WO1997036000A1

WO1997036000A1 - Esterification process

Info

Publication number: WO1997036000A1
Application number: PCT/EP1997/000834
Authority: WO
Inventors: Pieter Axel Pel; Cornelis Van Der Sar; Cock Verboom
Original assignee: Unichema Chemie B.V.
Priority date: 1996-03-27
Filing date: 1997-02-19
Publication date: 1997-10-02
Also published as: ID16510A

Abstract

The invention relates to a process for the preparation of fatty acid esters of alkylglycosides (III), by transesterification of an alkylglycoside (I) with an alkylester of a fatty acid (II), in the presence of the alkylglycoside ester (III) resulting from the transesterification of (I) with (II). The reaction is enzymatically catalysed. The relative amounts of the compounds (I), (II) and (III) at the start of the reaction are chosen such that the reaction is carried out in the homogeneous phase region of the ternary system of compounds (I), (II) and (III).

Description

ESTERIFICATION PROCESS

The present invention relates to the preparation of fatty acid esters of alkylglycosides by enzymatically catalysed transesterification.

Fatty acid esters of alkyl glycosides (or: alkyl glycoside esters) form a group of compounds of which many have surface active properties. More specifically, they form a class of mild surfactants or emulsifiers, having

(potential) applications in the personal care area (e.g. shampoos, facial cleansing bars) , fabrics washing, household cleaning, food products and many others.

There are several processes for the preparation of fatty acid esters of alkylglycosides. Basically, the reaction is an esterification of an alkylglycoside with a fatty acid. Both direct esterification of an alkylglycoside with a fatty acid as well as transesterification (involving an ester exchange reaction between a lower alkyl ester of a fatty acid and an alkylglycoside) are reported. Alkali or acid catalysed reactions as well as enzymatically catalysed reactions are known.

For many purposes it is desired to obtain fatty acid esters of alkyl glycosides which have a high content of mono¬ esters and a low amount of side products such as alkyl glycoside di-, tri- and poly esters, cracked products etcetera, since these may lead to less favourable properties, in particular surface active properties, and/or a bad odour and/or colour of the product.

The use of acid or alkali catalysed reactions for producing the compounds according to the invention is not very refined, and leads to numerous side reactions like e.g. formation of oligomers, breakdown of sugars and esterification of more than just one (on average) alcoholic moiety of the alkylglycoside. This is for many purposes undesired, since the (emulsifying) properties are changed and discoloration may occur. Enzymatically catalysed esterification of polyols is in general more specific, and is thus desired.

The direct esterification of alkyl glycosides with fatty acids suffers from a number of disadvantages. Firstly, in this esterification water is formed, which should preferably be removed, so as to shift the equilibrium towards the desired side. The water formed is difficult to remove from the system, due to its low vapour pressure at the temperatures employed. Furthermore, if an enzyme is employed, the high concentrations of water tend to inactivate such enzyme in this particular situation. Secondly, since an excess amount of fatty acid is to be used to achieve acceptable conversions, the excess (or a large proportion of it) has to be removed after the reaction. However, the removal of the fatty acids by distillation is cumbersome, due to the relatively high boiling points and the relatively high polarity of these fatty acids. Additionally, the high distillation temperatures needed may give rise to discoloration of the product. Although molecular distillation can be used with good separation results, this necessitates the use of expensive equipment.

Thus, to obtain alkylglycoside esters meeting the demands as set out above, these compounds should be manufactured by transesterification of alkylglycosides with alkyl esters of fatty acids in an enzymatically catalysed process.

Such a process has been disclosed in e.g. EP 507323 and EP 413307 (both Lion Corp.) . Herein, the products according to the invention are obtained by transesterification of alkylglycosides with an alkyl ester of the fatty acid using a lipase enzyme as a catalyst. Since the alkylglycoside and the alkyl ester of the fatty acid are not (well) miscible with each other, an organic solvent is added to the reaction mixture, in order to obtain a homogeneous reaction mixture. Such a homogeneous reaction mixture is needed in order to achieve an acceptable initial reaction rate, since heterogeneous reaction mixtures do not show an acceptable reactivity. Additionally, the solvent serves to lower the viscosity of the reaction system, which is desired for convenient processing, in particular in combination with a bed of immobilized enzymes so as to enable (semi-) continuous processing.

However, the use of such solvents has its disadvantages: use of a solvent in general leads to a lower yield, when compared to a process without a solvent. Also, the use of volatile organic solvents leads to an increased fire and explosion hazard. Furthermore, it is also difficult to remove such an organic solvent completely from the reaction mixture once the reaction is finalised. Such complete removal is desired since the alkylglycoside esters so produced are used in, inter alia, the cosmetics and personal care industry, and thus require to be solvent free. Additionally, they do not impart a "green", environmental friendly image to both the product and the producer. Furthermore, the use of a solvent may affect the performance of the enzyme employed.

Hence, there was a need for a convenient process for the preparation of fatty acid esters of alkyl glycosides by transesterification using an enzyme catalyst, and which reaction system may be carried out without the separate addition of a solvent, and which reaction system may be carried out in a continuous manner.

It has now been found that the above can be achieved by a process for the preparation of alkylglycoside esters by transesterification of an alkylglycoside (I) with an alkylester of a fatty acid (II) , in which a mixture comprising:

- an alkylglycoside (I) ,

- an alkylester of a fatty acid (II) , and

- the alkylglycoside ester (III) resulting from the transesterification of (I) with (II), is contacted with an enzyme catalyst, wherein the relative amounts of the compounds (I) , (II) , and (III) at the start of the reaction are chosen such that the composition is located in the homogeneous phase region of the ternary system of components (I) , (II) and (III) .

The alkylglycoside ester (III) is the compound to obtain.

Although the compounds (I) , (II) , and (III) are not miscible in all concentrations, it has been found that, within a reasonable degree of variation, for each ternary system containing alkylglycoside (I) , alkylester of a fatty acid (II) , and alkylglycoside ester (III) a range of compositions can be found in which these three components form a homogenous mixture. This range of compositions is located in the so-called homogeneous-phase area in a ternary phase diagram (see figure 1) . What relative amounts are needed for each of the compounds (I) , (II) , and (III) to obtain a homogeneous mixture cannot be given for each possible compound for (I) , (II) , and (III) . However, this can be determined by the person skilled in the art with only a reasonable amount of routine experimentation. Once the desired compound (III) is chosen, the choice for the starting compounds (I) and (II) is straight forward, and from that point on a ternary phase diagram can be prepared, indicating the relative amounts needed for achieving a homogeneous phase. It is herein to be understood that by "homogeneous phase" in this respect it is meant a liquid which appears as one homogenous (or single) phase as observed by the person skilled in the art, without a visible separation surface (e.g. meniscus) between two or more phases, at the temperature and pressure given (generally those about equal to the temperature and pressure at the start of the reaction) .

For maintaining a high reaction speed, it is preferred that the reaction mixture continues to be a single, homogeneous phase as the reaction proceeds. It was found that the present reaction system complies to that. The relative amounts of the compounds (I) , (II) , and (III) at the start of the reaction are chosen such that the reaction is carried out in the homogeneous phase region of the ternary system of compounds (I) , (II) and (III) .

Care has to be taken, that the starting composition is chosen such that the initial viscosity is not too high. In particular in continuous processing, but also in batch processes, it is desirable to keep the viscosity below 300 mPa.s. Preferably, the viscosity is below 250 mPa.s, or even more preferably below 200 mPa.s.

In determining what composition to start with, the amount of alkylglycoside ester (III) in the starting mixture is preferably kept low, since this is the product to be obtained. Since (trans)esterification is a reaction around an equilibrium, it is advantageous to start with an excess of one of the starting compounds. It was found that if an excess of alkylester of a fatty acid (II) is used, good yields are obtained. As an additional benefit, the viscosity thereby remains within reasonable limits during the complete reaction from starting point to end point. It is surprising that the viscosity remains quite low, since it would be expected that it rises upon the formation of the alkyl glycoside ester (III) . Also, any excess fatty acid alkyl ester can easily be removed after the reaction. The balance in relative amounts in the reaction system (i.e. in addition to compounds (II) and (III)) is made up by alkylglycoside (I) . Typical relative amounts of the three compounds in the starting mixture are very much dependent on the actual compounds to be prepared. In the ternary system the relative amount of alkylglycoside (I) is generally between 0.01 and 0.45, preferably between 0.05 and 0.25. In that same system, the relative amount of fatty acid alkylester (II) is typically between 0.20 and 0.98, preferably between 0.30 and 0.85. Likewise, the relative amount of alkylglycoside ester (III) is typically between 0.05 and 0.85, preferably between 0.1 and 0.45.

Preferably, the enzyme catalyst in the process according to the invention is in an immobilized form (e.g. as known in the art of esterification) . This may allow continuous processing. Preferably, such an enzyme catalyst comprises a lipase. More preferably, the lipase used is a thermostable lipase, such as derived from Candida antarctica (e.g. lipase A) as described in WO 88/02775, or derived from Muc_Ωr miehei.

Preferably, the process is carried out without the addition of a substantial amount of solvent. However, it may be that some solvent (e.g. lower alkyl alcohol such as ethanol) is introduced in the reactor in conjunction with one of the other reactants. For example, the alkylglycoside (I) employed generally contains a small amount of alkanol, following the manufacture of the alkylglycoside. Such a solvent is generally removed when lowering the pressure upon starting the reaction.

Depending upon the application of the obtained alkyl glycoside ester, it is preferred that the alkyl group of the alkylglycoside (I) has 1-4 carbon atoms. For application in personal care products ethylglycosides and methyl glycosides are generally preferred. Likewise, it is preferred that the alkyl group of the alkylester of a fatty acid (II) has 1-4 carbon atoms. It is most preferred that the alkylester of fatty acid (II) comprises a methyl ester or an ethylester. Depending upon its area of application, it is preferred that the alkylester of a fatty acid (II) comprises alkylesters of straight and branched chain, saturated or unsaturated fatty acids having a total number of carbon atoms of between 6 and 22. More preferred are alkyl esters of fatty acids which are selected from the group consisting of methyl laurate, ethyl laurate, methyl caprate, ethyl caprate, methyl oleate, ethyl oleate, methyl stearate, ethyl stearate, methyl iso-stearate and ethyl iso-stearate.

Although a wide variety of monoglycosides can be used in the reaction according to the invention, it is generally preferred that the glycosides comprise glucosides.

The reaction may suitably be employed by introducing in a reaction vessel:

- alkyl glycoside (I)

- an alkylester of a fatty acid (II)

- alkyl glycoside ester (III) - an enzymatic catalyst (in an amount of e.g. between 0.01 and 15% immobilized enzyme by weight, calculated on the total amount) .

Generally, the compound (I) is a mixture comprising the alkylglycoside, oligoglycosides and the free sugar itself, depending upon the manufacture of this compound. Similarly, compound (III) is generally a mixture comprising the alkylglycoside ester itself, in admixture with other components such as alkylglycoside and oligoglycoside (and the fatty acid ester thereof) .

The amounts should be chosen such that the mixture appears a one single, homogenous phase, at reaction conditions.

For example, a suitable (batch) process is carried out by lowering the pressure of the reactor vessel (after introducing the reaction compounds and the catalyst as described above) to below 100 mbar (typical) at the start of the reaction, so as to enable removal of the alcohols formed. The temperature is elevated and maintained at a temperature at which the enzymatic catalyst performs well (normally between 40 and 70°C) . The reaction may proceed for 5-100 hours, depending upon e.g. the temperature and the amount of catalyst. At the end of the reaction, the pressure is brought to atmospheric, and the mixture is allowed to cool to room temperature.

The mixture so obtained (now enriched in alkylglycoside ester content) may be employed directly, or it may be purified in any way known in the art, depending upon its future use.

The above process may be employed in a continuous manner, involving the continuous addition of starting compounds (I) and (II) to the reaction mixture, and the continuous removal of finalized product (III) . The reaction mixture may be circulated over a fixed catalyst bed.

The invention is now exemplified by the following examples, which are not to be seen as limiting the scope of the invention.

Preparation of the ingredients for the examples

The ingredients used in the examples were prepared separately. Below a description is given of the preparation of Ethyl Glucoside, the Ethyl Esters of Capric, Laurie and Oleic acid and the Ethyl Glucoside esters, used as ingredients for the examples. In the reaction system according to the invention, a certain amount of the alkylglycoside ester (III) , which is the desired end product, should be used when starting the reaction. Preferably, the alkylglycoside ester (III) used for this purpose is obtained using the reaction according to the invention. However, this is not possible when executing this reaction for the first time, and consequently, the alkylglycoside ester should be obtained first in another way, as known in the art, and as is set out below.

Synthesis of Ethyl Glucoside

In an 1.5 litre closed autoclave, 150.0 gram (0.83 moles) anhydrous glucose, 383 gram (8.3 moles) absolute ethanol and 9. 5 gram of a strong acidic ion exchange catalyst (Amberlyst 15 ex Rohm & Haas) were brought. The slurry was heated to 100 °C and continuously stirred. After a reaction time of 11 hours, the glucose conversion was approx. 95 %. The reaction product, an alcoholic EG solution, was bleached with 0.1 wt% active carbon (Norit SX Ultra) during 30 minutes at 40°C. The composition of the ethanol free product is: 75 wt% Ethyl Glucoside (substantially pure) , 4 wt% Glucose and 21 wt% Oligoglucosides. For the purpose of this invention, "EG product " is considered to be the mixture with the aforementioned composition.

Synthesis of Fatty Acid Ethyl Esters

In a 4 litre five-necked flask equipped with a mechanical stirrer, thermocouple, nitrogen supply, ethanol supply and a condenser, 1500 gram fatty acid and 3.0 gram (0.2 wt%) para-toluene sulphonic acid (pTSA) catalyst were brought. The mixture was heated to 120 °C and absolute ethanol was dosed with a speed of 220 ml. per hour. After a reaction time of 8 hours, the acid value was less than 1 mg KOH/g. The crude product was refined with a 50 wt% sodium hydroxide solution in water. After treatment with 0.20 wt% active carbon, 1.0 wt% Tonsil Optimum NFF and 1.0 wt% Dicalite the refined product had a purity of more than 99 wt%. Using this procedure, Ethyl Laurate (EL) , Ethyl Caprate

(EC) and Ethyl Oleate (EO) were prepared from respectively Laurie Acid (PRIFRAC 2922 ex Unichema International) , Capric Acid (PRIFRAC 2906 ex Unichema International) and Oleic Acid (PRIFRAC 6905 ex Unichema International) .

Synthesis of Ethyl Glucoside Esters

To obtain various alkyl glycoside esters for starting the reaction, Lauroyl-, Caproyl and Oleyl-EGE's were made by direct esterification using the procedure as described in patent WO 94/01575, under vacuum at 60°C of respectively Laurie acid (PRIFRAC 2922 ex Unichema International) ,

Capric acid (PRIFRAC 2906 ex Unichema International) and Oleic acid (PRIFRAC 6905 ex Unichema International) with EG product (see above) using 5.0 wt% immobilized Candida antarctica lipase as the catalyst (7100 PLU/gram) . The reactions were done with 20 molar% excess of the fatty acid. After the reaction the excess of fatty acid was removed by molecular distillation.

For the purpose of these examples, "Lauroyl EGE product " is to be understood a mixture comprising: 69 wt% Lauroyl EGE

(substantially pure) , 4 wt% Laurie acid, 7 wt% EG, 20 wt% oligoglucoside (ester) likewise, "Caproyl EGE product" is to be understood a mixture comprising: 63 wt% Caproyl EGE (substantially pure) , 2 wt% Capric acid, 8 wt% EG, 27 wt% oligoglucoside (ester) likewise, "Oleoyl EGE product " is to be understood a mixture comprising: 75 wt% Oleoyl EGE (substantially pure) , 2 wt% Oleic acid, 1 wt% EG, 22 wt% oligoglucoside (ester) .

The above mentioned EGE products were prepared to enable to start the reaction according to the invention initially. In all consecutive reactions the EGE produced according to the invention was used for starting the reactions. Examples

Comparative A; Synthesis of Lauroyl EGE by enzymatic interes sHfication of Ethyl Laurate and EG product without

EGE in the starting mixture

A mixture of 60.0 g dry EG, 65.8 g Ethyl Laurate and 0.60 g immobilized enzyme ( Candida antarctica lipase immobilized on Accurel, SP611, ex NOVO Nordisk; activity: 7100 PLU/g) were brought into a one-necked flask. The flask was continuously rotated in an oil-bath of 60 °C and vacuum of 20-25 mbar was applied. The Ethyl Laurate did not dissolve in the EG. After 27 hour, approximately 1.4 wt% Lauroyl EGE was found in the Ethyl Laurate layer. No Lauroyl EGE was found in the EG-layer.

1-. Synthesis of Lauroyl EGE by enzymatic interesterification of Ethyl Laurate and EG product in the presence of Lauroyl EGE product

In a 500 ml four-necked glass reaction vessel equipped with a mechanical stirrer, thermocouple and nitrogen supply, 205.05 gram reaction mixture was brought. The initial composition of the reaction mixture was: 15.0 wt% EG product as above, 45.0 wt% Ethyl Laurate and 40.0 wt% Lauroyl EGE product as above. The reaction was done at 60°C and a pressure of 28 mbar in the presence of 1.54 gram (0.75 wt%) immobilized enzyme ( Candida antarctica lipase immobilized on Accurel (SP611 ex Novo Nordisk; activity: 7100 PLU/gram) ) . During the reaction 7.5 1/hr nitrogen was supplied using a dippipe. After a reaction time of 36 hours the mixture was converted from a composition of 26.8 wt% EGE and 12.3 wt% EG to a mixture with 45.0 wt% EGE and 4.1 wt% EG (as analyzed by GC) . At the start of the reaction, the viscosity was 124 mPa.s, at the end of the reaction the viscosity appeared to be 138 mPa.s. 2. Synthesis of Laurovl EGE by enzymatic interesterification of Methvl Laurate and KG product in the presence of Lauroyl EGE product.

Lauroyl EGE was synthesized using the procedure as described in example 1 above. The initial composition of the reaction mixture was: 15.0 wt% EG product as above, 40.0 wt% Lauroyl EGE and 45.0 wt% Methyl Laurate as above (Methyl Laurate, ESTOL 1502 was supplied by Unichema International) . The reaction was done at 70°C and a pressure of 21 mbar in the presence of 2.05 gram (1.00 wt%) immobilized enzyme ( Candida antarctica lipase immobilized on Accurel (SP611 ex Novo Nordisk; activity: 7100 PLU/gram) . During the reaction 1.9 1/hr nitrogen was supplied using a dippipe. After a reaction time of 16.4 hours the mixture was converted from a composition of 28.6 wt% EGE and 13.6 wt% EG to a mixture with 49.5 wt% EGE and 3.5 wt% EG (as analyzed by GC) . At the start of the reaction, the viscosity was 47 mPa.s, at the end of the reaction the viscosity appeared to be 55 mPa.s.

3__j_ Synthesis of Caproyl EGE by enzymatic interesterification of Ethyl Caprate and EG product in the presence of Caproyl EGE product

Caproyl EGE was synthesized using the procedure as described in example 1. The initial composition of the reaction mixture was: 15.0 wt% EG product as above, 45.0 wt% Ethyl Caprate and 40.0 wt% Caproyl EGE product as above. After a reaction time of 41 hours the mixture was converted from a composition of 27.0 wt% EGE and 14.5 wt% EG to a mixture with 41.0 wt% EGE and 3.8 wt% EG. At the start of the reaction, the viscosity was 150 mPa.s, at the end of the reaction the viscosity appeared to be 103 mPa.s. 4_^. Synthesis of Qleoyl EGE by enzymatic interesterification of Ethyl Oleate and EG product in the presence of Oleoyl EGE product

Oleoyl EGE was synthesized using the procedure as described in example 1. The initial composition of the reaction mixture was: 14.0 wt% EG product as above, 45.0 wt% Ethyl Oleate and 41.0 wt% oleoyl EGE product as above. After a reaction time of 66 hours the mixture was converted from a composition of 39.9 wt% EGE, and 10.7 wt% EG to a mixture with 57.4 wt% EGE and 4.6 wt% EG. At the start of the reaction, the viscosity was 94 mPa.s, at the end of the reaction the viscosity appeared to be 180 mPa.s.

5__. Influence of the viscosity on the interesterification of EG product with Ethyl Laurate

To investigate the influence of the viscosity on the reaction rate, experiments were carried out with different compositions of the starting mixtures.

5.1 A starting mixture with a composition of 40.0 wt% Lauroyl EGE product, 50.0 wt% Ethyl Laurate and 10.0 wt% Ethyl Glucoside product has a viscosity of 48 mPa.s at 60 °C. After a reaction time of 38 hours using the reaction conditions as described in example 1, using 0.5% immobilized enzyme, the composition had changed from 26.5 wt% EGE and 8.2 wt% EG to 42.3 wt% EGE and 1.1 wt% EG. The final viscosity was 55 mPa.s. 5.2 A starting mixture with a composition of 40.0 wt% Lauroyl EGE product, 40.0 wt% Ethyl Laurate and 20.0 wt% Ethyl Glucoside product has a viscosity 182 mPa.s at 60 °C. After a reaction time of 28 hours using the reaction conditions as described in example 1, using 1.0% immobilized enzyme (Lipozyme SP 392) , the composition had changed from 26.5 wt% EGE and 14.2 wt% EG to 31.0 wt% EGE and 12.7 wt% EG. The final viscosity was 475 mPa.s.

It is clear that in the first case the reaction goes faster and in the second case the reaction goes slower.

Claims

1. A process for the preparation of alkylglycoside esters by transesterification of an alkylglycoside (I) with an alkylester of a fatty acid (II) , in which a mixture comprising:

- an alkylglycoside (I) ,

- an alkylester of a fatty acid (II) , and

- the alkylglycoside ester (III) resulting from the transesterification of (I) with (II) , is contacted with an enzyme catalyst, wherein the relative amounts of the compounds (I) , (II) , and (III) at the start of the reaction are chosen such that the composition is located in the homogeneous phase region of the ternary system of components (I) , (II) and (III) .

2. Process according to claim 1, characterized in that the relative amounts of compounds (I) , (II) , and (III) are chosen such that the single phase mixture has a viscosity at the start of the reaction of below 300 mPa.s.

3. Process according to claim 2, characterized in that the relative amounts of compounds (I) , (II) , and (III) are chosen such that the homogeneous mixture has a viscosity at the start of the reaction of below 200 mPa.s.

4. Process according to any of claims 1-3, characterized in that the enzyme catalyst is in an immobilized form.

5. Process according to any of claims 1-4, characterized in that the enzyme comprises a lipase.

6 . Process according to claim 5, characterized in that the lipase comprises Candida antarctica lipase A.

7. Process according to any of claims 1-6, characterized in that the process is carried out without the addition of a substantial amount of solvent,

8. Process according to any of claims 1-7, characterized in that the alkyl group of the alkylglycoside (I) has 1-4 carbon atoms.

9. Process according to claim 8, characterized in that the alkylglycoside (I) comprises ethylglycosides.

10. Process according to any of claims 1-9, characterized in that the glycosides comprise glucosides .

11. Process according to any of claims 1-10, characterized in that the alkyl group of the alkylester of a fatty acid (II) has 1-4 carbon atoms.

12. Process according to claim 11, characterized in that the alkylester of a fatty acid (II) comprises a methyl ester or an ethylester.

13. Process according to any of claims 1-12, characterized in that the alkylester of a fatty acid (II) comprises alkylesters of straight and branched chain, saturated or unsaturated fatty acids having a total number of carbon atoms of between 6 and 22.

14. Process according to claim 13 , characterized in that the alkyl esters of fatty acids are selected from the group consisting of methyl laurate, ethyl laurate, methyl caprate, ethyl caprate, methyl oleate, ethyl oleate, methyl stearate, ethyl stearate, methyl iso- stearate and ethyl iso-stearate.