WO2012131299A1

WO2012131299A1 - Process for producing lactate

Info

Publication number: WO2012131299A1
Application number: PCT/GB2012/000283
Authority: WO
Inventors: Edward Leslie Marshall; Richard Thomas BALE
Original assignee: Plaxica Ltd
Current assignee: Plaxica Ltd
Priority date: 2011-03-28
Filing date: 2012-03-28
Publication date: 2012-10-04
Anticipated expiration: 2013-09-28
Also published as: GB201105216D0

Abstract

A process for the production of a quaternary ammonium salt of lactic acid, comprising contacting at least one saccharide with at least one water-soluble quaternary ammonium hydroxide, is provided. Also provided are processes for the production of lactic acid, ester of lactic acid, lactic acid oligomer, lactide and polylactic acid, which processes involve the production of a quaternary ammonium salt of lactic acid. A quaternary ammonium salt of lactic acid and a water-soluble quaternary ammonium hydroxide is also provided.

Description

Process for producing lactate

The invention relates to a process for producing lactate, and in particular to a process for producing a quaternary ammonium salt of lactic acid.

Lactic acid is an important industrial chemical typically prepared from microbial fermentation of carbohydrates, although chemical processes for preparing lactic acid are also known. According to Boudrant et al, Process Biochem 40 (2005) p. 1642, "In 1987, the world production of lactic acid averaged approximately equal proportions being produced by chemical synthesis and fermentation processes". Such chemical syntheses typically employed the hydrocyanation of acetaldehyde. However, chemical processes of this type have long been regarded as undesirable on an industrial scale, and today virtually all large scale production of the lactic acid available commercially is manufactured by fermentation processes, see for example Strategic Analysis of the Worldwide Market for Biorenewable Chemicals M2F2-39, Frost and Sullivan, 2009. In a typical fermentation process, biomass is fermented with microorganisms to produce either D- or L- lactic acid. Current industrial manufacturers operate large-scale fermentation processes for the production of optically active lactic acid, and the patent literature is replete with improvements in such processes. The product of a fermentation process is usually an optically active lactate salt, arising from the neutralisation of optically active lactic acid with a base.

A number of chemical processes for the production of racemic lactic acid from carbohydrate sources are known. For example, GB 400,413, dating from 1933, describes an improved process for preparing lactic acid or lactates comprising reacting a carbohydrate-containing material with a strong alkali at a temperature of at least 200°C and at a pressure above atmospheric. An example is described in which cane sugar is reacted with calcium hydroxide at a temperature of about 210°C to 220°C and at a pressure of 25 to 30 atmospheres. The use of divalent cations in the alkaline degradation reaction, and in particular calcium, has been described as favouring the formation of lactic acid (see for example Carbohydrate Polymers, 2003, 51, 281-300, Knill and Kennedy; Sugar Technology Reviews, 1986, 13, 21 -52, De Bruijn et al).

US2007/066844 (Jackson et al) describes a process for producing lactate involving reaction of an aqueous hexose sugar solution with a basic anion exchange resin at a temperature of between 30° and 60° C. The use of a solid basic anion exchange resin leads to lactate produced in the process being bound to the resin, and allows removal of unreacted byproducts in solution from the solid-bound lactate.

The present inventors have now found an improved process which permits economic production of lactate in high yield, and which does not require the use of solid basic anion exchange resins, or divalent metal cations.

Accordingly, the present invention provides a process for the production of a quaternary ammonium salt of lactic acid, comprising contacting at least one saccharide with at least one water-soluble quaternary ammonium hydroxide.

Suitable saccharides include, for example, monosaccharides, such as hexose monosaccharides, for example glucose, fructose, and mannose. In one embodiment, the saccharide comprises glucose. In another embodiment, the saccharide comprises fructose. In another embodiment, the saccharide comprises mannose. Pentoses may also be used, for example xylose. Mixtures of saccharides may be used. For example, the saccharide may comprise a mixture of glucose and fructose. Saccharides may be obtained from any suitable saccharide source, for example glucose may be obtained from a higher saccharide such as sucrose, starch or cellulose. By way of example, a mixture of glucose and fructose (known as invert sugar) may be obtained from sucrose by enzymatic hydrolysis using a sucrase or invertase, or by heating an aqueous solution of the di saccharide in the presence of an acidic catalyst such as sulfuric acid, citric acid or ascorbic acid. Alternatively, glucose may be obtained by enzymatic hydrolysis (e.g. using an amylase) of starch contained in biomass feedstocks, for example maize, rice or potatoes.

The quaternary ammonium hydroxide should be sufficiently water soluble to enable reaction of saccharide to produce quaternary ammonium lactate in an aqueous medium, and thus should be at least sparingly soluble. Preferably, the quaternary ammonium hydroxide has a water solubility of at least 1 g/L at 30°C, more preferably at least l Og/L at 30°C, still more preferably at least 100g/L at 30°C, most preferably at least 300g/L at 30°C.

In one embodiment, the water-soluble quaternary ammonium hydroxide contains from 4 to 80 carbon atoms, preferably up to 72 carbon atoms, more preferably up to 60 carbon atoms, still more preferably up to 40 carbon atoms, yet more preferably up to 32 carbon atoms, still more preferably up to 24 carbon atoms, especially up to 16 carbon atoms. In one embodiment, the quaternary ammonium hydroxide contains from 24 to 80 carbon atoms, preferably from 24 to 72 carbon atoms, more preferably from 24 to 60 carbon atoms. In one embodiment, the quaternary ammonium hydroxide contains from 32 to 80 carbon atoms, preferably from 32 to 72 carbon atoms, more preferably from 32 to 60 carbon atoms.

Water-soluble quaternary ammonium hydroxides include tetraalkylammonium hydroxides and benzylalkylammonium hydroxides. In one embodiment, the water- soluble quaternary ammonium hydroxide is a tetraalkylammonium hydroxide. In another embodiment, the water-soluble quaternary ammonium hydroxide includes one or more benzyl group(s), i.e. it is a benzylalkylammonium hydroxide.

In one preferred embodiment, the quaternary ammonium hydroxide is a tetraalkylammonium hydroxide containing from 4 to 80 carbon atoms, preferably up to 72 carbon atoms, more preferably up to 40 carbon atoms, still more preferably up to 32 carbon atoms, yet more preferably up to 24 carbon atoms, especially up to 16 carbon atoms.

Examples of tetraalkylammonium hydroxides include tetramethylammonium, tetraethylammonium, tetrapropylammonium, tetrabutylammonium,

tetrapentylammonium, tetrahexylammonium, tetraheptylammonium,

tetraoctyl ammonium, tetranonylammonium, tetradecylammonium,

tetraoctadecylammonium, and trihexyltetradecylammonium hydroxides, and

Ν,Ν,Ν,Ν',Ν',Ν' -hexabutylhexamethylenediammonium dihydroxide.

An example of a benzylalkylammonium hydroxide is benzyltrimethylammonium hydroxide.

Mixtures of quaternary ammonium hydroxides may be used. For example, in one embodiment a mixture of tetraalkylammonium hydroxides produced from Aliquat 336® may be used. Aliquat 336® is a quaternary ammonium salt made by the methylation of mixed trioctyl/decylamine. In one preferred embodiment, the quaternary ammonium hydroxide is a mixture of tetraalkylammonium hydroxides each having one methyl group and having other alkyl groups which are octyl and/or decyl groups.

Unlike the process of US2007/066844, the process of the invention does not involve the use of a basic anion exchange resin as a reactant to produce the quaternary ammonium salt of lactic acid, and can thus be carried out in the liquid phase. The use of a basic resin has a number of disadvantages, for example, the ability to vary reaction temperature is limited compared to quaternary ammonium hydroxides due to thermal instability of the resin, yields decrease when the resin is reused, and the lactate produced is bound to the solid resin and requires treatment with acid to release lactic acid for further processing. The present invention provides significantly higher yields than known liquid phase processes using metal hydroxides such as calcium.

Optionally, the process of the invention may include the step of regenerating quaternary ammonium hydroxide from the quaternary ammonium salt of lactic acid, and recycling it to the process.

The process of the invention includes the step of contacting at least one saccharide with at least one water-soluble quaternary ammonium hydroxide. Without being bound by any particular theory, it is thought that the process of the invention involves reaction of at least one saccharide with at least one water-soluble quaternary ammonium hydroxide to produce the quaternary ammonium salt of lactic acid.

The process of the invention is typically carried out in the presence of one or more solvents. In particular, the step of contacting (e.g. reacting) the saccharide with the water- soluble quaternary ammonium hydroxide to produce the quaternary ammonium salt of lactic acid is normally carried out in an aqueous medium. Some commercial sources of saccharide and quaternary ammonium hydroxide contain water, and such feedstocks may readily be used in the process of the invention. In certain embodiments, the step of contacting (e.g. reacting) the saccharide with the water-soluble quaternary ammonium hydroxide may take place in the presence of additional water (i.e. additional to that present in the starting materials). The step of contacting (e.g. reacting) the saccharide with the water-soluble quaternary ammonium hydroxide may also, if desired, take place in the presence of one or more organic solvents, for example an oxygenate such as an alcohol, ester, ether, or ketone.

The ratio of quaternary ammonium hydroxide to saccharide should be sufficient to effect high conversion of saccharide to the quaternary ammonium salt of lactic acid. For example, when the saccharide comprises glucose, for each mole of glucose it may be preferable to use at least two moles of quaternary ammonium hydroxide (i.e. in such cases the molar ratio of quaternary ammonium hydroxide to saccharide is at least 2:1). Excess quantities of quaternary ammonium hydroxide may be used, for example the molar ratio of quaternary ammonium hydroxide to saccharide (calculated as monosaccharide) may be up to 10: 1. In one embodiment, the molar ratio of quaternary ammonium hydroxide to saccharide (calculated as monosaccharide) is from 2: 1 to 10: 1 , more preferably 2:1 to 8: 1 , yet more preferably 2: 1 to 5: 1, still more preferably from 2: 1 to 3: 1, yet more preferably from 2.0: 1 to 2.5: 1 , still more preferably from 2.0: 1 to 2.2:1. Alternatively, for example when operating the invention at a large scale where process economics may be important, the present invention may encompasses molar ratios of quaternary ammonium hydroxide to monosaccharide that are lower than 2:1. Thus, in a preferred embodiment, the molar ratio of quaternary ammonium hydroxide to saccharide (calculated as monosaccharide) is from 1.5:1 to 10:1 , more preferably from 1.5: 1 to 5:1 , still more preferably from 1.5: 1 to 3 :1 , yet more preferably from 1.5: 1 to 2.5: 1 , still more preferably from 1.8: 1 to 2.5: 1 , most preferably from 1.8: 1 to 2.2: 1.

The conversion of saccharide to the quaternary ammonium salt of lactic acid may be carried out at room temperature (e.g. from 15 to 30°C, for example at about 25°C), although the reaction is preferably carried out at elevated temperature, for example at a temperature of up to 120°C. Preferably, saccharide is contacted (e.g. reacted) with quaternary ammonium hydroxide at a temperature of from 60° to 100°C, more preferably from 70° to 9Q^aC. In one embodiment, saccharide is contacted (e.g. reacted) with quaternary ammonium hydroxide at 80°C. In another embodiment, saccharide is contacted (e.g. reacted) with quaternary ammonium hydroxide in water at reflux.

In one embodiment, the saccharide is monosaccharide, the molar ratio of quaternary ammonium hydroxide to saccharide is from 1.5: 1 to 10: 1, and saccharide is contacted (e.g. reacted) with quaternary ammonium hydroxide at a temperature of from 60 to l00°C.

In one embodiment, the saccharide is glucose, fructose and/or mannose, the molar ratio of quaternary ammonium hydroxide to saccharide is from 1.5:1 to 10:1 , and saccharide is contacted (e.g. reacted) with quaternary ammonium hydroxide at a temperature of from 60 to 100°C.

In one embodiment, the saccharide is glucose, fructose and/or mannose, the quaternary ammonium hydroxide is a tetraalkyl ammonium hydroxide, the molar ratio of quaternary ammonium hydroxide to saccharide is from 1.5:1 to 10:1, and saccharide is contacted (e.g. reacted) with quaternary ammonium hydroxide at a temperature of from 60 to 100°C.

In one embodiment, the saccharide is glucose, fructose and/or mannose, the quaternary ammonium hydroxide is produced from Aliquat 336®, the molar ratio of quaternary ammonium hydroxide to saccharide is from 1.5:1 to 10: 1 , and saccharide is contacted (e.g. reacted) with quaternary ammonium hydroxide at a temperature of from 60 to 100°C.

In one embodiment, the saccharide is glucose, fructose and/or mannose, the quaternary ammonium hydroxide is a benzylalkylammonium hydroxide, the molar ratio of quaternary ammonium hydroxide to saccharide is from 1.5:1 to 10:1, and saccharide is contacted (e.g. reacted) with quaternary ammonium hydroxide at a temperature of from 60 to 100°C.

In one embodiment, the saccharide is glucose, fructose and/or mannose, and the quaternary ammonium hydroxide has a water solubility of at least lOg/L at 30°C.

In one embodiment, the saccharide is glucose, the quaternary ammonium hydroxide is tetramethylammonium hydroxide, tetraethylammonium hydroxide, tetrapropylanunonium hydroxide, tetrabutylammonium hydroxide, tetrapentylammonium hydroxide, tetrahexylammonium hydroxide or benzyltrimethylammonium hydroxide, the molar ratio of quaternary ammonium hydroxide to saccharide is from 1.5:1 to 5: 1, and saccharide is contacted (e.g. reacted) with quaternary ammonium hydroxide at a temperature of from 60 to 100°C.

In one embodiment, the saccharide is glucose, the quaternary ammonium hydroxide is tetramethylammonium hydroxide, tetraethylammonium hydroxide, tetrapropylammonium hydroxide, tetrabutylammonium hydroxide, tetrapentylammonium hydroxide, tetrahexylammonium hydroxide or benzyltrimethylammonium hydroxide, the molar ratio of quaternary ammonium hydroxide to saccharide is from 1.5:1 to 2.5: 1, and saccharide is contacted (e.g. reacted) with quaternary ammonium hydroxide at a temperature of from 60 to 100°C.

The process of the present invention may be carried but in a batch, semi- continuous or continuous process.

The quaternary ammonium salt of lactic acid may be converted into lactic acid, and the present invention further provides a process for the preparation of lactic acid, which comprises producing a quaternary ammonium salt of lactic acid by a process according to the invention, and converting the quaternary ammonium salt of lactic acid into lactic acid. For example, lactic acid may be obtained by reaction of the quaternary ammonium salt with an acid such as hydrochloric acid or sulphuric acid. Lactic acid may be separated from other materials, for example by extraction into the organic phase of a biphasic organic:aqueous mixture and/or by distillation.

The quaternary ammonium salt may also be converted into an ester of lactic acid, for example by converting the quaternary ammonium salt into lactic acid, and reacting the lactic acid with an alcohol. Thus, the present invention further provides a process for the preparation of an ester of lactic acid, which comprises producing a quaternary ammonium salt of lactic acid by a process according to the invention, and converting the quaternary ammonium salt of lactic acid into the ester of lactic acid. The ester of lactic acid may be separated from other materials, for example by distillation.

The present invention also provides a process for the production of lactic acid oligomer, comprising producing a quaternary ammonium salt of lactic acid by a process according to the invention, and converting the quaternary ammonium salt of lactic acid into lactic acid oligomer.

The quaternary ammonium salt of lactic acid may also be reacted to form lactide, a cyclic dimer of lactic acid that is itself useful in the production of polylactic acid. The invention therefore further provides a process for the production of lactide, comprising producing a quaternary ammonium salt of lactic acid by a process according to the invention, and converting the quaternary ammonium salt of lactic acid into lactide. For example, the quaternary ammonium salt of lactic acid may be converted into lactic acid or an ester of lactic acid, and then converted into lactic acid oligomer (also known as a pre- polymer or oligomer of lactic acid), which is contacted with a transesterification catalyst to produce lactide. There are three forms of lactide, S,S-lactide (also known as L-lactide), R,R-lactide (also known as D-lactide), and R,S-lactide (also known as meso-lactide). Racemic and meso-lactide may be separated by standard separation techniques, for example by distillation, solvent extraction, or crystallisation.

Lactide may be polymerised to form polylactic acid. The invention therefore further provides a process for the production of polylactic acid, comprising producing lactide by a process according to the invention, and polymerising the lactide to form polyiactic acid. This polymerisation may be carried out by contacting lactide with a catalyst.

In another aspect, the present invention provides a quaternary ammonium salt of lactic acid and a water-soluble quaternary ammonium hydroxide.

The following example illustrates the invention.

Example 1 : Production of lactate using water-soluble quaternary ammonium hydroxides General procedure

60 mmol (3 eq.) of the relevant quaternary ammonium hydroxide (see Table 1 below) was added to either a 100 ml or 250 ml 3-necked round-bottom flask. The base solution was heated to an internal temperature of 80°C (monitored with a thermocouple placed inside the reaction mixture) and 20 ml of an aqueous 1 M glucose solution (20 mmol) was added using a syringe pump over 2 hours (flow rate = 10 rmVh). The mixture was allowed to cool for 30 minutes (whilst stirring). The mixture was then diluted to 100 ml using a volumetric flask and shaken to homogenise. A 1 ml sample was diluted with 4 ml HPLC water, approximately 1 g Amberlite® 120 resin was added and the mixture was shaken until the pH<7. The sample was then analysed by HPLC and the yield of quaternary ammonium lactate calculated. The procedure was carried out three times for each quaternary ammonium hydroxide, except in the case of PentjNOH and Hex₄NOH, which were carried out only once.

The general procedure outlined above was also carried out using 4.45 g (60 mmol) of Ca(OH)₂ in the following amount of water: a) 20 ml, b) 50 ml, c) 80 ml, instead of quaternary ammonium hydroxide. The procedure was carried out three times for Ca(OH)₂ at each dilution.

The results are shown in Table 1 below.

Table 1 - Quaternary ammonium hydroxide and calcium hydroxide base comparison (Reaction conditions: 1.0M glucose added to base at 80°C over 2 h)

It is clearly evident that yields of lactate are significantly lower with Ca(OH)2 than with quaternary ammonium hydroxides.

Claims

1. A process for the production of a quaternary ammonium salt of lactic acid, comprising contacting at least one saccharide with at least one water-soluble quaternary ammonium hydroxide.

2. A process as claimed in claim 1, wherein said saccharide is monosaccharide.

3. A process as claimed in claim 2, wherein said monosaccharide is selected from the group consisting of glucose, fructose and mannose.

4. A process as claimed in any one of claims 1 to 3, wherein said quaternary ammonium hydroxide comprises from 4 to 40 carbon atoms.

5. A process as claimed in any one of claims 1 to 4, wherein said quaternary ammonium hydroxide is a tetraalkylammonium hydroxide.

6. A process as claimed in claim 5, wherein said tetraalkylammonium hydroxide is tetramethylammonium hydroxide, tetraethylammonium hydroxide or

tetrabutyl ammonium hydroxide.

7. A process as claimed in any one of claims 1 to 4, wherein said quaternary ammonium hydroxide includes a benzyl group.

8. A process as claimed in claim 7, wherein said quaternary ammonium hydroxide is benzyltrimethylammonium hydroxide.

9. A process as claimed in any one of claims 1 to 8, wherein said quaternary ammonium hydroxide has a water solubility of at least lg/L at 30°C.

10. A process as claimed in any one of claims 1 to 9, wherein said saccharide is contacted with quaternary ammonium hydroxide at a temperature of from 20 to 120°C.

1 1. A process as claimed in claim 10, wherein said saccharide is contacted with quaternary ammonium hydroxide at a temperature of from 60 to 100°C.

12. A process as claimed in any one of claims 1 to 1 1, wherein the molar ratio of quaternary ammonium hydroxide to saccharide, calculated as monosaccharide, is from 1.5: 1 to 2.5: 1.

13. A process for the production of lactic acid, comprising producing a quaternary ammonium salt of lactic acid by a process according to any one of claims 1 to 12, and converting said quaternary ammonium salt of lactic acid into lactic acid.

14. A process for the production of an ester of lactic acid, comprising producing a quaternary ammonium salt of lactic acid by a process according to any one of claims 1 to 12, and converting said quaternary ammonium salt of l actic acid into said ester of lactic acid.

15. A process for the production oflactic acid oligomer, comprising producing a quaternary ammonium salt of lactic acid by a process according to any one of claims 1 to 12, and converting said quaternary ammonium salt oflactic acid into lactic acid oligomer.

16. A process for the production of lactide, comprising producing a quaternary ammonium salt oflactic acid by a process according to any one of claims 1 to 12, and converting said quaternary ammonium salt of lactic acid into lactide.

17. A process for the production of polylactic acid, comprising producing lactide by a process according to claim 16, and polymerising the lactide to form polylactic acid.

18. A quaternary ammonium salt of lactic acid and a water-soluble quaternary ammonium hydroxide.