DE1770511C3 - Ethyltrimethylpyrazine, process for its production and its use as a flavor substance - Google Patents

Description

The invention relates to Äthyltrimethylpyrazzin, a process for its preparation and its use as Aroma substance.

It has been found that ethyltrimethylpyrazine is an important component of cocoa flavor Compound is not actually a natural substance, as it only occurs through human action when roasting the Cocoa beans is created. It is to be regarded as inventive because, due to its humus-like smell, it could not be expected that it would be in Combination with other aromatic substances would enhance the cocoa-like taste note.

According to a preferred embodiment of the invention is ethyltrimethylpyrazine by reacting Trimethylpyrazine made with ethyl lithium

Preferably, the reaction is below room temperature, for example in the range of 0 to - 10 ⁰ C, advantageously in an inert solvent such as ether performed, After completion of the reaction, the solvent can be removed and the Äthyltrimethylpyrazin be recovered by distillation under reduced pressure. It is a colorless liquid.

The trimethylpyrazine used as starting material can advantageously be synthesized from butanedione and 1,2-diaminopropane and subsequent dehydrogenation of the heterocyclic intermediate, the desired pyrazine ring structure being obtained. The first stage of this reaction can be carried out at room temperature, for example in a solvent such as ether, be carried out as the reaction medium, with practically equimolar amounts of reactants be used. For example, the butanedione can be mixed with an ethereal solution of 1.2-Diiiminopropane are added. The implementation

usually completes within 4 to 5 hours,

to obtain 234-trimethyl-5,6-dihydropyrazine.

The dehydration of the dihydro intermediate

can according to the usual dehydration process be carried out, for example, by the Combination together with a basic substance, such as sodium or potassium hydroxide, heats it up The reaction is preferably carried out under, and after completion of, an inert atmosphere

The trimethylpyrazine can be implemented in any Wise can be obtained from the reaction medium, for example by distillation under reduced Pressure. The substance is a colorless liquid with a strong pyrazine odor.

¹ S According to the invention, ethyltrimethylpyrazine can also be prepared by one of the following processes.

(a) Implementation of 23-diaminobutane or , ο one of its salts with pentane-23-dk> n

The reaction can be carried out by mixing practically equimolar proportions of the reactants Stirring can be carried out, the mixture being z. B. lets react overnight Das Äthyltrimethylpyra Tin can be obtained by distillation under conditions similar to those given above. If the corresponding dihydropyrazine in Reaction mixture is detected, a dehydrogenation reaction can be carried out, for example by heating the mixture with a basic substance such as squid hydroxide.

The 23-diaminobutane used as starting material can, for example, by reducing Dimethylglyoxime, e.g. with Raney nickel or with

Lithium aluminum hydride.

(b) conversion of 23-diaminopentane or one of its salts with butanedione

This reaction can be carried out under conditions similar to those given in (a). That as 23-Diaminopentane used as the starting material can be produced by reducing methylethylglyoxime be, the latter compound for example by reacting pentane-23-dione with Hydroxylamine is produced.

(c) Implementation of an Äthyldimehtylpyrazins with methyllithium

All three isomers of ethyldimethylpyrazine 2-so ethyl-33-dimethyl-, 2-ethyl-5,6-dimethyl-, or 2-Ethyl-3,6-dimethyl-pyrazine can be used as starting materials, either alone or as a mixture, which contains two or all three isomers. The reaction of the pyrazine with the methyllithium is ss preferably in a solvent such as ether, carried out, practically equimolar amounts of the reactants are used. The Äthyltrimethylpyrazine can then by distillation from the Reaction medium is obtained a * ° The ethyldimethylpyrazine used as the starting material can be prepared using one of the following processes:

1. Ring halogenation of a dimethylpyrazine and ethylation of the halogenated compound via the

⁶ S Grignard connection.

2. Side chain halogenation of trimethylpyrazine and methylation of the halomethyl compound formed via the Grignard compound.

3. Methylation of a monosodium trimethylpyrazine.

4. Ring ethylation of dimethylpyrazine with ethyl lithium or ethyl bromide and aluminum chloride.

The conditions under which the reactions indicated above can be carried out are comparable to those described here in Connection with the production of Äthyltrimethyipyrazine or the other alkylpyrazines are given. to

(d) Implementation of trimethylpyrazine with ethyl bromide and aluminum chloride

The reaction participants can, for. B. be heated under reflux in a solvent such as carbon disulfide as the reaction medium. Small amounts of dimethylpyrazine and tetramethylpyrazine can also form, and the ethyltrimethylpyrazine is separated from the reaction mixture by fractional distillation or fractional crystallization of a salt

(e) Conversion of monosodium tetramethylpyrazine with a methyl halide

This implementation is preferably carried out in a * 5 Solvent carried out as the reaction medium, expediently methyl bromide is used as the halide. The sodium derivative of tetramethylpyrazine can be prepared by reacting tetramethylpyrazine with sodium amide or benzyl sodium.

If sodium amide is used, a solution of this reactant can first be prepared by dissolving sodium in liquid ammonia whereupon the tetramethylpyrazine to form the Sodium derivative is added.

(f) Reaction of 2-halosnimethyl-3,5,6-trimethylpyrazine with a methylation agent

This reaction is carried out by first forming a Grignard intermediate of the halomethyltrimethylpyrazine, which is then mixed with a methylation agent, such as methyl iodide or dimethyl sulfate, is reacted. If bromomethyltrimethylpyrazine is used as the starting material, then this substance is produced, for example, by reacting tetramethylpyrazine with N-bromosuccinimide will.

(g) ethylation of a 2-halo-3,5,6-trimethylpyrazine

The preferred starting material is 2-chloro-3,5,6-trimethylpyrazine. First, through implementation with Magnesium produced a Grignard derivative of this compound, whereupon this derivative was then combined with a Ethylating agents, such as diethyl sulfate, is ethylated Das SS Halo-trimethylpyrazine can expediently be carried out according to the method of CF. Koelsch and W.'H. Gumprecht (J.Org.Chem, 23, 1603 [1958]) will. In this process, trimethylpyrazine is converted into trimethylpyrazine-N-oxide with hydrogen peroxide then reacted with a phosphorus oxyhalide is implemented.

Ethyltrimethylpyrazine can also be used in small amounts through a conversion between ribose and ammonia or certain amino acids, such as «-aminobutyric acid, Lysine or threonine. Ethyltrimethylpyrazine has also been detected in roasted coffee and probably will when roasting others too

Get substances that contain sugar and amino acids.

Ethyltrimethylpyrazine can be added to various cocoa-containing products to give it a cocoa note to emphasize. Examples of these products are cocoa mixtures, drinking chocolate, chocolate objects with different shapes, such as sticks, filled candies, chocolate coatings, e.g. for biscuits, Confectionery and baked goods, chocolate pudding mixes and the like. Very satisfactory results are obtained by adding 1 to 10 parts by weight Ethyltrimethylpyrazine to 100,000 parts by weight of cocoa solids. Amounts at the lower limit of this Range (1-4 parts / 10 * parts) are used for products which have a high cocoa content, e.g. B. preferred for dark (egg .. safe) chocolate, whereas higher '. »narrow (5-10 parts / 10 * parts) products that contain less cocoa, such as milk chocolate or drink mixes, can be added. the Compound can also be incorporated into a synthetic cocoa flavor.

The following examples are given only to illustrate the invention. All parts are Parts by weight.

example 1 a) Production of trimethylpyrazine

116 g (1.35 mol) of butanedione are added dropwise to 100 g (136 mol) of U-diaminopropane in 200 ml of diethyl ether. The thick, white solution formed becomes clear and yellow after vigorous stirring for 4 to 5 hours. The ether is removed, with 158 g of 23,5-trimethyl-5,6-dihydropyrazine remaining, which are then refluxed for 3 to 5 hours with about 40 g of potassium hydroxide pellets. This operation is carried out under nitrogen After distilling off the reaction mixture under reduced pressure (59-63 ⁰ C, 9 mm Hg) to give 96 g trimethylpyrazine be obtained.

Analysis:

Calculated for C7H10N2: 122.0844 found (by mass): 122.0841; n% ^3-1.4970.

Gas chromatography: retention index (Kovats) = 1.005, when using a column with a Length of 6 m and a diameter of 03 cm, which contains Chromosorb W (45-60 meshes) and 20% silicone gum

Helium feed rate: 150 ml / min, temperature 160 ^° C

b) Production of Ethyltrimethylpyrazine

A solution of ethyl lithium is made from 6 g lithium and 47 g ethyl bromide according to the method of H. G i 1 m a η, J. A. B a e 1, C G. B r a η η e η et al., J. Am. Chem. Soc, 71, 1499 (1949)

This solution is cooled to -10 ° C., whereupon 39 g of trimethylpyrazine are added dropwise. The solution, which turns red and thickens, is stirred for 1.5 hours without cooling. It is then cooled again to -10 ° C, whereupon ice water is added until it has become clear. The mixture is extracted three times with ether and once with chloroform the extracts are dried over sodium sulfate and the solvents are evaporated the residue is at 85 to 90 ⁰ C (10 mm Hg) wherein Athyltrimethylpyrazin obtained with a purity of 95%; the rest consists essentially of tri- and tetramethylpyr-

azin. The product can be distilled again further cleaned.

Analysis:

Calculated for C ₉ Hi ₄ N ₂ : 150.1157, gelunden (mass spectrometry): 150.11149; jjf = 1.4893.

Gas chromatography (conditions as above): retention index (Kovats) -1150.

Infrared spectrum, liquid film (CsBr plates), grid instrument: Main bands at 2966 (strong \ 2943 (strong), 2878 (medium), 1655 (medium), 1454 (medium), 1415 (medium), 1372 (medium), 1205 (weak), 1172 (weak).

Example 2
(1) Production of 23-diaminobutane ^IJ

A mixture of dimethylglyoxime (11.6g) and Raney nickel alloy (17.7 g) is taken in proportions Stir and cool to 10 ° C of a sodium hydroxide solution (5%, 200 ml) was added and the reaction mixture was left to stand overnight. The diamine can then be extracted with a solvent; preferably it is converted to the hydrochloride (see F.H. Dickey et al, J. Am. Chem. Soc, 74, 944 [1952]), which is then dried by azeotropic distillation with isopropyl alcohol. It can then be in the can be used in the next synthesis stage without further purification.

In another embodiment, dimethylglyoxime (11.6 g) is mixed with excess lithium aluminum hydride (10 g) reduced in ether The reaction is carried out with stirring under reflux and the The solution is left to stand overnight. Then dry ethyl acetate is added and the solution becomes filtered and evaporated in vacuo leaving a concentrated solution of 23-diaminobutane in dry Ethyl acetate is obtained.

(2) Manufacture of ethyltrimethylpyrazine

Pentane-23-dione (10 g) in ether (100 ml) is added to a concentrated ethyl acetate solution of 23-diaminobutane obtained as noted above, and the mixture at wild overnight Room temperature stirred

After completion of the reaction, pure Äthyltrimethylpyrazin (10 mm Hg) is recovered by distillation at 85 to 90 ⁰ C under reduced pressure. The ethyltrimethylpyrazine can also be isolated from the reaction mixture by first forming a salt (e.g. the hydrochloride), whereupon the salt crystallizes out and then alkali is added to liberate the base.

According to a further embodiment, the ethyl acetate solution of 23-diaminobutane by a equivalent amount of dry 23-diaminobutane hydrochloride can be replaced. The hydrochloride will first suspended in ether, after which potassium hydroxide (2 g) is added to liberate the diamine.

Before the ethyltrimethylpyrazine is isolated, the reaction mixture can be subjected to gas chromatography Presence of the dihydro compound (2-ethyl-3,5,6-trimethyl-5,6, -dihydropyrazine) investigate. If this compound is found in significant quantities, it can be removed by heating the mixture with potassium hydroxide becoming dehydrated.

Example 3

Butanedione (8.6 g) witd a solution of 23-diaminopentane (10 g) (produced by reducing methylethylglyoxime with Raney nickel or LiAlH «) in anhydrous ether (100 ml) was added and the mixture was stirred overnight with occasional Heating allowed to react. After the reaction has ended, the mixture is evaporated and Pure ethyltrimethylpvrazine is used as in Example 2 obtained, with all existing dihydro compounds being dehydrated first.

Example 4 (1) Preparation of ethyldimethylpyrazines

Pentane-23-dk> n (0.2 mol) is added dropwise to one Solution of 1,2-diaminopropane (0.2 mol) in anhydrous Diethyl ether (200 ml) is added and the mixture is stirred vigorously until a clear solution is obtained (3–5 hours). Then the solvent is removed Analysis of the residue after preparative gas-liquid chromatography shows its presence of 3-ethyl-2,6-dimethylparazine (Kovats retention index - 1080) and 3-ethyl-2 £ -dimethylpyrazine (retention index = 1105).

A mixture of the corresponding dihydro compounds (retention index = 1130) is also detected. The reaction products are heated for 2-3 hours with potassium hydroxide chips (5 g) Complete dehydration of the pyrazine ring. The retention indices were with the same column and obtained under the same conditions as in Example 1.

(2) Manufacture of ethyltrimethylpyrazine

A mixture of ethyldimethylpyrazines prepared as described above becomes one cooled solution of methyllithium [obtained from methyl iodide (34 g) and lithium (1.4 g)]) in anhydrous Diethyl ether (200 ml) is added and the reaction is carried out for a few hours Solvent removed and the Äthyltrimethylpyrazine, as indicated in Example 2, from the residue won.

Example 5

Trimethylpyrazine (5 g) is mixed with ethyl bromide (5 g) in a carbon disulfide solution (100 ml) in the presence refluxed with aluminum chloride (11 g) as a catalyst. After the reaction has ended, is Ice water is added and the mixture is extracted with ether (3 × 50 ml). The solvent is then removed and ethyltrimethylpyrazine is, as indicated in Example 2, obtained from the residue.

Example 6

Sodium (0.7 g) is added in small portions to liquid ammonia (200 ml) followed by tetramethylpyrazine (4 g); the color changes from blue to red. Then methyl bromide is bubbled into the solution (6-8 g).

When all of the methyl bromide has been added, the ammonia is replaced by ether (100 ml) and the ethereal solution is dried over sodium sulfate. The solvent is then removed and the ethyltrimethylpyrazine is obtained from the residue as indicated in Example 2.

According to another embodiment, the tetramethylpyrazine in the residue can from the Solution are crystallized, being practically pure

Ethyltrimethylpyrazine remains in the mother liquor.

Example 7
(1) Production of bromomethyltrimethylpyrazine

Benzoyl peroxide (03 g) is added to a solution of tetramethyl pyrazine (4.1 g) in anhydrous carbon tetrachloride (150 ml), followed by N-bromosuccinimide (5.4 g). The one in a glass flask The solution present is irradiated with a 500 watt lamp and stirred for 2 hours. Then it is filtered and the filtrate, which contains bromomethyltrimethylpyrazine, is evaporated (retention index = 1320).

(2) Manufacture of ethyltrimethylpyrazine

Bromomethyltrimethylpyrazine (6.4 g) is added to anhydrous diethyl ether (100 ml), the magnesium shavings (0.8 g) contains, added. To the solution of the Grignard compound formed is added methyl iodide (4.3 g), and that The mixture is allowed to react with stirring for 24 hours.

Ice water is then added and the mixture is extracted with ether and the extract is dried over Sodium sulfate and removes the solvent. The ethyltrimethylpyrazine is, as indicated in Example 2, obtained from the residue. If desired, dimethyl sulfate can be substituted for methyl iodide Use methylating agents.

Examples

(1) Preparation of 2-chloro-3,5,6-trimethylpyrazine

Hydrogen peroxide (30%, 11.5 g) in acetic acid solution (100 ml) is mixed with trimethylpyrazine (12.2 g) as described by C. F. K o e 1 s c h and W. H. Gumprecht (J. Org. Chem., 23, 1603 [1958]). then phosphorus oxychloride (45 ml) is added to the pyrazine-N-oxide formed, the mixture becomes 15 Heated to reflux for minutes and allowed to react for 1 hour. Excess POCI3 is distilled off, whereby 2-chloro-3,5,6-trimethylpyrazine remains, which immediately can be used in the next stage.

(2) Manufacture of ethyltrimethylpyrazine

2-Chloro-3,5,6-trimethylpyrazine (15 g) turns to fine Magnesium turnings (2.4 g) were added to tetrahydrofuran (200 ml). The formed Grignard derivative is Diethyl sulfate (31 g) added and the reaction allowed to proceed overnight. Then set Ice water is added, the mixture is extracted with ether, the extract is dried over sodium sulfate and removed the solvent. The ethyltrimethylpyrazine is obtained from the residue as described in Example 2.

Example 9

5 ppm ethyltrimethylpyrazine (purity 95%; prepared according to Example 1) are 100 parts of a hot Added to beverage containing 3 parts cocoa solids and 12 parts sugar. Furthermore, a standard without the ethyltrimethylpyrazine produced.

A group of 10 experienced taste testers preferred the drink with the added ethyltrimethylpyrazine.

Example 10

Ethyltrimethylpyrazine becomes plain (dark) chocolate (55% cocoa solids) in an amount of 2 Parts per 100,000 parts cocoa added. The chocolate has a stronger, fuller taste than one Standard chocolate without the addition of ethyltrimethylpyrazine.

Example 11

Ethyltrimethylpyrazine becomes milk chocolate (15% cocoa solids) in an amount of 7 parts per 100,000 Parts of cocoa added. The chocolate has a more pronounced cocoa note.

example 12th It becomes a mixture of the following substances manufactured: Ethyl trimethylpyrazine 551 pieces Benzaldehyde 11 parts Furyl methyl ketone 4 pieces Ethyl benzoate 7 parts 2-phenylethyl acetate 86 parts Furfuryl alcohol 15 parts Acetophenone 31 pieces y-Butyro! acton 85 pieces 1-phenylethanol 44 parts 2-phenylethanol 166 pieces 1000 parts

5 ppm of this batch are 100 parts of hot water containing 5 parts of sugar and 0.01 part of vanillin added. The drink obtained has a pronounced cocoa note.

Claims (4)

Patent claims: 1. Ethyltrimethylpyrazine. 2. Process for the preparation of Äthyltrimethylpyrazzin, characterized in that one in itself known way either a) Trimethylpyrazine with ethyl lithium or an ethyl dimethyl pyrazine with methyl lithium or b) 23-diaminobutane or one of its salts with 23-pentanedione or 23-diaminopentane or one of its salts condensed with butanedione or c) Reacts trimethylpyrazine with ethyl bromide and aluminum chloride or d) monosodium telramethylpyrazine with a Reacts methyl halide or e) Halomethyl-trimethylpyrazine or Halogentrimethylpyrazine in the corresponding Converts Grignard compounds and these then methylated or ethylated 3. Use of ethyltrimethylpyrazine to flavor foods and beverages. 4. Use according to claim 3 for flavoring cocoa or cocoa products, in quantities from 1 to 10 parts by weight of ethyltrimethylpyrazine 100,000 parts by weight of cocoa.