Solid state synthesis of 5-oxo-1,4,5,6,7,8-hexahydroquinoline derivatives without using solvent and catalyst

A series of substituted 5-oxo-1,4,5,6,7,8-hexahydroquinoline derivatives have been synthesized from 1,3-diaryl-2-propen-1-one and 5,5-dimethyl-1,3-cyclohexanedione in the presence of ammonium acetate by solid state reaction at 80 ° C with high yields (82-92%) without using solvent and catalyst. This method provides several advantages such as operational simplicity, neutral condition, high yields and environment friendly.

The solid state reaction method is used more and more frequently in organic synthesis.Compared with traditional methods, this method is more convenient and easily controlled.A great number of organic reactions can be carried out in higher yields, shorter times, or milder conditions by the method.][17] In this paper we describe the synthesis of the substituted 5-oxo-1,4,5,6,7,8hexahydroquinoline derivatives from 5,5-dimethyl-1,3-cyclo-hexanedione and 1,3-diaryl-2propen-1-one in the presence of ammonium acetate by solid state reaction at 80 °C without using solvent and catalyst.When 1,3-diaryl-2-propen-1-one and 5,5-dimethyl-1,3-cyclohexanedione were treated with ammonium acetate at 80 °C for 2-5 h, the desired substituted 5-oxo-1,4,5,6,7,8hexahydroquinoline derivatives were obtained in good to excellent yields (82-92%).This method has not been reported before, it is an efficient synthesis by solid state reaction, not only the operational simplicity and without any solvent and catalyst, but also accord with the demands of green organic synthesis.(Scheme 1).In a typical general experimental procedure, a mixture of 5,5-dimethyl-1,3-cyclohexanedione 1, 1,3-diaryl-2-propen-1-one 2 and ammonium acetate were performed at 80 °C by solid state reaction, higher yields of products 3 were obtained.The results are summarized in Table 1.
According to the results we have obtained (Table 1), the effect of electron deficiency and the nature of the substituents on the aromatic rings (Ar not Ar') showed some effect on this conversion.The reaction gave higher yields of substituted 5-oxo-1,4,5,6,7,8-hexahydroquinoline derivatives when the aromatic rings (Ar) bear an electron-withdrawing substituents (Table 1), probably because the Michael addition is easier.
We propose the possible following mechanism to account for the reaction.Firstly, the active methylene of 5,5-dimethyl-1,3-cyclo-hexanedione 1 reacted with 1,3-diaryl-2-propen-1one 2 via Michael addition reaction to give addition product 4. Then the intermediate 4 was condensed with ammonium acetate, lose the acetic acid and water to afford the intermediate 5.
After that cyclised by the nucleophilic attack of NH 2 group on the carbonyl (C=O) moiety and gave the intermediate 6. Finally the intermediate 6 loses a water to give the expected product 3. (Scheme 2).In conclusion, we have described a general and highly efficient procedure for the preparation of substituted 5-oxo-1,4,5,6,7,8-hexahydroquinoline derivatives by the solid state reaction.This procedure offers several advantages including mild reaction conditions, cleaner reaction, high yields of products as well as a simple experimental and isolated procedure which makes it a useful and attractive process for the synthesis of these compounds.

Experimental Section
General Procedures.Melting points were determined in open capillaries and are uncorrected.IR spectra were recorded on a Bio-Rad FTS-40 spectrometer (KBr). 1 H NMR spectra were measured on a Bruker AVANCE 400 (400 MHz) spectrometer using TMS as internal reference and DMSO-d 6 as solvent.Elemental analyses were determined using Perkin-Elmer 2400 II elemental analyzer.General procedure for the preparation of 3. A mixture of 5,5-dimethyl-1,3-cyclohexanedione (1, 3 mmol), 1,3-diaryl-2-propen-1-one (2, 2 mmol), ammonium acetate (4 mmol) was stirred at 80 °C for a period as indicated in Table1.The completion of the reaction was monitored by TLC.After completion of the reaction, the mixture was cooled to room temperature, add ethanol (10 mL) to dilute mixture.The mixture was poured into 80 mL icewater, the precipitate was filtered off and washed with water, the crude products were got.The crude products were purified by recrystallization from ethanol (95%) to give 3. Data of compounds are shown below: Scheme 1 Scheme 2