WO2025174738A1 - Process of production of pentamethylene-1, 5-diamine - Google Patents

Abstract

A method is provided for the synthesis of pentane-1,5-diamine from L-lysine through thermal decarboxylation in the presence of an inert solid to form a carbamate precipitate from decarboxylation of L-lysine and the use of carbon dioxide released from the L-lysine.

Description

PROCESS OF PRODUCTION OF PENTAMETHYLENE- 1, 5-DIAMINE

FIELD OF THE INVENTION

The present invention relates to a method of production of 1, 5 -pentamethylene diamine (PMDA), commonly known as cadaverine, from L-lysine by the process of thermal decarboxylation.

BACKGROUND OF THE INVENTION

Polyamides (PA) are well-known polymers with important applications in the automobile, sports and lifestyle apparel industries. Diamines are an important raw material monomer component for the production of such polyamides. Currently, 6.6 million tons of petroleum-based polyamides are globally produced each year, among which the synthesized petrochemical product hexane- 1, 6-diamine or hexamethylenediamine (HMDA) is used primarily as a monomer.

Petrochemical-based polyamides are however known for contributing to the greenhouse effect, resulting in serious environmental issues. Therefore, research on biobased polyamides has gained more pace. Cadaverine, also known as 1, 5- pentamethylene diamine (PMDA), is an organic linear aliphatic diamine with five carbons, and a homologue of putrescine. Cadaverine, first discovered in a decaying corpse, is mostly formed during putrefaction of animal tissues, and in particular, is formed by the bacterial decarboxylation of lysine, i.e., during protein hydrolysis. PMDA other than being a natural-occurring polyamine fortunately also provides exceptional characteristics to polyamides prepared therefrom, such as high tensile strength, high melting points and resistance against organic solvents, as well as reduced water absorption and excellent dimensional stability. PMDA has consequently attracted significant interest as a possible biobased alternative to the dominant hexamethylenediamine monomer for the production of desirable bio-polyamides with reduced greenhouse gas impact as well as beneficial properties and performance attributes in a variety of application contexts.

Conventionally known methods of PMDA production include the catalyzed decarboxylation of a-amino acids as well as biosynthetic methods such as de novo biosynthesis from different carbon sources. Known methods for the catalyzed decarboxylation of a-amino acids are however low yielding and overly expensive, and in general, there is an unmet need of a commercially practical and economical method for producing an acceptable monomer grade purity PMDA product. Ideally, such a method would utilize the self-released carbon dioxide in the decarboxylation process of an a-amino acid such as L-lysine to reduce energy consumption as well as reduce the carbon footprint associated with the production of PMDA and of polyamides based thereon.

SUMMARY OF THE INVENTION

This section provides a general summary of the present invention, and is not a comprehensive disclosure of the full scope of all of its features.

In consideration of the above-mentioned unmet need(s), the present invention provides a PMDA production method that in one aspect improves the decarboxylation yield as well as the quality of PMDA produced from L-lysine. In another aspect, the present invention provides a PMDA production method via the decarboxylation of L- lysine which makes use of the carbon dioxide released through decarboxylation, and which would otherwise comprise a waste or require the investment of still other resources to productively use in some fashion.

A further object of the present invention is to provide a PMDA production method that provides sustainable economic benefits. Another objective of the present invention is to provide a PMDA production method that provides for easy separation of the final product from the reaction mixture.

More particularly, the method of the present invention involves carrying out the thermal decarboxylation at an elevated temperature of L-lysine in a reaction vessel comprising an inert solid and a non-polar solvent or solvent mixture (as well as the L- lysine), to provide a decarboxylation product mixture comprising a precipitate of pentane- 1, 5-diamine carbamate.

Thereafter, the decarboxylation product mixture is filtered and a retentate is obtained comprising inert solid and pentane- 1, 5-diamine carbamate precipitate. The retentate is then combined with heating with a non-polar solvent or solvent mixture in which PMDA is readily dissolved but from which PMDA is also readily separated, to both liberate CO2 from the pentane-1, 5-diamine carbamate and provide a solution of pentane- 1, 5-diamine in the solvent or solvent mixture in mixture with the inert solid (thus providing a filterable mixture in which most preferably the inert solid substantially alone remains in solid form). This solution mixture is then filtered in a second filtration step to remove the inert solid and provide a filtrate comprising pentane- 1, 5 -diamine solubilized in the solvent or solvent mixture. The obtained filtrate is further subjected to a separation step in order to separate the pentane- 1, 5 -diamine from the solvent or solvent mixture.

In certain embodiments, the L- lysine is sourced from plant feed via fermentation broth obtained from the fermentation of dextrose.

In certain embodiments, the non-polar solvent or solvent mixture employed for the formation of the PMDA carbamate precipitate comprises an aldehyde or ketone, such as methyl ethyl ketone or methyl isobutyl ketone.

In certain embodiments, the non-polar solvent or solvent mixture employed for forming a PMDA solution with the liberation of carbon dioxide from the PMDA carbamate may comprise a non-polar solvent and water, for example, an alcohol and water.

In certain embodiments, the method includes the step of washing at least a portion of the inert solid with water before recycling at least a portion of the inert solid to the reaction vessel for reuse in the method.

In certain embodiments, the method includes addition of CO2 in the reactor after the application of heat to cause a thermal decarboxylation of the L- lysine, for achieving higher yields of PMDA as a precipitate in the product mixture.

In certain embodiments, the inert solid may be selected from the group consisting of alumina, silica, sand, glass beads and silicon carbide, with glass beads being preferred.

In certain embodiments, the method employed for separation of PMDA from the non-polar solvent or solvent mixture comprises a distillation step.

In certain embodiments, at least the initial step for the production of PMDA carbamate may occur under a nitrogen or nitrogen-enriched atmosphere to remove air in a headspace of the reactor.

In certain embodiments, at least the initial step for the production of PMDA carbamates takes place under a nitrogen or nitrogen-enriched atmosphere at a temperature of not more than 175 degree Celsius over the span of not more than 2 hours.

In certain embodiments, at least a portion of the inert solid following the second filtering step is water-washed, dried and then recycled to the reactor to eliminate wastage. In still other embodiments, salts washed from the at least a portion of inert solids following the second filtration step are recycled to the fermentation step for producing additional L-lysine from dextrose.

In order to further appreciate the present invention in each of its respects and in the various embodiments as just summarized, reference may be had to the following detailed description, items, examples and claims and to the appended drawings, which collectively describe the present invention as claimed more particularly below.

BRIEF DESCRIPTION OF ACCOMPANYING DRAWINGS

A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings or figures, of which:

Figure 1 schematically illustrates the method of the present invention in one embodiment in relation to an associated dextrose fermentation to produce the L-lysine feedstock.

Figure 2 illustrates a proposed, non-limiting reaction mechanism/reaction pathway for the formation of PMDA from L-lysine in the manner of the present invention.

Figure 3 depicts the phases observed in the transformation of L-lysine to PMDA carbamate in the presence of an inert solid in the form of glass beads and in a nonpolar solvent medium (such as MEK) in a CSTR.

Figure 4 illustrates a short path distillation process for recovery of the desired PMDA product.

DETAILED DESCRIPTION OF THE INVENTION

The embodiments herein and the various features and advantageous details thereof are explained more fully with reference to the non-limiting embodiments that are illustrated in the accompanying drawings and the following description.

Turning now to Figure 1, a process embodiment 10 of the present invention is schematically shown, proceeding from a clarified and dewatered but otherwise unrefined L-lysine feedstock 12 which has been generated by a fermentation of dextrose (14) such as presently known and commercially practiced, for example, to provide a erode L-lysine fermentation broth (16) that is then filtered (18) to remove biomass and then dewatered (20) to provide the aforementioned L-lysine feedstock 12. Preferably, sufficient water is removed to provide an L-lysine feedstock 12 that contains about 20% of water or less.

The L-lysine feedstock 12 is fed into a reactor 22 as preferably a dried solid (see Fig. 3) along with an inert solid 24 whose role in the process 10 is to provide a wettable surface on which lysine solubilized in a non-polar solvent or solvent mixture 26 (also added to the reactor 22) can deposit and be heated to release carbon dioxide and on which a PMDA carbamate product can subsequently be formed at least in part from the released carbon dioxide, as well as from supplemental carbon dioxide optionally but preferably supplied to the reactor 22 (not shown) for promoting higher yields from the lysine feedstock 12 of PMDA carbamate all according to a presumed, non- limiting reaction pathway shown in Figure 2. The decarboxylation reaction and subsequent formation of PMDA carbamate are preferably conducted in a nitrogen-enriched atmosphere or substantially under a nitrogen blanket as suggested by the nitrogen feed stream 28 to reactor 22.

The contents 30 of reactor 22 following the conversion of the lysine feedstock 12 to PMDA carbamate are then filtered in a first filtration step 32, to provide a retentate comprised of the inert solid and preferably substantially all of the PMDA carbamate and a filtrate comprised of the non-polar solvent or solvent mixture, which can be recycled back in stream 34 to the reactor 22.

The retentate portion 36 is combined with heating with a non-polar solvent or solvent mixture 38 in which PMDA is readily dissolved but from which PMDA is also readily separated, to both liberate CO2 from the pentane- 1, 5-diamine (PMDA) carbamate in the retentate 36 (the CO2 stream overhead is not shown) and provide a solution of pentane- 1, 5-diamine in the solvent or solvent mixture in mixture with the inert solid in the retentate 36.

This mixture of inert solid and PMDA solution is then provided as stream 40 to a second filtration step 42, wherein the inert solids are recovered for recycling to the reactor 22 in stream 44 following a water wash step 46 to remove residual salts 48 from the initial fermentation broth 16. These residual salts can be recycled back to the dextrose fermentation 14, while the water-washed inert solids can be returned to the reactor 22 via stream 50 (as the supply of inert solid 24).

The filtrate 52 from the second filtration step 42, comprised of the desired PMDA product in solution with the non-polar solvent or solvent mixture supplied in stream 38, is then forwarded to a separation step 54 - preferably involving a simple distillation as suggested by the short path distillation shown in Figure 4 - for recovering a PMDA product 56 that is preferably already of a monomer grade purity but which can be further refined and purified as may be desired, using one or more well-known methods. The non-polar solvent or solvent mixture from which the PMDA has been separated can be recycled and comprise the solvent or solvent mixture 38 used to wash the retentate 36 from the first filtration step 32.

Suitable inert solids 24 are preferably readily filterable, efficiently convey heat for the thermal decarboxylation of the lysine feedstock 12 and for the release of carbon dioxide from the PMDA carbonate preliminary to the second filtration step 42 and provide a clean, smooth surface that is readily wetted by the lysine in solution for forming the PMDA carbonate in the reactor 22. Exemplary inert solids would be selected from the group consisting of alumina, silica, sand, glass beads and silicon carbide, with glass beads being preferred.

The nonpolar solvent or solvent mixture 26 used in the reactor 22 is preferably selected from the aldehydes and ketones, for example, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone or acetone, with methyl ethyl ketone being exemplary, while the nonpolar solvent or solvent mixture 38 used for forming a PMDA solution that is recovered from the second filtration step 42 as stream 52 is preferably comprised of an alcohol or an alcohol/water mixture, for example, ethanol or ethanol with water.

A temperature of from about 150 degrees (Celsius) to preferably not more than about 200 deg. C. maintained for from about 2 hours and preferably not more than about 5 hours with stirring will be employed in reactor 22.

EXAMPLES

Example 1 - PMDA synthesis with CO2 and inert solid

25 grams of Sigma Aldrich lysine (>98% purity), 90 grams of glass beads (having diameters in the range of 150-212 pm) and 500mL of methyl ethyl ketone were loaded into a IL Parr reactor. The reactor was purged with nitrogen 3 times to remove the air in the headspace. After purging, the reactor was pressurized with 200 psi nitrogen, heated to 180°C at a stirring speed of 940 RPM, and the temperature maintained for 2 hours. After this time, heating of the reactor was ended, and the reactor was cooled to room temperature. During the cooling process, when the temperature dropped to around 100°C, some of the nitrogen pressure was released and an additional 200 psi of carbon dioxide was supplied to the reactor. The PMDA carbamate solid formed was then filtered out from the mixture, and analyzed by ^]H NMR, ¹³C NMR and UPLC. The MEK organic layer was washed from the solid glass beads by decanting and was then analyzed by UPLC. In order to convert the PMDA carbamate solid into PMDA, the solid was first dissolved in ethanol/water mixture and heated, and then purified through short path distillation. The generated PMDA was analyzed by 1H NMR, ¹³C NMR and UPLC with 82% PMDA yield (with 94% distillation recovery with ethanol/water).

Example 2

4.1 g of 35-60 mesh silica gel, 5.3 g of lysine (Aldrich) and 1.3 g of isophorone were added to 57.2 g of methyl ethyl ketone in a 300 mL Hastelloy Parr reactor. The reactor with contents was then purged with nitrogen three times, and then was pressurized with nitrogen to 200 psig. After maintaining the reactant mixture at a temperature of 160°C for 1 hour with continuous stirring at 650 rpm, carbon dioxide was then added to a combined pressure of 450 psig and the reaction allowed to proceed for another 0.5 hours. The system was then cooled to ambient/room temperature, and the reactor contents processed in the same manner as in Example 1, with 75% PMDA yield.

Comparative Example 1. PMDA synthesis without CQ2, without inert solid

5.3 g of lysine (20- 40 mesh from lysine plant) and 1.3 g of isophorone were added to 56.1 g of methyl ethyl ketone (MEK) in a 300 mL Hastelloy Parr reactor. The system was purged with nitrogen three times, and then nitrogen was added to 200 psig. The reaction mixture was heated to and maintained at a temperature of 170°C for 1.5 hours with stirring at 650 rpm. The reactor was then cooled down to ambient/room temperature, and a product mixture including a viscous, sticky mass resulted. The mass was analyzed and indicated PMDA was present, and produced in a yield of 54%.

Claims

E CLAIM:

1. A method for production of pentane- 1 , 5-diamine from L-lysine comprising: a. preparing a reaction mixture comprising L-lysine or an L-lysine salt, an inert solid and a non-polar, aldehyde or ketone solvent at an elevated temperature; b. holding the reaction mixture at the elevated temperature for a time sufficient to cause at least some decarboxylation of the L-lysine and form a product mixture comprising a precipitate of pentane- 1, 5 -diamine carbamate and pentane-1, 5 -diamine; c. filtering the product mixture to provide a retentate comprising the inert solid and pentane-1, 5-diamine carbamate precipitate; d. heating the retentate with a solvent or solvent mixture to obtain a solution mixture comprising pentane-1, 5-diamine solubilized in the solvent or solvent mixture and inert solid dissolve thereby liberating carbon dioxide.

2. The method of claim 1 , wherein the solution mixture from step d is filtered to remove the inert solid leaving a filtrate comprising pentane-1, 5-diamine solubilized in the solvent or solvent mixture.

3. The method of claim 2, wherein the pentane-1, 5-diamine is filtered out from the solvent or solvent mixture in the filtrate.

4. The method of claim 1, wherein one or more L-lysine salts is produced from a fermentation broth from fermentation of dextrose.

5. The method of claims 1 -4, wherein at least a portion of the filtrate, comprising the non-polar, aldehyde or ketone solvent, obtained from step c is recycled to the reaction vessel.

6. The method of claim 2, wherein at least a portion of the filtered inert solids are recycled to the reaction vessel.

7. The method of claims 2 and 6, wherein at least a portion of inert solids is water- washed prior to recycling the same to the reaction vessel.

8. The method of claim 7, wherein salts washed from the at least a portion of inert solids is recycled for the dextrose fermentation to produce L-lysine.

9. The method of any of claims 1-8, wherein the solvent or solvent mixture comprises an alcohol.

10. The method of claim 9, wherein the solvent or solvent mixture is selected from ethanol or methanol.

11. The method of claim 10, wherein the solvent or solvent mixture consists of ethanol or a combination of ethanol and water.

12. The method of claim 3, further comprising a step of distilling the filtrate.

13. The method of claim 12, wherein at least a portion of the solvent or solvent mixture obtained from step d is recycled for combining with the retentate with heating.

14. The method of any of claims 1-13, wherein the decarboxylation of step b takes place under a nitrogen or nitrogen-enriched atmosphere, at a temperature of utmost 175 degree Celsius for 2 hours.

15. The method of any of claims 1-14, wherein the inert solid is selected from the group consisting of alumina, sand, silica, glass beads and silicon carbide.

16. The method of claim 15, wherein the inert solid is glass beads.

17. The method of any of claims 1-16, wherein the non-polar, aldehyde or ketone solvent is methyl ethyl ketone or methyl isobutyl ketone.

18. The method of claim 17, wherein the non-polar, aldehyde or ketone solvent is methyl ethyl ketone.

19. The method of any of claims 1-18, further comprising the step of adding carbon dioxide to the reaction vessel after heating the reaction mixture to the elevated temperature to form pentane- 1, 5-diamine carbamate.