An Efficient Carbonized Sugar Catalyzed Entry to 7,8-dihydro-2H- Chromen-5(6H)-ones

The present paper describes a facile entry to various substituted 7,8-dihydro-2H-chromen-5ones under neat conditions using simple carbonized sugar as a catalyst. The reaction was promoted by visible light under neat or in acetic acid as a solvent with a catalyst to afford the desired products in good to excellent yield. Mild conditions coupled with ease of operation make the protocol synthetically attractive and may find widespread application for the synthesis of chromenone scaffold.

Recently, the use of visible light as a source of energy to influence reactions under mild conditions has gained importance as a green procedure, and numerous reactions have been described by means of visible light [34][35][36]. This type of photo-activation of substrate very often minimizes by-products and requires much less time compared to thermal methods. This feature has dramatically improved visible light-mediated photochemical reactions of synthetic importance [37][38][39].
The inherent ability of carbon materials (CMs) as heterogeneous catalysts could be perceptive. Carbocatalysts are metal-free carbon materials such as activated carbon, single and multi-walled nanotubes, graphene oxide (GO), and fullerene. They have been explored for catalytic properties in a variety of reactions with great success. In particular, carbon-based nanocatalysts are breakthrough materials that exhibit enhanced catalytic performance as a consequence of their characteristic architecture and optoelectronic properties. This has led to replacing several metal catalysts used in organic transformations with graphene oxide-based carbocatalytic systems [40][41][42][43][44][45]. Herein, we demonstrate the efficient application of carbonized sugar (CS) as a catalyst for synthesizing various substituted 7, 8-dihydro-2H-chromen-5-ones under visible light.

Experimental
CS-GO Nanoparticles were prepared according to the method given in the literature reference [44,45]. All melting points were determined on an Electrothermal Gallenkamp apparatus. 1 H and 13 C NMR spectra were recorded on a Varian Gemini Spectrometer 300 and 75 MHz, respectively. IR spectra were recorded on Nicolet Fourier Transform spectrometer. Mass spectra were obtained on a 7070H or VG Autospec Mass spectrometer using the LSIMS technique. Thin-layer chromatography (TLC) was performed on GF-25U (Anal. Tech) plates and silica gel glass-packed plates.

General experimental procedure for the 7,8 dihydro-2H chromen-5(6H)-ones
In a typical experimental procedure, a mixture of 1,3-cyclohexanedione (1.0 mmol) and aliphatic α, β-unsaturated aldehyde (1.1 mmol), carbonized sugar (10 %) under neat conditions was stirred for the specified time in the presence of a 100 W tungsten lamp (Philips India Ltd.). The temperature was maintained in the range of 65-70 °C ( Table 2). After completing the reaction (as monitored by TLC), the mixture was diluted with methylene dichloride, and the catalyst was removed by filtration. Removal of the solvent under reduced pressure followed by purification over silica gel column with petroleum ether/ethyl acetate (1:3) as eluent afforded the corresponding 7,8-dihydro-2H-chromen-5(6H)-ones.

Results and Discussion
A model reaction was performed with 1,3-cyclohexanedione (1 mmol, 1a) and crotanaldehyde (1.1 mmol, 2a) under different conditions to optimize the reaction conditions and the results are summarized in Table 1. As is evident from Table 1, the nature of solvent has a significant effect on the product's rate of reaction and yield. The reaction of 1,3-cyclohexanedione (1a) with crotanaldehyde (2a) in MeOH (entry 1), MeCN (entry 2), and (Me) 2 CHOH (entry 3) solvents in the presence of visible light (100 W tungsten lamp) at 65-70 C and 10 % catalyst did not proceed to afford any product. However, the use of toluene (entry 4) and acetic acid (entry 5) as a solvent afforded the desired product 2-methyl-2,6,7,8-tetrahydro-5H-chromen-5-one (3a) in 68 % and 82 % yield, respectively. Further, the effect of visible light was studied in the presence and absence of a 100 W tungsten lamp (Philips India Ltd) at 65-70 C with 10% of catalyst separately. As expected, in the absence of visible light (dark reaction conditions), the reaction did not proceed to afford the desired product (entry 6). We then decided to study the reaction rate under neat conditions in the absence and presence of a catalyst under visible light (100 W tungsten lamp) irradiation. No product formation was observed without catalyst under visible light conditions even after 24 h stirring (entry 7), while the excellent yield of the product was obtained with 10% catalyst (entry 9). Further increase in catalyst quantity to 20 % did not dramatically affect the yield of the product (entry 10). The reaction temperature of 65-70 °C was maintained by regulating the light source every 10 min. Time interval and a further rise in temperature to 100 C (entry 11) did not have any desirable effect and led to a reduction in the yield of the product. This observation may be attributed to the instability of the product at a higher temperature under the reaction conditions The spectral analysis of compound 3a displays characteristic enone absorption at 1645 cm -1 in the IR spectrum with the expected peaks associated with two vinylic protons of 2H-pyranyl ring at δ 6.48 (d, J = 9.8 Hz, 1H) and 5.30 (dd, J = 10.3 Hz, 2.6 Hz, 1H) 1 H NMR spectrum. Mass spectral analysis showed m/z (rel. abund. %) 165.1 ([M+1] + , 100). No xanthene derivative was obtained in this case. Also, studies carried on the effect of catalyst loading for the test reaction using crotonaldehyde and 1,3-cyclohexanedione (mole rate 1.1:1), 5, 10, and 20 % of the catalyst under solvent-free conditions ( Table 1, entries 8-10) reveal that 10 % of catalyst afford best results in terms of yield and time (Scheme 1 and Table 1, entry 9) and a further increase in % of catalyst loading did not have any desirable effect in the yield (Table 1, entry 10). The catalyst can be recycled five times after filtration from the reaction mixture with a maximum 5 % variation in yield.

Reaction Mechanism
We speculate that the reaction proceeds in two steps: In the first step, the catalyst acts as a Lewis acid and facilitates condensation of the active methylene group with an aldehyde to yield the conjugated enone. In the second step, the enone, in turn, undergoes cyclization to afford the chromen-5-(6H)-one.

Conclusion
The present paper describes the application of CS-GO NPs as an efficient and green catalyst for one-pot entry to various substituted 7,8-dihydro-2H-chromen-5-ones under neat conditions. The protocol has potential merits in terms of simplicity, costeffectiveness, eco-friendly procedure, and catalyst reusability. The efficiency and nature of catalyst would allow widespread application of this protocol to synthesize sensitive and bioactive compounds bearing 7,8-dihydro-2H-chromen-5-one scaffold under mild conditions.