Bahador
Karami
*a,
S. Jafar
Hoseini
a,
Khalil
Eskandari
a,
Abdolmohammad
Ghasemi
b and
Hassan
Nasrabadi
a
aDepartment of Chemistry, Yasouj University, Yasouj, Iran. E-mail: karami@mail.yu.ac.ir; Fax: +98 7412224167; Tel: +98 7412223048
bIslamic Azad University, Gachsaran Branch, Gachsaran, Iran
First published on 27th October 2011
An efficient and environmentally adapted synthesis of xanthene derivatives by condensation of a wide range of aryl aldehydes and 1,3-cyclohexanediones in water using a catalytic amount of Fe3O4 nanoparticles is explained. The Fe3O4 nanoparticles were characterized by powder X-ray diffraction (XRD), transmission electron microscopy (TEM) and FT-IR spectroscopy.
Several polycyclic compounds containing the xanthene skeleton are isolated from natural sources.8 Xanthene and its derivatives are prepared by different methods, including the reaction of aryloxymagnesium halides with triethylorthoformate,9 cyclodehydration,10 trapping of benzynes by phenols,11 intramolecular phenyl carbonyl coupling reactions of benzaldehydes and acetophenones,12 and cyclocondensation between 2-hydroxy aromatic aldehydes and 2-tetralone.13 In view of the importance of xanthene derivatives, many methods for the synthesis of these compounds were reported including condensation of β-naphthol and aldehydes or acetals catalyzed by silica sulfuric acid, HCl/CH3COOH or H3PO4.14 However some of these methods involved long reaction times, and unsatisfactory yields. Therefore improvements in these syntheses have been sought continuously. In this work, preparation, high activation, and regeneration of Fe3O4 nanoparticles as a catalyst in organic synthesis have been shown.
A new method for the synthesis of 1,8-dioxo-octahydroxanthenes was obtained by condensation of 1,3-cyclohexanediones and benzaldehydes in the presence of magnetic nanoparticles Fe3O4 as an effective catalyst in water as a solvent (Scheme 1).
Scheme 1 Synthesis of 1,8-dioxo-octahydroxanthenes in the presence of 1,3-cyclohexanediones, benzaldehydes and magnetic nanoparticles Fe3O4. |
The synthesis mechanism of 1,8-dioxo-octahydroxanthene derivatives has been shown in Scheme 2.
Scheme 2 The suggested mechanism for synthesis of 1,8-dioxo-octahydroxanthene derivatives. |
Entry | Aldehyde 2 | Producta4 | Time (min) | Yieldb (%) | Mp (°C)/(lit.) |
---|---|---|---|---|---|
a Identified by comparison with authentic samples. b Refers to isolated yields. | |||||
1 | 8 | 96 | 202–204 (201–202)15 | ||
2 | 33 | 90 | 230–232 (230–232)15 | ||
3 | 53 | 88 | 215–217 (216–217)16 | ||
4 | 6 | 95 | 219–221 (221–223)16 | ||
5 | 42 | 89 | 226–227 (226–228)17 | ||
6 | 14 | 93 | 209–211 (210–212)18 | ||
7 | 19 | 92 | 223–225 (224–226)17 | ||
8 | 34 | 90 | 250–252 (249–252)19 | ||
9 | 40 | 86 | 189–191 (190–191)20 | ||
10 | 37 | 88 | 238–239 (236–239)10 | ||
11 | 16 | 90 | 245–247 (> 300)21 | ||
12 | 23 | 86 | 238–240 (236–238)22 | ||
13 | 10 | 95 | 271–273 (272–273)23 | ||
14 | 62 | 89 | 260–262 (262–263)15 | ||
15 | 9 | 92 | 224–227 (224–226)24 | ||
16 | 42 | 88 | 250–252 (249–252)9 | ||
17 | 45 | 86 | 170–172 (169–171)25 | ||
18 | 21 | 92 | 252–25526 |
Product | Total reusability | Yield (%) | Time (min) |
---|---|---|---|
1 | 96 | 8 | |
2 | 95 | 8 | |
3 | 95 | 9 | |
4 | 97 | 10 | |
5 | 97 | 9 |
Fig. 1 The reusability of the catalyst in the synthesis of 3,3,6,6-tetramethyl-9-phenyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione (Table 1, entry 1). |
Table 1, entry 6: mp, 209–211 °C; IR (KBr) (νmax, cm−1): 3050, 2995, 1660, 1620, 1480, 1375, 1188, 1090, 845; 1H NMR (400 MHz, CDCl3); δH (ppm): 1.04 (6H, s, 2 × CH3), 1.12 (6H, s, 2 × CH3), 2.24 (4H, s, 2 × CH2), 2.47 (4H, s, 2 × CH2), 3.78 (3H, s, OCH3), 3.81 (6H, s, 2 × OCH3), 4.72 (1H, s, CH), 6.52 (2H, s, Ar-H); 13C NMR (100 MHz, CDCl3); δC (ppm): 27.18, 29.36, 31.80, 32.17, 40.90, 50.75, 56.09, 60.68, 105.75, 115.57, 136.60, 139.73, 152.79, 162.34, 196.45.
Table 1, entry 7: mp, 223–225 °C; IR (KBr) (νmax, cm−1): 3040, 2990, 2970, 1660, 1620, 1500, 1360, 1200, 1160, 1180; 1H NMR (400 MHz, CDCl3); δH (ppm): 1.00 (6H, s, 2 × CH3), 1.11 (6H, s, 2 × CH3), 2.21 (4H, q, J = 16.4 Hz, 2 × CH2), 2.47 (4H, s, 2 × CH2), 4.73 (1H, s, CH), 6.91 (2H, m, Ar-H), 7.27 (2H, m, Ar-H); 13C NMR (100 MHZ, CDCl3); δC (ppm): 27.28, 29.26, 32.19, 40.84, 50.73, 114.71, 114.93, 115.49, 129.88, 139.99, 160.15, 162.58, 196.34.
Table 1, entry 9: mp, 189–191 °C; IR (KBr) (νmax, cm−1): 3065, 2960, 2880, 1660, 1615, 1450, 1375, 1200, 1160, 1138; 1H NMR (400 MHZ, CDCl3); δH (ppm): 1.01 (6H, s, 2 × CH3), 1.10 (6H, s, 2 × CH3), 1.18 (6H, d, J = 5.2 Hz, 2 × CH3), 2.21 (4H, m, 2 × CH2), 2.46 (4H, s, 2 × CH2), 2.79 (1H, bb, CH), 4.73 (1H, s, CH), 7.05 (2H, d, J = 6.8 Hz, Ar-H), 7.19 (2H, m, Ar-H); 13C NMR (100 MHz, CDCl3); δC (ppm): 23.90, 27.49, 29.21, 31.30, 32.21, 33.60, 40.90, 50.80, 126.12, 128.12, 141.39, 146.51, 162.15, 196.46.
Table 1, entry 11: mp, 245–247 °C; IR (KBr) (νmax, cm−1): 3040, 2957, 1666, 1620, 1462, 1425, 1365, 1200, 1162, 1003, 808; 1H NMR (400 MHz, CDCl3); δH (ppm): 0.97 (12H, s, 4 × CH3), 1.07 (12H, s, 4 × CH3), 2.18 (8H, s, 4 × CH2), 2.44 (8H, dd, 1J = 36.4 Hz, 4J = 17.6 Hz, 4 × CH2), 4.71 (2H, s, 2 × CH), 7.08 (2H, s, Ar-H), 7.27 (2H, s, Ar-H); 13C NMR (100 MHz, CDCl3); δC (ppm): 25.01, 27.66, 28.98, 30.74, 32.24, 40.85, 50.64, 115.70, 127.88, 141.74, 162.42, 196.36.
Table 1, entry 12: mp, 238–240 °C; IR (KBr) (νmax, cm−1): 3095, 2957, 1659, 1629, 1462, 1203, 1158, 769; 1H NMR (400 MHz, CDCl3); δH (ppm): 1.03 (12H, s, 4 × CH3), 1.08 (12H, s, 4 × CH3), 2.15 (8H, dd, 2J = 24 Hz, 4J = 16 Hz, 4 × CH2), 2.48 (8H, dd, 2J = 45.2 Hz, 4J = 17.6 Hz, 4 × CH2), 4.72 (2H, s, 2 × CH), 7.07–7.09 (3H, m, Ar-H), 7.15 (1H, s, Ar-H); 13C NMR (100 MHz, CDCl3); δC (ppm): 28.02, 29.57, 31.76, 32.56, 41.27, 51.27, 116.01, 126.84, 128.18, 144.04, 162.72, 196.66.
Table 1, entry 14: mp, 260–262 °C; IR (KBr) (νmax, cm−1): 3050, 2955, 1658, 1616, 1467, 1175, 1126, 827; 1H NMR (400 MHz, CDCl3); δH (ppm): 2.01 (4H, m, 2 × CH2), 2.26 (3H, s, CH3), 2.35 (4H, m, 2 × CH2), 2.59 (4H, m, 2 × CH2), 4.78 (1H, s, CH), 7.03 (2H, d, J = 7.2 Hz, Ar-H), 7.19 (2H, d, J = 7.2 Hz, Ar-H); 13C NMR (100 MHz, CDCl3); δC (ppm): 20.31, 21.07, 27.15, 31.22, 36.99, 117.00, 128.25, 128.83, 135.85, 141.56, 163.84, 196.56.
Table 1, entry 15: mp, 224–227 °C; IR (KBr) (νmax, cm−1): 3070, 2950, 1664, 1617, 1467, 1172, 830; 1H NMR (400 MHz, CDCl3); δH (ppm): 2.07 (4H, m, 2 × CH2), 2.35 (4H, m, 2 × CH2), 2.61 (4H, m, 2 × CH2), 4.88 (1H, s, CH), 7.48 (2H, d, J = 8.8 Hz, Ar-H), 8.10 (2H, d, J = 8.8 Hz, Ar-H); 13C NMR (100 MHz, CDCl3); δC (ppm): 20.22, 27.14, 32.23, 36.81, 115.70, 123.41, 129.42, 145.48, 151.73, 164.60, 196.45.
Table 1, entry 16: mp, 250–252 °C; IR (KBr) (νmax, cm−1): 3095, 2960, 1619, 1563, 1463, 1367, 1290, 1215, 1180, 1086, 1033, 1005, 814, 650; 1H NMR (400 MHz, CDCl3); δH (ppm): 1.86 (2H, s, CH2), 2.05 (3H, t, J = 12.4 Hz, CH2), 2.15 (1H, d, J = 8.4 Hz, CH2), 2.43 (2H, m, CH2), 2.57 (3H, t, J = 19.21 Hz, CH2), 2.75 (1H, d, J = 8.8 Hz, CH2), 4.58 (1H, s, CH), 6.91 (1H, d, J = 4.4 Hz, Ar-H), 7.13 (1H, s, Ar-H), 7.26 (1H, d, J = 4.4 Hz, Ar-H), 10.77 (1H, s, OH); 13C NMR (100 MHz, CDCl3); δC (ppm): 19.54, 19.87, 27.89, 27.97, 29.72, 35.95, 36.95, 112.02, 117.00, 117.26, 119.39, 126.92, 130.46, 130.68, 150.03, 170.73, 173.37, 197.09, 201.31.
Table 1, entry 17: mp, 170–172 °C; IR (KBr) (νmax, cm−1): 3050, 2990, 1660, 1620, 1450, 1200, 1130, 828; 1H NMR (400 MHz, CDCl3); δH (ppm): 1.19 (6H, d, J = 6.8 Hz, 2 × CH3), 2.01 (4H, m, 2 × CH2), 2.34 (4H, m, 2 × CH2), 2.61 (4H, m, 2 × CH2), 2.81 (1H, t, J = 7.2 Hz, CH), 4.80 (1H, s, CH), 7.06 (2H, d, J = 8 Hz, Ar-H), 7.19 (2H, d, J = 8 Hz, Ar-H); 13C NMR (100 MHz, CDCl3); δC (ppm): 20.28, 23.92, 27.15, 31.04, 33.59, 36.99, 117.03, 126.16, 146.52, 163.95, 196.64.
Fig. 2 The powder X-ray diffraction pattern of the Fe3O4 nanoparticles. |
Fig. 3 TEM image shows spherical Fe3O4 nanoparticles of 10–20 nm. |
Fig. 4 FT-IR spectra of Fe3O4 nanoparticles. |
Previously, xanthene and its derivatives have been synthesized under reflux for 4–5 h in dichloromethane or 1,2-dichloroethane as solvent in the presence of acid catalysts such as tetra-n-butylammonium fluoride.31 These synthetic methods afforded good yield, however, have limitations of long reaction times, harsh reaction conditions and often expensive catalysts.
Therefore in this work we report a simple, efficient and practical approach for the synthesis of xanthene derivatives in the presence of magnetic nanoparticles Fe3O4 as eco-friendly catalysts with high catalytic activity at 80 °C in water as a solvent (Scheme 1).
Under the given conditions several aromatic aldehydes 2 containing electron donating as well as electron withdrawing groups with different substitution patterns were effectively cyclized to give 9-aryl substituted 1,8-dioxo-octahydroxanthenes (Table 1). The product was isolated simply by filtration. Next, we examined the scope of the reaction by using various aromatic aldehydes, and the results are summarized in Table 1. In all the cases corresponding xanthene derivatives were obtained in good to excellent yields.
The Fe3O4 nanoparticle catalyst plays a crucial role in the success of the reaction. In the absence of the Fe3O4 nanoparticle catalyst, the reaction of 1,3-cyclohexanediones 1 and benzaldehyde derivatives 2 in the presence of the Fe3O4 powder as a catalyst could be carried out, but the product was obtained in very low yield after prolonged time (Table 3). Since metal oxides play the role as a heterogeneous catalyst in many chemical industries and the rate of reaction on the catalyst surface depends on the total surface area and the number of active sites on the catalyst, a good catalytic activity is obtained from smaller particle size and high surface area of the catalyst.32 As can be seen from Table 3, when the same weights of nanoparticle and powdered Fe3O4 were handled, the crucial role of Fe3O4 nanoparticles as a good catalyst was obviously revealed.
Entry | Aldehyde | Product | Nanoparticles Fe3O4 | Fe3O4 powder |
---|---|---|---|---|
Time (min)/Yielda (%) | Time (min)/Yielda (%) | |||
a Refers to isolated yields. | ||||
1 | 8/96 | 260/25 | ||
2 | 37/89 | 300/30 | ||
3 | 33/90 | 280/30 |
The nature of iron sites as Lewis acids causes the reactant with functional groups such as carbonyl (–CO), nitrile (–CN), hydroxyl (–OH), thiol (–SH) or sulfur dioxide (–SO2) and etc. to undergo chemical adsorption by interaction with the acidic surface of metal sites. In the aqueous phase, the water molecule gets associatively adsorbed with the Lewis basic oxygen lone pair orbital onto a Lewis acidic surface of the Fe site, then the substrate adsorbate bond gets established by interaction between the water HOMO orbital and empty Fe 3d orbitals that are energetically located in the lower conduction band region. Because of interaction between the carbonyl group of the substrate with Fe 3d orbitals of the catalyst, the carbonyl group of aldehyde was activated for nucleophilic attack in next steps and causes expedition of reaction progress.33–35
Comparison of this method with others for synthesis of 3,3,6,6-tetramethyl-9-phenyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8 (2H)-dione (Table 1, entry 1) as a model reaction is shown in Table 4.15,18,22,36–40
Entry | Catalyst | mol% | Solvent/Temp. (°C) | Time (min) | Reference |
---|---|---|---|---|---|
a p-Toluenesulfonic acid. b p-Dodecylbenzenesulfonic acid. c Trimethylsilyl chloride. d Tetrabutylammonium hydrogen sulfate. e 1-(Chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2,2,2]octane bis(tetrafluoroborate). f Polyphosphoric acid supported on silica. | |||||
1 | Nanoparticle Fe3O4 | 1 | H2O/80 | 8 | This work |
2 | p-TsOHa | 5 | MeOH, H2O/80 | 20 | 36 |
3 | DBSAb | 10 | H2O-Ultrasonic/25–30 | 60 | 37 |
4 | TMSClc | 100 | CH3CN/Reflux | 420 | 38 |
5 | TBAHSd | 10 | Dioxane, H2O/Reflux | 210 | 22 |
6 | DBSAb | 20 | H2O/Reflux | 180 | 39 |
7 | SelectfluorTMe | 10 | Solvent free/120 | 60 | 40 |
8 | PPA-SiO2f | 10 | Solvent free/140 | 30 | 15 |
9 | HClO4-SiO2 | 10 | Solvent free/140 | 180 | 15 |
10 | SbCl3-SiO2 | 10 | Solvent free/120 | 50 | 18 |
These results show that this catalyst provided the best conditions for the synthesis of xanthene derivatives than other catalysts and methods that were reported. We also studied the effect of the amount of the catalyst on this reaction. We found that the best amount of the catalyst is 1 mol% for the model reaction whereas the larger amounts of the catalyst did not improve the results to a greater extent (Table 5).
Product | mol% | Yield (%) | Time (min) |
---|---|---|---|
1 | 96 | 8 | |
5 | 96 | 8 | |
10 | 95 | 9 | |
20 | 94 | 9 |
Footnote |
† Electronic supplementary information (ESI) available. See DOI: 10.1039/c1cy00289a |
This journal is © The Royal Society of Chemistry 2012 |