JPH0149711B2 - - Google Patents

Description

[Detailed description of the invention]

This invention has the following general formula: (wherein R ₁ is an alkyl group having 1 to 6 carbon atoms, and R ₂ is an alkyl group having 1 to 4 carbon atoms) The present invention relates to intermediates for producing 2H-furan or their tautomers. Recently, researchers in the flavoring industry have turned their attention to furan derivatives of the above type. A literature review shows that these compounds have a very wide range of applications in food and beverages. For example, US Pat. No. 3,647,825 describes biscuits,
Kiyandei, thiolate, meat, processed meat, dairy products, processed foods made from eggs, fish, seed fish and vegetables, as well as concentrated powdered soups, dried fruit and nuts, canned fruit, soft drinks, liqueurs, wine and whisky. , instant coffee, and also cigars, cigarettes,
It is stated that it is advantageous to add 4-hydroxy-5-methyl-3-oxo-2H-furan to chewing gum and oral hygiene products such as toothpastes, mouthwashes and concentrated mouthwashes. U.S. Pat. No. 3,887,589 describes 2,5-diethyl-
It has been shown that the use of 4-hydroxy-3-oxo-2H-furan in bakery products can improve taste and give a fresh impression. U.S. Pat. No. 3,576,014 describes 4-hydroxy-2-methyl-5-as a raspberry or gooseberry flavor.
The use of ethyl-3-oxo-2H-furan and 4-hydroxy-2-ethyl-5-methyl-3-oxo-2H-furan is described. U.S. Patent No. 3,709,697 discloses 4-hydroxy-2-methyl-5 as an additive for enhancing the flavor of meat.
-ethyl-3-oxo-2H-furan and 4-
Hydroxy-2,5-diethyl-3-oxo-
It is suggested to use 2H-furan. Many synthetic methods have been proposed to produce furans of the above type. However, all of the proposed methods are either uneconomical multi-step laboratory processes that cannot be used to produce compounds on an industrial scale, or they require the use of very expensive natural products. It was either. Such natural products include, for example, rhamnose (1963 Proc.
Aw, Soc, Brewing Chemist 84), this compound is obtained only in small quantities and in insufficient quantities for use;
Moreover, its properties are unpredictable. It is therefore not suitable for use as a starting material for the production of furan on an industrial scale. References for previously proposed methods for producing these compounds include the Journal of Organic Chemistry (J.
Org, Chem,) Volume 31, No. 2391-2394 (1966),
Journal of Organic Chemistry Vol. 38, pp. 123-125 (1973), and U.S. Patent Nos. 3709697; 3647825; 3887589
No. 3576014; No. 3694466; No. 3694466;
3651097; 3853918; 3629292; and 3629293; US Patent No. 1440270; Swiss Patent No. 565168. According to the invention, a technically very simple and industrially viable process for producing furan derivatives of the above type is provided. The intermediate compound of this invention is obtained by condensing a dialkyl-alpha-alkyl diglycolic acid ester and an oxalic acid diester in the presence of an alkaline condensing agent to obtain a 2-alkoxycarbonyl-
producing a disodium salt of 3,4-dihydroxy-5-alkylfuran; and alkylating the disodium salt of 2-alkoxycarbonyl-3,4-dihydroxy-5-alkylfuran with a lower alkyl halide to obtain 2- The sodium salt of alkoxycarbonyl-4-hydroxy-2,5-dialkyl-3-oxo-2H-furan is obtained. 4-hydroxy-5-alkyl-3-oxo-
2H-furan is produced by (i) hydrolyzing the alkoxycarbonyl group of the disodium salt produced in the above process; (ii) decarboxylating the hydrolysis product; and (iii) 4-hydroxy-5-alkyl. - A step of recovering 3-oxo-2H-furan. The method of this invention is carried out by the reaction mechanism shown below. In the formula, R ₁ is an alkyl group having 1 to 6 carbon atoms, R ₃ is an alkyl group having 1 to 4 carbon atoms, and R ₄ is the same as the alkyl group represented by R ₂ above. M is an alkali metal ion and X is a halogen. Starting materials and are compounds that are easily prepared. The compound is a dialkyl alpha-alkyl diglycolic acid ester, prepared by the reaction of an alkyl halo-acetate (alkyl bromoacetate or alkyl chloroacetate) and an alkyl ester of an alpha-hydroxycarboxylic acid. The synthesis method for this compound is described by A. Soladie-Cavallo and P. Virase.
P.Vieles) is the 517th − of Bull.Soc.Chim.Fvauce.
518 (1967). Diethyl ester and dimethyl ester are preferred. Dialkyl oxalates () are inexpensive commercially available compounds. Diethyl ester and dimethyl ester are the most common compounds and are therefore also preferred for use in the reaction. However, equally good results can be obtained using other lower alkyl esters. By the reaction of alpha-alkyl diglycolic acid diester and dialkyl oxalate,
Disodium salt of 2-alkoxycarbonyl-3,4-dihydroxy-5-alkylfuran ()
is generated. The reaction is carried out in the presence of an alkaline condensing agent in an inert diluent or solvent. The condensing agent is preferably an alkali metal alkoxide of an alcohol having 1 to 4 carbon atoms or an alkali metal hydroxide. Condensing agents based on any of the alkali metals such as lithium, potassium and sodium can be used. Preferred alkaline condensing agents are sodium methoxide, sodium ethoxide and sodium hydride. Certain intermediate compounds of the reaction may be referred to as sodium salts in the following description. These compounds are as good as other alkali metal salts. The term inert diluent or solvent refers to an organic liquid that does not itself participate in the reaction or react in other ways with another reactant. Diluents can be either polar or non-polar. Therefore,
As such organic liquids, aliphatic hydrocarbons, aromatic hydrocarbons, alcohols, dimethylformamide, dimethylsulfoxide, ethers and nitriles can be used. Although the choice of diluent will affect the temperature at which the reaction is carried out, the necessary conditions for a particular diluent can be easily determined by experiment. In carrying out Reaction Scheme A, equimolar amounts of dialkyl-alpha-alkyl diglycolic acid ester and dialkyl oxalate (and) are prepared in a solution containing 2 equivalents of an alkaline condensing agent in an inert diluent at low temperature conditions. or added into suspension. The reaction begins substantially simultaneously with contact with the reactants. A preferred method is to remove the alcohol produced by the condensation reaction as the reaction progresses, thereby promoting completion of the reaction and, as a result, increasing the yield. This step is not critical to the formation of the 2-alkoxycarbonyl-3,4-dihydroxy-5-alkylfuran disodium salt intermediate. Once the reaction is complete, convert the disodium salt into 3,4-
Either acidified to the dihydroxy form and then regenerated, or immediately hydrolyzed and decarboxylated to form 4-hydroxy-5-alkyl-3-oxo-
2H-furan or may be used in the above reaction scheme without regeneration of the intermediate. In carrying out Scheme B, in which the intermediate compound is alkylated to form a 2.5-dialkyl substituted product, the use of a neutral diluent or solvent with a dipole moment is preferred. The reaction proceeds rapidly in the presence of such solvents. Dimethyl sulfoxide, dimethyl formamide, or at least 100% of one of these in toluene or another polar or non-polar organic liquid.
A mixture containing at least % by weight is preferred. Prior to the alkylation step, a stoichiometric amount of anhydrous organic or mineral acid is added to the reaction mixture to facilitate the conversion of the disodium salt to the monosodium salt. Because the monosodium salt is more soluble in the organic reaction medium, the alkylation reaction proceeds more rapidly and is more selective with the monosodium salt than with the disodium salt. The alkylation reaction is carried out using equimolar amounts of C1-C4 alkyl halide based on the compound. Any suitable alkyl halide can be used, such as alkyl chlorides, alkyl bromides and alkyl iodides. The reaction is about 20
C. to 80.degree. C., and reaction times vary from about 1 hour to 20 hours depending on temperature. It can be seen that the alkylation reaction is completed when the pH becomes constant at about 6.5 to 7.5. The initial alkylation product may be regenerated as in the case of the above compounds, or the hydrolysis and decarboxylation steps may be carried out immediately without an intermediate regeneration step. The conversion of the intermediate compound to the desired final product may be the same as in both reaction schemes A and B. In both cases, the ester is hydrolyzed to the alkali salt form and then decarboxylated. Ester hydrolysis is carried out using an alkali metal hydroxide according to ester hydrolysis methods known in the art. The resulting deesterified carboxylic acid groups are not stable and are therefore decarboxylated upon neutralization or acidification. As described above, intermediate reaction products and can be isolated and regenerated as necessary. These may be further treated subsequently by hydrolysis and decarboxylation as described above. In particular, it is useful to regenerate the product to an intermediate state, which can then be used to produce the alkylated final product as required. These intermediate products, i.e. small amounts of keto-
2-Alkoxycarbonyl-4-hydroxy-2,5-dialkyl-3-oxo-2H-furan (), in which enol tautomeric forms exist, is a new compound. In addition to using this compound as an intermediate in this invention, it has been found that it is also useful as an additive for several types of flavors. this is,
Intermediate compounds improve the body notes, increasing sweetness and making the taste rich and balanced. In this regard, this intermediate compound is useful in various applications such as pastry, soft drink, confectionery and as an ingredient in artificial sweetener compositions. The present invention will be further explained using the above examples. Reference example 1 2-ethoxycarbonyl-5-methyl-3,4
- Dihydroxyfuran in 3 liters of dry toluene in a 6 liter Mituro flask with a mechanical stirrer, addition funnel, thermometer, 30 cm Vigreux column connected to a dephlegmator and gas inlet tube.
A suspension containing 408 g of sodium ethoxide was charged. While stirring the suspension, 438 g of diethyl oxalate was added over 75 minutes under nitrogen conditions at 0°C. The resulting yellow reaction mixture was then charged with 612 g of diethyl alpha methyl diglycolate (A, Soladey-Caballo and P, Beales, Bull, Soc, Chim,
France, 1967, p. 517). The reaction mixture was stirred for an additional 2 hours at room temperature. The reaction mixture was then gradually warmed and the ethanol-toluene mixture was distilled until the vapor temperature reached 107°C. The reaction mixture was cooled to room temperature and stirred with 2 liters of water for 30 minutes. The reaction mixture was transferred to a separatory funnel, the toluene layer was separated and the aqueous layer was washed successively with diisopropyl ether and pentane. The aqueous solution was acidified with concentrated hydrochloric acid. The temperature was maintained at 0° C. during acidification. The solid product was filtered and dried to yield 425 g (76%) of 2-ethoxycarbonyl-5-methyl-3,4-dihydroxy-furan. The melting point when recrystallized from alcohol was 120-121°C. NMR (CDC1 ₃ ), 1.40 (3H, t), 2.28 (3H,
e), 4.40 (2H, q), 6.0 (2H, broad). Reference example 2 2-ethoxycarbonyl-5-methyl-3,4
- dihydroxyfuran 2 with mechanical stirrer, thermometer, reflux condenser protected by nitrogen inlet tube and calcium chloride tube
A solution containing 102 g of diethyl alpha methyl diglycolate and 73 g of diethyl oxalate in 1 liter of dry dimethylformamide was placed in a small Mitsuro Francesco. While stirring the reaction mixture at room temperature, 24 g of sodium hydride and 0.5 ml of ethanol were added. The reaction mixture was then heated to 90°C under nitrogen. At 90°C, an exothermic reaction accompanied by hydrogen evolution was observed. The temperature was held at 110°C for an additional 15 minutes. The reaction mixture was then cooled to room temperature before the solvent was removed in vacuo. The residue was dissolved in water and the aqueous solution was acidified with concentrated hydrochloric acid. The temperature was kept at 0°C during acidification. The solid product was filtered off and dried, yielding 2.2 g with a yield of 39.5 g (42.5%)
-Ethoxycarbonyl-5-methyl-3,4-di-hydroxyfuran was obtained. The melting point was 119°C to 120°C. Reference example 3 4-hydroxy-5-methyl-3-oxo-
2H-Furan 37.2 g of 2-ethoxycarbonyl-5-methyl-3,4-dihydroxyfuran and 32 g of sodium hydroxide were added to 450 g of sodium hydroxide for 20 hours at room temperature under nitrogen conditions.
The solution was kept in ml of water. The reaction mixture was acidified (PH3) with concentrated hydrochloric acid and then stirred at 50° C. for 4 hours and then continuously extracted with ether for 6 hours. The ether extract was dried and concentrated in vacuo until the total volume of the solution was reduced to approximately 50 ml. The ether solution was cooled to -70°C and then filtered. The solid product was washed with pentane and dried to yield 13 g (57%) of 4-hydroxy-5-methyl-
3-oxo-2H-furan was obtained. Alcohol-
The melting point when recrystallized from ether was 128.2°C to 129.6°C. NMR (CDC1 ₃ ), 2.26 (3H,
t), 2.26 (3H, t) 4.52 (2H, q), 6.9 (1H, broad). Example 4 2-ethoxycarbonyl-2,5-dimethyl-
3-Oxo-4-hydroxy-2H-furan 0.5 with equipment similar to that described in Example 1
Dry toluene in Little Mitsuro Francesco
180ml and dry dimethylformamide 20ml
A suspension containing 27.2 g of sodium ethoxide was charged. The suspension was incubated at 0°C for 15 min with stirring.
29.2g of diethyl oxalate was added. The yellow reaction mixture was then heated for 15 minutes at 0 to 5°C.
40.8g of diethyl alpha methyl diglycolate was added. The reaction mixture was stirred for an additional 30 minutes at room temperature. The reaction mixture was then gradually warmed up and then heated with ethanol until the vapor temperature reached 107°C.
The toluene mixture was distilled off. The reaction mixture was then cooled to 0 °C and 9.2 g of formic acid was added before
A solution of 9.2 g ethanol and 0.5 g sodium iodide in 60 ml dimethylformamide was added. Methyl bromide gas was bubbled through the reaction mixture at 40-50° C. while stirring the reaction mixture vigorously to bring the pH of the reaction mixture to 7.0-7.5. The solvent was removed in vacuo (complete removal of dimethylformamide is essential for optimal isolation of the solid product) and the residue was then dissolved in ether. The sodium bromide was separated off and the subsequent ether solution was concentrated in vacuo before pentane was added to the concentrated ether solution. The etherpentane solution was cooled and filtered. The solid product was washed with pentane, dried and recrystallized from cyclohexane, yielding 24 g (70%) of 2-ethoxycarbonyl-2,5-dimethyl-3-oxo-
4-Hydroxy-2H-furan was obtained. The melting point is
The temperature was 89.2 to 89.5°C. NMR ( _CDC13 ), 1.27
(3H, t), 1.65 (3H, e), 2.32 (3H, s), 4.22
(2H, q), 6.00 (1H, broad). Example 5 2-ethoxycarbonyl-2,5-dimethyl-
3-Oxo-4-hydroxy-2H-furan The procedure of Example 7 was repeated except that methyl iodide was used in place of methyl bromide.
22g (64%) of 2-ethoxycarbonyl-2,5
-dimethyl-3-oxo-4-hydroxy-2H
- Obtained a franc. The melting point was 89.8-90.2°C. Example 6 2-ethoxycarbonyl-2,5-dimethyl-
3-Oxo-4-hydroxy-2H-furan The procedure of Example 7 was repeated except that methyl chloride was used in place of methyl bromide. twenty three
g (67%) of 2-ethoxycarbonyl-2,5-
Dimethyl-3-oxo-4-hydroxy-2H-
Got a franc. The melting point was 89.7-90°C. Example 7 2-ethoxycarbonyl-2,5-dimethyl-
3-Oxo-4-Hydroxy-2H-Furan A 250 ml Mituro flask equipped with a mechanical stirrer and gas inlet was charged with a solution containing 3.4 g of sodium ethoxide in 100 ml of ethanol. 9.3 g of 2-ethoxycarbonyl-5-methyl-3,4-
Dihydroxy-furan and 0.5 g of sodium iodide were added. Methyl bromide gas was bubbled through the reaction mixture with vigorous stirring at 50-60°C until the pH of the reaction mixture was 6.5-7.0. After removing the solvent in vacuo, the residue was dissolved in ether. Separate the sodium bromide, concentrate the ether solution in vacuo and then distill the residue over a short Pigray column to 2-ethoxycarbonyl-2,
5-dimethyl-3-oxo-4-hydroxy-
2H-furan was collected. The yield when recrystallized from cyclohexane was 8.1 g (81%) and the melting point was 89.8-90.1°C. Reference Example 8 4-Hydroxy-2,5-dimethyl-3-oxo-2H-furan 9 in 50 ml of water at room temperature and nitrogen conditions for 20 hours
A solution containing g of 2-ethoxycarbonyl-2,5-dimethyl-3-oxo-4-hydroxy-2H-furan and 5.4 g of sodium hydroxide was retained. The reaction mixture was acidified with hydrochloric acid, stirred for 1 hour at 30°C, and then continuously extracted with ether for 6 hours. The ether extract was dried, the solvent removed in vacuo, and the residue was then dissolved in a mixture of 5 ml dry ether and 5 ml dry pentane. The solution was cooled to -10°C and filtered. The solid product was dried to yield 4.1 g (70%) of 4-hydroxy-2,5-dimethyl-3-oxo-2H-furan. The product isolated by NMR and 1R was 4-hydroxy-
It was identified as 2,5-dimethyl-3-oxo-2H-furan. The melting point was 82-84°C. Reference Example 9 4-Hydroxy-2,5-dimethyl-3-oxo-2H-furan In a 20 liter Mituro flask with a mechanical stirrer, addition funnel, thermometer, nitrogen inlet tube and 30 cm Bigley column connected to a dephlegmator. A suspension containing 1512 g of sodium methoxide in 15.5 liters of dimethylformamide was placed. While stirring the solution, 2044 g of diethyl oxalate was added over 90 minutes under nitrogen conditions at 5°C.
Then add 3 to the yellow reaction mixture at 2 to 5°C.
2856 g of diethyl-2-methyl-diglycolate was added over time. The reaction mixture was stirred for an additional 3 hours at room temperature. The reaction mixture was then gradually warmed to 90-100°C and kept at 100°C until the distillation of the alcohol was complete. The reaction mixture was cooled to room temperature and 649 g of formic acid was added. Methyl bromide was then bubbled into the reaction mixture at 40-50° C. until the PH of the reaction mixture was 7.0-7.5. After removing the solvent in vacuo, the residue was dissolved in a solution containing 2472 g of sodium hydroxide in 9 liters of water. The reaction mixture was kept at room temperature and nitrogen conditions for 20 hours, acidified with hydrochloric acid and then extracted successively with ether. After drying the ether extract and removing the solvent in vacuo, the residue was recrystallized from ether, yielding 916 g (51%) of 4
-Hydroxy-2,5-dimethyl-3-oxo-
2H-furan was obtained. The melting point was 80-82°C.
As examined by NMR and 1R, the monotonic product was the 4-hydroxy-
It was identified as 2,5-dimethyl-3-oxo-2H-furan. Reference Example 10 4-Hydroxy-2,5-dimethyl-3-oxo-2H-furan The method of Reference Example 9 was repeated using hydrogen chloride instead of formic acid. 4-hydroxy-2, with a yield of 48%.
5-dimethyl-3-oxo-2H-furan was obtained.
The melting point was 80-82°C. Reference Example 11 4-Hydroxy-2,5-dimethyl-3-oxo-2H-furan 100% dimethylformamide in a 1 liter Mituro flask equipped with a mechanical stirrer and gas inlet tube.
A suspension containing 34 g of sodium ethoxide was placed in a mixture of 30 ml of toluene and 30 ml of toluene. While stirring this suspension at room temperature and under nitrogen conditions, 93 g of 2-ethoxycarbonyl-5-methyl-3,4-
Dihydroxy-furan was added. Methyl bromide gas was bubbled into the reaction mixture at 30-40°C until the pH of the reaction mixture was 6.5-7.0. After removing the solvent in vacuo, the residue was dissolved in a solution of 80 g of sodium hydroxide in 350 ml of water.
The reaction mixture was kept under nitrogen for 20 hours at room temperature, acidified with hydrochloric acid, and then extracted successively with ether. Dry the ether extract to remove the solvent in vacuo,
Recrystallization of the residue from ether yielded 41.5
g (65%) of 4-hydroxy-2,5-dimethyl-3-oxo-2H-furan was obtained. The melting point was 81.5 to 83.1°C. Reference example 12 4-hydroxy-2-methyl-5-ethyl-3
-oxo-2H-furan and 4-hydroxy-2-ethyl-5-methyl-3-oxo-2H
- Furan Toluene in a 1 liter Mitsuro flask equipped with a mechanical stirrer, addition funnel, thermometer, nitrogen inlet tube and reflux condenser protected by a calcium chloride tube.
20.4 in 180ml and dimethylformamide 120ml
A suspension containing g of sodium ethoxide was added. While stirring this reaction mixture, 55.8 g of 2-
Ethoxycarbonyl-5-methyl-3,4-dihydroxyfuran was added. Temperature during addition is 20℃
Made it lower. To the resulting red clear solution was added 120 g of ethyl bromide over 15 minutes. The reaction mixture was then stirred for an additional 20 hours at 40°C.
The solvent was removed in vacuo and the residue was dissolved in ether. After separating the sodium bromide,
The ether solution was extracted with a cold solution of 5% sodium hydroxide. The aqueous solution was acidified with hydrochloric acid. The temperature was kept at 0° C. during this acidification. The acidified aqueous solution was then continuously extracted with ether for 6 hours. The ether extract was dried, the solvent removed in vacuo, and the residue was then distilled over a short Bigley column. 74−76
4-Hydroxy-2-methyl-5- at °C/0.3mm
Ethyl-3-oxo-2H-furan (40%) and 4-hydroxy-2-ethyl-5-methyl-3
The product was collected in the form of an isomeric mixture of -oxo-2H-furan (60%). Yield 15g (35%) n ²⁰ _D
1.5096, NMR (CC1 ₄ ) δ0.99 (t), 1.37 (t), 1.85
(m), 2.25 (s), 2.65 (q), 4.38 (m), 7.2 (
Broad, s). Reference example 13 4-hydroxy-2-methyl-5-hexyl-
3-oxo-2H-furan and 4-hydroxy-2-hexyl-5-methyl-3-oxo-
2H-furan 19.8 g of sodium in 130 ml of dry toluene and 15 ml of dry dimethylformamide in a 1 liter Mituro flask with a reflux condenser protected by a mechanical stirrer, addition funnel, thermometer, nitrogen inlet tube and calcium chloride tube. Ethoxide 19.8
A suspension containing g. After stirring for 10 minutes,
21.3 g of diethyl oxalate were added dropwise at 10° C. under nitrogen. Then add 10 to the resulting yellow reaction mixture.
40 g of diethyl alpha hexyl diglycolate was added dropwise at a temperature of -15°C. This diethyl alpha hexyl diglycolate is A. soradii.
Cavallo and P. Beales, Bull.Soc.Chim.
France, 1967, p. 517, boiling point 112°C/0.3mm, n ²⁰ _D 1.4345. The reaction mixture was stirred for an additional 15 minutes at room temperature and then slowly warmed up. Ethanol until the steam temperature reaches 110℃
The toluene mixture was distilled off. The reaction mixture was then cooled to 0° C. before adding 6.9 g of formic acid, followed by further addition of 6.9 g of ethanol and 100 ml of dimethylformamide. Methyl bromide gas was bubbled through the reaction mixture with vigorous stirring at 25-40°C until the pH of the reaction mixture was 7.0-7.5. After complete removal of the solvent in vacuo, the residue was dissolved in a solution of 200 ml of ether and 24.5 g of sodium hydroxide in 100 ml of water. The resulting slurry was stirred at room temperature under nitrogen for 20 hours. The mixture was then acidified with hydrochloric acid (PH=3.4). The temperature during acidification was kept at 20°C. The acidified aqueous solution was neutralized with a 10N aqueous sodium hydroxide solution to pH 6.8, and then extracted continuously with ether for 6 hours. The ether extract was dried and the solvent removed in vacuo. The residue was distilled on a short Pigray column. 4-Hydroxy-2 at 102℃/0.1mm
-Methyl-5-hexyl-3-oxo-2H-furan (55%) and 4-hydroxy-2-hexyl-5-methyl-3-oxo-2H-furan (45
%) of the product in the form of an isomeric mixture was collected. Yield was 12.5 g (42%), n ²⁰ _D =1.4935. NMR
(CDC1 ₃ ) δ0.9, 1.45(d), 2.28(d), 2.6(t)
,
4.5 (m), 7.3 (broad). Reference example 14 4-hydroxy-2-methyl-5-pentyl-
3-oxo-2H-furan and 4-hydroxy-2-pentyl-5-methyl-3-oxo-
The procedure of Example 16 was repeated except that instead of the stoichiometric equivalent of 2H-furan diethylalph-hexyl diglycolate, diethylalph-pentyl diglycolate was used. Diethyl alpha-pentyl diglycolate, Bull.Soc.Chim.France by A. Soladay-Caballo and P. Biele;
Produced by the method described in 1967, p. 517, with a boiling point of 106-
It was 108℃/0.2mm. 4-Hydroxy-2-methyl-5-pentyl-3-oxo-2H-furan (55%) and 4-hydroxy-2-pentyl-
5-Methyl-3-oxo-2H-furan (45%)
A mixture of was obtained with a yield of 52%. Boiling point is 102℃/0.4
mm, n ²⁰ _D = 1.4956, NMR (CDC1 ₃ ) δ0.84, 2.20
(d), 2.56 (t), 4.40 (m), and 6.9 (broad). Reference example 15 4-hydroxy-2-methyl-5-isobutyl-3-oxo-2H-furan and 4-hydroxy-2-isobutyl-5-methyl-3-oxo-2H-furan Stoichiometric equivalent of diethyl alpha - Reference example except that diethyl alpha-isobutyl diglycolate was used instead of hexyl diglycolate
13 methods were repeated. Diethylalphisobutyl diglycolate is Bu11.Soc.Chim.France by A. Soladay-Caballo and P. Beales,
It is manufactured by the method described in 1967, p. 517, and has a boiling point of 106-110°C/0.9mm. 4-hydroxy-2-methyl-5-isobutyl-3-oxo-
2H-furan (67%) and 4-hydroxy-2
-isobutyl-5-methyl-3-oxo-2H-
A mixture of furans (33%) was obtained in 57% yield. boiling point
97 _℃ /0.9mm, ^n20D =1.4998. NMR ( _CDC13 )
δ0.98, 1.44(d), 2.14(d), 2.51(d), 4.5(
m),
7.7 (broad). Reference example 16 4-hydroxy-2-methyl-5-butyl-3
-oxo-2H-furan and 4-hydroxy-2-butyl-5-methyl-3-oxo-2H
-Furan The procedure of Example 16 was repeated except that the stoichiometric equivalent of diethyl alpha-hexyl diglycolate was replaced with diethyl alpha-butyl diglycolate. Diethyl alpha-butyl diglycolate is described by A. Soladay-Caballo and P. Peeles, Bull. Soc. Chim. France, 1967, No.
Manufactured by the method described on page 517, with a boiling point of 90
-91℃/0.2mm. 4-hydroxy-2-methyl-5-butyl-3-oxo-2H-furan (50%) and 4-hydroxy-2-butyl-5
An isomeric mixture of -methyl-3-oxo-2H-furan (50%) was obtained in 40% yield. Boiling point 104℃/0.7
mm, n ²⁰ _D = 1.4998. NMR (CDC1 ₃ ) δ0.95 (3H),
1.44(d), 2.25(d), 2.60(t), 4.43(m), 6.
9 (Broad). Reference example 17 4-hydroxy-2-methyl-5-ethyl-3
-oxo-2H-furan and 4-hydroxy-2-ethyl-5-methyl-3-oxo-2H
-Furan The method of Reference Example 13 was repeated except that the stoichiometric equivalent of diethylalphahexyldiglycolate was replaced by diethylalpha-ethyldiglycolate. Diethyalphaethyl diglycolate, prepared by the method described by A. Soladay-Caballo and P. Peeles, Bn11. Soc. Chim. France, 1967, p. 517. boiling point 80−81
°C/0.2mm, ^n20D = _1.4255 . 4-hydroxyl-2-methyl-5-ethyl-3-oxy-
2H-furan (38%) and 4-hydroxy-2
An isomeric mixture of -ethyl-5-methyl-3-oxo-2H-furan (62%) was obtained in 46% yield. ^n20D _{_}
=1.5111 and the boiling point was 80-82°C/0.6mm. Reference example 18 4-hydroxy-5-ethyl-3-oxo-
2H-furan A suspension of 25.2 g of sodium ethoxide in 185 ml of dry toluene in a 1 liter Mitsuro flask with a reflux condenser protected by a mechanical stirrer, addition funnel, thermometer, nitrogen inlet tube and calcium chloride tube. I put it in. After stirring for 15 minutes, 27.1 g of diethyl oxalate were added dropwise at 10° C. under nitrogen. At 10−15 °C, the resulting yellow reaction mixture has 40.5
g of diethyl alpha-ethyl diglycolate was added dropwise. Diethyl alpha-ethyl diglycolate was prepared by the method described by A. Solladay-Caballo and P. Bieles, Bn11. Soc. Chim. France, 1967, p. 517, and has a boiling point of 80-
The temperature was 81° C./0.2 mm and n ²⁰ _D =1.4255. moreover
The reaction mixture was stirred at room temperature for 12 hours. Then,
The reaction mixture was gradually warmed up and the ethanol-toluene mixture was distilled off until the vapor temperature reached 104°C. The reaction mixture was then cooled to room temperature and
Stirred with ml of water for 30 minutes. The reaction mixture was then transferred to a separatory funnel and the toluene layer was separated off. A solution of 15.2 g of sodium hydroxide in 200 ml of water and 100 ml of ether were added sequentially to the aqueous layer. This mixture was heated at room temperature and under nitrogen conditions for 20 min.
Stir for hours. Acidify the reaction mixture with concentrated hydrochloric acid (PH
= 3) and then stirred at room temperature for 2 hours. The resulting solution was neutralized with 10N sodium hydroxide solution to adjust the pH.
6.8 and then extracted continuously with ether for 10 hours. The ether extract was dried and the solvent removed in vacuo, yielding 13.3 g of solid. Recrystallization from ether yielded 8.3 g (35%) of 4-
Hydroxy-ethyl-3-oxo-2H-furan was obtained. The melting point was 52-54°C. NMR
(CDC1 ₃ ) δ1.24 (t, 3H), 2.64 (q, 2H), 4.52
(d, 2H), 6.5 (s, 1H). Reference example 19 4-hydroxy-5-hexyl-3-oxo-
2H-Furan The method of Reference Example 18 was repeated except that the stoichiometric equivalent of diethyl alpha-hexyl diglycolate was replaced by diethylalphur-hexyl diglycolate. Diethyl alpha-hexyl diglycolate was prepared by A. Soladei-Caballo and P.
Bn11.Soc.Chim.France, 1967, p. 517, with a boiling point of 112.
°C/0.3mm, ^n20D = _1.4345 . 61 g of solid material was obtained. When recrystallized from ether, 20 g (30
%) of 4-hydroxy-5-hexyl-3-oxo-2H-furan was obtained. Melting point is 51-52℃.
NMR (CDC1 ₃ ) δ0.9 (3H), 1.3−1.8 (m, 8H),
2.60 (t, 2H), 4.49 (dd, 2H), 7.1 (broad
1H). Reference Example 20 4-Hydroxy-2,5-diethyl-3-oxo-2H-furan 1 liter Mitsuro flask with mechanical stirrer, addition funnel, thermometer, reflux condenser protected by nitrogen inlet tube and calcium chloride tube. 375ml to
A suspension containing 68 g of sodium ethoxide in DMF was placed. While stirring the reaction mixture,
Diethyl oxalate 73 under nitrogen conditions and 5°C
g was added dropwise. Then, after stirring for 15 minutes,
109 g of diethyl alpha-ethyl diglycolate was added dropwise at -10°C. The reaction mixture was stirred at room temperature for 12 hours, after which time the temperature was gradually increased. The reaction mixture was kept at 100° C. for 6 hours, during which time the ethanol was distilled off. The reaction mixture was stirred vigorously to form a viscous slurry. A total of 37g of ethanol was collected. The reaction mixture was then cooled to 20° C. and 46 g of formic acid was added, followed by 89.5 g of ethyl bromide and 9 g of sodium iodide over 30 minutes. Thereafter, the reaction mixture was stirred at 40° C. for a further 16 hours. The solvent was completely removed in vacuo and the residue was dissolved in a solution containing 88.3 g of sodium hydroxide in 500 ml of water. The resulting slurry was stirred at room temperature for 3 days under nitrogen. Then, hydrochloric acid (PH
The mixture was acidified with =3). The temperature during acidification was kept at 20°C. 10N acidified aqueous solution
The mixture was neutralized with an aqueous sodium hydroxide solution to a pH of 6.8, and then extracted successively with ether. After 6 hours the ether extract was dried and the solvent removed in vacuo to give 43.5 g of residue. After further extraction for 12 hours, 18.5 g of residue was obtained. Both residues were combined and distilled over a short Bigley column to 27
g (35%) of 4-hydroxy-2,5-diethyl-3-oxo-2H-furan was obtained. Boiling point 89℃/
_0.9mm , ^n20D =1.5090. NMR (CDC1 ₃ ) δ0.98 (t,
3H), 1.27 (t, 3H), 1.85 (m, 2H), 2.71 (q,
2H), 4.40 (m, 1H), 7.4 (broad s, 1H). Reference Example 21 Two types of cream flavoring agents were manufactured by mixing the following ingredients:

Table: Mixtures A and B were each added separately to an 8% sucrose solution in an amount of 0.2 g per liter. The test solutions were tasted and compared. The panel preferred the test solution containing Mixture B over the test solution containing Mixture A. This is because the test solution containing Mixture B exhibited richer, sweeter, and creamier characteristics than the test solution containing Mixture A. Reference Example 22 Two types of strawberry flavoring agents were manufactured by mixing the following ingredients.

【table】

Table: Mixtures A and B were each added separately to a drink containing 8% sucrose and 0.05% citric acid.
I compared the taste of this drink. The panel preferred the drink containing Mixture B to the drink containing Mixture A. This is because the drink containing Mixture B was richer, sweeter, and exhibited more balanced strawberry characteristics than the drink containing Mixture A.

Claims (1)

[Claims] 1 2-Alkoxycarbonyl-4-hydroxy-2,5-dialkyl-3-oxo-2H-furan or an alkali metal salt thereof.