An efficient catalyst-free protocol for the synthesis of quinoxaline derivatives under ultrasound irradiation

Abstracts

A highly efficient and facile method has been described for the synthesis of quinoxaline derivatives in good to excellent yields (80-99%) by condensation reaction of heterocyclic as well as aliphatic 1,2-diketones (R¹COCOR¹, R¹ = Et, Ph, p-MeC6H5, p-MeOC6H5, Furyl) with 1,2-diamines (1,2-(NH2)2C6H3R², R² = H, Br, NO2, PhCO). A systematic study was carried out to examine the influence of reaction media and electronic factors of the substrates on the reaction results.

ultrasound irradiation; catalyst-free; quinoxaline derivatives

Um método altamente eficiente e simples foi descrito para a síntese de derivados de quinoxalina em bons a excelentes rendimentos (80-99%) por reação de condensação de 1,2-dicetonas heterocíclicas ou alifáticas (R¹COCOR¹, R¹ = Et, Ph, p-MeC6H5, p-MeOC6H5, Furil) com 1,2-diaminas (1,2-(NH2)2C6H3R², R² = H, Br, NO2, PhCO). Um estudo sistemático foi realizado para examinar a influência do meio reacional e dos fatores eletrônicos dos substratos nos resultados das reações.

ARTICLE

An efficient catalyst-free protocol for the synthesis of quinoxaline derivatives under ultrasound irradiation

Wen-Xue Guo^I; Hui-Le Jin^I; Jiu-Xi ChenI, ^*; Fan Chen^I; Jin-Chang Ding^{I, II}; Hua-Yue WuI, ^*

^ICollege of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, 325027, China

^IIWenzhou Vocational and Technical College, Wenzhou, 325035, China

ABSTRACT

A highly efficient and facile method has been described for the synthesis of quinoxaline derivatives in good to excellent yields (80-99%) by condensation reaction of heterocyclic as well as aliphatic 1,2-diketones (R¹COCOR¹, R¹ = Et, Ph, p-MeC₆H₅, p-MeOC₆H₅, Furyl) with 1,2-diamines (1,2-(NH₂)₂C₆H₃R², R² = H, Br, NO₂, PhCO). A systematic study was carried out to examine the influence of reaction media and electronic factors of the substrates on the reaction results.

Keywords: ultrasound irradiation, catalyst-free, quinoxaline derivatives

RESUME

Um método altamente eficiente e simples foi descrito para a síntese de derivados de quinoxalina em bons a excelentes rendimentos (80-99%) por reação de condensação de 1,2-dicetonas heterocíclicas ou alifáticas (R¹COCOR¹, R¹ = Et, Ph, p-MeC₆H₅, p-MeOC₆H₅, Furil) com 1,2-diaminas (1,2-(NH₂)₂C₆H₃R², R² = H, Br, NO₂, PhCO). Um estudo sistemático foi realizado para examinar a influência do meio reacional e dos fatores eletrônicos dos substratos nos resultados das reações.

Introduction

Quinoxaline derivatives are well known in the pharmaceutical industry and have been shown to possess a broad spectrum of biological activities including antiviral, antibacterial, anti-inflammatory, askinase inhibitors, anticancer and anthelmintic agents.¹ Quinoxaline ring is a part of a number of antibiotics such as echinomycin, levomycin, and actinomycin, which are known to inhibit the growth of Gram-positive bacteria and are also active against various transplantable tumors.² Besides these, it has been reported for their application in dyes,³ efficient electroluminescent materials,⁴ organic semiconductors,⁵ building blocks for the synthesis of anion receptor,⁶ cavitands,⁷ dehydroannulenes,⁸ and DNA cleaving agents.⁹

In light of these significances, a variety of synthetic strategies have been developed for the preparation of quinoxaline derivatives. One of the most common methods is the condensation of 1,2-diamine with 1,2-dicarbonyl compounds in refluxing ethanol or acetic acid.¹⁰ Later, many improved methods has been reported for the synthesis of various quinoxaline derivatives using the Bi-catalyzed oxidative coupling,¹¹ microwave irradiation,¹² a solid-phase synthesis,¹³ and RuCl₂-(PPh₃)₃-TEMPO,¹⁴ MnO₂,¹⁵ POCl₃,¹⁶ zeolites,¹⁷ iodine,¹⁸ cerium ammonium nitrate,¹⁹ CuSO₄·5H₂O²⁰ and SA/MeOH,²¹ Montmorillonite K-10,²² Zn[(L)proline],²³ ionic liquid,²⁴ Ni-nanoparticles,²⁵ silica sulfuric acid,²⁶ NH₄Cl²⁷ as catalyst. Despite the progress, the state-of-the-art for the synthesis of these compounds remains less than ideal. Thus, the development of environmentally friendly benign, high-yielding and clean approaches for the synthesis of quinoxaline derivatives is still remains a highly desired goal in organic synthesis.

Ultrasonic-assisted organic synthesis as a green synthetic approach is a powerful technique that is being used more and more to accelerate organic reactions.²⁸ Compared with traditional methods, this method is more convenient and reactions can be carried out in higher yield, shorter reaction time and milder conditions.²⁹ As part of current studies on the development of green and efficient organic methodologies,³⁰ we herein report an efficient catalyst-free and practical method for the synthesis of quinoxaline derivatives under ultrasound irradiation at room temperature.

Results and Discussion

Initial studies focused on the screening of the solvents, bases as well as catalyst loading with the reaction of benzil and o-phenylenediamine as the model reaction at room temperature. Efforts were directed towards the evaluation of the synthesis of quinoxalines by ultrasound irradiation. With the same substrates, the reaction in ethanol, using ultrasound irradiation at room temperature afforded the products in excellent yield (98%) for 60 min. In contrast, the poor yields were obtained when the reactions were carried in boiling ethanol or in ethanol at room temperature without the aid of ultrasound irradiation (Table 1, entry 4). Thus, the efficacy of various solvents was investigated in the model reaction using benzil with o-phenylenediamine under ultrasound irradiation at room temperature and the results are summarized in Table 1. We examined aprotic solvents (such as CH₂Cl₂, CH₃CN, THF, DMSO, DMF, EtOAc, 1,4-dioxane) and protic solvents (such as H₂O, EtOH, and MeOH). Almost all of the solvents (such as CH₂Cl₂ (93%), CH₃CN (97%), THF (85%), DMSO (92%), DMF (84%), EtOAc (97%), and 1,4-dioxane (91%)) with the exception of H₂O (yield 42%) afforded the desired products in good yields. The protic solvent EtOH (yield 98%) came out as a superior solvent in this transformation.

With optimal conditions in hand, the reaction of various 1,2-diketones and with 1,2-diamines was examined to explore the scope of the reaction and the results are summarized in Table 2. The substitution groups on the aromatic ring associated with 1,2-diketone had no obvious effect on the yields. It was observed that electron-donating groups associated with aromatic 1,2-diketone decreased slightly the product yields (Table 2, entries 4-8). Moreover, we also examined the condensation of heterocyclic 1,2-diketone, such as 1,2-di(furan-2-yl)ethane-1,2-dione (Table 2, entries 9 and 10) with various 1,2-diamine. Similarly, the corresponding products 3i and 3j were obtained in excellent yield. When aliphatic 1,2-diketone, such as hexane-3,4-dione were used as reaction substrates, the desired products 3k and 3l were obtained in 80% and 81% yields, respectively (Table 2, entries 11 and 12). On the other hand, we investigated the influence of electronic factors of 1,2-diamine on the reaction results. It was observed that the reaction of 1,2-diamine bearing electron-donating group (-Me) on the benzene ring, such as 4-methylbenzene-1,2-diamine with various 1,2-diketones was examined and the corresponding products 3b, 3e and 3h were obtained in good yields (Table 2, entries 2, 5 and 8). However, the presence of an electron-withdrawing group on the benzene ring decreased the reactivity of the substrate. For instance, 1,2-diamines containing strongly electron-withdrawing group (-NO₂) on the benzene ring, such as 4-nitrobenzene-1,2-diamine afforded the corresponding products 3c and 3f in only 37% and 36% yields, respectively (Table 2, entries 3 and 6), which showed an obvious electronic effect.

Thus, further optimization studies were performed in order to develop a better system that was more functional group compatible. The most dramatic improvement was observed when the solvent was switched from EtOH to EtOH/acetic acid (AcOH). AcOH does work not merely as a solvent, but also as a promoter of the reaction. Therefore, the volume ratio of EtOH and AcOH was examined and the best results were obtained by carrying out the reaction in EtOH/AcOH with a ratio of 10:1 (v/v) (Table 3, entry 3).

Next, we explored the scope of the condensation of 1,2-diketones with electron-withdrawing groups with 1,2-diamines (Table 4). In all the case, the reaction proceeded smoothly and the desired products were obtained in excellent yields.

To check the versatility of this method, the present protocol was also applied to less nucleophilic aromatic diamine such as naphthalene-2,3-diamine (Table 4, entry 4). On the other hand, some heterocyclic 1,2-diketone such as furil was subjected for condensation reaction and the desired products was obtained in excellent yields (Table 4, entries 6-7). When aliphatic 1,2-diketone, such as 3,4-hexanedione was used as substrate, the desired products were also obtained with excellent yield (Table 4, entry 8). Finally, we also examined the reaction of unsymmetrical 1,2-diketons with o-phenylenediamine (Table 4, entry 9). Similarly, the corresponding products were obtained with excellent yield.

In summary, we developed a highly efficient and facile method for the quinoxalines from various 1,2-diketones and 1,2-diamines under ultrasound irradiation at room temperature. Compared to previous reported methodologies, the present protocol features simple experimental operations, lower reaction temperature, high reaction rates and excellent yields, which makes this method a useful and attractive strategy in view of economic and environmental advantages.

Experimental

All reagents were commercial available and used without any purification. Melting points were recorded on Digital Melting Point Apparatus WRS-1B and are uncorrected. IR spectra were recorded on a Bruker-EQUINOX55 spectrometer. ¹H NMR and ¹³C NMR spectra were recorded on a Brucker AC 300 instrument using CDCl₃ as the solvent with tetramethylsilane (TMS) as an internal standard at room temperature. Chemical shifts were given in δ relative to TMS, the coupling constants J are given in Hz. All reactions were conducted using standard Schlenk techniques. Column chromatography was performed using EM Silica gel 60 (300-400 mesh). Sonication was performed in Shanghai SY-5200DH water bath of the laboratory ultrasonic cleaner (with a frequency of 55 kHz and a constant output power of 150W; Shanghai Shengyuan ultrasonic instrument Co., Ltd.). All reactions were carried out in Schlenk tubes under the air, and the Schlenk tube was located in the water bath of the ultrasonic cleaner, where the surface of reactants is slightly lower than the level of the water. The reaction temperature was controlled at 22-25 ºC by addition or removal of water from ultrasonic bath.

General procedure for the preparation of quinoxalines 3

A mixture of 1, 2-diketone (1, 0.5 mmol), 1, 2-diamine (2, 0.5 mmol) and absolute ethanol (2 mL) or absolute ethanol/acetic acid (2 mL/0.2 mL) was irradiated under ultrasound in an open Schlenk tube at room temperature (22-25 ºC) until completion of the reaction. The progress of the reaction was monitored by TLC. After the reaction was completed, the reaction mixture was concentrated in vacuo and the residue was purified by flash column chromatography (eluted with a mixture of petroleum ether and ethyl acetate) on a silica gel (300-400 mesh) to give the product 3.

The spectral and analytical data of all compounds are given below.

2,3-Diphenyl-quinoxaline (3a)¹⁸

White solid, mp120-122 ºC, ¹H NMR (CDCl₃, 300 MHz): δ 8.20 (dd, J 6.3, 3.4 Hz, 2H),7.76 (dd, J 6.3, 3.4 Hz, 2H), 7.53 ca. 7.56 (m, 4H), 7.34 ca. 7.37 (m, 6H); ¹³C NMR (CDCl₃, 75 MHz): δ 153.48, 141.29, 141.26, 141.24, 139.12, 130.03, 129.98, 129.94, 129.90, 129.87, 129.85, 129.84, 129.82, 129.80, 129.24, 128.84, 128.30, 128.28, 128.26, 128.24; IR (KBr) ν_max/cm^-1: 3065, 1441, 1395, 1344, 768, 696.

6-Methyl-2,3-diphenylquinoxaline (3b)¹⁸

White solid, mp 135-137 ºC , ¹H NMR (CDCl₃, 300 MHz): δ 8.07 (d, J 8.5 Hz, 1H), 7.96 (s,1H), 7.50 ca. 7.53 (m, 5H), 7.32 ca. 7.35 (m, 6H), 2.62 (s, 3H); ¹³C NMR (CDCl₃, 75 MHz) δ 153.00, 152.26, 140.98, 140.16, 139.40, 138.92, 131.97, 130.59, 129.52, 129.02, 128.94, 128.39, 128.36, 128.30, 127.90, 127.71, 127.31, 126.89, 126.83, 21.59; IR (KBr) ν_max/cm^-1: 3053, 1615, 1488, 1447, 1341, 670.

6-Nitro-2,3-dipenylquinoxaline (3c)²³

White solid, mp 185-187 ºC, ¹H NMR (CDCl₃, 300 MHz): δ 9.08 (d, J 2.4 Hz, 1H), 8.53 (dd, J 9.1, 2.5 Hz, 1H), 8.30 (d, J 9.1 Hz, 1H), 7.55 ca. 7.58 (m, 4H), 7.35 ca. 7.44 (m, 6H); ¹³C NMR (CDCl₃, 75 MHz) δ 143.35, 139.74, 137.86, 137.79, 130.75, 130.66, 130.52, 129.67, 129.59, 129.54, 129.41, 129.26, 128.60, 128.52, 128.23, 127.21, 127.12, 125.40, 124.25, 123.07; IR (KBr) ν_max/cm^-1: 3439, 1614, 1520, 1397, 1340, 699.

2,3-Di-p-tolylquinoxaline (3d)¹⁸

White solid, mp147-148 ºC, ¹H NMR (CDCl₃, 300 MHz): δ 8.14 ca. 8.15 (m, 2H), 7.73 ca. 7.76 (m, 2H), 7.44 (d, J 8.0, 4H), 7.16 (d, J 7.9, 4H), 2.38 (s, 6H); ¹³C NMR (CDCl₃, 75 MHz) δ 153.17, 140.83, 138.44, 136.06, 129.40, 129.35, 128.80, 128.68, 21.05; IR (KBr) ν_max/cm^-1: 2914, 1608, 1467, 1397, 1339, 1217, 759.

6-Methyl-2,3-di-p-tolylquinoxaline (3e)¹⁸

White solid, mp135-136 ºC, ¹H NMR (CDCl₃, 300 MHz): δ 8.03 (d, J 8.5 Hz, 1H), 7.92 (s, 1H), 7.58 (d, J 1.8Hz, 1H), 7.41 (d, J 7.9 Hz, 4H), 7.14(d, J 8.0 Hz, 4H), 2.60 (s, 3H), 2.36 (s, 6H); ¹³C NMR (CDCl₃, 75 MHz) δ 153.02, 152.29, 140.89, 139.82, 139.29, 138.30, 138.22, 139.19, 131.69, 129.40, 128.64, 128.30 127.64, 21.60, 21.05; IR (KBr) ν_max/cm^-1: 3428, 2913, 1611, 1448, 1337, 822.

6-Nitro-2,3-di-p-tolylquinoxaline (3f)¹⁸

Yellow solid, mp 168-169 ºC, ¹H NMR (CDCl₃, 300 MHz): δ 9.04 (d, J 2.2 Hz, 1H), 8.49 (dd, J 9.1, 2.3 Hz, 1H), 8.25 (d, J 9.2 Hz, 1H), 7.45 ca. 7.49 (m, 4H), 7.18 (d, J 7.9, 4H), 2.39 (s ,6H); ¹³C NMR (CDCl₃, 75 MHz) δ 156.29, 155.67, 143.53, 140.00, 139.81, 135.36, 130.58, 129.79, 129.69, 129.16, 125.52, 123.00, 21.42; IR (KBr) ν_max/cm^-1: 3428, 2918, 1611, 1523, 1402, 1343, 828.

2,3-Bis(4-methoxyphenyl)quinoxaline (3g)¹⁸

White solid, mp 146-148 ºC, ¹H NMR (CDCl₃, 300 MHz): δ 8.13 (dd, J 6.3, 3.4 Hz, 2H), 7.73 (dd, J 6.3, 3.4 Hz, 2H), 7.50 (d, J 8.6 Hz, 4H), 6.88 (d, J 8.6Hz, 4H), 3.84 (s, 6H); ¹³C NMR (CDCl₃, 75 MHz) δ 159.81, 152.71, 140.74, 131.38, 130.92, 129.23, 128.68, 113.45, 55.00; IR (KBr) ν_max/cm^-1: 2930, 2836, 1605, 1511, 1344, 1293, 1246, 1173, 833.

2,3-Bis(4-methoxyphenyl)-6-methylquinoxaline (3h)¹⁸

White solid, mp 121-123 ºC, ¹H NMR (CDCl₃, 300 MHz): δ 8.00 (d, J 8.2 Hz, 1H), 7.90 (s, 1H), 7.46 ca. 7.56 (m, 5H), 6.87 (d, J 7.4 Hz, 4H), 3.83 (s, 6H), 2.59 (s, 3H); ¹³C NMR (CDCl₃, 75 MHz) δ 159.94, 152.84, 152.11, 141.07, 139.96, 139.47, 131.83, 131.19, 131.15, 128.47, 127.82, 113.68, 55.27, 21.86; IR (KBr) ν_max/cm^-1: 2925, 2835, 1606, 1343, 1292, 1248, 1175, 833.

2,3-Di-(furan-2-yl)quinoxaline (3i)¹⁸

Pale brown solid, mp 131-132 ºC, ¹H NMR (CDCl₃, 300 MHz): δ 8.12 (dd, J 6.3, 3.4 Hz, 2H), 7.72 (dd, J 6.3, 3.4 Hz, 2H), 7.61 (s, 2H), 6.66 (d, J 3.3 Hz, 2H), 6.55 (s, 2H); ¹³C NMR (CDCl₃, 75 MHz) δ 150.74, 144.13, 142.53, 140.53, 130.30, 129.02, 112.93, 111.85; IR (KBr) ν_max/cm^-1: 3103, 1566, 1484, 1397, 1328, 755.

2,3-Di(furan-2-yl)-6-methylquinoxaline (3j)¹⁸

Brown solid, mp 112-114 ºC, ¹H NMR (CDCl₃, 300 MHz): δ 8.01 (d, J 8.6 Hz, 1H), 7.91 (s, 1H), 7.56 ca. 7.61 (m, 3H), 6.55 ca. 6.62 (m, 4H), 2.58 (s, 3H); ¹³C NMR (CDCl₃, 75 MHz) δ 150.58, 143.78, 143.66, 140.78, 140.39, 132.45, 128.29, 127.63, 112.48, 112.23, 111.54, 21.59; IR (KBr) ν_max/cm^-1: 3106, 2918, 1485, 1323, 747.

2,3-Diethylquinoxaline (3k)²⁴

Yellow oil, ¹H NMR (CDCl₃, 300 MHz): δ 7.99 ca. 8.02 (m, 2H), 7.62 ca. 7.65 (m, 2H), 3.03 (q, J 7.5 Hz, 4H), 1.41 (t, J 4.5 Hz, 6H); ¹³C NMR (CDCl₃, 75 MHz) δ 156.87; 140.65, 128.28, 128.12, 28.00, 12.20; IR (KBr) ν_max/cm^-1: 2972, 1709, 1451, 1286, 764.

2,3-Diethyl-6-methylquinoxaline (3l)²⁴

Pale yellow oil, ¹H NMR (CDCl₃, 300M Hz): δ 7.85 (d, J 8.5, 1H), 7.74 (s, 1H), 7.43 (d, J 8.5, 1H), 2.98 (dd, J 14.9, 7.5 Hz, 4H), 2.51 (s, 3H), 1.37 (t, J 7.5 Hz, 6H); ¹³C NMR (CDCl₃, 75 MHz) δ 156.72, 155.90, 138.56, 130.49, 127.59, 127.05, 27.96, 27.91, 21.33, 12.32, 12.28; IR (KBr) ν_max/cm^-1: 2971, 1622, 1565, 1453, 821.

7-Bromo-2,3-diphenylpyrido[3,2-b]pyrazine (3m)³¹

Pale yellow solid, mp 154-155 ºC, ¹H NMR (CDCl₃, 300 MHz): δ 9.08 (d, J 1.4 Hz, 1H), 8.58 (t, J-1.0Hz, 1H), 7.48 ca. 7.58 (m, 4H), 7.24 ca. 7.32 (m, 6H); ¹³C NMR (CDCl₃, 75 MHz) δ 156.17, 155.14, 154.77, 139.04, 137.77, 137.47, 129.87, 129.50, 129.35, 129.26, 128.12, 127.91; IR (KBr) ν_max/cm^-1: 3396, 3057, 1393, 1331, 697.

(2,3-Diphenylquinoxalin-6-yl)(phenyl)methanone (3n)¹⁸

White solid, mp 139-140 ºC, ¹H NMR (CDCl₃, 300 MHz): δ 8.54 (s, 1H), 8.28 (s, 2H), 7.91 (d, J 7.4 Hz, 2H), 7.63 (d, J 7.3 Hz, 1H), 7.51 ca. 7.57 (m, 6H), 7.34 ca. 7.40 (m, 6H); ¹³C NMR (CDCl₃, 75 MHz) δ 195.74, 155.12, 154.58, 142.96, 140.18, 138.63, 138.30, 137.20, 132.41, 130.09, 129.80, 129.74, 129.25, 129.11, 128.48, 128.33; IR (KBr) ν_max/cm^-1: 3432, 3052, 1661, 1438, 1396, 1344, 1270, 698.

2,3-Diphenyl-[g]quinoxaline (3o)¹⁸

Yellow solid, mp188-189 ºC, ¹H NMR (CDCl₃, 300 MHz): δ 8.75.(s, 2H), 8.10 ca. 8.13 (m, 2H), 7.55 ca. 7.60 (m, 6H), 7.36 ca. 7.40 (m, 6H); ¹³C NMR (CDCl₃, 75 MHz) δ 153.87, 138.84, 137.64, 133.75, 130.59, 129.52, 129.06, 128.96, 128.69, 128.45, 128.23, 127.93, 127.53, 127.24, 126.91, 126.41, 126.18, 125.29; IR (KBr) ν_max/cm^-1: 3421, 3051, 1439, 1344, 1257, 1170, 695.

2,3-Di(furan-2-yl)-6-nitroquinoxaline (3p)³²

Orange solid, mp 164-166 ºC, ¹H NMR (CDCl₃, 300 MHz): δ 8.98 (d, J 2.4 Hz, 1H), 8.47 (dd, J 9.2, 2.5 Hz, 1H), 8.20 (d, J 9.2 Hz, 1H), 7.65 ca. 7.68 (m, 2H), 6.85 (dd, J 16.4, 3.5 Hz, 2H), 6.60 ca. 6.63 (m, 2H); ¹³C NMR (CDCl₃, 75 MHz) δ 149.81, 149.75, 147.57, 145.14, 144.66, 144.34, 143.84, 142.63, 138.87, 130.10, 124.99, 123.99, 123.28, 115.04, 114.17, 112.10, 111.96; IR (KBr) ν_max/cm^-1: 3388, 1574, 1522, 1477, 1337, 749.

7-Bromo-2,3-(furan-2-yl)pyrido[3,2-b]pyrazine (3q)³³

Dark brown solid, mp134-136 ºC, ¹H NMR (CDCl₃, 300 MHz): δ 9.05 (d, J 2.4 Hz, 1H), 8.56 (d, J 2.4 Hz, 1H), 7.58 ca. 7.62 (m, 2H), 7.04 (d, J 3.5 Hz, 1H), 6.76 (d, J 3.5 Hz, 1H), 6.55 ca. 6.59 (m,2H); ¹³C NMR (CDCl₃, 75 MHz) δ 154.92, 150.00, 149.77, 147.16, 144.76, 144.66, 143.43, 138.63, 135.64, 120.77, 114.76, 114.36, 112.08, 111.86; IR (KBr) ν_max/cm^-1: 3112, 1570, 1479, 1413, 1322, 758.

2,3-Diethyl-6-nitroquinoxaline (3r)³³

Pale yellow solid, mp 98-100 ºC, ¹H NMR (CDCl₃, 300 MHz): δ 8.78 (d, J 2.5 Hz, 1H), 8.31 (dd, J 9.1, 2.5 Hz, 1H), 8.03 (d, J 9.1 Hz, 1H), 3.04 (q, J 7.4 Hz, 4H), 1.41 (t, J 7.4, 6H); ¹³C NMR (CDCl₃, 75 MHz) δ 160.42, 159.42, 146.51, 143.19, 139.30, 129.65, 124.60, 121.60, 28.13, 27.91, 11.30, 11.24; IR (KBr) ν_max/cm^-1: 3430, 2976, 1614, 1525, 1339, 1275, 739.

2-(4-Chlorophenyl)-3-phenylquinoxaline (3s)³⁴

White solid, mp140-142 ºC, ¹H NMR (CDCl₃, 300 MHz): δ 8.16 ca. 8.20 (m, 2H), 7.78 ca. 7.81 (m, 2H), 7.47 ca. 7.53 (m, 4H), 7.31 ca. 7.39 (m, 5H); ¹³C NMR (CDCl₃, 75 MHz) δ 140.96, 140.86, 138.49, 137.17, 134.79, 130.91, 129.89, 129.83, 129.46, 128.91, 128.85, 128.68, 128.22, 128.16; IR (KBr) ν_max/cm^-1: 3429, 3054, 1590, 1484, 1396, 1341, 806.

Acknowledgments

We are grateful to the National Key Technology R&D Program (No. 2007BAI34B00) and the Natural Science Foundation of Zhejiang Province (No. Y4080107) for financial support.

Supplementary Information

Supplementary data are available free of charge at http://jbcs.sbq.org.br, as PDF file.

References

1. Sakata, G.; Makino, K.; Kuraswa, Y.; Heterocycles 1988, 27, 2481; He, W.; Meyers, M. R.; Hanney, B.; Spada, A.; Blider, G.; Galzeinski, H.; Amin, D.; Needle, S.; Page, K.; Jayyosi, Z.; Perrone, H.; Bioorg. Med. Chem. Lett. 2003, 13, 3097; Kim, Y. B.; Kim, Y. H.; Park, J. Y.; Kim, S. K.; Bioorg. Med. Chem. Lett. 2004, 14, 541.

2. Dell, A.; William, D. H.; Morris, H. R.; Smith, G. A.; Feeney, J.; Roberts, G. C. K.; J. Am. Chem. Soc. 1975, 97, 2497; Bailly, C.; Echepare, S.; Gago, F.; Waring, M.; Anti-Cancer Drug Des. 1999, 15, 291; Sato, S.; Shiratori, O.; Katagiri, K. J.; Antibiot. 1967, 20, 270.

3. Brock, E. D.; Lewis, D. M.; Yousaf, T. I.; Harper, H. H.; The Procter and Gamble Company: USA, WO 9951688, 1999.

4. Justin Thomas, K. R.; Marappan, V.; Jiann, T. L.; Chang-Hao, C.; Yu-ai, T.; Chem. Mater. 2005, 17, 1860.

5. Dailey, S.; Feast, J. W.; Peace, R. J.; Saga, R. C.; Till, S.; Wood, E. L.; J. Mater. Chem. 2001, 11, 2238; Brien, D. O.; Weaver, M. S.; Lidzey, D. G.; Bradley, D. D. C.; Appl. Phys. Lett.. 1996, 69, 881.

6. Jonathan, L. S.; Hiromitsu, M.; Toshihisa, M.; Vincent, M. L.; Hiroyuki, F.; Chem. Commun. 2002, 862.

7. Jonathan, L. S.; Hiromitsu, M.; Toshihisa, M.; Vincent, M. L.; Hiroyuki, F.; J. Am. Chem. Soc. 2002, 124, 13474; Peter, P. C.; Gang, Z.; Grace, A. M.; Carlos, H.; Linda, M. G. T.; Org. Lett. 2004, 6, 333.

8. Sascha, O.; Rudiger, F.; Synlett 2004, 1509.

9. Louis, S.; Marc, M. G.; Jory, J. W.; Joseph, P. B.; J. Org. Chem. 2003, 68, 4179.

10. Porter, A. E. A. In Comprehensive Heterocyclic Chemistry; Katritsky, A. R.; Rees, C. W.; eds.; Pergamon: Oxford, 1984, 157; Woo, G. H. C.; Snyder, J. K.; Wan, Z. K.; Prog. Heterocycl. Chem. 2002, 14, 279; Brown, D. J. In The Chemistry of Heterocyclic Compounds; Taylor, E. C.; Wipf, P., eds.; John Wiley& Sons: New Jersey, 2004.

11. Antoniotti, S.; Donach, E.; Tetrahedron Lett. 2002, 43, 3971.

12. Zhao, Z.; Wisnoski, D. D.; Wolkenberg, S. E.; Leister, W. H.; Wang, Y.; Lindsley, C. W.; Tetrahedron Lett. 2004, 45, 4873; Gris, J.; Glisoni, R.; Fabian, L.; Fernández, B.; Moglioni, A. G.; Tetrahedron Lett. 2008, 49, 1053; Mohsenzadeh, F.; Aghapoor, K.; Darabi, H. R.; J. Braz. Chem. Soc. 2007, 18, 297.

13. Wu, Z.; Ede, N. J.; Tetrahedron Lett. 2001, 42, 8115.

14. Robinson, R. S.; Taylor, R. J. K.; Synlett 2005, 1003.

15. Raw, S. A.; Wilfred, C. D.; Taylor, R. J. K.; Org. Biomol. Chem. 2004, 2, 788.

16. Venkatesh, C.; Singh, B.; Mahata, P. K.; IIa, H.; Junjappa, H.; Org. Lett. 2005, 7, 2169.

17. Bhosale, R. S.; Sarda, S. R.; Ardhapure, S. S.; Jadhav, W. N.; Bhusare, S. R.; Pawar, R. P.; Tetrahedron Lett. 2005, 46, 7183.

18. Steven, A. R.; Cecilia, D. W.; Richard, J. K. T.; Chem. Commun. 2003, 2286; Bhosale, R. S.; Sarda, S. R.; Ardhapure, S. S.; Jadhav, W. N.; Bhusare, S. R.; Pawar, R. P.; Tetrahedron Lett. 2005, 46, 7183; More, S. V.; Sastry, M. N. V.; Wang, C. C.; Yao, C. F.; Tetrahedron Lett. 2005, 46, 6345.

19. More, S. V.; Sastry, M. N. V.; Yao, C. F.; Green Chem. 2006, 8, 91.

20. Heravi, M. M.; Taheri, S.; Bakhtiari, K.; Oskooie, H. A.; Catal. Commun. 2007, 8, 211.

21. Darabi, H. R.; Mohandessi, S.; Aghapoor, K.; Mohsenzadeh, F.; Catal. Commun. 2007, 8, 389.

22. Huang, T. K.; Wang, R.; Shi, L.; Lu, X. X.; Catal. Commun. 2008, 9, 1143.

23. Heravi, M. M.; Tehrani, M. H.; Bakhtiari, K.; Oskooie, H. A.; Catal. Commun. 2007, 8, 1341.

24. Fang, D.; Gong, K.; Fei, Z.; Zhou, X.; Liu, Z.; Catal. Commun. 2008, 9, 317; Potewar, T. M.; Ingale, S. A.; Srinivasan, K. V.; Synth. Commun. 2008, 38, 3601.

25. Kumar, A.; Kumar, S.; Saxena, A.; De, A.; Mozumdar, S.; Catal. Commun. 2008, 9, 778.

26. Shaabani, A.; Maleki, A.; Chin. J. Chem. 2007, 25, 818.

27. Darabi, H. R.; Tahoori, F.; Aghapoor, K.; Taala, F.; Mohsenzadeh, F.; J. Braz. Chem. Soc. 2008, 19, 1646.

28. Xu, H.; Liao, W. M.; Li, H. F.; Ultrason. Sonochem. 2007, 14, 779.

29. Mason, T. J.; Peters, D.; Practical Sonochemistry, Power Ultrasound Uses and Applications, 2^nd ed., Ellis Horwood Publishers: Chicherster, 2002.

30. Chen, J. X.; Su, W. K.; Wu, H. Y.; Liu, M. C.; Jin, C.; Green Chem. 2007, 9, 972; Xiong, W.; Chen, J. X.; Liu, M. C.; Ding, J. C.; Wu, H. Y. Su, W. K.; J. Braz. Chem. Soc. 2009, 20, 367 and references cited therein.

31. Yin, L. X.; Liebscher, J.; Synthesis 2005, 8, 1345.

32. Srinivas, C.; Kumar, C. N. S. S. P.; Rao, V. J.; Palaniappan, S.; J. Mol. Catal. A: Chem. 2007, 265, 227.

33. Kawakami, J.; Duncton, M.; Sherman, D.; He, H. Y.; Kiselyov, A.; Pytowski, B.; WO pat. 2,005,007,099 2005. (CA 142:176856).

34. Ebisawa, A.; Inoue, T.; Jpn. Kokai Tokkyo Koho 09,188,874 1997. (CA 127:142616).

Received: February 12, 2009

Web Release Date: September 11, 2009

Supplementary Information

Figure S1 - Click to enlarge

Figure S2 - Click to enlarge

Figure S3 - Click to enlarge

Figure S4 - Click to enlarge

Figure S5 - Click to enlarge

Figure S6 - Click to enlarge

Figure S7 - Click to enlarge

Figure S8 - Click to enlarge

Figure S9 - Click to enlarge

Figure S10 - Click to enlarge

Figure S11 - Click to enlarge

Figure S12 - Click to enlarge

Figure S13 - Click to enlarge

Figure S14 - Click to enlarge

Figure S15 - Click to enlarge

Figure S16 - Click to enlarge

Figure S17 - Click to enlarge

Figure S18 - Click to enlarge

Figure S19 - Click to enlarge

Publication Dates

• Publication in this collection
  14 Oct 2011
• Date of issue
  2009

History

• Accepted
  11 Sept 2009
• Received
  12 Feb 2009