Synthesis and Crystal Structure of N-(Biphenyl-2-thiocarbamoyl)-4-(1,3-dichlorophenyl) Carboxamide

AAMER SAEEDULRICH FL?RKE(Department of Chemistry, Quaid-I-Azam University, Islamaad 45320, Pakistan)(Department Chemie, Fakult?t fur Naturwissenschaften, Universit?t Paderorn, Warurgerstrasse 100, D-33098 Paderorn, Germany)

Synthesis and Crystal Structure of N-(Biphenyl-2-thiocarbamoyl)-4-(1,3-dichlorophenyl) Carboxamide

AAMER SAEEDA①ULRICH FL?RKEBa(Department of Chemistry, Quaid-I-Azam University, Islamabad 45320, Pakistan)b(Department Chemie, Fakult?t fur Naturwissenschaften, Universit?t Paderborn, Warburgerstrasse 100, D-33098 Paderborn, Germany)

The synthesis of the title molecule was achieved by the reaction of 2,4-dichlorobenzoyl chloride with potassium thiocyanate in 1:1 molar ratio in dry acetonitrile to afford the corresponding isothiocyante in situ followed by the treatment with 2-aminobiphenyl.The structure of the target compound was established by elemental analysis, FTIR,1H,13C NMR and mass spectroscopy and unequivocally confirmed by the crystallographic data.The title compound crystallizes in the monoclinic space group P21/n with a = 13.356(2), b = 7.0761(11), c = 20.539(3) ?, β = 105.723(4)°, V = 1868.5(5) ?3and Z = 4.

synthesis, crystal structure, N-(biphenyl-2-thiocarbamoyl)-4-(1,3-dichlorophenyl) carboxamide;

1 INTRODUCTION

The last two decades have witnessed an unprecedented upsurge in the synthesis and applications of a wide range of 1,3-disubstituted thioureas.Thioureas have proved to be not only starting point for the synthesis of a diversity of heterocyclic com- pounds, a versatile family of ligands for complexa- tion with transition and post-transition metal ions and metal extraction but also exhibit a broad spectrum of bioactivities[1].Thus, 1-acyl-3-(2?-aminophenyl)thioureas are anti-intestinal nematode prodrugs[2], the thiourea derivatives of 4-azatricyclo[5.2.2.02,6]undec-8-ene-3,5-dione[3]and pyridazine[4]; 1-aroyl-3-arylthioureas[5]and 1-aroyl-3-(substituted-2-benzothiazolyl)thioureas exhibit potent antibacterial activity[6].N-Phenyl and N-benzoylthioureas are antimicrobial agents[7]and the fluorinated thioureas exhibit better antifungal than the antibacterial activity[8].In addition, biphenyl derivatives are used in the synthesis of antifungal agents like bifonazole, optical brightening agents, dyes and polychlorinated biphenyls (PCBs).The rotation around the single bond in biphenyls, and in particular the ortho-substituted ones, is sterically hindered exhibiting the atropisomerism.Some biphenyl thioureas having structures very closely related to that of the title compound have been used as organocatalysts for electrochemical reductions[9].Few related structures containing the biphenylthiourea scaffold include the N-(biphenyl-4-carbonyl)-N?-(4-chlorophenyl)thiourea[10], its 2-chloro-[11], 2-pyridylmethyl)-[12], and 6-methylpyridin-2-yl[13]analogs, but all of these compounds are derived from biphenylisothiocyanate, whereas in the present case it is obtained from the 2,4-dichlorobenzoyl isothiocyanate.Taking into account the aforesaid significance of thiourea motif, and the multifunc-tional value of biphenyl, the endeavor of the current work was the synthesis of thiourea containing biphenyl in a single structural entity in continuation of our structural and vibrational studies of such compounds[14-16].

2 EXPERIMENTAL

2.1 Synthesis of N-(biphenyl-2-thiocarbamoyl)-4-(1,3-dichlorophenyl) carboxamide (1)

A solution of 2-aminobiphenyl (1.5 mmol) in 20 mL dry acetonitrile was added dropwise to a two-necked round-bottomed flask containing an equimolar amount of 2,4-dichlorobenzoyl isothiocyanate (1.5 mmol) in 20 mL of acetonitrile.The mixture was refluxed for 3 h.On cooling, the reaction mixture was acidified with dil.hydrochloric acid.The solid product obtained on filtration was washed with water and recrystallized from an acetone:dichloromethane mixture (1:2).Colourless crystals were obtained on slow evaporation (yield 88%, m.p.: 147～148 ℃).Anal.Calcd.for C20H14N2Cl2OS: C, 59.86; H, 3.52, N, 6.98; S, 7.99%.Found: C, 59.91; H, 3.57; N, 6.94; S, 8.01%.1H NMR (300 MHz, CDCl3δ, ppm): 12.33 (s, 1H, CONH), 9.21 (s, 1H, CSNH), 7.14 (t, 1H, J=2.1 Hz, Ar–H), 7.33～7.40 (m, 4H, Ar–H), 7.36 (m, 4H, Ar–H), 7.47 (s, 1H, Ar–H), 7.63 (d,1H, J=4.8 Hz, Ar–H), 7.71 (d, 1H, J=4.8 Hz, Ar–H).13C NMR (75MHz, CDCl3, δ, ppm) 115.8, 116.1, 117.0, 117.3, 118.5, 123.3, 123.6, 124.4, 126.2, 126.3, 128.9, 129.8, 130.4, 137.0, 141.3, 149.8, 159.5, 162.7, 168.4 (C=S), 172.9 (C=O).GCMS: m/e: 400.02, 402.02, 401.0, 403.02, 404.01.

2.2 Structure determination

Colourless single crystal C20H14Cl2N2OS, Mr= 401.3 g/cm3, m = 0.47 mm-1.Monoclinic, space group P21/n, a = 13.356(2), b = 7.076(11), c = 20.539 (3) ?, β = 105.723(4)°, V = 1868.5(5) ?3, Z = 4, Dc= 1.427 Mg/cm3, F(000) = 824.Data were collected at 130(2) K on a Bruker[17]AXS SMART APEX CCD diffractometer using MoKα radiation; 17078 reflections were collected in the 1.64 2s(I)) = 0.048 and wR (all data) = 0.082, (Δρ)min= –0.48 and (Δρ)max= 0.67 e/?3.The selected bond lengths and bond angles are given in Table 1.

Table 1.Selected Bond Lengths (?) and Bond Angles (°)

3 RESULTS AND DISCUSSION

The synthesis of the title molecule is depicted in Scheme 1.A freshly distilled solution of 2,4-dichlorobenzoyl chloride in dry acetonitrile was treated with an equimolar quantity of potassium thiocyanate in dry acetonitrile to afford the 2,4-dichlorobenzoylisothiocyanate as intermediate.Treatment of the latter with an equimolar quantity of 2-aminobiphenyl in the same solvent furnished the title molecule (1).Colourless crystals suitable for X-ray diffraction study were obtained on slow evaporation from an acetone:dichloromethane mixture (1:2).

The thiourea was characterized by IR absorptions at 3350～3325, 3154～3125 (free and associated NH), 3031, 2902, 1672～1685 (carbonyl) and 1252cm-1(thiocarbonyl) groups, respectively.In the1H-NMR spectrum of the compound in addition to the signals for aromatic protons, the characteristic N–H singlets at δ 12.31 for CONH and 9.22 for CSNH ppm and in13C NMR the peaks for carbonyl and thiocarbonyl were observed at δ 172.91 and 168.41 ppm, respectively.Mass spectrum showed the characteristic isotopic cluster at m/z 400～404.

Scheme 1.Synthetic pathway to N-(biphenyl-2-thiocarbamoyl)-4-(1,3-dichlorophenyl) carboxamide

The molecular structure of 1 (Fig.1) shows almost planar thiourea moiety with torsion angles O(1)–C(2)–N(1)–C(1) and S(1)–C(1)–N(1)–C(2) to be 9.0(5) and 3.9(2)°, respectively.This is connected to the intramolecular N(2)–H··O(1) hydrogen bond.The thiourea plane O(1)C(2)N(1)C(1)S(1)N(2) makes a dihedral angle of 65.04(6)° with the dichloro-phenyl plane and one of 49.38(9)° with the the N(2)-connected aromatic ring.The two planes of the biphenyl group are twisted by 62.36(9)° along the C(14)–C(15) bond.Table 1 presents the selected bond lengths (?) and bond angles (°); in general, there are no unexpected geometric parameters compared to the structurally closely related 1-(2-chlorobenzoyl)-3-(2-trifluoromethyl phenyl)-thiourea[19]and 1-(2-chlorobenzoyl)-3-(2,3-dimethylphenyl)thiourea[20].Crystal packing (Fig.2) shows intermolecular N(1)–H··S(1) (–x+1, –y+1,–z) bonds (N–H 0.88 ?, H··S 2.66 ?, N–H··S 165.5°) that link molecules into centrosymmetric dimers stacked along the b-axis.These dimers are then linked via intermolecular N(2)–H··Cl(1) (x, y–1, z) interactions (H··Cl 2.78 ? and N–H··Cl 124.3°) to give endless rows in the b-direction.

Fig.1.Molecular structure of (1).Anisotropic displacement ellipsoids are drawn at the 50% probability level

Fig.2.Crystal packing viewed apprimately along the b-axis with hydrogen bonding pattern as dashed lines.H atoms not involved are omitted

4 CONCLUSION

An efficient synthesis of a novel thioureabiphe-nyl hybrid compound 1 is described.It is not only a versatile ligand for complexation but also an intermediate towards the synthesis of a range of heterocycles.The structural assignment was supported by spectroscopy, elemental analysis data and crystallographic studies.

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18 April 2014; accepted 30 March 2015 (CCDC 925012)

① Corresponding author.Aamer Saeed.E-mail: aamersaeed@yahoo.com

10.14102/j.cnki.0254-5861.2010-1479