FI72721C - VID FRAMSTAELLNING AV GAMMA-PYRONER SAOSOM MELLANPRODUKT ANVAENDBAR 6,6'OXI-BIS / 4-HALOGEN-2,6-DIHYDRO-3-PYRON / OCH FOERFARANDE FOER DESS FRAMSTAELLNING. - Google Patents

Description

The present invention relates to novel, 6,6'-oxy-bis / 4-halo-2,6-dihydro-3-pyronf7 and a process for its preparation which are useful as intermediates in the preparation of gamma-pyrones. 6,6'-oxy-bis / 4-halo-2,6-dihydro-3-pyrones7 useful in the preparation, and their preparation.

Maltol (2-methyl-3-hydroxy-4-oyron) is a naturally occurring substance found in the bark of young larch trees, pine needles and chicory. Previous technical manufacturing 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. Schem. Soc., 67 (1945) 2276 obtained maltol by hydrolysis of streptomycin salts in alkaline solution.

Chawla and McGonigal, J. Org. Chem., 39 (1974) 39 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. 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 Agr. Biol. Chem., 40 (5) (1976) 827-832. This compound had been previously synthesized by the method described in 3 (3 Patent 3,468,915).

The synthesis of gamma pyrones such as pyromeconic acid, maltol, ethyl maltol and other 2-substituted-3-hydroxy-gamma pyrones is described in U.S. Patent Nos. 3,130,204, 3,133,089, 3,140,239, 3,159,652, 3,365,459, 35 3,476,317, 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 2,72721 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. 3,365,459 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 gamma-pyrone of formula (I)

0H

ί il (I)

R

15 which method includes e.g. 6,6'-oxy-bis / 4-halo-2,6-dihydro-3-pyrone of formula (V); Γ! (v) x! .

20 R "0 \ O ^ X) · \ R

heating in an acidic aqueous solution, preferably at a temperature between 70 ° and 160 ° C, until the hydrolysis is substantially complete, wherein in the formulas R is hydrogen or lower alkyl and X is chlorine or bromine.

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

The process for the preparation of a new intermediate 6,6'-oxy-bis / β-halo-2,6-dihydro-3-pyrone is characterized in that 4-halo-6-hydroxy-2,6-35 dihydro- 3-pyrone of formula (II ") x 72721 3 fj (II")

HO ^ 0 R

5 wherein R and X are as defined above are dehydrated.

The dehydration is preferably carried out by heating the compound of formula (II ") at a temperature of about 40 ° C for 16 hours. The starting material of formula (II") can be prepared by reacting furfuryl alcohol in an aqueous solution, optionally with an additional solvent, at -10 ° to + 10 ° C. with two equivalents of halogenated oxygen-free. Preferred oxygen-free are chlorine and bromine. After stirring the reaction mixture for 30 minutes at room temperature, the pH is adjusted to 2 with a strong base and the reaction mixture is extracted as a solvent, for example ethyl acetate. Removal of the solvent gives 4-halo-6-hydroxy-2,6-dihydro-3-pyrone of formula (II ") which can be dehydrated by heating in vacuo to give 6,6'-oxy-bis / 4-20 halo-2 , 6-dihydro-3-pyronia7 ·

The following examples illustrate the preparation of the novel compounds of the invention.

In the examples where spectral data are reported, the chemical shift values of the NMR spectra are reported in 25 symbolic symbols commonly used in the literature and all shifts are expressed in # units (from tetramethylsilane): d = doublet q = quartet 30 m = multiplet

Example 1 6,6'-Oxy-bis, Z4-bromo-2-methyl-2,6-dihydro-3-pyrrone / (a) 4-bromo-6-hydroxy-2-methyl-2,6-dihydro Preparation of -3-pyrone 35

To a solution of 25 g of 1- (2-furfuryl) -1-ethanol in 125 ml of tetrahydrofuran and 125 ml of water at 0 ° C to 5 ° C was added dropwise 2.2721 equivalents of bromine. The temperature was maintained between 5 ° and 10 ° C throughout the addition. After the addition of bromine, the solution was stirred at room temperature for 30 minutes and the pH was adjusted to 2.1 with 2 M 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. The residue was chromatographed on silica gel, eluting with chloroform-ethyl acetate (95: 5). The product was an orange oil which was rechromatographed on silica gel with silica gel and eluted 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); 1.1-1.5 (3 H, m).

(b) Preparation of the final product 4-Bromo-6-hydroxy-2-methyl-2,6-dihydro-3-pyrone was heated under vacuum at 40 ° C for 16 hours. The resulting oily solid was crystallized from isopropyl alcohol to give 6,6'-oxy-bis-N-bromo-2-methyl-2,6-dihydro-3-pyrone7, m.p. 125 ° C.

20 Example 2

The procedure of Example 1 was repeated using a starting material compound of formula

I / O

rr 25 I i ho. '' N> ^ r to give a compound of formula f f r

K

wherein R is methyl or ethyl and X is chlorine.

35 R X Sp. (° C) CH 3 Cl 177 ° - 179 ° CH 2 CH 3 Cl 132 ° - 135 °

Claims (3)

A 6,6'-oxy-bis (J-halo-2,6-dihydro-3-pyrone) useful as an intermediate in the preparation of gamma-pyrones, characterized in that it has the formula (V) \ *, ^ V0 Λ Λ (v) s 0 R 10 wherein R is lower alkyl and X is chlorine or bromine. A process for the preparation of 6,6'-oxybis [4-halo-2,6-dihydro-3-pyrone 'of formula (V) χ χ! JI (v) R Qr '- wherein R is lower alkyl and X is chlorine or bromine, characterized in that 4-halo-6-hydroxy-2,6-dihydro-3-pyrone having formula (II ") 1 i I (II") HO υ R wherein R and X are as defined above, dehydrated. Process according to Claim 2, characterized in that the dehydration is carried out by heating the compound of formula (II ") at a temperature of about 40 ° C for 16 hours.