Alkylation by Enamines for Synthesis of some Heterocyclic Compounds

Compounds of 4-phenyl-3-butene-2-one (1) and 4-(4-chlorophenyl)-3-butene-2-one (2) were prepared by reaction of benzaldehyde or 4-chlorobenzaldehyde with acetone. Also 1,3-diphenyl-2-chloropropene-1-one (3) was synthesized from the reaction of benzaldehyde with 2-chloroacetophenone through Claisen-Shmidt condensation. The substituted ∆octalone-2 (4,5) was prepared by reaction of the compounds (1and2) with cyclohexanone through Michael addition followed by aldol condensation. Compounds (4,5) were reacted with alkyl halide, as 2-chloroacetophenone or 1,3-diphenyl-2-chloropropene-1-one (3), via enamines formation which then hydrolyzed to give compounds (6-9). Compounds (6,7) were reacted with hydrazine , urea and thiourea to afford compounds (10-15) . The structures of all synthesized compounds were confirmed by available physical and spectral means .


INTRODUCTION
In general, a compound that contains both a carbon-carbon double bond and a carbonoxygen double bond has properties that are characteristic of both functional groups (Morrison and Boyed, 1973).At the carbon-carbon double bond an unsaturated ester or unsaturated ketone undergoes electrophilic addition of acids and halogens, hydrogenation, hydroxylation and cleavage; at the carbonyl group it undergoes the nucleophilic substitution typical of an ester or the nucleophilic addition typical of a ketone.α,β-unsaturated carbonyl compounds, posses not only the properties of individual functional groups, but certain other properties besides.There are several general ways to make compounds of this kinds: the aldol condensation to make unsaturated aldehydes and ketones, dehydrohalogenation of halo acids and the Perkin condensation to make unsaturated acid.Aldol condensation are often used to close five-and six-membered rings, such ring closures generally take place with ease, even where a ketone condenses with a ketone.An important example is the Robinson annulation reaction (Jung, 1976;Takao, and Kobayashi, 1997;Hagiwara et al., 1994;Watson et al., 1995, Lejeune andLallemand, 1991), which has often been used in the synthesis of steroids and terpens.In this reaction a cyclic ketone is converted to another cyclic ketone, with one additional six-membered ring containing a double bond.The substrate is treated with methyl vinyl ketone (or a simple derivative of methyl vinyl ketone) and a base (March, 1977) .The enolate ion of the substrate adds to the methyl vinyl ketone in a Michael reaction to give a diketone which undergoes or is made to undergo an internal aldol condensation and subsequent dehydration to give the product .

Chemical and instrumentation :
All chemicals were purchased from Flucka and BDH chemical Ltd.The melting points were measured on Electrothermal 9300 Engineering LTD and were uncorrected .IR spectra were recorded on Infrared spectrophotometer Model Tensor 27, Bruker Co., Germany, using KBr disks.UV spectra were recorded on shimadzu Double-Beam spectrophotometer UV-210 A using chloroform as a solvent .
The theoretical calculations were computed using semi-empirical AM1 module in the CS chemoffice molecular modeling package .The data obtained from the minimized geometry were used for the theoretical calculations .

Preparation of 4-aryl-3-buten-2-ones (1,2) (Vogle, 1956)
A mixture of (0.395 mole 42g) of pure substituted benzaldehyde and (1.09 mole 80ml) of pure acetone in a 250 ml .flask equipped with a shacked mechanical stirrer and dropping funnel was immerse in a cold water bath and 10 ml of 10 % of sodium hydroxide was added slowly from a dropping funnel; adjust the rate of addition so that the temperature remains between 25 o and 30 o .The mixture was stirred or shacked mechanically at room temperature for a further 2 hours; alternatively securely stopper the flask and shake mechanically for the same period.Render the mixture just acidic to litmus paper by the addition of dilute hydrochloride acid, transfer to a separatory funnel, remove the upper organic layer, extract the lower aqueous layer with 20 ml of benzene and add the extract to the yellow upper layer.Wash the latter with 20 ml of water, and dry with anhydrous magnesium sulphate.Evaporate the benzene on a water bath.The solid was recrystallized from light petroleum ether (b.p. 40-60 o ) to give yellow crystals, (Table 1) .Preparation of 1,3-diphenyl-2-chloropropene-1-one (3) (Vogle, 1956) .
A mixture of (0.33 mole) of (1 or 2),(0.33mole 31ml) of cyclohexanone (150 ml) of diethyl ether and (300 ml) of (0.1 N) of sodium hydroxide was stirred in a bath of crushed ice for (3 hr.).Render the mixture just acid to litmus paper by the addition of dilute hydrochloric acid.Transfer to a reparatory funnel and remove the aqueous layer .Dry the organic layer with a little anhydrous magnesium sulphate.Evaporate the ether and then the product was recrystallized from petroleum ether to give (4 or 5) as pale yellow crystals (Table 2,3) .

RESULTS AND DISCUSSION
The structure of compounds (1,2) were elucidated by ultra violet and infrared spectra (Table 1), which showed sharp peaks at (1656, 1665 cm -1 ) due to carbonyl groups, a medium peak at (1560 , 1580 cm -1 ) due to (C = C) double bonds.Compound (3) was prepared by Claisen-Shmidt reaction.The spectral informations showed a sharp peak at (1668 cm -1 ) due to a carbonyl group, a medium peak at (1590 cm -1 ) due to (C = C) double bond (Sandler, and Karo, 1972).The U.V spectra of compounds (1-3) showed λmax at (330-335 nm) which indicated that conjugation was found between the (C = O) group and (C = C) group causing bathochromic shift (red shift) comparing with those which have no conjugation (starting materials) .
The range peaks at (1617-1627 cm -1 ) due to the (C = N) group and the range peaks at (1587-1613 cm -1 ) due to the cyclic double bond .

Table 1 :
Some physical properties and spectral data for compounds (1-3)