DE1618059B1 - Process for the production of isohumulone - Google Patents

Description

1 2

A distinctive feature of beer is that it has been set beneficial at the boiling point of the beer

Bitterness, the aqueous medium resulting from the bitter substances in the hops, is characterized in that

is called. The bitter substances, as they are in beer, precede the isomerization by adding at least

lie, are of the bitter substances of hops, a salt of elements of the second main or

and are only separated by a transition group or the iron group of the periodic

'reaction - isomerization' is formed. Here systems or from copper, aluminum, cerium or man-

arise from the little bitter and catalyzed in water and at a pH value below

poorly soluble hop resins, e.g. B. the humulones, 9, such as 4 to 8, works.

Isohumulones, which are readily soluble in beer and are strongly bitter. It is particularly advantageous to use it as a salt

This conversion takes place during normal brewing. Magnesium, calcium, nickel or manganese chloride

Process in the so-called hop or wort or cadmium acetate and carries out the isomerization

cook in front of you, it takes ₂ to 15 minutes at a pH value of 2 ¹ I,

about 5.5 instead of and runs very slowly and incompletely. B. Ba, of course

constantly from. With a cooking time of up to 2 hours, toxicological considerations do not allow for use

carries the maximum yield of 30 to 35% · ¹ exclude S if the isohumulone in the food

So it would be highly desirable to use Humulon Mitteltechnik, however, is theirs

quickly and gently, but with a good yield in suitability for isohümulon preparations that are used for further

To be able to transfer isohumulon. Intended for use in the chemical industry since the twenties

For years it has been known that isomerization is possible.

Humulone when boiling in aqueous alkaline solutions is particularly noticeable in the case of solutions with greater speed and with substantial pH values between 4 and 8. Without the addition of these, better yields occur (German patent metal salts, the reaction takes place at these pH values. Values font 413 913). The isomerization is only very slow and incomplete with aqueous solution (cf. Fig. 1 and soda or sodium hydroxide solution (OH ion concentration and 2). To denote this catalytic concentration n / 10000 or n / 1000) by 30- or 25 acceleration of the conversion of humulone to IsolOminutiges cooking. A similar humulon are shown in the figures. Reaction kinetic mode of operation is from Pet. Journ. d. Brass., 1948, p. 679, experiments shown at different temperatures, known. Isomerization reactions are also used as the reaction medium is a 0.1 molar sodium humulone in aqueous alkaline carbonate and acetate solution, to which the catalytically active phosphate buffer solutions with pH values of 8 to 13 30 metal salts in concentrations of 10 ~ ² mol / l are added (USA.- Patents 2 816 032 and 2 647 837. Further were pure metal salt solutions and British patent specification 855 401). In the British patent mentioned last (0.025 mol / l) (Fig. 2) it is shown that the different pH values for the conversion of humus-humulon isomerization only at pH 9.0 with ions used. This makes it possible to see how the speed is sufficient. In the extravagant figures, an additional Realistic Patent Specification 245 941 often describes how to achieve an acceleration of the structure. For comparison, br an d et al. The photochemical isomerization of the slow isomerization reaction in pure humulone to isohumulone. The implementation, however, is recorded in phosphate buffers. It should be emphasized that the sodium acetate in the reaction solutions is not suitable for production on an industrial scale. 40 the reaction itself is not required, but rather

The known alkaline isomerization of humus is only used to keep the pH constant, ion to isohumulone has the disadvantage that the conversion in this way can be shown that with the same conversion, frequently beyond isohumulone, the pH value is too low Activity of the various desired compounds can continue, e.g. B. is slightly different to metal salts. However, these are humulinic acids. The investigation of the isomerization obtained by alkaline salts of all the above metals for the catalysis of isomerization of pure humulone is useful. For the F i g. 1 and 2 Isohümulonpräparate with the help of the thin-layer the logarithm of the chromatography in the spectrophotometer shows that a whole series of measured humulone absorbance against the reaction-reaction products arise, the nature of which is plotted for the most part (according to Lambert's law and in some cases has not yet been clarified To obtain a 50 beer, the extinction of the concentration of directly pure isohumulone is therefore an expensive proportional).

Cleaning operation, e.g. B. the countercurrent distribution, ~ As can be seen from the figures, are

necessary. Salts of the metals Mg, Ca and Mn are quite catalytic

The object of the invention is now the fast and active and physiologically harmless. This metal-friendly production of isohumulone by means of iso salts, especially those of Mg *, is therefore pre-merged of humulon. applied, with the alkaline earth salts of

It has been found that the isomerization of pH is preferably around 7.

Humulone, e.g. B. in the form of the pure compound or in The isomerization usually takes place at

Form of material containing humulon, temperature increased to isohumulon, especially at the boiling point

by adding salts of certain polyvalent solvents or dispersants, preferably

Can accelerate metals considerably, even aqueous alcohol, but it was found that

at pH values below 9. even at temperatures of only 50 ° C a significant

The process according to the invention for the production of acceleration is present. In the case of isohumulone technically by isomerization of humulone particularly expedient temperatures of 70 to about or humulon-containing material at an elevated temperature of 65 100 ⁰ C (boiling point of the temperature preferably used in an aqueous medium, which is mixed with water-alcohol mixtures, especially water miscible organic solvent, such as premix 1: 1, is between about 70 and about 90 ⁰ C) methanol or ethanol, the reaction is züge- as solubilizers usually in a few minutes

3 4

finishes and needs even with relatively large poses. The reaction mixture is then heated in concentrations not exceeding 15 minutes and then in an oil bath preheated to 100 ° C. for 10 minutes. A period of 2 ¹ Z ₂ to 15 minutes is required for boiling (Kp. 80 ⁰ Q.

most useful with the preferred metals. After the solution has cooled down, it is

As the reaction medium, water 5-th sulfuric acid can in principle be used at a pH of 2.0 be acidified as a solubilizer and shaken out with ether. After this a water-miscible organic solvent drying the ether extract with sodium sulfate and has been added, since humulone itself in water distills off the solvent in the rotary compression molding machine table is not soluble. As mentioned, there are 3.45 g of light yellow water dampers in the flask Alcohol mixtures preferred. io oil (95% of theory), which when left standing in the

The refrigerator caused by the addition of metal salts crystallizes. Recrystallization accelerates the quantitative conversion of isooctane, colorless crystals from F. = 56 humulone to isohumulone, but this does not mean that up to 60 ° C. The isohumulone obtained in this way has only one advantage over the previously known analytical data (UV spectrum, IR mode of operation. The isohumulone samples obtained in the inventive catalytic spectrum, elemental analysis, thin-layer chromatotic reaction are measured) using methods customary up to now The products produced are also obtained particularly pure, as in the thin preparations and shows the typical layer chromatogram and also the countercurrent bitter isohumulone taste.
distribution in the system isooctane-phosphate-citrate buffer (pH 5.35) (Fig. 3) can be seen. 20th

The countercurrent distribution analysis of Isohumu Example 2

long mixing produced by alkaline isomerization

of humulone in boiling 0.2n- (Fig. 4) or 0, ln- In the reaction described in Example 1

(Fig. 5) sodium carbonate solution at pH 10. Apparatus be erhalfen while passing nitrogen, on the other hand clearly show the advantages 25 6.1 g MgCl ₂ · 6H ₂ O (3 x 10 ^-2 mole) in 40 ml of water are of humulinic acid. The solved by distribution. 10.0 g of a hop extract, which contains about 40% chromatography results obtained with humulone, are dissolved in 120 ml of ethanol, O, 2N sodium carbonate at pH 10 and 100 ° C and, if necessary, humulone isomerized from insoluble components according to a calibration curve . The ethanol solution of the hops, a mixture of the purest isohumulone and extract, is used to adjust the pH value with humulinic acid (approx. 1: 1). 15 ml of aqueous ln sodium hydroxide solution are added and poured into the

In some experiments, especially with Mg, reaction flasks are given. Then it is stirring the isohumulone already crystallized without pre-purifying and reading through the pH of the nitrogen after the work-up. Elaborate Reini reaction mixture adjusted to 7.5 and this supply operations such as heated to boiling under reflux for 10 minutes to achieve pure 35. the Isohumulone in the alkaline isomerization not work-up takes place as described in Example 1, are manoeuvrable are therefore not required. After examining the isomerized thus obtained

In contrast, the catalytic rearrangement provides hop extract with the usual methods, such as to the alkaline also a practically quantitative thin-layer chromatography, column chromatography yield of isohumulon, namely at least 95% 40 phie of polyamide powder and spectrophotometric compared to about 79% of the two best known alkä determination, this has been found in the starting product Isomerization process. keep humulone in 90% yield to isohumulone

The isomerization mixture is reacted in the usual way.

worked up. The reaction medium is used in the usual example 3

Acidified wisely, expediently with dilute acid 45

to a pH of 2, and with a solvent I _n of the reactants described in Example 1 for isohumulone, poured out. After drying apparatus, 4.1 g of sodium acetate (5 x 10- * mol), the solvent extract and distilling off the 0.262 g of nickel sulfate (IQ- * mol) in 50 ml of water under the solvent, the isohumulone remains. Stirring and bubbling nitrogen through dissolved. 0.363 g

The following examples illustrate the invention. 50 humulones (10 ~ ³ mol) are dissolved in 50 ml of ethanol,

adjusted with 1 ml of aqueous 1N sodium hydroxide solution and added to the reaction flask. The reaction mixture

_We heated Example 1 _(j for 10 minutes under reflux to boiling.

The pH, which is 7.5 at the beginning of the reaction,

During the reaction, drop 7 in a 250 ml HaIs flask with a 55 attached. After cooling, the stirrer and reflux condenser, immersing the single rod to room temperature, dilute sulfur electrode to measure the pH and nitric acid to pH acidified by 2 and a solution of 6.1 g of MgCi ₃ · ether is shaken out with an inlet pipe. Further processing is carried 6HjO (3 x 10- ² mol) in 50 ml water (at as in Example 1. After distilling off the ether instead of _a MgCl can MgSO ₄ with the same 60 remain 0.35 g, that is 96 % of theory, a success can be used). Through this solution flows back oily product in the flask. The physically one as an inert gas a slow stream of nitrogen. chemical indicators show that this is 3.6 g of humulone (10 ~ ² mol) in 120 ml of ethanol isohumulone,
dissolved, with in aqueous sodium hydroxide solution to a pH value

from 7.5 to 8 and placed in the reaction flask 65 Example 4

given. While stirring and passing further through

Nitrogen becomes the pH of the reaction solution with 50 g of ground hops with a humulone content

a few drops in sodium hydroxide solution to 7.5 to 8 - 4.7% are in 500 ml of ethanol for 10 minutes

heated to boiling, the extraction solution is suctioned off and the residue 2 times with about 200 ml Washed ethanol. The filtrate is concentrated until the humulone content reaches 3%. Corresponding a total resin content of about 10%.

In the reaction apparatus described in Example 1, 3 g of MgCl ₂ · 6H ₂ O are dissolved in 25 ml of water. While passing in nitrogen, 60 ml (corresponding to 1.8 g of humulone) of the extract described above are added to this solution. The pH value is adjusted to 8 with NaOH and the mixture is then heated rapidly.

At 50 ⁰ C, upon reaching the boiling point (79.5 ° C), and 2 ¹ J _2, 5, 7 ¹ I ₂ and 10 minutes after initial boiling control samples are taken. The study of these control samples by thin layer chromatography and spectrophotometry shows that the humulone is converted to 7'V ₈ minutes .in isohumulone. The pH falls to 7.2 during the isomerization.

Examples 5 to 7

The tests are carried out as indicated in Example 3 * 5 '- ■ . The catalysts used are 0.136 g of ZnCl ₂ (IO- ³ mol), 0.198 g of MnCl _{2 .4H 2} O (IO- ³ ) or 0.266 g of Cd acetate (10 mol) in each case. The reaction conditions and the amounts of the other components are as in Example 3. After about 20 minutes, the conversion is practically complete. The yields were determined by spectrophotometry and were about 95%.

Examples 8 and 9

The experiments are carried out as described in Example 1. Instead of MgCl ₂ , 4.4 g of CaCl ₂ · 2H ₂ O (3 · IO- ² mol) or 7.3 g of BaCl ₂ · 2H ₂ O (3 · IO- ² mol) are used as reaction accelerators. The reaction conditions and the amounts of the other components are as in Example 1. The conversion is practically complete after about 10 minutes. The yields were about 95%.

Under the name Humulon and Isohumulon is to be understood here, as usual, to mean the mixture of the -acids or the isomers thereof.

35 a pH of 3.4, a yield of about 95% is obtained. . . With a cooking time of 40 minutes and a pH of 4.0, the yield is about 95%.

12. If one uses 0.532 g of SrCl ₂ · 6H ₂ O (2 mmol) and works as in Example 11 with a boiling time of 10 or 20 minutes and a pH of 8.0, a yield of over 95 is obtained in each case %.

13. Sodium acetate solution (0.025 molar, 2.05 g / 500 ml water) and HgCl ₂ solution (10- ^s molar, 271.5 mg / 500 ml methanol) are mixed in a ratio of 1: 1. 90 ml of this mixture are _{heated to the boil while passing in N 2} , 10 ml of a methanolic 3 · 10 ^s molar humulone solution (== 10.7 mg humulone) are added and the pH is adjusted to 8.0. The boiling point of the reaction mixture is 76.5 ° C. Samples are taken from time to time. Since isohumulone forms a fairly stable complex with Hg, it cannot be measured directly. The complex is decomposed by acidification with 1On-H ₂ SO ₄ to a pH value of 0.5 or below, the reaction products are isolated and then measured. This leads to fluctuations in the measured values. The half-life for isomerization is about 10 minutes and the yield is over 90%.

14 are carried out following examples of strontium and iron, _the: Sales

15. each measured by the extinction at 325 ηιμ will. 95 ml of the 0.15 molar aqueous metal salt solution are heated to the boil and with a solution of 2 mg of humulone in 5 ml of methanol is added. Through ongoing sampling will the decrease in humulone concentration is determined.

50

Reaction
solution
0.025 MoIA t ° C PH value
25 ⁰ C Half-life
Time
Minutes 14th
15th SrCl ₂
FeSO ₄ 98 ° C
98 ° C 8.3
4.0 2.1
7.4

Examples 10 to 15

The following experiments are carried out analogously to the procedure of Example 3:

10, 0.56 g FeSO ₄ -7H ₂ O (2 mmol) are dissolved in 25 ml HgO and 40 ml ethanol, the solution is heated to boiling, 0.363 g humulone (1 mmol), dissolved in 35 ml ethanol, are added, and the mixture is kept at the boiling point for 10 minutes. The pH of the solution is 4.2 to 4.5. The yield determined by spectrophotometry is about 90%.
With a cooking time of 40 minutes and a pH of 4.0, the yield is 95%.

Analytical studies of the according to the present Isohumulons produced in the example showed that this was metal-free.

11. If 0.554 g of BeSO ₄ (2 mmol) is used, the procedure is otherwise as in Example 10, but with Iri F i g. 1 shows the kinetic course of the isomerization reaction for the metals calcium, magnesium, cadmium, manganese and nickel in sodium acetate solution under Na (humulon 7 · 10 ~ ^s m / l; water - methanol 85:15). The solution contains 0.1 m / l sodium acetate as a buffer. For

The conversion in pure buffer solution and in phosphate buffer (pH 5.5) is also measured at the same time. as The abscissa is the reaction time in minutes and the ordinate is the logarithm of the extinction at 360 ιημ given, because at this wavelength the specific

G5 absorbance for isohumulone = 0 and for humulone = 312 is. It can be seen that at the same pH, the catalysis accelerates the reaction

· ■ · "■■ 'caused by a few powers of ten.

7th Buffer 0.1 mol /!
Metal salt 0.01 mol / l / ⁰ C 8th Half-life Curve Phosphate buffer (96.9 ml 0.025 m KH ₂ PO ₄ 98.5 PH value
bet / ⁰ C 2 hours H ₂ PO ₄ - + 3.1 ml 0.025 m Na ₂ HPO ₄ ) 5.5 Na acetate 80 6 hours Ac Na acetate + CaCl ₁ , 80 7.0 22 minutes 1 Na acetate + MgCl ₂ 80 · 8.0 7.3 minutes 2 B Na acetate + MgCl ₂ 80 7.5 2.6 minutes 2c Na acetate + CdCl ₂ 70 8.0 5.9 minutes 3 Na acetate - + - MnCl ₂ 70 7.0 3.2 minutes 4e Na acetate + NiSO ₄ 70 7.5 2.5 minutes 5 6.5

In FIG. 2 shows the kinetic course of the catalysis by magnesium, barium, .Cer, calcium and nickel in pure metal salt solutions (unbuffered) under N ₂ (humulon 5-6 · 10 ~ ^s m / l; water-methanol 95: 5).

The reaction medium used in each case is 95 ml of the corresponding aqueous metal salt solution, the the humulone (2 mg) dissolved in 5 ml of methanol has been added.

Curve Reaction solution t ° C PH value Half-life 0.025 m / l 25 ⁰ C approximately 1 Phosphate buffer (28 ml 0.025 m KH ₂ PO ₄ 98 7.2 100 minutes + 72 ml 0.025 m Na ₂ HPO ₄ ) 2 Phosphate buffer (96.9 ml 0.025 m KH ₂ PO ₄ 98 5.5 100 minutes + 3.1 ml 0.025 m Na ₂ HPO ₄ ) 3 MgCl ₂ 50 8.0 24 minutes 4th BaCI ₂ 98 6.9 9 minutes 5 CeCl ₁ 98 4.2 10 mins 6th CaCl ₂ 98 6.6 2 minutes 7th MgCl ₂ 98 8.0 0.7 minutes 8th NiSO ₄ 98 4.7 0.7 minutes

The abscissa is again the reaction time in minutes and the ordinate is the logarithm of the extinction 360 πΐμ indicated. The reaction in the phosphate buffer is given for comparison purposes.

The F i g. 3 to 5 show the surprisingly larger ones Purity of isohumulone obtained by catalytic isomerization is made from humulone. compared to the known alkaline isomerization manufactured product.

F i g. 3 shows an isohumulone obtained by catalytic isomerization with MgCl ₂ . The number of fractions of the countercurrent distribution in the isooctane-phosphate-citrate buffer system (pH 5.35) is indicated on the abscissa, while the ordinate shows the extinction of the respective fraction samples at 276 Γημ.

F i g. 4 and 5, on the other hand, show the extinction of alkaline isomerized isohumulone measured with the same countercurrent distribution and the same wavelength. F i g. 4 shows a humulone isomerized by 0.2 n sodium carbonate at pH 10 and 100 ° C., while FIG. 5 shows humulone isomerized in 0.1 n Na ₂ CO ₃ at pH 10 and 100 ^° C. It can be seen that, for example, the product isomerized with O, 2N sodium carbonate has so much humulinic acid, which is a degradation product, that the reaction product is almost identical to a calibration curve for a mixture of the purest isohumulone and humulinic acid in a ratio of approximately 1: 1 .

Claims (3)

Patent claims: 1. Process for the production of isohumulone by isomerization of humulone or humulone-containing Material at elevated temperature in an aqueous medium, the one with water Miscible organic solvent, such as methanol or ethanol, added as a solubilizer has been. advantageous at the boiling point of the aqueous medium, thereby 'marked e t that the isomerization can be achieved by adding a salt of elements of the second main or Subgroup or the iron group of the periodic system or of copper, aluminum, Cerium or manganese catalyzes and works at a pH below 9, such as 4 to 8. 2. The method according to claim 1, characterized in that the salt is magnesium, calcium, Nickel or manganese chloride or cadmium acetate used. 3. The method according to claim 1 and 2, characterized in that the isomerization 2V is _{carried out for 2} to 15 minutes. In addition 1 sheet of drawings 109 529/380