Photoinduced Synthesis of New Diisochromenochromen-4-ones and Their Antimicrobial Activities

The diisochromenochromen-4-one 3a-3b, 4a-4c, 5a-6a   & 7 have been prepared from the photocyclization reaction of bischromen-4-one 2a-2e. The later compounds are obtained from the O-alkylation of the suitable 3-hydroxy-2-aryl-4H-chromen-4-one 1a-1e with 4,4′-bischloromethyl-diphenyl in dry acetone, anhydrous K2CO3, and PTC (Bu4N+I−) under refluxing conditions. The structures of compounds 2a-2e, 3a-3b, 4a-4c, 5a-6a   & 7 have been characterized from the rigorous analysis of their IR, 1H-NMR, 13C-NMR, ESI-Mass, and elemental analysis. The antibacterial and antifungal activities of the synthesized products were also evaluated against the Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Bacillus subtilis, and Aspergillus janus and Penicillium glabrum, respectively. Some of the tested compounds showed significant activity against the above-said microorganisms.


Introduction
Syntheses of six membered heterocyclic compounds have been the subject of major interest for researchers due to their significant biological activities [1][2][3][4][5][6][7][8][9][10][11][12]. The photochemical reaction of C=O compounds leads to the formation of many exotic carbocyclic and heterocyclic compounds, and these reactions are initiated through the intramolecular H-abstraction by the photoexcited carbonyl group from the γ and δ position to give 1, 4 and 1, 5-biradicals which finally collapse to the generation of many unique heterocyclic products [13][14][15][16][17][18][19][20]. 2-Aryl-3-alkoxy-chromen-4one is such substrates which can undergo γ H-abstraction to provide pyran derivatives from the cyclisation reaction of 1, 4-biradical and 2-aryl ring [21][22][23]. The bischromen-4-one is the bichromophoric molecules which are formed by joining two chromen-4-one moieties together through the carbon chain of varying length and structure, and photochemical reaction of these compounds may produce some interesting heterocyclic compounds. Generally, the heterocyclic compounds are obtained via multistage reaction in the presence of specific reagents and reaction conditions. We are aiming hereby to synthesize bispyran derivatives under the influence of light. This aspect has prompted us to investigate the synthesis of diisochromeno-chromen-4-ones from the photochemical reaction of bischromen-4-one 2a-2e built around the diphenyl spacer moiety. The major interest behind this study was to investigate the simple method and antimicrobial evaluations of new diisochromeno-chromen-4-ones.

Results and Discussion
The compound 2a-2e required for this study was obtained from the O-alkylation of the suitable 3-hydroxy-chromen-4-one [24][25][26] with 4,4 -bischloromethyldiphenyl in the presence of anhydrous K 2 CO 3 and Bu 4 N + I − (PTC) in dry acetone (Scheme 1). The reactions carried out in the absence of PTC provided very poor yield of the bischromen-4-ones and also involved very long reaction times. The monoalkoxy chromen-4-one formed in these reactions was removed by using column chromatography (60-120 mesh). The structures of 2a-2e were determined by means of their IR, 1 H-NMR, and ESI-MS spectral data (see the appendix).
The IR spectra of 2a-2e exhibited strong absorptions in the region of 1640-1650 cm −1 which indicated the presence anhyd. K 2 CO 3 /PTC/Δ/dry acetone Scheme 1 of conjugated C=O group. The major feature of their 1 H-NMR spectra was the appearance of sharp singlet at δ 5.11-5.35 which may be assigned to 3-OCH 2 group. The downfield appearance of this proton could be ascribed to their benzylic nature and placement near an electronegative oxygen atom. 13 C-NMR of these compounds revealed the most significant downfield signal at δ 176.13-175.01 (C=O group), another signal at δ 142.12-139.08 due to C-3 due of its direct linkage to oxygen atom, and remaining aromatic carbon atoms were resonating at δ 161.47-117.97. The most upfield resonance was found placed at δ 72.07-69.02 due to OCH 2 group.
The photochemical reaction of bischromen-4-ones 2a-2e was carried out under inert atmosphere in dry MeOH and THF (1 : 1) with Pyrex-filtered light from a 125 W Hg arc lamp. The progress of the photoreactions was monitored by TLC, and after about 8-10 hrs most of the starting compound was transformed to new products (Scheme 2). The column chromatographic separation of the reaction mixtures yielded 3a-3b, 4a-4c, 5a, 6a, and 7 in moderate yields. The structure of these products became evident from the comparison of their IR, 1 H-NMR, and 13 C-NMR spectra with those of starting compound 2a-2e (see the appendix).
The appearance of one IR absorption band in the carbonyl group region of 1630-1650 cm −1 indicates that these products are obtained involving the both side cyclization on the bischromen-4-one. The 1 H-NMR spectra of 3a and 3b were quite informative which gave broad singlet at δ 6.81-6.78 (H-1), dd at δ 5.85-5.80 (H-3), and another dd at δ 5.30-5.25 (H-4). The noticeable signals were centered at δ 5.01-5.05 (H-5) and 3.40-3.45 (H-4a) having coupling value of 11.0 Hz which describes their cis disposition at C-4a and C-5. The four-proton multiplet found at δ 2.95-2.92 may be assigned to H-2a. 13 C-NMR spectra of these compounds were also very helpful which showed resonances at δ 178.20-177.82 due to carbonyl group, at δ 39.00-38.80 and δ 32.00-31.05 due to C-4a and C-2, respectively. Another signal at δ 126.53 could be assigned to C-1 which was absent in their starting compounds.
The 1 H-NMR spectrum of 4a-4c was very simple which produced most of the resonances in aromatic region at δ 8.30-6.95, and a significant singlet at δ 5.85-5.78 (2H) may be allotted to H-5. 13 C-NMR of these compounds showed the suitable signals due to aromatic carbon in the region of δ 156.68-114.58, and the signals at δ 72.93-71.74 could be resulted by C-5.

Conclusion
This study provides the photochemical method for the preparation of new diisochromenochromen-4-one linked through the diphenyl moiety. The products have been obtained without using any specific and toxic reagent. The antimicrobial analysis of the prepared compounds has also been carried out and the importance of this work lies in the possibility that newly synthesized compounds (2a, 2b, 2c, 2d, 3a, 3b, 4a, 5a, and 6a) might be more efficacious derivatives against the tested bacterial and fungal strains. The investigations regarding the more biological studies of these bischromen-4-ones could be helpful in designing the potent antimicrobial agents.