A facile stereoselective synthesis of ( Z )-1,3-diaryl-2-( N -methylanilino)-2-propen-1-ones

The Claisen-Schmidt condensation of 1-aryl-2-( N -methylanilino)-1-ethanones with aromatic aldehydes in the presence of sodium hydroxide in aqueous alcohol led to the formation of hitherto unknown ( Z )-1,3-diaryl-2-( N -methylanilino)-2-propen-1-ones. The structure and stereochemistry of the products were elucidated from 1 H, 13 C and 2D NMR spectroscopic data and nuclear Overhauser effect.

In general, the interaction of the lone of pair of electrons on nitrogen with the double bond in enamines confers electrophilicity over the carbon attached to the nitrogen rendering the enamines prone to hydrolysis.Hence it was reasoned that if the amino group carries an aromatic ring, the availability of the lone pair of electrons on nitrogen for conjugation with the C=C bond would be diminished, as the lone pair could also interact mesomerically with the aryl ring attached to the nitrogen.Further, the steric interactions between the Me/aryl ring attached to nitrogen with the oxygen/3-aryl ring of the enone system of 3 could orient the nitrogen in such a way that the nitrogen lone pair is turned away from being parallel with the p-orbitals of the C=C bond, reducing the conjugation between the nitrogen and the C=C bond.The aforementioned nitrogen conjugation with the aromatic ring and the steric interactions diminishing the nitrogen conjugation with the C=C bond could, in turn, diminish the tendency of 3 to hydrolysis under the present reaction conditions involving aqueous alcoholic sodium hydroxide.
The 1-aryl-2-(N-methylanilino)-1-ethanones, 2 required for the synthesis of 3 were, in turn, obtained in excellent yields by the reaction of the appropriate phenacyl bromides, 1 with Nmethylaniline (Scheme 1) in the presence of potassium carbonate under solvent-free conditions.The present methodology is simple, eco-friendly, rapid and efficient compared to literature methods. 19,20In earlier works, 1-aryl-2-(N-methylanilino)-1-ethanones 2 were synthesized from the reaction of phenacyl bromides with N-methylaniline under reflux in ethanol.The physical constants of these compounds are comparable with those reported in the literature.
were obtained in 88%, 91% and 90% yields respectively in the present work.It is pertinent to note that in our recent work 21 on the synthesis of 2-arylindoles, we have obtained 2 as an intermediate under solvent-free conditions in presence of sodium bicarbonate and used it without purification in the next step and hence the yield of 2 could not be reported.

ARKAT
The structure of the enones is also consistent with the 1 H and 13 C NMR spectroscopic data as illustrated for 2-(N-methylanilino)-1,3-diphenyl-2-propen-1-one (3a).The three-protons singlet at 3.12 ppm and one-proton singlet at 6.97 ppm are assigned to N-methyl and benzylidene protons respectively.The distinct assignment of the signals of the benzene rings of 3 was made from the chemical shift of signals, multiplicity and H,H-COSY spectrum of 3 (Fig. 1).For instance, the doublet occurring far downfield at 7.77 ppm integrating for two protons with a J value of 8 Hz is assigned to the ortho hydrogens of the benzoyl ring.This signal correlates with a triplet at 7.38 ppm (J = 8 Hz) in the H,H-COSY spectrum which enables its assignment to the meta hydrogens of the benzoyl ring.Similarly, the signal of the meta hydrogens at 7.38 ppm correlates with the triplet at 7.47 ppm with a J value of 8 Hz.By similar considerations, the protons of remaining two phenyl rings have also been assigned.Other enones also showed similar features in their 1 H NMR spectra.The configuration of the double bond of 3 was found to be (Z) by nuclear Overhauser effect (NOE) experiment, wherein (i) the benzylidene proton at 6.97 ppm has a NOE correlation with the ortho hydrogens of the benzoyl ring and (ii) the para proton of the N-aryl ring appearing at 6.73 ppm also shows a NOE correlation with the meta protons of the 3-aryl ring that appears at 7.52 ppm. The

Experimental Section
General Procedures.The melting points reported in this work are uncorrected.The 1 H and 13 C NMR spectra of the (Z)-1,3-diaryl-2-(N-methylanilino)-2-propen-1-ones (3a-3j) were measured at 300 and 75 MHz respectively using Bruker (Avance) NMR instrument in CDCl 3 and the chemical shifts referenced to tetramethylsilane.Standard Bruker software was employed to obtain both the one-and two-dimensional NMR spectra.The various phenacyl bromides were synthesized using literature procedures. 22,23Elemental analyses of 3 were performed on a Perkin Elmer 2400 Series II Elemental CHNS Analyser available in our institution.Phenacyl bromide (0.25 g, 1.25 mmol) was taken in a clean, dry test tube and a pinch of anhydrous potassium carbonate was added.To this, distilled N-methylaniline (0.17 g, 1.57 mmol) was added and the reaction mixture mixed vigorously using a clean, dry glass rod.The reaction mixture got solidified immediately.
Stirring was continued for a few more minutes.To the reaction mixture, ice-cold water was added and stirred well to remove the potassium carbonate present in the reaction mixture.The greenish yellow 2-(N-methylanilino)-1-phenyl-1-ethanone was filtered at the pump, washed several times with ice-cold water, dried and crystallised from ethanol.

Synthesis of (Z)-1,3-diaryl-2-(N-methylanilino)-2-propen-1-ones (3).
To a mixture of sodium hydroxide (0.3 g) in water (3 ml), ethanol (2 ml) and 1-aryl-2-(N-methylanilino)-1-ethanone (5 mmol) kept at 0 o C, pure aldehyde (5 mmol) was added.After the addition of alcohol was over, the temperature of the reaction mixture was raised to about 25°C and stirred vigorously until the mixture became a thick mass.Then the flask was placed in a refrigerator overnight, the solid separated was filtered, washed with cold water and cold ethanol (3 ml), dried and crystallized from ethanol.