Nanocatalyzed Synthesis of Benzofuran Isomers ... - ACS Publications

Research Article pubs.acs.org/journal/ascecg

Hierarchically Porous Sphere-Like Copper Oxide (HS-CuO) Nanocatalyzed Synthesis of Benzofuran Isomers with Anomalous Selectivity and Their Ideal Green Chemistry Metrics Gunjan Purohit,† U. Chinna Rajesh,†,‡ and Diwan S. Rawat* Department of Chemistry, University of Delhi, Delhi 110007, India S Supporting Information *

ABSTRACT: Development of nanocatalysts for a chemical reaction with ideal values in green chemistry metrics is considered to be a challenging task to achieve sustainable chemistry. With this aim, we herein report a hierarchically porous sphere-like copper oxide (HS-CuO) nanocatalyst to afford benzofuranamine and dihydro-benzofuranamine isomers with anomalous selectivity via Oannulated A3 coupling among salicylaldehydes, secondary amines, and alkynes followed by cycloisomerization in the absence of base and solvent. The anomalous selectivity of benzofuran isomers was dependent on the electronic factors of substituents on salicylaldehyde and the type of secondary amines used in the coupling reaction. The HS-CuO nanocatalyst was recycled five times without significant loss in its catalytic activity. The present method offers several advantages over the reported methods such as wide substrate scope with anomalous selectivity in the products, high yields in short reaction time, avoided the usage of extra reagents such as additives/bases, and showed ideal values of green chemistry metrics such as low E-factor and process mass intensity (PMI), high atom economy (AE), reaction mass efficiency (RME), and carbon efficiency (CE). KEYWORDS: Hierarchically porous spheres, Copper oxide, Nanocatalysis, Benzofuran isomers, Green chemistry metrics

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INTRODUCTION Green chemistry metrics have played a significant role in quantification of chemical reaction efficiency with aims toward waste reduction in the environment.1−3 The foremost metrics such as E-factor, atom economy (AE), process mass intensity (PMI), reaction mass efficiency (RME), carbon efficiency (CE), etc. have been proposed to make synthetic chemists aware of sustainable practices.4 The optimization of reaction conditions for a chemical reaction to avoid the excess reagents and solvents using nanomaterials as recyclable catalysts is considered to be a challenging task to achieve the aforementioned goal.5−7 Hierarchically porous metal oxides consisting of building blocks in multiple length scales have attracted significant attention due to their unique properties to achieve sustainable applications in various fields including photocatalysis, photonic devices, chemical sensors, energy conversion and storage systems, and drug delivery.8−13 However, the catalytic potential of these hierarchically porous metal oxides has not been well studied in organic synthesis. Copper oxide is one such metal oxide that has found potential applications in various fields including catalysis.14−18 However, there are very limited methods for the synthesis of hierarchically porous copper oxide nanostructures to explore their wide range of applications in science and technology.19−21 To the best of our knowledge, the catalytic potential of hierarchically © 2017 American Chemical Society

porous copper oxide has not been studied for the synthesis of pharmacologically active heterocycles under green reaction conditions. Benzofuran(s) are such important O-heterocyclic scaffolds found in various natural products and pharmaceuticals with a wide range of biological activities such as anticancer, antioxidative, and anti-inflammatory properties (Figure 1).22−24 As a result, enormous synthetic strategies and methodologies have been developed for the construction of benzo[b]furan scaffolds such as decarboxylation of o-acylphenoxyacetic acids or esters,25−27 dehydrative cyclization of (α-(phenoxy)-alkyl ketones,28,29 palladium catalyzed cyclization of 2-(1-alkynyl)phenols,30,31 [3,3]-sigmatropic rearrangement of arenes etc.32 Recently, A3 coupling strategy, is a three-component coupling of an aldehyde, an alkyne and an amine,33 has been considered to be a sustainable tool with high atom economy to afford Nheterocyclic natural products34 and O-heterocycles including 2,3-disubstituted benzo[b]furans.35−40 However, most of the reported catalytic conditions generate excess waste along with desired product due to the usage of extra additives and base reagents, toxic organic solvents and nonrecyclable catalysts which limit their applications at industrial scale production. Received: February 16, 2017 Revised: May 20, 2017 Published: June 29, 2017 6466

DOI: 10.1021/acssuschemeng.7b00500 ACS Sustainable Chem. Eng. 2017, 5, 6466−6477

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ACS Sustainable Chemistry & Engineering

Figure 1. Biologically significant benzo[b]furan scaffolds.

There is a need of developing an efficient and sustainable method to afford these biologically significant benzofuran heterocycles. As a part of our ongoing effort toward nanocatalysis for green and sustainable chemistry,41−49 we herein report hierarchically porous sphere-like copper oxide (HS-CuO) nanocatalyzed synthesis of benzofuran isomers with anomalous selectivity and ideal green chemistry metrics.

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RESULTS AND DISCUSSION The calcination of malachite [Cu2CO3(OH)2] microspheres was performed at 450 °C for 4 h to afford hierarchically porous sphere-like copper oxide (HS-CuO) (Scheme 1). The thermal Scheme 1. Preparation of Hierarchically Porous Sphere-Like Copper Oxide (HS-CuO) Figure 2. PXRD of (a) malachite (MC) and (b) HS-CuO.

(−202), (020), (202), (−113), (−311), (113), (311), and (004), respectively. The grain size of the HS-CuO was found to be 20 nm as estimated using the Scherrer equation. The surface and internal morphologies of HS-CuO were characterized from SEM and TEM, respectively (Figures 3 and 4). SEM images revealed the surface morphology of HS-CuO as a hierarchical sphere-like nanoarchitecture with size ranges from 2 to 8 μm which were made up of self-assembly of CuO nanoparticles as shown in Figure 3.

decomposition of malachite into corresponding copper oxide is known in the literature.50 However, the release of carbon dioxide and water vapors from malachite microspheres generated large gaps among the building blocks of in situ generated copper oxide NPs to obtain HS-CuO (Scheme 1). Figure 2a shows the PXRD of commercially available malachite (MC). The powder X-ray diffraction pattern was indexed as pure malachite in the monoclinic space group P21/a with lattice parameters a = 9.402 Å, b = 11.864 Å, and c = 3.240 Å and β = 98.75° (Z = 4), and all of the phases are well matched with the reported data (JCPDS file no. 01-076-0660). The crystallite size of MC was found to be 11.4 nm as calculated by the Scherrer equation. HS-CuO was characterized by powder X-ray diffraction (PXRD) as shown in Figure 2b. The PXRD of HS-CuO NPs was indexed to the single phase monoclinic structure with lattice constants of a = 4.6963 Å, b = 3.4322 Å, and c = 5.1328 Å and β = 99.5289° (JCPDS: 80-1916). Diffraction peaks at 2θ = 32.45°, 35.35°, 38.71°, 48.80°, 61.99°, and 66.49° corresponded to the phases such as (110), (−110), (111),

Figure 3. SEM images of (a) malachite and (b−d) low to high magnified view of HS-CuO. 6467


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band at 517 cm−1 confirms the Cu−O stretching vibration of CuO (Figure 5b). The appearance of an extra peak at 1112 cm−1 corresponds to (−OH) stretching of adsorbed water on the HS-CuO surface (Figure 5b), and these results are well matched with the reported data.50 The BET surface area and pore size distribution of HS-CuO were studied using the nitrogen adsorption/desorption techniques as shown in Figure 6. The nitrogen adsorption/

Figure 4. TEM images (a−d) low to high magnified views of HS-CuO.

The TEM images showed the internal morphology of HSCuO as self-assembly of various CuO rods and spheres with size varies from 50 to 100 nm as shown in Figure 4. These results clearly supported the formation of porous hierarchical sphere-like nanoarchitecture by self-assembly of CuO NPs. The presence of functional groups on malachite such as O− H and (CO3)2− and Cu−O stretching in HS-CuO were characterized from FT-IR as shown in Figure 5. The peaks at

Figure 6. Nitrogen adsorption−desorption isotherms of HS-CuO.

desorption isotherm results revealed that the BET surface area of HS-CuO was about 97.2 m2 g−1 with the pore volume (Vm) and mean pore diameter found to be 0.37 cm3 g−1 and 15 nm, respectively.

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HS-CUO NANOCATALYZED SYNTHESIS OF SUBSTITUTED BENZOFURANAMINES Initially, a model reaction among 5-nitro-2-hydroxybenzaldehyde (1a), morpholine (2a), and phenylacetylene (3a) was performed using 4 mg of HS-CuO nanocatalyst at 110 °C in the presence of various solvents and neat conditions as shown in Table 1 (entries 1−11). In the presence of toluene, DMSO, DMF, and water solvents, the desired benzofuranamine product (4aaa) was observed in 94−96% conversions (entries 1−4, Table 1). In the case of green solvents such as glycerin, EG, and DEG, the product (4aaa) was formed in 80−92% conversions along with an intermediate (5a) in 8−20% conversions (entries 5−7, Table 1). Moreover, PEG was found to be the best suited solvent to afford the desired product (4aaa) exclusively in 100% conversion in 3 h at 110 °C (entry 8). To our delight, the product (4aaa) was obtained in 100% conversion under solvent free conditions in short reaction time 1.5 h (entry 9). The conversions in product formation were decreased upon the increase or decrease in catalyst loading from 4 mg under neat conditions (entries 10 and 11, Table 1). Next, we studied the effect of temperature on the progress of reaction using 4 mg of catalyst under neat conditions. The results showed that the decrease in temperature to 70 °C lead to a drastic drop in the progress of reaction to afford a trace amount of product (4aaa; entries 12 and 13). There was no progress in the reaction at room temperature even after prolonged reaction time under optimized reaction conditions (entry 14, Table 1). These results prompted us to investigate the wide applicability of the cyclization reaction in the presence

Figure 5. FT-IR spectrum of (a) malachite (MC) and (b) HS-CuO.

3409 and 3326 cm−1 correspond to −O−H stretching vibration of hydroxyl groups on malachite (Figure 5a). The presence of ν3 antisymmetric (CO3)2− stretching modes of carbonate groups of malachite were confirmed from two peaks at 1504 and 1394 cm−1. The band at 1050 cm−1 corresponds to ν1 (CO3)2− symmetric stretching vibration. The bands at 815 and 753 cm−1 are attributed to ν2 and ν4 bending modes of (CO3)2− as shown in Figure 5a. FT-IR of the calcined malachite (HS-CuO) showed the disappearance of O−H and (CO3)2−, and the appearance of a 6468


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ACS Sustainable Chemistry & Engineering Table 1. Optimization Study for HS-CuO Catalyzed Synthesis of Benzofuran (4aaa)a

entry

catalyst (mg)

solvent

temp. (°C)

time (h)

conversion of 4aaa (%)b

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23

HS-CuO (4) HS-CuO (4) HS-CuO (4) HS-CuO (4) HS-CuO (4) HS-CuO (4) HS-CuO (4) HS-CuO (4) HS-CuO (4) HS-CuO (8) HS-CuO (1) HS-CuO (4) HS-CuO (4) no catalyst CuBr2 CuSO4 CuCl2 Cu(OAc)2 CuI CuCN Cu(II)-HMc CuO/Fe2O3d CuI@CSPe

toluene DMSO DMF water glycerin EG DEG PEG neat neat neat neat neat neat neat neat neat neat neat neat neat neat neat

110 110 110 110 110 110 110 110 110 110 110 70 rt 110 110 110 110 110 110 110 110 110 110

3 3 3 3 3 3 3 3 1.5 1.5 1.5 10 24 24 2 2 2 2 2 2 2 2 2

96 96 94 90 80 80 92 100 100 92 75 trace no product

conversion of 5a (%)b

20 20 8

100 100 100 100 100 100 100 100 100

a

Reaction conditions: 5-nitro-2-hydroxybenzaldehyde (1a) (1 mmol), morpholine (2a) (1 mmol), phenylacetylene (1 mmol), and solvent (2 mL) at different temperature conditions. bConversions were calculated by analyzing the crude reaction mixtures by 1H NMR. cNanocatalysts preparation was reported in our previous work, ref 42. dNanocatalysts preparation was reported in our previous work, ref 43. eNanocatalysts preparation was reported in our previous work, ref 48.

Scheme 2. HS-CuO Catalyzed Synthesis of Benzofuran Derivatives

reaction of 5-nitro-2-hydroxybenzaldehyde (1a) and 3,5dibromosalicylaldehyde (1b) with various secondary amines such as morpholine (2a), thiomorpholine (2b), phenylpiperazine (2c), 1-(4-methylbenzyl)piperazine (2d), and substituted alkynes (3a−3g) under optimized reaction conditions as shown in Scheme 2. The study revealed that the presence of a strong electron withdrawing group on salicylaldehyde substrate favored the complete cycloisomerization of intermediate (5a) to afford benzofuran isomer (4) as shown in Table 2. In case of 3,5dibromosalicylaldehyde (1b) as a substrate, the yields of

of commercially available copper salts such as CuBr2, CuSO4, CuCl2, Cu(OAc)2, CuI, and CuCN (entries 15−20). The results revealed that none of these copper salts promoted the cycloisomerization of intermediate (5a). Moreover, the present catalytic system was compared with our previously reported copper based nanocatalysts such as Cu(II)-HM, CuO/Fe2O3, and CuI/CSP, and the results revealed that none of these screened nanocatalysts promoted the cycloisomerization of intermediate (5a) (entries 21−23). Next, we studied the generality of present catalytic system for the synthesis of diverse benzofuranamine derivatives from the 6469


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ACS Sustainable Chemistry & Engineering Table 2. HS-CuO Catalyzed Synthesis of Benzofuran (4) Derivativesa

a

Reaction conditions: substituted salicylaldehydes (1 mmol), secondary amines (1 mmol), and alkynes (1 mmol) under solvent free conditions at 110 °C. 6470


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ACS Sustainable Chemistry & Engineering Table 3. Optimization Study for HS-CuO Nanocatalyzed Synthesis of Dihydrobenzofuran 6caaa

a b

entry

catalyst (mg)

solvent

temp. (°C)

tme (h)

1 2 3 4 5 6 7 8 9 10

HS-CuO (4) HS-CuO (4) HS-CuO (4) HS-CuO (4) HS-CuO (4) HS-CuO (4) HS-CuO (4) HS-CuO (4) HS-CuO (4) HS-CuO (4)

toluene DMSO DMF ACN water glycerin DEG PEG EG neat

110 110 110 110 110 110 110 110 110 110

3 3 3 3 3 3 3 3 3 1.5

conversion of 6caa (%)b

conversion of 5c (%)b 98 99 98 97 98 96 94 92 90

96

Reaction conditions: 2-hydroxybenzaldehyde (1 mmol), morpholine (1 mmol), phenylacetylene (1 mmol), and solvent (2 mL) at 110 °C. Conversions were calculated from analyzing crude reaction mixtures by 1H NMR.

Scheme 3. Role of Secondary Amines to Afford Dihydrobenzofuran (6)

products 4bbb and 4bbc were relatively moderate such as 65% and 60%, respectively (Table 2). Moreover, the exclusive formation of the dihydrobenzofuranamine (6caa) isomer was observed with anomalous selectivity in the presence of salicylaldehyde (1c) as a substrate under the same reaction conditions (Table 3). These results promoted us to investigate the generality of the present method for exclusive synthesis of dihydrobenzofuranamines using salicylaldehyde (1c).

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be best to afford the dihydrobenzofuranamine 6caa exclusively in 96% conversion (entry 10, Table 3). In order to understand the role of other secondary amines, we performed reactions among salicylaldehyde (1c), secondary amines (2b−2g), and phenylacetylene (3a) using 4 mg of HSCuO nanocatalyst under optimized reaction conditions as shown in Scheme 3 and Table 4. The results showed that morpholine (2a) and thiomorpholine (2b) were found to be suitable secondary amines for cycloisomerization of the corresponding intermediates (5) to afford the dihydrobenzofurans (6) in 96 and 90% conversions, respectively (entries 1 and 2, Table 4). However, in the case of other secondary amines such as 2c, 2d, 2e, 2f, and 2g (Scheme 3), the corresponding intermediates (5) were obtained exclusively in 90−98% conversions and there was no further cycloisomerization observed (entries 3−7, Table 4). Moreover, the present method showed generality with a wide range of aromatic/aliphatic alkynes with salicylaldehyde (1c), morpholine (2a), and thiomorpholine (2b) to afford the corresponding dihydrobenzofurans (6) under optimized conditions as summarized in Table 5. It is noteworthy that all of the screened substrates proceeded smoothly to afford

HS-CUO NANOCATALYZED SYNTHESIS OF DIHYDROBENZOFURANAMINES

Initially, we studied the role of solvents and secondary amines on the anomalous selective cycloisomerization of the intermediate (5c) to afford the dihydrobenzofuranamine (6caa) isomer. A model reaction among salicylaldehyde (1c), morpholine (2a), and phenylacetylene (3a) was performed using 4 mg of HS-CuO nanocatalyst in the presence of various solvents at 110 °C as shown in Table 3. There was no further cycloisomerization of intermediate (5c) to afford the desired product 6caa in the presence of all screened solvents (entries 1−9, Table 3). To our delight, the neat condition was found to 6471


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ACS Sustainable Chemistry & Engineering Table 4. Study on the Role of Secondary Amines to Afford Dihydrobenzofuran (6)a entry

secondary amine (2)

time (h)

product 6 or 5

conversion of 6 (%)b

1 2 3 4 5 6 7

2a 2b 2c 2d 2e 2f 2g

1.5 1.5 6 6 6 6 6

6aaa 6cba 5cca 5cda 5cea 5cfa 5cga

96 90

Table 6. Quantification of Green Chemistry Metrics for 4aaa and 6caa

conversion of 5 (%)b

s. no. 1 2 3

92 90 98 94 95

4 5

a

Reaction conditions: 2-hydroxybenzaldehyde 1c (1 mmol), amines 2 (1 mmol), and phenylacetylene 3a (1 mmol) at 110 °C. bConversions were calculated from analyzing crude reaction mixtures by 1H NMR.

green chemistry metrics E-factor process mass intensity (PMI) reaction mass efficiency (RME) atom economy (AE) carbon efficiency (CE)

ideal value

product 4aaa

product 6caa

0 1 100%

0.11 1.11 90%

0.14 1.14 88%

100% 100%

95% 95%

94% 93%

values as shown in Table 6 (see the Supporting Information for detailed calculations). The plausible mechanism for the formation of benzofuran via O-annulated A3 coupling followed by cycloisomerization is well-known in the literature.38,40 The recyclability of the HS-CuO nanocatalyst was studied for a model reaction to afford benzofuranamines (4aaa) under optimized reaction conditions as shown in Figure 7. After completion of the reaction, ethanol was added to the reaction mixture to separate the solid HS-CuO from the organic layer by centrifugation. The catalyst was washed several times with ethanol and dried at 90 °C in an oven for 7 h. The recovered HS-CuO was reused in a model reaction to afford the product 4aaa in 92% yield. The same procedure was repeated four more times, and the results indicated that there was no significant loss in their catalytic activity even for the fifth cycle as shown in Figure 7. The stability of the recycled HS-CuO nanocatalyst was confirmed from TEM, PXRD, BET surface area, and pore

dihydrobenzofurans (6) in 87−93% yields (Table 5). However, the present catalytic system has limited scope for the wide range of secondary amines and salicylaldehyde derivatives. This is a first example of the Mannich type O-annulation reaction catalyzed by HS-CuO without additives or bases to afford a variety of structurally interesting dihydrobenzofuran molecules under green reaction conditions. Next, we quantified the green chemistry metrics for both model reactions to afford benzofuran (4aaa) and dihydrobenzofuran (6caa) under optimized reaction conditions as shown in Table 6. The results showed that the values of green chemistry metrics such as E-factor, process mass intensity (PMI), reaction mass efficiency (RME), atom economy (AE), and carbon efficiency (CE) are almost as close to their ideal

Table 5. HS-CuO Catalyzed Synthesis of Dihydrobenzofuran Derivatives under Solvent Free Conditions

a

Reaction conditions: 2-hydroxybenzaldehyde 1c (1 mmol), amines 2 (1 mmol), and phenylacetylenes 3 (1 mmol) at 110 °C. 6472


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152.5 °C; IR (υmax/cm−1, CHCl3): 2958, 2844, 2217, 1602, 1506, 1457, 1403, 1365, 1242, 1174, 1110, 1030, 977, 931, 832, 803, 748, 701, 661; 1H NMR (400 MHz, CDCl3) δ = 7.57 (d, J = 7.6 Hz, 1H), 7.48 (d, J = 8.3 Hz, 2H), 7.23 (t, J = 7.6 Hz, 1H), 6.88 (d, J = 8.3 Hz, 3H), 6.85 (s, 1H), 5.27 (s, 1H), 5.07 (s, 1H), 3.83−3.76 (m, 8H), 2.77 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ = 159.97, 157.07, 133.40, 129.76, 128.90, 120.82, 119.47, 116.51, 114.36, 114.10, 90.38, 80.15, 66.94, 60.80, 55.40 ppm; HRMS (ES): Calcd 323.1521, found 363.1516. (Z)-4-(2-(2-Phenoxyethylidene)-2,3-dihydrobenzofuran-3-yl)morpholine (6cae). Yellow oil; IR (υmax/cm−1, CHCl3): 3058, 2923, 2855, 1706, 1598, 1467, 1380, 1291, 1226, 1116, 1079, 1005, 938, 899, 755, 692; 1H NMR (400 MHz, CDCl3) δ = 7.37 (t, J = 7.6 Hz, 1H), 7.29−7.26 (m, 2H), 7.24 (d, J = 4.5 Hz, 1H), 7.02 (d, J = 7.6 Hz, 1H), 6.99−6.91 (m, 4H), 5.21 (t, J = 6.8 Hz, 1H), 4.92−4.87 (m, 1H), 4.85 (s, 1H), 4.83−4.80 (m, 1H), 3.69−3.60 (m, 4H), 2.65−2.59 (m, 2H), 2.50−2.45 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3) δ = 158.56, 157.81, 155.55, 129.84, 129.53, 126.25, 124.94, 122.34, 120.83, 114.95, 109.98, 101.51, 67.39, 66.87, 62.32, 48.69 ppm; HRMS (ES): Calcd 323.1521, found 363.1515. (Z)-4-(2-(2-(4-Bromophenoxy)ethylidene)-2,3-dihydrobenzofuran-3-yl)morpholine (6caf). Yellow oil; IR (υmax/cm−1, CHCl3): 2924, 2854, 1707, 1595, 1481, 1382, 1288, 1229, 1117, 1077, 1002, 898, 823, 756; 1H NMR (400 MHz, CDCl3) δ = 7.31 (s, 1H), 7.27 (d, J = 9.1 Hz, 2H), 7.19 (t, J = 7.6 Hz, 1H), 6.94 (t, J = 7.6 Hz, 1H), 6.87 (d, J = 7.6 Hz, 1H), 6.77 (d, J = 9.1 Hz, 2H), 5.09 (t, J = 6.8 Hz, 1H), 4.77 (s, 1H), 4.75−4.69 (m, 2H), 3.66−3.53 (m, 4H), 2.55−2.51 (m, 2H), 2.42−2.36 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3) δ = 157.67, 155.93, 132.28, 129.88, 126.25, 124.82, 122.44, 116.80, 112.97, 109.96, 100.89, 67.34, 66.84, 62.62, 48.67 ppm; HRMS (ES): Calcd 401.0627, found 401.0622. (Z)-N-Methyl-N-(2-(3-morpholinobenzofuran-2(3H)ylidene)ethyl)aniline (6cag). Brown oil; IR (υmax/cm−1, CHCl3): 2954, 2854, 2821, 1695, 1597, 1502, 1463, 1348, 1286, 1221, 1111, 1079, 1002, 933, 892, 861, 809, 743, 687; 1H NMR (400 MHz, CDCl3) δ = 7.39 (d, J = 6.8 Hz, 1H), 7.31 (d, J = 7.2 Hz, 1H), 7.28−7.24 (m, 1H), 7.03 (t, J = 7.6 Hz, 1H), 6.99 (d, J = 8.3 Hz, 1H), 6.83 (d, J = 8.3 Hz, 2H), 6.74 (t, J = 7.6 Hz, 1H), 5.00 (t, J = 6.8 Hz, 1H), 4.81 (s, 1H), 4.26 (t, J = 5.3 Hz, 2H), 3.69−3.61 (m, 4H), 3.00 (s, 3H), 2.63−2.58 (m, 2H), 2.47−2.42 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3) δ = 157.98, 154.44, 149.41, 129.74, 129.22, 126.27, 125.13, 122.06, 116.78, 113.20, 109.84, 101.92, 67.32, 66.64, 45.58, 47.94, 38.41 ppm; HRMS (ES): Calcd 336.1837, found 336.1832. 4-(2-(4-Methylbenzyl)-5-nitrobenzofuran-3-yl)morpholine (4aac). Yellow solid; m.pt. 107.1−107.9 °C; IR (υmax/cm−1, CHCl3): 3095, 2957, 2918, 2852, 1697, 1620, 1588, 1520, 1449, 1336, 1265, 1209, 1112, 1069, 1028, 983, 911, 880, 816, 736; 1H NMR (400 MHz, CDCl3) δ = 8.54 (s, 1H), 8.13 (d, J = 9.1 Hz, 1H), 7.42 (d, J = 8.3 Hz, 1H), 7.16− 7.11 (m, 4H), 4.15 (s, 2H), 3.88 (t, J = 4.5 Hz, 4H), 3.18 (t, J = 4.5 Hz, 4H), 2.32 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ = 156.35, 153.83, 143.54, 136.63, 134.12, 129.53, 129.40, 128.50, 126.63, 119.64, 116.32, 112.01, 67.64, 52.59, 32.25, 21.16 ppm; HRMS (ES): Calcd 352.1423, found 352.1418. 4-(5-Nitro-2-(2-phenoxyethyl)benzofuran-3-yl)morpholine (4aae). Yellow solid; m.pt. 104.4−105.9 °C; IR (υmax/cm−1, CHCl3): 2958, 2919, 2852, 1594, 1524, 1493, 1452, 1381, 1339, 1238, 1154, 1113, 1072, 1038, 887, 823, 731,

Figure 7. Recyclability of HS-CuO nanocatalyst for the synthesis of 4aaa.

volume characterization techniques (see the SI for details, Figure S1 and S2).

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CONCLUSIONS In summary, we developed a sustainable method for the synthesis of benzofuranamine and dihydro-benzofuranamine isomers with anomalous selectivity via an O-annulated A3 coupling strategy using the HS-CuO nanocatalyst in the absence of base and additives under solvent free conditions. The experimental results showed that the anomalous selectivity in benzofuran isomers depends on the electronic factors of substituents on salicylaldehyde substrate and the type of secondary amines used in the coupling reaction. The present method has several advantages to achieve sustainable chemistry and opens up a new scope to further explore the catalytic potential of hierarchically porous CuO NPs for regioselective synthesis of biologically significant heterocycles.

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EXPERIMENTAL SECTION

Preparation of HS-CuO Nanocatalyst. The preparation method is simple and cost-effective. Commercially available malachite microspheres (CAS No 12069-69-1; supplier Central Drug House (CDH) (P) Ltd., New Delhi, INDIA) were calcined at 450 °C in the presence of air for 4 h to afford a black powder (HS-CuO). General Procedure for the Synthesis of Benzofuran (4) and Dihydrobenzofuran (6). A mixture of salicyladehyde derivatives 1 (1 mmol), secondary amines 2 (1 mmol), phenylacetylenes 3 (1 mmol), and HS-CuO NPs catalyst (5 mg) was stirred at 110 °C under solvent free conditions until the reaction was completed as monitored by TLC. After completion, 6 mL of ethanol was added to the reaction mixture, and the catalyst was separated by centrifugation. The recovered catalyst was washed with ethanol 3−4 times to remove all adsorbed organic substrates from its surface and dried at 80 °C in vacuum oven to reuse it in further cycles. The organic layers were combined and evaporated to afford crude products, which were purified by flash chromatography. All unknown compounds (6cad, 6cac, 6caf, 6cag, 4aac, 4aae, 4aba, 4abb, 4abc, 4abd, 4abf, 4abg, 6cba, 6cbg, 4bbb, 4bbc, 4aca, 4ada, 4acb, 4acc, 4acd, 4ace, and 4acg) were characterized by 1H NMR, 13C NMR, IR, and mass spectral data and C, H, N, and S analysis. The 1H and 13C NMR spectra of known compounds (6caa, 6cab, and 4aaa) are in good agreement with reported data (see the SI).

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SPECTRAL DATA OF UNKNOWN COMPOUNDS (Z)-4-(2-(4-Methoxybenzylidene)-2,3-dihydrobenzofuran-3-yl)morpholine (6cad). Yellow solid; m.pt. 151.8− 6473


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ACS Sustainable Chemistry & Engineering 689; 1H NMR (400 MHz, CDCl3) δ = 8.55 (d, 4J = 2.2 Hz, 1H), 8.17 (dd, J = 9.16, 3.05 Hz, 1H), 7.46 (d, J = 9.1 Hz, 1H), 7.28 (t, J = 7.6 Hz, 2H), 6.96 (t, J = 7.6 Hz, 1H), 6.88 (d, J = 8.3 Hz, 2H), 4.35 (t, J = 6.1 Hz, 2H), 3.87 (t, J = 4.5 Hz, 4H) ppm; 13C NMR (100 MHz, CDCl3) δ = 158.45, 156.36, 151.41, 143.64, 130.74, 129.69, 126.69, 121.24, 119.79, 116.39, 114.50, 111.96, 67.63, 65.04, 52.66, 27.24 ppm ; HRMS (ES): Calcd 368.1379, found 368.1374. 4-(2-Benzyl-5-nitrobenzofuran-3-yl)thiomorpholine (4aba). Yellow solid; m.pt. 138.8−139.6 °C; IR (υmax/cm−1, CHCl3): 2923, 2830, 2360, 1630, 1525, 1452, 1385, 1342, 1276, 1211, 1126, 1073, 968, 893, 826, 742, 709: 1H NMR (400 MHz, CDCl3) δ = 8.43 (s, 1H), 8.04 (dd, J = 9.1, 2.2 Hz, 1H), 7.32 (d, J = 9.1 Hz, 1H), 7.23 (d, J = 7.6 Hz, 2H), 7.19− 7.14 (m, 3H), 4.08 (s, 2H), 3.32 (t, J = 4.5 Hz, 4H), 2.73 (t, J = 4.5 Hz, 4H) ppm; 13C NMR (100 MHz, CDCl3) δ = 156.20, 153.58, 143.55, 137.08, 130.76, 128.81, 128.59, 126.94, 126.76, 119.62, 116.20, 111.93, 54.51, 32.55, 28.81 ppm; HRMS (ES): Calcd 354.1037, found 354.1029. 4-(2-(4-Fluorobenzyl)-5-nitrobenzofuran-3-yl)thiomorpholine (4abb). Yellow solid; m.pt. 130.9−131.3 °C; IR (υmax/cm−1, CHCl3): 3096, 2920, 1600, 1516, 1450, 1384, 1339, 1272, 1220, 1124, 1069, 1017, 967, 893, 825, 738; 1H NMR (400 MHz, CDCl3) δ = 8.43 (s, 1H), 8.04 (dd, J = 9.1, 2.2 Hz, 1H), 7.32 (d, J = 9.1 Hz, 1 Hz), 7.23 (d, J = 6.8 Hz, 2H), 7.19−7.14 (m, 3H), 4.08 (s, 2H), 3.32 (t, J = 4.5 Hz, 4H), 2.73 (t, J = 4.5 Hz, 4H) ppm; 13C NMR (100 MHz, CDCl3) δ = 136.03, 156.19, 153.32, 143.59, 132.77, 130.78, 130.07, 126.68, 119.71, 116.26, 115.74, 111.96, 54.52, 31.72, 28.80 ppm; HRMS (ES): Calcd 372.0944, found 372.0936. 4-(2-(4-Methylbenzyl)-5-nitrobenzofuran-3-yl)thiomorpholine (4abc). Yellow solid; m.pt. 105.4−106.2 °C; IR (υmax/cm−1, CHCl3): 3734, 2922, 2828, 2359, 1626, 1523, 1451, 1384, 1341, 1274, 1208, 1125, 1070, 1022, 967, 893, 817, 741; 1H NMR (400 MHz, CDCl3) δ = 8.43 (s, 1H), 8.04 (d, J = 8.3 Hz, 1H), 7.32 (d, J = 9.1 Hz, 1H), 7.08−7.03 (m, 4H), 4.03 (s, 2H), 3.33 (t, J = 4.5 Hz, 4H), 2.74 (t, J = 4.5 Hz, 4H), 2.23 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ = 156.25, 153.88, 143.59, 136.62, 134.02, 130.65, 129.54, 128.51, 126.85, 119.63, 116.21, 119.97, 54.58, 32.18, 28.87, 21.54 ppm; Calcd 368.1195, found 368.1188. 4-(2-(4-Methoxybenzyl)-5-nitrobenzofuran-3-yl)thiomorpholine (4abd). Yellow solid; m.pt. 96.2−96.8 °C; IR (υmax/cm−1, CHCl3): 2921, 2835, 1611, 1517, 1450, 1339, 1249, 1122, 1031, 967, 903, 819, 725; 1H NMR (400 MHz, CDCl3) δ = 8.50 (s, 1H), 8.12 (dd, J = 9.1, 2.2 Hz, 1H), 7.40 (d, J = 9.1 Hz, 1H), 7.18 (d, J = 8.3 Hz, 2H), 6.85 (d, J = 8.3 Hz, 2H), 4.09 (s, 2H), 3.77 (s, 3H), 3.40 (t, J = 4.5 Hz, 4H), 2.82 (t, J = 4.5 Hz, 4H) ppm; 13C NMR (100 MHz, CDCl3) δ = 158.56, 156.21, 154.02, 143.56, 130.50, 129.60, 129.09, 126.68, 119.59, 116.19, 114.21, 111.93, 55.35, 54.56, 31.70, 28.85 ppm; 13C NMR (100 MHz, CDCl3) δ = 158.56, 156.21, 154.02, 143.56, 130.50, 129.60, 129.09, 126.83, 119.59, 116.19, 114.21, 111.93, 55.35, 54.56, 31.70, 28.85 ppm; HRMS (ES): Calcd 384.1175, found 384.1171. 4-(2-(2-(4-Bromophenoxy)ethyl)-5-nitrobenzofuran3-yl)thiomorpholine (4abf). Yellow solid; m.pt. 133.6−134.2 °C; IR (υmax/cm−1, CHCl3): 3095, 2854, 2358, 1724, 1627, 1587, 1524, 1483, 1456, 1387, 1341, 1278, 1240, 167, 1070, 1034, 963, 891, 823, 739; 1H NMR (400 MHz, CDCl3) δ = 8.51 (s, 1H), 8.16 (d, J = 9.1 Hz, 1H), 7.44 (d, J = 7.6 Hz, 1H), 7.36 (d, J = 8.3 Hz, 2H), 6.75 (d, J = 9.9 Hz, 2H), 4.28 (t, J = 6.8 Hz, 2H), 3.42 (t, J = 5.3 Hz, 4H), 3.30 (t, J = 6.8 Hz, 2H),

2.80 (t, J = 5.3 Hz, 4H) ppm; 13C NMR (100 MHz, CDCl3) δ = 157.55, 156.25, 151.19, 143.71, 132.48, 132.07, 126.83, 119.87, 117.33, 116.29, 113.40, 111.94, 65.31, 54.60, 28.85, 27.00 ppm; HRMS (ES): Calcd 463.3449, found 463.3454. N-Methyl-N-(2-(5-nitro-3-thiomorpholinobenzofuran2-yl)ethyl)aniline (4abg). Brown solid; m.pt. 100.5−101.4 °C; IR (υmax/cm−1, CHCl3): 3092, 2917, 2826, 2357, 1597, 1513, 1449, 1338, 1265, 1203, 1108, 1071, 1029, 958, 889, 815, 737, 690; 1H NMR (400 MHz, CDCl3) δ = 8.47 (s, 1H), 8.15 (dd, J = 9.1, 2.2 Hz, 1H), 7.46 (d, J = 8.3 Hz, 1H), 7.22 (t, J = 7.6 Hz, 2H), 6.72−6.68 (m, 3H), 3.75 (t, J = 7.6 Hz, 2H), 3.28 (t, J = 4.5 Hz, 4H), 3.08 (t, J = 6.8 Hz, 2H), 2.88 (s, 3H), 2.69 (t, J = 4.5 Hz, 4H) ppm; 13C NMR (100 MHz, CDCl3) δ = 156.14, 153.42, 148.27, 143.64, 131.65, 129.40, 126.80, 119.63, 116.73, 116.14, 112.16, 111.79, 54.62, 50.99, 38.64, 28.75, 23.76 ppm; HRMS (ES): Calcd 397.1470, found 397.1464. (Z)-4-(2-Benzylidene-2,3-dihydrobenzofuran-3-yl)thiomorpholine (6cba). Brown solid; m.pt. 103.1−103.7 °C; IR (υmax/cm−1, CHCl3): 3055, 2919, 2832, 2356, 1682, 1599, 1462, 1325, 1281, 1218, 1081, 1008, 958, 910, 828, 748, 694; 1 H NMR (400 MHz, CDCl3) δ = 7.62 (d, J = 7.6 Hz, 2H), 7.31−7.25 (m, 3H), 7.19 (t, J = 7.6 Hz, 1H), 7.15−7.10 (m, 1H), 6.95−6.92 (m, 2H), 5.76 (s, 1H), 4.88 (s, 1H), 2.96−2.91 (m, 2H), 2.75−2.70 (m, 2H), 2.60−2.52 (m, 4H) ppm; 13C NMR (100 MHz, CDCl3) δ = 158.07, 154.25, 135.09, 132.00, 129.70, 128.51, 126.42, 126.06, 124.09, 122.37, 110.33, 105.21, 69.67, 51.32, 28.72 ppm; HRMS (ES): Calcd 309.1186, found 309.1192. (Z)-N-Methyl-N-(2-(3-thiomorpholinobenzofuran2(3H)-ylidene)ethyl)aniline (6cbg). Yellow oil; IR (υmax/ cm−1, CHCl3): 1H NMR (400 MHz, CDCl3) δ = 7.67 (d, J = 7.67 (d, J = 8.3 Hz, 1H), 7.63−7.58 (m, 2H), 7.55 (d, J = 7.6 Hz, 1H), 7.33 (t, J = 6.8 Hz, 1H), 7.29 (d, J = 7.6 Hz, 1H), 7.14 (d, J = 8.3 Hz, 2H), 7.04 (t, J = 7.6 Hz, 1H), 5.29 (t, J = 7.6 Hz, 1H), 5.11 (s, 1H), 4.55 (d, J = 7.6 Hz, 1H), 3.30 (s, 3H), 3.22− 3.16 (m, 2H), 3.05−2.99 (m, 2H), 2.90 (t, J = 4.5 Hz, 4H) ppm; 13C NMR (100 MHz, CDCl3) δ = 157.84, 155.00, 129.67, 129.61, 126.11, 125.33, 122.08, 116.79, 113.23, 109.88, 101.31, 68.05, 51.14, 47.96, 38.45, 28.52 ppm; HRMS (ES): Calcd 352.4930, found 352.4924 4-(5,7-Dibromo-2-(4-fluorobenzyl)benzofuran-3-yl)thiomorpholine (4bbb). Yellow solid; m.pt. 138.6−139.5 °C; 1 H NMR (400 MHz, CDCl3) δ = 7.69 (S, 1H), 7.50 (s, 1H), 7.24−7.21 (m, 2H), 6.99 (t, J = 8.3 Hz, 2H), 4.10 (s, 2H), 3.30 (t, J = 4.5 Hz, 4H), 2.77 (t, J = 4.5 Hz, 4H) ppm; 13C NMR (100 MHz, CDCl3) δ = 163.03, 160.58, 152.59, 149.46, 133.03, 130.12, 130.49, 128.99, 121.68, 115.71, 115.50, 105.48, 54.40, 31.66, 28.84 ppm; HRMS (ES): Calcd 482.9302, found 482.9306. 4-(5,7-Dibromo-2-(4-methylbenzyl)benzofuran-3-yl)thiomorpholine (4bbc). Yellow solid; m.pt. 167.7−168.5 °C; 1 H NMR (400 MHz, CDCl3) δ = 7.61 (s, 2H), 7.44 (d, J = 8.3 Hz, 2H), 7.18 (d, J = 8.3 Hz, 2H), 5.01 (s, 2H), 3.01 (br s, 4H), 2.77 (br s, 4H), 2.38 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ = 153.49, 139.56, 135.22, 131.98, 130.92, 129.39, 123.57, 118.63, 111.37, 111.15, 91.65, 79.26, 61.67, 28.04, 21.68 ppm; HRMS (ES): Calcd 478.9554, found 478.9548. 1-(2-Benzyl-5-nitrobenzofuran-3-yl)-4-phenylpiperazine (4aca). Yellow solid; m.pt. 107.6−108.7 °C; IR (υmax/ cm−1, CH2Cl2): 3028, 2921, 2849, 1684, 1628, 1598, 1523, 1495, 1451, 1382, 1341, 1268, 1232, 1143, 1070, 1026, 937, 895, 822, 758, 739, 712, 693, 522; 1H NMR (400 MHz, 6474


Research Article

ACS Sustainable Chemistry & Engineering CDCl3) δ = 8.57−8.56 (m, 1H), 8.11 (dd, J = 9.1, 2.2 Hz, 1H), 7.39 (d, J = 8.3 Hz, 1H), 7.32−7.26 (m, 6H), 7.22 (t, J = 6.8 Hz, 1H), 6.99 (d, J = 8.3 Hz, 2H), 6.89 (t, J = 7.6 Hz, 1H), 4.19 (s, 2H), 3.37−3.30 (m, 8H) ppm; 13C NMR (100 MHz, CDCl3) δ = 156.31, 153.32, 151.44, 143.52, 137.26, 129.63, 129.27, 128.82, 128.63, 126.93, 126.68, 120.33, 119.60, 116.63, 116.43, 111.95, 52.45, 50.26, 32.68 ppm; HRMS (ES): Calcd 413.1739, found 413.1732. 1-(2-Benzyl-5-nitrobenzofuran-3-yl)-4-(4methylphenethyl)piperazine (4ada). Yellow solid; m.pt. 68.7−69.3 °C; IR (υmax/cm−1, CH2Cl2): 2922, 2851, 1601, 1524, 1495, 454, 1340, 1272, 1211, 1035, 700; 1H NMR (400 MHz, CDCl3) δ = 8.51 (s, 1H), 8.04 (dd, J = 9.1, 3.8 Hz, 1H), 7.32 (dd, J = 9.9, 1.5 Hz, 1H), 7.23 (d, J = 7.2 Hz, 3H), 7.20 (s, 2H), 7.18−7.12 (m, 4H), 4.11 (s, 2H), 3.20−3.18 (m, 5H), 2.82−2.78 (m, 2H), 2.67−2.61 (m, 8H) ppm; 13C NMR (100 MHz, CDCl3) δ = 156.37, 153.14, 143.55, 140.19, 137.36, 128.84, 128.67, 128.60, 126.93, 126.79, 126.30, 119.61, 116.55, 111.92, 60.76, 53.88, 52.31, 33.69, 32.70 ppm; HRMS (ES): Calcd 455.2188, found 455.2182. 1-(2-(4-Fluorobenzyl)-5-nitrobenzofuran-3-yl)-4-phenylpiperazine (4acb). Yellow solid; m.pt. 149.6−150.2 °C; IR (υmax/cm−1, CHCl3): 3437, 2917, 2849, 1598, 1510, 1450, 1382, 1342, 1267, 1220, 1054, 822, 772, 692, 617; 1H NMR (400 MHz, CDCl3) δ = 8.60−8.59 (m, 1H), 8.15 (d, J − 9.9 Hz, 1H), 7.43 (d, J = 9.1 Hz, 1H), 7.32 (t, J = 7.6 Hz, 2H), 7.27−7.23 (m, 2H), 7.03−6.98 (m, 4H), 6.92 (t, J = 6.8 Hz, 1H), 4.19 (s, 2H), 3.38−3.34 (m, 8H) ppm; 13C NMR (100 MHz, CDCl3) δ = 156.38, 153.17, 151.47, 143.64, 133.00, 130.16, 129.72, 129.36, 126.67, 120.49, 119.79, 116.73, 116.58, 115.84, 115.63, 112.05, 52.55, 50.36, 31.92 ppm; HRMS (ES): Calcd 431.1620, found 431.1616 1-(2-(4-Methylbenzyl)-5-nitrobenzofuran-3-yl)-4-phenylpiperazine (4acc). Yellow solid; m.pt. 130.7−131.7 °C; IR (υmax/cm−1, CHCl3): 3440, 2920, 2826, 1598, 1524, 1501, 1450, 1381, 1341, 1268, 1232, 1116, 1068, 1027, 936, 895, 820, 758, 738, 692, 617, 522; 1H NMR (400 MHz, CDCl3) δ = 8.59−8.58 (m, 1H), 8.14 (dt, J = 9.1, 2.2 Hz, 1H), 7.43 (d, J = 9.1 Hz, 1H), 7.34−7.30 (m, 2H), 7.19−7.12 (m, 4H), 7.02 (d, J = 8.3 Hz, 2H), 6.93 (t, J = 7.6 Hz, 1H), 4.18 (s, 2H), 3.37−3.36 (m, 8H), 2.33 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ = 156.38, 153.61, 151.53, 143.59, 136.60, 134.22, 129.56, 129.33, 128.55, 126.79, 120.39, 119.61, 116.70, 116.44, 111.98, 52.52, 50.35, 32.31, 21.16 ppm; HRMS (ES): Calcd 427.1895, found 427.1890. 1-(2-(4-Methoxybenzyl)-5-nitrobenzofuran-3-yl)-4phenylpiperazine (4acd). Yellow solid; m.pt. 96.2−96.5 °C; IR (υmax/cm−1, CH2Cl2): 2917, 2833, 1598, 1511, 1450, 1382, 1341, 1301, 1247, 1176, 1118, 1027, 937, 895, 818, 758, 737, 694, 522; 1H NMR (400 MHz, CDCl3) δ = 8.58 (s, 1H), 8.14 (d, J = 9.1 Hz, 1H), 7.32 (t, J = 7.6 Hz, 2H), 7.20 (d, J = 8.3 Hz, 2H), 7.02 (d, J = 8.3 Hz, 2H), 6.92 (t, J = 7.6 Hz, 1H), 6.86 (d, J7.6 Hz, 2H), 4.15 (s, 2H), 3.78 (s, 3H), 3.39−3.33 (m, 8H) ppm; 13C NMR (100 MHz, CDCl3) δ = 158.59, 156.37, 153.80, 151.52, 143.57, 130.74, 130.65, 129.67, 129.35, 126.78, 120.42, 119.63, 116.72, 116.47, 114.26, 111.99, 55.41, 52.54, 50.37, 31.87 ppm; HRMS (ES): Calcd 443.1845, found 443.1838. 1-(5-Nitro-2-(2-phenoxyethyl)benzofuran-3-yl)-4-phenylpiperazine (4ace). Yellow solid; m.pt. 147.9−148.5 °C; IR (υmax/cm−1, CH2Cl2): 3440, 2921, 2851, 1601, 1523, 1501, 1452, 1337, 1279, 1249, 1060, 933, 915, 880, 823, 762, 689, 617, 522; 1H NMR (400 MHz, CDCl3) δ = 8.56−8.55 (m, 1H), 8.20 (dd, J = 9.1, 2.2 Hz, 1H), 7.47 (d, J = 9.1 Hz, 1H),

7.32 (t, J = 7.6 Hz, 2H), 7.01 (d, J = 9.1 Hz, 2H), 6.94−6.90 (m, 2H), 6.88−6.85 (m, 1H), 5.97−5.92 (m, 2H), 5.45−5.40 (m, 2H), 3.43−3.34 (m, 8H) ppm; 13C NMR (100 MHz, CDCl3) δ = 156.45, 151.45, 148.76, 143.72, 130.54, 129.38, 126.84, 123.19, 120.79, 120.49, 116.91, 116.74, 116.21, 111.93, 52.49, 50.30, 29.79 ppm; HRMS (ES): Calcd 443.1840, found 443.1838. N-Methyl-N-(2-(5-nitro-3-(4-phenylpiperazin-1-yl)benzofuran-2-yl)ethyl)aniline (4acg). Yellow oil; IR (υmax/ cm−1, CH2Cl2): 3057, 2940, 2884, 2829, 1676, 1620, 1599, 1523, 1504, 1472, 1452, 1338, 1305, 1264, 1236, 1143, 1118, 1096, 1068, 1034, 1007, 977, 931, 909, 830, 737, 694, 523; 1H NMR (400 MHz, CDCl3) δ = 8.55−8.54 (m, 1H), 8.17 (dd, J = 9.1, 2.2 Hz, 1H), 7.48 (d, J = 9.1 Hz, 1H), 7.32 (t, J = 7.6 Hz, 2H), 7.22 (t, J = 7.6 Hz, 2H), 6.99 (d, J = 8.3 Hz, 2H), 6.92 (t, J = 6.8 Hz, 1H), 6.74 (d, J = 8.3 Hz, 2H), 6.70 (t, J = 7.6 Hz, 1H), 3.77 (t, J = 6.8 Hz, 2H), 3.28−3.22 (m, 8H), 3.14 (t, J = 6.8 Hz, 2H), 2.91 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ = 162.28, 154.01, 151.15, 149.13, 143.04, 129.20, 129.10, 126.87, 122.48, 122.30, 119.95, 117.02, 116.26, 113.20, 109.96, 104.46, 65.49, 49.48, 48.17, 47.84, 38.40 ppm.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acssuschemeng.7b00500. PXRD and TEM of recycled HS-CuO nanocatalyst; green chemistry metric calculations, spectral data of known and unknown compounds, 1H NMR and 13C NMR spectra of all compounds. (PDF)

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AUTHOR INFORMATION

Corresponding Author

*Fax: 91-11-27667501. Tel: 91-11-27662683. E-mail: dsrawat@ chemistry.du.ac.in. ORCID

Diwan S. Rawat: 0000-0002-5473-7476 Present Address ‡

Department of Chemistry, Indiana University, Bloomington, Indiana 47405, United States. Author Contributions †

These authors contributed equally to the work.

Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS D.S.R. thanks DU-DST PURSE grant, and University of Delhi, Delhi, India for financial support. G.P. thank DST project: EMR/2014/001127, and U.C.R. thanks UGC for research fellowships, respectively. We thank USIC−CIF, University of Delhi for assisting to acquire analytical data.

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REFERENCES

(1) Anastas, P. T.; Allen, D. T. Twenty-Five Years of Green Chemistry and Green Engineering: The End of the Beginning. ACS Sustainable Chem. Eng. 2016, 4, 5820−5820. (2) Constable, D. J. C.; Curzons, A. D.; Cunningham, V. L. Metrics to ’Green’ Chemistry-Which are the Best? Green Chem. 2002, 4, 521− 527. (3) Giraud, R. J.; Williams, P. A.; Sehgal, A.; Ponnusamy, E.; Phillips, A. K.; Manley, J. B. Implementing Green Chemistry in Chemical

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