INTRODUCTION:
The quinoxaline skeleton is a building block for the preparation of substances with pronounced biological activities, such as antimycobacterial,[I] antidepressant[II] and antitumor drugs.[III] Moreover, quinoxaline ring is a part of various antibiotics, such as Echinomycin, Levomycin and Actinoleutin that are known to inhibit growth of gram positive bacteria[IV] and are active against various transplantable tumors.[V] They have been also used as building blocks for the synthesis of organic semiconductors. [VI] Quinoxaline derivatives have been also applied for metal cations extraction. [VII] A number of methods have been developed for the synthesis of substituted quinoxalines.[VIII-XIII] The most common method for their preparation relies on the condensation of an aryl 1,2-diamine with a 1,2-dicarbonyl compound.8
Furthermore, there are several synthetic routes toward quinoxalines, including Bi-catalyzed oxidative coupling of epoxides with ene-1,2- diamines,[IX] heteroannulation of nitroketene N,S-aryliminoacetals with POCl3,[X] cyclization of α-arylimino oximes of α-dicarbonyl compounds, [XI] and from α-hydroxy ketones via a tandem oxidation process using Pd(OAc)2 or RuCl2-(PPh3)3-TEMPO[XII] as well as MnO2. [XIII] Nevertheless, most of these methods suffer one or more of the following drawbacks: unsatisfactory yield, long reaction time, critical product isolation procedures, the use of expensive and detrimental metal precursors, harsh reaction conditions, and no agreement with the green chemistry protocols, which limit their use. As part of our ongoing program to develop more efficient and environmentally benign methods for organic transformations using economic and ecofriendly materials as catalysts and reagents, [XIV] we have looked into the synthesis of quinoxaline derivatives via the condensation of 1,2-diamines with α-diketones in the presence of catalytic amounts of oxalic acid at room temperature (Scheme 1). It is worth noting that this present method has not the above mentioned drawbacks.
Scheme 1. Condensation of benzene-1,2-diamine with benzil.
EXPERIMENTAL:
All the research chemicals and solvents were procured from commercial sources and purified by standard procedures described in the literature. O- Phenylene diamine and benzil were purchased from Merck laboratory. All the chemicals and solvents used in studies were of GR grade, dried and purified before use. Melting points were obtained using capillary method and are uncorrected. The purification of synthesized compounds was performed by recrytallization with appropriate solvent system. Infrared spectra were recorded on FTIR spectrophotometer. The purity of the compounds was checked using TLC technique; spots were developed by exposure to iodine vapours and UV cabinet. Ultraviolet spectra were taken on UV 2401 (PC) S 220V double beam UV Spectrophotometer. Nuclear Magnetic Resonance spectra were recorded with AVANCE 300MHz, using CDCl3.
MATERIALS:
Methanol, Rectified Spirit, benzil and O-phenylene diamine, and ZnCl2, CoCl2, Oxalic acid, Ni(OAc)2, Mn (OAc) 2 were supplied from Rankem Chemical Co. and they were used as received.
METHODS:
SCHEME-IA: Preparation of 2-3 diphenyl quinoxalines from O- phenylenediamines and Benzil without Catalyst.
2.1 gm of benzyl and 1.1 gm of o-phenylenediamine were dissolved in 8.00 ml of rectified spirit separately by slightly warming in water bath. Mix both solutions in a beaker, slightly warm in water bath. Add sufficient water, allow cooling for 15 mins.
SCHEME-IB: Preparation of 2-3 diphenyl quinoxalines without using Catalyst in sonicator.
2.1 gm of benzyl and 1.1 gm of o-phenylenediamine were dissolved in 8.00 ml of rectified spirit separately in sonicator by little rise in temperature. Mix both solutions in a beaker, and placed in sonicator for 15 min at 60oC. Add sufficient water, allow cooling for 15 mins. Recrystallize the crude product from ethanol.
SCHEME-II-VI: synthesis of 2, 3- Diphenyl quinoxaline by using catalysts (ZnCl2, CoCl2, Oxalic acid, Ni(OAc)2, Mn (OAc) 2) in sonicator
2.1 gm of benzyl and 1.1 gm of o-phenylenediamine were dissolved in 8.00 ml of rectified spirit separately in sonicator by little rise in temperature. Mix both solutions in a beaker with appropriate catalyst, and placed in sonicator for few min at 60oC. Add sufficient water, allow cooling for 15 mins. After isolation of the product, the filtrate was extracted with CHCl3 (2×30 mL). The aqueous layer (including oxalic acid) was separated, and its solvent was evaporated to obtain pure oxalic acid. The recycled catalyst was used for the next run under identical reaction conditions.
Thin layer chromatography
In order to ascertain the purity and homogeneity of the synthesized compounds the thin layer chromatography was carried out. The solution of the compound was prepared in ethanol (10 mg/10 ml) silica gel G used as an adsorbent. The most suitable solvent system used, are given below in Table 1. The spots were located by using UV chamber. Rf value for each compound was calculated.
Table 1: Mobile phase used for determination of Rf value of synthesized compounds.
|
Sr. No |
Mobile Phase |
|
1 |
Pet. Ether: EtOAc (90:10) |
RESULTS AND DISCUSSION:
In order to find a suitable catalyst for the synthesis of quinoxalines from 1,2-diamines and α-Diketones, the reaction of benzene-1,2-diamine with benzil by using sonicator, was chosen as a model to get 2,3- diphenyl quinoxaline and its behavior was studied in the presence of various catalysts. The results are displayed in Table 1. As it can be seen from Table 2, oxalic acid as an organic catalyst afforded the better results with respect to the inorganic catalysts. Physiochemical parameters of synthesized compound like- physical constant (Melting point), Rf value, its calculated molecular weight and CHN analysis is mention in Table 3
Table 2:- The sonication of benzene-1, 2-diamine (1.1 gm) with benzil (2.1 gm) in the presence of different catalysts (0.2 mmol, 20 mol %) in EtOH.
|
Entry |
Catalyst |
Time (min) |
Yield (%) |
|
1 |
- |
25 |
22.2 |
|
2 |
ZnCl2 |
15 |
93 |
|
3 |
CoCl2 |
20 |
70 |
|
4 |
Ni(OAc)2 |
20 |
78 |
|
5 |
Oxalic acid |
10 |
81 |
|
6 |
Mn(OAc)2 |
15 |
68 |
Spectroscopical studies:
The synthesized compound was subjected to heir sprectroscopical studies, the outcome of all compounds are relatively similar and as described below:
λmax: 292 nm
IR: Characteristic IR (KBr) bands found at: 3065, 1441, 1395, 768, (νmax/cm-1).
1H NMR: (500 MHz, Chloroform) δ 8.06, 8.06, 8.01, 8.01, 8.01, 8.01, 7.53, 7.53, 7.43, 7.43, 7.43, 7.43, 7.41, 7.41.
MS (m/z): 282.12 (100.0%), 283.12 (21.8%), 284.12 (2.4%)
Table 3: Synthesized conjugates with physical constants
|
Method No |
M.P. (0C) |
Rf VALUE |
Mol. Wt. |
EXPERIMENTAL ANALYSIS |
|
1 |
122-126 |
0.72 |
282.34 |
C, 85.08; H, 5.00; N, 9.92 |
|
2 |
122-124 |
0.71 |
282.34 |
C, 85.08; H, 5.00; N, 9.92 |
|
3 |
122-124 |
0.72 |
282.34 |
C, 85.08; H, 5.00; N, 9.92 |
|
4 |
122-126 |
0.72 |
282.34 |
C, 85.08; H, 5.00; N, 9.92 |
|
5 |
122-124 |
0.72 |
282.34 |
C, 85.08; H, 5.00; N, 9.92 |
|
6 |
122-126 |
0.72 |
282.34 |
C, 85.08; H, 5.00; N, 9.92 |
CONCLUSIONS:
In summary, we have developed an efficient method for the synthesis of quinoxaline derivatives via the reaction of 1,2-diamines with α-diketones by using sonicator. This new strategy has several advantages, such as excellent yield, short reaction time, low cost, simple experimental as well as isolation procedures, and finally, it is in agreement with the green chemistry protocols.
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Received on 19.04.2011 Modified on 03.05.2011
Accepted on 13.05.2011 © AJRC All right reserved
Asian J. Research Chem. 4(6): June, 2011; Page 887-889-706