2 Physical Methods Part (iv) X-Ray Crystallography By A. F. CAMERON and N. J. HAIR Chemistry Department The University of Glasgow Glasgow W.2 Two reports of general interest to crystallographers and to those interested in crystallographic results have been published by the International Union of Crystallography Commission on Crystallographic Apparatus. The first' discusses a statistical evaluation of seventeen sets of data collected for D( +)-tartaric acid using a variety of diffractometers and diffractometer techniques. The results show that two scaled sets of experimental data will most probably differ by 6% by no less than 3% and by no more than 10%. It is concluded that there are unsuspected sources of error in data collection and that further experi- ments should be designed to examine such problems.The second report2 discusses the significance of calculated estimated standard deviations derived from least-squares refinement. For positional parameters calculated e.s.d.s. are not infrequently a factor of 2 too small and are on average 3 too small. For vibrational parameters the corresponding factors are 4 and 23. These results confirm that structures of possible high precision but real low accuracy are not uncommon. The number of reported structure analyses during 1970has increased as it has done in recent years and including inorganic structures the volume of crystallo- graphic work now occupies several thousand papers in any one year resulting in the exclusion of many interesting analyses from this report.We have classified the selected compounds very much as in previous reports but have made one important addition. As distinct from the structural studies of natural products the structure-activity relationship of biologically active molecules (including pharmacologically useful compounds) is now well established and we have included a section devoted to analyses undertaken specifically to investigate such problems. Multicyclic Small and Large Ring Compounds.-Analysis of the interesting tricyclic compound 3,4 :7,8-dibenzotricyclo[4,2,0,02*5]octa-3,7-diene (1),3reveals that the molecule is centrosymmetric and in the anti configuration with two planar benzocyclobutene systems on opposite sides of the planar central cyclo- butane ring. Conformational strain may affect rates of solvolysis and the S.C. Abrahams W. C. Hamilton and A. McL. Mathieson Acta Cryst. 1970 A26 1. W. C. Hamilton and S. C. Abrahams Acra Cryst. 1970 A26,18. B. L. Barnett and R. E. Davies Acra Cryst. 1970 B26,1026. A. F. Cameron and N. J. Hair structure of trans-bicyclo[4,2,0]octan-l-yl3,5-dinitrobenzoate (2)4 was studied to determine the effects of the ring strain in relation to solvolysis studies. In this case the cyclobutane ring is non-planar with a dihedral angle of 147" and the strain of the bicyclic system is accommodated by the cyclohexane ring which is in a slightly flattened chair conformation. Of the twenty-three non-hydrogen atoms seventeen are planar. The conformation of the bicyclo[3,2,2]non-6-ene system has been the subject of two analyses one of 5-norbornene-2,3-endo- dicarboxylic anhydride,' and the other of syn-3-exo-p-bromobenzo yloxybicyclo-[3,2,2]non-6-ene-8,9-endo-cis-dicarboxylic anhydride.6 In both molecules strain is relieved by slight flattening of the three-carbon bridge and there is no evidence of twisting of the bicyclic skeleton about the bridgehead axis.The existence of an almost flat cyclohexane ring has been confirmed by the investigation of trans-8,8-dibromo-1,4,4-trimethyltricyclo[5, 1,0,03.5 ]octane (3).' This compound Me Me (3) is unusual crystallographically in that it crystallises in the space group P1 with three molecules in the unit cell each molecule having a slightly different con- formation. Spectroscopic methods were unable to distinguish between the planar and rapidly-inverting boat conformations of 1,4-cyclohexadiene.However the analysis of 1,4-cyclohexadiene-1-glycine' shows that in this case the cyclo- hexadiene ring is planar. The cyclobutane ring of trans-1,2-cyclobutane dicar- boxylic acidg has been shown to be puckered with a dihedral angle of 150" and B. L. Barnett and R. E. Davies Acta Crysf.,1970 B26 326. R. Destro G. Filippini C. M. Gramaccioli and M. Simonetta Acta Cryst. 1969 B25,2465. A. F. Cameron and G. Ferguson J. Chem. SOC.(B) 1970,943. ' G. Reck Tetrahedron 1970,26 599. R. J. Jandacek and S. H. Simonsen J. Amer. Chem. SOC.,1969,91,6663. E. Benedetti P. Corradini and C. Pedone Acta Cryst. 1970 B26,493. Physical Methods-Part (iu) X-Ray Crystallography as a result the two carboxy-groups have a quasi-equatorial relationship.The analysis of perchloro[4]radialene (4)" is the first reported structural investigation of this system. The molecule is symmetrical and non-planar and although there is considerable theoretical and spectroscopic interest in the possibility of cross-conjugation between the exocyclic double bonds the normality of the bonded distances indicates that there is little conjugation. The related compound tri-isopropylidenecyclopropane(5)' has also been studied and although it is planar the cyclopropane bonds are only slightly shortened and the exocyclic double bonds are of normal length. The cis-azaridine substitution in cis-1 1 -(p-iodobenzenesulphony1)-1l-azabi-cyclo[8,1,0]undecane (6)'' results in a non-ideal conformation of the cyclodecane ring.On the other hand the cyclodecane rings in both 1-hydroxycyclodecyl dimethyl pho~phonate'~ each and trans-3,10-dibromocyclodecane-1,2-dione,14 possess the boat-chair-boat conformation. In the latter compound the bromine atoms occupy semi-axial positions and the orientations of the carbonyl groups are such that the number of short H-..H contacts is minimised. The centro- symmetric molecules of all-cis- 1,6-dichlorodeca- 1,3,6,8-tetraeneI5 are not (6) (7) unexpectedly found to be distorted from stable cyclodecane conformations. A sulphur analogue of cyclodecane perhydrodibenzo[ 1,2,3,6,7,8]hexathiecin (7),16 has the 8-synclinical and 2-antiperiplanar partial conformation and is directly comparable with cyclodecane.The molecules possess a (crystallographic) centre of inversion and deviations from the higher 2/m symmetry are not signi- ficant. The cyclododecane ring in 1-hydroxycyclododecyl dimethyl phosphonate' possesses 222 symmetry. Substituted Benzene and Other Aromatic Compounds.-Salts containing the anion radical 7,7,8,8-tetracyanoquinodimethanide(TCNQ) include some of the best electrically conductive organic compounds known. An analysis of one such salt triethylarnmonium-bis-(TCNQ),' reveals face-to-face stacking and the intermolecular distances are such that the activation energy required for an electron to move from (TCNQ)- to (TCNQ)' is 0.06eV. The dimensions of lo F. P. van Remoortere and F.P. Boer J. Amer. Chem. SOC. 1970,3355. I' V.H.Dietrich Acta Cryst. 1970 B26 44. H. Zacharis and L. M. Trefonas J. Heterocyclic Chem. 1970,7,755. l3 G. Samuel and R. Weiss Tetrahedron 1970,26,3005. l4 P.Groth Acta. Chem. Scand. 1970,24 1051. l5 0.Kennard D. G. Watson J. K. Fawcett and K. A. Kerr Tetrahedron 1970 26 607. l6 F. Lemmer F. Feher A. Gierin S. Hechtfischer and W. Hoppe Angew. Chem. 1970 82,319. G. Samuel and R. Weiss Tetrahedron 1970 26 3951. l8 H. Kobayashi Y. Ohashi F. Marumo and Y. Saito Acta. Crysr. 1970,B26,459. A. F.Cameron and N. J. Hair the aromatic ring in the p-sulphobenzene diazonium inner salt (8)’’ suggest that it is quinoid in character. The tilt of the carboxy-group in substituted benzoic (8) acids may be related to whether the substitution pattern is ortho diortho or para the last producing a very much smaller tilt.The gross effect of diortho substitution is shown by the tilt of 48.5” in 2,4,6-trimethylbenzoic acid,” whereas in 3,4,5- trimethylbenzoicacid” the tilt is only 5.1”. Other substituted benzenecompounds which have been studied include p-methylaminophenol sulphate (metol),” p-nitroperoxybenzoic acidYz3 and hexaiodoben~ene.~~ Considerable effort has been devoted to studies of multi-phenyl compounds. The angle between the aromatic rings in 4-a~ety1-3’-bromophenyl~~ is reported to be 386”,although this is probably influenced by crystal-packing forces. Similarly p-terphenyl (9)26is non-planar but in this case there is found to be significant shortening of those aromatic bonds which do not run in the direction of the molecule.The average value of the joining bonds is 1.496(6)A. 1,l‘-Binaphthyl is claimed to be the simplest example of an aromatic hydro- carbon with a formal double bond. The molecule possesses two-fold symmetry (9) and the configuration is cis with an angle of 68”between the two naphthalene planes. The linking bond length of 1.475(5)A is in good agreement with the theoretical value. Both hexa-m-phenylene (1 1) and penta-m-phenylene (12) are described in one paper.28 Relief from overcrowding in these molecules is achieved both by deformations of the benzene rings and by twists of ca. 18” about axes joining the mid-points of adjacent exocyclic bonds. In the molecule of 5,6,11,12,17,18-hexadehydrotribenzo[aei]cyclodecene (13),29 variations are l9 R.L. Sass and J. Lawson Acta Cryst. 1970 B26,1187. ” F.Florencio and P. Smith Acta Cryst. 1970 B26,659. ’ F. H. Cano S. Martinez-Carrera and S. Garcia-Blanca Acru Cryst. 1970 B26,972. 22 L. Cavalca G. F. Gasparri A. Mangia and G. Pelizzi Acru Cryst. 1970 B26,498. ” H.S. Kim S-C. Chu and G. A. Jeffrey Acra Cryst. 1970 B26,896. 24 R.J. Steer S. F. Watkins and P. Woodward J. Chem. SOC.(C) 1970 403. 25 H. H. Sutherland and T. G. Hoy Acta Crysf. 1969 B25,2385. 26 H.M. Rietveld E. N. Maslen and C. J. B. Clews Acta Cryst. 1970 B26,693. 27 K.A. Kerr and J. M. Robertson J. Chem SOC.(B) 1969 1 146. H. Irngartinger L. Leiserowitz and G. M. J. Schmidt Chem. Ber. 1970,103 1132.29 H. Irngartinger L. Leiserowitz and G. M. J. Schmidt Chem. Ber. 1970,103 1119. Physical Methods-Part (iv)X-Ray Crystallography N CJ C C (13) (14) observed in the aromatic C-C bond lengths as a result of differences in hybridisa- tion of the ring carbon atoms. The molecule possesses rn point-symmetry loss of am2 symmetry being ascribed to crystal-packing effects. The non-aromaticity of [16]annulene (14)30has been investigated by structure analysis. Although the molecule is almost planar and possesses non-crystallo- graphic S symmetry the bond distances show almost complete alternation with the average single bond (alternately trans and gauche) 1.454(12)A and the Br R Me (15) (16; R = N and 0) average double bond (alternately cis and trans) 1- 333(12) A.Other non-benzenoid aromatic compounds which have been studied include tr~polone,~ which forms hydrogen-bonded dimers and 5,7-dimethyl-Zphenylcyclopent[cd]azulene (15),32 which is almost planar with dimensions in good agreement with SCF calculations. 30 S. M. Johnson I. C. Paul and G. S. D. King J. Chem. SOC.(B) 1970,643. H. Shimanouchi and Y. Sasada Tetrahedron Letters 1970,2421. 32 H. J. Lindner J. Chem. SOC.(B) 1970,907. 48 A. F. Cameron and N. J. Hair Of relevance to studies of charge-transfer complexes are the analyses of the two fluorene derivatives 2-bromodiazofluorene (16; R = N2)33and 2-bromo- ketofluorene (16; R = O).34 Fluorene forms charge-transfer complexes with a wide variety of molecules and is often used when a substance is not suitably crystalline or when a heavy-atom derivative is required.An example of a structure determined using its fluorene complex derivative is provided by the analysis of the 1 :1 complex between hexahelicene (17)35 and 4-bromo-2,5,7- trinitrofluorenone. The analysis allowed examination of the helical conformation of the severely overcrowded hexahelicene molecule. An investigation of the 1 1 perylene-tetracyanoethylene complex36 reveals that the molecular planes are almost parallel. Tetracyanoethylene is also the basis of a novel anthracene add~ct.~’ The crystals of this adduct also contain methylene chloride complexed with the tetracyanoethylene and in one triclinic unit cell (space group PI)there are eight molecules of the anthracene-tetracyanoethylene adduct two molecules of methylene chloride and one molecule of tetracyanoethylene.In the molecular complex of quinone-resor~cinol,~~ the quinone and resorscinol molecules are alternately linked side by side to form infinite molecular chains. These chains are packed plane-to-plane by charge transfer the perpendicular distance between planes being 3.1 A. The complex of s-trinitrobenzene-s-triamin~benzene~’ has the component molecules stacked alternately in charge- transfer arrangements. This is the first analysis of a complex with s-triamino- benzene as donor molecule. 2-Methylthio-l-phenylvinyl-2,4,6-trinitrobenzene-sulphonate (lS)40 is an example of a self-complexing molecule and the crystal 0 H3CSC 0-SIt 9 H II NO* 33 A.Griffiths and R. Hine Acta Cryst. 1970 B26 34. 34 A. Griffiths and R. Hine Acta Cryst. 1970 B26 29. 35 I. R. Mackay J. M. Robertson and J. G. Sime Chem. Comm. 1969 1470. 36 I. Ikemoto K. Yakushi and H. Kuroda Acta Cryst. 1970 B26 800. 37 I. L. Karle and A. V. Fratini Acra Cryst. 1970 B26 596. 38 T.Ito M. Minobe and T. Sakurai Acta Cryst. 1970 B26 1145. 39 F.Iwasaki and Y. Saito Acta Cryst. 1970 B26 251. 40 M.Meyers and K. N. Trueblood Acta Cryst.. 1969 B25 2588. 49 Physical Methods-Part (iv)X-Ray Crystallography structure consists of molecular complexes formed between two molecules by use of the electron-accepting trinitrobenzene and electron-donating phenyl- t hiomethylethenyl moieties. Heterocyclic Molecules Containing Nitrogen Sulphur and Phosphorus.-Investigations of the stereoselectivity of N-quaternisation of heterocyclic compounds led to the analysis of l-ethyl- l-methyl-4-phenylpipridiniumper-~hlorate.~' The results show that the alkylating agent approaches from the axial position while the piperidinium ring is in a chair conformation.The nitroxide structure 2,2,6,6-tetramethyl-4-piperidinol-l-oxy14zis of interest because it is used as a 'spin-label' in structure-function studies of biological molecules. The analysis reveals that the nitroxide plane is twisted 21" from the plane of the ring. That substitution of methyl groups for the N-hydrogen atoms of diketopiperazine results in a significantly non-planar but flattened chair conformation is shown by an analysis of NN'-dimethyl-diket~piperazine.~~ A centrosymmetric chair conformation has also been found for 1,4-dimethyl- hexahydro-s-tetra~ine~~ in the solid state although there is the possibility of other conformations in solution.The analysis of N-phenyl-2,4,6-trimethylpyridiniumperchlorate (1 9)45 is the first examination of this type of compound and it is found that the planes of the two aromatic rings are inclined at 83.5",thus precluding the possibility ofextended conjugation. Two analyses of hydroxypyridine hydrochlorides are discussed in the same and again represent the first crystallographic examinations of this class of compound. The structures were studied because there is the possibility of tautomerism with the hydroxypyridinium cations being in equili-brium with the pyridone forms.However the dimensions of the two molecules 2-hydroxypyridinium chloride (20a) and 2,6-dihydroxypyridinium chloride (20b) show that in the solid state the pyridinium tautomeric form is preferred. (19) (201 The analysis of ( + )-1-m-bromobenzoyl-4-methylazetidin-2-one (21)47 deter- mines the absolute configuration of the n-iolecule the four-membered p-lactam ring of which is almost planar with the N-atom very slightly out of the plane of the other atoms. The imidazolidine ring of 1-thiocarbamoylimidazolidine-Zthione " W. Fedeli F. Mazza and A. Vaciago J. Chem. SOC.(B) 1970 1218. '' L. J. Berliner Acru Cryst. 1970 B26,1 198. 43 P. Groth Acra Chem. Scand. 1970,23 3155. 44 G. B. Ansell J.L. Erickson and D. W. Moore Chem. Comm. 1970,446. O5 A. H. Camerman L. H. Jensen and A. T. Balaban Acru Cryst. 1969 BE,2623. *' S. A. Mason J. C. B. White and A. Woodlock Terrahedron Letters 1969 5219. '' E. F. Paulus D. Kobelt and L. H. Jensen Angew. Chem. 1969,81 1048. A. F. Cameron and N. J.Hair has been shown to be planar with the thiocarbamoyl group tilted 2.8" from the plane of the ring.48 The structures of the addition products of thioureas and dimethyl acetylenedicarboxylate have been subject to much controversy but BrW an analysis of one product formed by the addition of N-thiocarbamoylpiperidine and dimethyl acetylenedicarboxylate has shown that in this case the product is 5-methoxycarbonylmethylene-2-piperidino-A2- 1,3-thiazol-4-one Analyses of 1,3-dimethyl-2(3H)-imidazolethione,50 1,l-dimethyl-3-phenylpy- razolium-5-0xide,~ 2-a~etyl-3-indazolinone,~ and 4-amino-3-hydrazino-5-mer-capto- 1,2,4-tria~ole,~~ were all undertaken to study the detailed geometries and dimensions of the five-membered heterocyclic rings in relation to the possibilities of electron delocalisation.In each case the molecule is or nearly is planar and while the results do not suggest the formation of aromatic structures they do suggest that extensive delocalisation takes place and that the allocation of formal single- or double-bond character may be misleading. Similar results are obtained for the tetrazole structures dehydrodithizone (23),54 anhydro-5-mer- capto-2,3-diphenyltetrazolium hydr~xide,'~and the 5-tetrazole ylide (24).56 Conformations of carbazole molecules have been studied by analyses of trans-6,8-dibromo-1,2,3,4a79a-hexahydro-4a,9-dimeth ylcarba~ole~ and 1,2,3,4,4a,9u-hexahydro-4~,9-propanocarbazolium hydro bromide.' Three studies of hexamethylenetetramine (HMT) derivatives have been reported.In the 1 :3 adduct of HMT and the phenol molecules are 48 G. Valle G. Cojazzi V. Busetti and M. Mammi Acta Crysf. 1970 B26,468. 49 A. F. Cameron N. J. Hair N. F. Elmore and P. J. Taylor Chem. Comm. 1970 890. 50 G. B. Ansell D. M. Forkey and D. W. Moore Chem. Comm. 1970,56. 51 W. H. de Camp and J. M. Stewart J. Heterocyclic Chem. 1970 7 895. 52 D. L. Smith and E. K. Barrett Acta Cryst. 1969 BE,2355. 53 N. W. Isaacs and C. H. L.Kennard Chem. Comm. 1970,631. 54 Y. Kushi and Q. Fernando Chem. Comm. 1969 1240. 5s Y. Kushi and Q. Fernando J. Amer. Chem. SOC.,1970,92 1965. s6 G. B. Ansell Chem. Comm. 1970,684. 57 A. Bloom and J. Clardy Chem. Comrn. 1970 531. 58 S. Gottlicher Chem. Ber. 1970 103 46. 59 T. H. JordanandT. C. W. Mak J. Chem. Phys. 1970 52 3790. Physical Methods-Part (iu)X-Ray Crystallography 51 linked to each HMT molecule by O-H..-N hydrogen bonds in the form of a three-leaved propeller. A notable feature of the structure is the existence of hollow channels through the crystal in which there is the possibility of inclusion of guest molecules. The 1 :1 adduct of HMT and tri-iodomethane6' is formed by C-He * -N hydrogen bonds and by intermolecular N.* .I charge-transfer bonds. A neutron and X-ray diffraction study of HMT itself6' resulted in the location of the lone-pair electrons on the nitrogen atoms. Amongst other nitrogen-heterocyclic compounds reported are the 28-membered ring dimeric model of Nylon 66 1,8,15,22-tetra-aza-2,7,16,21-tetraoxocyclo-octacosane (25),62 cyclotetrasarcosyl,63 and the perhydromethiodide of an unsymmetrical N-alkoxycarbonylazepine dimer (26).64 0 0 II I1 Me HN-C-(CH2),-C-NH I I H N -C-(CH 2)4 -C-NH II !I 0 0 Ph (27; R = 3-quinolyl) (28) Analyses65 of the thiathiophthenes (27) and (28) reveal that in (27) the S*..S and S.. .N distances are 2.364(7) 8 and 1.887(7) 8 respectively whilst in (28) the corresponding distances are 2.814(8) 8 and 1.717(7) 8,.These distances suggest that S-methylation weakens the S * -S interaction in (28) and allows formation of a formal S-N bond which probably does not exist in (27). This interpretation is supported by analyses of the isothiathiophthene (29)66 and the similar com- pound (30),67 in both of which the exocyclic S..-S distances are appreciably shorter than twice the van der Waals radius for sulphur and in which there is probably exocyclic S-S partial bond formation. The structure and conformation of cis-9-methy1thioxanthene-10-oxide6*is reported the phenyl rings being in- clined at 127" and the central ring about which the molecule is folded being quite rigid. 'O T. Dahl and 0.Hassel Acta Chem. Scand. 1970 24 377. '' J. A. Duckworth B. T. M. Willis and G.S. Pawley Acta Cryst. 1970 A26 263. 62 M. G. Northolt Acta Cryst. 1970 B26 240. 63 P. Groth Acta Chem. Scand. 1970 24 780. 64 S. M. Johnson and I. C. Paul J. Chem. SOC.(B) 1969 1244. 65 F. Leung and S. C. Nyburg Chem. Comm. 1970 707. 66 R. J. S. Beer D. Frew P. L. Johnson and I. C. Paul Chem. Comm. 1970 154. '' J. Slatten Acta Chem. Scand. 1970 24 1464. 68 J. Jackobs and M. Sundaralingam Acta Cryst. 1969 B25 2487. A. F. Cameron and N. J. Hair Two phosphorus analogues of pyridine 2,6-dimethyl-4-phenylphosphorin (3 1),69 and 1,1-dimethyl-2,4,6-triphenylphosphorin(32)” have been reported. In both cases the molecule possesses two-fold (or approximate two-fold) symmetry and the C-P distances of 1.743(5) 8 and 1.749(5) 8 respectively in each molecule suggest significant C-P 7t-bonding.The C-C distances have average values of 1-390(8).$ and in both cases the heterocyclic ring is planar. The ring of 1,1,4,4- 1,4-diphosphoniatetraethyl-2,5-dimethylcyclohexadiene- 1,4-dibromide7 is also planar although in this case it is suggested that the dimensions correspond to a diene rather than to a delocalised structure. Other six-membered phosphorus Me, MefJ PyJh / Me Me& Ph Ph R (31) (32) (33; R = Ph or CI) heterocyclic compounds studied include 1,2,3,4-tetrahydro-l,2,2,3,4,4-hexa-methylphosphinoline-l-oxide,722,4,6-tris-(2,2’-dioxybiphenyl)cyclotriphospha- propane- 1,3-diol cyclic ph~sphate,’~ ~ene,~~ and bis(cyclopentamethy1ene)-diphosphine di~ulphide.’~ There are also two reports of four-membered phos- phorus cyclic compounds 1-chloro-2,2,3,4,4-pentamethylphosphetan-l-oxide (33; R = Cl)76 and the corresponding phenyl derivative (33; R = Ph).77 The four-membered rings are puckered and the stereochemistry around the phos- phorus atom is considerably distorted from tetrahedral geometry.Hydrogen-bonding Studies and C1athrates.-Potassium hydrogen malonate has been investigated both by X-ray7* and by neutron diffra~tion’~ techniques. The hydrogen malonate residues which possess two-fold crystallographic symmetry are linked in infinite chains by very short hydrogen bonds [2-459(5) A] 69 J. C. J. Bart and J. J. Daly J. Chem. SOC.(A) 1970 563. 70 J. J. Daly J. Chem. SOC.(A),1970 1832. 71 R. L. R. Towns R.Majeste J. N. Brown and L. M. Trefonas J. Heterocyclic Chem. 1970 7 835. 72 Mazhar-U1-Haque J. Chem. SOC.(B) 1970 71 1. 73 H. R. Allcock M. T. Stein and J. A. Stanko Chem. Comm. 1970,944. 74 Mazhar-U1-Haque C. N. Caughlan. and W. L. Moats J. Org. Chern. 1970.35 1446. 75 J. D. Lee and G. W. Goodacre Acta Cryst. 1970 B26 507. 76 Mazhar-U1-Haque J. Chern. SOC.(B) 1970,934. 77 Mazhar-U1-Haque J. Chern. SOC.(B) 1970,938. 78 J. G. Sime J. C. Speakman and R. Parthasarathy J. Chem. SOC.(A) 1970 1919. 79 M. Currie and J. C. Speakman J. Chem. SOC.(A) 1970 1923. Physical Methods-Part (iu)X-Ray Crystallography which lie across centres of inversion. Both carboxy-groups are coplanar with the methylenic carbon atom. The neutron diffraction analysis allows precise location of the hydrogen atoms although the fact that the hydrogen bonds lie across crystallographic centres of inversion does not necessarily imply that the bonds themselves are symmetrical.Neutron and X-ray studies of a-oxalic acid dihydrate and its deuterium analogue have also been rep~rted.~*-~~ It is observed that the hydrogen bonds expand slightly on substitution of deuterium for hydrogen. These four analyses also show bonding and lone-pair electrons and the significance of these results is discussed along with the techniques necessary for their observation. The ethynyl H. -SOinteraction in crystals of methylprop-2-ynylammonium-p-brom~benzenesulphonate~~ has been investigated. The lowering of the C-H i.r. stretching frequency is in accord with the bonding of the acetylenic hydrogen atom to the sulphonate anion the C-H-* -0distance being 3.36 A.The crystal structure of acetic acid has been redetermined” at both +5 “C and -190 “C. The dimensions of the molecule do not vary significantly with the changes in temperature although there are minor changes in the packing of the hydrogen- bonded chains. The two C-O distances within the molecule are however significantly different C=O being 1-220(6)8 and C-O(H) 1.318(7) A. The previous determination indicated no significant difference between these bonds. Dianin’s compound (34;X = 0)86 and its sulphur analogue (34;X = S)87have both been investigated by X-ray techniques. Both compounds are versatile organic clathrates and form crystalline inclusion compounds with ethanol (34; X = 0 or S) chloroform and many other organic solvents.The structures are isomorphous six host-molecules of Dianin’s compound linking by hydrogen bonds to form a cavity which has an ‘hour-glass’ shape. The guest molecules tend to be disordered and varying cell dimensions with different guest molecules indicate that the cage can expand slightly to accommodate different sizes of guest molecules. 8o R. G. Delaplane and J. A. Ibers Acta Cryst. 1969 B25 2423. 81 T.M. Sabine G. W. Cox and B. M. Craven Acta Cryst.. 1969. B25.2437. 82 P. Coppens and T. M. Sabine Acta Cryst. 1969 B25 2442. P. Coppens T. M. Sabine R. G. Delaplane and J. A. Ibers Acta Cryst. 1969 B25 2451. 84 J. C. Calabrese A.T. McPhail and G. A. Sim J. Chem. SOC.(B) 1970 282. 85 I. Nahringbauer Acra Chem. Scand. 1970 24 453. 86 J. L. Flippen J. Karle and I. L. Karle J. Amer. Chem. Suc. 1970 92 3749. 87 D. D. Macnicol H. H. Mills and F. B. Wilson Chem. Cumm. 1969 1332. A. F. Cameron and N. J. Hair Natural Products.-Two analyses of the diterpenoid alkaloid denudatine (35) have been rep~rted.~~p*~ The alkaloid has an asitine-type skeleton and may therefore serve as an intermediate in the biogenetic transformation of asitine- type alkaloids to acanitum-type alkaloids. Denudatine is isolated from Delphinium denudatum from the seeds of which is isolated the other novel alkaloid delnudine (36).90 Two lunarine (37)derivatives have also been ~tudied,~',~~ both analyses correcting the structure and stereochemistry wrongly assigned on the basis of chemical and spectroscopic evidence.The cyclohexanone ring adopts a twist- boat conformation which is stabilised by cis fusion to the dihydrofuran ring. A rigid cage structure of a new type is found in stemofoline (38),93isolated from the stems and leaves of Stemona juponica. The molecule is closely related to (37) (38) protostemonine. Another alkaloid from the same source stemonine hydro- bromide hemih~drate,'~ has also been studied. The structure of yohimbane hydr~bromide,~~ the unsubstituted parent compound of yohimbine P-yohimbine and coryanthine has also been reported. Lappaconine (39),96 studied as the hydrobromide proves to have a ring system identical to that of lycotonine and contains an intramolecular hydrogen bond which is part of a heterologous bifurcated hydrogen-bond system.As part of a systematic study of the alkaloids F. Brisse Tetrahedron Letters 1969 4373. 89 L. H. Wright M. G.Newton S. W. Pelletier and N. Singh Chem. Comm. 1970 359. K. B. Birnbaum Tetrahedron Letters 1969 5245. 9L C. Tamura and G. A. Sim J. Chem. SOC.(B) 1970,991. 92 J. A. D. Jeffreys and G. Ferguson J. Chem. SOC.(B),1970 826. 93 H. Irie N. Masaki K. Ohno K. Osaki T. Taga and S. Uyeo Chem. Comm. 1970 1066. 94 H. Koyama and K. Oda J. Chem. SOC.(B) 1970 1330. 95 J. P. Fennessey and W. Nowacki Z. Krist. 1970 131 342. 96 G. I. Birnbaum Acta Cryst. 1970 B26 755. Physical Methods-Part (iv)X-Ray Crystallography of perennial rye-grass the crystal structure and base synthesis of perlolyrine have been described.Analysis of hunteracine (41),98 a quaternary alkaloid representative of a series of quaternary bases for which no structures had been OH (42) postulated verifies that although the molecule is quaternary there is no N-alkyl residue and the dihydroindole moiety has the -OH group at the P-position. Amongst other alkaloids whose structures and stereochemistries have been determined are hetidine,99 the solanum alkaloid solanocapsine,loo bromo- dihydroacronycine,' O' rhoeagenine,' O2 verticinone,'03 6-epimesembran01,'~~ narcissidine,' O5 dichotine,'06 and meloscine-N,-methobromide.'07 Solstitialin (42),'O8 isolated from yellow star thistle causes 'chewing disease' in horses.The X-ray analysis has determined the structure and absolute stereo- chemistry and has shown it to be the first guaianolide-type structure isolated from this source. Analysis of ( +)-dibromodehydrotetrahydrorugolosin,'09 a heavy-atom derivative of (+)-rugolosin (43) has also established the structures and stereochemistries of (-)-luteoskyrin and (-)-rubroskyrin. Recent studies have implicated amino-acids as biogenetic precursors of the cyanogenetic 97 J. A. D. Jeffreys J. Chem. SOC.(C),1970 1091. 98 R. H. Burnell A. Chapelle M. F. Khalil and P. H. Bird Chem. Comm. 1970 772. 99 S. W. Pelletier K. N. Iyer V. K. Bhalla M. G. Newton and R. Aneja Chem. Comm. 1970 393. 100 E. Hohne H. Ripperger and K. Schreiber Tetrahedron.1970. 26 3569. 101 J. Z. Gougoustas and B. A. Kaski Acta Cryst. 1970 B26 853. I02 C. S. Huber Acta Cryst. 1970 B26 373. 103 F. Brisse Acta Cryst. 1970 B26 171. 104 P. Coggon D. S. Farrier P. W. Jeffs and A. T. McPhail J. Chem. SOC.(B) 1970 1267. 105 J. C. Clardy W. C. Wildman and F. M. Houser J. Amer. Chem. SOC.,1970 92 1781. 106 N. C. Ling C. Djerassi and P. G. Simpson J. Amer. Chem. SOC.,1970,92 222. 107 W. E. Oberhansli Helu. Chim. Acta 1969 52 1905. 10s W. E. Thiessen and H. Hope Acta Cryst. 1970 B26 554. 109 N. Kobayashi Y. Iitaka and S. Shibata Acta Cryst. 1970 B26 188. A. F. Cameron and N. J. Hair (43) (44) glucosides. The investigation of the unusual structure of gyanocardin,' lo with its cyclopentenoid nucleus has shed light on the nature of a possible amino-acid precursor.The structure of the chromophore (44)'''from the fluorescent peptide produced by the iron-deficient Azobacter uinelandii has been determined and proves to be a zwitterion. The molecule is almost planar and forms a layer structure with each layer of organic molecules separated by a layer of water molecules. 5a-Acetoxy-6~-bromohexahydrophysalin A' ' has the biogenetically interesting and novel 13,14-seco-16,24-cyclo-C28-steroidal structure in which the spiro-ring system leads to very short non-bonded distances. Two analyses of pulchellin derivatives' '3*1l4 have proved the structure and stereochemistry of pulchellin which are both in agreement with the biogenetic pathway involving the guaiano- lide guaillardin.Crystallographic studies of terpenoids include an analysis of the ten-membered ring sesquiterpene pregeijerene (49,'' the trisubstituted double bonds of which have a trans configuration and analyses of shiromodiol acetate (46)Il5 and elephant01 p-bromobenzoate (47).'lS The @-orientations of the 14- and 15-methyl groups in shiromodiol are locked by the 4,Sepoxide; otherwise the epoxide would be inside the ring resulting in prohibitive transannular over-crowding. The structure of a triterpene dimethylester E -1actone from dammar resin is reported,'16 and indicates that the compound is probably formed by I LO H. S. Kim G. A. Jeffrey D. Panke R. C. Clapp R. A. Coburn and L. Long,jun. Chem. Comm. 1970,381. Ill J.L. Corbin I. L. Karle and J. Karle Chem. Comm. 1970 186. I12 M. Kawai T. Matsuura T. Taga and K. Osaki J. Chem. SOC.(B) 1970,812. I13 T. Sekita and S. Inayama Tetrahedron Letters 1970 135. I14 K. Aota C. N. Caughlan M. T. Emerson W. Herz S. Inayama and Mazhar-U1-Haque J. Org. Chem. 1970,35 1448. 115 R. J. McClure G. A. Sim P. Coggon and A. T. McPhail Chem. Comm. 1970 128. 116 S. Brewis T. G. Halsall H. R. Harrison and 0.J. R. Hodder Chem. Comm. 1970 891. 57 Physical Methods-Part (iv)X-Ray Crystallography oxidation of asiatic acid. The analysis of methyl-6a-bromo-12-methoxy-7-oxopodocarpate' ''resolves conflicting n.m.r. and spectroscopic configurational evidence for 6-bromo-7-0x0-diterpenoids. The origin and structure of a-caryo- phyllene alcohol' ' are discussed in a report which is one of a series describing sesq ui terpenoid investigations.A novel variant of squalene cyclisation is produced by the presence of a seven-membered ring in the bromoindole derivative of 3P-methoxy-21 -keto-A1 3-serratene.'lg The analysis of this compound has uniquely defined the absolute 0 stereochemistry of the serratene family. OctahydrodipyridoC1,2-a 1',2'-c] imidazol-10-ium bromide (48),' 2o which is isolated from orchids represents a type of compound not previously found in nature. Analyses of naturally-occurring sugars include the studies of coriose,'2 'raffinose pentahydrate,'22 and D-manno- 3-heptulose.' Biological Studies.-Reported crystallographic investigations of large biological molecules are becoming more numerous and have included two reports of observed diffraction from crystals of t-RNA'24,'25 which should make near- atomic resolution possible.Enzymes which have been studied include a-and y-chymotryp~in,'~~,'~~ carboxypeptidase A,128 human lysozyme,' 29 lactate dehydr~genase,'~' and ela~tase.'~' In some cases the structures of the enzymes are already known and the reported studies are of enzyme-substrate complexes which yield specific information about the enzyme-substrate binding and hence about the possible mode of action of the enzyme. l7 G. R. Clark and T. N. Waters J. Chem. SOC.(C) 1970 887. K. W. Gemmell W. Parker J. S. Roberts and J. M. Robertson J. Chem. SOC.(B) 1970,947. 'I9 F. H. Allen and J. Trotter J. Chem.SOC.(B),1970 721. lZo E. Soderberg and P. Kierkegaard Acta Chem. Scand. 1970 24 397. 12' T. Taga K. Osaki and T. Okuda Acta Cryst. 1970 B26 991. '22 H. M. Berman Acta Cryst. 1970 B26 290. lZ3 T.Taga and K. Osaki Tetrahedron Letters 1969 4433. H. H. Paradies and J. Sjoquist Nature 1970 226 159. 125 R.D. Blake J. R. Fresco and R. Longridge Nature 1970 225 32. '26 T. A. Steitz R. Henderson and D. M. Blow J. MoI. Biol. 1969,46 337. ''' G. H. Cohen B. W. Mathews and D. R. Davies Acta Crysf. 1970 B26 1062. lZ8 W. N. Lipscomb J. A. Hartsuck F. A. Quiocho and G. N. Reeke Proc. Nat. Acad. Sci. U.S.A. 1969 64 28. E. F. Osserman S. J. Cole I. D. A. Swan and C. C. F. Blake J. Mol. Biol. 1969,46 21 1. 130 D. J. Haas and M. G. Rossmann Acta Cryst. 1970 B26 998.13' H. C. Watson D. M. Shotton J. M. Cox and H. Muirhead Nature 1970 225 806. 58 A. F. Cameron and N. J. Hair Closely related to such studies are the more conventional X-ray examinations of the nucleotide and nucleoside constituents of proteins and other large biological molecules since the bases often have preferred conformations which persist in the biological environment and a knowledge of these conformations may be of assistance in the investigations of the larger molecules. There is also consider- able interest in the chemical and biological effects of U.V. irradiation of nucleic acids and the possible correlation between the stereochemistries of the photo- products and the biological consequences. As part of such studies the structures of the cis-antiphotodimer ofuracil,' 32 the cis-syn photodimer of 6-methyluracil,' 32 and of a photodimer of 1,3-dimethylthymine'33 have all been reported.The latter compound is of particular significance since the photodimerisation of thymine in DNA has been shown to be a major factor in the inactivation of micro- organisms by exposure to U.V. radiation. Closely related to this study of thymine is the analysis of dihydr~thymidine'~~ which is produced by catalytic reduction of thymidine resulting in only one diastereoisomer. The analysis of 4-thio~ridine'~~ has shown it to be the first pyrimidine nucleo- side proved to exist in the syn conformation. Investigations of S-bromoguano- sine136,137 and of 8-bromoadenosine show that these two purine nucleosides also exist in the unusual syn conformation and it is suggested that this rotational isomerism produced by the 8-substitution of bromides reflects the inability of Q replicase and E.coli transcriptase to use 8-substituted nucleoside triphosphates as substrates for RNA polymerisation. The 8-bromine also has a significant effect on the solid-state base packing. Guanosine itself has also been studied as guanosine-5'-phosphate trihydrateI3* and as guanosine dih~drate,'~~ and two analyses of the closelyrelated compound inosine' 39-141 are also reported. Sundaralingam and P~tkey'~~?'~~ have described DL-0-serine phosphate and L-0-serine phosphate. The molecule is a zwitterion and the studies were under- taken to investigate the hydrogen-bonding properties of biological phosphates in relation to biological phosphorylation and similar processes.The structure of a new natural amino-acid 2,3-cis-3,4-trans-3,4-dihydroxy-~-proline,'~~ isolated from the cell walls of Navicula pelliculosa has been reported as has the structure of m-proline hydrochloride. 145 132 J. Konnert J. W. Gibson I. L. Karle M. N. Khattak and S. Y. Wang Nature 1970 227 953. 133 N. Camerman and A. Camerman J. Amer. Chem. SOC. 1970,92,2523. '34 J. Konnert I. L. Karle and J. Karle Actu Cryst. 1970 B26 770. 13' W. Saenger and D. Suck Nature 1970,227 1046. 13' C. E. Bugg and U. Thewalt Biochem. Biophys. Res. Comm. 1969,37,623. 13' S. S. Tavale and H. M. Sobell J. Mol. Biol. 1970 48 109. '38 W. Murayama N. Nagashima and Y.Shimizu Acta Cryst. 1969 B25 2236. 139 U. Thewalt C. E. Bugg and R. E. Marsh Acta Cryst. 1970 B26 1089. I4O A. R. I. Munns and P. Tollin Actu Cryst. 1970 B26 1 101. 14' A. R. I. Munns P. Tollin H. R. Wilson and D. W. Young Actu Cryst. 1970 B26 1114. 142 E. Putkey and M. Sundaralingam Actu Cryst. 1970 B26 782. 143 M. Sundaralingam and E. Putkey Actu Cryst. 1970 B26 790. I. L. Karle Actu Cryst. 1970 B26 765. 145 Y. Mitsui M. Tsubodi and Y.Iitaka Actu Cryst. 1969 B25 2182. 59 Physical Methods-Part (iv) X-Ray Crystallography A study of the polynucleotide complex polyinosinic acid plus polydeoxycytidilic acid,'46 shows it to be a double-helical molecule similar in structure to RNA and the DNA-RNA hybrid of which it is an analogue.Other complexes reported'47 include the 1 :1 hydrogen-bonded complexes 1 -methyluracil-9-ethyl-8-bromo-2,6-diaminopurine and l-ethylthymine-9-ethyl-8-bromo-2,6-diaminopurine. These complexes exhibit different base-pairing configurations which suggest that the energy difference between them is small. The cyclic polypeptide composed of four glycine and two alanine units,148 and the cyclic dipeptides CYC~O-D-alanyl-~-alanyl'~~ have also been investigated. and cyclo-~-alanyl-~-alanyl~~~ The latter two compounds show conformational differences the DL-form being nearly planar while the LL-form is puckered. Other compounds studied include DL-N-chloroacetylalanine,' L-alanylglycine' ''and N-methyl-DL-leucylglycine hydrobromide.lS2 A feature of the preceding reports is the almost universal importance attached to the hydrogen bonding and packing of such molecules in the solid state since these factors may be extrapolated to the biological environments of the molecules.Flavin and flavanone derivatives have been the subjects of several analyses. Two charge-transfer complexes a flavin-naphthalenediol complex,' 53 and a riboflavin-hydroquinone complex' 54 have been studied the results suggesting that the flavin 'chelate site' may be significant in flavin-protein binding. Flavins are widely involved in biological energy-conserving redox processes and the analysis of the 'reduced' compound 5-acetyl-9-bromo- 1,3,7,8,10-pentamethyl- 1,5-dihydroisoalloxazine (49)' 55 shows that the molecule is folded about the N(5)-N(10) axis the dihedral angle being 35.5".In the oxidised state the molecule is planar as demonstrated by the analysis of the 'oxidised' neutral molecule 9-bromo-3,7,8,10-tetramethylisoalloxazine monohydrate (5O).ls6 On the other 146 E. J. O'Brien and A. W. MacEwan J. Mol. Biol. 1970,48 243. 14' G. Simundza T. D. Sakore and H. M. Sobell J. Mol. Biol. 1970,48,263. '" I. L. Karle J. W. Gibson and J. Karle J. Amer. Chem. SOC.,1970 92 3755. 14' E. Sletten J. Amer. Chem. Soc. 1970 92 172. 150 F. E. Cole Acta Cryst. 1970 B26 622. 151 M. H. J. Koch and G. Germain Acta Cryst. 1970 B26 410. R. Chandraseken and E. Subramanian Acta Cryst. 1969 B25 2599. 153 C. A. Langhoff and C. J. Fritchie jun. Chem. Comm. 1970,20. 154 C. A. Bear J. M. Waters and T.N. Waters Chem. Comm. 1970 702. P. E. Werner and 0.Ronnquist Acta Chem. Scand. 1970 24,997. 156 M. yon Glehn P. Kierkegaard and P. Norrestam Acta Chem. Scand. 1970 24 1490. 60 A. F. Cameron and N. J. Hair hand 10-methylisoalloxazinium bromide dihydrate,' 57 which is a model for protonated riboflavin shows only minor deviations from planarity. The structure of the flavanone obtusifolin (51),15' has been determined and an analysis of ribitol'59 shows that the conformation of the free molecule is identical to the of-$Me -HOW \ OH 0 (51) conformation of the ribitol residue in the isoalloxazine moiety of riboflavin. It is possible that this ribitol conformation may be a structural property of the ribitol molecule. The structures of many pharmacologically useful compounds have been studied in attempts to relate the detailed molecular geometries to the biological activities.Cholinergic molecules are amongst those which have been studied in this way. Acetylcholine itself has been studied as acetylcholine chloride160 which proves to possess a hitherto unsuspected conformation and as erythro( +-)-A,& dimethylacetylcholine iodide.'61 The structure and absolute stereochemistry of ( +)-trans-Zacetoxycyclopropyltrimethylarnmoniumiodide,I6* an analogue of acetylcholine have also been determined since the (+)-trans isomer is very much more active than the (-)-trans isomer. L-( +)-cis-2-(S)-Methyl-4-(R)-trimethyl-ammonium-methyl-1,3-dioxolan iodide (52)' 63 is a potent agonist of acetylcholine Me I-Me (52) (53) at the parasympathetic postganglionic (muscarinic) junction.Its conformation is very similar to that of other muscarinic agonists and the synclinal conforma-tion of the nitrogen relative to the ester or ether oxygen atom now seems well 15' R. B. Bates T. C. Sneath and D. N. Stephens J. Org. Chem. 1970 35 1625. Is8 P. Nurayanan K. Zechmeister M. Roehrl and W. Hoppe Tetrahedron Letters 1970 3643. s9 H. S. Kim G. A. Jeffrey and R. D. Rosenstein Acta Cryst. 1969 B25,2223. I6O J. K. Herdklotz and R. L. Sass Biochem. Biophys. Res. Comm. 1970 40 583. 16' T. F. Brennan F. K. Ross W. C. Hamilton and E. Shefter J. Pharm. Pharmacol. 1970 22 724. 162 C. Chothia and P. Pauling Nature 1970 226 541. 163 P. Pauling and T.J. Petcher Chem. Comm. 1969 1258. 61 Physical Methods-Part (iv)X-Ray Crystallography established in this class of compound. Analyses of the local anaesthetic procaine (53)'64 and of the 1 :1 procaine-bis-p-nitrophenylphosphate complex,'65 show that procaine has structural similarities to acetylcholine and other molecules active in the cholinergic system and suggest a common membrane receptor. A compound which is very similar to procaine 2-diethylamino-p-methoxybenzoate hydrochloride,'66 is also described as is the anti-cholinergic drug quinuclidinyl di-ma'-thienylglycollate.'67 The similarity of thalidomide N-(a-glutarimide)phthalimide,' 68 to both fiucleosides and barbiturates has prompted two X-ray determinations one of thalidomide itself,'68 and the other of 4-brom0thalidomide.~~~ It is thought that the biological significance of thalidomide may lie in the fact that it is an N-substituted phthalimide.Analyses of the barbiturate drug 5-ethyl-5-( 1-methylbuteny1)barbituric acid,17' and of chlorpromazine (Largactil) (54)' 71 are described the molecule of chlorpromazine being folded about the N-S axis with a dihedral angle of 139.4". Such folding is similar to that found in the flavins and is also a feature of the anti-depressive agent 5-(bromomethylene)-lO,l l-dihydro-5H-dibenzo[~cycloheptene,72 in which the seven-membered ring exists in a boat conformation and of thiethyl-perazine (55),173the two aromatic rings of which are inclined at 139". The analysis of isoproterenol sulphate dihydrate,' 74 a bronchodilatory agent shows that its conformation is identical to the conformations of ephedrine and noradrenalin which also display the same activity.Other drugs studied by X-ray analyses include the antimalarial and antileprotic agent 4,4'-di-aminodiphenyl sulphone cc-2-ethyl-5-methyl-3,3-diphenyltetrahydrof~ran,~ 76 R. Beall J. Herdklotz and R. L. Sass Biochem. Biophys. Res. Comm. 1970 39 329. 16' M. Sax J. Pletcher and B. Gustaffson Acta Cryst. 1970 B26,114. 166 R. Beall and R. L. Sass Biochem. Biophys. Res. Comm. 1970,40 833. 167 A. Meyerhoffer Acta Cryst. 1970 B26 341. F. H. Allen and J. Trotter Chem. Comm. 1970 778 C. S. Peterson Acta Chem. Scand. 1969 23 2389. I7O B. M. Craven and C. Cusatis Acta Cryst. 1969 B25 2291. 17' J.J. H. McDowell Acta Cryst. 1969 B25 2175. 172 J. J. H. McDowell Acta Cryst. 1970 B26 954. 173 K. Larsson Acta Chem. Scand. 1970,24 1503. M. Mathew and G. J. Palenik Biochem. Biophys. Res. Comm. 1970,39 123. C. Dickinson J. M. Stewart and H. L. Ammon Chem Comm. 1970 920. I" 76 P. Singh and F. R. Ahmed Acta Cryst. 1969 B25 2401. A. F. Cameron and N. J. Hair histamine diphosphate monohydrate,' 77 the sweetening agent saccharin,'78 silydianin,"' and sodium ascorbate .Iso Antibiotics studied include Gramicidin S"' and Monensin,'" isolated from Streptomyces cinnamonensis. Both molecules complex with metal ions and in the latter case it is suggested that it is the ability to complex with Na' and K+ ions and to make them soluble in lipid portions of cellular structures which may be responsible for the activity.The barium salt of antibiotic X-537A,183isolated from an unidentified Streptomyces and the structures of viocidic acid hydro- bromide' 84 and of 00'N-trimethylpyoluteorin's5 have all been described. There have been several analyses of steroids and of steroid-related structures including a conformational study of two 4,4-dimethyl-ster0ids,'~~and the structures of Sa-bromo-6/3 19-oxido-pregnan-3~-ol-20-one,'s 6/3,7/3-methylene-17/3-hydroxyandrost-4-en-3-one-17-acetate,1ss 8/3-methyltestosterone-l7/3-mono-bromoacetate,'89 and testosterone-17~-p-bromobenzoate.'89Testosterone has also been studied as the 1:1 testosterone-p-bromophenol complex.1g0 which reveals that it is the a-face of the steroid which is involved in the specific site binding of the steroid when it influences metabolic processes.The complex is significant because p-bromophenol resembles the portion of the tyrosine molecule available for complex formation in the protein backbone. Two synthetic com- pounds diethylstilbestr~l''~ and 1-p-(2-dimethylaminoethoxypheny1)-1,2-cis-diphenyl-b~t-l-ene,"~which display oestrogenic activity have both been studied. Diethylstilbestrol inhibits the binding of 17P-oestradiol to a stereospecific pro- teinaceous receptor in uterine cells and although the conformation of the mole- cule cannot resemble the conformation of the natural steroid rotation of the benzene rings results in the molecular dimensions being similar to the thickness of a steroidal oestrogen.17' M. V. Veidis G. J. Palenik R. Schaffrin and J. Trotter J. Chem. SOC.(A) 1969 2659. 17' Y. Okaya Acta Cryst. 1969 B25,2257. D. J. Abraham S. Takagi. R. D. Rosenstein R. Shiono H. Wagner L. Horhammer 0.Seligmann and N. R. Farnsworth Tetrahedron Letters 1970 2675. lSo J. Huoslef Acta Cryst. 1969 B25 2214. G. Camilletti P. de-Santis and R. Rizzo Chem. Comm. 1970 1073. M. Pinkerton and L. K. Steinrauf J. Mol. Biol. 1970,49 533. S. M. Johnson J. Herrin S. J. Lui and I. C. Paul Chem. Comm. 1970 72. P. Coggon,J. Chem. SOC.(B) 1970 838. Y. Utsumi A. Furusaki and Y. Tomiie Bull. Chem. SOC.Japan 1970,43 2640. G. Ferguson E. W. Macaulay J. M. Midgley J. M. Robertson and W. B. Whalley Chem. Comrn. 1970,954. E. M. Gopalakrishna.A. Cooper and D. A. Norton Acta Cryst. 1969 B25 2473. P. B. Braun J. Hornstra and J. I. Leenhouts Acta Cryst. 1970 B26 352. lE9 (B) 1970,443. H. Koyama M. Shiro T. Sato. and Y.Tsukuda J. Chem. SOC. 190 A. Cooper G. Kartha E. M. Gopalakrishna and D. A. Norton Acfa Cryst. 1969 B25 2409. C. M. Weeks A. Cooper and D. A. Norton Acra Cryst. 1970 B26,429. lg2 B. T. Kilbourn and P. G. Owston J. Chem. SOC.(B) 1970 I.