METHOD FOR THE PREPARATION OF 2,5-DIALKYL-4-HYDROXY-2, 3-DIHYDROFURAN-3-ONES

PROCEDE D'OBTENTION DE 2,5-DIALKYL-4-HYDROXY-2,3- DIHYDROFURAN-3-ONES

English Abstract

METHOD FOR THE PREPARATION OF 2,5-DIALKYL-4-HYDROXY-
2,3-DIHYDROFURAN-3-ONES.
ABSTRACT OF THE DISCLOSURE :
A method is disclosed for preparing certain 2,5-
dialkyl-4-hydroxy-2,3-dihydrofuran-3-ones, said method
comprising the step of cyclizing the corresponding diol-
diones with a cation exchange resin in an aqueous or an
aqueous-alcoholic medium and at the reflux temperature of
the reaction mixture. The method is cheap, convenient anc
dependable.

Claims

The embodiments of the invention in which an exclusive
property or privilege is claimed are defined as follows:


1. A method for the preparation of substituted dihydro-
furans of the formula
Image (I)

wherein R and R1 are methyl radicals or in which either radical
is a methyl radical whereas the other is an ethyl radical, by
cyclization of compounds of formula
Image (II)

wherein R and R1 have the meanings explained above, characterized
in that the cyclization reaction is carried out in the presence
of a catalyst composed by cation exchange resins and insoluble
in the reaction medium.

2. Method according to claim 1, characterized in that the
reaction is carried out at a temperature comprised between 50°C
and 150°C in an inert atmosphere.

3. Method according to claim 1 or 2, characterized in that
the reaction is carried out in an aqueous or an aqueous-alcoholic
solution.

Description

ZSS
. .

This invention relates to a novel method for the
preparation of 2,5-dialkyl-4-hydroxy-2,3-dihydrofuran-3-ones
having the formula:
HO O

~ (I)

R Rl

wherein the two R groups are methyl radicals or wherein one
of the R is a methyl radical and the other is an ethyl

radical starting from compounds of the formula:
-CH3 fH-CO-CO-lH-R

OH H , (II)
in which R is a methyl or an ethyl radical, by cyclization
in aqueous solutions in the presence of ion exchange resins
which are insoluble in the reaction medium. The product of
~formula (I) possess appreciable organoleptic properties so
that they are considerably interesting for the alimentary,
pharmaeeutieal and perfume industries.
The product of formula (II) can be obtained with

eeonomically acceptable methods (see for example L. Re and
G. Ohloff, USP 3 576 014 of Firmenich & Cie.; L. Re and V.

Caciagli, Ger. Offen. 2 426 051 of Snamprogetti S.p.A.)
Previously, the best method for obtaining the
compounds of formula (I) was based on the cyclization of the
preeursors of formula (II) by mineral or organie aeids,or

aeidie buffers soluble in the reaction medium.
The method aceording to the present invention affords
the following advantages over the prior method:
1) The eyelization agents, whieh must be used in a

great amount with respeet to the diol-dione with both methods,
can be recovered by mere filtration and reused.
2) The isolation of the furan derivative from the
reaction mixture is operatively simpler since it does not


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ZSi5

require the continuous removal of the product from the aqueous
phase with ethyl ether and can be effected by mere evaporation,
after filtration from the resin, of the aqueous filtrate,
followed by extraction of the product from the residue with
an appropriate solvent (preferably carbon tetrachloride) and
by evaporation of said solvent.
3) The furan derivatives isolated from the reaction
mixture do not require any further purification ~purity: 95~)
whereas for the preparation according to the previous method
of the derivative (I) in which the two R are methyl radicals,
a purification by sublimation must be made after the isolation
of the reaction raw product.
More detailedly, for thé preparation of the derivative
of formula (I),the starting diol-dione of formula (II) is
reacted in a mixture of water with a hydrophilic solvent
(such as methano, ethanol, dioxan and others) or, preferably
in pure water with a cation exchange resin (such as Amberlite
IR 122,* IR 124*, IR 112,* IR 200* or IR 120,* preferably with
the latter) at a temperature comprised between 50C and 150C
(preferably 100C) and in an inert atmosphere (such as nitrogen).
In the case of the diol-dione of formula (II) in which
R is an et~yl radical, the cyclization gives a mixture of the
two isomers 2-ethyl-5-methyl-2,3-dihydrofuran-3-one and 5-ethyl-
2-methyl-2,3-dihydrofuran-3-one in a ratio of about 2:1, which
can be used as such in the food, pharmaceutical and perfum
industries.
The working details will be clearer, anyhow, from the
scrutiny of the ensuing examples:
E X A M P L E
Preparation of 2,5-dimethyl-4-hydroxy-2,3-dihydrofuran-3-one
To 1.040 g of 2,5-dihydroxyhexane-3,4-dione (raw)
dissolved in 20 mls water are added 4.75 g of Amberlite IR

* Trademark 3
.~

255

120* resin and the mixture is refluxed with stirring in an
atmosphere of nitrogen during 4 hours.
The aqueous solution, upon filtration of the resin,
is neutralized with 2N-NaOH and evaporated to dryness under
vacuum at room temperature. The oily residue which is obtained
is extracted three times with a 10 ml portion of carbon tetra-
chloride each time. After removing the solvent in vacuum at
room temperature there is obtained a residue of 0.327 g (yield
32% from hexindiol) of 2,5-dimethyl-4-hydroxy'-2,3-dihydrofuran-
3-one, an oily substance which crystallizes spontaneously and
has a gas-chromatographic purity of 95% (the gas-chromatographic
analysis have been made with a Hewlett-Packard* instrument Model
7620-A equipped with thermoconductivity detector. Column 6-foot
by 1/8 in. of 4~ SE 30 on silanized Chromosorb G*(60-80 mesh)
170C for 6 mins, then 170C to 230C (30C per min.) with
8 mls/min helium, using eicosane as the internal standard) m.p.
60C - 70C, IR, mass and NMR spectra in accordance with
- literature (J.O. Rodin et al., J. Food Science, 30, 280 (1965)).
E X A M P L E 2
Preparation of 2-ethyl-5-methyl-4-hydroxy-2,3-dihydrofuran-
3-one, and 5-ethyl-2-methyl-4-hydroxy-2,3-dihydrofuran-3-one.
To 1.139 g of 2,5-dihydroxyheptane-3,4-dione (raw)
(prepared from 3-heptine-2,5-diol) dissolved in 20 mls water
are added 4.75 g of Amberlite IR 120* resin and the mixture
is refluxedin a nitrogen atmosphere for 6 hours. The aqueous
solution, after having filtering off the resin, is neutralized
with 2-N NaOH and evaporated to dryness under vacuum at room
temperature. The oily residue which is obtained is extracted
with three successive portion of 10 ml each of carbon tetra-
chloride. After removing the solvent under vacuum at room
temperature an oily residue is obtained, 0.325 g (yield 29% from
heptine diol), composed by a mixture of 2-ethyl-5-methyl-4-
* (trade mark)
-4-

1~ 2~5
hydroxy-2,3-dihydrofuran-3-one and 5-ethyl-2-methyl-4-hydroxy-
2,3-dihydrofuran-3-one (2:1 approx.) of a gaschromatographical
purity of 94% (gas chromatographic conditions as for 2,5-
dimethyl-4-hydroxy-2,3-dihydrofuran-3-one), b.p. 62C - 65C
(0.015 mmHg) with mass and NMR spectra in accordance with the
data of the literature.