FIELD OF THE INVENTION

The invention relates to a process for the preparation of /7-methylenequinones, in particular ethylene-bis(p-methylenequinones).

BACKGROUND OF THE INVENTION Stable methyl enequinones (p-quinomethides) of general formula (II) have been isolated from natural sources (safflower) and have interesting chemical and biological properties; for example, they are effective antioxidants (Kanehira, T. et al., Life Sciences (2003), 74(1), 87-97) and inhibit tyrosinase (JP 2004083466 and Kanehira, T. et al., Planta Medica (2003), 69(5), 457-459). Thanks to the poly-unsaturated structure, these compounds are intensely coloured (n = 1 : λ _max ~ 510 nm, ε ~ 150.000 M ^"1 cm ^'1 ). Compounds (II) are able to tightly bind proteins and polysaccharides, for which reason they have been used as natural dyes, in particular for dying silk, cotton and wool, and also as food dyes (JP 05279289).

The interest towards these compounds stems also from the fact that, by reduction of the quinone mojeties, conjugated phenols endowed with advantageous chemico-physical properties are obtained. It has been reported, for instance, that compounds (III) can be used as liquid crystals (Davis, R.;

Mallia, V. A.; Das, S.; Chem. Mater. 2003; 75(5); 1057-1063) and that from

l ,4-bis(p-hydroxyphenyl)butadiene (IV) a polymer having remarkable photoluminescence {Journal of Applied Polymer Science 2003; 89 (6); 1645-1651) and non-linear optical properties can be obtained (Mates, Thomas E. et al., Chemistry of Materials (1993), 5(2), 217-21). This phenol also proved effective as antitumoral (WO9904776, JP 11035454, EP 998924).

Quinones (II) are difficult to synthesize. However, three synthesis

(JP 06199724, JP 7278042, JP 9165353) and an extraction method from safflower cell cultures have been described (EP 474191 JP 05032903 CA

2050547) for the quinone with n = 1. One of these syntheses comprises the treatment of sinapic acid at 120 ⁰ C in methanol/water (JP 3337251), while the others require the use of various reagents (aldehydes, halides, phosphoranes etc.) in a complex reaction series and afford poor yields. There is therefore the need to develop a general method that allows to easily synthesize the quinones of formula (II) wherein n = 1 and the corresponding phenols, in high yields and possibly under mild experimental conditions.

DETAILED DESCRIPTION OF THE INVENTION

It has now been found that ethylene-bis(p-methylenequinones) can be obtained by oxidative coupling of two cinnamic acid molecules followed by decarboxylation.

Accordingly, the invention relates to a process for the preparation of compounds of general formula (I)

wherein R ₁ and R ₂ are independently hydrogen, linear or branched Ci-C ₄ alkyl, linear or branched C ₁ -C ₃ alkoxy, comprising the reaction of a compound of formula (V)

with an excess of oxidizing agent in the presence of one or more organic solvents at room temperature. The oxidizing agent is preferably selected from MnO ₂ , cumyl-hydroperoxide and the 2,2-biphenyl-l-picrylhydrazyl (DPPH) radical, while the organic solvent is preferably selected from methylene chloride, methanol, acetone, tetrahydrofurane, di methyl formamide, methylethylketone and mixtures thereof.

The process of the invention is particularly suitable for the preparation of a compound of formula (I) wherein R ₁ and R ₂ represent methoxy groups

(compound Ia). In this case the starting compound is sinapic acid (Va), the oxidant is preferably DPPH or MnO ₂ and the solvent is acetone or a methylene chloride/methanol mixture, preferably in a volume ratio of 1 : 1.

According to a further embodiment, the invention relates to a process for the preparation of a compound of formula (VI)

comprising the reduction of a compound of formula (I) wherein R ₁ and R ₂ represent methoxy groups with ascorbic acid. Preferably, the reaction is carried out in methylene chloride /methanol (1 : 1 , v/v) as solvent.

The compound of formula (VI) can be conveniently used for the determination of the chlorine and/or hypochlorite content in water. The method comprises preparing a methanol solution of compound (VI) having a concentration of about 0.1 mM, adding this solution to the water to be analysed and measuring the absorbance of the resulting solution at a wavelength of 515 nm. The chlorine content is then determined through a calibration line. Preferably, 50 μl of solution of compound (VI) are added to each ml of analysed water.

The method is based on the fact that, in the presence of Cl ₂ /hypochlorite, after few seconds the final solution turns pink due to the reaction:

The invention will be now illustrated in more detail by means of the following examples. EXAMPLES

Example 1 - Synthesis of compound (Ia)

100 mg sinapic acid (Va) is dissolved in about 150 ml of solvent and treated with an excess of oxidant (160 mg MnO ₂ ; 400 mg DPPH; 150 mg cumyl-hydroperoxide). The solution is stirred and kept in the dark at room temperature for about 3 hours. After filtration (in the case of MnO ₂ ) and evaporation of the solvent, the residue is purified by silica gel chromatography using acetone/methanol as eluent.

The table reports the yields for each oxidant and solvent used.

Table. Oxidants and solvents used in the synthesis of compound (Ia)

Oxidant Solvent Yield %

CH ₂ Cl ₂ /metanolo 1 : 1 (v/v) 70

MnO ₅ Methanol 70

Acetone 50

Cumyl-hydroperoxide THF 50

Acetone 60

DPPH THF 40

DMF 57

Methylethyl ketone 36

Example 2 - Synthesis of compound (VI)

50 mg of compound (Ia) are suspended in 100 ml CH ₂ Cl ₂ /methanol (1 : 1 , v:v); then 50 mg ascorbic acid are added and the resulting solution is stirred at 35-45°C in the dark for about 1 hour. After removal of the solvent, the product is extracted with CH ₂ Cl ₂ (10 ml x 4) in quantitative yield.