Structure and Absolute Configuration of l'-(p-Bromophenyl)-3'-ethyl-l',Y,4',5'- tetrahydro- 1,2-dideoxy-u-L-glucofuranoso[2,l-d]imidazole-2'-thione Monohydrate,* C15H19BrN204S.H20

M. MILLAN, C. F. CONDE, A. CONDE AND R. M,~RQUEZ 277 CRIADO, A., CONDE, A. & M.h.RQUEZ, R. (1983). Acta Cryst. C39, 122-125. CRIADO, A., CONDE, A. & MARQUEZ, R. (1984). Acta Cryst. C40, 188-190. GALBIS PI~REZ, J. A., AVALOS GONZALEZ, M., JIMIgNEZ REQUEJO, J. L. & PALACIOS ALBARRAN, J. C. (1983). Carbohydr. Res. 124, C15-C17. HAMILTON, W. C. (1959). Acta Cryst. 12, 609-610. International Tables for X-ray Crystallography (1974). Vol. IV. Birmingham: Kynoch Press. (Present distributor D. Reidel, Dordrecht.) LONGCHAMBON, F., OHANESSIAN, J., AVENEL, D. (~ NEWMAN, A. (1975). Acta Cryst. B31, 2623-2627. LONGCHAMBON, F., OHANESSIAN, J. (~ GILLIER-PANDRAUD, H. (1981). Acta Cryst. B37, 601-607. MAIN, P., FISKE, S. J., HULL, S. E., LESSINGER, L., GERMAIN, P., DECLERCQ, J.-P. & WOOLFSON, M. M. (1980). MULTANSO. A System of Computer Programs for the Automatic Solution of Crystal Structures from X-ray Diffraction Data. Univs. of York, England, and Louvain, Belgium. NARDELLI, M. (1983). Acta Cryst. C39, 1141-1142. OHANESSIAN, J., LONGCHAMBON, F. & ARENE, C. (1978). Acta Cryst. B34, 3666-3671. SHIMIZU, N., NISHIGAKI, S., NAKAI, Y. & OSAKI, K. (1982). Acta Cryst. B38, 2309-231 I. STEWART, J. M., KUNDELL, F. A. (~ BALDWIN, J. C. (1970). The XRA Y70 system. Computer Science Center, Univ. of Maryland, College Park, Maryland. TAYLOR, R. (~ KENNARD, O. (1982). J. Am. Chem. Soc. 104, 5063-5070. Acta Cryst. (1985). C41, 277-280 Structure and Absolute Configuration of l'-(p-Bromophenyl)-3'-ethyl-l',Y,4',5'- tetrahydro- 1,2-dideoxy-u-L-glucofuranoso[2,l-d]imidazole-2'-thione Monohydrate,* C15H19BrN204S.H20 By C. F. CONDE, M. MILLAN, A. CONDE AND R. M.~,RQUEZ Departamento de Optica y Secci6n de F[sica del Centro Coordinado del CSIC, Universidad de Sevilla, Spain (Received 27 June 1984; accepted 15 October 1984) Abstract. M r = 421-30, monoclinic, P2~, a = 7.531 (1), b=8.148(4), c= 14. 625 (2) ,~, fl=97.14(1) °, V= 890.5 (5) ,~3, Z= 2, Din= 1.58 (1), Dx= 1.571 Mg m -3, Mo Kct, 2 = 0.7107 ,~,/~ = 2.42 mm -1, F(000)=432, T= 300 K, R =0.065 for 1672 observed independent reflexions. The sugar ring adopts a 4T 3 conformation and the dihedral angle in the bicyclic system is 72.3 (4) °. A three-dimensional network of hydrogen bonds links the molecules to build up the crystal structure. Introduction. The structure determination of the title compound (I) was undertaken as part of a continuing research project in this laboratory involving glucimidazoles and imidazole C-nucleosides. During the past few years amino-sugars have been used in the preparation of these compounds (Garcia Gonz~lez, Fern/mdez-Bolafios & Lopez-Aparicio, 1976; Fern/mdez-Bolafios, Galbis P6rez & Zamora Mata, 1984; Galbis P6rez, Palacios Albarr~n, Jim~nez Requejo & AvaloN Gonzhlez, 1984) via 1-aryl- glucofuranosoimidazolidine-2-thiones. Some of these compounds, prepared in the Organic Chemistry Department of the University of Extremadura, have * IUPAC name: 6-(p-bromophenyl)-2-(l,2-dihydroxyethyl)-4- ethyl-3 -hydroxy-2,3,3 a,5,6,6a-hexahydrofurol 2,3-dlimidazole- 5(4H)-thione monohydrate. 0108-2701/85/020277-04501.50 been studied in order to establish the conformational details of the molecule in the solid state (for example, Estrada, Conde & M~rquez, 1983, 1984). Galbis P6rez et al. (1984) have reported the application of aminonitrile synthesis to the preparation of the new 2-deoxy-2-(ethylamino)-ct-L-glucopyranose hydrochloride and its reaction with 4-bromophenyl isothiocyanate, to afford the title compound. Its chemical nature was established from elemental analysis and spectroscopic IR and NMR data and the X-ray analysis was carried out to define the structural details. .OCH~ /0 ~ ~N /C,.,B, " OH OH \ C2H5 (I) • H20 Experimental. Single crystals in the form of colourless needles elongated along [100] prepared in the Organic Chemistry Department of the University of Extremadura and kindly supplied by Professor J. A. Galbis. D m by flotation method. Crystal 0.09 × 0.14 x 0.30 mm. Unit-cell parameters by least squares from 25 reflexions, 5 < 0 < 18 °. Enraf-Nonius CAD-4 diffractometer, graphite monochromator, 20 < 60 ° (-10 _< h _<10, 0<_k_<ll, 0</<20), to--20 scan © 1985 International Union of Crystallography 278 C 15H x9BrN204S.H20 mode. Two standard reflexions (103, 004): variation in intensity less than 2.5% of the mean value. 2745 independent reflexions measured, 1073 considered unobserved [I < 2a(/)]. Lorentz and polarization correction; no correction for absorption (/zR ~0.15) or extinction. Patterson function and heavy-atom method with the initial set of phases based on Br-atom position. Full-matrix least-squares refinement on F, anisotropic; difference Fourier synthesis revealed the 21 H-atom positions; isotropic temperature factor for each H atom equal to that of the atom bonded to it; further least-squares refinement including the positional parameters of the H atoms and anomalous-dispersion corrections for Br and S atomic scattering factors (International Tables for X-ray Crystallography, 1974) reduced R w to 0.071 (R = 0.065); weighting scheme based on a statistical count criterion (w= 1/a2). Br (A/O)max = 0.04. S = 2.05 for 217 refined parameters, s Final difference synthesis showed 0.40 > Ap > c(I) --0.30 e A -3. c(2) C(3) The enantiomorphic form of the molecule was refined c(4) separately and converged to a final R w value of 0.076 c(5) (R 0.071). The application of the ~' test (Hamilton, c(6) = C(7) 1965) indicates that the first enantiomorph is correct at c(8) a significance level much lower than 0.005 [Rw(2)/ c(9) c(10) Rw(1 ) = 1.092; ~'L1455,0.005 ~- 1.003] and, therefore, can c(11) be retained as the absolute configuration. Moreover, c(12) this absolute configuration is consistent with that c(13) C(14) defined by reference to the sugar moiety. Crystalc(15) lographic programs of the XRAY70 system (Stewart, o(1) 0(2) Kundell & Baldwin, 1970) were used throughout. 0(3) 0(4) 0(5) N(I) N(2) Discussion. Fractional atomic coordinates and equivalent isotropic temperature factors (Hamilton, 1959) for non-hydrogen atoms are given in Table 1.* Bond lengths and angles involving non-hydrogen atoms are listed in Fig. 1. Bond distances and angles in the imidazolidine ring agree with the mean values reported for analogous glucofuranoimidazolidine-2-thione compounds (Conde, Bernier & M~quez, 1980; Estrada, Conde & M~quez, 1983, 1984). The observed asymmetry for the N(1)-C(I) and N(2)-C(1) lengths (A/a = 3.5 1) indicates the influence of the substituents at N(1) and N(2) on the resonance: -S-C \ \ //N +- N- -s-c / \ N- ~N +- / * Lists of structure factors, anisotropic thermal parameters and H-atom parameters have been deposited with the British Library Lending Division as Supplementary Publication No. SUP 39834 (14 pp.). Copies may be obtained through The Executive Secretary, International Union of Crystallography, 5 Abbey Square, Chester CH 1 2HU, England. The imidazolidine ring is not planar; the ring atoms deviate significantly [~.(A/a)2= 156.5] from the leastsquares plane [the value of the total puckering amplitude (Cremer & Pople, 1975) is Q= 0.122 (10)A] and this feature, not found for monosubstituted [only at N(1)] glucofuranoimidazolidine compounds, has been observed also in a recently reported analogous structure (Estrada, Conde & M&rquez, 1983). Table 1. Atomic fractional coordinates equivalent isotropic temperature factors Ue q 1%" N- * * = ~,_.i=jUuai a i aiajcos(araj). (x 10 4) and (A 2 x 103) x y z UeQ 9014 (2) 10000 -21 (1) 607 (5) 5891 (4) 3728 (5) 2514 (2) 389 (9) 3943 (12) 4787 (15) 2400 (7) 260 (29) 2069 (14) 7112 (15) 2276 (7) 308 (34) 1012 (13) 5565 (12) 2538 (7) 235 (27) 366 (12) 6051 (15) 3449 (7) 294 (32) 1849 (13) 7221 (15) 3835 (6) 261 (30) 1455 (13) 8395 (15) 4592 (6) 292 (33) 3007 (14) 9499 (15) 4901 (8) 345 (37) 4983 (13) 7236 (12) 1589 (6) 208 (27) 5718 (15) 6453 (16) 884 (8) 372 (37) 6911 (15) 7311 (18) 406(8) 420(41) 7359 (15) 8912 (15) 636 (8) 337 (35) 6594 (16) 9698 (16) 1313 (8) 396 (39) 5425 (16) 8869 (17) 1809 (8) 378 (38) 2042 (16) 2651 (15) 2994 (9) 353 (39) 585 (22) 1816 (17) 2390 (14) 789 (69) 2274 (10) 8127 (10) 3054 (5) 308 (25) -1270 (9) 6957 (10) 3255 (6) 367 (26) 895 (1 I) 7503 (12) 5327 (5) 413 (28) 4545 (9) 8597 (13) 5279 (5) 417 (27) 2948 (11) 4691 (12) 5852 (7) 574 (36) 3781 (12) 6407 (12) 2089 (6) 309 (29) 2399 (12) 4279 (12) 2644 (6) 292 (28) ~ .&.,~c(15) C(14~l l l ,.; ,,fo '2&6,~, q'c° - / ,_ ~ b-"~e.o~ 8 b,q-2/"~ "-2.20 o .,7- .,~ $ c(ioi Br b~ Fig. 1. Bond lengths (A) and angles (o) in the molecule. (Standard deviations are in the ranges O.010-O.020A and 0-7-1.1 °, respectively.) C. F. CONDE, M. MILLAN, A. CONDE AND R. M/~RQUEZ 279 Bond lengths and angles in the furanosyl ring are close to the mean values observed for analogous compounds. The typical asymmetry of the endocyclic bonds O(1)-C(2) and O(1)-C(5) in these compounds due to anomeric effects seems to be present; however, the feature is difficult to establish in this case because of the high e.s.d.'s (A/tr-- 1.58). The glucofuranose ring is not planar as expected. In terms of the ring-puckering coordinates (Cremer & Pople, 1975)the amplitude and phase magnitudes are 0.373 (11) A and 125.5 (15) ° for the sequence O(1)-C(2)-C(3)-C(4)-C(5) and the resulting conformation corresponds to a puckering mode (4T3) similar to that found in a recently reported analogous compound (Estrada, Conde & M~rquez, 1983). The asymmetry parameter of Nardelli (1983a)is AC2[C(2)]=0.0052(46). The small value of the torsion angle O(1)-C(2)-C(3)-C(4)= 11.4 (10) ° is another feature of these compounds and may be attributed to distortion of the furanosyl ring due to the ring fusion. The two rings show a eis form of junction, as is found in analogous compounds, with the bonds at C(2) and C(3) nearly eclipsed. The dihedral angle between the least-squares planes through the imidazolidine and furanosyl rings is 72.9 (4) °. The phenyl ring, planar as expected [Z(A/a) 2 = 3.8; Z2= 7.8 at 95%], forms a dihedral angle of 47.2 (4) ° with the imidazolidine ring. Values of this dihedral angle in the range 45-80 ° were found in analogous compounds, except for the value of 15.1 (6) ° in the case of l'-phenyl- l',3',4',5'-tetrahydro-l,2-dideoxyglucofuran- oso[ 1,2-d]imidazol-2-one (Conde, Bernier & M/u'quez, 1980). The ethyl group is also twisted with respect to the imidazolidine ring as indicated by the torsion angle C(1)-N(2)-C(14)-C(15) =-120.1 (13) °. o Fig. 2. A view along [ 100] of the unit-cell contents. Hydrogen bonds are indicated by dashed lines. Table 2. Geometry of the possible hydrogen bonds X-H... Y X... Y (A) X-H (A) H... Y (A) X-H... Y (°) C(13)-H(13)...O(l) 3.223 (15) 0.94 (15) 2.53 (15) 130 (ll) C(6)-H(6)...O(2) 2.900(12) 0.80 (13) 2.39(15) 122 (14) C(15)-H(153)...O(1 ~) 3.359 (13) 1.04 (21) 2.53 (20) 136 (14) C(6)-H(6)...O(5 H) 3.463(13) 0.80(13) 2.78(14) 144(12) C(7)-H(71)...O(5 "~) 3.369(14) 0.85(15) 2.80(15) 126(13) O(5)-H(O51)...O(2 ~v) 2.945 (13) 1.08 (19) 2. l0 (18) 134 (14) O(5)-H(O52)...O(4 v) 2.806 (13) 1.06 (18) 1-89 (18) 143 (14) O(4)-H(O4)...S u~ 3.287 (9) 0-87 (15) 2.47 (15) 156 (13) Symmetry code: none x, y, z; (i) x, y - 1, z; (ii) -x, y + ½, -z + 1 ; (iii)-x+ l,y+½,-z+ l;(iv)-x,y-½,-z+ l;(v)-x+ 1,Y-½, --z+ I. Crystal paeking Fig. 2 shows the contents of the unit cell viewed down [100]. The crystal structure is stabilized by a three-dimensional hydrogen-bonding network; there are also two intramolecular interactions [C (13)-H (13)... O(1) and C(6)-H(6)...O(2)] that could also be hydrogen bonds (Jeffrey & Maluszynska, 1982; Berkovitch-Yellin & Leiserowitz, 1984). Molecules are linked to form chains parallel to [010] by C(15)-H(153)..-O(1)(x, y - 1, z) hydrogen bonds. On the other hand molecules are linked along [100], through the hydration water molecule, by two hydrogen bonds: O(5)-H(O51)...O(2)(-x, y- ½, -z + 1) and O(5)-H(O52)...O(4)(-x + 1, y-½, -z + 1). Finally, each molecule is linked to the neighbour related by a twofold screw axis by O(4)-H(O4)...S(-x + 1, y + ½, -z + 1). Details of the geometry of these hydrogen bonds are given in Table 2. For the two O-H...O contacts listed in Table 2 involving the hydration water molecule, the values of the d parameter, defined as the difference between the sum of the van der Waals radii and the interatomic distance (Taylor & Kennard, 1982), are 0.60 and 0.81 A respectively, both satisfying the rule d > 0.3 A. For the short C-H...O interactions only the intramolecular contact C(6)-H(6)...O(2) has a value d_~ 0.3 and the angles C--H...O are, in all cases, far from the ideal linear configuration. However, a high dispersion in experimental values of C-H...O angle is found for interactions with d > 0-3 (Taylor & Kennard, 1982). Finally, the existence of short O--H...S contacts has been found in other imidazolidine-2-thione compounds and, perhaps, it could be associated with the negative charge at S in the resonance forms of the thiourea system. No other intermolecular contact significantly shorter than the sum of the van der Waals radii has been detected. The molecular geometry and crystal packing were computed by PARST (Nardelli, 1983b). The authors thank Professor J. Galbis for supplying the crystals and for helpful discussions on chemical aspects and Professor A. L6pez-Castro for collecting the diffractometric data. The present work is part of a research project supported by a grant from the CAICYT of the Government. 280 C 15H 19BrN 2045.H20 References BERKOVITCH-YELLIN, C. & LEISEROWITZ, L. (1984). Acta Cryst. B40, 159-165. CONDE, A., BERNIER, F. & MARQUEZ, R. (1980). Acta Cryst. B36, 3048-3052. CREMER, D. & POPLE, J. A. (1975). J. Am. Chem. Soc. 97, 1354-1358. ESTRADA, M. D., CONDE, A. & MARQUEZ, R. (1983). Acta Cryst. C39, 1418-1421. ESTRADA, M. D., CONDE, A. & MARQUEZ, R. (1984). Acta Cryst. C40, 898-901. FERNANDEZ BOLAI~IOS, J., GALBIS P~REZ, J. A. & ZAMORA MATA, F. (1984). An. Quim. 80C. In the press. GALBIS P~REZ, J. A., PALACIOS ALBARRAN, J. C., JIMI~NEZ REQUEJO, J. L. & AVALOS GONZALEZ, M. (1984). Carbohydr. Res. 129. In the press. GARC1A GONZALEZ, F., FERNANDEZ BOLAI~IOS, J. & LOPEZ APARICIO, F. J. (1976). Am. Chem. Soc. Syrup. Ser. 39, 207-226. HAMILTON, W. C. (1959). Acta Cryst. 12, 609-610. HAMILTON, W. C. (1965). Acta Cryst. 18, 502-510. International Tables for X-ray Crystallography (1974). Vol. IV. Birmingham: Kynoch Press. JEFFREY, G. A. & MALUSZYNSKA, n. (1982). Int. J. Biol. Macromol. 4, 173-185. NARDELLI, M. (1983a). Acta Cryst. C39, 1141-1142. NARDELLI, M. (1983b). Comput. Chem. 7, 95-98. STEWART, J. M., KUNDELL, F. A. & BALDWIN, J. C. (1970). The XRA Y70 system. Computer Science Center, Univ. of Maryland, College Park, Maryland. TAYLOR, R. & KENNARD, O. (1982). J. Am. Chem. Soc. 104, 5063-5070. Acta Cryst. (1985). C41,280-282 Structure of Naproxen,* C14H1403 BY K. RAVIKUMAR,~ S. S. RAJAN~ AND VASANTHA PATTABHI Department of Crystallography and Biophysics, University of Madras, Guindy Campus, Madras-600025, India AND E. J. GABE§ Department of Chemistry, National R esearch Council of Canada, Ottawa, Canada K 1A OR 9 (Received 27 December 1983; accepted 17 October 1984) Abstract. An effective inhibitor of cyclo-oxygenase. Mr=230.25 , monoclinic, P21, a= 13.3150(10), b = 5.7765 (4), c= 7.8732 (4)A, fl= 93.88 (1) °, V= 604.2 (1)A 3, Z= 2, Din= 1.25 (2) (flotation), D~= 1.265 Mg m -3, 2(Mo Ka 1) = 0.70926/~, #(Mo Ka) = 0.095 mm -1, F(000) = 244, T= 296 K, final R(F) = 0.061 for 1037 observed reflections. The rotation of the carboxyl group with respect to the benezene ring, which seems to be connected with anti-inflammatory potential, is similar to the other two substituted propionic acids already reported. The benzene rings in the naphthyl group are inclined at an angle of 5.2 (2) °. Introduction. The title compound, an effective inhibitor of the cyclo-oxygenase responsible for biosynthesis of prostaglandins, was obtained from Dr Natarajan, Institute of Basic Medical Sciences, Madras. It exhibits anti-inflammatory, analgesic and antipyretic activity in man (Goodman & Gilman, 1980). The analysis of its structure was undertaken to help to establish the structure-activity relationship in propionic acid derivatives. * IUPAC name: (+)-2-(6-methoxy-2-naphthyl)propionic acid. 5" Contribution No. 654 from the Department of Crystallography and Biophysics, University of Madras, Madras-600 025, India. $ To whom correspondence should be addressed. § NRC No. 24032. Experimental. Single crystals were grown by slow evaporation of a saturated solution in benzene at room temperature. Crystal 0.3 × 0.3 x 0.3 mm, mounted parallel to its long axis (b) and aligned to place this along the instrument (0 axis. Picker PDP8E four-circle diffractometer at the National Research Council, Canada. Graphite-monochromatized Mo Kct radiation, 0/20 scan technique, line profile analysis (Grant & Gabe, 1978), 20 < 60 °, 1167 unique reflections with -15 < h < 15, 0 < k < 6, 0 < l < 9; 1037 with /net > 2.5tr(Inet) based on counting statistics. Intensities for measured direct-beam polarization (Le Page, Gabe & Calvert, 1979) and Lorentz effects. Absorption corrections not applied. Unit-cell parameters from the least-squares refinement of the setting angles of 40 reflections with 20 > 40 °. Structure solved by direct methods with MULTAN (Germain, Main & Woolfson, 1971). E values larger than 1.5 used for phase generation; solution from the set having the highest combined figure of merit. The E map revealed the 17 non-hydrogen atoms. All 14 H atoms located from the AF map. Full-matrix refinement was completed with anisotropic temperature factors for non-hydrogen atoms and isotropic for H atoms. Final R(F)= 0.061 and Rw(F) = 0.053 for observed reflections; R = 0.074 and R w = 0.053 for all reflections; w = 1/a2(Fo) based on counting statistics; goodness of fit 2.6. The final difference synthesis showed no peaks above 0.3 e A-3; 0108-2701/85/020280-03501.50 © 1985 International Union of Crystallography