CS203923B2 - Process for preparing gamma-pyrones - Google Patents

Abstract

The gamma-pyrones of formula I in which the symbols have the meaning given in Claim 1 are obtained by a simple and economic "one-pot" process by reaction of a furfuryl alcohol of formula III with at least 2 equivalents of a halogenated oxidising agent, in aqueous solution at a temperature of between -50 DEG and +50 DEG C, and then the reaction mixture is heated until hydrolysis of the intermediate formed is virtually complete. The gamma-pyrones obtained can be used as products which enhance flavour and fragrance in food and cosmetic preparations. <IMAGE>

Description

The invention relates to a process for the preparation of γ-pyrons, and in particular to the preparation of γ-pyrons by a one-step process from furfuryl alcohols, which involves hydrolysis of certain intermediates, some of which are novel and prepared from the corresponding furfuryl alcohols using halogen-containing oxidizing agents.

Maltol (2-methyl-3-hydroxy-4H-pyran-4-one) is a naturally occurring compound found in the bark of young larch, pine, pine and chicory. The first industrial production was the destructive distillation of wood. The synthesis of maltol from 3-hydroxy-2- (1-piperidylmethyl) -1,4-pyrone was reported by Spielman and Freifelder in J. Am. Chem. Soc., 69, 2908 (1947). Schenck and Spielman, J. Am. Chem. Soc., 67, 2276 (1945), obtained maltol by alkaline hydrolysis of streptomycin salts. Chawla and McGonigal, J. Org. Chem., 39, 3281 (1974) and Lichtenthaler and Heidel, Angew. Chem., 81, 998 (1969), disclose the synthesis of maltol from protected sugar derivatives. Shono and Matsumura, Tetrahedron Letters 17, 1363 (1976), describe a five-step synthesis from methylfurfuryl alcohol.

The isolation of O-methyl-4-ethyl-4-hydroxy-4 H -pyran-4-one as one of the characteristic components of the sweet aroma in molasses refining is reported in Hiroschi Ito, Agr.

Biol. Chem., 40 (5), 827-832 (1976). This compound was previously synthesized as described in U.S. Patent 3,468,915.

The synthesis of γ-pyrons such as pyromeconic acid, maltol, ethyl maltol, and other 2-substituted 3-hydroxy-γ-pyrones is described in U.S. Patent Nos. 3,130,204, 3,133,089, 3,140,239, 3,159,652 , 3,365,469, 3,376,317, 3,468,915, 3,440 183 and 3,446,629.

Maltol and ethylmaltol enhance the aroma and aroma of various food products. In addition, these compounds are useful as additives for perfumes and essences. The 2-alkenylpyromeconic acids disclosed in U.S. Patent No. 3,644,635 and the 2-arylmethylpyromeconic acids disclosed in U.S. Patent No. 3,365,469 inhibit bacterial and fungal growth and are useful for enhancing odor and flavor in foods and beverages and as flavor enhancers. perfume.

The invention relates to a process for the preparation of? -Pyrons of the general formula I

A ^0M (I) where

R is hydrogen, C 1 -C 4 alkyl, phenyl or benzyl;

R '' is hydrogen or C 1 -C 4 alkyl, characterized in that it is heated in an aqueous acidic solution preferably at a temperature of 70 to 160 ° C until complete hydrolysis of the 4-halopyran of formula II

where

R and R '' have the above meaning and

X is a chlorine or bromine atom, wherein the intermediate compound of formula II above is prepared by reacting a furfuryl alcohol of formula III with an organic or organic acid before heating, or alternatively the acid can be liberated in situ during the preparation of intermediates as described below.

Examples of suitable solvents for this reaction are water, C 1 -C 4 alkanol or diol, preferably methanol, C 2 -C 10 ether, preferably tetrahydrofuran or isopropyl ether, low molecular weight ketone, preferably acetone, low molecular weight nitrile, ester or amide .

In the reactions described above, chlorine or bromine chloride is used as the preferred halogen-containing oxidizing agent.

The invention further relates to a novel and easy synthesis of the χ-pyrons of formula I above, namely maltol (2-methyl-3-hydroxy-4H-pyran-4-one) and related compounds by a process without isolation of intermediates using furfuryl alcohol of formula III above.

In this procedure, without isolation of the intermediates, furfuryl alcohol in an aqueous medium is treated with two equivalents of a halogen-containing oxidizing agent and the reaction mixture is then heated to hydrolyze the intermediate. This process without isolation of intermediates can be illustrated by the following formula:

(II n wherein R and R '' are as defined above in an aqueous solvent at a temperature of -50 to 50 ° C, preferably at room temperature with at least two equivalents of a halogen-containing oxidizing agent selected from the group consisting of chlorine, bromine, bromine chloride, hypochlorous acid , hydrobromic acid, or mixtures thereof, wherein the reaction is continued until complete.

The acid used for the hydrolysis may be added to the reaction mixture, for example by dissolving the compound of formula II in an aqueous

where

R is hydrogen, alkyl of 1 to 4 carbon atoms, phenyl or benzyl,

R '' is hydrogen or C 1 -C 4 alkyl and

XY is C12, V2, ClBr, HOC1, HOBr or a mixture thereof. The overall reaction is shown in the following scheme:

(III) oxidizing agent ·

open-chain tautomer

H — COH i

R cu

AND

CH i

C = O i

open-chain tautomer.

Lefebvre and collaborators J. Med. Chem. 16, 1084 (1973) have shown that furfuryl alcohols can be directly converted to 6-hydroxy-2H-pyran-3 (6H) -ones when a peracetic acid such as peracetic acid or m-chloroperbenzoic acid is used as the oxidizing agent. The first step in Lefebre's work utilizes a peracid in an organic solvent and probably results in a 6-acetoxy- or 6-m-chlorobenzyloxy derivative of pyran, which is then hydrolyzed to the 6-hydroxy compound during water treatment. Water is not used in the first stage of the reaction as it would adversely affect the course of the reaction. In any case, the growth by Lefebvre and coworkers cannot directly lead to the conversion of furfuryl alcohol to χ-pyron.

The use of an aqueous halogen-containing oxidizing solution is critical to the process for preparing the products of the invention. Furfuryl alcohol can be pure oxidized to 6-hydroxy-2H-pyran-3 [6H] -one using one equivalent of a halogen-containing oxidizing agent in water or an aqueous organic solvent. It is surprising and unexpected that 6-hydroxy-2H-pyran-3 (6H) -ones can be converted to χ-pyrones. 6-Hydroxy-2H-pyran-3 [6H] -one can be regarded as the aldehyde semiacetal and as such can undergo a number of undesirable reactions such as further oxidation and aldol type condensation. Using two equivalents of the halogen-containing reagent in water or an aqueous organic solvent, the reaction proceeds smoothly from furfuryl alcohol to χ-pyron. This novel process without isolation of intermediates has the advantage of using inexpensive halogen-containing oxidizing agents, Cl 2 Bn, BrCl, HOCl, HOBr or mixtures thereof. Isolation of the desired χ-pyrone is greatly simplified since the solvent, oxidizing agent and mineral acid formed as a by-product are volatile and can be removed in vacuo to give the crude χ-pyron directly in high yield by simple concentration.

The process without isolation of the intermediates is carried out by dissolving furfuryl alcohol in water or water together with an organic solvent. As such a solvent, a water-miscible or water-immiscible solvent may be used and may be selected from a wide variety of solvents such as C 1 -C 4 alkanols or C 1 -C 4 diols, for example methanol, C 2 -C 10 ethers carbon ketones such as tetrahydrofuran or isopropyl ether; low molecular weight ketones such as acetone, low molecular weight nitriles, low molecular weight esters and low molecular weight amides. Preferred solvents are C 1 -C 4 alkanols, C 2 -C 10 ethers, and methanol is most preferred. The solution is maintained at a temperature of -50 to 50 ° C, preferably -10 to 10 ° C. To this solution was added the desired furfuryl alcohol, and at the same time a halogen containing oxidizing agent (two equivalents) was added to the reaction mixture. The temperature of the reaction mixture is maintained at -50 to -50 ° C, preferably -10 to 10 ° C during halogen addition. If a low boiling solvent is used, it is removed by distillation after the addition is complete. The reaction mixture is then heated to a temperature at which the hydrolysis proceeds to a sufficient extent, for example 70 to 160 ° C. Generally, a temperature of 100 to -110 ° C is used for hydrolysis. Heating is continued until complete hydrolysis of the 4-halenedihydropyran intermediate (usually 1 to 2 hours). The acid necessary to catalyze this final hydrolysis is liberated in situ by cleavage of the acid from the intermediate during the course of the reaction. If desired, additional acid may be added.

The halogen-containing oxidizing agent is selected from the group consisting of chlorine, bromine, bromide, hypochlorous acid or hypobromic acid or mixtures thereof. Bromine chloride is a commercially available gas. It can be prepared in situ by adding chlorine to a sodium or potassium bromide solution or by adding bromine to a sodium or potassium chloride solution. Preferably, hypochlorous acid and hypobromic acid can be liberated in situ by adding aqueous acid (HCl, H2SO4 or HBr) to a solution of an alkali metal or alkaline earth metal hypochlorite or hypobromite, such as NaOCl, KOCl or Ca [OCl2]. Preferred halogen atom-containing oxidizing agents according to their cost are chlorine and bromine chloride prepared in situ.

The following examples illustrate the preparation of? -Pyrons by the process of the present invention and the preparation of various intermediates.

In the examples where spectral data are reported, NMR shifts are reported in accordance with conventional symbols and all shifts are in -5 units using tetramethylsilane as standard.

s - singlet d = doublet t = triplet. q = quartet m = multiplet br - wide.

Example 1

In a three-necked round-bottom flask equipped with a magnetic stirrer, tube - gas inlet, thermometer, and dropper - was placed 20 mL tetrahydrofuran and 50 mL water. The solution is cooled to room temperature at 0-10 ° C. The dropper was charged with a solution of 1- (2-furyl) -1-ethanol (0.089 mol) - in 20 ml tetrahydrofuran and this solution was added dropwise to the stirred reaction flask while being introduced through the gas inlet tube. chlorine (0.30 mol). The rate of addition is such that all. the alcohol is added with the first 1.3 and 1.5 equivalents of chlorine - (about 30 minutes), maintaining the temperature below 10 ° C. The reaction mixture was heated to reflux and tetrahydrofuran was removed by distillation. When the reaction mixture reached a temperature of about 105 ° C, a reflux condenser was added and heating to boiling was carried out for about two hours. The reaction mixture was then filtered while hot, cooled, adjusted to pH 2.2 and cooled to 5 ° C. Crystallization and filtration gave 3.43 g of crude 3-hydroxy-2-methyl-γ-pyrone (maltol). The aqueous filtrate was extracted with chloroform to give a second crop of 2.58 g of maltol. Distillation of the combined solids and crystallization from methanol gave 5.5 g (49%) of pure maltol, mp 159.5-160.5 ° C.

Example 2

The procedure of Example 1 was repeated under the various conditions outlined in Table I using the furfuryl alcohols of the formula

R

Tabulk.a I

Method . without isolation of intermediates, chlorine as oxidizing agent.

R solvent temperature (° C) of oxidation temperature (° C) of hydrolysis yield (%) CH3 methanol 10 100 ALIGN! 45 CH3 methanol 5 110 56 CH3 methanol —5 104 60 CH3 methanol —10 104 77 CH3 methanol —20 106 62 to 67 CH3 THF 10 105 49 CH3 acetone —5 110 36 CH3 CH5CN —5 110 29 CH3 EtOAc 0 110 26 CH3 none 10 110 17 to 30 CH3 benzene 10 110 26 CH3 methylisobutylketone 5 110 44 CH3 · .. isopropyl alcohol 0 110 49 CH2CH3 methanol 5 110 49 CH2CH3 methanol —10 110 58 CH2CH3 THF 10 110 47 H methanol —10 110 57 CH3 methanol —30 110 50

THF = tetrahydrofuran EtOAc-ethyl acetate

Example 3

The process of Example 2 was repeated with comparable results. using the following solvents:

ethanol n-propanol isobutanol n-butanol t-butanol dioxane ethyl ether isopropyl ether dimethoxyethane 2-methoxyethanol e-ethoxyethanol ethylene glycol.

Example 4

To a three-necked round-bottomed flask equipped with a stirrer, a gas inlet tube and a dropper was added 20 mL of tetrahydrofuran, 50 mL of water and sodium bromide (0.20 mol). The solution is cooled to 0 to 22 ° C. A solution of 1- (2-furyl) -1-ethanol (0.18 mol) in 20 ml tetrahydrofuran was added dropwise and added dropwise to a rapidly stirred reaction flask while using a gas feed tube for chlorine gas (0.40 mol). . The rate of addition of the alcohol is such that a yellow-orange color is maintained. Cooling the ice bath keeps the temperature below 20 ° C. Once all the alcohol and chlorine were added to the reaction flask, the temperature was allowed to rise to boiling point and tetrahydrofuran. distills off. . The isolation procedure of Example 1 was used to isolate 12.47 g of pure maltol (55% yield). Substantially the same results are obtained when potassium bromide is replaced with sodium bromide.

Example 5

Method according to. of Example 4 was repeated under the various conditions outlined in Table 2 using the furfuryl alcohols of the formula

Table 2

One-step procedure using BrCl as oxidation. agent prepared. in situ by adding chlorine to NaBr.

R. solvent temperature (° C). Temperature. (° C) oxidation yield. hydrolysis ..... (%)

CHs THF СИз THF СНз THF СИз isopropyl ether СНз ethyl ether СНз acetone СНз : СИзОН СНгСНз THF No. : THF. thf = tetrahydrofuran

20 May . 104 ... 55 27 · ::: 110: .5.4 15 · .-. :: '110 .. ·;.: ·. . 52 25 110 ' 46 20 May 110: . ·. 4з 15 Dec 105 47

: 110:. Y: .32

16 11з ^: · ... 47 20 May 109 .48

Example 6

To a three-necked round-bottomed flask equipped with a magnetic stirrer, gas inlet tube, thermometer and dropper was added 50 mL of tetrahydrofuran and 50 mL. water. This solution was then cooled to 0 ° C and slowly introduced (0.10 mol) into the reaction flask. chlorine, and simultaneously 1- (2-furyl) -1-ethanol (0.09 mol) was added dropwise. The temperature of the reaction mixture was allowed to rise above 10 ° C. . Bromine (0.10 mol) was then added and the reaction mixture was heated to reflux. Isolation according to Example 1 yielded 5.7 g of maltol.

Here: 7. . ·. ./g ·; .: 1. :: - '

Four-necked. flask. fitted with a thermometer, a condenser and a. two. .kapačkami. 50 ml of tetrahydrofuran are added. and · -. 50 ml. water. a. the solution is cooled to 10 ° C. To this well mixed solution is added simultaneously. ze. two droplets. bromine (0.20 mol). a. 1- (2-Furyl-) -1-ethanol (0.09 mol). Temperature. The mixture is maintained at 15 ° C. The reaction mixture was then heated to 75 ° C for 10 hours. Maltol was isolated as in Example 1 (53% yield).

Example

Way . by example. .7. is repeated under the different conditions listed in Table 3 for.

use of furfuryl alcohol formula

Table 3 R solvent temperature (° C) of oxidation temperature - (° C) of hydrolysis yield (%) CH5 THF 15 Dec 75 53 CH3 CH3OH 5 105 47 CHs none 15 Dec 100 ALIGN! 30 CH2CH3 THF 25 105 47 H THF 15 Dec 100 ALIGN! 45 CH3 THF 50 100 ALIGN! 20 May

THF = tetrahydrofuran

Example 9

A 2.8 M sodium hypochlorite solution was prepared by introducing chlorine (42.6 g) into a solution of 48 g of sodium hydroxide in 150 ml of water at 0 ° C. A solution of 1- (2-furyl) -1-ethanol (0.05 mol) in 15 ml tetrahydrofuran and 15 ml water was prepared in a three-necked round-bottom flask and cooled to 5 ° C. While maintaining the pH from -1.0 to 0.8 by the addition of 6 N HCl, 21.7 ml of sodium hypochlorite solution are added dropwise to the reaction flask over 33 minutes while maintaining the temperature below 5 ° C. Concentrated hydrochloric acid (15 ml) was added, the reaction mixture was warmed, and tetrahydrofuran was distilled off. Heating is then carried out for a further one hour. Maltol was isolated as described in Example 1.

Substantially the same results are obtained when sodium hypobromite is used instead of sodium hypochlorite.

Example 10

To a solution of 1- (2-furyl) -1-ethanol (0.05 mol) in 15 mL of tetrahydrofuran and 15 mL of water at -5 ° C was added 21.7. ml of -2.8 M sodium hypochlorite solution. Into the reaction flask with a feed tube. . of chlorine (0.05 mol) was introduced while maintaining the temperature below 5 ° C. The reaction mixture is then heated to boiling and the tetrahydrofuran is removed by distillation. Heating is then continued for an additional hour. The reaction mixture was cooled and the maltol was isolated as described in Example 1.

Example 11

A three-necked round-bottomed flask was charged with a solution of ml of water and 20 ml of tetrahydrofuran and cooled to 0 ° C. A solution of 1- (2-furyl) -1-ethanol (0.89 mol) in 25 ml tetrahydrofuran was added dropwise while BrCl (0.30 mol) was introduced via the gas inlet. The rate of addition is such that the first 1.3-1.5 equivalents of BrCl are added simultaneously with all furfuryl alcohol and the temperature is maintained below 30 ° C. The reaction mixture was heated to boiling and tetrahydrofuran was removed by distillation. When the temperature reached - 105 ° C, a reflux condenser was connected and the reaction mixture was heated at reflux for two hours. The reaction mixture was cooled and the maltol was isolated as in Example 1.

Example 12

In a three-necked round-bottomed flask equipped with a magnetic stirrer, a thermometer and a dropper was placed 25 ml tetrahydrofuran and 50 ml water. To this solution was added 1- (2-furyl) -1-ethanol (0.89 mol) in 25 ml tetrahydrofuran and bromine (0.16 mol) was added dropwise while maintaining the temperature below 15 ° C. When the addition is complete, 0.10 mol of chlorine is introduced through the gas inlet and the reaction mixture is heated to boiling. Maltol was isolated from the cooled solution according to the procedure of Example 1.

Example 13

6-hydroxy-2-methyl-2 H -pyran-3 (6 H) -one

To a solution of 25 g of 1- (2-furyl) -1-ethanol in 125 mL of tetrahydrofuran and 125 mL of water at 5 ° C was added 1 equivalent of bromine. The temperature is maintained by adding between -5 and 10 ° C. The solution was adjusted to pH 2.1 and extracted with ethyl acetate (3 X 50 mL). The ethyl acetate extract was dried and evaporated to give a yellow oil. The oil is chromatographed on silica gel, eluting with chloroform / ethyl acetate (3: 1) to give 4.8 g of a pure oil which is identical to 6-hyd203923 roxy-2-methyl-2H-pyran-3 (6H) according to spectral data. by one prepared from 6-methoxy-2-methyl-2H-pyran-3 (6H) -one by acid hydrolysis [Tetrahedron ketters 27, 1973 (1971)].

IR (CHCl3) 3700, 3300, 1700 cm @ -1.

NMR (CDCl 3, δ S): 6.8-7.1 (1H, dd), 6.0-7

6.2 (1H, d), 5.6 (1H, broad s, interchangeable D20), 5.4 to 5.5 (1H, d), 4.8 to 5.0 (1H, q), 3 to 1.6 (3H, t).

Example 14

The process of Example 13 was repeated using the furfuryl alcohol of formula

wherein R is hydrogen or ethyl.

Ethyl Compound: IR (CHCl3) 3600, 3340, 1706 cm @ -1.

Hydrogen Compound: IR (CMN1) 3565, 3300, 1703 cm @ -1.

Example 15

4-bromo-6-hydroxy-2-methyl-2 H -pyran-3 (6 H) -one

To a solution of 25 g of 1- (2-furyl) -1-ethanol in 125 ml of tetrahydrofuran and 125 ml of water at 0-5 ° C was added dropwise 2.2 equivalents of bromine while maintaining the temperature at 5-10 degrees Celsius. at the end of the addition, the solution was stirred at room temperature for 30 minutes and the pH was adjusted to 2.1 with 2N sodium hydroxide solution, the reaction mixture was extracted with ethyl acetate (3.times.100 ml), the ethyl acetate extracts were combined, dried with magnesium sulfate, filtered and evaporated to dryness. The residue is chromatographed on silica gel, eluting with a 95: 5 mixture of chloroform and ethyl acetate to give an orange oil which is rechromatographed on silica gel and eluted with 95: 5 chloroform / ethyl acetate.

NMR (CDCl 3, δ): 7.3 (1H, d), 5.6 (1H, d),

4.7 to 5.0 (1H, q), 1.1 to 1.5 (3H, m).

Example 16

The procedure of Example 15 was repeated using the furfuryl alcohol of formula

HIM

wherein R is hydrogen or ethyl.

Ethyl compound

4-bromo-6-hydroxy-2-ethyl-2H-pyran-3 (6H) -one, NMR (CDCl3, < 5), 1.4 (1H, d), 4.6-4.9 (1H, m), 1.8 to 2.2 (2H, m), 1.0 to 1.3 (3H, t) ·

Compound with hydrogen

4-bromo-6-hydroxy-2 H -pyran-3 (6 H) -one, NMR (CDCl 3, 5 5) 7.4 (1H, d), 5.5 (1H, d), 4.6 (2H, dd).

Example 17

A solution of 4-bromo-6-hydroxy-2-methyl-2H-pyran-3 (6H) -one is prepared by dissolving the compound in either aqueous inorganic or aqueous organic acid. The solution was then heated to boiling, cooled to room temperature and adjusted to pH 2.1 with 6 N sodium hydroxide solution, then extracted with chloroform. Concentration yields maltol. The acids used, the reaction time and the yields of maltol are as follows:

acid 1S concentration reaction. time (h) 18 yield (%) HCl 32 2 68 HCl 32 5 52 HCl 18 5 35 HCl 25 3 49 HBr 18 5 24 H2SO4 35 2 26 H3PO4 35 • · .. 2 ' 29 CH3COOH 35 2 69 CFsCOOH 100 ALIGN! 3 36 HNO3 35 3 0.4 CF3COOH 100 ALIGN! 3 70 CHsCOOH 100 ALIGN! 3 77 HCOOH 100 ALIGN! 3 24 H2SO4 35 5 48

Alternatively, organic solvents such as benzene and toluene may be used together with acidic materials such as p-toluenesulfonic acid and ion exchangers ("Amberlite" IR 120).

Example 1 8

The process of Example 15 was repeated using chlorine instead of bromine and using the appropriate furfuryl alcohols. He'll be ready. the following compounds:

Methyl: 4-chloro-6-hydroxy-2-methyl-2H-pyran-3 (6H) -one. 7.1 (1H, d),

5.8 (1H, 1H). 4.6 to -5.0 (1H, m, 4.4) (1H, broad), 1.2 to 1.5 (3H, m).

Ethyl: 4-chloro-6-hydroxy-2-ethyl-2H-pyran-3 (6H) -one NMR (CDCl 3, δ): 7.0 to 7.0. 7.1 (1H, d); 6.0 (2H, m), 4.4-5.0 (1H, m),

1.6 to 2.1. (2H, m · m), 0.9 to Д (3Η, 1).

Compound with hydrogen: 4-chloro-6-hydroxy-2H-pyran-3 (6H) -one. NMR (CDCl 3, δ): 7.1 to 7.1

7.2 (1H, d), β (1H, d), 4.4 to. 4.9 (2H, dd) (DUO addition).

Example d. . 1.9

Way. . by. . example. 15 'se. repeats. for preparation . of the compounds

HIM

X

under reflux. Maltol (34%) was isolated as described in Example 1.

Example 2.1

6-Methyl-2-ethyl-3-liydroxy-4H-pyran-4-one

To a three-necked round-bottomed flask was added 28 mL of methanol and 38 mL of water. The solution was cooled to -15 ° C. and 0.166 mol

Of 5-methyl-2- (2-hydroxypropyl) furan (J. Org. Chem. 26 1673 (1960) and 0.416 mol of chlorine. The temperature is maintained between -16 and -8 ° C during the addition. The solution was heated to boiling for three hours, cooled to room temperature, adjusted to pH 2.1 and extracted with chloroform (3.times.100 ml). the organic phases were washed with water, brine and dried over magnesium sulfate, the organic solution was filtered and evaporated to give a dark solid, the solid was recrystallized twice from methanol to give 8.06 g (30% yield) white Sublimation gave the pure product, mp 157-159 ° C.

H, 6.54; Found:% C, 62.33; 62.05%, 6.44. % H.

NMR (CDCl 3, δ): 6-CH 3, 2.33 (3H, s), 2-CH 3, 1.30 (3H, t), 2H, 2.75 (2H, quartet) H, 6.23 (1H, s).

Example 2 2

2,6-Dimethyl-3-methoxy-4H-ur-4 (O-r-one

To a three-necked round-bottomed flask was added 28 mL of water and 32 mL of methanol and the mixture was cooled to -15 ° C. The solution is simultaneously added

0.169 mol of 5-methyl-2- (u-hydroxyethyl) furan (J. Org. Chem. 26, 1673 (1960) and 0.416 mol of chlorine) The temperature is maintained at -15 to -10 ° C during the addition. R is propyl, butyl, phenyl or benzyl, X is bromo or chloro.

Example 20

A solution of 4-bromo-6-hydroxy-2-methyl-2H-pyran-3 (6H) -one (0.0025 mol) in 20 ml of 35% phosphoric acid was heated at room temperature for 5 hours at reflux temperature and then heat to boiling for three hours. The cooled solution was adjusted to pH 2.1 and extracted with chloroform (3 X 100 mL). The chloroform extracts were combined, washed with water and brine and dried over magnesium sulfate. After filtration and evaporation, the residue, a dark oil, is chromatographed on silica gel with methylene chloride / ethyl acetate 95: 5. The product is isolated by evaporation and recrystallized from methanol. A tan solid (25% yield) was obtained and sublimation gave white crystals of m.p. 161-163 ° C.

For C7H8O2: calculated: 59.99% C, 5.75% H, found: 59.83% C, 5.82% H.

NMR (CDCl3, <5): 6-CH3, 2.33 (3H, s), 2-NH2,

2.26 (3H, s), 5-H, 6.10 (1H, s).

Claims (2)

OBJECT OF INVENTION A process for the preparation of χ-pyrons of formula I A process according to item 1 for the preparation of a γ-pyrrone of the formula IA (R) wherein R is hydrogen, alkyl of 1 to 4 carbon atoms, phenyl or benzyl and R '' is hydrogen or alkyl of 1 to 4 carbon atoms characterized in that the furfuryl alcohol of the formula III wherein R is hydrogen, C1-C4 alkyl, phenyl or benzyl, characterized in that the furfuryl alcohol of the formula IIIA (II IA) (III) wherein R and R '' have as defined above, is reacted in an aqueous solvent at a temperature of from -50 to -50 ° C with at least two equivalents of a halogen-containing oxidizing agent selected from the group consisting of chlorine, bromine, bromochloride, hypochlorous acid, hypobromic acid or mixtures thereof; to complete the reaction to give 4-halo-dihydropyran of formula II wherein R and R '' are as defined above and X is chlorine or bromine and the intermediate, 4-halo-dihydropyran is then heated to a temperature in the range of 70 to 160 ° C in aqueous acidic medium until complete hydrolysis to give the desired γ-pyrone of formula (I). wherein R is as defined above, reacted in an aqueous solvent at a temperature of from -50 to +50 ° C with at least two equivalents of a halogen-containing oxidizing agent selected from the group consisting of chloro, bromo, bromo chloro, hypochlorous acid, hypobromic acid or mixtures thereof to complete the reaction to give 4-halo-dihydropyran of formula IIA HO (IIA) wherein R is as defined above and X is chlorine or bromine and the intermediate, 4-halo dihydropyran of formula IIA is then heated to 70-160 ° C in aqueous acid until complete hydrolysis to give the desired γ- a pyrone of formula IA.