An efficient synthesis of 8-aryl-9 H -cyclopenta[ a ][4,7]phenanthroline derivatives catalyzed by iodine

A series of 10,11-dihydro-8-aryl-9 H -cyclopenta[ a ][4,7]phenanthroline derivatives was prepared by a three-component reaction of aromatic aldehyde, quinolin-6-amine and cyclopentanone using iodine as catalyst. The structure of 4e is confirmed by X-ray diffraction analysis


Introduction
In recent years, multi-component reactions (MCRs) have become important tools in modern preparative synthetic chemistry because they increase the efficiency by combining several operational steps without isolation of intermediates or changing the reaction conditions. 1 MCRs have emerged as valuable tools for the preparation of structurally diverse chemical libraries of drug-like heterocyclic compounds. 2Owing to their convergence and productivity, the MCRs have attracted considerable attention from the organic synthetic chemistry point of view. 3he phenanthrolines and their derivatives are well known compounds for their metallic complexes.The latter possess remarkable physiological and pharmacological activities.Their activities include anticancer (copper(II)), 4 antiinflammatory (copper(II)), 5 antitumor (Pt(II)), 6 antimicrobial (copper(II)), 7 and antibacterial activity (Y(III)). 8In addition, it was reported that phenanthroline derivatives themselves also had commendable antitumor activity. 9ozlov et al. 10 reported that Schiff base containing quinoline fragment, could react with cyclopentanone or cyclohexanone to produce 4,7-phenanthrolines, which was promoted by HCl,

Results and Discussion
Treatment of aromatic aldehyde 1, quinolin-6-amine 2 and cyclopentanone 3 in THF in the presence of 5 mol% iodine at reflux condition afforded the corresponding 10,11-dihydro-8-aryl-9H-cyclopenta[a] [4,7]phenanthroline 4 in good yields (Scheme 1).Using the conversion of 2-bromobenzaldehyde 1a, quinolin-6-amine and cyclopentanone as a model, several parameters were explored as shown in Table 1. the reaction did not take place at reflux in the absence of iodine (Table 1, Entry 1).Similar reactions were attempted in the presence of 1, 5 and 10 mol% of I2.The results from Table 1 show that 5 mol% I2 at reflux in THF is sufficient to initiate the reaction.Higher loading of the catalyst had no significant influence on the reaction yield.(Table 1, entries 4-6).The yield of 4a was also dependent on temperature (entries 2-4), proceeding smoothly at reflux.Different solvents were also tested, and THF appeared to be the best medium for this transformation (entry 4 vs. 7-10).
This process can tolerate both electron-donating (alkyl and alkoxy-) and electronwithdrawing (halogen) substituents on the aromatic aldehydes (Table 1).In all cases, the reactions proceeded efficiently at reflux to afford the corresponding cyclopenta[a] [4,7]phenanthrolines in good yields.The structures of the products 4a-4j were characterized by IR, 1 H NMR and HRMS, all the data were good agreement to their structures.The structure of 4e was additionally confirmed by X-ray diffraction analysis.Crystal data for 4e: C21H15FN2; M = 314.35,Orange block crystals, 0.655 × 0.410 × 0.087 mm, Monoclinic, space group P 21/c, a = 8.6497 ( 2 3 and Table 4, respectively.The X-ray diffraction analysis of 4e indicates that the five-numbered ring (C2, C3, and C13~C15) is slightly distorted, forming an envelope conformation: the atoms C13, C2, C15 and C13 are coplanar, while the atom C14 deviates from the defined plane by 0.451(3) Å.The pyridine ring nearly parallel to the above basal plane and adjacent quinoline ring, forming the dihedral angles of 5.2 (1) and 6.0 (1), respectively, and make a dihedral angle of 33.6 (1) to the benzene ring (C16~C21).
The X-ray diffraction analysis of 4e reveals that there is no hydrogen bond in the crystal structure.It should be noted that there is intermolecular π-π interaction between the two neighboring benzene rings (C4-C8 and C12), symmetry code: -x, 1-y, -z), which are parallel to each other.The centroid-to-centroid distance, plane-plane distance and displacement distance are 3.996(3), 3.507 and 1.917 Å, respectively, which indicate the existence of intermolecular π-π interaction.The above π-π interactions link the adjacent molecules forming dimers along b axis (Figure 2).

Figure 2. The π-π interaction in the crystal structure
According to the literature, 12 we think that iodine catalyzes the reaction as a mild Lewis acid.The mechanism was tentatively proposed as shown in Scheme 2. The Schiff base I may be formed by the reaction of aromatic aldehyde and quinolin-6-amine firstly.And then imino-Diels-Alder reaction between the iodine-activated Schiff base II and enol form of 3 takes place to form intermediate III, followed by isomerization and dehydration results in dihydroquinoline IV, which is further oxidized by air to afford aromatized cyclopenta[a] [4,7]

Conclusions
In conclusion, we found a mild and efficient method for the synthesis of 8-aryl-9Hcyclopenta[a] [4,7]phenanthroline derivatives via three-component reaction of aromatic aldehyde, quinolin-6-amine and cyclopentanone using iodine as catalyst.The features of this procedure are mild reaction conditions, good yields and operational simplicity.

Experimental Section
General.Melting points were determined in open capillaries and are uncorrected.IR spectra were recorded on a Tensor 27 spectrometer in KBr pellet. 1 H NMR spectra was obtained from a solution in CDCl3 with Me4Si as internal standard using a Bruker-400 spectrometer.HRMS analyses were carried out using a Bruker-micro-TOF-Q-MS analyzer.

Procedure for the synthesis of cyclopenta[a][4,7]phenanthrolines (4).
A dry 50 mL flask was charged with aromatic aldehyde (2.0 mmol), quinolin-6-amine (0.288 g, 2.0 mmol), cyclopentanone (0.176 g, 2.1 mmol), THF (10 mL) and I2 (0.1 mmol, 0.026 g).The reaction mixture was stirred at reflux for 16-28 h, and then a small amount of DMF was added to the mixture, until all the precipitate was dissolved.The products 4 were obtained by filtration, when the mixture was allowed to cool down to room temperature.

4 Scheme 2 .
Scheme 2. The possible reaction mechanism of the products 4.

Table 4 .
The selected bond angles of 4e