DEHYDROZINGERONE ANALOGUES: REACTION OF O-ALKYL DERIVATIVES OF VANILLIN AND METHYL CYCLOPROPYL KETONE

O-Alkyl vanillines and methyl cyclopropyl ketone rea cts under ClaisenSchmidt conditions yielding corresponding enone der ivatives, dehydrozingerone analogues with cyclopropane ring fragment, ( E)-1-cyclopropyl-3-(4-alkoxy-3methoxyphenyl)prop-2-en-1-ones. All new compounds w ere well characterized by IR, H and C NMR spectroscopy and physical data.

Conjugate enone system which is presented in the dehydrozingerone is structurally different from chalcones; instead of the aryl group to the carbonyl is attached the methyl one.Their enone system could be easily transformed into some usable heterocyclic derivatives (ABDEL- RAHMAN et al., 2007;KALIRAJAN et al., 2009).
It is therefore, not surprising that many synthetic methods have been developed for the preparation of heterocycles starting from chalcone precursors that have been tested for their antimicrobial activities.
Knowing that cyclopropane ring is present in a huge number of natural isolated molecules (such as terpenes, fatty acids, alkaloids, steroids…) it is not a surprise that many of them show different biological activities, from enzyme inhibition of herpes proteases (PINTO et al., 1996;WITVROUW et al., 1999) to antibiotic, herbicidal, antitumor, and antiviral properties (BOGER et al., 2001;FAUST, 2001;YOSHIDA et al., 2004).Well known are chrysanthemic acid, pyrethrin and pyrethroid derivatives, compounds related to natural and synthetic insecticides, with good insecticidal activities (SAKAGUCHI et al., 1998;CONCELLON et al., 2007).
All new products were characterized by their spectral data (IR, 1 H NMR and 13 C NMR).

General remarks
All starting chemicals were commercially available and used as received, except that the solvents were purified by distillation.Chromatographic separations were carried out using silica gel 60 (Merck, 230-400 mesh ASTM) whereas silica gel on Al plates, layer thickness 0.2 mm (Merck), was used for TLC.IR spectra were recorded on a Perkin-Elmer One FT-IR spectrometer with a KBr disc, ν in cm cm -1 ; NMR spectra were recorded on a Varian Gemini 200 MHz spectrometer (200 MHz for 1 H and 50 MHz for 13 C), using CDCl3 as solvent and TMS as the internal standard. 1H and 13 C NMR chemical shifts were reported in parts per million (ppm) and were referenced to the solvent peak; CDCl3 (7.26 ppm for 1 H and 76.90 ppm for 13 C).Multiplicities are represented by s (singlet), d (doublet), t (triplet), q (quartet) and m (multiplet).Coupling constants (J) are in Hertz (Hz).
Compounds 8a and 8f are known compounds and their chemical synthesis was published earlier (COGNACQ, 1978; KUMAR and DHAR, 1995), while compounds 8b-e are new compound and their structure and spectral data are given.

General procedure for synthesis of (E)-1-cyclopropyl-3-(4-alkoxy-3methoxyphenyl)prop-2-en-1-one, 8a-f
NaOH (3 g) was dissolved in 20 mL of water and cooled to 15 °C and 15 mL of ethanol was added.Into a cold solution, with intensive stirring, methyl cyclopropyl ketone (10 mmol in 5 mL of ethanol) was added dropwise during 30 min.Reaction mixture was kept at temperature under 20 °C.Corresponding O-alkyl vanillin (10 mmol) was dissolved in a 10 mL of ethanol and added dropwise into a reaction mixture and stirred for next 6 h.Then mixture is left overnight in refrigerator.Product crystallize from 60% ethanolic solution as white powder.
The separated solid was filtered, washed with water, dried and recrystallized from ethanol.
In some cases, products do not separate as solid.Following procedure was applied to isolate them: ethanol from reaction mixture was evaporated under reduced pressure while product remains as oily residue.Products were extracted with CH2Cl2 (3×50 mL); organic layer was washed with water and dried over anhydrous Na2SO4.Solvent was distilled off and products crystallize in some cases on standing or from ether.