PROCESS FOR MAKING TETRAHYDROISOALPHA ACIDS

Abstract: A method of preparing tetraphydroisoalpha acids from beta acids wherein undesired impurities are removed. Beta acids are hydrogenated in a (C1-C6)alkanol oxidized and isomerized to produce tetrahydroisoalpha acids. The improvement comprises using a high boiling point solvent to remove the (C1-C6)alkanoyl by azeotrope prior to isomerization.

Description: PROCESS FOR MAKING TETRAHYDROISOALPHA ACIDS Background Art The field of art to which this invention is directed is processes for making hop flavors. Hops have been used for centuries to flavor beer and are considered, along with water, yeast, and malt, to be an essential ingredient. Since the sixties, following elucidation of the structure of the hop bittering compounds in the fifties by such pioneering investigators as Rigby and Verzele, various forms of chemically modified hop extracts have found their way into commercial application. A goal of present brewing technology is to make reproducible brews. Difficulties are encountered at every step in the brewing process. Difficulties include unwanted variations in yeast cultures, in hops, in malt, in adjuncts, in times, in temperatures, and the human element of the brewhouse. Beer presents a subtle combination of carbonation, foam, mouth feel, bitterness, and aroma when smelted and swallowed. Whatever can be done to improve the reproducibility and control of even one variable is exceptionally important. Hop flavors have attracted widespread interest in recent years for use in controlling and standardizing the flavoring of beer including ale, especially by post- fermentation treatment. U.S. Patent No. 4,778,691 teaches that unidentified hop-derived substances, when present during fermentation, are either metabolized or removed by the yeast. However, when they are added post-fermentation, they complex or esterify with the alcohol present to give undesirable fruity-estery-fatty or stout type of aromas during normal storage of the beer. Therefore, a post-fermentation hop flavored fresh beer may be acceptable, but one aged for several weeks may not. U.S. Patent No. 4,778,691 also states that the prior art is not effective in removing the undesirable impurities. For example, Todd (U.S. Patent No. 4,002,683) removes humulinic acid, tannins, sugars, and gushing promoters. Humphrey (U.S. Patent No. 4,302,479) performs a highly acidic wash of an organic solvent solution of extract. Neither procedure, because of the very acidic pH used for purification, removes neutral materials. Lance (U.S. Patent No. 4,395,431) elutes these substances with the alpha acids, and does not remove or separate them. Westermann (U.S. Patent No. 3,798,332), concentrates them with his so-called pure isoalpha acids. The procedure of Humphrey (U.S. Patent No. 3,875,316) also does not remove them. In contrast, U.S. Patent No. 4,778,691 teaches the extraction of impurities by agitating the hop flavor with water at a pH of 4 to 12 and extracting the impurities from the organic phase into the aqueous phase. Also, U.S. Patent Nos. 5,013,572 and 5,013,571 , the disclosures of which are hereby incorporated by reference, teach the removal of certain odors from hop extracts by a steam stripping process. Finally, U.S. Patent Nos. 3,552,975 and 3,923,897 teach the production of tetrahydroisoalpha acids from beta acids by a process including hydrogenolysis of beta acids to form desoxyalpha acids, oxidation of desoxyalpha acids to form tetrahydroalpha acids and isomerization of tetrahydroalpha acids to form tetrahydroisoalpha acids. Although there has been some research into the removal of undesirable odors and odor-forming compounds from hop flavors, there is a continuing search for more efficient, effective methods. Summary of the Invention The present invention is directed to a process for preparing hop flavors that includes the removal of undesired impurities from the hop flavor. The process comprises an improved process for conversion of beta acids to tetrahydroisoalpha acids. The beta acids are hydrogenated in a (C.-C 6 )alkanol to produce desoxytetrahydroalpha acids, the desoxytetrahydroalpha acids are oxidized to produce tetrahydroalpha acids and the tetrahydroalpha acids are isomerized to produce tetrahydroisoalpha acids. The improvement comprises dissolving the desoxytetrahydroalpha acids in a high boiling point solvent and removing the (C,- C 6 )alkanol by azeotrope prior to isomerization. Preferably, the alkanol is removed prior to oxidation with the peracid and the high boiling point solvent is toluene. This process makes a significant advance in the field of processes for making hop additives by providing a process for the production of tetrahydroisoalpha acids (devoid of certain odors) from beta acids. The advantage of the process is that it utilizes certain solvents (e.g., toluene) to aid in the removal of alcohols used in an initial process step. Other features and advantages will be apparent from the specification and claims. Detailed Description of the Invention The starting material for this process is beta acids having the formula: In commercial processes, the beta acids are derived from hops where they exist as different homologs, stereoisomers, optical isomers, and combinations thereof. Typically, the primary homologs are those in which R is isopropyl, isobutyl or sec-butyl. Beta acids can be isolated from hops by a process in which the organic components of the crushed hop cones are extracted by liquid C0 2 . The beta acids are then separated from the alpha acids using an aqueous extraction at a pH of about 8 to about 8.3. In addition, the synthetic production of beta acids has been described, albeit at low yields, by for example, K. G. Drewett, D. R. J. Laws, J. Inst. Brew.. 76, 188-190, (1970). The beta acids are used to prepare desoxytetrahydroalpha acids having the following formula: wherein R is isopropyl, isobutyl or sec-butyl. The desoxytetrahydroalpha acids are used to prepare tetrahydroalpha acids having the following formula: wherein R is isopropyl, isobutyl or sec-butyl. The processes of this invention are used to produce reduced isoalpha acids, preferably tetrahydroisoalpha acids (THIAA) having the formula: where R is isopropyl, isobutyl or sec-butyl. THIAA as produced by the processes of this invention has two sites of optical activity in the ring, thus contains cis and trans stereoisomers. The process of this invention comprises the reduction of beta acids to form desoxytetrahydroalpha acids, the oxidation of the desoxytetrahydroalpha acids to form tetrahydroalpha acids and the isomerization of the tetrahydroalpha acids to form THIAA. A high boiling point solvent is used to remove undesirable odor forming constituents. More specifically, the reduction process involves using a reducing medium comprising hydrogen gas, preferably in the presence of a noble metal catalyst. The process comprises adjusting, if necessary, the pH of a solution of the beta acid to the desired range, and if necessary, adding buffering agents (described below) as desired and exposing the beta acid to hydrogen at elevated temperatures and pressures, typically in the presence of a hydrogenation catalyst. Any source of hydrogen gas may be used in the hydrogenation of this invention. However, the reaction may be performed under a mixture of hydrogen with a safe and reaction inert gas such as nitrogen. Preferably, the process uses a hydrogenation catalyst, such as a noble metal, which increases the speed of the reaction. It is especially preferred that palladium is utilized as it has been found to provide high yields, good purity and short reaction times in contrast to other hydrogenation catalysts. Typically, the catalyst is disposed on a finely divided support material. Preferable support materials included finely divided carbon, barium carbonate, barium sulfate, calcium carbonate and alumina. Suitable carbon supported palladium catalysts are well known in the art. Typically, the reduction is performed at a pressure of about atmospheric to about 100 psig and higher (e.g., 2000 psig). Generally, a higher pressure increases the rate of reaction. Preferably, the reaction is performed at a pressure of about 40 psig to about 60 psig because of typical equipment constraints. Any temperature can be used at which the beta acids are in solution (e.g., those described below); however, preferably, the temperature is about 50°C to about 200°C because below about 50°C the beta acids may come out of solution and above about 200° C the reactants may be degraded. Optimum reaction time depends on the pressure, temperature, reactant concentration, catalyst amount, etc.; however, for typical conditions of 50 psig, 100°C, 20% by weight beta acids, and 2% by weight catalyst, reaction times of about 4 hours to about 6 hours are normal. A (C C 6 ) alkanol is used as a solvent and preferably methanol is used. Typically concentrated sulfuric or hydrochloric acid is added to the solution prior to hydrogenolysis. Significantly, the thus-formed (C,-C 6 ) alkanol solution of desoxytetrahydroalpha acids is then combined with a suitable high boiling point solvent and the alcohol is removed by azeotropic distillation. Alternatively, the alcohol/ desoxytetrahydroalpha acids solution may be concentrated prior to addition of the high boiling solvent and subsequent distillation. The azeotropic distillation may be assayed to assure that the alcohol has been removed. Alternatively, the azeotropic removal of the (C.-C 6 )alkanol may be delayed until later, however, it must be performed prior to the transformation of the tetrahydroalpha acids to the isoalpha acids (e.g., the addition of base). In addition, if desired the azeotropic distillation may be repeated at different times to assure removal of the alkanol. Any high boiling point, reaction inert solvent which is a solvent for the desoxytetrahydroalpha acids may be used. By high boiling point is meant that the solvent has a boiling point significantly above that of the (C,-C 6 )alkanol, i.e. greater than 100°C. By reaction inert is meant a solvent which does not interact with starting material, reagents, intermediates or the desired product in a manner which adversely affects the yield of the desired product. Typical solvents include C 8 -C 15 hydrocarbons, aromatics, chlorinated aliphatics of C 4 or higher, esters and ethers. Exemplary aromatics include toluene, xylenes, ethylbenzene, chlorobenzenes, and chlorotoluene. Exemplary aliphatics include isomeric octanes, isomeric nonanes, isomeric undecanes and isomeric dodecanes. Exemplary chlorinated aliphatics include isomeric dichlorobutanes, isomeric dichlorobutenes, isomeric dichlorohexanes and isomeric dichlorohexenes. Exemplary esters include propyl acetate, butyl acetate and ethyl butyrate. Exemplary ethers include butyl ether, isobutyl ether, diglyme and triglyme. Preferred solvents include toluene, xylene, isooctane, decane, diglyme, butyl acetate and 1 ,2-dichlorobenzene. The resulting desoxytetrahydroalpha acids solution is then oxidized using a peracid to produce tetrahydroalpha acids. Typically water is added, and the reaction is run in a two phase system. In general, any peracid (e.g., peralkanoic acid) may be used that provides the desired tetrahydroalpha acids such as perbenzoic and monoperpthalic acid, however peracetic acid is preferred. Oxidation can be facilitated by using an excess of peracetic acid at ambient or slightly elevated temperatures in one hour or less. This is described in more detail in U.S. Patent No. 3,923,897 the disclosure of which is hereby incorporated by reference. The resulting tetrahydroalpha acids solution is then isomerized to isoalpha acids in the above described high boiling point solvent/water solution at temperatures which are typically below about 50° C and ordinarily at ambient temperature. The procedure for transforming the tetrahydroalpha acids into isoalpha acids involves contact of an aqueous solution of a metal ion with the high boiling point, reaction inert, organic solvent/water solution of the tetrahydroalpha acids under conditions whereby the tetrahydroalpha acids remain dissolved in the organic solvent. The temperature can be and conveniently is below about 50° C; the pH of the water phase is maintained above about 7, preferably at least 8.0 and preferably 13 or below. At temperatures less than about 80°C, a metal ion selected from the group consisting of calcium and magnesium ions is preferably present and it is especially preferred that the calcium ion is employed. Alternately, the isomerization can occur without the addition of alkali metal cations at a temperature of about 80 °C or higher. The mixture is held until isomerization occurs, the solvent is removed and the metal ions are removed, preferably by washing the product contained in the solvent with dilute acid prior to removal of the solvent. This process is described in greater detail in U.S. Patent Nos. 3,923,897 and 3,522,975 the disclosures of which are hereby incorporated by reference. This process removes a variety of undesired impurities from the hop flavors. In particular the process is well suited for removing odor- or aroma-forming impurities or contaminants. Although not fully understood these impurities impart fruity, estery, fatty, or sour type aromas, to hop flavors. It is believed these impurities are typically present at levels of about 0.1 ppm to about 100 ppm. It is believed some of these impurities are a result of using alcohols (e.g., methanol) in the production of the hop flavors. This process results in purified hop flavors. By purified is meant essentially void of the odor forming impurities described above. This may be tested for by the organoleptic test described below. The test sample is dissolved in 95% alcohol to obtain a concentration of 1 -2% of the hop flavor. The exact concentration of the hop flavor in the alcohol solution is determined by HPLC. A 6 1 /2 oz. bottle of sparking mineral water is uncapped and a quantity of alcohol solution calculated to give an overall concentration of 5 ppm of hop flavor is added. The bottle is recapped and inverted 2 or 3 times to mix it. The bottle is stored in a refrigerator for at least 18 hours prior to tasting. The samples are divided into sets of four. Each set includes a control prepared from analytically pure hop flavor. The samples are assigned arbitrary code numbers. A 1-2 oz. portion of each sample of a set is poured into a clean glass marked with the code number and distributed to a panel of four tasters. Members of a panel are instructed to record their separate impressions of the aroma and flavor of each sample. Results are considered significant if three of the four panel members agree that there is or is not odor. If results are ambiguous, the evaluation is repeated with solutions containing 10 ppm of hop flavor. This process makes a significant contribution to the beer brewing industry by providing a simple effective method of removing undesirable odors from hop flavors. The process is more efficient than purification processes that use acid oil precipitations because with those processes some hop flavor is removed with the odor causing impurities. It should be understood that the invention is not limited to the particular embodiments shown and described herein, but that various changes and modifications may be made without departing from the spirit and scope of this novel concept as defined by the following claims. EXAMPLE 1 Crystalline beta acids (25 gm) were added to a flask containing 200 mL of methanol, followed by 7.35 gm of concentrated sulfuric acid at 20-25 °C with stirring. The solution was stirred for 1 hour, then 5.0 gm of 5% palladium on carbon catalyst prewet with 5 gm of water was added to the solution. The mixture was placed in a Parr bottle and hydrogenated at 50 PSI and 50°C for 2 hours. It was then cooled to 0-5°C and the catalyst was filtered off. The spent catalyst was then washed with methanol. The layers were combined, and most of the methanol was stripped off under vacuum, keeping the temperature below 40° C. Water (100 mL) and 100 mL of toluene were added to the solution. It was then stirred for 15 min, and the layers separated. Toluene (50 mL) was added to the aqueous layer, the mixture was stirred for 5 minutes, the layers separated, and the organic layers combined. Solvent (10 ml) was distilled off at atmospheric pressure. This removed the remaining methanol. Water (50 mL) was added to the solution from above and then 16.5 gm of 35% peracetic acid in acetic acid over 1 hour at 25 °C was added. The reaction was stirred for one hour after addition, then another 4.95 gm of peracetic acid solution was added. The aqueous layer was separated and discarded, and the organic layer concentrated to 125 mL under reduced pressure. Water (125 mL) was added to the above solution. With stirring, the pH of the aqueous phase was adjusted to 10-11 with 50% KOH; being careful to keep the pH below 12.0 during the addition. Potassium carbonate (0.5 gm) was added, and the mixture heated to 100°C for 6 hours with stirring. The pH was periodically monitored, and 50% KOH was added to keep the pH at 10.5 as needed. The solution was then cooled to 60° C. The toluene layer was separated and discarded and then 50 mL of hexane was added. The mixture was acidified to pH <2 with 50% sulfuric acid. The organic layer was separated and the aqueous layer discarded. Water (150 mL) was added to the organic layer and the pH adjusted to 10.5 with 50% KOH; being careful to keep the pH below 12.0 during the addition. The aqueous layer was separated and about 20 mL of solvent was removed under reduced pressure. This yielded 12.37 gm of THIAA potassium salt in 200 mL of aqueous solution (62%). The material had no trace of the fruity odor frequently observed with other THIAA preparations. EXAMPLE 2 In an analogous preparation to Example 1 , the isomerization step was run with one equivalent of magnesium chloride at room temperature. This produced material with no fruity odor. EXAMPLES 3 AND 4 In analogous preparations to Example 1 , the hydrogenolysis step was run with ethanol and isopropanol as solvents. This produced two materials with no fruity odor. EXAMPLES 5 AND 6 As a contrasting example to Examples 1-4, the Example 1 process was performed except, when the hydrogenolysis solution was extracted with hexane or methylene chloride instead of toluene, the final products had a fruity odor.

Claims: CLAIMS What is claimed is: 1. A process for conversion of beta acids to tetrahydroisoalpha acids comprising: hydrogenating the beta acids in a (C.-C 6 )alkanol to produce a material, said material including desoxytetrahydroalpha acids and a (C,-C 6 )alkanol; oxidizing the desoxytetrahydroalpha acids in the presence of an organic peracid oxidizing agent in an organic solvent/aqueous solution, said solution including at least some of the (C,- C 6 )alkanol,to produce tetrahydroalpha acids; and isomerizing the tetrahydroalpha acids in the presence of alkali, in an organic solvent/aqueous solution, said solution including at least some of the (C,-C 6 )alkanol wherein the improvement comprises: dissolving the desoxytetrahydroalpha acids in a high boiling point solvent, said solvent having a boiling point above about 100°C; and removing the (C^C^alkanol by azeotrope prior to isomerization. 2. The process as recited in claim 1 wherein the is removed by azeotrope prior to oxidation with the peracid. 3. The process as recited in claim 2 wherein the high boiling point solvent is toluene, xylene, isooctane, diglyme, butylacetate or 1 ,2-dichlorobenzene. 4. The process as recited in claim 3 wherein said high boiling point solvent is toluene.

Inventors: HAY BRUCE A, HAY, BRUCE, A.
Applicants: HAY BRUCE A, PFIZER, HAY, BRUCE, A., PFIZER INC.
Application year: 1995
Main classification: C12C3
IPC codes: C12C3