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to study the effect of solvent on the synthesis of novel quinoxaline derivatives

Research Article Open Access
Poonam M More*, Shradha R Jedge, Sandip S Kshirsagar and Rajesh J Oswal
JSPM’s Charak College of Pharmacy and Research, Gat No720/1&2, Nagar Road, Wagholi, Pune-07, India
*Corresponding author: Poonam M More
JSPM’s Charak College of Pharmacy and Research
Gat No720/1&2, Nagar Road
Wagholi, Pune-07, India
E-mail: sanpals24@rediffmail.com
 
Received August 24, 2012; Published October 31, 2012
 
Citation: More PM, Jedge SR, Kshirsagar SS, Oswal RJ (2012) To Study the Effect of Solvent on the Synthesis of Novel Quinoxaline Derivatives. 1:408. doi:10.4172/scientificreports.408
 
Copyright: © 2012 More PM, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
 
Abstract
 
Reaction of 2,3-diketoquinoxaline in presence of ferric chloride and hydrazine hydrate gives 2-hydrazino- 3-hydroxyquinoxalin (4) which on reaction with various aldehydes in appropriate solvent gives 3-Hydroxy-2-(2’- hydroxy-3-methoxy benzylidine) hydrazine quinoxaline. The structure of compounds 5a-5l has been confirmed by IR and TLC data.
 
Keywords
 
Quinoxaline; NMDA receptor
 
Introduction
 
Quinoxaline and its analogs constitute the active class of the compound. Further 3-Hydroxy-2-(2’-hydroxy-3-methoxy benzylidine) [1-3] hydrazine quinoxaline are well famed for their antimicrobial activities. In the light of above fact we have synthesized some 3-Hydroxy-2-(2’-hydroxy-3-methoxy benzylidine) [4,5] hydrazine quinoxalines new derivatives incorporating quinoxaline moiety with the hope to possess better antimicrobial activity [4-7].
 
Experimental
 
All melting points are determined in an open capillary tube and are found to be uncorrected. IR spectra (cm-1) were recorded on a FTIR- 8400 s Shimadzu system. Proton Magnetic Resonance spectra (HNMR) were recorded on Bruker AC-300F NMR spectrometer (300 MHz) using DMSO-δ 6 as solvent and Tetramethyl silane (TMS) as internal standard. All chemical shifts values were recorded as δ (ppm). Success of each step was confirmed by TLC during reaction.
 
2,3-Diketoquinoxaline
 
o-Phenylene diamine (0.25 mole), oxalic acid (0.36 mole) and ferric chloride (0.1 g) and dimethyl formamide (10 ml) were placed in microwave in 800W, and cooled. The solid separated was filtered and washed. m.p. <300°C, yield 82%; colorless needle shaped crystals. IR (KBr) 3350, 2928, 1658, 1593, 1028 cm-1.
 
3-chloroquinoxaline-2-ol
 
2,3-Diketoquinoxaline (0.01 mole) on treatment with ferric chloride and zinc metal yielded 2-chloro-3-hydroxy quinoxaline.
 
2-Hydrazino 3-hydroxy quinoxaline (4)
 
The chloro compound (0.015 mole) and hydrazine hydrate (0.02 mole 99%) in ethanol (25 ml) microwave at 800W for few min. to yield 2-hydrazino 3-hydroxy quinoxaline. m.p 170°C, yield 89%. The product was recrystallized with ethanol to give a pure compound. IR (KBr) 3288 cm-1 and 3186 cm-1 (for NH of NH2), 1625 cm-1 (C=N Str), 1191 cm-1 (-C-N Str). 1H NMR (DMSO-δ6): δ 2.52 (s, 3H) 4.23 (br, 2H, NH2 D2O exchangeable) 6.2 (br, 1H, NH) 7.77 and 7.87 (d, 2H, quinoxaline ring protons) ppm C13 NMR showed signals at δ 127.98 (d, C-5), 129.68 (d, C-7), 127.69 (d, C-8), 140.98 (s, C-9), 141.18 (s, C-10), 147.07 (s, C-2), 152.00 (s, C-3), 127.98 (d, C-5).
 
3-Hydroxy-2-(2’-hydroxy-3-methoxy benzylidene) hydrazine quinoxaline (5)
 
A mixure of compound 4 (0.01 mole) and benzaldehyde (0.01 mole) in methanol was placed in microwave at 800W. The product separated was isolated and neutralized with sodium bisulphate to get 3-hydroxy- 2-(4’-methoxybenzelidene) hydrozino yield 76%; m.p 184°C.
 
IR (KBr) 3540 cm-1 (- NH Str), 1623 cm-1 (C=N Str), 1498 cm-1 (-NH def) 1045 cm-1 (-CoCH3). 1H NMR (DMSO-δ6): 3.89 (s, 3H, -OCH3), 7.0 and 7.22 (d, 2H, quinoxaline ring protons), 8.4 (s, 1H, N=CH-), and 9.11 (s, 1H, -NH-N) ppm. Above synthesis were performed using different solvent as mentioned in table 1, and found difference in their reaction time and percentage yield. Synthesis of 2-substituted thiazolidione derivatives Catalyzed by FeCl3 has been performed as per above method and were shown in table 2.
 
Table 1: The effect of solvent and Temperature on the Synthesis of 2,3-Diketoquinoxaline.
 
Table 2: The Synthesis of 2-substituted thiazolidione derivatives Catalyzed by FeCl3 under Ultrasound.
 
Results and Discussion
 
For the Synthesis of 2,3-Diketoquinoxaline we were used different solvents at same reaction temperature found different reaction time with multiple yields. It can shows that 1,4-dioxane, ethanol and DMF gives highest yield at low reaction time under microwave synthesis.
 
The chemical synthesis initiate with the reaction of o-Phenylene diamine 1 and Oxalic acid were mixed in ferric chloride and dimethyl formamide to yield 2,3-Diketoquinoxaline 2, which on treatment with ferric chloride and zinc metal yielded 2-chloro-3-methyl quinoxaline (3). The chloro compound and hydrazine hydrate were placed in microwave for few min. to yield 2-hydrazino 3-hyroxy quinoxaline (4). A mixture of compound 4 and different aromatic aldehydes in methanol placed in microwave to give 3-hydroxy-2-(arylidene hydrazine) quinoxaline 5. The structure of all the newly quinoxaline derivatives were confirmed on the basis of their spectral and analytical data. The IR spectrum of compound 4 showed a sharp doublet at 3286 cm-1 and 3188 cm-1 due to to the NH stretch of NH2. On condensation with carbonyl compounds, these bands disappear and a band at 3298 cm-1 is observed due to NH stretch of NH=N group. The 1H NMR spectrum of compound 4 showed a broad signal at δ 4.25 due to NH2 protons and at δ 6.5 the characteristics of NH proton. The compound on condensation with carbonyl compounds the hydrazone formed shows the disappearance of NH2 proton signals, while that of NH proton signal is shifted up field at δ 9.12 as a result of de shielding effect of CH=N- group. The proton of azomethane group is lead to a sharp singlet at δ 8.4. The multiplet signals at δ 6.9-8.4 are the characteristics of the aromatic protons. A sharp signal appears at δ 3.93, the characteristics of the protons of -OCH3. In case of 2-p-anisyl-3-(3’hydroxyquinoxalin-2’yl-amino) 4 thiazolidinone gave a sharp signal at δ 3.69 the characteristics of the proton of –CH2 group of 4-thiazolidinone ring. The NMR spectrum of 1-N-(3’-hydroxyquinoxalin-2’yl-amino) 4- mehoxybenylidine-3- chloro-2-azetidinone gave two doublets at δ 4.67 and δ 3.75 due to the two hydrogen atoms on C3 and C4 carbon atom respectively.
 
Acknowledgement
 
Authors are thankful to University of Pune for providing analytical facility and also thankful to Prof. T.J.Sawant for providing necessary facilities and continuous encouragement.
 
 
References