Crystal Structure of Norfloxacin Methanol Solvate: C16H18FN3O3 CH3OH H2O

24卷12期结构化学(JIEGOU HUAXUE)Vol. 24，No. 122005. 12Chinese J. Struct. Chem.1359~1362Crystal Structure of Norfloxacin MethanolSolvate: C16HgFN;O;:CH;OH :H2OPWANG Ying2 SUN Li-Wei WANG Wei YAN Lian-He(Water Treatment Institute, Nanjing University of Science and Technology, Nanjing 210094, China)ABSTRACTNorfloxacin methanol solvate (1 ethyl-fluoro-1,4-dihydro 4 oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid methanol solvate) has been prepared. The crystal and molecular struc-tures of the title compound, C16HsFN;O;:CH;OH H2O, were determined by X-ray diffraction me-thod. The compound crytallizes in monoclinic, space group P2|/c with a = 7.8660(16), b= 22.525(5), c= 10.253(2) Aa= 108.31° , M,= 369.39, V= 1724.7(6) A, Z=4, De= 1.423 g/cm', F(000)=784, R = 0.0557 and wR = 0.1224. The TGA analysis indicates that it decomposes completely at723.75 C.Keywords: crystal structure, norfloxacin, methanol solvate1 INTRODUCTION .Norfloxacin (0.16 g, 5 mmol) and PdCl2 (0.02 g) inmethanol solution. The brown solution was filteredNorfloxacin (H-Norf = 1-ethyl-6-fluoro- 1 ,4 dihy-and the filtrate was stood undisturbed. Single crys-dro-4-oxo-7-( l-piperazinyl)-3-quinoline carboxylictals suitable for X-ray analysis were obtained by slow-acid), a quinolone type compound, is widely used asly evaporating the methanol solvent at 20 C.an antibacterial drug which targets the bacterial type2.2 TGA analysisII DNA topoisomerase (gyrase)h2. Suggested modesThermal analysis was performed under pure nitro-of action for H-Norf are either inhibition of metal-gen atmosphere with Shimadzu TGA-50 (20 C/min)loenzyme DNA-gyrase or interaction with the DNA2.3 X-ray structure determinationmolecule via a metal complex intermediate, and itA selected crystal of the title compound was mountedhas been proposed that metal ion complex could beon a Bruker P4 diffractometer equipped with a gra-involved in these interactions with DNA3.41. Whilephite-monochromated MoKa radiation (n = 0.71073the reaction of Norfloxacin with PdCl2 in methanolA) for the data collection by using an )-scan modesolution did not obtain the predicted product but thein the range of 2.28<0<25.969 at 20 C. Usual Lp andtitle compound whose crystal structure and TGAempirical absorption corrections were carried out withanalysis are reported in this paper.SADABS'SI program. The structure was solved bydirect methods and refined by full-matrix least-squares2 EXPERIMENTALtechniques on F using SHELXTL6l soft-ware pack-age. All nonH atoms were anisotropically refined.2.1 Preparation of the title compoundThe hydrogen atoms were located from the differ-The title compound was prepared by refluxingence Fourier map and refined isotropically. The finalReceived 16 May 2005; accepted 28 June 2005 (CCDC 257195)②Coresponding author. Wang Ying, borm in 1965, engineering master, researcher, doing中国煤化工researches on organic synthesis. E mail: wangying 7012003 @ yahoo. com.cnMHCNMH G.WANG Y. et al: Crystal Structure of Norfloxacin1360MethanolSolvate: CLsH&FNQ CH,OH H2ONo. 12R = 0.0557 and wR = 0.1224 (w = 1/[σ(F3) +X-ray Crystallography". The crystal data and refine-(0.0712P)2+ 0.0000P], where P=(F。2 + 2F7)13) forment parameters are given in Table 1, and the non-1118 observed reflections with I > 2σ(). The mole-hydrogen atomic coordinates and thermal parameterscular graphics was created using SHELXTLO, andin Table 2. The selected bond distances and bondatomic scattering factors and anomalous dispersionangles are listed in Table 3.corrections were taken from International Tables forTable 1. Crystal Data and Structure Refinement for the title compoundFormulaCiHIsFN;O3 CHzOH H2OM369.39 .Crystal size (mm )0.25 x0.23 x0.17Crystal systemMonoclinicSpace groupP21cTemperature (K)Unit cell dimensionsa= 7.8660(16)A d= 90°b= 2.25(5)5 A d= 108.31(3)°c= 10.253(2) Aa= 90°Volume (A),Z1724.76), 4De (g/cm)1.423i (mm~)0.112F(000)784它range for data cllection2.28 to 25.96。Range ofh, k,1_9≤h≤0,0≤k≤26,-11≤l≤12Reflections ollcted 1 unique3336/ 3115 (Rm= 0.0901)Completeness to theta = 25.96Data 1 rstraints 1 parameters315/1/245Goodness-of-fit on 20.919 .Final R indicesR= 0.0557, wR =0.1224R indices (all data)R= 0.2109, wR = 0.1787(Ao)maxLargest diff. peak and hole (e/A)0.273, -0.252Table 2. Atomic Coordinates (x 10) and Equivalent IsotropicDisplacement Parameters (A x 10) for the Title Compound_Atom x_UeAtom_v_UeF -1846(4) 5087(1) 877(2)55(1)C(8) 1749(6)5539(2) 3888(4) .34(1)(1) 4974(5) 3413(2) 7863(3;69(1)C(9)2110(5)4995(2) 4591(4)29(1)0(2) 3147(5) 2848(1) 6291(3)59(1)C(10)3821(6)4416(2) 6451(4)34()0(3) 561(4) 34661) 4198(3)52(1)C(11) 4309(6)5505(2) 6572(4)40(1)N() 3433(4) 4950(1) 5876(3)33(1)C(12) 5523(7)5418(2) 8014(4)56(2)N(2)48(5)6125(2)1913(3)36(1)2(13) 37(7)6139(2) 506(4)44(1)N(3) -391(5) 7225(2) 457(3)1(1)C(14)-1089(7) 663(2)46()C(1) 777(6) 3348(2) 6765(5)7(1)C(15)- -364(7) 7191(2) 1908(4)C(2) 3036(6) 3895(2) 5955(4)33(C(16) 684(7)5673(2) 2651(4)45(1)2(3) 1521(6) 3896(2)4698(4)C(175654(10) 8091(2) 1880(7)93(3)4001(4)0(W1) 2978(5)7270(2) 103(4)77()C(5) -128(6) 4532(2) 2731(4)5(1)O(4) 2721(14) 8235(3) 2672(8) 94(3)*C(6)- -504(6) 5064(2) 2066(4)0(5)4361(18) 8023(4) 2793(11) 89(3)*2(7) 431(6)5584(2) 2612(4)Ueq is defined as one third of the trace of the orthogonalized Uj tensor.*: The occupancy factors of O(4) and O(5) are 0.58 and 0.42, respectively.中国煤化工MHCNMH G.2005 Vol. 12结构化学(JIEGOU HUAXUE)Chinese J. Struct. Chem.1361Table 3. Selected Bond Lengths (A) and Bond Angles (°) for the Title CompoundBondDist.1.340(4)N(2)- C(13)1.466(5)C(5)- C(6)1.363(6)0(1)- C(1)1.228(5)N(3)-C(14)1.478(6)C(6)-C(7)1.403(6)0(2)- C(1)1.263(5)N()-C(15)1.483(5)C(7)-C(8) .1.395(6)0(3)- C(3)1.236(5)C(1)-C(2)1.498(6)C(8)- C(9)1.405(5)N(1)- C(10)1.331(5)C(2)- C(10)1.350(6)C(11)-C(12) 1.996)N(1)- C(9)1.403(5)C(2)- C(3)1.455(6)C(13)- C(14)1.534(6)N(1)-C(11)1.497(5) .C(3)- C(4)1.480(5)C(15)-C(16)1.491(6)N(2)-C(7)C(4)- C(5)1.388(6)C(17)- -0(5) 1.592(1)N(2)-C(16)1.469(5)C(4)-C(9)1.404(5)0(4)- 0(5)_ 1.345(14)_Angle()Angle( )_Angle _C(10)-N(1)-C(9) 118.7(3)0(2)- -C(1)-C(2) 118.8(4)C(5)- C(6)-F .118.3(4C(10)- N(1)-C(11) 122.4(3)0(3)-C()-C(2)126.1(4;P-C(6)- C(7)119.7(4)C(9)- N()- -C(11) 118.8(3)0(3)- -C(3)- C(4) 120.1(4)C(5)- -C(6) _C7) 122.0(4)C(7)-N(2)-C(16) 118.0(3)C(3)-C(2)-C(1) 124.14C(12)-C(1)-N(1) 14.64)C(7)-N(2)-C(13) 15.(3)5C(10)-C(2)-C(3) 18.84)N(2)- C(13)-C(14) 108.7(4)C(16)-N(2)- -C(13) 110.9(3)C(10)- C(2)-C(1) 17.04) .N()-C(14)- C(13) 10.04) .C(14)- N(3) C(15) 109.8(3) .C(8)- C(7)-N(2) 122.8(4)N(3)- C(15)-C(16) 112.6(4)0(1)-C(1)-0(2) 123.74)C(6)-C(7)-N(2) 19.(4)N(2)- C(16) -C(15) 109.3(4)00)-C1)-C(2) 117.5(4) .0(4)-0(5)-C(17) 133.1(9)3 RESULTS AND DISCUSSIONscheme, and Fig. 3 depicts the crystal packing in theunit cellThe thermal analysis curves of the title compoundare shown in Fig. 1.The first slow weight loss takesplaces from 53.99 to 158.5 C losing methanol andC12water. Then from 158.5 to 723.8 C, the weight lossis fast with 99.1% in total. In the temperature rangeemof 300~350 C, the C-N bonds of the molecule are1101118)1616)Cisypossibly broken. And finally in the 500~ 700 C re-C(2]19)CI7gion, the benzene ring of the molecule is possible toCcndecompose.16)CI13)1 !。C(3)(5)13)10Fig. 2. Molecular structure of the title .8Ccompound with atomic numbering scheme6C402(0 100 200 300 400 500 600 700 800Templa]Fig. 1. TG diagram of the title compoundFig. 2 shows a perspective view of the monomeric中国煤化工unit of the title compound with atomic numberingFig. 3. CrystaTYHC N M H Ge title compound.WANG Y. et al: Crystal Structure of Norfloxacin1362MethanolSolvate: CriH&FNQ CH,OH. H2ONo. 12A crystal of C16HusFN;O;:CH3OHH2O was obtai-mum atom deviations of each plane are 0.043, 0.002,ned from methanol solution. The structure consists0.04, 0.063 A respectively. The dihedral angles be-of the norfloxacin molecule, one methanol and onetweensplanes1and2,1and4,3and4,and2and4water molecules. The F- C(6) distance is 1.340(4) Aare 6.3(2), 4.14(15), 4.88(15) and 5.2(2)°, respec-The C -C bond lengths are normal and the C _0 onestively.of 1.228(5)~1.263(5) A are in good agreement withThere is 8-δ stacking between pyriding and ben-those of related compoundsl8. The C(3)-0(3) bondzene rings of the adjacent molecule. cg(I): N(1)length (1.236 A) is shorter than that of C18H18FN;O3:C(9) C(4) C(3) C(2) C(10); cg(J): C(4) C(5)2DCl2D20(1.326 A)4.C(6) C(7) C(8) C(9)(-x, 1-y, 1-z). The di-The N(2)- C(7) bond lengths (1 .403 A) are as longhedral angle between planes I and J is 2.51° with theas the other N C bond length, which is indicative ofcentroid distance of 3.575(3) A Perpendicular dis-considerable single bond character. The C(10)-N(1)tance of Cg(I) on ring J is 3.534 A and that of Cg(I)(1.331(5) A) and C(9)- -N(1)(1.403(5) A) bond lengthson ringI 3.509 Adisplay the typical pattern observed for these mole-In solid state, there are four intermolecular hydro-cules with one shorter and one longer C -N bonds,gen bonds and seven weak intermolecular inter-e.g, quinolinolato (1.338(7) and 1.380(7) A)?.actions. The hydrogen bond lengths (A) are listed inThe piperazine ring of norfloxacin adopts a nor-Table 4. The O(W1)- -H(W1A)..O(1)(1-x,1-y, 1-z)mal tC chair conformation. The atoms of 0(1), N(1),hydrogen bond is 2.683(5) A a lttle longer than thatC(1), C(2), C(3) and C(10) lie in plane 1, and 0(3),of pure water (2.83 A)"0l.C(2), C(3) and C(4) in plane 2. While the F, 0(3),AIll above intermolecular interactions in this struc-C(2), C(3), C(4), C(5) and C(6) atoms form plane 3,ture connect Norfloxacin methanol and H2O togetherand F, N(1), N(2), C(2),C(3), C(4), C(5), C(6), C(7),to form a one-dimensional network stacked by VanC(8), C(9) and C(10) generate plane 4. The maxi-der Waals' interaction, as shown in Fig. 3. .Table4. Hydrogen Bond Lengths (A and Bond Angles(°)H_D-H..A _D...AD- H-AO(W1) -H(WIA)..0(1)0.851.862.683(5164N(3)- H3)..(WI)2.422.787(6)104N(3)- H3)..(3)0.902.302.827(5)110(4)-4H(4))..0(W1)91.912.689(9)15C(0)-1H(0)-.1)2.292.683(5)10C(13)- H3A)...962.242.883(5)124C17)-H(7)-.020.92.172.788(6)12a:1-x,1-y,1-z b:-x, 1/2+y, 1/2-2 c:x, 3/2-y, 1/2+zREFERENCES1) Chen, Z. F; Xiong, R. G.; Zhou, J. L; Guo, z. J.; You, x. Z.; Fun, H. K. J. Chem. Soc., Dalton Trans 2000, 4013- 4014.(2) Wang, G. P; Zhu, L. G.; Yu, Q s. J. Inorg. Chem. 2003,. 19, 179-182.(3) Chen, Z. F; Xiong, R. G.; Zhang J; Chen, X. T; Xue, Z. L; You, X. Z. Inorg. 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