Formulations for imparting aroma to food products

Abstract

The present invention relates to a method for producing a formulation for imparting aroma to products, in particular food products, semi-luxury foods, cosmetics or pharmaceuticals, and dietary supplements, which formulation preferably comprises at least one (Ia): JPEG2025538416000133.jpg42114 and / or at least one (alkyl)pyrazine of formula (Ib): (Alkyl)pyrazine (wherein R 1 , R 2 , and R 3 represents a group as defined in the claims).

Description

[Technical Field]

[0001] The present invention relates to a formulation for imparting aroma to food products, semi-luxury foods (luxury foods), cosmetics or pharmaceuticals, and dietary supplements, and to a method for producing such a formulation. [Background technology]

[0002] Among pyrazines substituted with one or more alkyl or cycloalkyl groups, highly potent aroma compounds are known to exist naturally, some of which have very low odor thresholds. Alkylpyrazines, such as 2-ethyl-3,5-dimethylpyrazine or 2,3-diethyl-5-methylpyrazine, have an earthy odor. Corrillone pyrazine (also known as 5-methyl-6,7-dihydrocyclopentapyrazine or nutty pyrazine) is a flavoring compound with a strong odor. This odor may be described as sweet, nutty, roasted, toasty, earthy, or cereal, coffee, or popcorn-like. Corrillone pyrazine is found in the natural flavors of coffee and many nuts. In the flavor industry, this compound is used, for example, to enhance the aroma of popcorn.

[0003] It has been shown in the prior art that the addition of alkyl-substituted pyrazines, either alone (Patent Document 1) or in combination with other compounds (Patent Document 2), to food or delicatessen products improves the flavor of the products. Patent Document 1 discloses three reactions for producing alkyl-substituted pyrazines: the reaction of a diketone with ethylenediamine, the reaction of an alkyllithium with a dialkylpyrazine, and the reaction of sodium amide with an alkylpyrazine.

[0004] Various approaches for the preparation of pyrazines have been described in the literature (Non-Patent Document 1). Classical synthetic routes involve the use of various metal compounds. For example, pyrazines can be prepared by the condensation of 1,2-diaminoalkanes with 1,2-dicarbonyl compounds using copper(II) oxide and manganese oxide as oxidants. [ka]

[0005] Pyrazines can also be obtained by condensation of two molecules of α-aminoketones or α-aminoaldehydes. The resulting dihydropyrazines are converted to pyrazines using oxidizing agents such as salts of divalent mercury. [ka]

[0006] Patent Document 3 discloses a method for preparing pyrazine by a gas-phase catalytic reaction at 300° C. to 600° C. in the presence of a zinc-containing catalyst using a diol and a diamine as starting compounds. [ka]

[0007] US Patent No. 4,929,999 (Firmenich SA) discloses the use of two different hydroxyketones to prepare unsymmetrically substituted alkylpyrazines: 1,3-dihydroxypropan-2-one is reacted with an acyloin of formula (III) to give the substituted pyrazine shown in the diagram below. [ka]

[0008] However, the hydroxyketones and dihydroxyketones used are relatively unstable and expensive.

[0009] Pyrazines can be prepared by various synthetic routes, but all currently known methods have certain drawbacks, including the use of solvents and metal compounds, some of which are highly toxic, as well as low yields of the desired product and high reaction temperatures.

[0010] The toxicity of catalysts and solvents can lead to environmental and health risks, making occupational health and safety considerations necessary both in the production and use of these catalysts. Ensuring the necessary safety in the face of toxicological and health problems that primarily arise in the workplace requires complex and costly measures. Furthermore, some of the catalysts used are very expensive compounds, meaning that the purchase, disposal, or recycling of these catalysts can have a negative impact on the price of the final product.

[0011] Another method for obtaining pyrazines involves isolating these compounds from animal materials using known separation techniques, such as steam distillation of cooked pork liver. Pyrazines, including alkylpyrazines, acetylpyrazines, cyclopentapyrazines, and quinoxalines, are known to account for the largest group of aroma compounds in cooked pork liver (Non-Patent Document 2). Pyrazines are a type of so-called reaction flavors. These aroma-active compounds are formed during cooking, frying, and / or baking and are among the substances responsible for the typical aroma of processed foods. According to Flavorings Regulation (EC) No. 1334 / 2008, in the production of reaction flavors used as food additives, heating must not exceed 15 minutes at a maximum temperature of 180°C. This limit is intended to roughly correspond to typical kitchen conditions during food processing.

[0012] In the meat sector, the formation of reaction flavors such as unsubstituted, mono- or polysubstituted pyrazines from aroma precursors as part of the Maillard reaction and Strecker degradation of amino acids has already been extensively studied (e.g., Non-Patent Documents 3 and 4). Pyrazines are formed during the dimerization of α-aminoketones, which are formed during the oxidative deamination and decarboxylation of α-amino acids and α-dicarbonyl compounds. However, the use of animal material as a starting material is questionable from an animal welfare perspective and undesirable from a consumer perspective. Furthermore, the yields obtained from this method are so low that it is not economically viable.

[0013] Patent Document 5, which describes a method for preparing a formulation containing at least one (alkyl)pyrazine, can be considered the closest prior art to the present invention. This prior art method allows the preparation of natural corrillone pyrazine (CP) from cyclotene, L-serine, and acetic acid without using metal compounds or animal starting materials. A drawback of this prior art method is the use of an excess of L-serine, preferably in a ratio of cyclotene to L-serine of 1:3. Furthermore, the prior art method uses highly flammable solvents, such as diethyl ether, to isolate the desired product. [Prior art documents] [Patent documents]

[0014] [Patent Document 1] U.S. Patent No. 3,579,353 [Patent Document 2] UK Patent Application Publication No. 1401096 [Patent Document 3] U.S. Patent No. 4,097,478 [Patent Document 4] German patent no. 69518206 [Patent Document 5] German Utility Model Publication No. 202021104269 [Non-patent literature]

[0015] [Non-Patent Document 1] Ong et al., Borneo Journal of Resource Science and Technology, 2017, 7(2), pp. 60-75 [Non-patent document 2] Mussinan CJ and Walradt JP (1974) Volatile Constituents of Pressure Cooked Pork Liver, J. Agrc. Food Chem., 22, No. 5, 827-831 [Non-patent document 3] Belitz, HD, Grosch, W., Schieberle, P. (2007): Textbook of Food Chemistry. 6th ed., Springer Verlag, Heidelberg, pp. 378-382 [Non-patent document 4] R. Wilhelm (2015), "Comparative studies on volatile aroma compounds during the roasting of beef and pork liver as well as of roasted goose liver and goose foie gras)", Dissertation, Hannover University of Veterinary Medicine Summary of the Invention [Problem to be solved by the invention]

[0016] Therefore, there remains a need for a method for producing a formulation comprising at least one (alkyl)pyrazine that does not have any of the aforementioned drawbacks and that, moreover, does not use metal catalysts or materials of animal origin. A further object of the present invention is to proceed in the most economically viable and resource-efficient way possible. [Means for solving the problem]

[0017] This objective has been achieved in a surprisingly simple manner by a method for producing a formulation, which comprises the following steps: (a) providing at least one compound according to formula (II) or formula (III) or formula (IIIa), preferably a compound according to formula (II) or formula (III): R 2 -C(O)-C(O)-R 3 (II) or R 2 -C(O)-C(OH)=R 3 (III) or R 2 -C(O)-CH(OH)-R 3 In (IIIa), R 2 and R 3 are the same or different and independently represent hydrogen or C 1~4 represents alkyl, or R 2 and R 3 are bonded to each other and together form the formula [ka] or [ka] forming a group of the formula: A, B, C, and D are each independently hydrogen or C 1~4 represents alkyl, (b) providing an α-amino acid; (c) contacting at least one compound according to formula (II) or formula (III) or formula (IIIa), preferably at least one compound of formula (II) or formula (III), with at least one α-amino acid from step (b); Including, At least one solvent suitable for the production of food products and having a boiling point of at least 140°C is used, preferably propylene glycol, glycerol, triethyl citrate, diacetin, monoacetin, and / or triacetin, said solvent being added before and / or during step (c).

[0018] Thus, according to the present invention, the reaction is carried out in solution using a solvent or solvent mixture as described herein. It is particularly preferred to use a solvent mixture that is suitable for food production and that includes a solvent having a boiling point of at least 140°C. As used herein, the term "boiling point" refers to the boiling point at atmospheric pressure (1013.25 mbar).

[0019] Thus, a combination of solvents can also be used, at least one of which has a boiling point of at least 140° C. The solvent having a boiling point of at least 140° C. is preferably selected from the group consisting of propylene glycol, glycerol, diacetin, monoacetin, triacetin, triethyl citrate, or mixtures thereof. Additional solvents can be added, such as water, ethanol, and / or propanol.

[0020] During this process, the following chemical transformations occur: [ka]

[0021] Any α-amino acid may be used to prepare the (alkyl)pyrazine of formula (Ia), but proteinogenic α-amino acids are preferred, selected from the group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, selenocysteine, threonine, tryptophan, tyrosine, valine, and mixtures thereof.

[0022] The method of the present invention makes it possible to produce pyrazines that have not been commercially used until now, such as 2,5(6)-diethyl-3,6(5)-dimethylpyrazine, obtained from acetylpropionyl (10) and an amino acid. The isolated isomer mixture exhibits a strong peanut aroma even at dosages as low as 10 ppm in the product. The product may be selected from the group consisting of food products, semi-luxury foods, cosmetics or pharmaceuticals, and dietary supplements. [ka]

[0023] In the method according to the invention, it is particularly preferred that at least one of the solvents used contains at least one hydroxyl group. This hydroxyl group-containing solvent may be selected from the group consisting of propylene glycol (PG), glycerol (also known as propane-1,2,3-triol), diacetin, monoacetin, triethyl citrate, and mixtures thereof. These hydroxyl group-containing solvents may be mixed with at least one other solvent, such as triacetin or water.

[0024] According to the method of the present invention, when only one of the diketones of formula (II) or formula (III) is contacted with at least one α-amino acid, at least one "symmetric" (alkyl) pyrazine of formula (Ia) can be obtained in both positional isomers. For example, the following "symmetric" (alkyl) pyrazine of formula (Ia) can be obtained by the method according to the present invention: 2,5-Diethyl-3,6-dimethylpyrazine [ka] pyrazine [ka] 2,3,5,6-Tetraethylpyrazine [ka] 4,12-Dimethyl-2,8-diazatricyclo[7.3.0.03,7]dodeca-1,3(7),8-triene [ka] 4,10-Dimethyl-2,8-diazatricyclo[7.3.0.03,7]dodeca-1(9),2,7-triene [ka] 1,2,3,4,6,7,8,9-octahydrophenazine [ka] 2,5(6)-diethylpyrazine [ka] 2,5(6)-dimethylpyrazine [ka]

[0025] According to the method of the present invention, two or more different diketones of formula (II) or formula (III) are contacted in the presence of at least one α-amino acid to obtain at least one "unsymmetric" (alkyl) pyrazine of formula (Ia'). "Unsymmetric" (alkyl) pyrazine of formula (Ia') is understood to mean a pyrazine in which the pyrazine ring is formed from two different diketones of formula (II) or formula (III). [ka]

[0026] In the (alkyl)pyrazine of formula (Ia'), R 2’ and R 3’ are the same or different and independently represent hydrogen or C 1~4 represents alkyl, or R 2’ and R 3’ are combined with each other and together form the expression [ka] or [ka] forming a group of wherein A, B, C, and D are each independently hydrogen or C 1~4 Represents alkyl.

[0027] The process according to the invention makes it possible to obtain, for example, "unsymmetric" (alkyl) pyrazines of formula (Ia') below: 2-Methylpyrazine [ka] 2-Ethylpyrazine [ka] 2,3-Dimethylpyrazine [ka] 2,3-Diethylpyrazine [ka] 2-Ethyl-3-methylpyrazine [ka] 2-Ethyl-5(6)-dimethylpyrazine (cocoapyrazine) [ka] 2,3-Diethyl-5-methylpyrazine [ka] Corilon pyrazine (or 5-methyl-6,7-dihydro-5H-cyclopentapyrazine) [ka] 2(3),5-dimethyl-6,7-dihydro-5H-cyclopentapyrazine [ka] 2,3,5-trimethyl-6,7-5H-dihydrocyclopentapyrazine [ka] 2-Ethyl-3,5,6-trimethylpyrazine [ka] 2,3,5-trimethylpyrazine [ka] 5,6,7,8-Tetrahydroquinoxaline (cyclohexapyrazine) [ka] Methyl-5,6,7,8-tetrahydroquinoxaline [ka]

[0028] It has surprisingly been found that the use of a compound of formula (II) or formula (III) in combination with at least one α-amino acid, preferably an α-amino acid of formula (IV), results in the formation of a second (alkyl)pyrazine of formula (Ib) in addition to formula (Ia). [ka]

[0029] In the α-amino acid of formula (IV), E represents S or O, and R 1 represents hydrogen or methyl. The α-amino acids of formula (IV) include serine, cysteine, threonine, and mixtures thereof.

[0030] In the case of the (alkyl)pyrazine of formula (Ib), the α-amino acid, preferably the α-amino acid of formula (IV), plays an important role since its carbon skeleton is incorporated into the (alkyl)pyrazine. This means that the α-amino acid of formula (IV) functions not only as a nitrogen source but also as a reducing agent in the Strecker degradation, as described in the literature (J. AGR. FOOD CHEM., VOL. 20, NO. 5, 1972 1081).

[0031] In a preferred embodiment of the invention, apart from the α-amino acid(s), no organic acids such as acetic acid or propionic acid are used in the method. In a further preferred embodiment of the invention, the formulation does not contain any organic acids such as acetic acid or propionic acid apart from the α-amino acid(s).

[0032] Influence of the solvent on the ratio of the two (alkyl)pyrazines (Ia) and (Ib) in the reaction with an amino acid, preferably an amino acid of formula (IV): As already mentioned, obtaining the (alkyl)pyrazine of formula (Ib) is highly preferred when using an amino acid of formula (IV), because in this case the carbon skeleton of the amino acid is incorporated into the pyrazine. According to the method described in the present invention, the ratio of two pyrazines, such as (alkyl)pyrazine (Ia) and (alkyl)pyrazine (Ib), can be significantly influenced by selectively choosing the reaction parameters to obtain the desired (alkyl)pyrazine in high yield.

[0033] Surprisingly, it has been found that the choice of solvent in the process according to the invention, in particular the addition of a solvent carrying a hydroxy group, preferably propylene glycol, glycerol (also known as propane-1,2,3-triol), monoacetin, triethyl citrate and / or diacetin, can influence the ratio of the two pyrazines according to formula (Ia) and formula (Ib) and their overall yield.

[0034] It has been found that when a solvent bearing one or more hydroxyl groups, preferably glycerol or propylene glycol, is used as the sole solvent, (alkyl)pyrazines of formula (Ia) are formed particularly preferentially and in short reaction times. Decreasing the proportion of solvent bearing one or more hydroxyl groups (and correspondingly increasing the proportion of triacetin) increases the proportion of (alkyl)pyrazines of formula (Ib) obtained. However, this also adversely affects the reaction rate, so omitting the solvent bearing hydroxyl group(s) can reduce the overall yield of (alkyl)pyrazines (Ia) and (Ib) and can incur additional costs due to longer reaction times. The addition of a catalytic amount of at least one solvent bearing one or more hydroxyl groups, such as glycerol or propylene glycol, i.e., 0.01 mol % to 5 mol % relative to the compound according to formula (II) or (III), has been observed to have the greatest yield-enhancing effect.

[0035] This solvent-dependent product selectivity now also allows cost-effective access to new pyrazines not previously commercially available, such as 2,5(6)-diethyl-3,6(5)-dimethylpyrazine, obtained from acetylpropionyl (10) and amino acids according to formula (IV). The isolated isomer mixture (i.e., a mixture of 2,5-diethyl-3,6-dimethylpyrazine and 2,6-diethyl-3,5-dimethylpyrazine) exhibits a strong peanut aroma even at low doses of 10 ppm in food and other products. As shown in the table below, by appropriately selecting the solvent, a higher ratio of 2,5(6)-diethyl-3,6(5)-dimethylpyrazine (Ia) to (alkyl)pyrazine of formula (Ib) can be obtained. [ka]

[0036] [Table 1]

[0037] If a higher proportion of (alkyl)pyrazine of formula (Ib) is desired in the reaction with the α-amino acid of formula (IV), triacetin or a solvent combination containing triacetin should be used. A mixture of triacetin and at least one solvent containing at least one hydroxyl group is preferred. This solvent containing one or more hydroxyl groups can be selected from the group consisting of propylene glycol, glycerol, diacetin, monoacetin, triethyl citrate, water, and mixtures thereof. The reaction time in a solvent combination containing triacetin is shorter than that in pure triacetin as the solvent. A mixture of triacetin and diacetin or a mixture of triacetin and glycerol is particularly preferred. Triacetin (or glycerol triacetate, E1518) is an ester of glycerol and acetic acid. In the food industry, triacetin is used, inter alia, as a softener or flavor carrier in chewing gum. Triacetin is a natural component of papaya.

[0038] In terms of the yield of the (alkyl)pyrazine of formula (Ib), it is particularly advantageous for the reaction mixture in step (c) to have a triacetin to diacetin ratio in the range of 99:1 to 1:1, preferably in the range of 20:1 to 5:1, and most preferably 19:1. Surprisingly, it has been found that even small amounts of glycerol have a significant effect similar to that of diacetin. It is particularly advantageous for the reaction mixture in step (c) to have a triacetin to glycerol ratio in the range of 99:1 to 99.99:0.01, preferably in the range of 99.5:0.5 to 99.9:0.1, and most preferably 99.84:0.16.

[0039] The mixtures comprising (alkyl)pyrazines of formula (Ia) and (alkyl)pyrazines of formula (Ib) obtainable by the process according to the invention can be used for the manufacture of products such as food products, semi-luxury foods, cosmetics or pharmaceuticals, and dietary supplements.

[0040] The (alkyl)pyrazine of formula (Ia) and the (alkyl)pyrazine of formula (Ib) can be separated from each other. For this purpose, any separation technique known to those skilled in the art can be used. For example, distillation, crystallization, or chromatography can be used as a separation technique. The (alkyl)pyrazine of formula (Ia) or the (alkyl)pyrazine of formula (Ib) isolated by these separation techniques can be used to produce products such as food products, semi-luxury foods, cosmetics or pharmaceuticals, and dietary supplements.

[0041] For example, when 2,3-pentanedione and L-threonine were reacted in a solvent mixture containing (catalytic amounts of) triacetin and glycerol, at least two distinct pyrazine fractions were isolated (i.e., separated from each other). The first pyrazine fraction contained (alkyl)pyrazines of formula (Ib), i.e., cocoa pyrazines, which consist of two isomers (2-ethyl-3,5-dimethylpyrazine and 2-ethyl-3,6-dimethylpyrazine). It was found that the isomer ratios in the cocoa pyrazine product produced by the method of the present invention differ significantly from those in commercially available cocoa pyrazine products. While the ratio of cocoa pyrazine isomer 1 (2-ethyl-3,5-dimethylpyrazine) to cocoa pyrazine isomer 2 (2-ethyl-3,6-dimethylpyrazine) in the commercially available product is approximately 40:60, the ratio of cocoa pyrazine isomer 1 to cocoa pyrazine isomer 2 in the fraction produced by the method of the present invention is greater than about 60:40. Surprisingly, it has been found that the ratio of cocoa pyrazine isomers significantly influences the overall sensory potency of a cocoa pyrazine product. For example, the cocoa pyrazine fraction produced by the method of the present invention is significantly more potent than commercially available variants (such as ethyl dimethyl pyrazine from Riverside Aromatics), i.e., it has approximately a 20% increase in flavor. This makes the cocoa pyrazine product of the present invention more economically viable (lower cost of use).

[0042] Thus, in a preferred embodiment, the present invention relates to a formulation comprising 2-ethyl-3,5-dimethylpyrazine and 2-ethyl-3,6-dimethylpyrazine in a molar ratio of at least 50:50, preferably at least 55:45, and most preferably at least 60:40. Particularly preferred are formulations comprising 2-ethyl-3,5-dimethylpyrazine and 2-ethyl-3,6-dimethylpyrazine in a molar ratio of 50:50 to 70:30, preferably 55:45 to 65:35. In a further preferred embodiment, the present invention relates to a formulation comprising 2-ethyl-3,6-dimethylpyrazine and 2-ethyl-3,5-dimethylpyrazine in a molar ratio of at least 50:50, preferably at least 55:45, and most preferably at least 60:40. Particularly preferred are formulations comprising 2-ethyl-3,6-dimethylpyrazine and 2-ethyl-3,5-dimethylpyrazine in a molar ratio of 50:50 to 70:30, preferably 55:45 to 65:35. The present invention also relates to products containing such formulations, in particular food products, semi-luxury foods, cosmetics or pharmaceuticals, and dietary supplements.Furthermore, the present invention relates to a method for producing a formulation containing 2-ethyl-3,5-dimethylpyrazine and 2-ethyl-3,6-dimethylpyrazine, which method comprises reacting 2,3-pentanedione with an α-amino acid, preferably L-threonine, in a solvent mixture containing at least one solvent containing at least one hydroxy group, the solvent mixture preferably containing triacetin and glycerol.

[0043] The second pyrazine fraction obtained consisted of an isomeric mixture of (alkyl)pyrazines of formula (Ia), namely 2,5-ethyl-3,6-dimethylpyrazine and 2,6-ethyl-3,5-dimethylpyrazine. [ka]

[0044] According to a further aspect, the present invention provides a method for producing a formulation, comprising the steps of: (a) providing at least one compound according to Formula (II) or Formula (III) or Formula (IIIa): R 2 -C(O)-C(O)-R 3 (II) or R 2 -C(O)-C(OH)=R 3 (III) or R 2 -C(O)-CH(OH)-R 3 In (IIIa), R 2 and R 3 are the same or different and independently represent hydrogen or C 1~4 represents alkyl, or R 2 and R 3 are bonded to each other and together form the formula [ka] or [ka] forming a group of the formula: A, B, C, and D are each independently hydrogen or C 1~4 represents alkyl, (b) providing α-amino acids, particularly proteinogenic α-amino acids; (c) contacting at least one compound according to formula (II) or formula (III) or formula (IIIa) with at least one α-amino acid; Including, The present invention relates to a process wherein at least one solvent containing at least one hydroxy group is added before and / or during step (c). Thus, according to the present invention, the reaction is carried out in solution using a solvent or solvent mixture as described herein.

[0045] The solvent containing at least one hydroxy group is preferably selected from the group consisting of propylene glycol, glycerol (also known as propane-1,2,3-triol), monoacetin, triethyl citrate, diacetin, and mixtures thereof.

[0046] Preferably, the solvent containing at least one hydroxy group forms part of the solvent mixture added before and / or during step (c). In a preferred embodiment, the solvent containing at least one hydroxy group comprises 0.01 to 10 weight percent of the solvent mixture. In a particularly advantageous embodiment, the solvent mixture comprises a solvent that does not contain a hydroxy group, preferably triacetin.

[0047] In a preferred embodiment, the solvent containing at least one hydroxy group is used in a ratio of 0.01 mol % to 5 mol % relative to the compound of formula (II) or formula (III) or formula (IIIa).

[0048] According to a further aspect, the present invention relates to (alkyl)pyrazines, in particular (alkyl)pyrazines of formula (Ia): [ka] and / or (alkyl)pyrazines of formula (Ib) [ka] The present invention relates to the use of a solvent containing at least one hydroxy group to increase the yield in a process for producing During the ceremony, R 1 represents hydrogen or methyl, R 2 and R 3 are the same or different and independently represent hydrogen or C 1~4 represents alkyl, or R 2 and R 3 are bonded to each other and together form the formula [ka] or [ka] forming a group of wherein A, B, C, and D are each independently hydrogen or C 1~4Represents alkyl.

[0049] Particularly preferred is a process for preparing the (alkyl)pyrazine, as described above, in which at least one solvent containing at least one hydroxy group is added before and / or during step (c) thereof.

[0050] According to a further aspect, the present invention relates to the use of a solvent comprising at least one hydroxy group for adjusting the molar ratio of (alkyl)pyrazines of formula (Ia) and formula (Ib) in a process for preparing (alkyl)pyrazines. [ka] [ka] During the ceremony, R 1 represents hydrogen or methyl, R 2 and R 3 are the same or different and independently represent hydrogen or C 1~4 represents alkyl, or R 2 and R 3 are bonded to each other and together form the formula [ka] or [ka] forming a group of wherein A, B, C, and D are each independently hydrogen or C 1~4 Represents alkyl.

[0051] Particularly preferred is a process for preparing the (alkyl)pyrazine, as described above, in which at least one solvent containing at least one hydroxy group is added before and / or during step (c) thereof.

[0052] According to a further aspect, the present invention provides a method for producing a formulation comprising the steps of: (a) providing at least one compound according to Formula (II) or Formula (III): R 2 -C(O)-C(O)-R 3 (II) or R 2 -C(O)-C(OH)=R 3 In (III), R 2 and R 3 are the same or different and independently represent hydrogen or C 1~4 represents alkyl, or R 2 and R 3 are bonded to each other and together form the formula [ka] or [ka] forming a group of wherein A, B, C, and D are each independently hydrogen or C 1~4 represents alkyl, (b) providing α-amino acids, particularly proteinogenic α-amino acids; (c) contacting at least one compound according to formula (II) or formula (III) with at least one α-amino acid; Including, The reaction is carried out in solution, The present invention relates to a method in which at least one solvent is used that is suitable for the production of food products and has a boiling point above 140°C.

[0053] Features of embodiments according to different aspects of the present invention may also be combined with one another.

[0054] Addition of ammonium salts Natural quality amino acids, and in particular L-serine, which is used as the sole nitrogen source in the method of claim 1, are relatively expensive, so there was a need for more cost-effective alternatives.

[0055] This object has been achieved in a surprisingly simple manner by using the method according to claim 2, which method further comprises adding at least one ammonium salt. It is particularly advantageous if the at least one ammonium salt is added in one portion in step (c).

[0056] It has been found that the use of ammonium salts allows the amount of α-amino acid, preferably the α-amino acid of formula (IV), to be reduced by 50%, while the yield of the desired product, i.e., the (alkyl)pyrazine of formula (Ib), remains the same. If the amount of amino acid is not reduced, i.e., the molar ratio of the compound of formula (II) or formula (III) or formula (IIIa) to the α-amino acid remains at 1:2, a significant increase in yield is achieved by adding an ammonium salt, preferably two equivalents of an ammonium salt. Furthermore, it has been observed that fewer by-products are formed during purification, significantly simplifying the process.

[0057] The ammonium salt used is preferably an inorganic ammonium salt or an organic ammonium salt. Particularly preferred is an ammonium salt selected from the group consisting of ammonium halides, ammonium phosphates, ammonium sulfates, ammonium carbonates, ammonium bicarbonates, and ammonium carbamates, ammonium salts of organic acids, and mixtures thereof. Particularly preferred is ammonium chloride.

[0058] Herein, the ammonium salt is added in a molar ratio to the amino acid, preferably the amino acid of formula (IV), in the range of 4:1 to 0.1:1, preferably in the range of 2:1 to 0.5:1, most preferably in a ratio of 1:1.

[0059] A solvent, preferably at least one organic solvent, most preferably triacetin, may be added before and / or in step (c). More specifically, the solvent may be added to the compound according to formula (II) or formula (III) or formula (IIIa) and / or the α-amino acid, preferably the α-amino acid of formula (IV), before step (c). In an advantageous embodiment, the process according to the invention comprises, before step (c), The method includes a further step (c1) of adding at least one solvent to the compound according to formula (II) or formula (III) or formula (IIIa), thereby obtaining a solution in which the amount of compound according to formula (II) or formula (III) or formula (IIIa) depends on the solubility of this compound or these compounds in the solvent or combination of solvents used. Solutions maximally saturated with compounds of formula (II) or formula (III) or formula (IIIa) are preferred. Most preferably, the amount of compound of formula (II) or formula (III) or formula (IIIa) in the solvent is up to 40% by weight, most preferably about 2% to 10% by weight, based on the total weight of the solution.

[0060] In step (c), the solution obtained in step (c1) is added dropwise or all at once to the α-amino acid with constant stirring, and the mixture is heated to a maximum temperature of about 180°C, preferably about 100°C to 140°C, and most preferably about 110°C to 130°C.

[0061] It has been found to be particularly advantageous if, prior to step (c), the solution obtained in step (c1) is divided into two doses, the ratio of the first dose to the second dose being in the range of 1:10 to 1:4, preferably in the range of 1:7 to 1:3, most preferably 1:4.

[0062] In a further advantageous embodiment, the process according to the invention comprises, after step (c1), A further step (c2) is included in which a first dose of the solution obtained in step (c1) is mixed with an α-amino acid, preferably an α-amino acid of formula (IV), and the mixture is heated to a maximum temperature of about 180°C, preferably between about 100°C and 140°C, most preferably between 110°C and 130°C.

[0063] In step (c), the second dose of the solution obtained in step (c1) is added dropwise to the mixture obtained in step (c2) under constant stirring.

[0064] In a further advantageous embodiment of the present invention, water, especially distilled water, is used as a solvent in addition to triacetin. It has been found that the amount of water can affect the yield. It is particularly advantageous if, in step (c), the reaction mixture has a ratio of water to the compound according to formula (II) or formula (III) or formula (IIIa) in the range of 40:1 to 10:1, preferably in the range of 30:1 to 20:1, and most preferably 21:1.

[0065] The method according to the present invention may further comprise adding water in step (c), which may be added in one portion to the mixture comprising the α-amino acid and the solution obtained in step (c1) comprising at least one compound of formula (II), (III), or (IIIa).

[0066] Furthermore, the addition of solvent mixtures such as triacetin and diacetin in combination with the addition of at least one ammonium salt has been found to be particularly advantageous in that improved yields and shorter reaction times are achieved.

[0067] Furthermore, it was found that the enhanced reaction control afforded by the addition of ammonium salts also allowed for a reduction in the amount of solvent or solvent mixture. The total reaction volume could be reduced by half (less than 4 mol%) without a significant loss in yield, which would not have been possible without the addition of ammonium salts. This not only improves the economic efficiency of the method, but also leads to a more environmentally friendly alternative, with simplified purification, relatively high yields, and last but not least, half the amount of waste.

[0068] In another embodiment of the present invention, step (c) comprises adding water dropwise to the mixture obtained in step (c2) while constantly stirring. The water is added simultaneously with the addition of the solution obtained in step (c1). However, the water is added separately, i.e., without mixing with the second dose of the solution obtained in step (c1). The rate of addition of water is equal to the rate of addition of the solution obtained in step (c1).

[0069] In the context of the present invention, the radical "C" in the compound of formula (II) or formula (III) or formula (IIIa) 1~4 "Alkyl" represents methyl, ethyl, propyl or butyl, preferably methyl.

[0070] The compound of formula (II) or formula (III) or formula (IIIa) is preferably (1) 2-hydroxy-3-methyl-2-cyclopenten-1-one (also known as cyclotene or MCP), [ka] (2) glyoxal, [ka] (3) 2-oxopropanal, [ka] (4) diacetyl, [ka] (5) 2-hydroxycyclopentanone (2-hydroxycyclopent-2-en-1-one), [ka] (6) 2-hydroxy-3-methyl-cyclopentanone, [ka] (7) 2-hydroxy-3,4-dimethylcyclopentanone (2-hydroxy-3,4-dimethylcyclopent-2-en-1-one), [ka] (8) 3,5-dimethylcyclopentanedione (2-hydroxy-3,5-dimethyl-2-cyclopenten-1-one), [ka] and (9) 2-hydroxycyclohexanone (2-hydroxycyclohex-2-en-1-one), [ka] (10) Acetylpropionyl (acetylpropionyl or 2,3-pentanedione), [ka] (11) 3,4-hexanedione, [ka] is selected from the group consisting of (1) 2-hydroxy-3-methyl-2-cyclopenten-1-one (cyclotene), [ka] or (10) Acetylpropionyl (acetylpropionyl or 2,3-pentanedione) [ka] is particularly preferred.

[0071] The α-amino acids of formula (IV) are in particular selected from the group consisting of L- / D- / (RS)-serine, L- / D- / (RS)-cysteine, L- / D- / (RS)-threonine and mixtures thereof, preferably L- / D- / (RS)-serine and L- / D- / (RS)-cysteine, particularly preferably L-serine or L-cysteine, most preferably L-serine. The amino acids used can be obtained, for example, by enzymatic hydrolysis of vegetable proteins, if it is desired that the flavoring end product or substance obtained from these amino acids is of natural quality.

[0072] The molar ratio of the compound of formula (II) or formula (III) or formula (IIIa) to the α-amino acid, preferably the α-amino acid of formula (IV), can be in the range of 1:1 to 1:5. In the process known from Patent Document 5, the preferred ratio of the compound of formula (II) or formula (III) or formula (IIIa) to the α-amino acid of formula (IV) is 1:3. Surprisingly, it has been found that in the process according to the invention, this ratio can be as low as 1:2, for example 1:1 to 1:2. This leads to the economic advantages of the process according to the invention.

[0073] The reaction in step (c) is carried out at a maximum temperature of approximately 180°C, preferably at a temperature in the range of approximately 100°C to 140°C, more preferably at a temperature in the range of approximately 110°C to 130°C, and most preferably at 125°C. During the course of the reaction, water formation has been observed. The reaction in step (c) is particularly carried out over a period of up to 40 hours, preferably up to 24 hours, more preferably 1 hour to 12 hours, and most preferably up to 6 hours.

[0074] The progress of the reaction in step (c) can be monitored by gas chromatography (GC) analysis. When the compound of formula (II) or formula (III) is no longer detected, the reaction is stopped, for example, by cooling the reaction mixture to room temperature, and optionally, the reaction mixture is neutralized using a basic solution. Preferably, a solution of an alkali hydroxide such as a sodium hydroxide solution or a potassium hydroxide solution can be used as the basic solution.

[0075] Following step (c), the process may further comprise a further step (c1) of isolating the resulting (alkyl)pyrazine of formula (Ia) and / or formula (Ib) from the crude product obtained in step (c).

[0076] The isolation in step (c1) is preferably carried out by rectification, optionally under reduced pressure. Alternatively, after adjusting the pH, the crude product may be concentrated and purified by solid phase extraction (SPE). Fraction(s) containing (alkyl)pyrazines of formula (Ia) and / or formula (Ib) can be obtained with a purity of at least 95% by weight. The fraction obtained by the method according to the present invention may contain one or more (alkyl)pyrazines. The fraction containing multiple (alkyl)pyrazines can optionally be used as further formulation(s). For example, a fraction containing both trimethylpyrazine and tetramethylpyrazine can be isolated.

[0077] Another extraction of the crude product from the reaction mixture can be achieved by co-distillation with propylene glycol (PG). For this purpose, a mixture of glycerol and PG (3:2) is added to the reaction mixture at room temperature and then distilled under reduced pressure. The PG thus distilled serves as a carrier for the pyrazine formed.

[0078] In a particularly preferred embodiment of this method, 2-hydroxy-3-methyl-2-cyclopenten-1-one (cyclotene) is used as the compound of formula (II) or (III), L-serine is used as the α-amino acid of formula (IV), and triacetin or a triacetin-containing mixture is added as a solvent. Triacetin not only dissolves cyclotene, but may also be significantly advantageous in isolating the target product, such as corrillon pyrazine. Because triacetin has a higher boiling point than corrillon pyrazine, the target product, corrillon pyrazine, can be isolated to the desired purity by rectification.

[0079] It was observed that the addition of a solvent mixture containing triacetin and diacetin in combination with the addition of ammonium chloride further improved the process in terms of yield, selectivity, and atom economy.

[0080] The closest prior art document, U.S. Patent No. 5,849,633, discloses the isolation of desired products, such as corrillon pyrazine, by extraction with diethyl ether in a Likens-Nickerson apparatus. Diethyl ether is undesirable for industrial use because it forms a highly flammable vapor-air mixture. The use of triacetin as a solvent avoids the use of diethyl ether.

[0081] Even more surprisingly, an increase in the yield of the desired product was observed compared to the method known in Patent Document 5. In the method of the present invention, the yield of corilon pyrazine can be up to approximately 30 mol%, in contrast to the method described in Patent Document 5, in which the yield of corilon pyrazine is only approximately 6 mol%. The corilon pyrazine-containing fraction obtained after purification and isolation can have a purity of at least 95% by weight.

[0082] Further subject matter encompassed by the present invention includes formulations, in particular those produced by the process according to the invention, which contain at least one (alkyl)pyrazine of formula (Ia). [ka] During the ceremony, R 2 and R 3 are the same or different and independently represent hydrogen or C 1~4 represents alkyl, or R 2 and R 3 are bonded to each other and together form the formula [ka] or [ka] forming a group of wherein A, B, C, and D are each independently hydrogen or C 1~4 Represents alkyl.

[0083] The formulation according to the invention may further comprise at least one (alkyl)pyrazine of formula (Ib). [ka] During the ceremony, R 1 represents hydrogen or methyl, R 2 and R 3 are the same or different and independently represent hydrogen or C 1~4 represents alkyl, or R 2 and R 3 are bonded to each other and together form the formula [ka] or [ka] forming a group of wherein A, B, C, and D are each independently hydrogen or C 1~4 Represents alkyl.

[0084] The (alkyl)pyrazine of formula (Ia) and the (alkyl)pyrazine of formula (Ib) can be separated from each other. For this purpose, any separation technique known to those skilled in the art can be used. For example, distillation, crystallization, or chromatography can be used as a separation technique. The (alkyl)pyrazine of formula (Ia) or the (alkyl)pyrazine of formula (Ib) isolated by these separation techniques can be used to produce products such as food products, semi-luxury foods, cosmetics or pharmaceuticals, and dietary supplements.

[0085] The (alkyl)pyrazine of formula (Ib) can be produced from at least one α-amino acid as the sole nitrogen source. Preferably, a combination comprising at least one α-amino acid and at least one ammonium salt is used as the sole nitrogen source for producing at least one (alkyl)pyrazine according to formula (Ib). Most preferably, a combination consisting of at least one α-amino acid and at least one ammonium salt is used as the sole nitrogen source for producing at least one (alkyl)pyrazine of formula (Ib).

[0086] The formulation preferably contains about 99.9 wt. %, preferably at least about 95 wt. %, of at least one (alkyl)pyrazine according to formula (Ib). Furthermore, the minimum amount of at least one (alkyl)pyrazine according to formula (Ib) in a formulation according to the present invention is about 0.01 wt. %. Preferably, the formulation according to the present invention contains at least about 0.1 wt. % of at least one (alkyl)pyrazine according to formula (Ib) in one or more solvents suitable for the manufacture of food products. For example, when isolating a formulation by SPE using ethanol as a solvent, a product containing at least about 0.1 wt. % to about 0.2 wt. % of at least one (alkyl)pyrazine according to formula (Ib) can be obtained. When co-distilled with PG, a product containing at least about 2 wt. % to about 3 wt. % of at least one (alkyl)pyrazine according to formula (Ib) can be obtained.

[0087] Particularly preferred are (alkyl)pyrazines of formula (Ib), wherein: R 1 represents hydrogen, R 2 and R 3 are bonded to each other and together form the formula [ka] forming a group of the formula: A represents methyl, and B and C represent hydrogen.

[0088] 5-methyl-6,7-dihydro-cyclopentapyrazine (corrillon pyrazine), [ka] pyrazine, [ka] 2-methylpyrazine, [ka] 2,6-dimethylpyrazine, [ka] 2,5-dimethylpyrazine, [ka] 2,3-dimethylpyrazine, [ka] 2,5,6-trimethylpyrazine, [ka] 2-ethyl-3,5-dimethylpyrazine, [ka] 2-ethyl-3,6-dimethylpyrazine, [ka] 2,3-diethyl-5-methylpyrazine, [ka] 2-methyl-6,7-dihydro-5H-cyclopenta[b]pyrazine, [ka] 2,5-dimethyl-6,7-dihydro-5H-cyclopenta[b]pyrazine, [ka] 5,6,7,8-tetrahydroquinoxaline (cyclohexapyrazine), [ka] and 2-methyl-5,6,7,8-tetrahydroquinoxaline, [ka] 2-ethyl-3-methylpyrazine (also known as filbert pyrazine), [ka] 2-ethylpyrazine, [ka] 2,5-diethyl-3,6-dimethylpyrazine, [ka] 2,6-diethyl-3,5-dimethylpyrazine, [ka] tetraethylpyrazine, [ka] 2,3-diethylpyrazine, [ka] Most preferred are (alkyl)pyrazines of formula (Ia) or (Ib) selected from the group consisting of:

[0089] The formulations according to the invention are preferably alcohol-free, particularly preferably ethanol-free.

[0090] Formulations comprising at least 95% by weight of 5-methyl-6,7-dihydro-cyclopentapyrazine (Corrillon Pyrazine) for imparting fragrance to products such as food products, semi-luxury foods, cosmetics or pharmaceuticals, and dietary supplements represent a preferred subject of the present invention.

[0091] Formulations comprising at least 95% by weight of 2,5(6)-diethyl-3,6(5)-dimethylpyrazine for perfuming products such as food products, semi-luxury foods, cosmetics or pharmaceuticals, and dietary supplements represent a preferred subject of the present invention.

[0092] Further objects encompassed by the present invention include products containing the formulation according to the invention, in particular food products, semi-luxury foods, cosmetics or pharmaceuticals, and dietary supplements. The proportion of the formulation according to the invention in this product is up to approximately 1000 ppm, preferably about 10 -3 ppm to about 750 ppm, and most preferably about 0.1 ppm to 150 ppm.

[0093] The formulations according to the invention can be used to impart fragrance to products, in particular food products, semi-luxury foods, cosmetics or pharmaceuticals, or dietary supplements. For this purpose, the products, in particular food products, semi-luxury foods, cosmetics or pharmaceuticals, or dietary supplements, are contacted with the formulations according to the invention.

[0094] Furthermore, the present invention relates to a method for producing a product, in which a formulation according to the invention is brought into contact with the product, in particular a food product, semi-luxury food, cosmetic or pharmaceutical product, and a dietary supplement.

[0095] The present invention is illustrated by the included examples, but is not intended to be limited to the specifically described embodiments. The present invention also relates to any combination of preferred embodiments, unless they are mutually exclusive. The term "about" or "approximately" in combination with a numerical value is understood to mean that the value is at least 10% higher or lower, or 5% higher or lower, and in each case 1% higher or lower. DETAILED DESCRIPTION OF THE INVENTION [Example]

[0096] Example 1 Starting materials: L-serine (500 mmol, 52.5 g) Cyclotene (250 mmol, 28 g) as a 5% solution in triacetin (560 g) Distilled water (95g)

[0097] L-serine (500 mmol, 52.5 g) is mixed with 112 g of cyclotene solution (5% solution in triacetin) and the mixture is heated to approximately 110°C.

[0098] The remaining cyclotene solution (448 g) and distilled water were placed in a dropping funnel and added only when the temperature of the mixture reached 110°C. The mixture was stirred at 110-120°C. The progress of the reaction was monitored by GC analysis. When cyclotene was no longer detected in the reaction mixture, the reaction was stopped (for example, by cooling to room temperature), and the mixture was treated using a rectification apparatus to obtain corrillon pyrazine having a purity of at least 95% by weight. The resulting product was analyzed by GC-FID.

[0099] Example 2 L-serine (105 mmol, 11.1 g) is mixed with 116 g of cyclotene solution (5% solution in triacetin) and 20 g of distilled water. The mixture is heated to 120°C with constant stirring. The progress of the reaction is monitored by GC analysis. When cyclotene is no longer detected in the reaction mixture, the reaction is stopped and the mixture is treated using a rectification apparatus to obtain corrillon pyrazine with a purity of at least 95% by weight.

[0100] Example 3 L-serine (2500 mmol, 263 g) was mixed with 600 g of cyclotene solution (5% solution in triacetin) and heated to approximately 110-120°C. Additional cyclotene solution (2280 g) and distilled water were added to the addition funnel only when the mixture reached 110°C. The mixture was stirred at 110-120°C. The reaction progress was monitored by GC analysis. When no more cyclotene was detected in the mixture, the reaction was stopped and the mixture was adjusted to pH 12 using 30% NaOH solution. The resulting mixture was passed through an SPE column and subsequently eluted with ethanol. This ethanol extract contained 10,000-12,000 ppm of cholorilone pyrazine and can be labeled as a natural flavor extract.

[0101] Example 4 L-serine (121 mmol, 13.9 g) is mixed with cyclotene (121 mmol, 13.9 g), 138 g of glycerol, 91.8 g of propylene glycol, and 45.9 g of water. The mixture is heated to 120 °C. The reaction progress is monitored by GC analysis. The reaction is stopped when cyclotene is no longer detected in the mixture. The mixture is slowly heated to 160 °C, the pressure is reduced to 10 mbar, and the mixture is distilled under reduced pressure (40 mbar). The collected fractions contain 1000 ppm to 5000 ppm of cholilron pyrazine in PG.

[0102] Example 5 L-serine (420 mmol, 44.2 g) is provided with cyclotene (210 mmol, 24.3 g) in a triacetin / diacetin mixture in a 9:1 ratio (1 L). The mixture is heated to 125°C with constant stirring. The progress of the reaction is monitored by GC analysis. When no more cyclotene is detected in the reaction mixture and approximately 19 mol% of cholilon pyrazine is obtained (which is the case after approximately 72 hours), the reaction is stopped and the mixture is treated using a rectification apparatus to obtain cholilon pyrazine with a purity of at least 95% by weight.

[0103] Example 6 Starting materials: L-serine (420 mmol, 44.1 g); Cyclotene (210 mmol, 24.3 g); ammonium chloride (420 mmol, 22.5 g); Triacetin (463 g) and diacetin (24.0 g).

[0104] L-Serine (2 equivalents), ammonium chloride (2 equivalents), and cyclotene (1 equivalent) were placed in a 1-liter three-neck flask equipped with a reflux condenser and a KPG stir bar, along with triacetin (10 equivalents) and diacetin (0.6 equivalents). The mixture was heated to 125°C with constant stirring. The reaction progress was monitored by GC analysis. The reaction was stopped when no cyclotene was detected in the reaction mixture (approximately 32 hours later). The yield was determined by GC analysis to be approximately 29.3 mol% based on the molar amount of cyclotene used. The crude mixture was treated using a rectification apparatus.

[0105] Examples 7 to 11 Example 7 was carried out similarly to Example 5, except that, unlike Example 5, Example 7 had a 19:1 ratio of triacetin to diacetin.

[0106] Examples 8 to 12 were carried out in the same manner as Example 6, but the components such as L-serine, ammonium chloride, and solvent and their respective amounts were changed compared to Example 6 (see Table 1).

[0107] [Table 2]

[0108] As can be seen from Table 1, the addition of ammonium chloride increases the yield. By using ammonium chloride in combination with a solvent mixture such as triacetin and diacetin (see Example 10), the amount of L-serine can be reduced by 50%, while achieving a comparable yield of the target product, i.e., corrillone pyrazine, within a shorter reaction time compared to the reaction without ammonium chloride and diacetin (see Example 8).

[0109] If the amount of L-serine is not reduced, it is observed that the addition of ammonium salts in combination with solvent mixtures such as triacetin and diacetin significantly increases the yield and further shortens the reaction time (see Example 6). Furthermore, it can be observed that fewer by-products that interfere with purification are produced, greatly simplifying the process.

[0110] Furthermore, it was found that the amount of solvent or solvent mixture could be reduced (see Example 12). The total reaction volume could be reduced by half without a significant loss of yield, which would not have been possible without the addition of ammonium salts. This not only improves the economic efficiency of the process, but also leads to a greener alternative with simplified purification, relatively high yields, and last but not least, half the amount of waste.

[0111] Example 12 Starting materials: L-threonine (22 mol, 2.62 kg); 2,3-pentadione (11 mol, 1.1 kg); ammonium chloride (22 mol, 1.12 kg); Triacetin (55 mol, 12.1 kg) and glycerol (8.8 mmol, 0.8 g).

[0112] L-threonine (2 equivalents), ammonium chloride (2 equivalents), and 2,3-pentanedione (1 equivalent) were placed in a 20-liter, three-necked flask equipped with a reflux condenser and a KPG stir bar, along with triacetin (5 equivalents) and glycerol (0.0008 equivalents). The mixture was heated to 140°C with constant stirring. The reaction progress was monitored by GC analysis. The reaction was stopped when no more 2,3-pentanedione was detected in the reaction mixture (approximately 8 hours). The yields determined by GC analysis were approximately 40 mol% for the isomeric mixture of 2-ethyl-3,5(6)-dimethylpyrazine (an (alkyl)pyrazine of formula (Ib)) and 20 mol% for the isomeric mixture of 2,5-diethyl-3,6(5)-dimethylpyrazine (an (alkyl)pyrazine of formula (Ia)), based on the molar amount of 2,3-pentanedione used. The crude mixture was further processed using a rectification apparatus.

[0113] Examples 13 to 17 The reactions described in Examples 13 to 17 were carried out in 20 mL crimp-top vials. The purpose of these experiments was to investigate the effect of various solvents and ammonium salts on the ratio of pyrazines of formula (Ia) and (Ib). To this end, 0.5 g of 2,3-pentanedione (2 mmol) and 1.0 g of serine (10 mmol) were dissolved in 5 mL of each solvent. The mixture was then heated to 140°C for 24 hours with stirring. After cooling, the ratio of pyrazines Ia and Ib was determined by GC-FID.

[0114] [Table 3]

[0115] As can be seen from Table 2, the addition of ammonium chloride increases the overall yield of pyrazine. This is particularly evident in Example 16, where the overall yield was only 25.6%, significantly lower than the overall yields of 55.2% to 66.7% obtained in Examples 13 to 15 and 17.

[0116] The addition of hydroxy-containing solvents such as glycerol and propylene glycol can increase the proportion of pyrazines of formula (Ia) obtained, as can be seen from a comparison of Example 13 with Examples 14 to 17. In catalytic amounts (Examples 14 and 15, 0.15% glycerol), this increases the overall yield, but when used as the sole solvent (Example 17), the selectivity shifts significantly toward pyrazines of formula (Ia).

Claims

1. 1. A method of producing a formulation, comprising: (a) at least one of formula (II) or formula (III) or formula (IIIa): R ２ -C(O)-C(O)-R ３ (II) or R ２ -C(O)-C(OH)=R ３ (III) or R ２ -C(O)-CH(OH)-R ３ (IIIa) (In the formula, R ２ and R ３ are the same or different and independently represent hydrogen or C １～４ represents alkyl, or R ２ and R ３ are bonded to each other and together form the formula: 【Chemistry 1】 or 【Chemistry 2】 wherein A, B, C, and D are each independently hydrogen or C １～４ providing a compound according to the formula (I), wherein the group represents an alkyl group; (b) providing alpha-amino acids, particularly proteinogenic alpha-amino acids; (c) contacting at least one compound according to formula (II) or formula (III) or formula (IIIa) with at least one alpha-amino acid; Including, at least one solvent is used which is suitable for the production of food products and has a boiling point of at least 140°C, in particular propylene glycol, glycerol, triethyl citrate, diacetin, monoacetin and / or triacetin, The method, wherein the solvent is added before and / or during step (c).

2. 10. The process of claim 1 carried out in the presence of at least one ammonium salt.

3. The alpha-amino acid in step (b) is represented by formula (IV): 【Transformation 3】 (wherein E represents O or S, R １ The method according to claim 1 or 2, wherein the amino acid is an alpha-amino acid according to the formula (I) where I represents hydrogen or methyl.

4. The compound according to formula (II) or formula (III) or formula (IIIa) (1) 2-hydroxy-3-methyl-2-cyclopenten-1-one (cyclotene) 【Chemistry 4】 (2) glyoxal 【Transformation 5】 , (3) 2-oxopropanal 【Transformation 6】 (4) diacetyl 【Transformation 7】 , (5) 2-hydroxycyclopentanone (2-hydroxycyclopent-2-en-1-one) 【Transformation 8】 , (6) 2-hydroxy-3-methylcyclopentanone 【Chemistry 9】 , (7) 2-hydroxy-3,4-dimethylcyclopentanone (2-hydroxy-3,4-dimethylcyclopent-2-en-1-one) 【Chemistry 10】 (8) 3,5-dimethylcyclopentanedione (2-hydroxy-3,5-dimethyl-2-cyclopenten-1-one) 【Chemistry 11】 , and (9) 2-hydroxycyclohexanone (2-hydroxycyclohex-2-en-1-one) 【Chemistry 12】 (10) acetylpropionyl(2,3-pentanedione) 【Chemistry 13】 , (11) 3,4-hexanedione 【Chemistry 14】 (12) Methylglyoxal 【Chemistry 15】 is selected from the group consisting of (1) 2-hydroxy-3-methyl-2-cyclopenten-1-one (cyclotene) 【Chemistry 16】 or (10) acetylpropionyl(2,3-pentanedione) 【Chemistry 17】 The method according to any one of claims 1 to 3, wherein:

5. 5. The method according to any one of claims 1 to 4, wherein the alpha-amino acids in step (b) are selected from the group consisting of L- / D- / (RS)-serine, L- / D- / (RS)-cysteine, L- / D- / (RS)-threonine and mixtures thereof, preferably L- / D- / (RS)-serine and L- / D- / (RS)-cysteine, more preferably L-serine or L-cysteine, most preferably L-serine.

6. 6. The method according to any one of claims 1 to 5, wherein the molar ratio of the compound according to formula (II) or formula (III) or formula (IIIa) to said alpha-amino acid is from 1:1 to 1:5, preferably 1:

2.

7. 7. The method according to any one of claims 2 to 6, wherein the molar ratio of ammonium salt to at least one amino acid is in the range of 4:1 to 0.1:1, preferably in the range of 2:1 to 0.5:1, most preferably in a ratio of 1:

1.

8. The method according to any one of claims 1 to 7, wherein the solvent is selected from the group consisting of propylene glycol, glycerol, diacetin, monoacetin, triacetin, triethyl citrate, or a mixture thereof, and water, ethanol, propanol may be further added as a solvent.

9. the reaction in step (c) is accomplished at a maximum temperature of approximately 180°C, preferably in the range of approximately 100°C to 140°C, and most preferably in the range of approximately 110°C to 130°C; A method according to any one of claims 1 to 8, in particular achieved over a period of up to 40 hours, preferably up to 24 hours, more preferably between 1 hour and 12 hours, most preferably up to 6 hours.

10. The resulting formulation comprises at least one compound of formula (Ia): [Chemistry 18] (In the formula, R ２ and R ３ are the same or different and independently represent hydrogen or C １～４ represents alkyl, or R ２ and R ３ are bonded to each other and together form the formula: 【Chemistry 19】 or 【Chemistry 20】 wherein A, B, C, and D are each independently hydrogen or C １～４ 10. The method of claim 1, comprising forming a group (alkyl)pyrazine according to the formula (1), wherein the group represents alkyl.

11. The resulting formulation comprises at least one (alkyl)pyrazine according to formula (Ia) and at least one (alkyl)pyrazine according to formula (Ib): 【Chemistry 21】 (In the formula, R １ represents hydrogen or methyl, R ２ and R ３ are the same or different and independently represent hydrogen or C １～４ represents alkyl, or R ２ and R ３ are bonded to each other and together form the formula: 【Chemistry 22】 or 【Chemistry 23】 wherein A, B, C, and D are each independently hydrogen or C １～４ 11. The method of claim 1, wherein the (alkyl)pyrazine is a substituted or unsubstituted alkyl group.

12. A formulation, in particular a formulation produced by the method according to any one of claims 1 to 11, At least one compound of formula (Ia): 【Chemistry 24】 (Alkyl)pyrazines according to and / or at least one compound of formula (Ib): 【Chemistry 25】 and (alkyl)pyrazines according to the formula: During the ceremony, R １ represents hydrogen or methyl, R ２ and R ３ are the same or different and independently represent hydrogen or C １～４ represents alkyl, or R ２ and R ３ are bonded to each other and together form the formula: 【Chemistry 26】 or 【Chemistry 27】 wherein A, B, C, and D are each independently hydrogen or C １～４ Forming a group of (representing alkyl), formulation.

13. 13. The formulation of claim 12, comprising at least one (alkyl)pyrazine according to formula (Ia) and at least one (alkyl)pyrazine according to formula (Ib).

14. The (alkyl)pyrazines according to formula (Ia) and formula (Ib) are preferably 5-methyl-6,7-dihydro-cyclopentapyrazine (Corrillon pyrazine), pyrazine, 2-methylpyrazine, 2,6-dimethylpyrazine, 2,5-dimethylpyrazine, 2,3-dimethylpyrazine, 2,5,6-trimethylpyrazine, 2-methyl-6,7-dihydro-5H-cyclopenta[b]pyrazine, 2,5-dimethyl-6,7-dihydro-5H-cyclopenta[b]pyrazine, 5,6,7,8-tetrahydroquinoxaline (cyclohexapyrazine), and 2-methyl-5,6,7,8-tetrahydroquinoxaline, 2-ethyl-3-methylpyrazine, 2-ethyl-3,5-dimethylpyrazine, 2-ethyl-3,6-dimethylpyrazine, 2-ethyl-3,5,6-trimethylpyrazine, 2,3-diethyl-5-methylpyrazine, 2-ethylpyrazine, 2,5-diethyl-3,6-dimethylpyrazine, 2,6-diethyl-3,5-dimethylpyrazine, 2,3-diethyl-5,6-dimethylpyrazine, tetraethylpyrazine, and 2,3-diethylpyrazine, is selected from the group consisting of Formulations according to claim 13, wherein 5-methyl-6,7-dihydro-cyclopentapyrazine (corrillon pyrazine) or 2,5(6)-diethyl-3,6(5)-dimethylpyrazine are particularly preferred.

15. A formulation according to any one of claims 12 to 14, comprising 2-ethyl-3,5-dimethylpyrazine and 2-ethyl-3,6-dimethylpyrazine in a molar ratio of at least 50:50, preferably at least 55:45, most preferably at least 60:

40.

16. Products, in particular food products, semi-luxury foods, cosmetics or pharmaceuticals, and dietary supplements, comprising a formulation according to any one of claims 12 to 15.

17. 12. Products, in particular food products, semi-luxury foods, cosmetics or pharmaceuticals, and dietary supplements, comprising at least one (alkyl)pyrazine according to formula (Ib), produced by the method according to any one of claims 1 to 11.

18. A formulation, in particular a formulation produced by the method according to any one of claims 1 to 11, comprising at least one compound of formula (Ib): 【Chemistry 28】 (In the formula, R １ represents hydrogen or methyl, R ２ and R ３ are the same or different and independently represent hydrogen or C １～４ represents alkyl, or R ２ and R ３ are bonded to each other and together form the formula: 【Chemistry 29】 or 【Transformation 30】 wherein A, B, C, and D are each independently hydrogen or C １～４ A formulation comprising an (alkyl)pyrazine according to the formula (1), wherein the (alkyl) represents a group forming (alkyl).

19. 1. A method of producing a formulation, comprising: (a) at least one of formula (II) or formula (III) or formula (IIIa): R ２ -C(O)-C(O)-R ３ (II) or R ２ -C(O)-C(OH)=R ３ (III) or R ２ -C(O)-CH(OH)-R ３ (IIIa) (In the formula, R ２ and R ３ are the same or different and independently represent hydrogen or C １～４ represents alkyl, or R ２ and R ３ are bonded to each other and together form the formula: 【Chemistry 31】 or 【Chemistry 32】 wherein A, B, C, and D are each independently hydrogen or C １～４ providing a compound according to the formula (I), wherein the group represents an alkyl group; (b) providing alpha-amino acids, particularly proteinogenic alpha-amino acids; (c) contacting at least one compound according to formula (II) or formula (III) or formula (IIIa) with at least one alpha-amino acid; Including, A process wherein at least one solvent containing at least one hydroxy group is added before and / or during step (c).

20. 20. The method of claim 19, wherein the solvent containing at least one hydroxy group is propylene glycol, glycerol (also known as propane-1,2,3-triol), monoacetin, triethyl citrate, and / or diacetin.

21. 21. A method according to claim 19 or 20, wherein said solvent comprising at least one hydroxy group forms part of a solvent mixture added before and / or during step (c).

22. 22. The method of claim 21, wherein the solvent containing at least one hydroxy group comprises from 0.01% to 10% by weight of the solvent mixture, preferably from 0.05% to 1% by weight.

23. 23. The method according to claim 21 or 22, wherein the solvent mixture comprises a solvent that does not contain a hydroxy group, preferably triacetin.

24. 24. The method according to any one of claims 19 to 23, wherein the solvent comprising at least one hydroxy group is used in a ratio of 0.01 mol % to 5 mol % relative to the compound according to formula (II) or formula (III) or formula (IIIa).

25. (Alkyl)pyrazines, in particular those of formula (Ia): 【Transformation 33】 and / or (alkyl)pyrazines of formula (Ib): 【Transformation 34】 (Alkyl)pyrazines (In the formula, R １ represents hydrogen or methyl, R ２ and R ３ are the same or different and independently represent hydrogen or C １～４ represents alkyl, or R ２ and R ３ are bonded to each other and together form the formula: 【Chemistry 35】 or 【Transformation 36】 wherein A, B, C, and D are each independently hydrogen or C １～４ 25. Use of a solvent containing at least one hydroxy group to increase the yield in a process for producing a compound (which forms a group of alkyl), in particular in a process according to any one of claims 19 to 24.

26. In a process for preparing (alkyl)pyrazines, in particular in a process according to any one of claims 19 to 24, a compound of formula (Ia) and formula (Ib): 【Chemistry 37】 【Transformation 38】 (In the formula, R １ represents hydrogen or methyl, R ２ and R ３ are the same or different and independently represent hydrogen or C １～４ represents alkyl, or R ２ and R ３ are bonded to each other and together form the formula: 【Chemistry 39】 or 【Chemistry 40】 wherein A, B, C, and D are each independently hydrogen or C １～４ The use of a solvent containing at least one hydroxy group to adjust the molar ratio of (alkyl)pyrazine to (alkyl)pyrazine forming groups (representing alkyl).

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