Aluminum Phosphate Catalyzed Free Solvent Preparation of β-enamino Esters

Alu minu m phosphate (AlPO4) efficiently catalyzed the condensation of 1,3-ketoesters with primary amines under free solvent conditions. The catalyst has been prepared and characterized by powder XRD and FT-IR studies. The AlPO4 synthesis was performed in water at roo m temperature fro m AlCl3 and H3PO4 in the presence of ammonia solution. Resultant material showed good catalytic efficiency in condensation of 1,3-ketoesters with primary amines using a domestic micro wave oven with no solvent. The reaction was complete in 7 min to afford β-enamino esters in a high yield and high selectivity.

The use of microwave irradiation in the presence of catalysts or mineral-supported reagents, under solvent-free conditions [36], provides a simp le chemical process with special attributes such as enhanced reaction rates, higher yields, greater selectivity and ease of manipulation [37].

Instruments
NMR studies were performed on a Bruker Advance 300 spectrometer in CDCl 3 . chemicals shifts are given in ppm relative to external TM S and coupling constant (J) in Hz. Infrared spectra (IR) were obtained on a Bru ker-TENSOR 27 spectrometer instrument. X-ray d iffraction patterns (XRD) were obtained with a Philips X'Pert MPD d iffracto meter using Cu Ka radiation (k = 1.54178 Å). Mass spectra were recorded on a GC-MS Varian star 3400 CX. Optical rotation was measured at roo m temperature using an ATA GO polax-D polarimeter . M icro wave irradiations were carried out in a domestic micro wave oven Model AVM 510/WP/WH (700 W). The products' physical and spectroscopic data were compared with those reported in the literature.

Procedure of Catal ytic Studies
In a typical experiment 1.7 mmo l of ketoester, 1.7 mmo l of amines and 0.17 mmo l of AlPO 4 were used, the heterogeneous mixture was transferred to a micro wave oven at 60 W for the time indicated in Table 1. At the end of the reaction, 10 mL o f d istilled water were added to the residue and extracted with d iethyl ether (3 × 25 mL). The o rganic layer was dried over Na 2 SO 4 , and the solvent was removed under vacuum. Pu re β-enamioesters was obtained by column chromatography over silica gel using hexane/ethyl acetate as eluent. All isolated pure products were fully characterized by 1 H, 13 C NM R and Mass spectra compared with the known compounds [17].

Catalyst Characterizati on
Structural properties of the prepared AlPO 4 were characterized using FT-IR and XRD analysis.   [38][39][40]. FTIR spectra of PO 4 3in AlPO 4 show the antisymmetric stretching mode (ν 3 ) in 1000-1200 cm -1 region and the ν 4 mode in 400-560 cm -1 region. The observed bands in 1600-1700 and 3000-3500 cm -1 region are attributed to the water bending and stretching vibrations, respectively [40]. These water bands confirmed that the product is in hydrate form AlPO 4 xH 2 O.
XRD pattern of the synthesized AlPO 4 powder samples showed that all peak positions and relative peak intensities of AlPO 4 matched well with those of the standard XRD pattern. All the diffract ion peaks orientated along (200), (110), (111) and (310) correspond to the well-crystalline monoclinic AlPO 4 phases (JCPDS Card No. 00-051-1674) as observed from Fig. 2.

Catalyst Acti vi ty Studies
In a typical experiment, equimo lar rat io of ketoester and primary amine were mixed in the presence of a catalytic amount of AlPO 4 (10 mo l%) without solvent to obtain the corresponding enaminoester in good yields ( Table 1). The reaction was completed within the indicated time under micro wave irradiat ions using a domestic micro wave oven. No by-products were obtained (scheme 1).

Scheme 1. Condensation of Ketoesters with primary amines
The condensation of various primary amines with ketoesters, was investigated, providing the corresponding enamino esters in good to excellent y ields. A mong these, aliphatic amines were more reactive and gave the corresponding β-enamino ester in excellent yields 95%-98% (Table 1, entries 1-5). Th is protocol efficiently condensed anilines having electron donating groups in position 4 (e.g., F, Br, Me and OMe) with ketoesters to produce the corresponding β-enamino esters in excellent yields (Table 1, entries [8][9][11][12], whereas in the presence of electron withdrawing group (NO 2 ) a high decrease in the y ield was observed (Table 1, entry 10). In the presence of amines possessing sterically hindering groups on the aromatic rings, the process required longer time (6 to 7 min) to obtain reasonable yield (Tab le 1, entries 13,15) when compared to other amines.
Under the same react ion conditions, the condensation of naphthylamine and ketoester affords the corresponding β-enaminoester in a moderate yield after 7 min (Entry 16).
It is noteworthy that optically act ive amine was converted into the corresponding β-enamino ester 6 without any racemizat ion. The optical rotation was found to be [α] D 20 = −623, c=1.25, in Et OH matched the literature values (entry 6) [41][42].
The reaction proceeds cleanly leading to formation of the pure product as determined by chromatography, avoiding any tedious work up. The stereoselectivity of the reaction is confirmed by 1 H NMR spectra. The signal of the -NHgroup appearing at a lower field (δ > 8.2 pp m) indicated the formation of an intramolecular hydrogen bond, which stabilized the enamines as a (Z) configuration [17][18][19] (Scheme 1).

Conclusions
Microwave irradiation in solvent-free conditions of primary amines and ketoesters using AlPO 4 as catalyst leads to the formation of β-enaminoesters compounds in good to excellent yields. The reaction emp loys a simple catalyt ic system resulting in shorter reaction time than the conventional procedure. The advantages of the novel and facile methodology are precluding volatile, clean process, economic and environ mental procedure.