2 Physical Methods Part (v) X-Ray Crystallography By A. F. CAMERON Chemistry Department University of Glasgow Glasgow G 12 8QQ 1 Introduction The current twelve-month period covered by this report has seen the continued publication of a large number of crystallographic examinations of organic com- pounds. Within this body of published work however it is possible to identify certain trends. Thus groups of workers may study series of compounds which are sufficiently large to indicate significant structural trends but more impor- tantly they are able to achieve this object in a relatively short space of time. More- over apart from studies of natural products it is now fairly unusual to encounter the heavy-atom method the use of direct methods for light-atom structures being commonplace.It would seem that the accuracy which may be achieved by use of diffractometer techniques of data collection for light-atom structures has resulted in a renewed interest in the detailed bonding effects which may be detected and studied by X-ray crystallography. In this context we observe an increasing number of publications in which genuinely ‘long’ C(sp3)-C(sp3) bonds are reported. As in previous years the large volume of published work necessitates that this article can describe no more than a small number (ca. 10%) of the organic studies which have been reported. Those analyses which are included for discussion have therefore been chosen in an attempt to present a spectrum of the crystallographic studies of organic molecules which are currently being reported and to give some impression of the relevance of the results to modern chemistry.2 Conformation and Bonding Several analyses have been undertaken to study the bonding and conformations of ylides. Compounds of this type which have been examined include the ammonium ylides (1) and (2)’’ and the sulphonium ylide (3),2 all of which are (1) (2) N. A. Bailey S. E. Hull G. F. Kersting and J. Morrison Chem. Comm. 1971 1429. J. P. Schaefer and L. L. Reed J. Amer. Chem. SOC.,1972 94 908. 90 Physical Methods-Part (v) X-Ray Crystallography I I Me Me (34 (3b) stabilized by the carbonyl function. The delocalization of the negative charge into the carbonyl groups of all three molecules is evidenced both by the lengths of the C-CO bonds [1.36 A in (1); 1.34 8,in (2); 1.400(6) 8,in (3)] and also by the lengths of the carbonyl bonds themselves [respectively 1.27 1.30 and 1.248(5)A].In the case of (3) it is suggested that the canonical form (3b) contri- butes 85 % to the structure. (+)-3-Diazocamphor (4)3 is also an ylide but in contrast to the geometries of the previous molecules the dimensions [C-CO 1.448(9);C=O 1.215(8) 8,]suggest that the additional stability of diazoketones over the corresponding diazoalkanes results from only minor contributions from the enolate forms of the ketonic derivatives. An allene-type geometry has been observed for di-p-tolylcarbodi-imide (5),4 in which the two C-N=C planes are approximately normal (38') to each other and in which the central N=C=N valence angle has a value of 170.4(4)".An interesting feature of this molecule is that the two C=N bonds have significantly different lengths [1.204(4) and 1.223(5) A] which are thought to result from dif- ferent values of the torsion angle (7.8" and 19.8") about the N-C(pheny1) bonds the longer bond being associated with the larger angle. Diphenylmethylene- aminodimesitylborane (6)' also proves to have an allene-type geometry the C-B-C and Ph-C-Ph planes being inclined at 87". The length of the B=N bond is 1.408,. Small-ring compounds which have been studied include diphenylcyclopro- penethione (7a),6 which is planar with the exception of the phenyl rings which are twisted out-of-plane by 4". The S=C bond has a length of 1.630(2)& and the non-equivalence of the C-C bonds within the cyclopropene ring [C=C A.F. Cameron N. J. Hair and D. G. Morris J.C.S. Perkin II 1972 1331. A. T. Vincent and P. J. Wheatley J.C.S. Perkin II 1972 687. G. J. Bullen and K. Wade Chem. Comm. 1971 1122. L. L. Reed and J. P. Schaefer J.C.S. Chem. Comm. 1972 528. A. F. Cameron (mesityl) C Ph \ / B=N=C / (mesityl) C \Ph Ph Ph Ph Ph (6) (74 (7b) 1.338(2);C-C 1.403(2)A]indicates that the structure is not well defined in terms of the zwitterionic form (7b) which would probably exhibit the equivalent bond lengths previously demonstrated for the cyclopropenium ion. Cyclobutane derivatives which have been examined include the head-to-head allene dimers (8) and (9),7 and the photo-cycloaddition product The analyses of (8) and (9) are the first to be reported for compounds containing the 1,2-dimethylenecyclo- butane group.In both molecules the chlorine atoms are trans and neither the cyclobutane rings nor the butadiene moieties are planar. The configuration of (10) is consistent with the suggestion that the photo-addition starts at C-3 and that rotational equilibration of the diradical intermediates is completed before ring-closure. In this case also the cyclobutane ring is non-planar with a dihedral angle of 149.3'. Me Me phYph CI C1 c1-c1 or (53 + C! The analyses of the oxazepines (11)9 and (12)" are representative of the con- formational studies of seven-membered heterocyclic compounds. Both molecules adopt boat conformations and the bond lengths are consistent with their being ' S.R. Byrn E. Maverick 0. J. Muscio K. N. Trueblood and T. L. Jacobs J. Amrr. Chem. SOC.,I97 1,93 6680. F. P. Boer and P. P. North J.C.S. Perkin 11 1972 416. B. Jensen Acta Cryst. 1972 B28 774. lo B. Jensen Acta Cryst. 1972 B28 771. Physical Methods-Part (u) X-Ray Crystallography conjugated trienes. Another seven-membered ring derivative 4,5-dihydrothiepin 1,l-dioxide (13),11 exhibits unusually short C=C bonds (1.31 1 A). It is suggested that this effect may arise from the electronegativity of the >SO group. The Ph C,H,-p-Br (11) (12) eight-membered ring of (14)12 is constructed from the three planar groups N-C-C-CH N-C-C-CH, and N-P-N.The phosphorus atom is tetrahedral and the mean P-N bond length is 1.644 A. The bonding environ- ments of the nitrogen atoms are planar and it is suggested that they are sp2 hybridized. Cyclohexasulphur-1,3-di-imide(15) proves to have a crown con- f~rmation,'~ but does not possess the expected mirror symmetry. The average S-S and N-S bond lengths are respectively 2.055(2) and 1.672(4) A. 0 .C' Both 1,2,3,4-tetrathiadecalin( 16)' and cis-1,4,5,8-tetraoxadecalin ( 17)' adopt chair-chair conformations. The geometry of (16) is noteworthy for the small values of the dihedral angles at the three S-S bonds (68.3,66.1 and 69.1") and (17) is said to be a unique example of two adjacent anomeric moieties incor- porated in a bicyclic system with C symmetry.Several bicyclo[3,3,l]nonane compounds which are unsubstituted at positions 3 and 7 have also been shown to adopt chair-chair conformations although the cyclohexane rings are distinctly flattened. However in cases where there are bulky endo substituents either at position 3 or at position 7 it has been predicted that a boat-chair conformation would be more favourable. Thus for (18) and its 2-hydroxy-analogue it has been argued that boat-chair geometry would relieve the Br -H-C-7 interaction which would otherwise occur in the chair-chair form. An analysis of (18)16 I' H. L. Ammon M. R. Smith and E. Kelso Acra Cryst. 1972 B28 246. ' * T. S. Cameron J.C.S. Perkin II 1972 591. l3 H. J. Postma F. van Bolhuis and A. Vos Acta Cryst. 1971 B27 2480. l4 F. Feher A.Klaeren and K.-H. Linke Acta Cryst. 1972 B28 534. l5 B. Fuchs I. Goldberg and U. Shmueli J.C.S. Perkin II 1972 357. I' P. D. Cradwick and G. A. Sim J. Chem. Sac. (B) 1971 2218. A. F. Cameron confirms the boat-chair conformation in this instance and reveals additionally that this conformation is adopted despite the almost eclipsed positions of the bromine and carbonyl moieties [Br -0 3.05 A]. Heterocyclic molecules which exhibit extensive delocalization have been studied in some depth. 1,8-Naphthyridine (19)17 proves to be non-planar with the two rings twisted in opposite directions about the bridgehead C-C bond. The twisting is attributed to repulsion between the nitrogen lone-pair electrons since the molecule is planar when co-ordinated to a metal atom via the nitrogen atoms.2-Oxazolidinone (20a)' was examined to investigate the molecular geometry in the light of the unusual ability of the molecule to complex with a wide variety of compounds such as phenols aspirin saccharin iodine etc. The molecule is planar and the dimensions indicate that (20b) and (20c) are major resonance components thus resulting in a high degree of polarization which may well be responsible for the unusual complexing properties. Both (21a) and (2lb)" are pyrazolinone azomethine dyes. Neither molecule is planar but (21a) deviates more from planarity than does (21b) the dihedral angles between rings A and B having values of 56.6 and 13.9" respectively. The dimen- sions of the azomethine linkages in the two molecules also differ significantly [N-C 1.399(3) N=C 1.297(3)8 in (21a); N-C 1.399(3) N=C 1.292(3)8 in (21b)j and it is concluded that for these two molecules at least the azomethine linkage is not an isoenergetic system.The influence of the heteroatom on the delocalization properties of certain molecules is exemplified by the analyses of (22a) and (22b).20 Chemically the two molecules are quite different the 7-amino-group of (22a) undergoing ex- tremely facile nucleophilic substitution whereas that of (22b) reacts much less li A. Clearfield M. J. Sims and P. Singh Acra Cryst. 1972 B28 350. J. W. Turley Acta Cryst. 1972 B28 140. l9 D. L. Smith and E. K. Barrett Acta Cryst. 1971 B27 2043. *' E. Shefter B. E. Evans and E. C. Taylor J. Amer. Chem.SOC.,1971 93 7281. Physical Methods-Part (v) X-Ray Crystallography N 6NY Ry-yR d -”X (22) a;X = 0 b;X = S NEt (21) a; R = H b;R=Me readily. There is also ready photo-addition to the 6,7-bond of (22a) a property which is not found in (22b) and its analogues. The analyses reveal that whereas (22b) is extensively delocalized throughout the whole molecule (22a) is de- localized only in the pyrimidine ring and may be thought of as a pyrimidine ring with a pair of strongly electronegative substituents (oximes). The suscepti- bility of (22a) to nucleophilic attack at C-7 may therefore be attributed to an elec- tron deficiency at that atom while the facile photo-reduction may be ascribed tentatively to a high formal oxidation state.It is also worthy of comment that the 6,7-bond has a length of 1.330 8 in (22a) and 1.355 8 in (22b) this being the largest difference between the pyrimidine rings of the two molecules. A similar conclusion results from the examination of 5-chloro-2,1-benzisothiazole(23),2 the dimensions of which suggest that it is almost completely delocalized. This is in contrast to the incomplete delocalization of the benzisoxazole analogues and there is again a difference in the chemical reactivities of the sulphur and oxygen compounds. Both chemical and n.m.r. evidence indicate that whereas 11,1l-difluoro-1,6- methano[lO]annulene shouId possess the annulene structure (24) the corre- sponding 11,ll-dimethyl derivative should possess the bisnorcaradiene struc- ture (25).A previous analysis22 had confirmed this prediction in the case of the difluoro-compound and a more recent study of the dimethyl -analogue2 indi- cates that it is structurally quite different from (24),the structure (25) being more appropriate. It must be stated however that the validity of this latter conclusion necessitates regarding the C-1 -C-6 distance of 1.80 8 as an extremely long and weak bond. (23) (24) (25) 21 M. Davis M. F. Mackay and W. A. Denne J.C.S. Perkin II 1972 565. 22 C. M. Gramaccioli and M. Simonetta Tetrahedron Letters 1971 173. 23 R. Bianchi A. Mugnoli and M. Simonetta J.C.S. Chem. Comm. 1972,1073. 96 A. F. Cameron 'Long' C(sp3)-C(sp3) bonds are also a feature of several cage molecules such as the ethano-bridged diadamantane (26),24 and the heterocyclic derivatives (27)25 and (28),2" although in none of these cases do any of the bonds approach the values observed in (25).In such molecules the long bonds are usually those bonds about which the substituents are fully eclipsed. Thus in (26) the ethano- bridging bond has a length of 1.552(2)A and the bond forming the junction of the fused piperazine rings in (27) has a length of 1.574(3)A. In the case of (28) which is the photodimer of 5,6,7,8-tetrahydro-2-quinolone, the long bonds [1.623(3)A] are those which affect the dimerization and their length is associated with the facile reversal of the dimer of the monomeric state. @ o)g$o N Investigations of long bonds involving sulphur atoms continue apace.Of particular relevance to such structural studies are the recently published CND0/2 calculation^^^ for asymmetrically substituted thiathiophthens. These calcula- tions predict that 2-methyl and 2-phenyl substituents cause lengthening of the S-S bond in the substituted ring and that in the phenyl-substituted case the lengthening depends on the angle of twist of the phenyl group relative to the thiathiophthen. 3-Methyl and 3-phenyl substituents are predicted to cause a shortening of the relevant S-S bond although the effect is very small for the phenyl-substituted molecule. These results are not only confirmed by previous analyses of the thiathiophthens but also gain further support from the subse- quent analyses of the diaza-analogues (29)28 and (30).29 In the case of (29) there is little difference between the inclinations (2.9 and 7.0") of the two phenyl rings relative to the heterocyclic system and the S-S bonds [2.319 2.328 A] are very similar.However in the 2,5-dianilino derivative (30) one aniline group is in- clined at 51" to the heterocyclic system and is associated with a short s-S bond [2.225(3)A] whereas the angle of inclination of the other aniline substituent (1 1") is reflected in an S-S bond length of 2.475(3)A. (29) (30) 24 S. T. Rao and M. Sundaralingam Acta Cryst. 1972 B28,694. 25 R. D. Gilardi Acta Cryst.,1972 B28 742. 26 J. N. Brown R. L. R. Towns and L. M. Trefonas J. Amer. Chem. Soc. 1971,93 7012. 2' L. K. Hansen A. Hordvik and L. J. Saethre J.C.S. Chem. Comm. 1972 222.28 A. Hordvik and L. Milje J.C.S. Chem. Comm. 1972 182. 29 A. Hordvik and P. Oftedal J.C.S. Chem. Comm. 1972 543. Physical Methods-Part (11) X-Ray Crystallography In molecules where there are approximately linear arrangements of four sulphur atoms a much wider variation of S-S distances is observed. Thus in (31)30the S-1-S-2 [2.482(1)A] S-2-S-3 [2.209(1)A] and S-3..-S-4 [2.965(1) A] distances indicate that the S-1-S-2-S-3 sequence constitutes a formal thia- thiophthen resonance system which is relatively unperturbed by the presence of S-4. However this structure may be contrasted with the structures of (32)3’ [S-l-S-2 and S-3-S-4 2.062 A; S-2**.S-3 2.863 A] and (33)32 [S-l..-S-2and S-3.-*S-4 2.8 A ; S-2-S-3 2.2 A] in which no thiathiophthen structures are apparently established although the relatively long S..-Scontacts of ca.2.8 A must represent some degree of interaction however weak. R (33) R = Me or Ph Bonding situations comparable to those of the thiathiophthens may also be identified in molecules containing oxygen or nitrogen replacing one or more of the sulphur atoms. In (34)33 the N-S distances are considerably longer [1.901(5) 1.948(5) A] than an N-S single bond whereas (35)34 contains a short S..-O[2.255(8)A] interaction. In the case of(35),the length of the carbonyl bond (35) (34) is 1.269(14)A and the authors suggest that there is now evidence of correlation between Av values for ketones and the strengths of the S..*Ointeractions in which they are involved. 30 J.Sletten Acta Chem. Scand. 1971 25 3577. 31 J. Sletten Acra Chem. Scand. 1972 26 873. ’* J. E. Oliver J. L. Flippen and J. Karle J.C.S. Chem. Comm. 1972 1153. 33 A. Hordvik and K. Julshamn Acra Chem. Scand. 1972 26 343. 34 R. Pinel Y. Mollier E. C. Llaguno and I. C. Paul Chem. Comm. 1971 1352. A. F. Cameron 3 Solid-state Rearrangements and Intermolecular Interactions Several analyses have been devoted to studying the courses of solid-state reactions and rearrangements. For example the benzophenone oxime-0-picryl ethers (36a-c) not only undergo Beckmann rearrangements in solution to form [cia the intermediates (37a-c)] the respective picryl anilides (38a-c) but on heat- ing have also been observed to undergo the same reaction in the crystalline state to produce identical products.This observation prompted a crystallographic in~estigation~~ (Table) of (36a-c) and (38a-c) which also included full analyses Table Crystallographic data for the derivatives (36a4) and (38a-c) Volume per molecule Compound Space group A3 Packing fraction" 0.95 0.96 0.99 " The packing fraction is defined as 1 -A/T where A is the difference in molecu-lar volumes and T is the volume of the larger molecule. of (36b) and (36c). This study reveals that the conversions (36aj 38a) and (36b +38b) give rise to a contraction of only about 5% in cell volume and that the conversion (36c -+ 38c) produces no measurable contraction. In those re- arrangements where the molecular shapes and interplanar spacings of the start- ing materials suggest minimal disruption of the crystal the products in fact p-X-C6 H4\ /O-Pic pic -0 \ -+ /C=N p-Y-C,H4 P-X-C,H /C=N \C,H,-p-Y (36) (37) a;X = Y = H b;X = Br Y = H c; X = H,Y = Br C6H4-p-Y (38) separate as micro-crystallites which have no net orientation with respect to the parent crystal.However it is possible to construct models of the products which have space-filling characteristics similar to those of the reactants and this may 35 J. D. McCullough I. C. Paul and D. Y. Curtin J. Amer. Chem. Sac. 1972 94 883. Physical Methods-Part (v) X-Ray Crystallography 99 well account for the tendency of the products to remain in the matrix of the starting material. In another case the pho to-dimer izat ion of 2-benzy l-5-p-br omobenzylidene-cyclopentanone (39),36it proved possible to complete an analysis of the dimer but crystal decomposition prevented more than an initial investigation of the monomer.However both monomer and dimer crystallize in the same space group Pbca with unit cells of similar volume (< 3.5 % difference) and it would seem that the small changes in cell dimensions are sufficient to allow the dimeriza- tion to take place without drastic reorganization of the molecular arrangement. C,H,-p-Br flBr / hv Ph *H-Ph Ph 0 H 0 (39) C,H ,-p-Br In both previous examples the overall reaction has comprised two elements. Firstly there is the reorganization in the solid-state arrangement of the molecules and secondly there is the formation of new chemical bonds to establish the products the exact sequence of events probably depending on an intimate inter- dependence of the two processes.However it is possible to have a solid-state transformation which involves only a spatial rearrangement of the molecules without the attendant chemical changes of the previous two cases. Thus di- methyl 3,6-dichloro-2,5-dihydroxyterephthalate(40)37occurs in yellow and OH OH (40) white crystalline forms and it is possible to convert the yellow into the white form. Analyses of both crystalline modifications reveal that both forms crystal- lize in space group Pi (yellow form one molecule per cell a = 9.595 b = 4.301 c = 7.970 A cc = 114" 19' /l = 94" 58' y = 106" 9' ;white form two molecules per cell a = 9.842 b = 7.841 c = 10.576& ct = 116" 23' /l = 124" lo' 7 = 88" 59').The planar centrosymmetric molecules of the yellow phase are stacked along b and are characterized by an internal hydrogen bond. In the structure of the white phase the molecules are non-planar the methoxycarbonyl groups being 36 D. A. Whiting J. Chem. SOC.(C) 1971 3397. 37 S. R. Byrn D. Y.Curtin and I. C. Paul J.Amer. Chem. SOC.,1972 94 890. A. F. Cameron rotated out of the benzene plane by 86" 28' and 72" 38' and although the mole- cules are again stacked along b they are in this case linked by intermolecular hydrogen bonding. Comparison of the two crystal structures reveals that the yellow --+ white transformation involves a change from intra- to inter-molecular hydrogen bonding a change in conformation from planar to non-planar and also a flipping of every aromatic ring through 180°C.Rather less dramatic but nevertheless significant differences are observed on comparison of the room-temperature and liquid-nitrogen-temperature phases of Wurster's Blue perchlorate [(TMPD)ClO,] (41).38 In both cases the TMPD+ (41) ions are stacked along a the ions being equidistant in the room-temperature phase but with alternating aromatic . aromatic interplanar separations in the low-temperature phase. However despite the alternating distances in the latter form a close examination reveals that equidistance is maintained in the N N interionic separations as a result of side-stepping and flexing of the molecules.-N distances in both forms are very similar. Moreover the N Other investigations of interactions between molecules and ions in the solid state have included analyses of several charge-transfer complexes such as NN'-dibenzyl-4,4'-bipyridylium di-i~dide~~ and (morpholiniumf),(7,7,8,8-tetracyano-quin~dimethane);-.~' In addition two studies of hydrogen bonding41p4* have revealed the existence of a dihydrated oxonium ion H,O:. 4 Natural Products Related and Biologically Active Molecules 11-&-Retinal (42)43acts as a photochemical sensor in visual systems and in the dark is covalently linked to proteins (opsins) in the retina. The primary event in the visual excitation process is the conversion of the 1 1-cis-isomer into all-trans- retinal.In an effort to provide information which will contribute towards a Me Me Me OA H 38 J. L. de Boer and A. Vos Acta Crysl. 1972 B28 835. 39 J. H. Russell and S. C. Wallwork Acta Cryst. 1971 B27 2473. 40 T. Sundaresan and S. C. Wallwork Acta Cryst. 1972 B28 491. 41 J.-0. Lundgren Acta Cryst. 1972 B28 475. 42 J.-0. Lundgren and P. Lundin Acta Cryst. 1972 B28 486. 43 R. D. Gilardi I. L. Karle and J. Karle Acta Cryst. 1972 B28 2605. Physical Methods-Part (u) X-Ray Crystallography 101 detailed understanding of the visual process analyses of both isomers have been undertaken. The chain of all-tr~ns-retinal~~ proves to be extended although it is both markedly curved within its general plane and is also slightly bent normal to the plane.The main feature of the side-chain of 11-cis-retinal is the signifi- cantly non-zero torsion angle about the C-12-C-13 single bond such that the conversion of the 11-cis into the all-trans isomer involves both a rotation of 180" about the C-11-C-12 double bond. and also a rotation of ca. 141" about the C-12-C-13 bond. Although chemically different both diphenylhydantoin (43)45 and diazepam (44)4hshow similar anticonvulsant drug activities. An examination of both compounds reveals that despite the chemical differences the space-filling charac- teristics are very similar. In particular the relative orientations of the phenyl rings and the carbonyl groups in the two molecules are directly comparable. Me H (43) (44) This observation leads to a tentative and preliminary suggestion that the latter feature may be pertinent to anticonvulsant activity.It has also been suggested that many local anaesthetics owe their activity at least in part to an ability to complex with phospholipids in neural membrane the resulting complex being instrumental in blocking nerve conduction. Previous studies of phosphate complexes of the local anaesthetics procaine and phenacaine have led to the additional suggestion that it is the hydrogen-bond donor capabilities of such molecules which are of significance in the biological complex formation. These studies have now been extended by analyses of the bis-p-nitrophenyl phosphate complex of benzocaine (ethyl-4-aminoben~oate)~'and of lidocaine hexafluoro- arsenate (45).48 In the case of the benzocaine complex all the hydrogen atoms of Me Me (45) 44 T.Hamanaka T. Mitsui T. Ashida and M. Kakudo Acta Cryst. 1972 B28 214. 4s A. Camerman and N. Camerman Am Crysr. 1971 B27 2205. 46 A. Camerman and N. Camerman J. Amer. Chem. SOC.,1972,94 268. 47 J. Pletcher M. Sax and C. S. Yoo Acta Crysr. 1972 B28 378. 48 A. W. Hanson Acta Cryst. 1972 B28 672. A. F Cameron the protonated amino-group participate in Nf -H -0 hydrogen bonding with the phosphate group. The amino-group of lidocaine is also protonated and is sttrongly hydrogen bonded to the carbonyl-oxygen atom of a neighbouring molecule while the amido-group is weakly hydrogen-bonded [N-H. * -F 3.040(5)A] to the hexafluoroarsenate moiety.Terpenoid structures which have been examined include the sesquiterpenoid germacradienolide lactones eupacunin (46),49 liatrin (4’3,’’and melampodin (48).’ Both eupacunin and liatrin show significant anti-leukaemic and tumour- inhibitory properties and are in addition the first recognized germacranolide Me ‘rl ,Me Me%cHz (46) R = angeloyl ‘0 (47) MeO.+O cis-cis dienes. In contrast melampodin possesses a cis-trans geometry which results in severe distortions of the molecular geometry evidenced by torsion angles of 24 and 8” about the rrans and cis double bonds respectively. The structures of the diterpenes (-)-kaur-15-en-19-a1 (49)52 and 12-hydroxydaphne- toxin tribromoacetate (50)’ have also been determined. Although the former superficially resembles a steroid it proves to have an absolute stereochemistry exactly opposite to that normally observed for steroids.12-Hydroxydaphne-toxin has a molecular structure very similar to the structures of phorbol and 49 S. M. Kupchan M. Maruyama R. J. Hemingway J. C. Hemingway S. Shibuya T. Fujita P. D. Cradwick A. D. U. Hardy and G.A. Sim J. Amer. Chem. Soc. 1971 93 49 14. S. M. Kupchan V. H. Davies T. Fujita M. R. Cox and R. F. Bryan J. Amer. Chem. Soc. 1971 93 4916. S. Neidle and D. Rogers J.C.S. Chem. Comm. 1972 140. 52 I. L. Karle Acra Crysr. 1972 B28 585. 53 J. Coetzer and M. J. Pieterse Acta Cryst. 1972 B28 620. Physical Methods-Part (v) X-Ray Crystallography 103 neophorbol. There have also been several analyses of unusual steroids.9-0x0-9,l l-secogorgost-5-ene-3~,ll-diol 11-acetate (51)’’ and 23-demethylgorgosterol (52)54are cyclopropane-containing marine steroids while 4,4-dichloro-2a-aza-~-homocoprostan-3-one(53)’ contains an elactam ring. The analyses of two Me H-0 Me (49) OCOCH,Br (50) HO .. Me Me MeMe HO ” ci ‘CI (52) (53) crystalline modifications of 2,4-dibrom~estradiol~reveal that the same steroid molecule in three different crystalline environments (one modification contains two independent molecules per asymmetric unit) may well show significant variations in conformation. It is concluded that steroid conformations are s4 E. L. Enwall D. van der Helm I. N. Hsu T. Pattabhiraman F. J. Schmitz R. L. Spraggins and A. J. Weinheimer J.C.S.Chem. Comm. 1972 215. 55 H. Altenburg D. Mootz and B. Berking Acta Crysr. 1972 Bt8 567. s6 V. Cody F. DeJarnette W. Duax and D. A. Norton Acta Cryst. 1971 B27 2458. 104 A. F. Cameron influenced both by non-bonded intermolecular contacts and also by inter- molecular hydrogen bonding and that in the absence of other evidence care must be exercised when extrapolating from the results of a crystallographic determination. Other natural products and related derivatives which have been extensively examined include alkaloids sugars amino-acids and other constituents of proteins etc. Novel alkaloid structures are represented by the pyridine alkaloids maytoline (54)57and sceletium alkaloid A (55),'* and by the tetrahydroimi- dazo[ 1,2-a]pyrimidine alkaloid alchorneine (56).59 Sugars which have been studied include the septanose 3-0-acetyl-1,2 :4,5-di-O-isopropylidene-or-~-gluco-septanose (57h6' the seven-membered ring of which has a distorted chair OMe 0 AcO ._ H Ac (54) (55) Me OMe Me ' I CH Me-py>.-< Me Br-" H H Me (57) """;YY 0IOH HCH20H CH,OH OH OH H OH OH H (59) 5' R.F. Bryan and R. hl. Smith J. Chem. SOC.(B) 1971 2159. 58 P. W. Jeffs P. A. Luhan A. T. McPhail and N. H. Martin Chem. Comm. 1971 1466. 59 M. Caserio and J. Guilhem Acta Cryst. 1972 B28,151. 6o E. T. Pallister N. C. Stephenson and J. D. Stevens J.C.S. Chem. Comm. 1972 98. Physical Methods-Part (u) X-Ray Crystallography CH,OH CH,OH (60) conformation and the disaccharide 3,6-anhydro-~~-~-glucosyl-1,4 :3,6-dian-hydro-P-D-fructoside (58),6 which contains a highly strained tricyclic furanose moiety.The structures of the trisaccharides 1-kestose (S9)62 and planteose dihydrate (60)63have also been determined the latter proving to have an overall circular conformation in which the glucose and galactose units are hydrogen- bonded to the same hydroxy-group of a neighbouring molecule. " N. W. Isaacs and C. H. L. Kennard J.C.S. Perkin 11 1972 582. " G. A. Jeffrey and Y. J. Park Acta Cryst. 1972 BZS,257. 63 D. C. Rohrer Acta Cryst. 1972 B28 425.