A green and efficient multicomponent one-pot synthesis of Hantzsch polyhydroquinoline was achieved by

the condensation of aldehydes, dimedone, ethylacetoacetate and ammonium acetate at room temperature

using environmentally benign modified Montmorillonite supported Ni0-nanoparticles as catalyst. The well

dispersed Ni0-nanoparticles having a high surface to volume ratio have promising features for the reaction

such as easy removal of the catalyst, solvent-free, shorter reaction time, high product yields (about 95%)

and easy work up procedure. There is no significant effect of electron withdrawing or donating nature of

substituent on aldehydes in the formation of polyhydroquinoline derivatives

DUTTA , D

Dutta, D K

Saikia, L

IR@NEIST - North East Institute of Science and Technology (CSIR)

Catalysis Communications 19 (2012) 1–4Contents lists available at SciVerse ScienceDirectCatalysis Communicationsj ourna l homepage: www.e lsev ie r .com/ locate /catcomShort CommunicationEfﬁcient clay supported Ni0 nanoparticles as heterogeneous catalyst for solvent-freesynthesis of Hantzsch polyhydroquinolineLakshi Saikia, Dipanka Dutta, Dipak Kumar Dutta ⁎Materials Science Division, CSIR-North East Institute of Science and Technology, Jorhat, 785 006, Assam, India⁎ Corresponding author. Tel.: +91 376 2370 081; faxE-mail address: dipakkrdutta@yahoo.com (D.K. Dutt1566-7367/$ – see front matter © 2011 Elsevier B.V. Alldoi:10.1016/j.catcom.2011.12.013a b s t r a c ta r t i c l e i n f oArticle history:Received 27 October 2011Received in revised form 5 December 2011Accepted 8 December 2011Available online 16 December 2011Keywords:Hantzsch polyhydroquinolineDimedoneMontmorilloniteNi0-nanoparticlesA green and efﬁcient multicomponent one-pot synthesis of Hantzsch polyhydroquinoline was achieved bythe condensation of aldehydes, dimedone, ethylacetoacetate and ammonium acetate at room temperatureusing environmentally benign modiﬁed Montmorillonite supported Ni0-nanoparticles as catalyst. The welldispersed Ni0-nanoparticles having a high surface to volume ratio have promising features for the reactionsuch as easy removal of the catalyst, solvent-free, shorter reaction time, high product yields (about 95%)and easy work up procedure. There is no signiﬁcant effect of electron withdrawing or donating nature ofsubstituent on aldehydes in the formation of polyhydroquinoline derivatives.© 2011 Elsevier B.V. All rights reserved.1. Introduction4-Substituted 1,4-dihydropyridine (DHP) nucleus comprises alarge family of medicinally important compounds such as Ca2+ chan-nel blockers and some of the representative compounds of this classpossess acaricidal, insecticidal, bactericidal and herbicidal activities[1]. 1,4-Dihydropyridine possesses a variety of biological activities,such as, vasodilator, bronchodilator, anti-atherosclerotic, antitumor,geroprotective, hepatoprotective and antidiabetic agent [2–5]. Photo-catalytic oxidation of these compounds to pyridine derivatives consti-tutes the principal metabolic pathway in biological systems [6].Therefore, oxidative aromatization of DHPs has been a subject ofgreat interest of organic and medicinal chemists.Realizing the importance of polyhydroquinoline derivatives, severalsynthesis methods have been reported, like conventional heating [7],reﬂuxing in acetic acid [8] andmicrowave irradiation [9] and ultrasound[10]. Different other approaches for the syntheses of polyhydroquinolinederivatives using various catalysts, such as TMSCl [11], ionic liquids[12,13], L-proline [14], polymers [15], Yb(OTf)3 [16], Sc(OTf)3 [17],HClO4–SiO2 [18], cerric ammonium nitrate [19], heteropoly acid [20],p-TSA [21], HY-zeolite [22] and Mont. K10 [23] have also been reportedand some of the methods are associated with several shortcomingssuch as long reaction times, expensive reagents, harsh reaction condi-tions, low-product yields and the use of large quantity of volatile organicsolvents.In recent years, heterogeneous catalysts are gaining more impor-tance due to environmental and economic factors. The efﬁciency can: +91 376 2370 011.a).rights reserved.be improved by using nanosized catalysts because of their small sizeand large surface to volume ratio. It has been observed that Ni0-nanoparticles as catalysts offer great attention for awide range of appli-cations in organic transformations such as chemo-selective oxidativecoupling of thiols [24], reduction of aldehydes and ketones [25–27], hy-drogenation of oleﬁns [28] and support for hydrogen adsorption [29].Recently, the progress in the ﬁeld of solvent-free reactions is gainingsigniﬁcance because of their high efﬁciency, operational simplicity andenvironmentally benign processes. The multi-component reactionsare powerful tools in the modern drug discovery process and allowfast, automated and high throughput generation of organic compounds.The possibility of performing multi-component reactions undersolvent-free conditions with a heterogeneous catalyst could enhancetheir efﬁciency from an economic as well as an ecological point of view.Herein, wewould like to report Hantzsch polyhydroquinoline deriv-ative synthesis catalyzed by modiﬁed Montmorillonite supported Ni0-nanoparticles under solvent-free conditions, using aromatic aldehyde,dimedone, ethylacetoacetate and ammonium acetate. This method notonly preserves the simplicity, but also consistently gives the corre-sponding products in good to excellent yields. The modiﬁed clay sup-port has paved the way for better dispersion of the Ni0-nanoparticleswhich results in higher catalytic activity.2. Experimental2.1. Materials and methodNaturally occurring Montmorillonite contains impurities like silicasand, iron oxide, etc. and were puriﬁed by dispersion cum sedimenta-tion technique [30] to collect the b2 μm fraction. The reagents wereAr-CHO +O O+OC2H5O O NH4OAc/CatalystRT, No solventNHOCOOC2H5Ar1 432Scheme 1. Modiﬁed Montmorillonite supported Ni0-nanoparticle catalyzed synthesis of polyhydroquinone under solvent-free condition.2 L. Saikia et al. / Catalysis Communications 19 (2012) 1–4purchased from Acros Organic, Aldrich, Spectrochem and Merck andused as received from the supplier without further puriﬁcation.2.2. Preparation of clay supported Ni0-nanoparticlesThe preparation of modiﬁed Montmorillonite and supported Ni0-nanoparticles was carried out as reported earlier [31]. In a syntheticmethodology, a known amount of acid treated clay was taken in a100 ml beaker to which 10 ml (0.05 mM) aqueous solution of Ni(CH3COO)2 was added under vigorous stirring condition. The stirringwas continued for 5–6 h followed by evaporation to dryness in rotaryevaporator. The dry composite thus obtained was dispersed in 50 mlethylene glycol in a double necked round bottom ﬂask and reﬂuxedfor 6 h under nitrogen atmosphere to form an in situ solid productof Ni0-nanoparticles. The materials were recovered, washed withmethanol until it was free from ethylene glycol and dried at about40 °C for 12 h. The Ni loading in the supported catalysts wasdetermined by AAS analysis and found to be 4.85 wt.%.2.3. CharacterizationThe modiﬁed clay support and supported Ni0-nanoparticles werecharacterized by using PXRD, surface area analyzer and transmissionelectron microscopy (TEM) studies [32]. The powder XRD was recordedin Rigaku Ultima IV machine with Cu Kα radiation (λ=1.5409 Å).The textural properties measured by using Autosorb-1 (Quantachome,USA) and transmission electronmicroscopy (TEM) image were recordedon a JEOL JEM-2011 electron microscope.2.4. Synthesis of Hantzsch polyhydroquinoline derivativesTo a mixture of aromatic aldehyde (1 mmol), dimedone (1 mmol),ethylacetoacetate (1 mmol), and ammonium acetate (1.5 mmol) in a10 ml round bottom ﬂask, modiﬁed Mont. supported Ni0-nanoparticlecatalyst (25 mg) was added [Scheme 1]. Themixture was homogenizedand stirred at room temperature for 20–25 min, the progress of the re-action was monitored by thin layered chromatography. After comple-tion, 10 ml dichloromethane was added to the reaction mixture; the10 20 30 40Intensity (Counts/Sec)2 Theta (degree)Unactivated MontAt-MontFig. 1. Powder XRD pattern of unactivated and acid treated Montmorillonite (At-Mont.).catalyst was removed by ﬁltration and washed with dichloromethaneand acetone. Then, the liquid portion was extracted with ethyl acetateand water to remove any unreacted ammonium acetate; the organiclayer was dried over sodium sulfate and concentrated in vacuum toafford the crude products. The pure product was obtained by recrystal-lization from ethanol.3. Results and discussionThe XRD patterns of modiﬁed Montmorillonite (AT-Mont.) alongwith parent clay are shown in Fig. 1. The signiﬁcant structural modi-ﬁcation of Montmorillonite was reﬂected in their relative intensityand location of basal spacing (d001). The parent Montmorilloniteclay exhibited an intense basal peak at 2θ=7.06°, corresponding tobasal spacing of 12.5 Å. When the clay is activated with mineral acidunder controlled conditions for different time periods, the intensitydue to basal spacing (d001) decreases. From the XRD [Fig. 2], the char-acteristic peaks at 2θ=44°, 51.8° and 76° marked by their indices(111), (200) and (222) indicate the formation of Ni0 in the nanoparti-cles. The TEM study [Fig. 3] also reveals the formation of well dispersedNi0-nanoparticles of size less than 10 nm onmodiﬁedMontmorillonite.The supported Ni0-nanoparticles were investigated as a catalyst inthe synthesis of polyhydroquinoline derivatives i.e. condensation ofbenzaldehyde, dimedone, ethylacetoacetate, and ammonium acetate inthe presence of catalytic amount of Ni0-nanoparticles under solvent-free conditions at room temperature, which afforded product 4a in 95%yield [Table 1]. Such reaction occurs with a wide range of aromatic alde-hydes carrying either electron-donating or electron withdrawing sub-stituents in the ortho, meta, and para positions [Table 1]. The productswere established by comparing their melting points and the spectraldata for selected compounds. A possible explanation for the betteryield in solvent-free conditions is that the eutectic mixture having uni-form distribution of the reactants brings the reacting species in closeproximity to react than in solvent.To investigate the effects of solvent, the condensation reaction ofbenzaldehyde, dimedone, ethylacetoacetate, and ammonium acetatein various organic solvents at room temperature using 4.85 wt.% Ni0-nanoparticles as the catalyst was carried out. About 75% of the expected40 50 60 70 80150020002500300035004000Intensity (Counts/Sec)2 (degree)(111)(200)(222)Fig. 2. Powder XRD pattern of Ni0-nanoparticles supported onmodiﬁedMontmorillonite.Fig. 4. TEM of Ni0-nanoparticles recovered after run no. 1 of the Hantzsch condensation.Fig. 3. Representative TEM image of Ni0-nanoparticles on modiﬁed Montmorillonite.3L. Saikia et al. / Catalysis Communications 19 (2012) 1–4product 4a was obtained when the solvent was ethanol. Obviously, thepolar solvents such as ethanol and acetonitrile [Table 2] were muchbetter than non polar solvents. It was observed that in the presence ofsolvent the reaction takes more time to give high yields of productunder similar ratio of the reactants. This may be due to the competitiveadsorption of the solvent with the substrate molecule on the catalystsurface; hence reaction under solvent-free condition gives better yieldsin less time. The model reaction was carried out without any catalyst,but the product formation was in poor yield. Therefore, the catalystplays an important role in the success of the reaction in terms of rateand yields of Hantzsch polyhydroquinoline derivatives. The reactionwas also investigated with acid activated Mont. alone as catalyst andonly a negligible amount of product formationwas observed. Therefore,it is evident that supported Ni0-nanoparticles are the active sites.Table 1Modiﬁed Montmorillonite supported Ni0-nanoparticle catalyzed Hantzsch condensation.Sr. no. Ar Time (min) Yield %4a C6H5 15 954b 2-Cl.C6H4 15 914c 4-Cl.C6H4 15 884d 2-NO2.C6H4 20 874e 3-NO2.C6H4 15 854f 4-NO2.C6H4 20 894g 2-OH.C6H4 25 824h 4-OH.C6H4 25 874i 4-OMe.C6H4 20 924j 4-NMe2.C6H4 25 864k 2,4-Cl.C6H3 10 91Reaction condition: aromatic aldehydes (1 mmol), dimedone (1 mmol), ethylacetoacetate(1 mmol), ammonium acetate (1.5 mmol) and catalyst — 25 mg, room temperature.Table 2Effect of solvent on Hantzsch polyhydroquinoline synthesis.Solvent Reaction time (h) Yield (%)C2H5OH 4 75CH3CN 4 66Ph–CH3 4 40CH2Cl2 4 37No solvent 15 min 95Reaction condition: benzaldehyde (1 mmol), dimedone (1 mmol), ethylacetoacetate(1 mmol), ammonium acetate (1.5 mmol) and catalyst — 25 mg, room temperature.The reusability of supported Ni0-nanoparticles was tested undersimilar reaction condition. The catalyst was separated by ﬁltration,washed, dried and reused for Hantzsch condensation for a fresh reac-tion mixture up to run no. 4. The results in Fig. 5 showed that there isa decrease in product yield in subsequent reuse i.e. 95% in run no. 1 de-creased to 81% in run no. 4. The stability of the used catalyst recoveredafter run no. 1was investigated byHRTEM [Fig. 4] and there is no signif-icant change in size or shape of theNi0-nanoparticles. The nanoparticleswere well dispersed on the support and sized in the range of 3–10 nm.The effect of nickel loading of 1.0, 3.0 and 4.85 wt.% of the catalyst, onthe condensation reaction of benzaldehyde, dimedone, ethylacetoace-tate, and ammonium acetate was investigated and the correspondingyields of 41.3%, 69% and 95% were found. This clearly indicates that4.85 wt.% of Ni nanoparticles showed the best efﬁcacy.A comparison of the efﬁciency of catalytic activity of the modiﬁedMontmorillonite supported Ni0-nanoparticles with several previousmethods is presented in Table 3. The results show that the presentmethod is better compared to some of the earlier reports in termsof yield and reaction time.020406080100432% of Product YieldNo. of Run1Fig. 5. Reusability of supported Ni0-nanoparticles catalyst for the reaction of benzalde-hyde (1 mmol), dimedone (1 mmol), ethylacetoacetate (1 mmol), ammonium acetate(1.5 mmol) and catalyst — 25 mg.Table 3Comparison of catalytic activity of modiﬁedMontmorillonite supported Ni0-nanoparticleswith several known catalysts.Entry Condition Yield (%) Ref.1 Yb(OTf)3, EtOH, rt, 5 h 90 [16]2 Sc(OTf)3, EtOH, rt, 4 h 93 [17]3 CAN, EtOH, rt, 1 h 92 [19]4 p-TSA, EtOH, rt, 2 h 93 [21]5 HY-Zeolite, CH3CN, rt, 2 h 93 [22]6 Modiﬁed Mont. supported Ni0-nanoparticles,solvent-free, 0.25 h95 This work4 L. Saikia et al. / Catalysis Communications 19 (2012) 1–44. ConclusionIn conclusion, we have reported that four-component Hantzschcondensation reaction can effectively be performed with modiﬁedMontmorillonite supported Ni0 nanoparticle catalyst without usingany organic solvent. The yield of Hantzsch polyhydroquinoline deriva-tives obtained was up to 95% at room temperature. So, the present pro-cedure provides an efﬁcient and very simple method for the synthesisof polyhydroquinoline derivatives. The advantage of this method is itsfacile conditions and the product can be isolated very easily with excel-lent purity and that toowithout the use of column chromatography andthe catalyst is recyclable. The simplicity of the present process makes itan interesting alternative to other approaches. The catalyst is expectedto contribute to the development of environmentally benign methodsand forms a part of the nanomaterial chemistry.5. 1H NMR of few representative compoundsCompound 4a: 1H NMR (300 MHz, CDCl3) 0.96 (s, 3H), 1.07 (s, 3H),1.18 (t, 3H), 2.15–2.36 (m, 4H), 2.38 (s, 3H), 4.06 (q, 2H), 5.07(s, 1H), 5.8 (s, 1H), 7.06–7.34 (m, 5H);Compound 4e: 1H NMR (300 MHz, CDCl3) 0.94 (s, 3H), 1.08(s, 3H), 1.21 (t, 3H), 2.11–2.26 (m, 3H), 2.30–2.38 (m, 4H), 3.67(q, 2H), 5.15 (s, 1H), 6.88 (s, 1H), 7.34 (t, 1H);Compound 4i: 1H NMR (300 MHz, CDCl3) 0.96 (s, 3H), 1.07 (s, 3H),1.21 (t, 3H), 2.13–2.28 (m, 3H), 2.34–2.38 (m, 4H), 3.75 (s, 3H),4.07 (q, 2H), 5.03 (s, 1H), 5.82 (s, 1H), 6.72–6.76 (m, 2H),7.21–7.24 (m, 2H);Compound 4j: 1H NMR (300 MHz, CDCl3) 0.97 (s, 3H), 1.08 (s, 3H),1.23 (t, 3H), 2.10–2.26 (m, 3H), 2.30–2.37 (m, 4H), 2.87 (s, 6H),4.08 (q, 2H), 4.96 (s, 1H), 5.88 (s, 1H), 6.62 (d, J=8.2 Hz, 2H),7.16 (d, 2H).AcknowledgmentsThe authors are grateful toDr. P. G. Rao, Director, North East Instituteof Science and Technology (CSIR), Jorhat, Assam, India, for his kind per-mission to publish the work. Dr. P. Sengupta, Head, Materials ScienceDivision is acknowledged for his constant support and encouragement.Thanks are also due to CSIR, New Delhi for the ﬁnancial support(Network Project NWP 0010 and OLP-3700 Non Network Project).References[1] D. Mauzeral, F.H. Westheimer, Journal of the American Chemical Society 77 (1955)2261.[2] F. Bossert, H. Meyer, E. Wehinger, Angewandte Chemie (International Edition inEnglish) 20 (1981) 762.[3] H. Nakayama, Y. Kasoaka, Heterocycles 42 (1996) 901.[4] T. Godfraid, R. Miller, M. Wibo, Pharmacological Reviews 38 (1986) 321.[5] A. Sausins, G. Duburs, Heterocycles 27 (1988) 279.[6] D. Zhang, L.Z. Wu, L. Zhou, X. Han, Q.Z. Yang, L.P. Zhang, C.H. Tung, Journal of theAmerican Chemical Society 126 (2004) 3440.[7] S. Margarita, O. Estael, V. Yamila, P. Beatriz, M. Lourdes, Q. Margarita, L.S. Jose, N.Hector, B. 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Efficient clay supported Ni0 nanoparticles as heterogeneous catalyst for solvent-free

synthesis of Hantzsch polyhydroquinoline

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Efficient clay supported Ni0 nanoparticles as heterogeneous catalyst for solvent-free synthesis of Hantzsch polyhydroquinoline

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