Struct Chem (2006) 17:91–95DOI 10.1007/s11224-006-9003-7

ORIGINAL PAPER

Synthesis and crystal structure analysis of2-(4-methyl-2′-biphenyl)-4-amino-1,2,4-triazole-3-thiolS. Nanjunda Swamy · Basappa · S. Naveen ·B. Prabhuswamy · M. A. Sridhar ·Javaregowda S. Prasad ·Kanchugarakoppal S. Rangappa

Received: 24 August 2005 / Accepted: 1 November 2005 / Published online: 11 May 2006C© Springer Science+Business Media, Inc. 2006

Abstract The bioactive compound 2-(4-methyl-2′-bip-henyl)-4-amino-1,2,4-triazole-3-thiol, F.W. 282.09 was syn-thesized, characterized by spectroscopic techniques andconfirmed by X-ray crystal structure analysis. The ti-tle compound crystallizes in monoclinic class under thespace group P21/c with cell parameters, a = 11.273(3) Å,b = 17.245(1) Å, c = 7.413(1) Å, β = 97.742(5)◦ and Z = 4.The structure exhibits inter-molecular hydrogen bonding ofthe type N–H···S.

Keywords 1,2,4-Triazole . Crystal structure . Tautomerism

Introduction

Compounds of 1,2,4-triazole derivatives exhibit diverse phar-macological activities [1] such as fungicidal, insecticidal,bactericidal, herbicidal, anti-tumour [2], anti-inflammatory[3], CNS stimulant [4]. They also find applications as dyes,lubricants, analytical reagents [5] and antiviral agents [6].The complexes containing 1,2,4-triazole ligands possessspecific magnetic properties [7]. The compound losartanpotassium, a non-peptide small molecule bearing biphenylaromatic group and imidazole, combines an angiotensin II

S. Nanjunda Swamy · .Basappa · B. Prabhuswamy ·K. S. Rangappa (�)Department of Studies in Chemistry, University of Mysore,Manasagangotri, Mysore 570006, Indiae-mail: rangappaks@yahoo.com, rangappaks@chemistry.uni-mysore.ac.in

S. Naveen · M. A. Sridhar · J. S. PrasadDepartment of Studies in Physics, University of Mysore,Manasagangotri, Mysore 570006, India

receptor (type AT1) antagonist and diuretic property. In thelight of the above observations, the incorporation of theactive 1,2,4-triazole nucleus to the biphenyl ring is part ofour continued effort towards the synthesis and study of thebiological properties of condensed nitrogen and sulphurheterocycles [8–10]. We report the synthesis and X-raycrystal structure analysis of a possible bioactive molecule,2-(4-methyl-2′-biphenyl)-4-amino-1,2,4-triazole-3-thiol (4).

Experimental

The synthesis of 2-(4-methyl-2′-biphenyl)-4-amino-1,2,4-triazole-3-thiol 4 was obtained by using 4-methyl-2′-cyano-biphenyl as shown in Scheme 1. The synthesis of the titlecompound 4 involves the oxidation of nitrile to the corre-sponding acid 2. The 4-methyl-2′-biphenyl carboxylic acidis esterified and hydrazinated to obtain the pure crystallinehydrazide 3. The crystalline hydrazide was reacted with car-bon disulphide in the presence of alcoholic KOH to obtainpotassium salt of thiocarbohydrazide followed by the addi-tion of the hydrazine hydrate to obtain the title compound 4.

The melting points were determined on SELACO-650hot stage apparatus and are uncorrected. IR (KBr) spectrawere recorded on a Jasco FT/IR-4100 Fourier transform in-frared spectrometer, 1H NMR were recorded on ShimadzuAMX 400, spectrometer by using CDCl3 as solvent and TMSas an internal standard (Chemical shift in ppm). Elementalanalyses were obtained on a vario-EL instrument. Thin layerchromatography (TLC) was conducted on 0.25 mm silica gelplates (60F254, Merck). Visualization was made with ultra-violet light. All extracted solvents were dried over Na2SO4

and evaporated with a BUCHI rotary evaporator. Reagentswere obtained commercially and used as received.

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92 Struct Chem (2006) 17:91–95

Scheme 1

Synthesis and characterization

General procedure for the preparationof 4-methyl-2′-biphenyl carboxylic acid 2

Compound 4-methyl-2′-cyano-biphenyl (2 g, 10 m mol) anda solution of 30% NaOH solution (10 mL) in 10 mL methanolwas refluxed for 3–4 h. After completion of the reaction (ben-zene: ethyl acetate: 7.5:2.5 used for TLC), the reaction masswas cooled, 6–8 mL of water was added. The reaction masswas acidified using 50% concentrated HCl and extractedwith diethyl ether thrice (10 × 3 mL), washed with water,dried with anhydrous sodium sulphate. Solvent was distilledcompletely. n-hexane (5–6 mL) was added, cooled to 5–8◦C,solid obtained was filtered. MP:146◦C.

General procedure for the preparationof 2-(p-tolyl)-methyl benzoate

4-methyl-2′-biphenyl carboxylic acid (1.5 g) was refluxed for3–4 h with 6.5 mL of methanol containing five to six drops ofconcentrated H2SO4. After completion of the reaction (ben-zene: ethyl acetate: 7:3 used for TLC), the reaction mass wasextracted with dichloromethane thrice (10 × 3 mL). The sol-vent was evaporated under vacuum, oily compound obtainedwas taken for the next step.

General procedure for the preparationof 2-(p-tolyl)-benzoic hydrazide 3

2-(p-tolyl)-methyl benzoate (1.0 g, 4.42 m mol) in 6–8 mL ethanol was added dropwise with 100% NH2NH2·H2O(6.5 mL), refluxed for 8–10 h. After completion of the re-action (benzene: ethyl acetate: 6.5:3.5 used for TLC), thesolvent was evaporated under vacuum completely. To theresidue obtained, 5–6 mL of water was added, stirred at 5–8◦C and filtered. Pure crystalline compound was obtained byrecrystallizing in ethyl acetate. M. P: 75◦C.

General procedure for the preparation of 2-(4-methyl2′-biphenyl)-4-amino-1, 2,4-triazole-3-thiol 4

Compound 3 (1 g, 4.42 m mol) with CS2 (0.6 mL) and KOH(0.56 gm) in ethanol was refluxed for 8–10 h. The reac-tion mixture was cooled to room temperature for 2 h. Thesolid was filtered, washed with chilled methanol to obtainpure salt, potassium 2-(p-tolyl)-benzoic hydrazide thiofor-mate. Salt obtained was refluxed with 100% NH2NH2.H2O(4–5 mL) for 4–6 h. After completion of the reaction (ben-zene:ethyl acetate: 7:3 used for TLC), the reaction mass wascooled to room temperature and acidified with 50% concen-trated HCl, filtered at cold condition. The white crystals wereobtained by slow evaporation technique using ethyl acetateas solvent, M. P:185◦C.

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Table 1 Experimental X-ray crystallography data of molecule 4

Empirical formula C15H14N4 SFormula weight 282.36Temperature (K) 293(2)Wavelength (Å) 0.71073Crystal system MonoclinicSpace group P21/cCell dimensionsa (Å) 11.2730(3)b (Å) 17.2450(15)c (Å) 7.4130(10)b (◦) 97.742(5)Volume (Å3) 1428(2)Z 4Density (calculated) (Mg/m3) 1.313Absorption coefficient (mm−1) 0.222F(0 0 0) 592Theta range for data collection (◦) 2.17–32.40Index ranges − 16 ≤ h ≤ 16

− 25 ≤ k ≤ 25− 8 ≤ l ≤ 8

Reflections collected 7415Independent reflections 4030 [R(int) = 0.0267]Refinement method Full-matrix least-squares on F2

Data/restraints/parameters 4030/0/183Goodness-of-fit on F2 1.097Final R indices [I>2σ (I)] R1 = 0.0611, ωR2 = 0.1885R indices (all data) R1 = 0.0860, ωR2 = 0.2184Extinction coefficient 0.056(8)Largest diff. peak and hole (eÅ−3) 0.431 and − 0.481

IR(cm−1): 3325–3327 (–NH2), 495 (s, C=N), 1245 (C=S),2616 (S–H)1H NMR: 7.92–7.98 (dd, 2H, Ar–H), 7.73–7.78 (t, 1H,Ar–H), 8.1 (d, 1H, Ar-H), 7.4–7.46 (d, 2H, Ar–H), 14.3(s, 1H, S–H),C H N S Calcd. for C15H14N4S: C, 63.8; H, 5.0; N, 19.84;S, 11.36 Found: C, 63.64; H, 5.12; N, 19.65; S, 11.14.

X-ray structure determination of 4

A single crystal of the title compound with dimensions of0.3 mm × 0.3 mm × 0.2 mm was chosen for X-ray diffrac-tion studies. The measurements were made on a DIPLaboImage Plate system with graphite-monochromated MoKα

radiation. Thirty-six frames of data were collected in os-cillation mode with an oscillation range of 5◦. Image pro-cessing and data reduction were done by using Denzo [11].The reflections were merged with Scalepack. The peakswere successfully indexed with primitive monoclinic lat-tice. The structure was solved using maXus [12–14]. All thenon-hydrogen atoms were revealed in the first map itself.Initially, full-matrix least-squares refinement for 4030 re-flections with isotropic temperature factors for all the non-hydrogen atoms was carried out. Subsequent refinements

Table 2 Atomic coordinates and equivalent thermal parameters ofthe non-hydrogen atoms

Atom x y z Ueq

C1 0.5000(2) 0.2195(1) 0.4319(3) 0.0497(6)C2 0.6197(2) 0.2054(2) 0.4242(4) 0.0561(6)C3 0.6542(2) 0.1404(2) 0.3373(4) 0.0571(6)C4 0.5687(2) 0.0884(1) 0.2586(3) 0.0489(5)C5 0.4474(2) 0.1002(1) 0.2668(3) 0.0386(4)C6 0.4129(2) 0.1671(1) 0.3549(3) 0.0392(4)C7 0.2862(2) 0.1827(1) 0.3713(3) 0.0385(4)N8 0.2159(2) 0.1373(1) 0.4649(3) 0.0398(4)N9 0.2561(2) 0.0722(1) 0.5678(3) 0.0656(7)C10 0.1038(2) 0.1696(1) 0.4548(3) 0.0405(4)N11 0.1138(2) 0.2323(1) 0.3525(3) 0.0462(5)N12 0.2249(2) 0.2418(1) 0.2991(3) 0.0459(5)S13 − 0.0120(6) 0.1373(4) 0.5545(9) 0.0515(2)C14 0.3582(2) 0.0420(1) 0.1857(3) 0.0390(4)C15 0.3718(2) − 0.0355(1) 0.2370(3) 0.0510(6)C16 0.2881(3) − 0.0904(1) 0.1676(4) 0.0550(6)C17 0.1894(2) − 0.0710(1) 0.0446(3) 0.0479(5)C18 0.1766(2) 0.0062(1) − 0.0092(3) 0.0478(5)C19 0.2589(2) 0.0619(1) 0.0614(3) 0.0440(5)C20 0.0983(3) − 0.1309(2) − 0.0299(4) 0.0638(7)

Note. [Ueq = (13

) ∑i

∑j Ui j (ai × a∗

j )(ai × a j )].

Table 3 Bond lengths and bond angles

Atoms Length Atoms Length

C1–C2 1.380(4) N8–N9 1.399(2)C1–C6 1.400(3) C10–N11 1.334(3)C2–C3 1.376(4) C10–S13 1.679(7)C3–C4 1.386(4) N11–N12 1.373(3)C4–C5 1.393(3) C14–C15 1.392(3)C5–C6 1.405(3) C14–C19 1.394(3)C5–C14 1.489(3) C15–C16 1.386(3)C6–C7 1.475(3) C16–C17 1.382(4)C7–N12 1.305(3) C17–C18 1.392(3)C7–N8 1.367(3) C17–C20 1.508(3)N8–C10 1.374(3) C18–C19 1.387(3)

Atoms Angle Atoms Angle

C2–C1–C6 120.4(2) N11–C10–N8 102.2(2)C3–C2–C1 120.2(2) N11–C10–S13 130.5(2)C2–C3–C4 120.0(2) N8–C10–S13 127.3(2)C3–C4–C5 121.2(2) C10–N11–N12 114.2(2)C4–C5–C6 118.4(2) C7–N12–N11 104.0(2)C4–C5–C14 119.8(2) C15–C14–C19 117.8(2)C6–C5–C14 121.8(2) C15–C14–C5 119.6(2)C1–C6–C5 119.8(2) C19–C14–C5 122.6(2)C1–C6–C7 118.8(2) C16–C15–C14 120.7(2)C5–C6–C7 121.3(2) C17–C16–C15 121.8(2)N12–C7-N8 110.1(2) C16–C17–C18 117.6(2)N12–C7–C6 125.1(2) C16–C17–C20 121.6(2)N8–C7–C6 124.8(2) C18–C17–C20 120.8(2)C7-N8–C10 109.4(2) C19–C18–C17 121.1(2)C7–N8–N9 124.7(2) C18–C19–C14 121.1(2)C10–N8–N9 125.7(2)

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Fig. 1 Representation oftautomerism of compound 4

were carried out with anisotropic thermal parameters fornon-hydrogen atoms and isotropic temperature factors forhydrogen atoms, which were placed at chemically acceptablepositions. The residuals finally converged to R1 = 0.0611.Details of crystal data and refinement are given inTable 1. (for full crystallographic data refer to CCDC no.281806).

Results and discussion

The final positional coordinates with equivalent isotropictemperature factors for all the non-hydrogen atoms are givenin Table 2. Table 3 gives the bond distances and bond an-gles of the non-hydrogen atoms.The bond lengths and bond

angles are in good agreement with the standard values. Thetitle compound shows strong tautomerism. It tautomerisesfrom N-amino thiol A to B as shown in the Fig. 1. The ORTEPof the molecule at 50% probability is shown in Fig. 2.The dihedral angles between the planes 1 & 2, 1 & 3 and2 & 3 are 64.21(12)◦, 53.68(12)◦ and 53.14(12)◦, respec-tively. The structure exhibits intermolecular hydrogen bondof the type N–H···S. The intermolecular hydrogen bond isN11–H11···S13 (3.332(2) Å, 131◦) with symmetry code x;1/2 − y; − 1/2 + z. The packing of the molecules of 4 whenviewed along the a-axis indicates that the molecules are inter-linked by hydrogen bonds as shown in Fig. 3. This polymer-like structure may play an important role in the biologicalactivity of the compound and the studies pertaining to theseare underway.

Fig. 2 ORTEP of the molecule4 at 50% probability

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Fig. 3 Packing of themolecules of 4 along the a axis.The dashed lines represent theintermolecular hydrogen bonds

Acknowledgements The authors are grateful to Department ofScience and Technology, Government of India, New Delhi for financialsupport under the projects DV6/15/DST/2005-06 and SP/I2/FOO/93.The CHNS data obtained from the instruments by DST-FIST and NMRResearch Institute, IISC, Bangalore for the NMR spectral analysisis greatly acknowledged. One of the authors Nanjunda Swamy S.thanks CSIR, Govt. of India for the award of CSIR-Senior ResearchFollowship.

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