Novel Dihydroquinoline Derivatives Facile Synthesis

apologue Dihydroquinoline Derivatives Facile SynthesisFacile discount of unused dihydroquinoline-3,3-dicarbonitriles in the comportment of glacial acetic acrimonious as catalyst beneath solvent-free conditionsMasoud Nasr-Esfahani* and Elham KanaaniDepartment of Chemistry, Yasouj University, Yasouj, IranAbstr telephone numberA serial of novel dihydroquinoline derivatives were synthesized development malononitrile, 2-aminobenzoic demigod and benzaldehydes in the front man of a catalytic amount of acetic hot, without the usage of any additional co-catalyst, under solvent-free conditions. The reaction is characterized by high efficiency, easy workup, wide purification of the products and availability of catalyst.Keywords Dihydroquinoline derivatives, Acetic panelling, Malononitrile, 2-Aminobenzoic acid, solvent-free creationHeterocyclic compounds including nitrogen, have an important role in organic chemistry. Among these compounds, the quinoline derivatives have attracted great attention because of their coating in biological and pharmacological fields. They act as antimalarial,1-3 anti-psychotic,4 antihypertensive,5 anti-parasitic,6 anthelmintic,7 antitubercular,8 antiasthmatic,9 antifungals,10,11 anticancer,12 anti-inflammatory,13 anti-HIV,14 anti-AIDS,15 and antineoplastic.16A few promising compounds with quinoline ring system be shown as 13 compounds (Fig. 1). Furthermore, quinoline derivatives can be used in the discount of fungicides, biocides, alkaloids and flavoring agents,17 as soundly as these compounds find use in manufacturing a wide variety of food and lake colors. They could generate a sharp green electroluminescence and have the high quantum efficiency of emission in the blue and the green region.18 Therefore, in regard to these observations and importance of pharmaceutical and biological of these compounds, herein we study the solvent-free entailment of novel dihydroquinoline derivatives in presence of glacial acetic acid as cata lyst.In the context of green chemistry, the development of clean technologies is rattling important in organic and medicinal chemistry. The use of available and nontoxic catalysts and replacing solution reactions with solvent-free ones atomic number 18 some cases that can help reduction and elimination of harmful effects of chemical reactions.19The volatile temperament and toxicity of many organic solvents that argon widely used for organic reactions have propounded a stark threat to the environment. Therefore, in recent years, the design of solid-state reaction has received much attention from the eco-friendly synthesis viewpoint. Solvent-free techniques represent several significant synthetic benefits including savings in money, time and products, and simplicity of the experimental unconscious process and work-up technique.In recent times application of nontoxic catalysts such as glacial acetic acid in chemical reactions has been an area of interest. Acetic acid is an clarif ied polar protic solvent and can act as a mild and good catalyst for the promotion of the organic reactions. Other factors that stimulate the use of acetic acid include the price of catalyst and simplicity of the work-up procedure.In this research, we report the synthesis of 4-oxo-2-aryl-1,2-dihydroquinoline-3,3(4H)-dicarbonitriles, that involves both steps, in presence of glacial acetic acid under solvent-free conditions. AcOH is an efficient, inexpensive and available acid and in recent decades has been recognizing as a mild catalyst in organic synthesis.20Results and DiscussionIn lengthening of our studies in the development of the synthetic methodologiesfor the preparing of fine chemicals and heterocyclic compounds of biological importance,21-25 herein, we were interested in reporting the synthesis of novel dihydroquinoline derivatives in the presence of the glacial acetic acid as a mild and efficient catalyst. This synthesis involves two steps firstly, 2-(2-aminobenzoyl) mal ononitrile intermediate (6) was synthesized via the glacial acetic acid-catalyzed reaction of 2-aminobenzoic acid (4) with malononitrile (5) under solvent-free condition. Subsequently, the novel dihydroquinoline derivatives (8)were prepared by addition of benzaldehyde derivatives (7) to the compartmentalisation reaction and attack on the intermediate 6 and followed by intermolecular cyclization (Scheme 1, Table 1).The main advantage ofthis reaction that was carried out with AcOH is that the percentage of peripheral products was low and the recrystallization was as well much easier.The 1H proton magnetic resonance spectrum of 8b showed a singlet identified as CH ( = 4.263 ppm), and a signal at 7.831 ppm for NH group. The signals appear in the 7.308-8.197 ppm are assigned for smelling(p) rings protons. The proton decoupled 13CNMR spectrum of 8b compound exhibited 14 distinct resonances that confirmed the proposed structure.The infrared frequency spectra (IR) of these compounds s how NH bonds appearing at 3388-3453 cm-1. The bands found at 2210-2229 cm-1 are attributed to the CN groups. The intense bands appearing at 1695-1700 cm-1 are assigned to carbonyl groups. The peaks in the region of 1025-1350 cm-1 are assigned for (C-N) stretching vibration.The proposed mechanism in which acetic acid has catalyzed this conversion was depicted in Scheme 3. Initially, the proton of acetic acid activates carbonyl group of 2-aminobenzoic acid (3) to achieve intermediate 9 and thus increases the electrophilicity carbonyl carbon of acid. In the following, nucleophilic addition of intermediate 10 was done by intermediate 9 and following the passing game of H2O intermediate 6 was produced. In the next step, with the addition of an aromatic aldehyde to the reaction mixture, the carbonyl group of aldehyde was activated by acetic acid to give intermediate 11 thus increases the electrophilicity of carbonyl carbon of aldehyde 7 . The reaction proceeds by nucleophilic addition o f the amino group of 6 to the activated aldehyde to afford intermediate 12 and following loss of H2O intermediate 13 was produced. Finally, with intermolecular cyclization of intermediate 13 the product 8 was produced (Scheme 2).ConclusionsIn summary, a novel class of dihydroquinoline derivatives 8 was obtained using 2-aminobenzoic acid, malononitrile and aromatic aldehydes in presence of AcOH as catalyst under solvent-free conditions. These novel compounds as potentially useful compounds with possible biological and pharmaceutical activities can be employ in various fields such as medicinal and agricultural areas. The most important features of this communications protocol are an inexpensive and available catalyst, simple purification, easy work-up, with the desired products being isolated in excellent yields.Experimental SectionChemicals and reagents were purchased from Merck, Fluka, and Aldrichchemical companiesand were used without further purification. IR spectra were recorded applying a FT-IR JASCO-680 spectrophotometer in KBr with absorptions in cm-1. The 1H NMR (400 MHz) and 13C NMR (100 MHz) spectra were recorded on a Bruker 400 MHz Ultrashield spectrometer in DMSO-d6 solution with TMS as an internal standard. Mass spectra were recorded by the Fisons Trio 1000 (70 ev). All melting points were measured on a Barnstead Electrothermal (BI 9300) apparatus in open capillary tubes and all are uncorrected. The progress of the reaction was monitored by thin layer chromatography (TLC).General procedure for the synthesis of dihydroquinoline derivatives using AcOHFirstly, a mixture of malononitrile 5 (1.0 mmol, 0.06 g), 2-aminobenzoic acid 4 (1.0 mmol, 0.14 g) and glacial acetic acid (o.2 ml), was heated at 80 C under solvent-free conditions with conjunction stirring for the 6 h (reactions were monitored by TLC). Subsequently, with the formation of intermediate 6, aromatic aldehyde 7 (1.0 mmol) was added to the reaction mixture, and the mixture was stirred unde r reflux for the suitable time (reactions were monitored by TLC). After completion of the reaction, ethyl ethanoate was added and the obtained mixture filtered and then washed with water. After that, the obtained crude products were recrystallized in ethyl acetate to afford the unmingled product in 70-87% yields (table 1). The products were characterized by IR, 1H NMR, 13C NMR and mass spectroscopic methods.2-(4-nitrophenyl)-4-oxo-1,2-dihydroquinoline-3,3(4H)-dicarbonitrile (8a)Brown solid, Mp 238-240 CIR (KBr, cm-1) 3440, 3165, 2225, 1695, 1509, 1417, 1344, 1203, 1160, 833, 572 1H NMR (400 MHz, DMSO-d6) 8.39 (t, 2H, J = 7.8 Hz, aromatic CH), 8.30 (d, 1H, J = 7.6 Hz, aromatic CH), 8.15 (t, 2H, J = 7.8 Hz, aromatic CH), 8.07 (s, 1H, NH), 7.91 (t, 1H, J = 8.4 Hz, aromatic CH), 7.69-7.63 (m, 2H, aromatic CH ), 4.62 (s, 1H, CH) 13C NMR (100 MHz, DMSO-d6) 203.81, 162.54, 149.23, 148.75, 138.52, 131.44, 129.52, 126.17, 124.65, 118.15, 116.19, 111.06, 60.24, 56.02 MS (m/z) 318.1C17H10N4O3 +, 293.1 C16H11N3O3+, 246.1 C16H12N3+, 234.1 C16H12NO+, 184.1 C11H8N2O+, 277, 170, 127, 101, 89, 75.Acknowledgements We are grateful to the Yasouj University for supporting this work.SUPPORTING INFORMATIONExperimental method, IR, 1H NMR, 13C NMR, Mass and MP for this article can be found via the Supplementary Content section of this articles webpage.Broom, A. 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Synthesis of 4-oxo-2-aryl-1,2-dihydroquinoline-3,3(4 H)-dicarbonitriles using AcOH doorRProductTime 1 (h)Time 2 (h)Yield (%) aMp (C)8a4-NO26587238-2408b4- Cl6687201-2048c2,4- Cl26684177-1798d4- Br6874217-2258e4- OMe6977206-2088f4- Me6969140-142a Isolated yield.Scheme 2 Proposed mechanism for the formation of dihydroquinolines 8.