WO2013026727A1

WO2013026727A1 - A method for separating compounds of similar structure.

Info

Publication number: WO2013026727A1
Application number: PCT/EP2012/065774
Authority: WO
Inventors: Raymond MARRIOTT; Matthew GOULD
Original assignee: Bangor University
Priority date: 2011-08-24
Filing date: 2012-08-11
Publication date: 2013-02-28
Also published as: GB201114622D0; GB2493943A

Abstract

This invention relates to the separation of constituents of a mixture comprising compounds having similar structures using carbon dioxide in both liquid and supercritical states. The process claimed is especially concerned with a two-step supercritical fluid chromatography method applied to the separation of cardol and cardanol from technical cashew nut shell liquids.

Description

A METHOD FOR SEPARATING COMPOUNDS OF SIMILAR STRUCTURE.

Field of the invention.

This invention relates to the fractionation of compounds of similar structure from mixtures using supercritical fluids, for example the separation of technical Cashew Nut Shell Liquid (CNSL) comprising the constituents cardol and cardanol.

Brief description of the prior art.

Cashew nut shell liquid (CNSL) is a by-product of the cashew nut industry. Two different types are available commercially: natural or solvent extracted CNSL, and technical CNSL.

Natural CNSL is extracted from the shells using a non polar solvent such as hexane or a non polar solvent alternative such as supercritical carbon dioxide as described in the literature, (e.g. S.V.Shobha, B.Ravindranath, J.Agric.Food.Chem. 1991 , 39, 2214-2217). Natural CNSL consists mostly of anacardic acid (an alkenyl salicylic acid), cardol and cardanol. The composition of natural CNSL varies from batch to batch, and also by place of origin. A typical composition comprises 65 wt% of anacardic acid, 20 wt% of cardol, 10 wt% of cardanol, the remainder being polymeric material.

Technical CNSL is extracted by roasting the shells or by any other heating methods. Such heating process transforms (decarboxylates) anacardic acid into cardanol. The composition of technical CNSL also varies by batch, country of origin and heating method. A typical composition comprises 65 wt% of cardanol, and 15 wt% of cardol, the remainder being polymeric material.

Separation of the constituents in technical CNSL can be achieved by column chromatography at laboratory scale. That method is however not applicable for industrial scale applications. Distillation techniques have been developed in order to separate the constituents. They do not give pure products however. Indeed cardanol that is available

commercially is not free from cardol given the close boiling points of the two compounds. The elevated heat required to distil cardanol induces polymerisation, thereby preventing the subsequent isolation of cardol. The polymerised residue after distillation is commercially available as Residol.

US-4352944 disclosed modifications of CNSL using an amine. This amine was used to create a Mannich salt with the cardol constituent. The subsequent distillation did not isolate pure cardanol.

US-7825284 disclosed a similar approach describing part of the distillation process using boric acid.

US-7781623 also disclosed a similar approach describing part of the distillation process using acetic anhydride.

Srinavasa Rao ef a/ (P.Phani Kumar, R.Paramashivappa, P.J.Vithayayil, P.V.Subba Rao, A.Srinavasa Rao, J.Agric.Food.Chem, 2002, 50, 4705-4708) reported a method to separate the constituents of technical CNSL using a mixture of ammonia and methanol, followed by extraction with hexane in order to isolate cardanol, and ethyl acetate/hexane in order to isolate cardol. This process was carried out on reaction scales up to 1 kg with claimed efficiencies of 93-95%.

Supercritical carbon dioxide extraction with the use of an isopropyl alcohol co-solvent was reported in JP-5000979. It was shown to separate cardol and cardanol.

Cardanol was separated into the supercritical phase and cardol remained in the isopropyl alcohol residue phase.

Philip et al. (J.Y.N Philip, J. D.C.Francisco, E.S.Dey, J.Buchweishaija, L.LMkayula, L.Ye., in J.Agric.Food.Chem, 2008, 56, 9350-9354) have reported the use of supercritical carbon dioxide to separate anacardic acid from natural CNSL when adsorbed onto a solid support. This method isolated pure anacardic acid but did not separate cardanol from cardol. Summary of the invention.

It is an objective of the present invention to provide a simple and efficient method for separating compounds having a similar structure and different polarity from a mixture.

It is another objective of the present invention to separate cardol and cardanol from technical cashew nut shell liquid.

It is also an objective of the present invention to obtain cardol and cardanol in pure form.

The foregoing objectives have been realised as described in the independent claims. Preferred embodiments are described in the dependent claims.

Detailed description of the invention.

Accordingly, the present invention discloses a method for extracting two or more compounds from a mixture comprising several compounds having a similar structure, said structure consisting of a phenol group carrying 0, 1 , or 2 additional OH groups and at least one alkyl group having at least 5 carbon atoms, with the exception of anacardic acid, said method comprising the steps of:

a) dissolving the compound in an inert solvent if it is in solid form or using it neat or dissolved in a solvent if it is in liquid form;

b) providing an inert adsorbing;

c) loading the dissolved or liquid compound of step a) onto the support of step b) d) separating a first molecule having a first structure with a first solvent having a first polarity, until complete or partial separation is achieved;

e) separating the same molecule as in step d) if it was partially separated, and/or a second molecule having a second structure with a second solvent having a second polarity until complete or partial separation is achieved;

f) optionally, continuing the separation process until all desired molecules are separated; g) soaking the support resulting from step e) or of step f) into an organic solvent; h) decanting or filtering the organic solvent from the support and subsequently evaporating or distilling said organic solvent;

i) retrieving the remaining unseparated residues,

characterised in that the first compound to be extracted is that that has the smallest number of OH groups.

The mixture from which the compounds are fractionated is preferably selected from naturally occurring mixtures, for example cashew nut shell liquid or other similar substances comprising different kinds of phenol groups.

The mixture to be separated needs to be adsorbed onto the support and therefore provided in liquid form. Mixtures that occur in solid form must be dissolved in a solvent. Mixtures that occur in liquid form can be used as such or may be dissolved in an organic solvent, for example acetone. The solvent can then be removed by evaporation or distillation.

The inert adsorbing supports that can be used in the present invention can be either neutral, or basic or acidic and can be selected from any support material known in the art, but they must be inert towards the components of the mixture. They can for example be glass beads, but preferably they have a large surface area and therefore are provided in a finely grinded form or in a porous form.

The support can be selected from any porous material. It is typically selected from silica, alumina, montmonrillionite, magnesium silicate, aluminium silicate, zeolite, polystyrene beads, chitosan. Suitable support material can for example be selected from Celite S^®, Celite 110^®, Celite 209^®, Celite 281 ^®, Celite 503^®, Celite 512M^®, Celite 545^®, Celite 545AW^®, Celite 560^®, Celite 577F^®, Celite 535^® all produced by Celite Corp., acid Alumina (Alumina A), basic Alumina (Alumina B), neutral Alumina (Alumina N), Ascarite^® and Florisil^® both produced by Sigma-Aldrich, Bentonite, Kaolinite, Fuller's Earth, produced by Sigma-Aldrich.

Preferably the porous support material has the following typical properties;

- pores having a diameter ranging from 7.5 to 30 nm; - porosity ranging from 1 to 4 cm³ /g;

- specific surface area is not particularly limited, it typically ranges between 5 to 250 m² /g; and

- an average particle diameter ranging from 1 to 150 μιτι.

The nature of the support has an influence on the binding strength between support and adsorbed material. It can be complex such as celite or bentonite and have little binding strength. Alternatively it can be an acidic or neutral or basic alumina and offer strong binding. The support is thus selected or tailored according to the desired level of separation or according to the nature of the material to be separated.

The amount of loading of the compound onto the support is not very restricted as long as the loaded powder remains a free flowing powder. It ranges typically between 5 wt% and 60 wt% based on the weight of the loaded powder. Preferably it ranges between 20 wt% and 55 wt% and more preferably between 30 wt% and 50 wt%.

The solvent that is used in the separation process is carbon dioxide in the liquid state or in the supercritical state, alone or in combination with a co-solvent. Preferably it is used alone and it is a major advantage of the present invention that the same solvent can be used as first solvent in step d) and as second solvent in step e), by simply changing the conditions of temperature and pressure, . The same solvent can thus be used to separate two compounds of different structure.

In a preferred embodiment according to the present invention, carbon dioxide is used alone for the full separation.

The first molecule to be separated, typically the molecule which has a single hydroxyl group, is separated first using carbon dioxide in liquid state. Liquid carbon dioxide is less polar than supercritical carbon dioxide. The separation is carried out at a temperature of less than 31 °C and at a pressure of less than 73 bars.

Preferably the temperatures ranges between 0 °C and 20 °C, more preferably it is of about 5 °C. Preferably the pressure ranges between 55 bars and 70 bars, more preferably it is of about 65 bars. The second molecule to be separated, typically the molecule which has 2 hydroxyl groups, is separated using carbon dioxide in the supercritical state. The separation is carried out at a temperature higher than 31 °C and at a pressure higher than 73 bars. Preferably the temperature ranges between 31 °C and 200 °C, more preferably between 31 °C and 80 °C. Preferably the pressure ranges between 73 bars and 1100 bars, more preferably between 200 bars and 700 bars. Most preferably the temperature is of about 50 °C and the pressure is of about 500 bars.

The third molecule, if present, is separated by increasing the polarity of the separating solvent. This can be achieved by increasing the temperature and pressure with respect to the previous separating conditions, such as for example, a temperature of 100 °C and a pressure of 1100 bars.

Alternatively, it can be carried out by adding an organic co-solvent to the carbon dioxide and keeping the same temperature and pressure as in the previous separation. The co-solvent can be selected for example from ethanol or methanol.

A preferred embodiment according to the present invention discloses a method for separating cardol and cardanol from technical cashew nut shell liquid (CNSL) that comprises the steps of:

a) optionally dissolving CNSL in an organic solvent;

b) loading neat CNSL or the dissolved compound of step a) onto an inert porous adsorbing support;

c) separating cardanol with liquid dioxide at a temperature ranging between 0 and 20 ^°C and under a pressure of from 55 to 70 bars until all or part of cardanol has been separated;

d) separating the remaining cardanol, if present, or cardol with supercritical carbon dioxide at a temperature ranging between 31 and 200 ^°C and under a pressure ranging between 200 and 700 bars until complete or partial separation is achieved;

e) optionally soaking the support resulting from step d) in an organic solvent; f) decanting or filtering carbon dioxide from the support and subsequently

evaporating or distilling said organic solvent; g) retrieving the residual cardanol, if present, and cardol.

The separated compounds find use in different applications. For example, the cardol and cardanol separated from cashew nut shell oil can be used in the fields of herbicides, antioxidants, UV protection.

Examples

Example 1

15 g of technical CNSL was tumbled onto 50 g of Celite 545^® purchased from World Minerals at ambient temperature (20 °C). The support had a surface area of 12 m²/g and a porosity of 0.015 cm³/g (N.I.Lulova, A.V.Kuz'mina, N.M.Koroleva, Chemistry and Technology of Fuels and Oils, volume 2, issue 9, pages 658-661 ). The resulting product was a slightly pink free flowing powder with no visible lumps. The mixture was cooled to 5°C overnight. 49.5g of this powder was packed into a 100ml separation vessel and the extraction was carried out at a temperature of 5°C, and under a pressure of 65 bar, with a rate of 8g of carbon dioxide per minute, and for a period of time of 2 hours. 3.04 g of cardanol was isolated as yellow oil, with a purity of 98.6% by high performance liquid chromatography (HPLC).

The separation was continued using the same conditions for a further 4 hours. A further 5.53 g of cardanol was isolated as yellow oil, with a purity of 95.6% by HPLC. The separation was continued using the same conditions for a further hour. A third portion, 0.389 g of a yellow oil was collected, with a purity of 81 .6% by HPLC.

After this crossover fraction, the separation conditions were changed to a

temperature of 50 °C, a pressure of 500 bar, and a C0₂ rate of 8 g per minute. The separation was carried out for a period of time of 1 .5 hours. 1 .32 g of cardol were isolated as viscous orange oil, in pure form by HPLC.

The overall recovery of pure cardol compared to the theoretical yield was 77.87%.

The overall recovery of >95% pure cardanol compared to the theoretical yield was 95.6%. Example 2

14.98 g of technical CNSL was tumbled onto 49.9 g of Silica purchased from

Fluorochem at ambient temperature (20 °C). The support had a particle size of 100μιτι and a particle size of 0.02μιη. The resulting product was a slightly pink free flowing powder with no visible lumps. The mixture was cooled to 5°C overnight. 33.89g of this powder was packed into a 100ml separation vessel and the extraction was carried out at a temperature of 5°C, and under a pressure of 65 bar, with a rate of 8g of carbon dioxide per minute, and for a period of 10 hours. 3.38 g of cardanol was isolated as a pale yellow oil, with a purity of 100% by high performance liquid chromatography (HPLC).

The separation conditions were changed to a temperature of 50 °C, a pressure of 500 bar, and a C0₂ rate of 8 g per minute. The separation was carried out for a period of of 2 hours. 1 .66 g of a pale yellow oil was isolated. Analysis by HPLC showed a mixture of cardanol (96.3%) and cardanol (3.7%). The support was removed from the separation vessel and soaked in ethyl acetate. The ethyl acetate extract was concentrated by rotary evaporation. 1 .68g of residue was isolated as a dark red oil, with HPLC showing cardol (93.7%) with the remainder being anacardic acid.

Example 3

24.13 g of technical CNSL was tumbled onto 80.1 Og of acidic alumina purchased from Sigma Aldrich at ambient temperature (20 °C). The resulting product was a slightly pink free flowing powder with no visible lumps. The mixture was cooled to 5°C overnight. 101 .80g of this powder was packed into a 100ml separation vessel and the extraction was carried out at a temperature of 5°C, and under a pressure of 65 bar, with a rate of 8g of carbon dioxide per minute, and for a period of 10 hours. 14.42 g of cardanol was isolated as a pale yellow oil, with a purity of 100% by high performance liquid chromatography (HPLC).

The separation conditions were changed to a temperature of 50 °C, a pressure of 500 bar, and a C0₂ rate of 8 g per minute. The separation was carried out for a period of of 2 hours. 0.87g of a pale yellow oil was isolated. Analysis by HPLC showed this to be cardanol of 100% purity. The support was removed from the separation vessel and soaked in ethyl acetate. The ethyl acetate extract was concentrated by rotary evaporation. 3.72g of residue was isolated as a dark red oil. Analysis by HPLC showed this to be cardol of 100% purity.

Example 4

24.02 g of technical CNSL was tumbled onto 80.17g of neutral alumina purchased from Sigma Aldrich at ambient temperature (20 °C). The resulting product was a slightly pink free flowing powder with no visible lumps. The mixture was cooled to 5°C overnight. 103.35g of this powder was packed into a 100ml separation vessel and the extraction was carried out at a temperature of 5°C, and under a pressure of 65 bar, with a rate of 8g of carbon dioxide per minute, and for a period of 10 hours. 12.7g of cardanol was isolated as a pale yellow oil, with a purity of 100% by high performance liquid chromatography (HPLC).

The separation conditions were changed to a temperature of 50 °C, a pressure of 500 bar, and a C0₂ rate of 8 g per minute. The separation was carried out for a period of of 2 hours. 1 .24g of a pale yellow oil was isolated. Analysis by HPLC showed this to be cardanol of 100% purity. The support was removed from the separation vessel and soaked in ethyl acetate. The ethyl acetate extract was concentrated by rotary evaporation. 5.35g of residue was isolated as a dark red oil. Analysis by HPLC showed this to be a mixture of cardol (49.5%) and cardanol (50.5%).

Example 5

24.12 g of technical CNSL was tumbled onto 80.60g of basic alumina purchased from Sigma Aldrich at ambient temperature (20 °C). The resulting product was a slightly pink free flowing powder with no visible lumps. The mixture was cooled to 5°C overnight. 103.81 g of this powder was packed into a 100ml separation vessel and the extraction was carried out at a temperature of 5°C, and under a pressure of 65 bar, with a rate of 8g of carbon dioxide per minute, and for a period of 10 hours. 11 .50g of cardanol was isolated as a pale yellow oil, with a purity of 100% by high performance liquid chromatography (HPLC). The separation conditions were changed to a temperature of 50 °C, a pressure of 500 bar, and a C0₂ rate of 8 g per minute. The separation was carried out for a period of of 2 hours. 1 .24g of a pale yellow oil was isolated. Analysis by HPLC showed this to be cardanol of 100% purity. The support was removed from the separation vessel and soaked in ethyl acetate. The ethyl acetate extract was concentrated by rotary evaporation. 5.35g of residue was isolated as a dark red oil. Analysis by HPLC showed this to be a mixture of cardol (49.5%) and cardanol (50.5%).

Claims

CLAIMS.

1 . A method for extracting 2 or more compounds from compounds comprising several compounds having a similar structure, said structure consisting of a phenol moiety carrying 0, 1 , or 2 additional OH groups and at least one alkyl group having at least 5 carbon atoms, with the exception of anacardic acid, said method comprising the steps of:

a) dissolving the mixture in an organic solvent if it is in solid form or using it neat or dissolved in a solvent if it is in liquid form;

b) providing an inert porous adsorbing support;

c) loading the dissolved or liquid mixture of step a) onto the support of step b) d) separating the first molecule having a first structure with a first solvent having a first polarity until complete or partial separation is achieved;

e) separating the same molecule as in step d) if it was partially separated, and/or the second molecule having a second structure with a second solvent having a second polarity until complete or partial separation is achieved;

f) optionally, continuing the separation process until all desired molecules are separated;

g) soaking the support resulting from step e) or step f) into an organic solvent; h) decanting or filtering the organic solvent from the support and subsequently distilling or evaporating said organic solvent;

i) retrieving the remaining unseparated residues.,

characterised in that the first molecule to be extracted is that that has the smallest number of OH groups.

2. The method of claim 1 wherein the organic solvent of step a) is selected from acetone, methanol or ethyl acetate.

3. The method of claim 1 or claim 2 wherein the inert adsorbing support is

selected from silica, alumina, montmonrillionite, magnesium silicate, aluminium silicate, zeolite, polystyrene beads, chitosan or glass beads.

4. The method of any one of the preceding claims wherein the inert adsorbing support is porous and has a surface area ranging between 5 and 250 m²/g

5. The method of any one of the preceding claims wherein the solvent used in the separation is carbon dioxide.

6. The method of claim 4 wherein the solvent additionally comprises an organic co-solvent.

7. The method of any one of the preceding claims wherein the first molecule is separated with carbon dioxide at a temperature ranging between 0 and 20 ^°C and under a pressure ranging between 55 and 70 bars.

8. The method of any one of the preceding claims wherein the second molecule is separated with carbon dioxide at a temperature ranging between 31 and 200 ^°C and under a pressure ranging between 73 and 1100 bars.

9. The method of any one of the preceding claims wherein the starting material is cashew nut shell liquid and the separated compounds are cardanol as first molecule and cardol as second molecule.