Pyranopyridines show biological activities including antipsychotic , anti-inflammatory , anti-asthma , antiallergic  and antibacterial . These activities make benzopyranopyridines attractive targets in organic synthesis. A number of procedures have been developed for the preparation of pyranopyridines using K2CO3 , Et3N [7,8] and NaOH . Despite the use of these ways, there remains a need for further new methods for the synthesis of benzopyranopyridines. GQDs have achieved intense attention owing to the remarkable features containing biological , biomedical , drug delivery , photocatalysts , surfactants , electrochemical biosensing , electrocatalytic , Li-ion battery , optical properties and photovoltaic applications , photoluminescence [19-20], bioimaging properties , and catalytic activity . Potential applications of N-graphene quantum dots were lately reviewed on the basis of theoretical and experimental studies [23-26]. Preparation of the highly efficient nanocomposite catalysts for the synthesis of organic compounds is still an attractive challenge. To attain larger surface area, nanocatalysts are functionalized by active groups [27-29]. The decoration of the nanoparticles with GQDs prevents the aggregation of fine particles and thus increases the efficient surface area and the number of reactive sites for an effective catalytic reaction. The -SO3H and -COOH groups can be used as acid catalysts for many reactions [22-30]. Herein, we reported the use of Co3O4/NiO@GQDs@SO3H nanocomposite as an efficient catalyst for the preparation of benzopyranopyridines through a four-component reaction of salicylaldehydes, thiols and 2 equiv of malononitrile under reflux condition in ethanol (Scheme 1).
Materials and characterization
The powder X-ray diffraction was taken on a Philips diffractometer of X’pert Company with monochromatized Cu Kα radiation (λ = 1.5406 Å). The X-ray photoelectron spectroscopy (XPS) spectra were determined on an ESCA-3000 electron spectrometer. The microscopic morphology of nanocatalyst was performed by SEM (MIRA3). The thermogravimetric analysis (TGA) curves are gained by V5.1A DUPONT 2000. The magnetic measurement of samples was registered in a vibrating sample magnetometer (VSM) (Iran, Kashan Kavir). Surface area was carried out using nitrogen adsorption measurement (Micrometrics ASAP-2000).
Preparation of Co3O4/NiO nanoparticles
NiCl2 and Co(NO3)3 with 1:3 molar ratio were dissolved in ethylene glycol. The appropriate amount of aqueous ammonia solution (28 wt%) was added to the above solution until the pH value reached 10. The transparent solution was placed in autoclave at 150 °C for 4h. The obtained precipitate was washed twice with CH3OH and dry at 60 °C for 8h. Finally, the product was calcined at 500 °C for 2h.
Preparation of Co3O4/NiO@N-GQDs nanocomposite
1 g citric acid was dissolved into 20 mL deionized water, and stirred to form a clear solution. 0.3 mL ethylenediamine was added to the above solution and mixed to gain a clear solution. Then, 0.1 g of Co3O4/NiO nanoparticles was added to the mixture. The mixture was stirred at room temperature within 5 minutes. Then, the solution was transferred into a 50 ml Teflon lined stainless autoclave. The sealed autoclave was heated to 180°C for 12 hours in an electric oven. Finally, as-prepared nanostructured Co3O4/NiO@GQDs was obtained, washed several times with deionized water and ethanol, and then dried in an oven until constant weight was obtained.
Preparation of Co3O4/NiO@GQDs@SO3H nanocom-posite
1000 mg of Co3O4/NiO@N-GQDs nanocom-posite was dispersed in dry CH2Cl2 (10 mL) and sonicated for 5 min. Afterward, chlorosulfonic acid (0.8 mL in dry CH2Cl2) was added drop-wise to a cooled (ice-bath) mixture of Co3O4/NiO@N-GQDs, during 30 min under N2 with vigorous stirring. The mixture was stirred for 2 h, while the residual HCl was removed by suction. The resulted Co3O4/NiO@GQDs@SO3H nanocomposite was separated, washed several times with dried CH2Cl2 before being dried under vacuum at 60 °C.
General procedure for the synthesis of benzopy-ranopyridines
A mixture of salicylaldehyde (1.5 mmol), malononitrile (3 mmol), a desired thiol (1.5 mmol), and Co3O4/NiO@GQDs@SO3H nanocatalyst (4 mg) were stirred in 5 mL ethanol under reflux condition. The reaction was monitored by TLC. The formed precipitate was isolated by filtration. The product was dissolved in DMF (8 mL) and the catalyst was filtered. Then, water (5 mL) was added to the filtrate which resulted in the crystallization of the product. The resulting crystalline structure was filtered and dried with a vacuum pump. Spectra data 4a and 4c compounds are presented:
2,4-Diamino-5-(phenylthio)-5H-benzopyrano[2,3-b]pyridine-3-carbonitrile 4a: yellow solid, m.p. 220–222 ºC. IR (KBr): ν = 3425, 3354 (NH2), 2200 (C≡N), 1625 (C=N), 1574, 1414 (C=C), 695 (C-S-C) cm-1. 1H NMR (400 MHz, DMSO-d6): δ (ppm) = 5.71 (s, 1H, H-5), 6.52-6.72 (2H, m), 6.70-6.74 (3H, m), 6.95 (s, 2H, NH2), 7.06-7.14 (4H, m, NH2 and ArH), 7.16-7.35 (m, 2H,). 13C NMR (100 MHz, DMSO-d6): δ (ppm) = 43.2, 70.7, 86.8, 116.3, 116.7, 121.4, 123.4, 128.7, 128.8, 129.6, 129.9, 134.3, 137.5, 150.8, 156.5, 159.8, 160.8. – Analysis for C19H14N4OS: calcd. C 65.88, H 4.07, N 16.17, S 9.26. Found C 65.80, H 4.18, N 16.02, S 9.18.
2,4-Diamino-5-[(phenylmethyl)thio]-5H-benzopyrano[2,3-b]pyridine-3-carbonitrile 4c: yellow solid, mp 175–177 ºC. IR (KBr): ν = 3375, 3437 (NH2), 2202 (C≡N), 1625 (C=N), 1542 and 1484 (C=C), 702 (C-S-C) cm-1. 1H NMR (400 MHz, DMSO-d6): δ (ppm) = 3.52 (ABq, 2H, J = 12Hz, CH2), 5.40 (s, 1H), 6.56 (bs, 2H, NH2), 6.84 (bs, 2H, NH2), 7.04–7.25 (m, 7H, ArH), 7.35 (m, 2H, ArH). 13C NMR (100 MHz, DMSO-d6): δ (ppm) = 35.1, 44.2, 70.8, 87.2, 117.5, 118.4, 119.2, 122.7, 124.3, 124.5, 129.7, 133.4, 133.4, 136.5, 143.8, 152.8, 159.5, 160.4; Analysis for C20H16N4OS: calcd. C 66.65, H 4.47, N 15.54, S 8.90. Found C 66.48, H 4.52, N 15.42, S 8.82.
RESULTS AND DISCUSSION
In the beginning, we prepared Co3O4/NiO nanoparticles by easy techniques. A hydrothermal method was utilized for the preparation of N-GQDs . Sulfonated graphene quantum dots were prepared using chlorosulfonic acid . The XRD patterns of Co3O4/NiO, Co3O4/NiO@N-GQDs and Co3O4/NiO@GQDs @ SO3H nanocomposite are indicated in Fig. 1. The XRD pattern confirms the presence of both NiO (JCPDS No.22-1189) and Co3O4 (JCPDS No 65-3103).
The SEM images of Co3O4/NiO and Co3O4/NiO@ GQDs@SO3H nanocomposite are indicated in Fig. 2. The SEM images of the Co3O4/NiO@GQDs@SO3H nanocomposite showed the formation of uniform particles, and the energy-dispersive X-ray spectrum (EDS) confirmed the presence of Co, Ni, O, S and C species in the structure of the nanocomposite (Fig. 3).
Magnetic properties of nanocomposites before and after their being decorated with GQDs were tested by vibrating-sample magnetometer (VSM) (Fig 4). The lower magnetism of the as-synthesized Co3O4/NiO@GQDs@SO3H compared with the Co3O4/NiO was ascribed to the antiferromagnetic behavior of GQDs as a dopant. These results display that the magnetization properties decrease by coating and functionalization [33-34].
The FT-IR spectra of Co3O4/NiO, Co3O4/NiO@N-GQDs and Co3O4/NiO@GQDs @ SO3H nanocomposite are indicated in Fig. 5. The absorption peak at 3330 cm-1 related to the stretching vibrational absorptions of OH. The peaks at 461, 568, 657 cm-1 corresponded to the Ni-O, Co+2-O and Co3+-O, respectively. The characteristic peaks at 3442 cm-1 (O-H stretching vibration), 1706 cm-1 (C=O stretching vibration), 1126 cm-1 (C-O-C stretching vibration) appear in the spectrum of
Fig. 5b. The peak at approximately 1474-1582 cm-1 is attributed to C=C bonds. The presence of sulfonyl group is also verified by the peaks appeared at 1214 and 1120 cm−1. The broad peak at 3340 cm-1 is related to the stretching vibrational absorptions of OH (SO3H) (Fig 5c).
The BET specific surface area of Co3O4/NiO and Co3O4/NiO@GQDs@SO3H nanocomposites was determined by the nitrogen gas adsorption-desorption isotherms (Fig. 6). The results presented that the BET specific surface area of Co3O4/NiO was improved from 12.24 to 32.44 m2/g after modification with GQDs, therefore, more active sites were introduced on Co3O4/NiO@GQDs@SO3H surface.
Thermogravimetric analysis determines the thermal stability of the Co3O4/NiO@GQDs@SO3H nanocomposite (Fig. 7). The curve indicates a weight loss about 14.06 % from 150 to 500 ºC which are attributed to the oxidation and degradation of GQD.
The X-ray photoelectron spectroscopy (XPS) analysis of Co3O4/NiO@GQDs@SO3H nanocom-posite is indicated in Fig. 8. In the wide-scan spectrum of nanocatalyst, the predominant components are Ni 2p3/2 (854.4 eV), Ni 2p1/2 (873.4 eV), Co 2p3/2 (780.4 eV), Co 2p1/2 (792.6 eV), O 1s (529.8 eV), N 1s (400 eV), C 1s (284.5 eV) and S 2p (164.3 eV).
Initially, we carried out four-component reaction of salicyladehyde (1.5 mmol), malononitrile (3.0 mmol) and benzenethiol (1.5 mmol) as a model reaction. The model reaction was performed by morpholine, p-TSA, NaHSO4NiO, Co3O4, Co3O4/NiO, Co3O4/NiO@GQDs and Co3O4/NiO@GQDs@SO3H nanocomposite. The best results were gained in EtOH and we received the convincing results for the reaction in the presence of Co3O4/NiO@GQDs@SO3H nanocomposite (4 mg) under reflux conditions (Tables 1). A series of salicylaldehydes and different thiols were studied under optimum conditions (Table 2). The results were good in yields.
We also determined recycling of Co3O4/NiO@GQDs@SO3H nanocomposite as a catalyst for the model reaction under reflux conditions in ethanol. The results showed that nanocomposite can be reused several times without noticeable loss of catalytic activity (Yields 90 to 88%) (Fig. 9).
A plausible mechanism for the preparation of benzopyranopyridines using Co3O4/NiO@GQDs@SO3H nanocomposites is indicated in Scheme 2. Firstly, salicylaldehyde reacts with 1 equiv of malononitrile to form intermediate I1 and subsequent intramolecular addition of the hydroxyl group to the C≡N gives the cyclic intermediate I2. This compound undergoes addition with thiophenol 3 to afford phenylsulfanylchromene I3. The intermediate I3 reacts with another equiv of malononitrile to form intermediate I4, followed by intramolecular cyclization to form intermediate I5. Finally the chromenopyridine P was formed by the tautomerization of the imino group to the amino group. The SO3H groups distributed on the surface of Co3O4/NiO@GQDs activate the C=O, C=NH and C≡N groups for better reaction with nucleophiles.
In this study, we described the synthesis of benzopyranopyridines using Co3O4/NiO@GQDs@SO3H nanocomposite as a superior catalyst under reflux conditions. The procedure offers several advantages including environmental friendliness, significantly shorter reaction time, reusability of the catalyst and low catalyst loading.
The authors are grateful to the University of Kashan for supporting this work under grant no. 159148/XII.
CONFLICT OF INTEREST
The authors declare that they have no conflict of interest.