FI72720B - 4-HALOGEN-DIHYDROPYRONFOERENING FOER ANVAENDNING SOM MELLANPRODUKT VID FRAMSTAELLNINGEN AV 3-HYDROXI-4-PYRONER OCH FOERFARANDE FOER DESS FRAMSTAELLNING. - Google Patents

Description

1,72720 A 4-halo-dihydropyrone compound useful as an intermediate in the preparation of 3-hydroxy-4-pyrones and a process for its preparation 5 Separated from patent application 771934.

This invention relates to novel 4-halo-dihydropyrone compounds of formula (II ') useful as intermediates in the preparation of 3-hydroxy-4-pyrones.

10 X

Wherein R is hydrogen or lower alkyl and X is chlorine or bromine, and their preparation.

Maltol (2-methyl-3-hydroxy-4-pyrone) is a naturally occurring substance found in the bark of young larch trees, pine needles and chicory. Previous technical production has taken place by dry distillation of wood. The synthesis of maltol from 3-hydroxy-2- (1-piperidylmethyl) -1,4-pyrone has been described by Spielman and Freifelder in J. Am. Chem. Soc. 69 (1947) 2908. Schenck and Spielman, J. Am. Chem. Soc. 67 (1945) 2276, obtained maltol hydroly-25 by reacting streptomycin salts in an alkaline solution.

Chawla and McGonigal, J. Org. Chem. 39 (1974) 3281 and Lichten-Thaler and Heidel, Angew. Chem. 81 (1969) 998, have described the synthesis of maltol from protected carbohydrate derivatives. Shono and Matsumura, Tetrahedron Letters No.

30 17 (1976) 1363, have described a five-step synthesis of maltol starting from methyl furfuryl alcohol.

The isolation of 6-methyl-2-ethyl-3-hydroxy-4-pyrone as a typical sweet-smelling ingredient in molasses processing is described by Hiroshi Ito in Article 35 Agr. Biol. Chem. 40 (5) (1976) 827-832. This compound had previously been synthesized by the method described in U.S. Patent 3,468,915.

The syntheses of 2,72720 3-hydroxy-4-pyrones such as pyromeconic acid, maltol, ethyl maltol and other 2-substituted 3-hydroxy-4-pyrones are described in U.S. Patent Nos. 3,130,204, 3,133,089, 3,140,239, 3,159 652, 3,365,459, 5,376,317, 3,468,915, 3,440,183 and 3,446,629.

Maltol and ethyl maltol increase the taste and aroma of various foods. In addition, these compounds are used as ingredients in perfumes and essences. The 2-alkenyl-pyromeconic acids described in U.S. Patent No. 3,644,635 and the 2-arylmethylpyromeconic acids described in U.S. Patent No. 3,365,469 prevent the growth of bacteria and fungi and are useful in flavoring and flavor enhancers. as fragrance enhancers in perfumes.

Patent application 771934 discloses a process for the preparation of 3-hydroxy-4-pyrone derivatives by acid hydrolysis from a 3-pyrone derivative. In this case, the 3-hydroxy-4-pyrone of formula (I)

O

20 A

OH

I jT (I)

v O R

wherein R is hydrogen, alkyl of 1 to 4 carbon atoms, or benzyl, prepared from 4-halo-2,6-dihydro-3-pyrone or 6,6'-oxy-bis-4-halo-2, 6-dihydro-3-pyronist% 7 of formula (II)

X

30 I

^ JL (11)

R '(O' R

wherein R is hydrogen, alkyl of 1 to 4 carbon atoms, or benzyl, R 'is hydrogen, lower alkyl, acetyl, or optionally 2- (lower alkyl) substituted 4-halide-hydropyranyl, and X is chlorine or bromine .

72720

The acid required for the hydrolysis can be added to the reaction mixture, eism. dissolving the compound of formula (II) in an aqueous solution of an inorganic or organic acid before heating; or alternatively the acid may be formed in situ in the preparation of intermediates as described below.

The above compound of formula (II) can be prepared by reacting a compound of formula (IV) wherein R and R 'are as defined above in a solvent, -50 ... + At 50 ° C, preferably at room temperature, with at least one equivalent of a halogenated oxidant selected from chlorine, bromine, bromine chloride, alichloroacid, alibromic acid or a mixture thereof until the reaction is substantially complete.

Examples of suitable solvents for use in this reaction include water, alkanol or diol having 1 to 4 carbon atoms, preferably methanol, ether having 2 to 10 carbon atoms, preferably tetrahydrofuran or isopropyl ether, a low molecular weight ketone, preferably acetone, a low molecular weight nitrile, ester or amide.

The 4-halohydropyran compounds of formula (II ') are novel.

The process according to the invention for the preparation of the novel compounds of the formula (II1) is characterized in that the 2- (1-hydroxyalkyl) furan of the formula (III)

Ooh - ^ (III)

35 XR

72720 wherein R is as defined above, is reacted in an aqueous solution of tetrahydrofuran with at least two equivalents of a halogenated oxidant which is chlorine or bromine at a temperature of -50 to + 50 ° C to give a compound of formula (II ').

The halogen-containing oxidant is chlorine or bromine, preferably chlorine.

In a preferred embodiment of the invention, the fufuryl alcohol is reacted in an aqueous solution of tetra-10 hydrofuran at a temperature of -10 to + 10 ° C with two equivalents of a halogenated oxidant. After stirring for 30 minutes at room temperature, the reaction mixture is adjusted to pH 2 with a strong base and the reaction mixture is extracted with a solvent such as ethyl acetate.

Removal of the solvent gives 4-halo-6-hydroxy-2,6-dihydro-3-pyrone of formula (II ').

The following examples illustrate the preparation of the 4-halo-dihydropyrone compounds of the invention.

In the examples where spectral data are reported, the values of the chemical shifts of the 20 NMR spectra are given by the symbolic symbols commonly used in the literature and all shifts are expressed in ^ units (from tetramethylsilane): s = singlet 25 d = doublet t = triplet q = quartet m = multiplet br = broad Example 1 4-Bromo-6-hydroxy-2-methyl-2,6-dihydro-3-pyrone 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, 2.2 equivalents of bromine were added dropwise. The temperature was maintained between 5 and 10 ° C throughout the run. After the addition of bromine, the solution was stirred at room temperature for 30 minutes and the pH was adjusted to 2.1 with 2N NaOH solution. The reaction mixture was extracted with ethyl acetate (3 x 100 mL). The ethyl acetate extracts were combined, dried over MgSO 4, filtered and evaporated to dryness. Residue 5 was chromatographed on silica gel eluting with chloroform-ethyl acetate (95: 5). The product was an orange oil which was rechromatographed on silica gel eluting with chloroform-ethyl acetate (95: 5).

NMR (CDCl 3, δ) 7.3 (1H, d); 5.6 (1 H, d); 4.7-5.0 (1 H, q); Δ 1.1-1.5 (3 H, m).

Example 2

The procedure of Example 1 was repeated using fufuryl alcohol of the formula

CV

R

to give a compound of formula 20X

HO ^ 25 wherein R is hydrogen or ethyl.

Ethyl compound: 4-bromo-6-hydroxy-2-ethyl-2,6-dihydro-3-pyrone NMR (CDCl 3, δ) 7.4 (1H, d); 4.6-4.9 (1 H, m); 1.8-2.2 (2 H, m)? 1.0-1.3 (3 H, t).

Hydrogen compound: 4-bromo-6-hydroxy-2,6-dihydro-3-pyrone NMR (CDCl 3, δ) 7.4 (1H, d); 5.5 (1 H, d); 4.6 (2 H, d-d). Example 3

The procedure of Example 1 was repeated using chlorine and appropriate furfuryl alcohols instead of bromine to give the following compounds: 6,72720 N-ethyl: 4-chloro-6-hydroxy-2-methyl-2,6-dihydro-3-pyrone NMR (CDCl 3, δ) : 7.1 (1 H, d); 5.8 (1 H, d); 4.6-5.0 (1 H, m); 4.4 (1H, br.s.); 1.2-1.5 (3 H, m).

Ethyl: 4-chloro-6-hydroxy-2-ethyl-2,6-dihydro-3-pyrone NMR (CDCl 3, δ): 7.0-7.1 (1H, d); 5.6-6.0 (2 H, m); 4.4-5.0 (1 H, m); 1.6-2.1 (2 H, m); 0.9-1.1 (3 H, t).

Hydrogen: 4-chloro-6-hydroxy-2,6-dihydro-3-pyrone 10 NMR (CDCl 3, δ): 7.1-7.2 (1H, d); 5.6 (1 H, d); 4.4-4.9 (2H, d-d) added).

Claims (2)

7 72720 A 4-halo-dihydropyrone compound useful as an intermediate in the preparation of 3-hydroxy-4-pyrones, characterized in that it has the formula (II ') X f ^ ^ T0 hcA o- ^ r (I1') 10 wherein R is hydrogen or lower alkyl and X is chlorine or bromine. A process for the preparation of a 4-halogenated dihydropyrone compound of formula (II ') 15 1 (11') H 2 O 2 R 20 wherein R is hydrogen or lower alkyl and X is chlorine or bromine, characterized in that that 2- (1-hydroxyalkyl) furan of formula (III) Of wherein R is as defined above is reacted in an aqueous solution of tetrahydrofuran with at least two equivalents of a halogenated oxidant which is chlorine or bromine, -50. At a temperature of + 50 ° C to give a compound of formula (II ').