WO2009135229A1

WO2009135229A1 - A method of producing cyclic diols

Info

Publication number: WO2009135229A1
Application number: PCT/ZA2009/000030
Authority: WO
Inventors: Bernard Zeelie; Nico Rust; Shaun Gouws; Gary Morris Dugmore; Batsho Mpuhlu
Original assignee: Afrepell Technologies (Proprietary) Limited
Priority date: 2008-04-22
Filing date: 2009-04-23
Publication date: 2009-11-05

Abstract

The invention described a method of producing a 5-alkyl-2-α-hydroxyalkyl-cyclohexanol of the formula (I), the method including the step of exposing a 6,7-unsaturated aldehyde or ketone starting material of the formula (II) in a two phase reaction system, one phase being an aqueous phase, to an acid catalyst at a temperature of above 100 degree Celcius [deg C] and 250 deg C, the amount of acid being between about 0.05 and 4.0 % (m/m) to produce the 5-alkyl-2-α-hydroxyalkyl-cyclohexanol (I).

Description

A METHOD OF PRODUCING CYCLIC DIOLS

INTRODUCTION

This invention relates to the synthesis of diols. In particular, this invention relates to a method of producing a 5-alkyl-2-α-hydroxyalkyl-cyclohexanol by exposing a 6, 7-unsaturated aldehyde or ketone starting material to an acid catalyst.

BACKGROUND TO THE INVENTION

The compound para-menthane-3,8-diol, IUPAC name 2-(1-hydroxy- isopropyl)-5-methylcyclohexan-1-ol), derivatives thereof and structurally related compounds thereof are useful in the manufacture of certain insect repellent products. In order to commercialize these products a method of producing these compounds on a large scale is required. Several prior art methods are known for the production of para-menthane-3,8-diol (PMD). These methods include the extraction of PMD from natural oils and the synthesis of PMD from a variety of starting materials such as m-cresol/thymol, pulegone, limonene or citronellal. Taking into account factors such as product purity requirements, costs, the availability of raw material, the complexity of the process and the like, the acid catalysed cyclisation of citronellal offers the best scope for commercial application. The acid catalyzed synthesis of PMD from citronellal essentially involves the ring closure of citronellal to give PMD with a number of different pulegols and PMD acetals being produced as by-products as shown in Scheme 1 :

Scheme 1 : General schematic of PMD synthesis from citronellal and dilute sulphuric acid.

However this cyclisation process and variations thereof suffer from several drawbacks. These include long reaction times and the production of significant amounts of the PMD acetal by-product. This, in turn, necessitated an additional recrystallisation as product purification step. In addition, the operation of such production methods in batch processes results in processes with fixed annual production capacities. A need exists for a process for producing para-menthane-3, 8-diol and other structurally related molecules more efficiently than prior art processes.

SUMMARY OF THE INVENTION

According to a first aspect of the present invention there is provided a method of producing a 5-alkyl-2-α-hydroxyalkyl-cyclohexanol of the formula (I)₁

(I) where R₁ to R₄ are independently selected from the group comprising hydrogen, C₁-C₅ alkyl groups including methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert- butyl and straight or branched pentyl groups, the method including the step of exposing a starting material being a 6, 7-unsaturated aldehyde or ketone of the formula (II),

(H) or the dimer formed from the reaction of the aldehyde or ketone with the reaction product, where R₁ to R₄ are as defined in formula (I), in a two phase reaction system, one phase being an aqueous phase containing an acid catalyst at a temperature of between about 100 degrees Celcius (deg C) and 250 deg C, the amount of acid being between about 0.05 and 4.0 % (m/m) (mole/mole).

According to a second aspect of the present invention, there is provided a 5-alkyl-2-α-hydroxyalkyl-cyclohexanol of the formula (I)

(I) where R₁ to R₄ are independently selected from the group comprising hydrogen, C₁-C₅ alkyl groups including methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert- butyl and straight or branched pentyl groups, whenever produced by a method as hereinbefore described.

DETAILED DESCRIPTION OF THE INVENTION

The dimer formed from the reaction of the aldehyde or ketone with the reaction product may be 2-(2,6-dirnethylhept-5-enyl)-4,4,7-trimethyl-2H- 3,4,5,6,7,8,4a,8a-octahydro-3-oxachromene (referred to as the product-acetal) formed from citronellal and PMD.

The 6, 7-unsaturated aldehyde or ketone may be a C₆-C₁₂ unsaturated aldehyde or ketone with an unsaturated C-C bond in the 6, 7 position of the unsaturated alicyclic aldehyde or ketone. The substituents R₁ to R₄ of the aldehyde or ketone may independently be selected from hydrogen, C₁-C₅ alkyl groups such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, straight or branched pentyl or the like. In particular, the 6, 7-unsaturated aldehyde may be citronellal.

The two phase system may comprise an aqueous phase and an organic phase. The organic phase may comprise the starting material (substrate), or a mixture of the starting material and the product-acetal. Accordingly, the method may comprise producing the diol by reacting the starting material, or its mixture with product-acetal, in a two-phase reaction system where one phase comprises the starting material and the other phase comprises the acid catalyst in water. Alternatively the organic phase may comprise the starting material and a solvent such as an alkane solvent or an aromatic solvent. The starting material may thus be dissolved in a non-reactive solvent to aid dispersion thereof in the aqueous catalyst phase. Examples of alkane solvents that may be used include hexane, iso-alkanes such as iso-pentane, and examples of aromatic solvents include alkyl-aromatics such as toluene and xylene and/or mixture thereof. The type and amount of solvent used is not restricted but it is preferred that no additional solvent be used in a preferred embodiment of the invention.

The type of acid catalyst which can be used may vary and suitable acid catalysts may include inorganic acids such as sulphuric acid, hydrochloric acid, and phosphoric acid, as well as organic acids such as thfluoroacetic acid, methanesulfonic acid, toluene sulfonic acid and the like. The acid catalyst may be in the form of a solid acid catalyst, typical examples being strong acid ion exchange resins such as Nafion H, or Amberlyst 15 (registered trade marks) and/or mixtures thereof. Preferred acid catalysts are sulphuric acid and hydrochloric acid.

The concentration of the acid catalyst used in the method of the invention is important as the catalyst concentration affects not only the speed of the reaction, but more importantly the reaction selectivity. Increasing the acid concentration will increase the rate of the cyclisation. However, increasing the acid concentration will also increase the rate of product-acetal formation. Thus, the preferred acid concentration should be selected so to give an acceptable reaction rate without increasing the amount of product-acetals above acceptable levels.

The amount of acid catalyst is dependent upon the reaction temperature and it is preferable that the acid concentration be decreased as the reaction temperature is increased. Thus, the preferred acid concentration, irrespective of the nature of the acid catalyst, is in the range 0.05 to 4.0% (m/m) in the aqueous phase of the reaction mixture, more preferably 0.1 to 1.5% (m/m) in the aqueous phase of the reaction mixture and most preferably in the range 0.15 to 1.0% (m/m) in the aqueous phase of the reaction mixture with lower concentrations being preferred at higher temperature settings.

The Applicant has found that the reaction temperature of the cyclisation reaction is critical as it plays a significant role in steering the reaction pathway through the desired mechanistic pathway. Thus, the preferred reaction temperature is in the range of between about 100 to 250 deg C, and more preferably in the range of about 120 to 170 deg C. The preferred reaction temperature may be more than 101 deg C, more preferably more than 105 deg C, more preferably more than 1 10 deg C, more preferably more than 115 deg C, most preferably more than 120 deg C.

The preferred reaction temperature is less than than 250 deg C, more preferably less than 240 deg C, more preferably less than 230 deg C, more preferably less than 220 deg C, more preferably less than 210 deg C, more preferably less than 200 deg C, more preferably less than 190 deg C, more preferably less than 180 deg C, most preferably less than 170 deg C.

The reaction pressure will be selected so as to keep all of the reaction components in the liquid phase and is accordingly not restricted. The preferred reaction pressure range may be between about 1 atm and 300 atm, and is more preferably between about 1 atm and 250 atm. The ratio of the volumes of the aqueous to organic phases is not limited provided that the volume of the aqueous phase is sufficient to provide for adequate dispersion of the organic phase so as to provide a sufficiently large interfacial area for efficient mass transfer between the two phases. Thus, the preferred volume ratio of the aqueous phase to the organic phase may be in the range of about 10:1 and is preferably in the range of about 6:1 irrespective of whether a solvent is used to dissolve the starting material.

The method may include allowing the cyclisation reaction to proceed until about 30 - 95 (weight by weight or by weight) w/w% and, more preferably, about 40 - 80 w/w% of the original starting material has reacted.

Any apparatus capable of providing conditions for efficient, turbulent mixing whilst maintaining the desired reaction temperature and pressure may be used in the method of the invention and the process of the invention may be carried out in a batch process, a semi-continuous process or a continuous process. Thus, batch reactors with efficient stirring (well-mixed reactors), either alone or in combination with other batch reactors in a cascade, or tubular reactors capable of providing turbulent mixing across the entire reaction path length may be used. Tubular reactors capable of turbulent mixing are especially preferred for the process of the invention. No limit is placed on the size of either the batch or tubular reactor, provided such reactors are capable of providing the desired mixing of the two reacting phases, as well as maintaining the desired reaction temperature and pressure.

Turbulent mixing in tubular flow reactors can be achieved in many different ways, for example by packing the tubular reactor with an inert solid packing such as silicon carbide spheres, stainless steel mesh or the like or by providing a fixed internal structure specifically designed to achieve high mixing efficiencies inside the tube, for example as is found in many commercial static mixing tubes.

Turbulent mixing is also dependent upon the rate of flow of reagents through a fixed tube. When the internal diameter of the tubular reactor is small enough, turbulent mixing may even be achieved in the absence of any internal packing or structuring, provided that the rate of reagent flow is kept sufficiently high. When the tubular reactor contains internal packaging or structuring, the flow rate required to provide the desired level of mixing will be determined by the nature and shape of the internal packing or structuring.

The length of any form, packed or unpacked, with or without fixed internal structuring, to give a certain reactor residence time, will also depend upon the size of the tubular reactor, the nature of any internal packing or structuring, the flow rate used, as well as the applied reaction pressure. Thus, by varying these parameters, it is possible to determine the optimum length of a specific tubular reactor to achieve a desired substrate conversion.

According to the method of the invention, the desired substrate conversion should be such that a low concentration of acetal by-product (product- acetal) is formed during the cyclisation. In particular, the amount of product- acetal formed during the cyclisation should be less than about 3w/w% based on the amount of starting material and, more preferably, less than about 2w/w% based on the amount of starting material. As mentioned above, these specifications are achieved by maintaining the conversion of the citronellal substrate in the range of about 30 - 95w/w% and, more preferably, in the range of about 40 - 80w/w%.

To reduce the reactor residence time further and keep the length of the reactor as short as possible, it is preferred that at least one, and in a preferred embodiment, both the aqueous catalyst phase and the organic phases be preheated to the desired reaction temperature before mixing together in the continuous reactor.

Batch reactors may also be used provided that efficient mixing of the organic and aqueous phases can be achieved. The size of the batch reactor is not limited, but smaller reactors in which a higher degree of mixing, and in which better temperature control can be achieved are preferred. Any suitable mixing device may be used in a batch reactor provided that the degree of mixing throughout the batch reactor is constant and capable of providing a near suspension of the organic phase in the aqueous phase. Typical mixing devices capable of meeting these objectives include, by way of example, high shear mixers, propeller-type mixers in combination with a system of fixed baffles, high speed pumps recycling through a system of static mixing tubes and the like.

In a batch reactor, it is possible to add the substrate either in one single batch or continuously over a period of time.

As in the case of a continuous reactor, the residence time in a batch reactor will be selected to keep the substrate conversion at levels where the formation of product-acetal are kept below about 3w/w% based on the amount of starting material initially added and, more preferably, below about 2w/w% of the amount of starting material initially added. In the case of citronellal this can be achieved by restricting the substrate conversion to a range of about 30 - 90w/w% of the starting material initially added and, more preferably to a range of about 30 - 80w/w%.

The actual reactor residence time will depend on the rate at which the starting material is added to the reactor, the efficiency of the mixing in the reactor and the reaction temperature. The inventors have found that the length of reaction time, more specifically the length of time that the product is kept in contact with certain reaction intermediates, the higher the amount of product- acetals will be in the reactor exit stream. It is therefore desirable to reduce the reactor residence time as far as practically feasible as this reduces the amount of product-acetals formed. For small batch reactors with a high degree of mixing and with efficient heat exchange capabilities, and where the starting material is added in a single batch to the reactor, the preferred reactor residence time is in the range of about 5 - 60 minutes and, more preferably, in the range of about 5 - 30 minutes. For continuous reactor systems, even shorter reactor residence times may be practically feasible, especially when performing such reactions under conditions of high temperature. For continuous reactors, the preferred reactor residence time is in the range of about 0.1 - 5.0 minutes, more preferably in the range about 0.2 - 3.0 minutes. (For avoidance of doubt, 0.1 minutes is 6 seconds.)

The method may thus include conducting the cyclisation in a continuous process in a reactor, the preferred reactor residence time in the reactor being in the range of about 0.1 - 5.0 minutes and, more preferably, in the range of about 0.2 - 3.0 minutes. In such cases, it is preferred that both the starting material phase and the water/catalyst phase be pre-heated to the desired reaction temperature before mixing together.

For traditional batch processing it is not absolutely necessary to add the starting material to the aqueous phase containing the catalyst. It may, for example, be practically more efficient to first mix the water and starting material phases at the desired reaction temperature in the reactor before adding a preheated solution of the catalyst in water. This modification does not change any of the preferred embodiments as described above.

The reactor exit stream, from either a batch or a continuous reactor, consists of an aqueous phase and an organic phase which can be separated by any of the known phase separation methods known in the art.

The hot aqueous phase may either be recycled, optionally after adjusting with additional catalyst, or used as a heating source for evaporation of un-reacted starting material before recycling to the reactor system.

In the case of citronellal, the desired reaction product, which consists of various PMD isomers, are contained within the organic phase separated from the reactor exit stream and may be separated from un-reacted citronellal, residual water, the product-acetal by-products and (iso)pulegol intermediate product by various methods including evaporation under vacuum. The manner in which the vacuum evaporation is performed is not limited and maybe carried out in a batch, semi-batch or continuous manner depending on the nature of the apparatus being used. A preferred method of product separation and purification is by selective crystallisation of the desired reaction product by the addition of small amounts of selected solvents including alkanes, iso-alkanes, cycloalkanes, or inert aromatic solvents such as toluene, xylene and the like, to the crude reaction product from a prior vacuum evaporation or reaction step, cooling for about 6 - 36 hours at temperatures between about 0 deg C and about 20 deg C, followed by vacuum filtration of solid product, and finally washing with cold inert solvent.

In order for the selective crystallization to function as desired, it is preferred that the product concentration in the crude product be at least 60% by mass, more preferably, more than 70% by mass. The crude product may either be the raw reactor product following phase separation of the aqueous and organic phases, or the heavy fraction from a prior vacuum evaporation step.

The nature of the solvent used for the selective crystallization step must be such that it preferentially dissolves the product-acetal by-product. Preferred solvents include alkanes (such as pentane, hexane, heptane, and the like), C₅ - C₈ iso-alkanes, cycloalkanes, such as cyclohexane, and inert aromatic solvents such as toluene and xylene. The preferred solvents for the selective crystallization process are alkanes (pentane, hexane, etc.), and cycloalkanes (cyclohexane).

The amount of solvent used during the selective crystallization process determines the quality, the yield and rate of crystallization of the reaction product. The amount of added solvent is preferably in the range of about 5 - 40% by mass of the crude reaction product, more preferably in the range of about 10 - 30% by mass of the crude reaction product.

The temperature at which the crystallization is carried out will determine the rate of crystallization and the completeness of crystallization. As a result, lower temperatures are preferred for the crystallization process to reduce crystallization times.

Washing of the crystallised product improves product quality by removing residual product-acetals. To reduce loss of product during these washings, it is preferred that the solvent used for washing be between about -20 deg C and about 20 deg C, more preferably between about -10 deg C and about 15 deg C. The washing procedure would typically entail mixing of the solid with the cold wash solvent, followed by vacuum filtration. It is preferred that the wash step be repeated as many times as is required to reduce the product-acetal concentration in the final product to below desired levels. In most instances, two successive wash steps are sufficient, but further washings can give a product of exceptional purity.

Persons skilled in the art will know that the mother liquor from the selective crystallization step, as well as the wash solvent, contain residual product. This residual product may be recovered by partial evaporation of the solvent, followed by crystallization and washing as contemplated above. Alternatively, the solvent may be removed in its entirety and the mixture of product and by-product (product-acetal) simply recycled to the reaction zone.

SPECIFIC DESCRIPTION

The invention will now be described with reference to the following figures in which:

Figure 1 shows the yield of PMD as a function of temperature and the amount of acid catalyst; and

Figure 2 shows the yield of PMD as a function of temperatures and the amount of acid catalyst, shown in 3 axes.

The Applicant has found that PMD is formed by the acid catalysed cyclisation of citronellal by either one or both of two possible mechanistic pathways. The Applicant has further found that the preferred pathway is highly dependent upon the reaction temperature, whilst other factors such as the amount of acid catalyst play a far lesser role in determining the actual pathway followed, provided the catalyst is capable of providing protons to catalyse the reaction. The presence of two reaction pathways can clearly be seen from a contour plot of the experimental response as shown in Figure 1.

The graph shown in Figure 1 clearly shows the increase in the PMD values to the right of the Figure (high temperature). The contour lines show that the PMD value is maintained irrespective of acid concentration - thus at any value of temperature (above about a coded value of 0.5 on the X-axis), the same high PMD value can be achieved by decreasing the acid concentration as the temperature is increased. The yield of PMD can therefore be increased by either increasing the acid loading, or raising the reaction temperature above a certain temperature. This observation led the Applicant to determine the effect of reaction variables, and in particular the reaction temperature, on the reaction mechanism and on the outcome of the synthetic reaction.

The graph shown in Figure 2 clearly shows a "trough" running through the response surface (front to back). The presence of such a trough is indicative of the existence of two mechanistic pathways since the change in reaction variables affects the reaction differently on either side of the trough. The yield of PMD increases both to the left and to the right of this trough, but it can clearly be seen that the effect of increasing temperature increases the yield of PMD much more significantly on the right hand side.

EXAMPLES

The invention is now illustrated by means of the following examples which are intended for illustrative purposes only, and which are not to be construed as to limit the scope of the invention and/or Figure 1 which shows the yield of PMD as a function of temperature and amount of acid catalyst in accordance with the method of the invention. Comparative Example 1 (Cyclisation of citronellal)

A bench-scale PMD synthesis reaction was carried out using a 500 ml jacketed glass reactor, a heated feed vessel, and an over-head stirrer fitted with a four-blade stainless steel impeller, thermometer and two integral baffles. The reactor temperature was set to a temperature of 60 deg C by circulating heating fluid, kept at the desired constant temperature (± 0.5 deg C) in a constant temperature bath. Dilute sulphuric acid (14Og of a 0.53% (m/m) solution 0.00757mol) was added to the reactor and allowed to equilibrate to the desired reaction temperature. Citronellal (30.08g; 0.193mol), pre-heated to the desired reaction temperature, was added to the reactor drop-wise over a period of 60 minutes, while the reactor was agitated at a stirring rate of 2000 rpm. The reaction was allowed to proceed for a further 6 hours following completion of the citronellal addition step.

Once the reaction had stopped, the reactor contents were drained into a separating funnel and allowed to settle for 1 minute after which the aqueous phase was drained off. The organic phase was washed with 5Og of a 2.5% (w/v) solution of NaHCO₃ to remove any residual sulphuric acid catalyst. The mixture was allowed to settle for approximately 2 minutes after which the bottom aqueous phase was drained off.

Residual water was removed from the organic phase on a rotary evaporator. The crude product was then distilled under vacuum (1 15 deg C and 8 mBar) to recover citronellal and pulegol. The desired product PMD was recovered as a thick viscous liquid from the bottom of the still and analyzed by means of gas chromatography. In different embodiments, the yield of PMD varied between 80 - 90 % and typically contained up to about 10 % of pulegol, up to about 7% PMD-acetal and about 2- 5% of un-reacted citronellal. Comparative Examples 2 - 16

The experiment described in Example 1 was repeated several times with slight modifications in the reaction temperature, amount of catalyst used, and the ratio of the aqueous catalyst phase relative to the organic citronellal phase as indicated in Table 1. In all of the examples of Table 1 , the citronellal starting material was added in a single batch to the pre-heated aqueous catalyst mixture, and the reaction was allowed to proceed for only 30 minutes before the reaction was stopped and worked up as described for Example 1. The results obtained for these experiments, namely the amount of citronellal (mmol), amount of PMD (mmol), and amount of PMD-acetal (mmol) are summarised in Table 1.

Table 1

Based on citronellal consumed Examples 17 - 23

The reaction as described in Example 1 was repeated using a continuous flow apparatus which consisted of a % inch stainless steel tube, 5.6m in length, which was packed with 30 grit silicon carbide pieces. The packed tube was connected to a tube in tube axial heat exchanger, 20 cm in length, which was kept at 0 deg C to cool down the reaction mixture before exiting the plant. A control valve was placed after the axial heat exchanger to restrict the flow of the system, and to maintain a pressure sufficient to keep all the reagents in the liquid phase when operating at reaction temperatures above 100 deg C.

The packed tube was connected to two semi-preparative high performance liquid chromatography pumps via either a simple T-piece, or via a caterpillar micro-mixing device (Institute of Microchemische Technik). This allowed the continuous feeding of reagents to the packed tube in any desired ratio at combined flow rates up to 500ml/min. The entire plant assembly was immersed in a heated oil bath to heat and maintain the system at the desired reaction temperature (±0.2 deg C).

During run 17 (Table 2) the bath temperature was set to 85 deg C and allowed to equilibrate. Once the equilibrium temperature was reached the pumps were switched on allowing for a pre-dose of dilute sulphuric acid phase (0.5% m/m) at 65ml/min for 120 seconds. Thereafter the flow rate of the aqueous phase was reduced to 52ml/min, whilst introducing pure citronellal at 13ml/min therefore allowing both streams to combine and mix as they flowed through the continuous system. The control valve was adjusted until the pressure of the system measured 20 bars.

After 240 seconds a sample was taken from the end of the tube in tube heat exchanger by running the reaction mixture into a 100ml of (2.5% w/v) solution of sodium bicarbonate (NaHCO₃) for 100 seconds to neutralise and stop the reaction. Following the neutralisation step, 2 ml of the neutralised organic phase was added to 18 ml of n-heptane, dried with 1 gram of anhydrous sodium sulphate, and analyzed by gas chromatography.

All subsequent examples were performed in a similar manner by increasing the reaction temperature by 10 deg C intervals up to a temperature of 145⁰C.

Examples 24 - 49

The example as described in Examples 17 - 23 were repeated but using different lengths of packed tubing and varying the reaction conditions as illustrated in Table 3, below.

Table 3

Example 50 - 51

Examples 50 and 51 illustrate the separation and purification of PMD from crude reaction mixtures.

For example 50, 1 part by mass of n-hexane was added to 4 parts of the crude product from a batch synthesis reactor after phase separation and the mixture thoroughly mixed. The mixture was cooled to -18 ⁰C for 24 hours which results in the formation of an opaque-white solid product which was filtered under vacuum and washed once with 50 ml ice cold n-hexane before drying in air at 8O⁰C. The results obtained for this recrystallisation study are summarised in Table 4.

For example 51 , a sample of crude product obtained following vacuum evaporation of unreacted citronellal and pulegol intermediate was treated in the same manner as described above. The resultant filter cake was washed twice with cold solvent. The results obtained are summarised in Table 4.

Table 4: Results for the crystallisation of the crude PMD

Fraction Component Amount (MoI %) Amount (MoI %)

Citronellal 13.17 13.32

Pulegol 0.10 0.11

Crude Product

PMD 84.57 85.49

Acetal 2.15 1.09

Citronellal 0.86 0.87

Recrystallised pulegol 0.00 0.00

Product PMD 98.1 1 98.62

Acetal 1.03 0.52

Table 5: Results for the selective crystallisation of PMD

The present invention provides an improved process for the production of PMD from citronellal by exploiting specific experimental conditions so as to drive the reaction through a desired mechanistic pathway that ensures high yields of the desired product with minimal or negligible levels of impurities in very short reaction times. It is an advantage of the present invention that production can occur in a continuous fashion as opposed to the traditional batch equipment. It is a further advantage of the present invention that product recovery and purification can be achieved through a simple continuous evaporation step. The process of the present invention can be achieved by performing the synthesis reaction in a device that ensures highly efficient mixing of the two-phase aqueous/organic system at reaction temperatures and pressures that favour the desired mechanistic pathway. Whilst studying the batch synthesis of PMD from citronellal in the presence of dilute acids by means of advanced statistical methods, the present inventors have been able to manipulate the reaction conditions in a manner that directs the course of the reaction through a specific mechanistic pathway that was not known previously. As a result, a production process has been developed which not only produces PMD more rapidly (a reduction of the reaction time from several hours to a few seconds), but which also produces significantly lower levels of by-products. In addition, this new process lends itself to flexible operation, because it can be operated in a batch, semi-batch, or continuous manner. Further advantages of this new and improved process for the production of PMD are that the process is less labour intensive and more energy efficient than equivalent processes described in the art. The Applicant has found that the synthesis of PMD from citronellal can be carried out in a manner that is intrinsically different from procedures described in the art, and which offers numerous advantageous over such procedures.

Claims

1. A method of producing a δ-alkyl^-α-hydroxyalkyl-cyclohexanol of the formula (I),

(I) where R₁ to R₄ are independently selected from the group comprising hydrogen, C₁-C₅ alkyl groups including methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl and straight or branched pentyl groups, the method including the step of exposing a starting material being a 6, 7- unsaturated aldehyde or ketone of the formula (II),

(H) or the dimer formed from the reaction of the aldehyde or ketone with the reaction product, where R₁ to R₄ are as defined in formula (I), in a two phase reaction system, one phase being an aqueous phase containing an acid catalyst at a temperature of between about 100 degrees Celcius (deg C) and 250 deg C, the amount of acid being between about 0.05 and 4.0 % (m/m).

2. A method according to claim 1 wherein the 6, 7-unsaturated aldehyde or ketone is a C₆-Ci₂ unsaturated alicyclic aldehyde or ketone with an unsaturated C-C bond in the 6, 7 position of the unsaturated alicyclic aldehyde or ketone.

3. A method according to claim 1 or 2 wherein the 6, 7-unsaturated aldehyde is citronellal.

4. A method according to any one of claims 1 to 3 wherein the two phase reaction system includes an organic phase which comprises the starting material dissolved in a non-reactive solvent and an aqueous catalyst phase.

5. A method according to claim 4 where the non-reactive solvent is selected from alkane solvents including hexane, iso-alkanes including iso-pentane and aromatic solvents including alkyl-aromatics including toluene and xylene and/or mixtures thereof.

6. A method according to any one of the claims 1 to 5 wherein the acid catalyst is selected from inorganic acids including sulphuric acid, hydrochloric acid and phosphoric acid, organic acids including trifluoroacetic acid, methanesulfonic acid, toluene sulfonic acid and solid acid catalysts including strong acid ion exchange resins including Nafion H, or Amberlyst 15 (registered trade marks) and/or mixtures thereof.

7. A method according to claim 1 where the reaction pressure is selected so that the reaction components are in the liquid phase.

8. A method according to claim 4 where the volume ratio of the aqueous phase to the organic phase is in the range of about 10:1.

9. A method according to any one of claims 1 to 8 which is a batch process, a semi-continuous process or a continuous process.

10. A method according to any one of claims 1 to 9 wherein the reaction temperature is in the range of about 120 deg C to 170 deg C.

11. A method according to any one of claims 1 to 10 wherein the reaction is continued until about 30 to 95w/w% (by weight) of the starting material has reacted.

12. A method according to any one of claims 1 to 11 wherein an amount of product-acetal formed is less than about 3w/w% (by weight) of the starting material.

13. A method according to claim 12 wherein the product-acetal is included with or as a starting material.

14. A method according to any one of claims 1 to 15 carried out in a reactor capable of turbulent mixing.

15. A method according to claim 14 wherein the reaction materials have a reactor residence time of about 0.1 to 60 minutes.

16. 5-alkyl-2-α-hydroxyalkyl-cyclohexanol of the formula (I)

where Ri to R₄ are independently selected from the group comprising hydrogen,

C₁-C₅ alkyl groups including methyl, ethyl, propyl, isopropyl,

butyl, isobutyl, tert- butyl and straight or (j) branched pentyl groups, whenever produced by a method according to claim 1.