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Micron Particles of AlN/Al: Efficient,Novel, and Reusable HeterogeneousCatalyst for the Synthesis ofBis(indolyl)methanesSunil U. Tekale a , Suresh S. Shisodia a , Sushma S. Kauthale a ,Vivekanand B. Jadhav a , Nilesh S. Kanhe b , Sudha V. Bhoraskar b &Rajendra P. Pawar aa Department of Chemistry, Deogiri College, Aurangabad, Indiab Department of Physics, University of Pune, Ganeshkhind, Pune,IndiaAccepted author version posted online: 02 Jan 2013.Version ofrecord first published: 04 Apr 2013.

To cite this article: Sunil U. Tekale , Suresh S. Shisodia , Sushma S. Kauthale , Vivekanand B. Jadhav ,Nilesh S. Kanhe , Sudha V. Bhoraskar & Rajendra P. Pawar (2013): Micron Particles of AlN/Al: Efficient,Novel, and Reusable Heterogeneous Catalyst for the Synthesis of Bis(indolyl)methanes, SyntheticCommunications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,43:13, 1849-1858

To link to this article: http://dx.doi.org/10.1080/00397911.2012.674169

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MICRON PARTICLES OF AlN/Al: EFFICIENT, NOVEL,AND REUSABLE HETEROGENEOUS CATALYST FORTHE SYNTHESIS OF BIS(INDOLYL)METHANES

Sunil U. Tekale,1 Suresh S. Shisodia,1 Sushma S. Kauthale,1

Vivekanand B. Jadhav,1 Nilesh S. Kanhe,2

Sudha V. Bhoraskar,2 and Rajendra P. Pawar11Department of Chemistry, Deogiri College, Aurangabad, India2Department of Physics, University of Pune, Ganeshkhind, Pune, India

GRAPHICAL ABSTRACT

Abstract The present work introduces for the first time the catalytic utility of micron

particulate aluminium nitride (AlN/Al) as a novel and reusable heterogeneous catalyst

for the synthesis of bis(indolyl)methanes involving the electrophilic substitution of indoles

on aldehydes. The catalyst is recyclable and works without any significant change in its

catalytic activity.

Keywords Aluminium nitride; bisindolylmethanes; heterogeneous catalyst

INTRODUCTION

Recently the use of solid acids as heterogeneous catalysts has receivedconsiderable attention in different areas of organic synthesis. Among different het-erogeneous catalysts, the application of nano- and microparticulate materials forthe synthesis of heterocyclic molecules is an active and developing research area insynthetic organic chemistry.[1,2] The micro- and nanoparticulate material increasescatalytic activity because with decreasing particle size the surface-to-volume ratioincreases, leading to larger surface area for the reaction to occur. Thus, nanotechnol-ogy provides increased catalytic efficiency of heterogeneous catalysts for carrying outseveral organic transformations.

Although Lewis acid–catalyzed organic transformations are well reported inthe literature some of the traditional Lewis acids can be easily decomposed or deac-tivated and many times stoichiometric amounts of these reagents are essential for the

Received February 4, 2012.

Address correspondence to Rajendra P. Pawar, Department of Chemistry, Deogiri College,

Aurangabad 431005, MS, India. E-mail: rppawar@yahoo.com

Synthetic Communications1, 43: 1849–1858, 2013

Copyright # Taylor & Francis Group, LLC

ISSN: 0039-7911 print=1532-2432 online

DOI: 10.1080/00397911.2012.674169

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reaction. Strong Lewis acidic conditions are not favorable in organic synthesis,because the products formed during the reaction may decompose if the reaction iscontinued for a prolonged time.[3] Such traditional catalysts may be replaced bysome modern nanocatalysts.

Indoles and their derivatives constitute an important class of organic com-pounds possessing a broad spectrum of pharmacological and biological activitiesincluding cytotoxic, antibacterial, and insecticidal activities.[4,5] Bis(indolyl)-methanes, which are cruciferous substances normally found in marine sources,induce apoptosis in human cancer cells by modulating certain cancer-causingmetabolites and therefore serve as anticancer agents. They also have antioxidativeproperties.[6] Further, these compounds promote the beneficial estrogen metabolismin human being. Thus, bis(indolyl)methanes have become interesting targets fororganic chemists and pharmacologists.

The simple and the straightforward protocol for the synthesis of bis(indolyl)-methanes is the electrophilic substitution of indoles with aldehydes using differentcatalysts. Numerous methods have described the synthesis of bis(indolyl)methanesemploying protic acids and Lewis acids such as RuCl3 � 3H2O

[7] ZrOCl2,[8]

Cu(BF4)2 � SiO2,[9] Cu(NO3)3. 3H2O,[10] LaCl3.7H2O,[11] and ZrCl4,

[12] andsupported catalysts including HClO4-SiO4,

[13] fluoroboric acid on silica gel, [14]

PEG-supported sulfonic acid, [15] ionic liquids, [16,17] and zeolites. [18] Ultrasound-[19]

and microwave-[20] promoted synthesis are also well documented in the literature.Some Lewis acids are deactivated or sometimes decomposed by nitrogen of indoles.

Certain Lewis acids such as BF3 and AlCl3 also promote this reaction, but theygenerate harmful wastes that pose environmental problems. Many of these methodssuffer from several limitations such as use of toxic metal ions and hazardous sol-vents, high costs, use of corrosive reagents, and cumbersome workup procedure.Thus, the development of facile and environmentally friendly synthetic methodsfor the preparation of bis(indolyl)methanes constitutes an active area of investi-gation in pharmaceutical and organic synthesis.

In the present work, the reusability, ecofriendliness, and operational simplicityof micron particulate aluminium nitride (AlN) encouraged us to use it for the firsttime as a catalyst besides its utility in electronic, semiconductor, and opticalmaterials for the synthesis of heterocyclic molecules such as bisindolylmethanesvia the electrophilic substitution of indoles with different aldehydes and ketones.Herein, we report a novel protocol for the synthesis of biologically potentbis(indolyl)methanes using a catalytic amount of micron particulate AlN=Al(10wt%) (Fig. 1).

RESULTS AND DISCUSSION

The electrophilic substitution of indole with carbonyl compounds catalyzed bythe micron particulate AlN=Al catalyst afforded good to excellent yields of theproducts, and the conversions were observed to be dependent on the nature of sub-stituent present on the aromatic ring of aldehyde. The aromatic aldehydes havingelectron-withdrawing groups on the aromatic ring react faster than electron-donating groups. It was observed that ketones required a longer reaction time andthe corresponding products were obtained in moderate yields as compared to

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Table 1. Yield and reaction time of AlN=Al-catalyzed various bisindolylmethanes

Entry X Aldehyde=ketone Product Time (h) Yield (%) Mp (�C)

1 H 2 94 187–189

2 H 2 90 179–181

3 H 1.5 94 76–77

4 H 1.5 90 109–111

5 H 1.8 88 96–97

6 H 1.2 90 221–222

(Continued )

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Table 1. Continued

Entry X Aldehyde=ketone Product Time (h) Yield (%) Mp (�C)

7 H 1.4 84 86–88

8 H 1.5 88 110–111

9 H 1.5 89 120–122

10 H 2 83 319

11 Me 1.2 90 241–243

12 Me 2 87 207–209

(Continued )

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aldehydes (Table 1). This striking difference in the reactivity can be explained on thebasis of mild catalytic activity and bulkiness of the carbonyl group of ketones.

To optimize the reaction conditions, AlN=Al (10wt%) was employed as thecatalyst for the electrophilic substitution of indole on 4-chlorobenzadehyde in differ-ent solvents such as tetrahydrofuran (THF), CH2Cl2, MeOH, EtOH, PhCH3, andMeCN at 50 �C. Among these solvents, ethanol was observed to be efficient. Theeffect of reaction conditions on the reaction between indole and aldehydes issummarized in Table 2. The increasing amount of the catalyst resulted in nosignificant increase of yield after 10wt% of the catalyst: hence 10wt% of the catalystwas found to be appropriate. On establishing these conditions and applying thisprotocol, a series of bis(indolyl) methanes were obtained.

Table 1. Continued

Entry X Aldehyde=ketone Product Time (h) Yield (%) Mp (�C)

13 Me 1.5 87 246–248

14 H 2 63 162–164

15 H 2 53 238–240

Table 2. Effect of reaction conditions on the synthesis of bisindolylmethanesa

Entry Amount of catalyst (wt%) Time (h) Yield (%)

1 5 1.5 81

2 10 1.5 92

3 15 1.5 94

4 20 1.5 94

aReactions carried out on 4-chlorobenzaldehyde at 80 �C.

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EXPERIMENTAL

All the chemicals used were analytical-reagent AR grade (SD Fine Chemicals)and used without further purification. The catalyst was prepared by the thermalplasma method. Melting points of the products were recorded using capillaries openat one end and were uncorrected. 1H NMR spectra were recorded on a 400-MHzVarian spectrophotometer in CDCl3 solvent with tetramethylsilane (TMS) as thestandard. Infrared (IR) spectra were recorded on a Bruker Vector 22 FTIR spectro-photometer using KBr discs. Exact mass of the samples was recorded on Shimadzumass analyzer. The progress of the reaction was monitored by thin-layer chromato-graphy (TLC; 20% ethyl acetate:hexane).

Catalyst Synthesis

The catalyst was synthesized in a direct current-transferred arc thermal plasmareactor consisting of double-walled stainless steel material. A block of Al(�40mmdiameter and 20mm wide) was melted in liquid nitrogen at about 70–100 A currentand 50–60V operating voltage. The heat of plasma melts the Al block, which oncooling forms crystalline AlN.

Catalyst Characterization

The synthesized catalyst was characterized by scanning electron microscope(SEM) studies, Raman spectrum, and particle-size analysis (Beckmann CounterDesla particle-size analyzer).

Morphology of the catalyst. The morphology of the catalyst was studied bySEM analysis. Figure 2(a) shows the SEM image of the catalyst. The crystals containhexagonal AlN phase along with cubical-Al phase.

Particle-size determination. The average volume fractions of AlN and Alwere around 70% and 30% respectively, which was confirmed by the particle-sizeanalysis [Fig. 2(b)].

Raman analysis. Crystalline quality of postprocess AlN powder was ana-lyzed by Raman spectroscopy (Fig. 3). The space group of wurtzite AlN is C46v(P63mc) with all atoms occupying the C3V sites. Six Raman-active modes may bepresent: 1A1 (TO)þ 1A1 (LO)þ 1E1 (TO)þ 1E1 (LO)þ 2E2.[2] Postprocess AlNpowder sample was investigated using LabRamHR_Raman and MicroPLspectrom-eter with 514-nm Ar laser as excitation source. Figure 3 shows the Raman spectrumof postprocess AlN powder. The mode E2

1at 247.5 cm�1 is only observed under vis-ible (k¼ 514 nm) or near infrared (k¼ 785 nm) and the peak at 514.19 is acousticovertone.[21] Three Raman active phonon modes of A1 (TO), E2 (high), and E1

Figure 1. AlN=Al-catalyzed synthesis of bisindolylmethanes.

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(TO) at 611.82, 655.08, and 668.06 cm�1 respectively are observed. Observed Ramanpeaks are in good agreement with published results.[22] There are no other impuritypeaks observed in the spectrum.

Typical Procedure for the Condensation of Indoles with CarbonylCompounds Using Micron Particulate AlN/Al as the Novel Catalyst

In a typical model condensation reaction the micron particles of AlN=Al(10wt%) catalyst were added to a mixture of carbonyl compound (10mmol) andindole (20mmol) in ethanol (10mL) and the resulting mixture was refluxed at80 �C for an appropriate time as specified in Table 1. After completion of the reac-tion as indicated by TLC (20% ethyl acetate:hexane) the reaction mass was diluted

Figure 2. (a) Faceting hexagonal AlN crystals and some Al particles are embedded in the crystals.

Figure 2. (b) Particle-size distribution of the catalyst as determined by Beckmann counter particle-size

analyzer. (Figure is provided in color online.)

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with ethyl acetate and the catalyst was filtered off. The catalyst was washed severaltimes with ethyl acetate. The combined washings were concentrated and the pureproduct was obtained by recrystallization from ethyl acetate and petroleum ether.The recovered catalyst was subjected to further recycling study and works withoutsignificant change in its catalytic activity (Table 3).

All the products reported are known compounds and were identified by com-parison of their physical and spectral data with those of authentic samples known inliterature.

Compound 1a. Brown solid, mp 187–189 �C; IR(KBr) cm�1 3396, 3010,2832, 1610, 1509, 1454, 1418, 1336, 1219, 1094; 1H NMR (400MHz, CDCl3) dppm 3.78 (3H, s), 5.84 (1H, s), 6.66 (2H, d), 6.81 (2H, d), 7.02 (2H, t), 7.24–7.40(6H, m), 7.90 (2H, br, s, NH); ESMS¼ 352 (Mþ), Elemental analysis cal: C,81.79; H, 5.72; N, 7.95. Found: C, 80.94; H, 5.81; N, 7.65.

Compound 1d. Faint yellow solid, mp 109–111 �C; IR (KBr) cm�1 3407,3022, 2840, 1617, 1587, 1455, 1417, 1337, 743; 1H NMR (400MHz CDCl3) d ppm5.84 (s, 1H), 6.6 (d, 2H), 7.01 (dd, 2H), 7.2 (m, 4H), 7.4 (m, 6H), 7.95 (2H, br, s,NH), ESMS 429(Mþ). Elemental analysis cal: C, 68.84; H, 4.27; N, 6.98. Found:C, 68.66; H, 4.51; N, 6.58.

Table 3. Reusability of AlN=Al in the electrophilic substitution of indole

with 4-chlorobenzaldehyde

Run Time (h) Yield (%)a

1 2 94

2 2 92

3 2 91

4 2 89

aRefers to pure isolated product in the case of 4-chlorobenzaldehyde.

Figure 3. Raman spectrum of postprocessed AlN=Al crystals. (Figure is provided in color online.)

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Compound 2a. Yellow solid, mp 241–243 �C; IR (KBr) cm�1 3385, 3056,2913, 2844, 1618, 1593, 1515, 1461, 1424, 1385, 1341, 1223, 852; 1H NMR(400MHz CDCl3) d ppm 2.09 (s, 6H), 6.059 (s, 1H), 6.85–6.92 (m, 4H), 7.05 (d,2H), 7.25 (d, 2H), 7.4 (d, 2H), 7.83 (s, 2H), 8.1 (s, 2H) ESMS 395 (Mþ). Elementalanalysis cal: C, 75.93; H, 5.35; N, 10.63. Found: C, 73.77; H, 5.31; N, 10.64.

Compound 2b. Brown solid, mp 207–209 �C; IR (KBr) cm�1 3396, 3047,2958, 2995, 1608, 1510, 1458, 1340, 1218, 1033; NMR (400MHz CDCl3) d ppm2.05 (s, 6H), 3.8 (s, 3H), 5.95 (s, 1H), 6.8 (dd, 2H), 6.9 (dd,2H), 7.0 (m, 6H), 7.2(d, 2H), 7.73 (2H, br, s, NH); ESMS 409(Mþ). Elemental analysis cal: C, 82.07;H, 6.36; N, 7.36. Found: C, 81.9; H, 6.089; N, 7.02.

CONCLUSION

In summary, we have developed a simple, rapid, and efficient method for thesynthesis of bis(indolyl)methanes as biologically interesting compounds via the con-densation of indoles with carbonyl compounds using micron particulate aluminiumnitride as a novel catalyst in excellent yield. The striking features of this new protocolare cleaner reaction profiles, simple experimental and workup procedures, good con-versions, and shorter reaction times to afford the products in excellent yield.

ACKNOWLEDGMENTS

The authors acknowledge BRNS (DAE) India for funding the research project.We thank the principal of Deogiri College, Aurangabad (MS), India, for encourage-ment and providing laboratory facilities during the work. We are also sincerelythankful to S. V. Bhoraskar (ES), Department of Physics, University of Pune(MS), India, for providing the catalyst and valuable suggestions during the work.

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