyde used, and in the presence of at least one mixed oxide catalyst consisting of SiO2 and Al2O3.

Description

Process for the preparation of cyclic enols

Description:

The present invention describes an improved process for carrying out cyclizing en-real ions of unsaturated aldehydes to cyclic enols, in particular from the class of the terpenes.

The central key step of the established synthetic approaches to menthol, an important aroma chemical, is the acid or Lewis acid catalyzed

Cyclization of citronellal to isopulegol. The isopulegol is generally obtained in the form of mixtures of the four isomers isopulegol, neo-isopulegol, neoiso-isopulegol and iso-isopuiegol.

Menthol is obtained from the main isomer, isopulegol, for example, by further process steps. To increase the economy, there has always been a desire to maximize the isopulegol content of the mixture of isomers produced.

More recently, processes have been developed which allow isomeric mixtures of isopulegol to be refined economically to menthol. Before this

Processes which are suitable for making mixtures of isopulegol and its stereoisomers accessible in a particularly simple and economical manner, preferably using heterogeneous catalyst systems, appear increasingly interesting in the background.

For example, N. Ravasio et al., Hetereogenous Catalysi and Fine Chemicals IV, HU Blaser, A. Baiker, R. Prins (editors), Elsevier Science BV (1997), 625-632, describe by mixed SiO ₂ / TiO ₂ -, SiO ₂ / ZrO ₂ and SiO ₂ / AI ₂ O ₃ kogels induced intramolecular ene reactions. As a model reaction, the conversion of citronellal to isopulegol was investigated with various calcined catalyst systems at a reaction temperature of 90 ° C and with variation of the solvent.

W. G. Dauben et al., Tetrahedron Letters, vol. 33, no. 5, 603-606 describe the silica gel-catalyzed cyclization of unsaturated carbonyl compounds, including the cyclization of citronellal to isopulegol in dichloromethane under high pressure.

PJ Kropp describes the same reaction under atmospheric pressure in J. Org. Chem. 1995, 60, 4146-4152. Here too, the above-mentioned cyclization was achieved by silica gel catalysis in dichloromethane as solvent. A method for producing isopulegol from citronellal is already claimed in US Pat. No. 2,117,414, in which citronellal is heated in substance with commercially available silica gel.

In addition to carrying out a reaction in hexane, L. N. Misra et al. in Revista Italiana E.P.P.O.S. LXII, n.7, 365 -366, 1980 the conversion of citronellal to isopulegol by heating citronellal mixed with silica gel to 210 ° C. Depending on the reaction time, up to 73.9% of isopulegoliso are obtained, which, however, occur with significant impurities.

In Chemistry Letters, 1797-1798, 1089, K. Arata et al. the cyclization of citronellal to isopulegol in the presence of SiO ₂ / Al ₂ O ₃ catalysts with an Al ₂ O ₃ content of 13 or 15%. The catalysts are calcined at 500 ° C. in each case before the cyclization reaction carried out in toluene.

J. Ipaktschi et al. (Chemical reports, 123 (1990) 1591-1593) describe microwave-induced reactions of organic substrates in the zeolite cavity. Here u. a. Citronellal adsorbed on previously activated Y zeolite and either irradiated with a microwave oven or heated to 140 ° C. In both cases, mixtures of the four stereoisomeric isopulegols are obtained.

In addition, GB-A 2332 156 describes heterogeneous microporous catalysts based on sulfated metal oxides and their use for the production of isopulegol from citronellal.

The object of the present invention was to find a process for the cyclization of unsaturated aldehydes to cyclic or heterocyclic enols which is particularly suitable for cyclizing citronellal in such a way that isomer mixtures of isopulegol are obtained which, in addition to the four stereoisomers of isopulegol, have as few other components as possible or contain impurities and thus directly, ie without further purification or separation steps, e.g. Recycle for the synthesis of menthol.

According to the invention, a process for converting unsaturated aldehydes to cyclic or heterocyclic enols by cyclizing ene reaction was found, which is characterized in that the cyclization in the presence of small amounts of solvent, based on the amount of aldehyde used, up to 10% by weight and in the presence of at least one mixed oxide catalyst consisting of SiO ₂ and Al ₂ O ₃ . The reaction can be represented, for example, by the following reaction scheme:

The radicals R ¹ , R ² , R ³ and R ⁴ are, for example, each independently hydrogen C to Cβ-alkyl, C ₂ - to C ₆ -alkenyl, C ₆ - to C ₁₀ -aryl and C ₇ - to Gι ₂ - Aralkyl in question. The hydrocarbon radicals can still carry substituents which are inert under the reaction conditions, for example halogen such as fluorine, chlorine, bromine, iodine, OR ⁵ or NR ⁶ R ⁷ , where R ⁵ , R ⁶ and R ⁷ independently of one another are d- to C ₆ -alkyl, C ₆ to C ₁₀ aryl and C ₆ to C ₁₂ aralkyl.

The bridge between the reacting ene and the aldehyde function is generally chosen so that cyclic or heterocyclic systems with a total of 5 to 10, in particular 5 to 6, ring members are obtained. These cycles can also contain 1 or 2 heteroatoms such as oxygen or nitrogen, the nitrogen carrying either hydrogen or a hydrocarbon radical which is inert under the reaction conditions, and / or include 1 or 2 double bonds.

Optionally substituted, cyclic systems having 5, in particular 6, carbon atoms and optionally 1 to 2 double bonds in the ring are preferably prepared.

The process according to the invention is carried out in the presence of as little solvent as possible, i.e. below about 10% by weight, in particular less than about 2% by weight, of solvent (in each case based on the amount of aldehyde to be reacted), preferably carried out without solvent.

Solvents are to be understood here and in the following as all organic or inorganic solvents, regardless of their boiling point. Organic solvents are understood in particular to mean both aliphatic solvents, such as heptane, isooctane or dichloromethane, and aromatic solvents, such as toiuol or chlorobenzene, in each case halogen-free or halogenated. Inorganic solvents are also to be understood in particular as water. Suitable catalysts for carrying out the process according to the invention are mixed oxide catalysts which consist of SiO ₂ and Al ₂ O ₃ (so-called SiO ₂ / Al ₂ O ₃ kogels). The composition of these mixed oxide catalysts can in principle be varied over the entire possible range. However, preference is given to using mixed OCid catalysts which consist of more than 50% by weight of SiO ₂ . Mixed oxide catalysts which contain about 85 to about 99.5% by weight of SiO ₂ are particularly preferred in the production process according to the invention. The catalysts can be used in pure form or as a mixture of mixed oxide catalysts of various compositions.

Such ischemic oxide catalysts are usually easily and economically accessible and are usually also commercially available. They are widely used as support materials for so-called supported catalysts, on the surface of which a catalytically active substance is normally applied. In the case of the process according to the invention, it is possible to dispense with the application of such a catalytically active substance, since the mixed oxides according to the invention as such are already catalytically active.

The mixed oxide catalysts according to the invention can be produced in a variety of ways. Manufacturing methods for SiO ₂ / A! ₂ O ₃ -Kogele are described for example in detail in:. Ullmann's Encyclopedia of Industrial Chemistry, ^5th Ed, Vol A23, pages 583-660; Kirk-Othmer: Ecyclopedia of Chemical Technology, 3 " ¹ Ed .., Vol. 20, pp. 748-780 and also in RK Her: The Chemistry of Silica, Wiley Interscience, 1979, pp. 462 - 621.

Mixed oxide catalysts with a BET surface area of about 50 to about 800 m ² / g, particularly preferably from about 100 to about 600 m ² / g, and an average particle size of about 5 to about 500 μm are preferably used in the process according to the invention. particularly preferably from about 10 to about 250 μm.

Usually, based on the amount of unsaturated aldehyde to be reacted, about 0.1 to about 30% by weight of the mixed oxide catalyst or mixture of mixed oxide catalysts is used. Up to about 20% by weight, particularly preferably up to about 10% by weight, of the catalyst is preferably used. The use of about 0.5 to about 5% by weight of the selected catalyst system is very particularly preferred for carrying out the process according to the invention.

The cyclization reaction is advantageously carried out at temperatures from about 0 ° C. to about 150 ° C. It is then usually after about 5 minutes to about 3 days completed. It is particularly advantageous to work at elevated temperatures of about 50 ° C to about 130 ° C. Within this temperature range, the reaction is particularly preferably carried out at about 70 ° C. to about 100 ° C. The reaction time is then usually about 10 minutes to about 10 hours.

The reaction can be carried out both in air and under an inert gas atmosphere.

The process according to the invention can be used, for example, to use cyclic enols of the formula I

in which

R ¹ , R ² , R ³ , R ⁴ each independently represent hydrogen or a C to C ₆ alkyl or C to C ₆ alkenyl radical which is optionally substituted by halogen, OR ⁵ or NR ⁶ R ⁷ and

R ⁵ , R ⁶ , R ⁷ each independently represent hydrogen, d- to C ₆ -alkyl, C ₆ - to Cio-aryl or C ₆ - to C ₁₂ -aralkyl, where

R ⁶ and R ⁷ together can also be - (CH ₂ ) _m -, where m is an integer from 2 to 7, and

A for a branched or unbranched chain of 2 to 6 carbon atoms, which are linked to one another by single or double bonds and which may optionally be interrupted by one or more nitrogen and / or oxygen atoms and which may be interrupted by halogen, OR ⁵ and / or NR ⁶ R ⁷ can be substituted, by cyclization of unsaturated aldehydes of the formula II

where the substituents R ¹ to R ⁷ and A have the meaning given above.

The radicals R ² , R ³ and R ⁴ can be varied widely, but usually represent hydrogen or a C to C ₆ alkyl or C _r bis which is optionally substituted by halogen, OR ⁵ and / or NR ⁶ R ⁷ C ₆ alkenyl group. Halogen is to be understood as fluorine, chlorine, bromine or iodine.

Examples of d- to C ₆ -alkyl radicals are: methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1-methylbutyl, 2- Methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1, 1-dimethylpropyl, 1, 2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methyl pentyl, 1,1-dimethylbutyl, 1, 2-dimethylbutyl, 1, 3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1, 1, 2-trimethyl propyl, 1,2,2-trimethyl propyl, 1-ethyl-1-methyl propyl and 1-ethyl-2-methyl propyl. Among them, the radicals methyl, ethyl, propyl, 1-methylethyl, butyl, pentyl, hexyl and 1,1-dimethylethyl are preferred.

Examples of its d- to C ₆ -alkenyl radicals include: ethenyl, 1-propenyl, 2-propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl 1-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 1-pentenyl, and 2-pentenyl.

The radicals mentioned can carry one or more different halogen, OR ⁵ and / or NR ⁶ R ⁷ substituents. R ⁵ , R ⁶ and R ^{7 are} usually hydrogen, d- to C ₆ -alkyl, C ₆ - to C ₁₀ -aryl or C ₇ - to C ₁₂ -aryalkyl, where d- to C ₆ -alkyl are the above has the meaning given, C ₆ - to C ₁₀ -aryl is, for example, phenyl or naphthyl and C ₇ - to C ₁₂ -aryl, for example phenylmethyl, 1-phenylethyl, 2-phenylethyl, 1-phenylpropyl, 2-phenylpropyl or 3-phenylpropyl, is preferably phenylmethyl or 1-phenylethyl. The radicals R ⁶ and R ⁷ together can also mean - (CH ₂ ) _m -, where m is an integer from 2 to 7. M is preferably 4 or 5, so that R ⁶ and R ⁷ together with the enclosed heteroatom form a 5- or 6-membered ring.

A stands for a branched or unbranched chain of 2 to 6 carbon atoms, which are linked to one another by single or double bonds. The chain can optionally be interrupted by one or more nitrogen and / or oxygen atoms and optionally carry one or more different halogen, OR ⁸ and / or NR ⁹ R ¹⁰ substituents, R ⁸ or R ⁹ and R ^{10 being} the can have the same meanings as R ⁵ or R ⁶ and R ⁷ . A preferably represents an unsubstituted, branched chain of 5 carbon atoms, which are each linked to one another by single bonds.

Accordingly, the process according to the invention is also preferably suitable for the preparation of mixtures of the four stereoisomers of isopulegol, that is to say isopulegol, neo-isopulegol, neoiso-isopulegol and iso-isopulegol, in each case in racemic or in optically active form by catalytic cyclization of racemic or optically active Citronellal.

The process is particularly suitable for the preparation of isomer mixtures of isopulegol which are suitable, without further purification or separation, as starting materials or intermediates in chemical transformations, e.g. as part of a synthesis of the menthol to be further implemented. Another feature of the process according to the invention is that it is suitable for producing isomer mixtures of isopulegol, which predominantly consist of isopulegol itself. The process allows particularly economical reaction control under solvent-free conditions and moderate temperatures as well as the reuse of the inexpensive catalyst systems.

Citronellal with a purity of at least 90% is preferred as the starting material. Citronellal with a purity of at least 95%, very particularly preferably at least 98%, in each case in racemic or optically active form, is particularly preferably used.

The optically active form of citronellal here is understood to mean mixtures of the two enantiomeric forms of citronellal, in which these are not contained in equal parts. In addition to the racemic citronellal which is particularly preferred as the starting material, optically active citronellal, which consists of at least 90%, particularly preferably at least 95% and very particularly preferably at least 98%, of the R-enantiomer D-citronellal, implement accordingly. This can be of natural as well as synthetic origin.

Citronellal, which contains up to about 10% by weight of a solvent or a mixture of different solvents, is suitable for the implementation in the process according to the invention. However, preference is given to using citronellal which contains up to about 5% by weight, particularly preferably up to about 2% by weight, of solvent. Citronellal, which is essentially solvent-free, is very particularly preferably used.

In order to carry out the process according to the invention, the citronellal to be reacted and containing up to about 10% by weight of solvent is admixed with the catalyst used according to the invention without further addition of solvents or solvent mixtures.

In a particularly preferred embodiment of the process according to the invention, the citronellal to be reacted is mixed with about 5% by weight of a SiO ₂ / Al ₂ O ₃ mixed oxide catalyst, which consists of about 85 to 99.5% by weight of SiO ₂ and about 15 to 0.5 wt .-% of Al ₂ O ₃ , added and heated to about 85 to 95 ° C for about 4 h. The reaction mixture is then freed from the heterogeneous catalyst system, if appropriate after cooling to room temperature or partial cooling, by means of separation methods which are known per se to the person skilled in the art. Filtration is advantageously carried out for this purpose.

The catalysts separated off in this way can generally be reused. The reuse in the context of a further implementation according to the invention is particularly advantageous. The catalysts or catalyst mixtures intended for reuse can either be used immediately, without further treatment or purification, for a further reaction or, after separation, can first be washed or dried in a suitable manner. In addition, they can be calcined by methods familiar to a person skilled in the art before further use. Advantageously, continuous calcination, e.g. in the form of a fluidized bed calcination or in a rotary kiln.

The product mixture obtained after the removal of the catalyst is notable for high purity and usually contains about 80 to about 98% by weight of a mixture of the four isomers of isopulegol. The reaction conditions are preferably chosen so that a reaction product is obtained which consists of at least 90% by weight of a mixture of the isopulegol isomers. The above-described, particularly preferred embodiment of the process according to the invention gives products which are at least 95% by weight from a mixture of isopulegol isomers. These mixtures generally consist of at least 50%, preferably at least 60%, of the main isomer isopulegol itself.

A suitable choice of the reaction temperature can, above all, reduce the formation of undesired by-products in accordance with the requirements placed on the product. An increase in the reaction temperature tends to lead to an increase in the formation of high molecular weight by-products, which can sometimes interfere with further processing of the product mixture of stereoisomeric isopulegols and thus necessitate further purification of the crude product.

Through the procedure described as a particularly preferred embodiment of the process according to the invention, mixtures of isomers of isopulegol which are essentially free of high molecular weight by-products and thus, when using the desired purity criteria of the product, corresponding citronellal are obtained as immediate reaction product for immediate further use , e.g. in a large-scale synthesis of menthol.

The advantages of the method according to the invention are evident in implementations of any scale, but above all come to full use in industrial applications, for which the method is particularly suitable.

The following examples serve to illustrate the method according to the invention, but without restricting it in any way:

Examples

example 1

Production of a mixed oxide catalyst used according to the invention

A mixture consisting of 370.6 kg of a hydrogel containing 32.8 kg of SiO ₂ and 4.6 kg of the pseudoboehmite Pural (corresponding to 3.24 kg of Al ₂ O ₃ ) and 4 kg of water is sprayed in a spray tower and the spray tower is discharged at 120 ° C dried. The mixed oxide catalyst obtainable in this way consists of 91% by weight of SiO ₂ and 9% by weight of Al ₂ O ₃ . It has a density of 491 g / l, a BET surface area of 428 m ² / g and an average particle size of 0.048 mm.

Example 2

Preparation of a mixture of isomers of isopulegol by catalytic cyclization of citronellal under solvent-free conditions

A mixture of 1000 g of citronellal and 50 g of the mixed oxide catalyst prepared as described in Example 1 is stirred at 90 ° C. for 4 h. After cooling, the catalyst is filtered off and a product mixture is obtained in quantitative yield, which consists of 96% of a mixture of the four diastereomers of isopulegol. The diastereomer mixture thus obtained consists of 64.6% of the main isomer isopulegol.

Claims

claims

1. A process for converting unsaturated aldehydes to cyclic or heterocyclic enols by cyclizing ene reaction, characterized in that the cyclization in the presence of small amounts of solvent, based on the amount of aldehyde used, up to 10% by weight and in the presence of at least one from Si0 ₂ and Al ₂ 0 ₃ existing mixed oxide catalyst.

2. The method according to claim 1 for the preparation of 5- to 6-membered cyclic enols.

3. Process according to claims 1 and 2, characterized in that Citronellal is implemented.

4. The method according to claims 1 to 3, characterized in that the mixed oxide catalyst or the mixed oxide catalysts used contains or contain 85 to 99.5% by weight of SiO ₂ .

5. Process according to claims 1 to 4, characterized in that one carries out the cyclization in the presence of, based on the amount of aldehyde used, up to 2% by weight of a solvent.

6. Process according to claims 1 to 5, characterized in that the cyclization is carried out under essentially solvent-free conditions.

7. Process according to claims 1 to 6, characterized in that, based on the amount of aldehyde used, 0.1 to 20 wt .-% of the catalyst or catalyst mixture is used.

8. Process according to claims 1 to 7, characterized in that, based on the amount of aldehyde used, 0.5 to 10 wt .-% of the catalyst or catalyst mixture is used.

9. The method according to claims 1 to 8, characterized in that one carries out the cyclization at temperatures from 0 to 150 ° C.

10. The method according to claims 1 to 9, characterized in that one carries out the cyclization at temperatures of 70 to 100 ° C.

11. The method according to claims 1 to 10 for the preparation of a mixture of cyclic enols containing isopulegol, neo-isopulegol, neoiso-isopulegol and iso-isopulegol.

12. The method according to claims 1 to 11, characterized in that the reaction product contains at least 80 wt .-% of the isomer mixture of isopulegol, neo-isopulegol, neoiso-isopulegol and iso-isopulegol.

13. The method according to claims 1 to 12, characterized in that the reaction product contains at least 90 wt .-% of the isomer mixture of isopulegol, neo-isopulegol, neoiso-isopulegol and iso-isopulegol.

14. The method according to claims 1 to 13, characterized in that the isomer mixture obtained as the reaction product consists of at least 50% of isopulegol.