Method for the production of ester compounds

Abstract

The current invention relates to a method for the large-scale production of an ester compound, said method comprises adding a volume of a first acid to a mixture of one 5 or more alcohols and one or more catalysts, wherein the one or more alcohols are at least 50% of said alcohol-catalyst mixture and wherein during the addition of said first acid, wherein the resulting reaction mixture is at least 10 L and wherein said reaction mixture is stirred and subjected to an ultrasonic wave. 10

Description

[0001] METHOD FOR THE PRODUCTION OF ESTER COMPOUNDS

[0002] FIELD OF THE INVENTION

[0003] The present invention relates to a method for the large-scale production of an ester compound.

[0004] BACKGROUND

[0005] Esters are common in organic chemistry and biological materials, and are known in many applications. Ester compounds are versatile with wide-ranging applications in industries such as food, pharmaceuticals, cosmetics, and materials science. They are commonly synthesized through esterification reactions, wherein an alcohol reacts with an acid in the presence of a catalyst. Industrial style production of esters are known under the form of Fischer esterification which is a thermodynamically controlled process characterized by its slowness and the amount of energy it requires to heat the reaction. Because of the long duration of the Fischer method and the large energy quantities requires to heat the reaction for a long time, there is ongoing research aimed at enhancing efficiency, reducing reaction time and reducing energy consumption.

[0006] Such a new method to produce ester compounds is known from US9393544. US9393544 describes a method of preparing an ester compound, wherein a carboxylic acid is added to a mixture of glycerol and acetone in the presence of a sulfuric acid catalyst, and wherein an ultrasonic wave is applied to induce an esterification reaction.

[0007] The method described in US9393544, particularly utilizing power densities of 70-500 W / cm2in conjunction with ultrasonic waves for ester synthesis, presents notable challenges when one would consider transitioning to industrial-scale applications. Industrial-scale ultrasonic equipment capable of delivering the specified power densities may not be readily available on the market. Custom-designed or specialized equipment might be necessary, adding complexity and cost to the production process. Additionally, the consumption of large quantities of energy and resources contributes to the carbon footprint of the process.

[0008] The method disclosed in US9393544 method primarily focuses on laboratory-scale experiments, with examples often involving small volumes. Transitioning to industrial-scale production would require significant adjustments to accommodate larger reaction volumes while maintaining efficiency and yield.

[0009] The present invention aims to resolve at least some of the problems and disadvantages mentioned above.

[0010] SUMMARY OF THE INVENTION

[0011] The invention pertains to a method for the large-scale production of an ester compound according to claim 1. Said method is suitable to apply at a large industrial scale and is advantageous in regards to energy consumption, reduction of reaction time, yield and scalability.

[0012] DETAILED DESCRIPTION OF THE INVENTION

[0013] The present invention concerns a method for the large-scale production of an ester compound wherein an ultrasonic wave is applied. The present invention is intended to increase the yield of the esterification reaction by applying an ultrasonic wave during said reaction. The process is energetically favorable, and faster than thus far known and conventional processes in the art, thereby drastically reducing the cost. The process also allows for the large scale production of esters.

[0014] Unless otherwise defined, all terms used in disclosing the invention, including technical and scientific terms, have the meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. By means of further guidance, term definitions are included to better appreciate the teaching of the present invention.

[0015] As used herein, the following terms have the following meanings:

[0016] "A", "an", and "the" as used herein refers to both singular and plural referents unless the context clearly dictates otherwise. By way of example, "a compartment" refers to one or more than one compartment.

[0017] "Comprise", "comprising", and "comprises" and "comprised of" as used herein are synonymous with "include", "including", "includes" or "contain", "containing", "contains" and are inclusive or open-ended terms that specifies the presence of what follows e.g. component and do not exclude or preclude the presence of additional, non-recited components, features, element, members, steps, known in the art or disclosed therein.

[0018] Furthermore, the terms first, second, third and the like in the description and in the claims, are used for distinguishing between similar elements and not necessarily for describing a sequential or chronological order, unless specified. It is to be understood that the terms so used are interchangeable under appropriate circumstances and that the embodiments of the invention described herein are capable of operation in other sequences than described or illustrated herein.

[0019] The recitation of numerical ranges by endpoints includes all numbers and fractions subsumed within that range, as well as the recited endpoints.

[0020] The expression "% by weight", "weight percent", "%wt" or "wt%", here and throughout the description unless otherwise defined, refers to the relative weight of the respective component based on the overall weight of the formulation.

[0021] The expression "% by volume", "volume percent", or"% v / v", here and throughout the description unless otherwise defined, refers to the relative volume of the respective component based on the overall volume of the formulation.

[0022] Whereas the terms "one or more" or "at least one", such as one or more or at least one member(s) of a group of members, is clear per se, by means of further exemplification, the term encompasses inter alia a reference to any one of said members, or to any two or more of said members, such as, e.g., any >3, >4, >5, >6 or >7 etc. of said members, and up to all said members.

[0023] Unless otherwise defined, all terms used in disclosing the invention, including technical and scientific terms, have the meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. By means of further guidance, definitions for the terms used in the description are included to better appreciate the teaching of the present invention. The terms or definitions used herein are provided solely to aid in the understanding of the invention.

[0024] Reference throughout this specification to "one embodiment" or "an embodiment" means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrases "in one embodiment" or "in an embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment, but may. Furthermore, the particular features, structures or characteristics may be combined in any suitable manner, as would be apparent to a person skilled in the art from this disclosure, in one or more embodiments. Furthermore, while some embodiments described herein include some but not other features included in other embodiments, combinations of features of different embodiments are meant to be within the scope of the invention, and form different embodiments, as would be understood by those in the art. For example, in the following claims, any of the claimed embodiments can be used in any combination.

[0025] The current invention describes a method for the large-scale production of an ester compound.

[0026] In an embodiment, said method comprises the step of mixing one or more alcohols, one or more acids and a catalyst. Preferably, either the one or more alcohols or the one or more acids are first mixed with the catalyst to obtain an alcohol-catalyst mixture or an acid-catalyst mixture, wherein in a second step either the one or more acids or the one or more acids are added to the alcohol-catalyst mixture or the acidcatalyst mixture, respectively.

[0027] In an embodiment said method comprises adding a volume of a first acid to a mixture of one or more alcohols and one or more catalysts, wherein the one or more alcohols are at least 50% of said alcohol-catalyst mixture, wherein the resulting reaction mixture is at least 10 L and wherein said reaction mixture is stirred and subjected to an ultrasonic wave.

[0028] In another embodiment said method comprises adding a volume of one or more alcohols to a mixture of one or more acids and one or more catalysts, wherein the one or more acids are at least 50% of said acid-catalyst mixture, wherein the resulting reaction mixture is at least 10 L and wherein said reaction mixture is stirred and subjected to an ultrasonic wave.

[0029] In an embodiment the alcohol-catalyst mixture at the beginning comprises at least 50% by volume alcohol, more preferably at least 60% alcohol, more preferably 65% alcohol, more preferably 70%. In an embodiment this percentage of alcohol is 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%. In an embodiment this percentage is a value between 50 and 100%. In an embodiment this percentage is between 50 and 95%. In an embodiment this percentage is between 50 and 90%. In an embodiment this percentage is between 50 and 85%. In an embodiment this percentage is between 50 and 80%. In an embodiment this percentage is between 50-75%. In an embodiment this percentage is between 50-70%. In an embodiment this percentage is between 50-60%. In an embodiment this percentage is between 60-70%. In an embodiment this percentage is between In an embodiment this percentage is between 75-100%. In an embodiment this percentage is between 75-85%. In an embodiment this percentage is between 85-95%. In an embodiment this percentage is between 85% and 90%. In an embodiment this percentage is between 50 and 60%. In an embodiment this percentage is between 60 and 70%. In an embodiment this percentage is between 70 and 80%. In an embodiment this percentage is between 80 and 90%. In an embodiment this percentage is between 90 and 100%.

[0030] In an embodiment the volume is at least 10 L, 20 L, 30 L, 40 L, 50 L, 60 L, 70 L, 80 L, 90 L, 100 L, 110 L, 120 L, 130 L, 140 L, 150 L, 160 L, 170 L, 180 L, 190 L, 200 L, 210 L, 220 L, 230 L, 240 L, 250 L, 260 L, 270 L, 280 L, 290 L, 300 L, 310 L, 320 L, 330 L, 340 L, 350 L, 360 L, 370 L, 380 L, 390 L, 400 L, 410 L, 420 L, 430 L, 440 L, 450 L, 460 L, 470 L, 480 L, 490 L, 500 L, 510 L, 520 L, 530 L, 540 L, 550 L, 560 L, 570 L, 580 L, 590 L, 600 L, 700 L, 800 L, 900 L, 1000 L, 1500 L, 2000 L, 2500 L, 3000 L, 3500 L, 4000 L, 5000 L. In an embodiment the volume is in a range between 10 L and 5000 L, preferably between 100 L and 5000 L, more preferably between 500 L and 5000 L, even more preferably between 1000 L and 5000 Lor even between 2500 L and 5000 L.

[0031] In an embodiment the one or more alcohols are at least 90% of said alcohol-catalyst mixture. In an embodiment this percentage is 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%. In an embodiment this percentage is a range between 90-99%.

[0032] In an embodiment the first acid is added incrementally, step-wise or gradually to said alcohol and catalyst reaction mixture. In an embodiment the total amount of first acid is added in two separate steps. In an embodiment the total amount of acid is added in is 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, steps. In an embodiment, the volumes added in each step differ or are the same. In an embodiment, the amount of the first acid added in each step will increase. In another embodiment, the amount of the first acid added in each step will decrease. In an embodiment, the timeframe between each step is at least 1 minute, at least 2 minutes, at least 3 minutes, at least 4 minutes, at least 5 minutes, at least 6 minutes, at least 7 minutes, at least 8 minutes, at least 9 minutes, at least 10 minutes, at least 15 minutes, at least 20 minutes. In an embodiment, said timeframe between each acid addition is between 30 seconds and 60 minutes, more preferably between 1 minute and 45 minutes, between 1 minute and 30 minutes, between 1 minute and 20 minutes, between 1 and 15 minutes, between 1 and 10 minutes, between 1 and 5 min.

[0033] In an embodiment, the first acid is added to the reaction mixture at a rate of between 0.01 ml / sec to 1 ml / min. In an embodiment the first acid is added to the reaction mixture at a rate of 1 ml / min to 100 ml / min. In an embodiment this rate is in a range between 100 ml / min to 500-1000 ml / min. In an embodiment this rate is in a range between ll / min to 101 / min. In an embodiment this rate is in a range between 101 / min to 1001 / min. In an embodiment this rate is in a range between 101 / min to 751 / min. In an embodiment this rate is in a range between 101 / min to 501 / min. By implementing a controlled addition rate of carboxylic acid, the invention ensures precise regulation of the reaction kinetics and equilibrium dynamics. Unlike traditional methods where acid is introduced rapidly, potentially leading to non-uniform mixing and inefficient utilization of catalyst, the approach of the invention allows for gradual and uniform distribution of acid throughout the reaction mixture. This controlled addition rate promotes optimal interaction between reactants and catalyst, facilitating efficient protonation of the carboxylic acid and subsequent ester formation.

[0034] This incremental or stepwise addition of the said first acid, means that there is a higher ratio of available catalyst to enhance the reaction between said first acid and the alcohol in the bulk phase. This incremental addition also means the amount of free alcohol in the bulk phase of the reaction that can absorb the free water that is formed by the reaction between alcohol and said first acid. This absorption is thus possible because the ratio between free alcohol and free acid is large enough for free water to get absorbed by free alcohol. The presence of excess alcohol can help minimize the concentration of water in the reaction mixture. By keeping the water dissolved and evenly distributed within the alcohol, it reduces the chance of water negatively impacting the reaction equilibrium.

[0035] In the reverse case, incremental addition of alcohol to an acid-catalyst mixture means that there is a higher ratio of available catalyst to enhance the reaction between said one or more alcohols and the acid in the bulk phase. Furthermore, the incremental addition can facilitate the management of water formed during the reaction. By controlling how much alcohol is available at any given time, the reaction can be maintained in a state where water removal (either by physical means or by chemical methods like using a water-absorbing agent) is more effective, thus driving the reaction towards ester formation.

[0036] In an embodiment the amount of free water in the reaction is less than 20% (by v / v), more preferably less than 15%, more preferably less than 10%, more preferably less than 5%, more preferably less than 1%. In an embodiment the amount of free water is in range between 1 and 20 %, more preferably between 1 and 10%, more preferably between 1 and 5%. The exact amount of free water per reaction will differ according to which ester is being formed. Additionally one wants to limit the amount of free water because water is a byproduct of esterification that typically needs to be removed at the end of the reaction.

[0037] In an embodiment the ratio of the total weight of the alcohol and the added volume of the first acid at the initiation of the esterification reaction is at least 50:1 per minute. In an embodiment this ratio is 49:1, 48:1, 47:1, 46:1, 45:1, 44:1, 43:1, 42:1, 41:1, 40:1, 39:, 38:1, 37:1, 36:1, 35:1, 34:1, 33:1, 32:1, 31:1, 30:1, 29:1, 28:1, 27:1, 26:1, 25:1, 24:1, 23:1, 22:1, 21:1, 20:1, 19:1, 18:1, 17:1, 16:1, 15:1, 14:1, 13:1, 12:1, 11:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1. In an embodiment this ratio is in a range between 50:1 per minute and 10:1 per minute. In an embodiment this ratio is in range between 10:1 per minute and 1:1 per minute.

[0038] In an embodiment the ratio of the molar concentration of the catalyst and the molar concentration of the first acid at the initiation of the esterification reaction is at least 1:1, more preferably at least 2:1. In an embodiment this ratio 3:1 , 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1. In an embodiment this ratio is in a range between 1:1 to 10:1.

[0039] In an esterification reaction, the catalyst to acid ratio plays an important role in determining the efficiency and yield of the reaction. Esters are typically formed through the reaction between an alcohol and an acid in the presence of an acidic catalyst. The catalyst functions to facilitate the reaction by protonating the carbonyl oxygen of the first acid, making it more susceptible to nucleophilic attack by the alcohol. This protonation step lowers the activation energy barrier, thus increasing the rate of ester formation. The ratio of catalyst thus directly influences the concentration of active catalytic species available in the reaction mixture.

[0040] Furthermore, the catalyst-to-acid ratio can affect the equilibrium position of the esterification reaction. According to Le Chatelier's principle, increasing the concentration of one reactant (in this case, the catalyst) will shift the equilibrium towards the formation of products to counteract the change. Therefore, maintaining an optimal ratio of catalyst to acid can drive the equilibrium towards the desired ester product, enhancing the overall yield of the reaction. It's also important to note that excessive amounts of catalyst can sometimes lead to side reactions or degradation of the desired product. Therefore, finding the right balance in the catalyst to acid ratio is crucial to achieving high yields of ester product while minimizing unwanted byproducts, most importantly minimizing water formation.

[0041] By carefully controlling the rate of acid addition, we can maintain an appropriate concentration of catalyst relative to the acid, thus promoting efficient protonation of the carboxylic acid and accelerating the esterification process. This approach addresses a key limitation encountered in conventional esterification methods, where rapid mixing can lead to uneven distribution of reactants and catalyst, resulting in suboptimal reaction conditions and reduced yields.

[0042] In an embodiment the ratio of free alcohol to free acid during the addition of the acid is between 200:1:1 and 1:1, preferably the ratio ranges from between 200:1 and 50:1 at the beginning to between 10:1 and 1:1 at end of the process. Maintaining a higher ratio of free alcohol to free acid helps to drive the esterification reaction towards completion by ensuring that the alcohol is present in excess, thereby promoting higher yields of ester products. In addition, this ratio can enhance the selectivity of the reaction, minimizing the formation of undesired by-products. Thirdly, it can lead to improved reaction kinetics, potentially reducing the time required for the esterification process. Additionally, operating with a higher ratio of free alcohol to free acid may contribute to better control over the reaction conditions, leading to increased reproducibility and consistency in product quality.

[0043] In an embodiment, the total reaction volume comprises:

[0044] between 10 and 80 % (v / v) of one or more alcohols;

[0045] between 0.01 and 10 % (v / v) of one or more catalysts;

[0046] between 10 and 80 % (v / v) of a first acid. In an embodiment the catalyst is present in the alcohol-catalyst mixture in an amount of minimum 0.1 % % by weight. In an embodiment this is percentage of 0.1%, 0.25%, 0.50%, 0.75%, 1% , 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%. In an embodiment the catalyst concentration is in a range of 0.1-10%. In an embodiment this concentration is in a range of 0.1-7.5%. In an embodiment this concentration is in a range of 0.1-5%. In an embodiment this concentration is in a range of 0.1-3%. In an embodiment this concentration is in a range of 0.1 to 2% In an embodiment this concentration is in a range of 0.1 to 1%.

[0047] By ensuring a minimum catalyst concentration of 0.1% (w / v) in the alcohol-catalyst mixture, the invention promotes efficient catalysis of the esterification reaction. The presence of the catalyst facilitates the protonation of the acid, thereby lowering the activation energy barrier and enhancing the rate of ester formation. This controlled catalyst concentration ensures that sufficient catalytic activity is maintained throughout the reaction, leading to improved reaction kinetics and enhanced product yield. Moreover, the optimized catalyst concentration facilitates better control over the reaction parameters, such as temperature and pH, leading to improved reproducibility and scalability of the esterification process. This allows for the method to be applied effectively across a range of reaction scales, from laboratory-scale experiments to industrial production.

[0048] Additionally, the careful regulation of catalyst concentration ensures chemical safety and minimizes the environmental impact of the esterification process. By utilizing the catalyst judiciously, the invention reduces waste generation and resource consumption, aligning with principles of sustainable chemistry and green manufacturing practices

[0049] In an embodiment the alcohol is glycerol. In another embodiment said alcohol is chosen from glycerol, acetone, methanol, ethanol, propanol, isobutanol, ethylene hlyceol, propylene glycol, benzyl alcohol, cyclohexanol, octanol, decanol, hexanol, pentanol, diethylene glycol, trimethylolpropane, or a mixture thereof. In an embodiment this could be any chemical compound that has a hydroxyl group.

[0050] In an embodiment the first acid is chosen from formic acid, acetic acid, propionic acid, butyric acid, valeric acid, caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid, undecylenic acid, lauric acid, tridecyclic acid, myristic acid, pentadecyclic acid, palmitic acid, margaric acid, stearic acid, nonadecylic acid, arachidic acid, or a mixture thereof. The list of acids given herein is provided as an example only and is not intended to be limiting.

[0051] In an embodiment the reaction mixture is stirred using a propeller with a speed of between 100 and 1000 rpm, preferably between 200 and 800 rpm, or even between 300 and 600 rpm. This combination of stirring and ultra sonification facilitates thorough mixing and promotes uniform distribution of reactants and catalyst throughout the reaction medium. The application of ultrasonic waves induces cavitation, generating localized regions of extreme conditions characterized by high temperatures and pressures within the reaction mixture. This controlled cavitation process enhances the efficacy of the esterification reaction by accelerating the formation of ester bonds. This means a shortening of reaction time. Furthermore because of the incremental addition of said first acid to the reaction mixture the amount of free alcohol in the bulk phase of the reaction that can absorb the free water that is formed by the reaction between alcohol and said first acid. This absorption is thus possible because the ratio between free alcohol and free acid is large enough for free water to get absorbed by free alcohol. By stirring the reaction mixture with adequate propeller speed.

[0052] In an embodiment the catalyst added is an acid (different from the first acid), preferably a non-carboxylic acid such as hydrochloric acid or phosphoric acid. Catalysts typically speed up a reaction by reducing the activation energy or changing the reaction mechanism. Other catalysts suited to be used in the context of the current invention include H2SO4, HF, H3PO4, HCI and p-toluene sulfonic acid and Lewis acids. However the catalyst in the method could be any compound with catalytic capabilities suitable for esterification reactions, such as such as scandium triflate. The list of catalysts given herein is provided as an example only and is not intended to be limiting.

[0053] The catalyst can also be a metal catalyst, such as tin, titanium, and zinc, such as dibutyltin oxide, titanium isopropoxide, and zinc acetate, or a solid acid catalyst such as zeolites, and silica-supported acids.

[0054] The reaction mixture is subjected to an ultrasonic wave. The application of ultrasonic waves have been found to induce cavitation, generating localized regions of extreme conditions characterized by high temperatures and pressures within the reaction mixture. This controlled cavitation process enhances the efficacy of the esterification reaction by accelerating the formation of ester bonds. Moreover, the cavitation phenomenon induces vigorous turbulence and liquid circulation throughout the reactor, effectively intensifying chemical reactions. The energy released during cavitation, occurring at numerous sites simultaneously, generates conditions conducive to the acceleration of chemical transformations, even at ambient conditions. Additionally, the dissociation of vapors trapped within cavitation bubbles yields reactive free radicals, further augmenting the rate of esterification reactions. These free radicals serve to propagate and catalyze the formation of esters, contributing to enhanced reaction kinetics. By harnessing the power of cavitation, this shortens the reaction time for the production of esters, paving the way for cost-effective and environmentally sustainable manufacturing processes.

[0055] In an embodiment the application of the ultrasonic wave is performed at a power density between 1 to 10 W / m3. In an embodiment the power density is between 1 to 5 W / m3. It is however preferred that the method is optimized such that a low power density is needed, so that the method in its whole is more energy sufficient. In previous similar methods on lab-scale much higher power densities were used, which made upscaling impossible.

[0056] In an embodiment the application of the ultrasonic wave is performed for a period of between 1 to 60 min, more preferably between 1 and 50 minutes, between 1 and 45 minutes, between 1 and 30 minutes, between 1 and 25 minutes, between 1 and 20 minutes, between 1 and 15 minutes, between 1 and 10 minutes. The choice for the period of time to apply an ultrasonic wave to the reaction mixture depends on maximizing the efficiency and minimizing energy consumption of the reaction.

[0057] In an embodiment the esterification reaction is carried out at a temperature of between 5 and 100° C. This means less heating is necessary in comparison to traditional production and thus less energy is needed for the reaction to take place. This makes the reaction more energy efficient and more cost efficient. In an embodiment the temperature is in a range between 25°C and 75°C. In an embodiment the temperature at which the reaction is carried out is 5°C, 6°C, 7°C, 8°C,9°C,10°C, 11°C, 12°C, 13°C, 14°C, 15°C, 16°C, 17°C, 18°C, 19°C, 20°C, 21°C, 22°C, 23°C, 24°C, 25°C, 26°C, 27°C, 28°C, 29°C, 30°C, 31°C, 32°C, 33°C, 34°C, 35°C, 36°C, 37°C, 38°C, 39°C, 40°C, 41°C, 42°C, 43°C, 44°C, 45°C, 46°C, 47°C, 48°C, 49°C, 50°C, 51°C, 52°C, 53°C, 54°C, 55°C, 56°C, 57°C, 58°C, 59°C, 60°C, 61°C, 62°C, 63°C, 64°C, 65°C, 66°C, 67°C, 68°C, 69°C, 70°C, 71°C, 72°C, 73°C, 74°C, 75°C, 76°C, 77°C, 78°C, 79°C, 80°C, 81°C, 82°C, 83°C, 84°C, 85°C, 86°C, 87°C, 88°C, 89°C, 90°C, 91°C, 92°C, 93°C, 94°C, 95°C, 96°C, 97°C, 98°C, 99°C, 100°C. In an embodiment this temperature is in a range between 5°C and 90°C. In an embodiment this temperature is in a range between 5°C and 80°C. In an embodiment this temperature is in a range between 10°C and 90°C. In an embodiment this temperature is in a range between 10°C and 80°C. In an embodiment this temperature is in a range between 10°C and 75°C. In an embodiment this temperature is in a range between 10°C and 60°C. In an embodiment this temperature is in a range between 10°C and 50°C. In an embodiment this temperature is in a range between 10°C and 40°C. In an embodiment this temperature is in a range between 25°C and 100°C. In an embodiment this temperature is in a range between 35°C and 100°C. In an embodiment this temperature is in a range between 45°C and 100°C. In an embodiment this temperature is in a range between 35°C and 75°C.

[0058] In an embodiment the ester is prepared at a yield of 40% or more. This high yield is achieved due to the specific process as discussed herein.

[0059] In an embodiment of the method the produced ester compound is a simple aliphatic ester, alkyl aryl ester, aromatic ester, acyclic ester, cyclic ester, phosphoester, polyester, glyceride or a carbonate ester.

[0060] The ester compounds that are formed could be from various categories and have various applications such as:

[0061] 1) Simple Aliphatic Esters: These esters are formed by the combination of straight-chain or branched-chain carboxylic acids with alcohols. Examples include methyl acetate (formed from methanol and acetic acid), ethyl propionate (ethanol and propionic acid), and butyl butyrate (butanol and butyric acid).

[0062] 2) Alkyl Aryl Esters: Combining aromatic carboxylic acids with alcohols yields alkyl aryl esters. Examples include benzyl acetate (benzoic acid and benzyl alcohol), phenyl propionate (propionic acid and phenol), and methyl benzoate (methanol and benzoic acid).

[0063] 3) Aromatic Esters: Aromatic esters are formed by the esterification of aromatic carboxylic acids with alcohols. Examples include ethyl benzoate (benzoic acid and ethanol), methyl salicylate (methanol and salicylic acid), and phenyl acetate (acetic acid and phenol).

[0064] 4) Acyclic Esters: These esters are characterized by having open-chain structures. Common examples include ethyl acetate (acetic acid and ethanol), propyl propionate (propionic acid and propanol), and butyl acetate (acetic acid and butanol). 5) Cyclic Esters (Lactones): Lactones are cyclic esters formed by intramolecular esterification. Examples include y-Butyrolactone (formed from y- hydroxybutyric acid), 6-Valerolactone (6-hydroxyvaleric acid), and e- Caprolactone (e-hydroxycaproic acid).

[0065] 6) Flavor and Fragrance Esters: These esters contribute to the aroma and taste of various foods and fragrances. Examples include ethyl butyrate (found in pineapple), isoamyl acetate (banana flavor), and methyl anthranilate (grape fragrance).

[0066] 7) Phosphoesters: Phosphoesters contain a phosphorus atom bonded to three organic groups. Examples include triethyl phosphate, trimethyl phosphate, and tris(2-chloroethyl) phosphate.

[0067] 8) Polyesters: Polyesters are polymers formed by the condensation polymerization of dicarboxylic acids and diols. Examples include polyethylene terephthalate (PET), polybutylene adipate-co-terephthalate (PBAT), and polylactic acid (PLA).

[0068] 9) Esters Used in Cosmetic / Personal Care Products: These esters are commonly found in skincare, haircare, and cosmetic formulations. Examples include glyceryl stearate, isopropyl myristate, and cetyl palmitate.

[0069] 10) Esters Used as Plasticizers: These esters are added to plastics to improve flexibility and durability. Examples include diethyl phthalate (DEP), dibutyl phthalate (DBP), and dioctyl adipate (DOA).

[0070] 11)Glycerides, such as a mono-, di-, tri-, glyceride are esters formed from one molecule of glycerol and one fatty acid molecule. These compounds find widespread applications in the food industry as emulsifiers, stabilizers, and lubricants due to their amphiphilic nature, which enables them to interact with both water and oil phases. Additionally, monoglycerides serve as intermediates in the synthesis of various derivatives, including pharmaceuticals, cosmetics, and surfactants.

[0071] 12)Carbonate ester, which are esters of carbonic acids. Examples such as dimethyl carbonate, ethylene carbonate, propylene carbonate are used as solvents, dimethyl carbonate is also a mild methylating agent.

[0072] Each category encompasses a wide range of ester compounds, each with unique properties and applications across various industries. The above list is meant to be used as an example list and by no means is meant to be interpreted as limiting.

[0073] In an embodiment the produced ester is monoproprionin, monoformin, deethyl carbonate, dimethyl carbonate, ethyl acetate, or propylene carbonate. In an embodiment the method as described herein is carried out in an IBC container. This ensures operation efficiency, since IBC containers are easy to set up and maintain. Conducting the method within an IBC container streamlines the scaling-up process, offering a seamless transition to even larger production volumes. Additionally, the use of an IBC container facilitates various operational aspects such as efficient transportation, storage, and handling of the reaction materials.

[0074] After the synthesis of an ester, isolating the desired product typically involves separating it from the reaction mixture and any by-products or unreacted starting materials. Several methods can be employed for the isolation of esters, depending on the specific reaction conditions and the properties of the target compound. Some common techniques include: extraction, distillation, crystallization, drying and crystallization. The employed techniques for purifying the desired ester, will differ for each ester.

[0075] By employing the method as disclosed herein, the synthesis of ester compounds on a large scale is achieved with enhanced efficiency and yield. The synergistic effects of controlled acid addition, ultra sonification, stirring and catalyst availability contribute to the successful realization of high-quality ester products, making this approach applicable on large-scale ester production processes.

[0076] The invention is further described by the following non-limiting examples which further illustrate the invention, and are not intended to, nor should they be interpreted to, limit the scope of the invention.

[0077] EXAMPLES

[0078] Example 1.

[0079] In an Intermediate Bulk Container (IBC) containing 700 kg of glycerol and 20 kg of sulphuric acid catalyst, the method as described herein is employed for the synthesis of monoformin (synonym: formic acid 2,3-dihydroxypropyl ester). The mixture is subjected to ultrasonic waves generated by a 1.5 kW ultrasonic probe. This ultrasonic energy facilitates the reaction kinetics. The propeller promotes mixing of all reaction components.

[0080] During the synthesis process, a carboxylic acid, namely formic acid, is incrementally added into the mixture at a rate of 10 liters per minute. This addition is carefully controlled to optimize the reaction conditions and ensure efficient conversion of reactants to the desired product. The ultrasonic probe is continuously applied throughout the entire batch duration, ensuring uniform distribution of energy and consistent reaction conditions.

[0081] As a result of this method, a 1020 kg batch of monoformin, with a yield of 60%, is successfully produced within a timeframe of 30 minutes. This rapid production rate, coupled with the efficient utilization of ultrasonic energy, underscores the effectiveness of the present invention in streamlining ester synthesis processes.

[0082] Example 2.

[0083] Example 1 was repeated with ethanol and 1% by weight sulphuric acid catalyst. The method as described herein is employed for the synthesis of ethyl acetate. Acetic acid was added with a flow of 50 liter per minute where ratio between acid and catalyst was maintained at 5-1 factor per minute. To disperse the bubbles over whole mixture 200 rpm was enough. The temperature range is carefully controlled between 40°C and 70°C.

[0084] Reaction Conditions

[0085] • At 1 bar and 40°C, the esterification reaction produces a product containing approximately 60% ethyl acetate within 15 minutes. With removal of water, 90% yield was reached in in 10 minutes.

[0086] • At 2 bar and 40°C, equilibrium is reached in 14 minutes, with a similar 60% ethyl acetate yield and a small amount of residual ethanol remaining in the system. With removal of water, 90% yield was reached in in 9 minutes.

[0087] • At 3 bar and 40°C, the reaction completes in 13 minutes, maintaining the same ester yield while further reducing reaction time. With removal of water, 90% yield was reached in in 9 minutes.

[0088] • At 1 bar and 50°C, the esterification reaction produces a product containing approximately 60% ethyl acetate within 14 minutes. With removal of water, 90% yield was reached in in 9 minutes.

[0089] • At 2 bar and 50°C, equilibrium is reached in 13 minutes, with a similar 60% ethyl acetate yield and a small amount of residual ethanol remaining in the system. With removal of water, 90% yield was reached in in 8 minutes.

[0090] • At 3 bar and 50°C, the reaction completes in 12 minutes, maintaining the same ester yield while further reducing reaction time. With removal of water, 90% yield was reached in in 7 minutes. • At 1 bar and 60°C, the esterification reaction produces a product containing approximately 60% ethyl acetate within 14 minutes. With removal of water, 90% yield was reached in in 9 minutes.

[0091] • At 2 bar and 60°C, equilibrium is reached in 13 minutes, with a similar 60% ethyl acetate yield and a small amount of residual ethanol remaining in the system. With removal of water, 90% yield was reached in in 8 minutes.

[0092] • At 3 bar and 60°C, the reaction completes in 12 minutes, maintaining the same ester yield while further reducing reaction time. With removal of water, 90% yield was reached in in 7 minutes.

[0093] • At 1 bar and 70°C, the esterification reaction produces a product containing approximately 60% ethyl acetate within 13 minutes. With removal of water, 90% yield was reached in in 8 minutes.

[0094] • At 2 bar and 70°C, equilibrium is reached in 12 minutes, with a similar 60% ethyl acetate yield and a small amount of residual ethanol remaining in the system. With removal of water, 90% yield was reached in in 7 minutes.

[0095] • At 3 bar and 70°C, the reaction completes in 11 minutes, maintaining the same ester yield while further reducing reaction time. With removal of water, 90% yield was reached in in 6 minutes.

[0096] Reactor Design and Energy Efficiency:

[0097] It has been found that the reactor requires an energy input of only 1.5 kW to produce up to 1,000 liters of product in a single reaction run. The compact design ensures minimal energy loss while providing consistent reaction conditions.

[0098] Pressure and Temperature Optimization

[0099] It has been found that pressures above 3 bar or temperatures above 70°C do not significantly enhance the reaction rate or yield.

[0100] The invention may thus be described according to the following embodiments:

[0101] 1. A method for the large-scale production of an ester compound, said method comprises adding a volume of a first acid to a mixture of one or more alcohols and one or more catalysts, wherein the resulting reaction mixture is at least 10 L, wherein the one or more alcohols are at least 50% of said alcohol- catalyst mixture and wherein during the addition of said first acid, said reaction mixture is stirred and subjected to an ultrasonic wave. 2. The method of embodiment 1, wherein the one or more alcohols are at least 90% of said alcohol-catalyst mixture.

[0102] 3. The method of any of the previous embodiments wherein said first acid is added incrementally, step-wise or gradually to said alcohol-catalyst mixture.

[0103] 4. The method of any of the previous embodiments, wherein the ratio of the total weight of the alcohol and the added volume of the first acid at the initiation of the esterification reaction is at least 50:1 per minute.

[0104] 5. The method of any of the previous embodiments, wherein the ratio of the molar concentration of the catalyst and the molar concentration of the first acid at the initiation of the esterification reaction is at least 1:1, more preferably at least 2:1.

[0105] 6. The method of any of the previous embodiments, wherein the esterification reaction is carried out at a pressure of between 1 and 5 bar, preferably between 1.1 and 5 bar.

[0106] 7. The method of any of the previous embodiments, wherein the esterification reaction is carried out at a temperature of between 5 and 140° C, preferably between 45 and 100°C.

[0107] 8. The method according to embodiment 6 or 7, wherein the esterification reaction is carried out at a pressure between 1 and 3 bar and a temperature between 35 and 75°C.

[0108] 9. The method of any of the previous embodiments, wherein the one or more catalysts are present in the alcohol-catalyst mixture in an amount of minimum 0.1% by weight.

[0109] 10. The method according to any of the previous embodiments, wherein the alcohol is glycerol.

[0110] 11. The method of any of the previous embodiments wherein the first acid is chosen from formic acid, acetic acid, propionic acid, butyric acid, valeric acid, caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid, undecylenic acid, lauric acid, tridecyclic acid, myristic acid, pentadecyclic acid, palmitic acid, margaric acid, stearic acid, nonadecylic acid, arachidic acid or a mixture thereof.

[0111] 12. The method of any of the previous embodiments, wherein the amount of free water in the reaction is less than 20% (by v / v).

[0112] 13. The method of any of the previous embodiments wherein the catalyst is a second acid, preferably a non-carboxylic acid such as hydrochloric acid, sulfuric acid or phosphoric acid. 14. The method of any of the previous embodiments, wherein applying the ultrasonic wave is performed at a power density of between 1 to 10 W / m3.

[0113] 15. The method of any of the previous embodiments, wherein applying the ultrasonic wave is performed for a period of 1-60 min.

[0114] 16. The method of any of the previous embodiments, wherein the ester is prepared at a yield of 40% or more.

[0115] 17. The method of any of the previous embodiments, wherein the produced ester compound is a simple aliphatic ester, alkyl aryl ester, aromatic ester, acyclic ester, cyclic ester, phosphoester, polyester, glyceride or a carbonate ester.

[0116] 18. The method according to any of the previous embodiments, wherein said method is performed in an IBC container.

[0117] It is supposed that the present invention is not restricted to any form of realization described previously and that some modifications can be added to the presented example of fabrication without reappraisal of the appended claims. For example, the present invention has been described referring to the addition of an acid to an alcohol-catalyst mixture, but it is clear that the invention can be applied for instance to a process comprising the addition of an alcohol to an acid-catalyst mixture.

Claims

CLAIMS1. A method for the large-scale production of an ester compound, said method comprises adding a volume of a first acid to a mixture of one or more alcohols and one or more catalysts, wherein the resulting reaction mixture is at least 10 L, wherein the one or more alcohols are at least 50% of said alcohol- catalyst mixture and wherein during the addition of said first acid, said reaction mixture is stirred and subjected to an ultrasonic wave.

2. The method of claim 1, wherein the one or more alcohols are at least 90% of said alcohol-catalyst mixture.

3. The method of any of the previous claims wherein said first acid is added incrementally, step-wise or gradually to said alcohol-catalyst mixture.

4. The method of any of the previous claims, wherein the ratio of the total weight of the alcohol and the added volume of the first acid at the initiation of the esterification reaction is at least 50:1 per minute.

5. The method of any of the previous claims, wherein the ratio of the molar concentration of the catalyst and the molar concentration of the first acid at the initiation of the esterification reaction is at least 1:1, more preferably at least 2:1.

6. The method of any of the previous claims, wherein the esterification reaction is carried out at a pressure of between 1 and 5 bar, preferably between 1.1 and 5 bar.

7. The method of any of the previous claims, wherein the esterification reaction is carried out at a temperature of between 5 and 140° C, preferably between 45 and 100°C.

8. The method according to claim 6 or 7, wherein the esterification reaction is carried out at a pressure between 1 and 3 bar and a temperature between 35 and 75°C.

9. The method of any of the previous claims, wherein the one or more catalysts are present in the alcohol-catalyst mixture in an amount of minimum 0.1% by weight.

10. The method according to any of the previous claims, wherein the alcohol is glycerol.

11. The method of any of the previous claims wherein the first acid is chosen from formic acid, acetic acid, propionic acid, butyric acid, valeric acid, caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid, undecylenic acid, lauric acid, tridecyclic acid, myristic acid, pentadecyclic acid, palmitic acid,margaric acid, stearic acid, nonadecylic acid, arachidic acid or a mixture thereof.

12. The method of any of the previous claims, wherein the amount of free water in the reaction is less than 20% (by v / v).

13. The method of any of the previous claims wherein the catalyst is a second acid, preferably a non-carboxylic acid such as hydrochloric acid, sulfuric acid or phosphoric acid.

14. The method of any of the previous claims, wherein applying the ultrasonic wave is performed at a power density of between 1 and 10 W / m3.

15. The method of any of the previous claims, wherein applying the ultrasonic wave is performed for a period of 1-60 minutes.

16. The method of any of the previous claims, wherein the ester is prepared at a yield of 40% or more.

17. The method of any of the previous claims, wherein the produced ester compound is a simple aliphatic ester, alkyl aryl ester, aromatic ester, acyclic ester, cyclic ester, phosphoester, polyester, glyceride or a carbonate ester.

18. The method according to any of the previous claims, wherein said method is performed in an IBC container.