826 J. Chem. SOC. (B), 1970 Crystal Structure and Absolute Stereochemistry of Lunarine Hydriodide Hydrate By 3. A. D. Jeffreys,' Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow C1 G. Ferguson, Department of Chemistry, University of Glasgow, Glasgow W2 Lunarine, C35H31N,0,, an alkaloid from L unaria biennis Moench and L. rediviva L., forms a hydriodide hydrate, crystals of which are orthorhombic, space-group P2,2,2, with Z = 4 in a unit cell of dimensions a = 11 -60, b = 16.53, c = 14.01 8. The crystal structure and absolute stereochemistry have been determined by single-crystal X-ray analysis. Atomic co-ordinates and temperature factors were determined by Fourier and least-squares calculations and 2372 reflections were refined to R 0.1 15. The alkaloid contains a spermidine chain in which the terminal nitrogen atoms are present as amides of p-hydroxycinnamic acid residues that are linked to give a 3-0x0- hexahydrodibenzofuran system, the C,-unit in the spermidine chain being the nearer to the reduced ring of the latter system.The absolute stereochemistry is the reverse of that selected earlier (C. Tamura. G. A. Sim. J. A. R. Jeffreys, P. Bladon, and G. Ferguson, Chem. Comm., 1965, 485). LUNARINE, C,H,,N304, is one of the alkaloids produced by Lunaria biennis Moench (Cruciferae), a native of south-eastern Europe, and cultivated in Britain (common name Monesty),l and by the central European species L. rediviva L.2 Chemical degradation and spectroscopic evidence revealed the chief structural components of the base, and led to its formulation as (la), or (lb).3 H H (1) a l z = 3 , m = 4 b $2 = 4, m = 3 The structure of the base, as its hydriodide hydrate, has been determined by the heavy-atom method to be (2).At an early stage in this work we learned that the (1) (1) '7 !9 2 0 22 11 i 5 pJ 10 same base, as the hydrobromide monohydrate, was under study at the University of Illinois, and preliminary results were announced j ~ i n t l y . ~ The absolute stereochemisty is now found to be the reverse of that selected earlier. 1 E. Steinegger and T. Reichstein, Pharm. Ada Helv., 1947, 22, 258; 0. R. Hansen, Acta Chem. Scand., 1947, 1. 657; H. G. Boit, Cham. Bey., 1954, 87, 1082; M.-M. Janot and J. Le Men, Bull. SOC. chim. France, 1966, 1841. 3 S. Huneck, Nahrwiss., 1962, 49, 233. EXPERIMENTAL Lunarine was dissolved in an excess of 2hl-hydrochloric acid , and concentrated potassium iodide solution was added when crystals of lunarine hydriodide hydrate were rapidly deposited.Prisms elongated along a, with (011) pro- minent were obtained by crystallization from water. Crystal Data.-Lunarine hydriodide hydrate, CS5HS1N3O4,- HI,H,O, M = 583.49, Orthorhombic, a = 11.60, b = 16-53, ation), 2 = 4, D, = 1.443, F(000) = 1192. Space group P2,2,2, (DZ4 No. 19) from systematic absences. Cu-K, radiation, h = 1.542 k ; p(Cu-Ka) = 106-4 crn.-l. Crystallografihic Measurements.-The symmetry and cell dimensions were derived from oscillation and rotation photographs about a, and from Weissenberg photographs about all three axes, with Cu-K, radiation.As the salt is efflorescent, each crystal was mounted in a sealed capillary of Lindemann glass containing a little water. Weak reflections at (005) and (009) are considered to be Reninger reflections from 017 and 017 respectively.6 The intensity data from the layers 0-10k2, were collected as equi-inclination multiple-film Weissenberg photographs, and estimated visually ; accidentally absent reflections were assessed at half the locally observable minimum. Five crystals were used for data collection. The intensities were corrected for polarization and crystal rotation, but not for absorption, and 2372 independent structure-factors evaluated. Structure Determination.-A three-dimensional Patterson map yielded approximate co-ordinates for the iodide ion ; that for y was $.Thus the first Fourier map, using weighted coefficients, had false mirror planes normal to b at y = 8, $. However, the map also showed a well resolved chain of atoms p(1), C(16), C(17), C(18), C(19), N(3)], and these, weighted as carbon, sufficed to decompose the false symmetry . Later, when the sites of all atoms except C(2), C(13), and C(20)-(22) had been determined [C(21) lies close to the false plane at y = $ and C(20) and C(22) are nearly mutual mirror images therein], the chemistry3 of the alkaloid enabled 0(1), 0(2), 0(3), and O(4) to be recognised as oxygen, and N ( l ) and N(2) as nitrogen, while O(5) was G = 14.01 A, U = 2686 A*, D, = 1.446 0.003 (by flot- 3 P. Potier, J. Le Men, M.-M. Janot, P. Bladon, A. G. Brown, and C. S. Wilson, Tetrahedro.ort Letters, 1963, 293, and references cited.4 C. Tamura, G. A. Sim, J. A. D. Jeffreys, P. Bladon, and G. Ferguson, Chem. Comm., 1965, 486. 6 J. C. Speakman, Acta Cryst., 1966, 18, 670.827 Phys. Org. identified as the oxygen of a water molecule by its isolation. The next round of calculation enabled all the atoms to be located; and, as one atom in the centre of the spermidine residue lay only 2.9 A from the oxygen of the water mole- cule, the position of the remaining nitrogen atom was revealed. Up to this point the temperature factor, U , for the iodide ion had been set at 0.045, while for the other atoms it was set at 0-05. Three rounds of Fourier refine- ment, using individual values for U and termination-of- series corrections reduced R to 0.159; and eight rounds of block-diagonal least-squares refinement with anisotropic temperature factors for the iodide ion reduced R to 0.115.On each of the nets 1-5kE, five Bijvoet pairs were selected. Comparison with the calculated inequalities shows that twenty-four observations are in agreement, and the re- maining calculated inequality is a weak one. The weighting scheme used in the refinement was: when the values of p were adjusted during refinement the final values were: PI = 100, pa = 0.01, p 3 = 0.001. TABLE 1 Atomic co-ordinates, as fractions of the unit cell edges, with ; temperature factors, d w = w - exp(-P,(sin e/1)211[l 3- P2IFoI + P,l~o121P standard deviations (A x u in (A21 44 Y / b z/c u(z) u I 1.02323 1 0-26091 "(T' 0.21659 1 See 0.15043 0.41023 O(3) 0.18572 0.11880 N(l) 0.07071 N(2) 0.24292 N(3) 0.21294 0-12753 0.02383 C( 3) - 0.04669 C(4) -0.07174 - 0.04009 - 0.08867 0.08508 C(7) 0.17637 C(S) 0.20024 0.28619 :[!!I) 0.33689 C(11) 0.30310 0.22283 :[;:] 0.11740 C( 14) 0-06650 0.10348 0.07967 0.04488 0.14744 0-10955 :[i$ 0.26986 C(21) 0.21285 0.26463 El:] 0-31443 0.27685 :[:ti 0.32128 Final anistropic iodide ion: Ull 0.0645 uz, 0.0610 14 0-54076 14 1.01034 19 0.89983 17 1.37407 15 0.87611 14 0.79665 17 0-92515 16 0.70801 17 0.68985 16 0.70760 16 0.58063 14 1.16276 17 0.83271 16 1.40622 18 0.59088 16 1.61814 18 0.79820 16 0.80180 23 0.80937 21 0.73445 22 0.87822 20 0.76702 24 0.89008 21 0.87089 23 0.81140 20 0.92708 18 0.78424 16 0.90856 19 0.84522 18 0.95830 19 0.85200 18 1.05267 21 0.91063 18 1007677 26 0.96172 23 1.00948 22 0.95332 20 0.91190 20 0.89521 18 0.89120 20 0-70065 19 0.94170 18 0.67345 15 1.02156 20 0.59269 18 1.06305 19 0.49863 17 1.19619 22 0.60493 20 1.30176 26 0.54627 25 1.35513 22 0-57247 20 1.46123 20 0-66795 19 1.49702 23 0-74197 21 1.53900 25 0.82042 23 1.51350 26 0.86899 25 1.35035 23 0.87593 21 1.24949 26 0.91764 23 1.17865 temperature parameters U J ~ 7733 0.0712 13 16 13 15 15 13 15 15 16 20 19 20 19 16 17 17 18 21 19 17 18 16 18 17 19 24 20 17 20 21 24 20 22 (A2) below 0.0694 0.0923 0.0724 0.0866 0-0841 0.0538 0.0663 0.0645 0.0512 0.0736 0.0706 0.0729 0.067 1 0-0501 0.0568 0.0681 0.0694 0.0766 0,0682 0.0586 0.0618 0.0605 0.0616 0.0575 0-0674 0-0835 0.0682 0.0610 0.0738 0.0779 0.0829 0.0696 0.0807 for the In the structure-factor calculations the atomic scattering factors used were those given in ref. 6.Observed and calculated structure factors are listed in Supplementary Publication No. SUP 20007 (39 pp., 1 microfiche).* Table 1 * See note about Supplementary Publications in the Notice to Authors, No. 7, on the inside cover of J . Chew. SOC. (A), 1970, No. 11. gives the final co-ordinates of the atoms, their standard deviations (derived from the final least-squares matrix), and temperature factors. The co-ordinates plotted on right- handed axes define the absolute stereochemistry of the molecule, which is the reverse of that selected earlier.4 Figure 1 shows one asymmetric unit in projection onto the C I- b=@5 0 6 0 FIGURE 1 The environs of one molecule, viewed down the a axls bc plane, and Formula (2) the numbering system for the atoms.Table 2 lists the Bijvoet inequalities used to derive this stereochemistry. Table 3 lists interatomic distances, valency angles, and some non-bonded interactions. Table 4 gives the mean TABLE 2 Bijvoet pairs used to determine the absolute stereo- The subscripts plus and minus refer to the chemistry. indices hkl, and hkl respectively Index I 4- 11- Fc+alFc-= 1 1 2 <1 1.03 1 1 4 (1 0.72 1 1 12 >1 1.27 1 6 1 <1 0.95 1 9 1 >1 2.04 2 1 6 >1 1.67 2 1 12 >1 1.78 2 2 1 <1 0.85 2 3 1 <1 0.60 2 3 2 (1 0.52 3 2 2 >1 1-93 3 3 3 (1 0.30 3 5 1 >1 1-97 3 7 1 >1 2.66 3 14 1 <1 0.59 4 1 3 >1 1-94 4 1 4 >1 1-21 4 2 1 >1 1-68 4 2 8 <1 0.54 4 7 1 <1 0.58 6 1 1 >1 1.16 6 1 5 >1 1.81 6 7 1 <1 0.72 6 7 2 >1 1.12 6 12 1 > I 1.14 estimated standard deviations for bond lengths of different types, for valency angles, and the mean values for lengths and angles of selected types of bond, together with the means 6 ' International Tables for X-Ray Crystallography,' vol.111, Kynoch Press, Birmingham, 1962.828 J. Chem. SOC. (B), 1970 of some previously measured values. Our values are similar to those already determined, and all the values for individual bond-lengths and angles averaged in this table lie within 30 of the appropriate mean. Table 5 gives some out-of-plane distances. The atoms of the benzene ring [C(7)-(12)] are coplanar, with the adjacent atoms 0(3), C(6), and C(25) all on the same side of this plane. In the two acrylamide residues [C( 13)-( 15), O( 1), N( 1) and TABLE 3 Some interatomic distances (A) and valency angles (degrees) bond lendhs C( 1)-0 (3) C( 1)-c(2) CU)-c(6) C(2)-C(3) C(3)-0(4) C(3)-C(4) C(41-cI5) c (5)-c (6) C(7)-C(8) C(8)-C(9) c (9)-C( 10) C( 1 0)-C( 1 1) C( l l ) - C ( 12) :I:]:: 1; )3) C(7)-C(12) C(9)-C(25) C( 12)-0 (3) Valency angles C(1)-0(3)-C( 12) C(6)-C(1)-0(3) C( 6)-C( 1)-C( 2) C(l)-C(2)-C(3) C(2)-c(3)-0 (4) C( 2)-C( 3)-c (4) C( 3)-C(4)-C( 5) C(4)-C(3)-0 (4) C (4)-C (5)-C( 6) C (5)-C ( 6)-C ( 1) C (5)-C (6)-C( 13) C( 1)-C(6)-C( 13) C (5)-C (6)-C (7) C( 7)-C( 6)-C (1 3) C ( 6)-C ( 7)-C ( 1 2) C( 8)-C (7)-C (12) C ( 8)-C( 9)-C( 10) C ( 8)-C (9)-C ( 2 5) CP)-C(6)-C(7) C(6)-C(7)-C(8) C(7)-C(8)-c(9) c ( 10)-c (9)-c (25) c (9)-c (1 0)-C( 1 1) 1.44 1-54 1-59 1.47 1.23 1.50 1.56 1.54 1.61 1.51 1.36 1.37 1.43 1.40 1-49 1.43 1-37 1.43 107 109 111 110 120 120 121 110 112 114 117 97 110 111 106 128 110 122 116 123 118 119 118 " C(13)-C(14) C(l4)-C( 15) C ( 15)-0 (1) C( 15)-N( 1) C( 16)-N (1) C( 16)-C( 17) C( 17)-C ( 18) C (1 8)-C ( 19) C(19)-N(3) C (20)-N (3) c (20)-C(2 1) c (2 1)-c (22) c (22)-X (2) C (2 3) -N (2) C (2 3)-0 (2) C (23)-C (24) C(24)<(25) C( 10)-€(11)-c(12) C( 1 1)-C( 12)-C( 7) C( 13)-c ( 14)-C( 15) C(7)-C( 12)-0(3) C(6)-C(13)-C( 14) C( 14)-C( 15)-0 (1) C( 14)-C (15)-N( 1) 0 (l)-C( 15)-N ( 1) C( 15)-N( l ) - C ( 16) N (1)-C( 16)-C( 1 7) C( 16)-C( 17)-C (1 8) C( 17)-C( 18)-C( 19) C (1 8)-C ( 19)-N (3) C( 19)-N(3)-C(20) N (3)-C (20)-C (2 1) C( 2 1)-C(22)-N( 2) C(22)-N(2)-C(23) N( 2)-C (23)-0 (2) N( 2)-C( 2 3 ) X (24) 0 (2)-C (23)-C (24) c (20)-C( 2 1)-C( 22) c (2 3)-c (24)-c (2 5) C( 24)-c (25)-C( 9) 1-34 1.52 1.26 1.33 1.49 1-54 1-56 1-61 1-47 1.47 1.51 1-47 1-54 1-29 1.27 1.48 1-31 117 112 124 117 119 120 114 125 120 108 107 111 109 116 115 116 107 123 126 115 118 130 125 C(23)-(25), 0(2), N(2)], the lengths of corresponding bonds are the same within experimental error, as are the sizes of corresponding angles at the carbon atom of each amide function.In neither case is the system -C:C*(:O)*N: planar. but the out-of-plane distances for the group C(13) ... N(1) are larger than for the other group. In a normal lactone, the atoms C*C(:O)-O*C are p1anar;Q in the two analogous amide residues in this molecule, C*C(:O)-N*C, the atoms of the group containing O(2) and N(2) are coplanar, while those of the group containing O(1) and N(1) are not.The reason for this difference is that the latter function is in- volved in hydrogen bonding (see later). The best planes G. Giglio, A. M. Liquori, and R. Puliti, Acta Cryst., 1966, 20, 652. 8 (a) E. Giglio, A. M. Liquori, R. Puliti, and A. Ripamonti, Acta Cryst., 1966, 20, 652; (b) Y. Iittaka and Y. Huse, ibid., 1965, 18, 110. through the atoms of the benzene ring, and of the acryl- amide residue are inclined at an angle of 20.2". Examination of a model shows that the hydrogen atoms of the methylene groups of the spermidine chain are all TABLE 4 Averages of selected valency parameters. Values in parentheses are the means of previously published values * Bond lengths (A). Mean, over whole molecule: C(.@)-C(sP3) 1.55 (1.54) C( ar)-C( ar) 1.39 (1.39) 0 II -.C=C-C-N--C a b c d a 1.33 (1.36) b 1.50 (1.44) c 1-31 (1.33) d 1.47 (1.48) e 1.26 (1.24) Spermidine chain Ref.7 Ref. 8(a) Ref. 8(b) C(s93)-C(s93) 1-54 (1.54) (1.51) (1.53) (1.52) C(sP3)-N(sP3) 1-47 (1.48) (1.48) (1.50) (1.50) Bondangle (") 111 - (112) (111) (111) at -CH,- Mean estimated standard deviations, over all values : Bond lengths (A) C-C 0.029 C-N 0.026 C-0 0.025 Bond angles (all types) 2.4' * Taken from Clzem. SOC. Special Publ., No. 18, 1965, unless otherwise stated. staggered; and the values (Table 6) for the lengths of the 1,4-intramolecular approaches agree with this finding. The mean bond-lengths and valency angles within the spermidine chain are not significantly different from those in spermidine TABLE 5 derivation of the plane are italicized Out-of-plane distances (A), Atoms omitted in the C(7) 0.02 C(10) C(11) -0.01 C(8) -0.02 0.01 c(9) 0.00 0.00 :!!3? 0.08 0.02 0.04 - 0.01 0.20 0.62 -0.11 -0.11 0.12 - 0.1 1 0.11 0.61 0.56 0(2) 0.00 N(2) -0.04 C(23) 0.02 C(24) 0.07 C(25) -0.05 0.04 - 0.07 - 0.01 0.15 -0.11 0.00 - 0.08 0-07 - 0.06 0.07 0.00 0.00 - 0.01 0.01 - 0.01 A.McL. Mathieson and J. C. Taylor, Tetrahedron Leftem, 1961, 590; J. F. McConnell, A. McL. Mathieson, B. P. Schoen- born, ibid., 1962, 445; G. A. Sim, Anm. Rev. Phys. Chern., 1967, IS, 57.Phys. Org. trihydrochloride which crystallises with an extended chain,' or in salts of spermine (H,N*[CH,],*NH*[CH,],*NH- [CH,],- -NH,) whose tetrahydrochloride has the chain extended,sa and whose hydrated phosphate has the chain folded.sb The valency angle C(l)-C(6)-C(7) of 97", and the bond C (6) -C (7), 1.6 1 long are unexceptional ; similar small valency angles, one of whose 'arms' is a long bond, at a quaternary carbon in a five-membered ring have been reported for some steroids.10 The cyclohexanone ring is folded, approximately about the line C(2) C(5), into a TABLE 6 Some intramolecular contacts (A) C(4) - - - C(7) 0(1) .* * C(13) 2-84 C(2) - * C(13) O(1) - * * C(16) C(3) - * - C(6) O(2) . * * C(25) C(4) - - - C(13) O(3) . * C(3) 2.73 C(5) * - * C(14) O(3) . * * C(5) 3.36 C(6) - - C(15) O(3) * - C(13) 3.62 C(7) - * C(14) O(4) * * * C(l) C(7) * * * C(25) O(4) . * * C(5) C(8) - - - C(13) N(l) * * C(13) 3.60 C(8) - - - C(24) N(1) * * * C(18) C(9) * * * C(23) N(2) * - * C(20) C(14) - - * C(16) N(2) .* - C(25) C(15) * - * C(17) N(3) * * * C(17) C(16) * * * C(19) N(3) - * - C(22) 3.84 C(18) * * C(20) 2.82 2-90 2.94 O(2) 9 * * C(22) 3.52 3.64 3.03 3.02 3.60 3-87 C(l) * * * C(4) 2.93 C(19) * C(21) C(l) . * * C(14) C(21) * * ' C(23) 3.77 C(2) . * - C(5) 2.80 C(22) - - C(24) 3.58 2.95 3-20 3.95 2.9 1 3.84 3-23 3-72 3.10 2.92 3.91 3-79 3.71 3-92 3-16 3-24 3-58 3-81 sltew-boat. This conformation is dictated more by intra- molecular forces than by the requirements of crystal packing, as the same conformation is displayed by the hydrobromide ; the two salts crystallize in different space- groups, with different hydrogen bonding. Table 7 lists the closer intermolecular contacts. The TABLE 7 Intermolecular contacts (a) Hydrogen bonded (A) N(3) * - - O(l1) N(3) - * * O(5II) O(4) * * - O(5I") 2.69 2.87 2.99 Interaction angles a t N(3) (") C ( 1 9)-N (3)-C( 20) 116 C(19)-N(3) .O(1') 107 C(19)-N(3) * * 0(5I*) 101 C(20)-N(3) - * O(1') 115 C(20)-N(3) * O(5II) 111 O(l1) * - N(3) * * - O(5II) 105 Interaction angle a t 0(1) C(15)-0(1) * * - N(31V) 142 (b) Involving the iodide ion (A) I * * * C(21V) I * * C(22V) 3.99 I * + * O(1fl) 3.95 I * * ' C(20V) 4.08 I - - * O(3n) 4.21 4.33 I * * C(12VI) 4.62 (G) van der Waals (A) (< 3.8 A) C(19) * * - O(l1) 3-42 C(19) * * O(5II) 3.46 C(18) * - * O(1') 3-51 C(4) - - - O(5'II) 3.52. C(20) - - - 0(11) 3-58 C(3) * * - O(5III) 3.61 C(21) * * * O(5II) 3.62 O(51') 3.67 Eg). '. '. b(5111) 3.68 C(21) * - * C(29 3.68 N(3) - - - C(153 3-76 N(3) * - * C(16') 3-77 C(16) - - O(63 3.79 The Roman numerals as superscripts refer to the following equivalent positions : I & - - , 1 - y , 4 + z 5, 4 + y, 8 - 2 IV 4 - x , 1 - y, -* + z I1 3, y , 1 + z v g - x x , l - y , - - Q + z VI Q - x , 1 - y , --Q+z I11 iodide ion is located only by van der Waals forces, its six nearest neighbours being C(20), C(21), and C(22) of one molecule, 0(3), C(1), and C(12) of another.The inter- atomic distances involved are all of the order of the sum (4.16A) of the covalent radii of >CH2 (2-0A) and the iodide ion (2-16 A).11 Figure 2 shows the molecular packing projected down the c axis. The molecules are held together by hydrogen bonds, the most important one being N(3) **. 0(1) (2.69 A). This is relatively short for an NH *-. 0 bond, and its strength is reflected in the distortion (see earlier) of the acrylamide residue involved. There is an analogous short (2.68A) bond in spermine phosphate of the type NH O(phos- phate).& By contrast, the hydrogen bonds involving the water molecule are relatively long. There are thirteen '14 - +- f7 FIGURE 2 The molecular packing, viewed down the G axis. Items heavily outlined are closer to the observer than those lightly outlined van der Waals contacts (3.8 A, other than those which are hydrogen-bonded. Of these, seven involve the oxygen, 0(5), of the water molecule. Thus the latter seems little more than a space-filler between molecules with rather weak intermolecular bonding. We thank Dr. Bladon for a sample of lunarine. The structure was solved and refined using the KDF 9 computer a t the University of Glasgow with programs written by Professor D. W. J. Cruickshank and Drs. D. R. McGregor, K. W. Muir, D. R. Pollard, J. G. Sime, and J. G. F. Smith. Final Bijvoet calculations and the determination of the molecular geometry were made by use of programs from the University of Sussex, made available by Professor G. Sim and Dr. A. McPhail, and adapted for the ICT 1905 at the University of Strathclyde by one of us (J.A.D. J.). [9/1094 Received, June 27th, 19691 lo A. Cooper, C. T. Lu, and D. A. Norton, J . Chern.. SOC. (B), 1968, 1228; Y. Tsukuda, T. Sato, and M. Shiro, ibid., 1968, 1387, and references therein. 11 L. Pauling, ' The Nature of the Chemical Bond,' Cornell University Press, Ithaca, New York, 1960, pp. 261, 514.