Process for preparing hydroxyphenyl carboxylic acid esters using catalytic transesterification

Abstract

A process for preparing hydroxyphenylcarboxylic acid esters, comprising a catalytic transesterification step using an alkali metal carbonate or alkali metal bicarbonate as a catalyst, wherein: (a) a container is provided in which a hydroxyphenylcarboxylic acid ester is attached directly to a phenol ring or an alkyl chain C m H 2m (b) a mixture of the two components is heated above the melting point of the two components and a vacuum is applied; and an alkali metal carbonate or alkali metal bicarbonate, either already present in step (b) or added to the liquid mixture in step (c), is used to carry out the transesterification reaction. The use of the alkali metal carbonate or alkali metal bicarbonate as a catalyst results in a safe, sustainable, and environmentally friendly process that avoids toxic by-products and does not require extensive preparation.

Description

[Technical Field]

[0001] The present invention relates to a novel process for preparing hydroxyphenyl carboxylates and the novel and inventive use of catalysts applied therein. [Background technology]

[0002] Carboxylic acid esters can generally be prepared by reacting a carboxylic acid with an alcohol. This reaction can be autocatalytic or catalyzed, for example, by a Bronsted or Lewis acid. Metal compounds such as alkoxides, carboxylates, and chelates of titanium, zirconium, tin, zinc, and aluminum are often used as catalysts.

[0003] Although the catalytic properties of these metal catalysts are satisfactory, removing catalyst residues from the esterification product is difficult. For purification, the crude ester is generally first mixed with an alkali metal hydroxide to neutralize unconverted or incompletely converted acids (partial esters), and the free alcohol is removed by steam distillation. After drying the product by short vacuum distillation, the catalyst residues are then removed by filtration. The catalyst residues generally have a sticky, gel-like consistency, and filtration is usually only possible using filter aids such as activated carbon, wood flour, cellulose, or celite. Nevertheless, such filtration under these circumstances still has serious drawbacks. Long filtration times are required, and a large amount of product is retained in the filter cake, resulting in a low ester yield.

[0004] Carboxylic acid esters can also be prepared by transesterification. For example, hydroxyphenyl carboxylates of formula (I), shown further below, act as antioxidants in many areas of the chemical industry and are known to be prepared by various methods, including many transesterification processes (e.g., U.S. Pat. Nos. 3,330,859, 3,944,594, 4,085,132, 4,228,297, 4,536,593, 4,594,444, 4,618,700, and 4,716,244). However, these processes have not been entirely satisfactory. Thus, for example, titanium compounds used as catalysts are often difficult to separate from the reaction mass. Once disposed of, they often have to be disposed of using cumbersome procedures, requiring the disposal of filtration residues.

[0005] In particular, catalyst residues in the product can lead to unwanted oxidation reactions that discolor the product.

[0006] Therefore, much effort has been made to improve these processes.

[0007] For example, aluminum alcoholates, which are already known as esterification and transesterification catalysts and which have been used for the preparation of allyl β-phenylpropionate by transesterification for the perfume industry (FR-A-1 490 341), are also proposed for use in these processes.

[0008] For example, U.S. Pat. No. 5,481,023 describes the use of aluminum alcoholates as catalysts to obtain hydroxycarboxylates in good yields and cleanly, without separation and oxidation problems, using environmentally acceptable auxiliaries.

[0009] While this use may solve some of the problems mentioned above, other problems still remain.

[0010] For example, as mentioned above, catalyst residues may not only cause visual or aesthetic defects such as the aforementioned coloration or discoloration of the product, but may also be considered to be significant with respect to environmental, toxicity, or food safety issues.

[0011] When aluminum is used as a catalyst for the preparation of compounds or materials that are subsequently used in the manufacture of food containers, the latter must be free of aluminum residues resulting from the application of aluminum as a catalyst.

[0012] In this regard, the Agency has adopted a regulation on the safety of dietary aluminium, which establishes an acceptable weekly intake of 1 mg aluminium per kg body weight per week. Applying previous exposure estimates for food contact materials, the migration limit would have to be set at 8.6 mg aluminium per kg food.

[0013] However, European authorities have deemed it appropriate to limit the contribution to overall exposure from exposure via food contact materials, for example by applying a 10% allocation factor to migration limits derived using traditional methods. A migration limit of 1 mg aluminium per kg of food is therefore considered appropriate for food contact materials. This leads to a restriction that plastic materials and articles that come into contact with food must not release aluminium in amounts that exceed a specific migration limit of 1 mg aluminium per kg of food or food simulant (Commission Regulation (EU) 2016 / 1416 of 24 August 2016 amending and amending Regulation (EU) No 10 / 2011 on plastic materials and articles intended to come into contact with food).

[0014] Therefore, in view of increasingly stringent regulations for consumer safety and environmental protection, there is a strong need for new, improved and sustainable processes for preparing compounds that are subsequently applied in the process of preparing food containers or other materials that come into contact with food.

[0015] Therefore, in view of the above, it is therefore an object of the present invention to develop a transesterification process which, while striving for continuous improvement, still meets the requirements in terms of technical performance, but in addition takes into account consumer safety and environmental issues.

[0016] Surprisingly, it has now been found that by using alkali metal bicarbonates or alkali metal carbonates, where the alkali metal is either sodium or potassium, as catalysts for these transesterification processes, the hydroxycarboxylates and other hydroxycarbonyl derivatives described below can be obtained cleanly in good yields in an environmentally friendly and sustainable manner, without separation and oxidation problems. Not only are the hydroxycarboxylates and other hydroxycarbonyl derivatives obtained by improved processes (e.g., simplified filtration, use of readily available non-toxic catalysts, etc.), but the resulting products themselves are characterized by low permeability and a significantly lower proportion of by-products (if any), thereby providing superior quality and making them safe for consumers and suitable for environmentally friendly applications.

[0017] Alkali metal carbonates or alkali metal hydrogen carbonates, also commonly and hereinafter referred to as alkali metal bicarbonates, have been described in prior art transesterification processes, but the claimed sodium or potassium salts themselves have never been used as the sole catalyst for the transesterification process according to the present invention.

[0018] Chinese Patent No. 112048030 relates to a polyethylene-grafted hindered phenol antioxidant and its preparation method, which comprises mixing a polyethylene containing a hydroxyl group in its side chain with a propionate derivative and subjecting the mixture to a transesterification reaction under the action of a catalyst. The catalyst is selected from tin compounds, titanium compounds, alkali metal compounds, and alkaline earth metal compounds, with (n-butyl)tin oxide, (dibutyl)tin dilaurate, lithium amide, and sodium amide being preferred. Illustrative catalysts include dibutyl maleate, calcium hydroxide, and tin t-butoxide.

[0019] JP 6-107596 A relates to a method for preparing tetrakis[3-(3,5-dialkyl-4-hydroxyphenyl)propionyloxyalkyl]methane via catalytic transesterification, and the basic catalyst can be selected from a number of catalysts presented. Examples of the catalysts used include lithium methoxide, calcium oxide, and tin t-butoxide.

[0020] EP 0608089 relates to alkoxyalkylene glycol esters of substituted phenylpropionic acid and their use as antioxidant stabilizers for organic materials susceptible to oxidative degradation, such as synthetic polymers and resins. The esters in EP 0608089 can be prepared by various esterification methods, including transesterification between alkylene glycol monoethers and substituted phenylpropionic acid esters. The reaction can be carried out in the presence of a transesterification catalyst, including, for example, alkali metals, alkali metal amides, alkali metal alkoxides, alkali metal hydroxides, titanium(IV) alkoxides, and metal oxide salts, with alkali metal alkoxides being explicitly preferred. While alkali metal carbonates and alkali metal bicarbonates are also listed in this list, they are not described for this purpose and are merely used as cleaning agents after the completion of the transesterification reaction. For example, the resulting ester is isolated by conventional techniques, and the reaction mixture is washed and neutralized with dilute mineral acid (e.g., dilute hydrochloric acid or sulfuric acid) or aqueous alkali (e.g., aqueous sodium bicarbonate), and then washed with 5% aqueous sodium bicarbonate and water, as in Example 1.

[0021] Similar conditions are found in the same applicant's Japanese Patent Application Laid-Open No. 8-092165, which describes a novel waxy antioxidant with a low pour point and excellent antioxidant effect. This antioxidant contains an ester obtained by reacting a substituted phenylalkanoic acid with an alkylene oxide adduct of a polyhydric alcohol as the active ingredient, and alkali metal carbonates and alkali metal bicarbonates are also listed among the many optional transesterification catalysts. However, they are not described for this purpose and are only used as cleaning agents after the transesterification reaction is completed. In Example 4, after the transesterification reaction is carried out, the reaction solution is cooled to room temperature, and 0.1 N hydrochloric acid, water, and a 4% aqueous sodium bicarbonate solution are used for washing.

[0022] Furthermore, EP 3067343, particularly relating to a novel antioxidant and polyurethane foam, mentions a process involving transesterification between an alkylene glycol monoether and a substituted phenylpropionic acid ester, and further mentions that this can be carried out in the presence of a transesterification catalyst that can be selected from, for example, alkali metals, alkali metal hydrides, alkali metal amides, alkali metal alkoxides, alkali metal hydroxides, alkali metal carbonates, alkali metal bicarbonates, alkali metal and alkaline earth metal carboxylates (e.g., acetates or formates), aluminum alcoholates and phenates, titanium (IV), metal oxides, or organic acids, mineral acids, and sulfonic acids. In particular, sulfuric acid as the mineral acid and p-toluenesulfonic acid as the sulfonic acid are preferred. Alkali metal alkoxides are also preferred.

[0023] Thus, in all three of the prior art documents EP 0608089, EP 3067343, and JP 8-092165, the transesterification catalyst used was either p-toluenesulfonic acid or a metal oxide such as sodium methoxide, sodium acetoxide, or titanium(IV) tetrabutoxide. None of the prior art discusses any of the aforementioned problems and challenges to be overcome, nor does it propose to select an alkali metal carbonate or bicarbonate even randomly, nor does it mention addressing such issues. In fact, the alkali metal bicarbonate was added to the reactant mixture only after the transesterification step had taken place, for an entirely different purpose: as a washing agent.

[0024] As can be seen from the prior art cited herein above, the transesterification reaction process is known as a preparation method in the field of antioxidants, and many optional transesterification catalysts are mentioned.However, even if alkali metal (bi)carbonates are found to be mentioned in this prior art, they are mentioned as being used for various functions such as halide scavengers or detergents, and are only exemplified as the latter, but are not exemplified as transesterification catalysts, and neither their capabilities nor advantages regarding the problem solved by the present invention are mentioned.

[0025] Chinese Patent No. 104447333 discloses a method for preparing isooctyl 3,5-di-tert-butyl-4-hydroxyphenylpropionate by reacting methyl 3,5-di-tert-butyl-4-hydroxyphenylpropionate with isooctyl alcohol in the presence of lithium carbonate for 4-8 hours at 140-170°C under a vacuum of 0.07-0.08 MPa. The selection of various counterions exhibits significant variability and unpredictable effects. The specific interactions between the counterions and other reactants present can lead to surprising and unexpected results. The use of Li2CO3, therefore, cannot be considered as constituting the specific use of potassium or sodium.

[0026] USSR Patent Application Publication No. 1014213 describes a method for producing pentaerythryl-tetrakis-[β-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate] by transesterification of methyl (3,5-di-tert-butyl-4-hydroxyphenyl)-propionic acid methyl ester with pentaerythritol. USSR Patent Application Publication No. 1014213 discusses prior art methods up to 1981, whereby transesterification is carried out in the presence of a catalyst such as an alkali metal, its alcoholate hydride, or, in particular, lithium hydroxide. The drawbacks of this method related to the use of this explosive catalyst are addressed. USSR Patent Application Publication No. 1014213 also discusses the drawbacks of an alternative method using sodium methylate as a catalyst, which is sensitive to the presence of moisture in the initial reagents and requires special storage and dosage conditions.

[0027] The advantages of the transesterification process proposed in USSR Patent Application Publication No. 1014213 are explained by the use of readily available and inexpensive catalysts, which addresses the technical aspects of the transesterification process, such as shortening the reaction time, avoiding the catalyst neutralization step, and eliminating the generation of wastewater, but certainly does not address modern issues regarding environmental sustainability and consumer safety.

[0028] In particular, it is noted that the objectives set out in USSR Patent Application Publication No. 1014213 are achieved by using a catalyst consisting of a mixture of potassium carbonate, sodium carbonate and phenol, the weight ratio being 1:1.5-2:2.5-3.

[0029] The first essential difference is that the present invention uses a single compound selected from alkali metal carbonates or alkali metal bicarbonates as catalyst for the transesterification step, rather than a mixture.

[0030] In particular, the present invention does not require the presence of aromatic compounds such as phenol for use as a catalyst. Phenol is a protoplasmic poison with many actions. Its hydrophilic and lipophilic properties allow phenol to easily penetrate cell membranes, denaturing proteins along the way (explaining its widespread use as a disinfectant), ultimately leading to a corrosive effect that results in cell death and necrosis, as well as coagulation necrosis.

[0031] Clearly, phenol should be avoided at all costs for food applications.

[0032] Furthermore, the weight ratio of potassium carbonate to sodium carbonate to phenol of 1:1.5-2:2.5-3 indicates that phenol has a significant ratio of about 1:1, 2.5-3 to 2.5-3, compared to the combination of two alkali metal carbonates (1 + 1.5 to 1 + 2), thereby demonstrating that phenol is required in a non-negligible amount.

[0033] Besides the consistency and toxicity of the catalyst mixture, further technical parameters and features of the present invention differ significantly from those described in USSR Patent Application Publication No. 1014213.

[0034] The process of USSR Patent Application Publication No. 1014213 describes a transesterification step in which alkali metal carbonates are used, but said process differs from the transesterification step of the present invention in many technical features and parameters.

[0035] Soviet Patent Application Publication No. 1014213 provides a method for obtaining pentaerythryl-tetrakis-(5-(3,5-ditertbutyl-4-hydroxyphenyl)-propionate, which comprises heating the starting methyl ester (3,5-ditertbutyl-1-4-hydroxyphenyl)-propionic acid and pentaerythritol to 135-150°C and subjecting them to a residual pressure of 20-100 mmHg for 9 hours in the presence of a catalyst used in an amount of 6-10% of the weight of the starting methyl ester.

[0036] The required concentration of the catalyst according to the present invention is rather low, since it is preferably added to the mixture of the starting methyl ester (compound of formula (II)) and the compound of formula (III) in a concentration range of less than 10% by weight, preferably less than 5% by weight.

[0037] Furthermore, as can be seen from the examples provided below, the transesterification step of the present invention is carried out for 1 to 8 hours, preferably 4 to 6 hours, and best results, i.e., best conversion, are expected, whereas USSR Patent Application Publication No. 1014213 describes the transesterification reaction as requiring 9 hours.

[0038] Finally, the transesterification yield obtained according to the process of USSR 1014213 is 78-83% (expressed as GC area %), whereas the conversion according to the present invention reaches at least 82.62%-89.69% for sodium carbonate and up to 93.20% for potassium bicarbonate, thereby showing a much higher efficiency compared to USSR 1014213.

[0039] Ter Haar Ruud et al. in Carbohydrate Research (vol. 346, no. 8, June 2011, pp. 1005-1012) discusses the synthesis of hydroxy-aryl esters of glycosidic polyols and non-reducing oligosaccharides. To enable enzymatic coupling of sugars to proteins, several disaccharides and trisaccharides were hydroxyarylated using anhydrous transesterification with methyl 3-(4-hydroxyphenyl)propionate catalyzed by potassium carbonate. Although K2CO3 is used as the catalyst, the reaction mixture is completely anhydrous and requires DMSO (dimethyl sulfoxide) as an activating solvent, a polar aprotic solvent. However, the present invention does not require the presence of any solvent, and the use of an activating solvent such as DMSO would lead to undesirable side effects. Additionally, this publication exclusively focuses on sugar chemistry, a specialized branch of organic chemistry. Sugar molecules are composed solely of the organic elements carbon, oxygen, and hydrogen. However, the highly specific arrangement of carbon, hydrogen, and oxygen atoms, forming a ring structure, provides sugar molecules with unique chemical properties that make their chemical behavior different from and incomparable to that of non-sugar organic molecules. Sugar molecules are highly chemically sensitive, especially with respect to heating. Therefore, transesterification processes in sugar chemistry that require the presence of activating solvents such as DMSO cannot be applied to non-sugar chemistry. Summary of the Invention [Means for solving the problem]

[0040] The present invention therefore further relates to the use of an alkali metal carbonate or alkali metal bicarbonate as a catalyst for the preparation of a compound of formula (I) by reacting a compound of formula (II) with a compound of formula (III), as shown below.

[0041] An inventive improvement to the process is the use of alkali metal carbonates or alkali metal bicarbonates as catalysts, which results in a safe, sustainable, and environmentally friendly process that avoids toxic by-products and does not require extensive adjustments.

[0042] The objective, surprisingly, a) The container is directly connected to the phenol ring or to an alkyl chain C m H 2m and a substituted phenol containing a carboxylic acid methoxy ester moiety indirectly linked to a fatty alcohol via b) a mixture of the two components is heated above the melting points of the two components and a vacuum is applied; c) Achieved by a transesterification process in which an alkali metal carbonate or alkali metal bicarbonate is added to the liquid mixture and transesterification is carried out.

[0043] This process is particularly characterized by being carried out in a water-free, non-aqueous environment. In the context of the present invention, water-free means that no added water is required. On the contrary, the addition of water would interfere with the desired transesterification reaction, since it would lead to hydrolysis.

[0044] However, it may be acceptable for some residual water to be present in the compound, such as water of crystallization of sodium bicarbonate.

[0045] Nevertheless, the starting compounds are preferably, but not necessarily, dried before the transesterification reaction. Generally, heating and drawing a vacuum on the vessel is already sufficient to remove residual water from the starting compounds.

[0046] The transesterification reaction begins as soon as the alkali metal carbonate or alkali metal bicarbonate is added to the mixture of the two components and the mixture is heated.

[0047] This process can be carried out in two alternative ways: when carried out continuously, the individual steps are carried out in serially connected, continuously operated equipment, or alternatively, the process can be carried out batchwise.

[0048] The exchange reaction type concept can be used not only for fatty alcohols but also for other linear, branched or cyclic alkyl derivatives bearing 1, 2, 3 or 4 functional groups selected from HO, H2N or HS. DETAILED DESCRIPTION OF THE INVENTION

[0049] The process according to the present invention comprises the step of reacting a compound of formula (I) [ka] (In the formula, R1 and R2 are each independently hydrogen or linear or branched C1-C8 alkyl; m is either 0 or an integer selected from 1, 2, or 3; n is an integer selected from 1, 2, 3, or 4, and A is OR3 when n is 1, and R3 is C4-C 20 Alkyl or C5-C 12 cycloalkyl, or A is a group of the formula -OC when n is 2 x H 2x -O-, OC x H 2x -SC x H 2x -O, -NH-C x H 2x -NH- or -O-(CH2CH2O) a CH2CH2O- (In the formula, x is an integer selected from 2 to 8, and a is an integer selected from 1 to 12 or A is a group of formula H3C-C when n is 3 x H 2x -C(C y H2y O-)3, -OC x H 2x -CH2(O-)-C y H 2y -O- (wherein x and y are each independently an integer selected from 1 to 8) or A has the formula —C(—CH—O—) when n is 4. by transesterification, [ka] The compound of formula (III) [ka] and the process step of the transesterification reaction between the compound of formula (II) and the compound of formula (III) is characterized in that it is initiated by adding a catalyst consisting of an alkali metal bicarbonate or alkali metal carbonate selected from NaHCO3, Na2CO3, KHCO3 and K2CO3, present in its undissolved solid form.

[0050] In one embodiment of the process according to the invention, the integer m in formula (I) or (II) is 2.

[0051] In one embodiment of the process according to the present invention, R1 and R2 are both independently selected from linear or branched C1-C4 alkyl.

[0052] In one embodiment of the process according to the present invention, R1 and R2 are both the same linear or branched C1-C4 alkyl, preferably R1 and R2 are both tert-butyl.

[0053] In one embodiment of the process according to the present invention, R1 and R2 are both tert-butyl.

[0054] In one embodiment of the process according to the invention, the integer n in formula (I) or (II) is 1.

[0055] In one embodiment of the process according to the present invention, the integer n in formula (I) or (II) is 1, and R3 of OR3 in A is C8-C 18 It is alkyl.

[0056] In one embodiment of the process according to the present invention, the integer n in formula (I) or (II) is 1, and R3 of OR3 in A is C8 alkyl.

[0057] In one embodiment of the process according to the invention, a compound of formula (I.1) is obtained. [ka]

[0058] In one embodiment of the process according to the present invention, the integer n in formula (I) or (II) is 1, and R3 of OR3 in A is C 18 It is alkyl.

[0059] In one embodiment of the process according to the invention, a compound of formula (I.2) is obtained. [ka]

[0060] In one embodiment of the process according to the invention, the integer n in formula (I) or (II) is 2.

[0061] In one embodiment of the process according to the invention, the integer n in formula (I) or (II) is 2, and A in formula (I) or (III) is a group of formula -OC x H 2x -O-, where x is 6.

[0062] In one embodiment of the process according to the invention, a compound of formula (I.3) is obtained. [ka]

[0063] In one embodiment of the process according to the invention, the integer n in formula (I) or (II) is 2, and A in formula (I) or (III) is of the formula OC x H 2x -SC x H 2x -O, where x is 2.

[0064] In one embodiment of the process according to the invention, a compound of formula (I.4) is obtained. [ka]

[0065] In one embodiment of the process according to the invention, the integer n in formula (I) or (II) is 2, and A in formula (I) or (III) is a group of formula -NH-C x H 2x -NH-, where x is 6.

[0066] In one embodiment of the process according to the invention, a compound of formula (I.5) is obtained. [ka]

[0067] In one embodiment of the process according to the invention, the integer n in formula (I) or (II) is 2, and A in formula (I) or (III) is a group of formula -O-(CH2CH2O) a It has the formula CH2CH2O-, where a is 2.

[0068] In one embodiment of the process according to the invention, a compound of formula (I.6) is obtained. [ka]

[0069] In one embodiment of the process according to the invention, the integer n in formula (I) or (II) is 2, and A in formula (I) or (III) is a group of formula -O-(CH2CH2O) a It has the formula CH2CH2O-, where a is 1 to 8.

[0070] In one embodiment of the process according to the invention, the integer n in formula (I) or (II) is 2, and A in formula (I) or (III) is a group of formula -O-(CH2CH2O) a It has the formula CH2CH2O-, where a is an average of 2.

[0071] In one embodiment of the process according to the invention, a compound of formula (I.7): [ka] In this case, a compound of the formula:

[0072] In one embodiment of the process according to the invention, a compound is obtained, wherein the unit [ka] may be absent in compounds of formula (I.7) (a is 0).

[0073] In one embodiment of the process according to the invention, a compound is obtained, wherein the unit [ka] is repeated up to seven times in compounds of formula (I.7) (a is 7).

[0074] In one embodiment of the process according to the invention, the integer n in formula (I) or (II) is 3.

[0075] In one embodiment of the process according to the invention, the integer n in formula (I) or (II) is 3, and A in formula (I) or (III) is a group of formula HC-C x H 2x -C(C y H2y O-)3, -OC x H 2x -CH2(O-)-C y H 2y -O-, wherein x and y are each independently an integer selected from 1 to 8.

[0076] In one embodiment of the process according to the invention, the integer n in formula (I) or (II) is 4.

[0077] In one embodiment of the process according to the invention, the integer n in formula (I) or (II) is 4 and A is a group -C(-CH2-O-)4.

[0078] In one embodiment of the process according to the invention, compounds of formula (I.8) are obtained. [ka]

[0079] The compounds of formulae (II) and (III) used in the novel process for obtaining compounds of formula (I) are known and can be prepared by known processes, and the compounds of formulae (I.1) to (I.8) known per se can be obtained by the novel and inventive process according to the present invention.

[0080] The compounds of formula (I) obtained in the practice of this invention are typically used to protect organic materials susceptible to thermal, oxidative and / or photodegradation, including plastic materials and lubricants, and some are commercially available.

[0081] Compared to prior art processes, the process of the present invention has several advantages.

[0082] At the end of the reaction, the catalyst, alkali metal (bi)carbonate, is dispersed as a salt in the final melt and can simply be filtered off, without first being deactivated by hydrolysis and precipitating.

[0083] In addition to eliminating the washing step, further addition of other reactants such as "washing agents" or "halide scavengers" is not required.

[0084] The remaining catalyst residues are very small (maximum 10 ppm alkali metal on average) and, especially in the case of sodium, are not relevant with regard to toxicity and food contact regulations (by comparison, aluminum residues form the basis of regulatory limits for food safety).

[0085] Particular attention is drawn to the fact that in the process according to the invention discoloration of the reaction mass and of the product is avoided: the problem of discoloration caused by the catalyst, mentioned at the outset, does not arise.

[0086] In general, the resulting products exhibit long-term stability, which increases their shelf life and leads to a more sustainable solution.

[0087] When sodium bicarbonate is applied as a catalyst in the transesterification, the transmittance is even better than potassium bicarbonate, since the latter shows lower transmittance values ​​and appears visually "colored". Thus, sodium bicarbonate does not show any effect on color, even when applied at higher dosages in the process according to the invention.

[0088] The methanol produced can be easily evaporated from the reaction mixture, thereby removing it from the equilibrium and leading to high conversions towards the desired products.

[0089] Optionally, remaining excess raw material can be distilled by standard methods or alternatively removed by recrystallization.

[0090] The novel process does not require any solvent. The process can be operated with only the two reactants and the catalyst present. All components, i.e., the two reactants and the catalyst, can be present in the solid state. Alternatively, one reactant can be melted into a liquid material, or both reactants can be liquid. The catalyst can be present initially, i.e., in a mixture with one or both reactants, or it can be added later, all at once or in portions, and dispersed in a solid, semi-liquid, or liquid mixture of the reactants. The transesterification begins once the catalyst is added and the mixture is heated.

[0091] Preferably, the reaction is water-free. By water-free, it is meant that no additional water is added to the reactant mixture. Some moisture in the reactants may be tolerated (up to 0.1% by weight moisture content) due to optional hygroscopic properties of the reactants. Preferably, the reactant mixture is heated at the start of the reaction to remove moisture from the chemical reactants.

[0092] Therefore, the novel process does not require the presence of a solvent.

[0093] However, the novel process can also be carried out in the presence of a primarily inert organic solvent, which may simply serve dilution purposes.

[0094] Typically, the optional organic solvent is selected from aliphatic or aromatic hydrocarbons such as pentane, hexane, heptane, octane, decalin, cyclohexane, benzene, toluene, xylene, mesitylene, dichloromethane, chloroform, tetrachloromethane, bromoform, petroleum ether, tetrahydrofuran or mixtures thereof.

[0095] However, activating solvents such as dimethylformamide (DMF), dimethylacetamide (DMAc or DMA), N-methyl-2-pyrrolidone (NMP), hexamethylphosphoramide (HMPA), and dimethyl sulfoxide (DMSO) are not suitable for the process according to the invention. Their interaction with the reactants of the reaction mixture would lead to undesirable side effects and by-products. For example, DMSO, one of the most powerful organic solvents, is considered a disadvantageous solvent in this context because it dissolves inorganic salts and is cumbersome and difficult to remove from the reaction mixture, potentially leading to unwanted toxic residues.

[0096] The transesterification reaction can be carried out in a temperature range of 120 to 220°C. Preferably, the transesterification reaction can be carried out in a temperature range of 130 to 200°C, more preferably 150 to 190°C.

[0097] The transesterification reaction can be operated at atmospheric pressure of 1000 mbar (specifically 1013 mbar), but is preferably operated in the lower range of 300 to 1 mbar. Preferably, the transesterification reaction is operated in the range of 200 to 1 mbar, more preferably 100 to 1 mbar.

[0098] As methanol is formed during the reaction, the pressure may change during the course of the reaction. For example, the pressure may increase proportionally to the amount of methanol formed. When methanol is removed, it is advantageous to reduce the pressure until the excess methanol is separated from the component of formula (III).

[0099] The catalyst may be added to the reaction mixture of the compound of formula (II) and the compound of formula (III) at a concentration of less than 10% by weight, preferably less than 5% by weight.

[0100] Conveniently, the catalyst is added to the reaction mixture in a concentration range of from 0.1 to 5% by weight, more preferably from 0.2% to 2% by weight, most preferably from 0.25 to 1% by weight.

[0101] Conventional procedures such as stirring the reaction mixture are useful.

[0102] Furthermore, as already mentioned above, the transesterification reaction step of the present invention takes 1 to 8 hours, preferably 4 to 6 hours.

[0103] Once the reaction is complete, the alkali metal (bi)carbonate dispersed in the liquid mixture can be easily removed by filtration. As further noted above, the filtration process is very simple and does not require multiple filtration steps or additional filter aids.

[0104] Contrary to the catalysts discussed in the prior art, by acidifying the reaction mass with an acid, there is no need to destroy the remaining concentrate or use cleaning agents. Also, due to its harmlessness and ubiquity regarding consumer safety and environmental concerns, no additional precautions need to be taken. As already indicated further above, the methanol formed during the reaction is easily removed by simple evaporation during the reaction at high temperatures, and the remaining methanol is removed when a vacuum is finally applied.

[0105] The product of formula (I) can optionally be crystallized directly by cooling and seeding the reaction melt or by dissolving the reaction melt in a suitable solvent and cooling the solution to effect seeded crystallization. In such cases, suitable solvents include the above-mentioned hydrocarbons such as pentane, hexane, heptane, octane, cyclohexane, decalin, petroleum ether or mixtures thereof, aromatic hydrocarbons such as benzene, toluene or xylene.

[0106] However, because the process is simple and the catalyst is harmless, this additional step should be omitted in order to save energy, as no advantage is perceived.

[0107] Generally, approximately equal amounts of ester (II) and alcohol (III) are used, i.e., a ratio of about 1:1 is applied. However, there may be a slight excess (about 1-2% by weight) of more volatile reactants, which will be subsequently removed by distillation.

[0108] Thus, depending on the volatility, the ratio of reactant (II) (or III) per equivalent of reactant (III) (or II) is conveniently 0.8:1 to 1.3:1, preferably 0.85:1 to 1.2:1, the ratio being higher for more volatile reactants. [Example]

[0109] GC method: The samples were analyzed by gas chromatography (GC). This method qualitatively detects the individual components of the sample according to their individual retention times. The concentration of each component in the sample is expressed as a percentage of its peak area as gas chromatography area percent [GC area %]. Peak assignments were made by measuring the individual starting materials and the products as single components.

[0110] An Agilent Technologies gas chromatograph was equipped with an Optima 5 MS Accent (50 m × 0.2 mm × 0.35 μm, Macherey-Nagel) column. The injection temperature was 280 °C, and the injection volume was 0.2 μL. A 1:50 split ratio was used. The carrier gas was hydrogen at a constant flow rate of 3.0 mL / min. The initial temperature was 50 °C with a hold time of 2 min. The subsequent gradient was 25 °C / min to 300 °C with a hold time of 19 min. The detector temperature was 320 °C, and the total run time was 31 min.

[0111] HPLC method: The samples were analyzed by high performance liquid chromatography (HPLC). This method qualitatively detects the individual components of the sample according to their individual retention times. Quantification is performed by the HPLC area % method at a wavelength of 275 nm. Peak assignments were made by measuring the individual starting materials and the products as single components.

[0112] An Agilent Technologies high-performance liquid chromatograph was equipped with a Halo C8 column (150 × 3.0 mm, AMT). The injection volume was 3.0 μL. The flow rate was 1.0 mL / min. The temperature was 30 °C. The instrument was run under gradient elution conditions. Mobile phase A was acetonitrile / water 70:30 (v / v). Mobile phase B was acetonitrile / methyl tert-butyl ether (MTBE) 70:30 (v / v). The gradient ran from 100% mobile phase A to 100% mobile phase B for 12 min, with mobile phase B held for an additional 3 min. The detection wavelength was 275 nm.

[0113] The invention is illustrated in more detail by the following non-limiting examples in which parts and percentages are by weight unless otherwise specified.

[0114] NaHCO3 Example - Catalyst Dosage and Pressure-Time Process Variations General Procedure for Examples 1-9 Methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate (326 g, 1.12 mol) and stearyl alcohol (300 g, 1.10 mol) were charged to the vessel under a nitrogen flow and heated. When the temperature of the reaction mixture reached 130 °C, a vacuum (20 mbar) was applied. After 20 minutes, the vessel was vented with nitrogen and the temperature was increased to 200 °C. At an internal temperature of 190 °C, NaHCO (6.2 g for 1 wt %, 3.1 g for 0.5 wt %, and 1.5 g for 0.25 wt %) was added, and the reaction was carried out under various pressure-time steps. Product yields are expressed as the conversion of the target molecule in the resulting reaction mixture in terms of GC area %.

[0115] The various catalyst loadings and pressure-time steps are outlined in Table 1.

[0116] [Table 1]

[0117] All examples in Table 1 show very high conversion rates exceeding 90 GC area %. For example, for Example 8, which had a conversion rate of 90.22 GC area %, the catalyst usage was 0.25 wt.% of the total usage in the vessel, and the reaction was first carried out at a pressure of 200 mbar for 2 hours, after which the pressure was reduced to 10 mbar for 4 hours, resulting in a total reaction time of 6 hours. In comparison, for Example 4, which had a conversion rate of 93.48 GC area %, the catalyst usage was 1 wt.% of the total usage in the vessel, and the reaction was first carried out at a pressure of 200 mbar for 1 hour, after which the pressure was reduced to 100 mbar for another 1 hour, after which the reaction was carried out at 10 mbar for 4 hours. The total reaction time for Example 4 was 6 hours.

[0118] Example of Na2CO3 General Procedure for Examples 10-11 Methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate (326 g, 1.12 mol) and stearyl alcohol (300 g, 1.10 mol) were charged to the vessel under a nitrogen flow and heated. When the internal temperature of the reaction mixture reached 130 °C, a vacuum (20 mbar) was applied. After 20 min, the vessel was vented with nitrogen and the temperature was increased to 200 °C. At an internal temperature of 190 °C, Na2CO3 (6.2 g, 58.5 mmol, 1 wt%) was added, and the reaction was carried out under various pressure-time steps. Product yields are expressed as the conversion of the target molecule in the resulting reaction mixture in terms of GC area %.

[0119] The various pressure-time steps are outlined in Table 2.

[0120] [Table 2]

[0121] Both examples in Table 2 show high conversion rates of over 80 GC area %. It can be seen that within the same time frame of 6 hours, conversion can be improved by reducing the pressure to 200 mbar or less from the beginning (Example 11) compared to a transesterification process where the pressure is maintained at room temperature of 1013 mbar for one-third of the time (2 hours) (Example 10).

[0122] Examples of variations in catalyst addition Procedure for Example 12 Under a nitrogen flow, the vessel was charged with methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate (326 g, 1.12 mol) and stearyl alcohol (300 g, 1.10 mol) and heated. When the internal temperature of the reaction mixture reached 130°C, a vacuum (20 mbar) was applied. After 20 minutes, the vessel was vented with nitrogen and the temperature was increased to 200°C. At an internal temperature of 190°C, NaHCO3 (3.10 g, 0.5 wt%) was added. The reaction was initially carried out at atmospheric pressure for 2 hours. After that, an additional 0.5 wt% NaHCO3 (3.10 g) was added, the pressure was reduced to 100 mbar for 2 hours, and finally, the reaction was carried out at 50 mbar for 2 hours.

[0123] The product was obtained in a yield of 91.04%, which is expressed as the GC area % conversion of the target molecule in the resulting reaction mixture.

[0124] [Table 3]

[0125] No significant change in conversion was observed compared to Example 1, where only one addition of 1 wt. % total NaHCO3 was made at the beginning of the reaction and the reaction was further carried out under similar pressure-time steps.

[0126] Examples of various extract variations Example 23: Synthesis of poly(oxy-1,2-ethanediyl)-alpha-[3-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]-1-oxopropyl]-omega-[3-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]-1-oxopropoxy][CAS No. 36541-61-4] Under a nitrogen flow, a vessel was charged with methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate (340 g, 1.16 mol), PEG200 (97.0 g, 485 mmol), and NaHCO3 (1.10 g, 0.25 wt%) and heated at ambient pressure. When the internal temperature of the reaction mixture reached 140 °C, a vacuum of 200 mbar was applied. After 1 h of reaction time, a gradual reduction in pressure was initiated, ultimately maintaining 20 mbar after 2 h of total reaction time. After 3 h of reaction time, the temperature was gradually increased to 190 °C. These conditions (temperature of 190 °C and pressure of 20 mbar) were then maintained for an additional 6 h of reaction time. The final product was obtained in 98% yield, which is expressed as the GC area % conversion of the target molecule in the resulting reaction mixture.

[0127] Example 24: Synthesis of tetrakis[3-(4-hydroxy-3,5-di-tert-butylphenyl)propionyloxymethyl]methane [CAS number 6683-19-8] Under a nitrogen flow, the vessel was charged with methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate (341 g, 1.16 mol), pentaerythritol (44.6 g, 327 mmol), and NaHCO (1.45 g, 0.25 wt%) and heated at ambient pressure. After reaching an internal temperature of 190° C., the pressure was gradually reduced from 1013 mbar to 20 mbar within 1 hour, and the reaction mixture was maintained under these conditions (temperature of 190° C. and pressure of 20 mbar) for an additional 5 hours.

[0128] The final product was obtained in 76% yield, which is expressed as HPLC area % conversion of the target molecule in the resulting reaction mixture.

[0129] Example 25: Synthesis of 2-ethylhexyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propanoate 2,2'-methylenebis(6-tert-butyl-4-methylphenol) [CAS No. 144429-84-5] Under a nitrogen flow, a vessel was charged with methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate (341 g, 1.16 mol) and 2-ethylhexanol (173 g, 1.33 mol) and heated at ambient pressure. When the internal temperature of the reaction mixture reached 160°C, NaHCO3 (1.28 g, 0.25 wt%) was added, followed by a stepwise reduction in pressure from 1013 mbar to 200 mbar and maintained for 1 hour. The temperature was then increased stepwise to reach 180°C, and the pressure was finally reduced to 80 mbar. The total reaction time after the addition of NaHCO3 was 6 hours.

[0130] The product was obtained in 89% yield, which is expressed as GC area % conversion of the target molecule in the resulting reaction mixture.

[0131] Example 26: Synthesis of ethylene bis(oxyethylene) bis[3-(5-tert-butyl-4-hydroxy-m-tolyl)propionate][CAS No. 36443-68-2] Under a nitrogen flow, a vessel was charged with methyl 3-(3-tert-butyl-4-hydroxy-5-methylphenyl)propionate (431 g, 1.72 mol), triethylene glycol (128 g, 852 mmol), and NaHCO (1.40 g, 0.25 wt%) and heated at ambient pressure. When the internal temperature of the reaction mixture reached 120 °C, the pressure was reduced from 1013 mbar to 200 mbar. Within 1 h, the temperature was increased to reach 180 °C while maintaining the pressure. The temperature was then maintained at 180 °C while the pressure was reduced to finally reach 20 mbar over 2 h, and maintained under these conditions for an additional 8 h. The product was obtained in 89% yield, expressed as the weight percent of the target molecule in the resulting reaction mixture.

[0132] Example of transmittance measurement General Procedure for Examples 13-14-22 Methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate (326 g, 1.12 mol) and stearyl alcohol (300 g, 1.10 mol) were charged to the vessel under a nitrogen flow and heated. When the internal temperature of the reaction mixture reached 130 °C, a vacuum (20 mbar) was applied. After 20 minutes, the vessel was vented with nitrogen and the temperature was increased to 200 °C. At an internal temperature of 190 °C, the catalyst (6.2 g, 58.5 mmol, 1 wt%) was added. The reaction was first carried out at atmospheric pressure for 2 hours, then the pressure was reduced to 100 mbar for 2 hours, and finally the reaction was carried out at 50 mbar for 2 hours. The mixture was discharged from the vessel under a nitrogen flow and filtered under inert conditions. The transmittance of the sample was then measured at 425 nm and 500 nm in toluene (c = 0.1 g / mL).

[0133] The results of the permeability measurements are listed in Table 4.

[0134] [Table 4]

[0135] The values ​​in Table 4 reflect that the 99.9% transmittance using NaHCO3 and Na2CO3 as catalysts indicates near complete transmittance by being "colorless," or colorless, while the transmittance of KHCO3, while still above 90% at both wavelengths, is slightly below that of NaHCO3 and appears to be visually slightly colored with a tan tint. Similarly, K2CO3, similar to KHCO3, exhibits a slight yellow tint.

[0136] Comparative examples using other catalysts General Procedure for Examples 15-20 Methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate (326 g, 1.12 mol) and stearyl alcohol (300 g, 1.10 mol) were charged to the vessel under a nitrogen flow and heated. When the internal temperature of the reaction mixture reached 130 °C, a vacuum (20 mbar) was applied. After 20 minutes, the vessel was vented with nitrogen and the temperature was increased to 200 °C. At an internal temperature of 190 °C, catalyst (6.2 g, 58.5 mmol, 1 wt%) was added. The reaction was first carried out at atmospheric pressure for 2 hours, then the pressure was reduced to 100 mbar for 2 hours, and finally the reaction was carried out at 50 mbar for 2 hours. Product yields are expressed as the GC area % conversion of the target molecule in the resulting reaction mixture.

[0137] The various catalysts used are listed in Table 5.

[0138] [Table 5]

[0139] The data presented in Table 5 demonstrate that alkali metal bicarbonates or alkali metal carbonates can be a substitute for other catalysts used in transesterification, and in particular, alkali metal bicarbonates can be as effective as aluminum catalysts, but without the drawbacks discussed above.

[0140] Comparative Example with Reference to Prior Art (USSR Patent Application Publication No. 1014213) General Procedure for Example 21 Methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate (261 g, 891 mmol) and stearyl alcohol (240 g, 883 mmol) were charged to the vessel under a nitrogen flow and heated. When the internal temperature of the reaction mixture reached 130 °C, a vacuum (20 mbar) was applied. After 20 minutes, the vessel was vented with nitrogen, and a catalyst mixture of K2CO3, Na2CO3, and phenol (3.90 g K2CO3, 7.80 g Na2CO3, 11.9 g phenol, total: 4.71 wt%) was added at an internal temperature of 140 °C. The reaction was initially carried out at 200 mbar for 0.5 hours, then the pressure was reduced to 100 mbar over 0.5 hours, and finally the reaction was carried out at 80 mbar for 8 hours.

[0141] Finally, after a reaction time of 9 h, the conversion of the target molecule in the resulting mixture (expressed as GC area %) was 88.88%.

[0142] The yield of the obtained product was analyzed by gas chromatography (GC), and the individual desired components were detected according to their individual retention times, and their concentrations were determined as percentages of their respective peak areas as GC area %.

[0143] A total of 2.28% conversion (expressed as GC area %) consisted of several detected unknown by-products formed during the comparative transesterification reaction, while 8.84% of unconverted extractables was also found to be detected.

[0144] For comparison, in Example 4 according to the invention, the use of only 1 wt. % NaHCO as a catalyst in the transesterification process according to the invention resulted in only 0.34 GC area % total amount of undesirable compounds detected by GC, which were found to be simply impurities of the extract.

[0145] In addition to the relatively high amount of by-products obtained according to the prior art process using the mixture of three catalysts, the permeability results were also unfavorable.

[0146] The transmittance of the samples was measured at 425 nm and 500 nm in toluene (c=0.1 g / mL). The results of the transmittance measurements are listed in Table 6 below.

[0147] [Table 6]

Claims

1. Formula (I) 【Chemistry 1】 (In the formula, R １ and R ２ are each independently hydrogen or a linear or branched C １ ~C ８ is alkyl, m is 0 or an integer selected from 1, 2, or 3; n is an integer selected from 1, 2, 3, or 4; and A is OR when n is 1 ３ and R ３ is C ４ ~C ２０ Alkyl or C ５ ~C １２ cycloalkyl, or When n is 2, A is a group of the formula -O-C ｘ H ２ｘ -O-, O-C ｘ H ２ｘ -S-C ｘ H ２ｘ —O, —NH—C ｘ H ２ｘ -NH- or -O-(CH ２ CH ２ O) ａ CH ２ CH ２ O- (In the formula, x is an integer selected from 2 to 8, and a is an integer selected from 1 to 12. have or A is a group of formula H when n is 3 ３ C-C ｘ H ２ｘ -C(C ｙ H ２ｙ O-) ３ , —O—C ｘ H ２ｘ -CH ２ (O-)-C ｙ H ２ｙ -O- (wherein x and y are each independently an integer selected from 1 to 8) have or A is a group of formula -C(-CH ２ -O-) ４ (having by transesterification, comprising the step of: 【Chemistry 2】 The compound of formula (III) 【Transformation 3】 and the process step of said transesterification reaction between the compound of formula (II) and the compound of formula (III) is reacted with a compound of formula (II) ３ , Na ２ CO ３ , KHCO ３ and K. ２ CO ３ 1. A non-aqueous process characterized by being initiated by the addition of a catalyst consisting of an alkali metal bicarbonate or alkali metal carbonate selected from the group consisting of:

2. 2. The process of claim 1, wherein m is 2.

3. R １ and R ２ are each independently a linear or branched C １ ~C ４ 3. The process of claim 1 or 2, wherein the alkyl is alkyl.

4. R １ and R ２ The process of claim 1 or 2, wherein both are tert-butyl.

5. n is 1, and R ３ is C ８ ~C １８ The process of any one of claims 1 to 4, wherein the alkyl is alkyl.

6. n is 4 and A is the group —C(—CH ２ -O-) ４ The process according to any one of claims 1 to 4, wherein

7. 10. The process of claim 1 carried out in the absence of a solvent.

8. The catalyst is NaHCO ３ or Na ２ CO ３ 2. The process of claim 1, wherein

9. The catalyst is NaHCO ３ 9. The process of claim 8, wherein

10. 2. The process of claim 1, wherein the reaction is carried out in a temperature range of 120 to 220°C, preferably 130 to 200°C, more preferably 150 to 190°C.

11. 10. The process of claim 1 operated at an atmospheric pressure of 1000 mbar or less.

12. 12. The process of claim 11 operated in the range of 300 to 1 mbar, preferably 200 to 1 mbar, more preferably 100 to 1 mbar.

13. 10. The process of claim 1, wherein after the reaction, the catalyst is removed from the resulting product by filtration.

14. 2. The process of claim 1, wherein the catalyst is added to the mixture of the compound of formula (II) and the compound of formula (III) at a concentration of less than 5 wt%, preferably 0.1 to 5 wt%, more preferably 0.2 to 2 wt%, and most preferably 0.25 to 1 wt%.

15. 2. The process of claim 1, wherein the transesterification process step is carried out for 1 to 8 hours, preferably 4 to 6 hours.

16. 10. The process of claim 1 in the presence of an organic inert solvent selected from pentane, hexane, heptane, octane, decalin, cyclohexane, benzene, toluene, xylene, mesitylene, dichloromethane, chloroform, tetrachloromethane, bromoform, petroleum ether, tetrahydrofuran, or mixtures thereof.

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