Journal of Crystallographic and Spectroscopic Research, Vol. 16, No. 2, 1986

Structure of 1,1,3(RS),6,6,8(RS)-hexamethyl-cislOb(SR),lOc(SR)-perhydro-lH,6H3a( SR) ,5a( SR) ,8a( SR) , l Oa(SR)-tetraazap yrene determined by X-ray diffraction methods. A semiempirical method of structure solution P. GLUZIlqSKI,* J. W. KRAJEWSKI, and Z. URBAIqCZYK-LIPKOWSKA Institute of Organic Chemistry, Polish Academy of Sciences 01-224 Warsaw, Poland and J. BLEIDELIS and A. I~EMME

Institute of Organic Synthesis Academy of Sciences of the Latvian SSR, Riga-6, USSR (Received July 14, 1985)

Abstract

The crystal and molecular structure of the title compound hexamethyl-perhydrotetraazapyrene (I) has been determined by X-ray diffraction methods. The compound crystallizes in the triclinic system, space group P]-, with cell dimensions a = 7.715(1), b = 10.580(2), c = 11.926(2) i , and a = 94.37(1) ~ = 104.87(1) ~ and 3' -= 107.27(1) ~ Since the usual direct methods failed, the structure was solved by a semiempirical optimization of packing a model of I in the unit cell, in terms of the van der Waals' intermolecular energy. The atomic parameters at the most energetically favored position were then refined by least squares against 2396 observed unique reflections, giving a final R of 0.067. The semiempirical solution used here seems to be limited to particular cases. The molecule of I consists of two fused piperazine and two fused hexahydropyrimidine rings, having slightly distorted chair conformations. The rings form a folded cis-lOb, lOc system of almost exact C2 point group symmetry. The lone methyl groups in positions 3 and 8 (at the folding) are found to be axially attached. The geminal methyl groups in positions 1 and 6 are situated away from the folding. 271 0277-8068/86/0400-0271505.00/0

9 1986 Plenum Publishing Corporation

272

Gluzifiski et ai.

Introduction

cis- 10b, l Oc-Perhydro- l H,6H-3a,5a,8a, lOa-tetraazapyrene ( cis-PT AP ) and its polyalkyl derivatives are obtained by condensation of 1,4,8,11-tetraazacyclotetradecane derivatives with glyoxal (Choifiski, 1974; Caulkett et al. 1977, 1978; Alcock et al. 1980; Choiriski and Kolifiski, 1980). It was shown by the above authors that cis-PTAP and its derivatives exist in folded conformations, most intriguing from a stereochemical point of view. Several of them have been the objects of X-ray diffraction studies in recent years (Krajewski et al., 1977; Caulkett et al., 1977, 1978; Alcock et al., 1980; Gluzifiski et al., 1980; Gluzifiski et al., 1982), confirming the approximate, or exact in the case of cisPTAP, C2 point group symmetry of the cis-perhydrotetraazapyrene system in the molecules. At the same time, the chemical inequality of 1,3-substitution positions has been shown by some authors. Thus, the 1,1,3,6,6,8-hexamethylcis-PTAP, apart from axial or equatorial substitution of lone methyl groups,

Structure

ofClsHa4N4

273

could exist in two diastereoisometric forms, one of which (nap 94~ (II) was obtained by Choifiski (1974) and Alcock et al. (1980) from rac-5,5,7,12,12,14hexamethyl- 1,4,8,11-tetraazacyclotetradecane.

8

7 ~

~9

10

3a

/

~

lOa

lOb

2

II

Another expected diastereoisomer has been isolated recently from a glyoxal condensation with the same substrate (Zbied, 1980; Choifiski et al., 1985), which prompted us to determine its stereochemical structure by X-ray diffraction. Nomenclature note. The title compound (I) is diastereoisomeric with respect to 1,1,3(RS),6,6,8(RS)-hexamethyl-cis-10b(RS), lOc(RS)-perhydro1H,6H-3a(SR),5a(SR),8a(S),lOa(SR)-tetraazapyrene (mp 94~ (II) mentioned above. The IUPAC rules for position numbering mean that the comapound names of these diastereoisomers may be distinguished by an R,S-configuration description of chiral centers only. In this case they differ in configuration at 10b and 10c. In order to avoid the use of complex names and to refer to these compounds clearly, the authors introduced in their earlier papers (Gluzifiski et al., 1980, 1982) the informal reference to compounds I and II as " c l o s e , " if

274

Gluzifiski et al.

the geminal methyl groups are attached to the carbon atoms situated at the folding of the molecule, and "remote," if they are attached at positions away from the folding, respectively.

Experimental

X-ray diffraction measurements A well-shaped, colorless crystal of I (rap 113-114~ from n-hexane, size 0.3 x 0.18 x0.78 ram) was selected for X-ray diffraction measurements on a Syntex P21 diffractometer, graphite-monochromated Cu K c~ radiation was used. The cell parameters (Table 1) were refined by a standard XTL System (Syntex P21 package) against 20 reflections. A total of 3056 unique reflections (2396 of I > 2a~) was collected, with stability control on two reflections at 50 reflection intervals (decay was negligible). The reflections were corrected for Lorentz and polarization but not for absorption effects. The P1 space group was assumed as the more likely, thus implying one molecule in a general position in an asymmetric unit.

Attempts at solution by direct methods Numerous attempts at solving the crystal structure by direct methods [programs SHELX 76 (Sheldrick, 1976), and SULTAN 78 (Main, 1978)] failed for both P1 and P1 space groups. The electron density maps gave a so-called "honeycomb" effect, or revealed the molecular skeleton at the wrong position when

T a b l e 1. C r y s t a l l o g r a p h i c data for I Molecular formula M o l e c u l a r weight Crystal system Space group Density Cell constants

Cell v o l u m e Multiplicity N u m b e r o f electrons/cell Radiation Linear a b s o r p t i o n coefficient Scanning mode S c a n n i n g region Diffractometer

CI8H34N4 Mr = 3 0 6 . 4 8 triclinic

ei Dc = 1.148(1)og c m - t a = 7.715(1) A b = 10.580(2) c = 11.926(2) c~ = 9 4 . 3 7 ( 1 ) ~ /3 = 1 0 4 . 8 7 ( l ) 3' = 107.27(1) V,, = 886.1(3) ~ 3 Z=2 F(000) = 340 X(Cu/Kc0 = 1.54178 ~t(Cu/Ke0 = 0 . 3 7 m m co/20 20max = 150 ~ Syntex P2t

t

Structure of CIsH~4N4

275

checked by F c calculations. The analysis of normalized structure factors revealed a large number of unusually high E values distributed evenly over all parity groups (some above 5.0; over 200 reflections of E > 2.5). This caused failures of the tangent procedure. The trouble may be explained in terms of a two-fold symmetry axis present in the molecule, a noncrystallographic symmetry element. It leads to a violation of a required assumption in the KatieHauptmann calculation of normalized structure factors--that the atoms in the asymmetric unit are randomly distributed. A similar, but not so critical effect was observed earlier for diastereoisomer I I (space group P21/c) (Gluzifiski et al., 1980). Semiempirical modelling of the crystal structure The simplicity of the space group P]- assumed for I and a knowledge of the chemical structure of I (which is rigid at room temperature) gave rise to the idea that is should be possible to find an optimal packing of the molecules in the P1 unit cell, and so to establish the positions of the molecules in this way. The intermolecular interactions in I seem to be predominantly of the van der Waals type, and dipole-dipole interactions may be neglected. A Cartesian model of I with minimized intramolecular strain energy was calculated by use of the program MM1 (Allinger et al., 1975) starting from coordinates of a cis-PTAP model (Riddell et al., 1982). The optimized Cartesian coordinates were converted into fractional coordinates (methyl groups taken as single bodies), using experimental cell dimensions, assuming a randomly placed molecule centroid but orienting the molecule according to one of the " b e s t " solutions from direct methods. The coordinates were introduced into the program EENY (Motherwell, 1974) which was used for packing calculations. A set of up to 21 inverted equivalent molecules with various translations surrounding the original molecule was generated. Then the position of the original molecule was varied in three dimensions within [0,0,0] and [1/2,1/2,1/2] (grid 0.25 A), causing opposite shifts of all inverted molecules. A set of interaction energy maps was calculated in this way. They revealed one energy minimum much deeper than any other. The positional coordinates for the new centroid thus found were refined by a steepest-descent procedure. Then a new set of similar energy maps was calculated using the coordinates of the shifted molecule and varying three Eulerian angles as mapping variables (grid 15~ This revealed two minima of a similar energy level (difference within 2 kcal mol-J) at two different orientations of the molecule. Two angle sets thus obtained, together with the centroid coordinates found previously, were refined separately using the same procedure as above. This resulted in two possible semiempirical structure solutions which were then checked by calculation of Fc structure factors (with scale refinement) for 2396 observed reflections (overall B = 3 .~2). The R factors obtained were 0.41 and 0.96, thus indicating unambiguously the more promising result.

Gluzifiski et al,

276

Three cycles of a full-matrix, least-squares refinement of positional and individual isotropic thermal parameters (program CRYLSQ in the X-RAY 70 system, Stewart et al., 1970) for all nonhydrogen atoms (scattering factors taken from International Table for X-ray Crystallography, 1974) decreased R to 0.165, with the maintainance of proper molecular geometry and reasonable temperature factors. After further anisotropic refinement the positions of hydrogen atoms were calculated geometrically and refined in the isotropic mode (with B factors fixed a s Beq of the adjacent atom + 1 ,~2). The last step of refinement gave R = 0.067 (R w = 0.076, w = 1/a2F)at the A/a value < 0.1. The calculated final Ap map revealed no peaks higher than 0.4 e A -3 Discussion

Comments on the semiempirical method The zero approximation of the crystal structure for I, obtained by the semiempirical method described above, may be considered as sufficiently good for further refinement. Figure 1 shows a projection of the molecule in the zero approximation and in the final refined status. The average and maximum shifts for nonhydrogen atoms of I resulting from refinement were 0.173 and 0.422 A , respectively. However, the method cannot be considered as general. Its use is limited

Fig. l. Molecule I projected on to the ab plane of the crystal in its zero approximation (thin lines) and final refined positions.

Structure of C~sH34N4

277

to very special cases only: (i) the molecular structure of the compound must be predicted well enough for a reasonable Cartesian model of the molecule to be built. A rigidity of the molecule is desirable in order to eliminate the possibility of large conformational changes under the influence of crystal forces. (ii) the molecule must not have strong intermolecular interactions, like hydrogen bonding, since they would cause large changes of molecular conformation which are not predictable, and such interactions are difficult to parametrize. (iii) the space group must be simple enough to limit to a reasonable level the number of symmetry-equivalent molecules to be generated. On the other hand, if the spatial surroundings of the original molecule by its equivalents are not "tight," it may escape at the energy mapping off the surrounding space, and false maps will be produced. The molecular structure of I The refined fractional coordinates for I with their Beq values are given in Tables 2 and 3. Figure 2 shows the ORTEP (Johnson, 1965) diagram of a single molecule with crystallographic atom labelling. An overview of bond lengths Table 2. Fractional atomic coordinates ( x 104) and equivalent temperature factors (~,~) for nonhydrogen atoms in I

N(1) C(2) C(3) N(4) C(5) C(6) C(7) N(8) C(9) C(10) N( 11 ) C(12) C(13) C(14) C(15) C(16) C(17) C(18) C(19) C(20) C(21 ) C(22)

x

y

z

B~q~

- 1507(4) - 1272(6) - 2585(6) -2109(4) -3382(5) -2848(5) -2728(5) - 1553(4) 472(5) 1599(5) 1129(4) 2315(5) 1644(6) -507(6) - 924(5) - 2146(5 ) -5527(6) - 2933 (6) -4630(6) 2314(6) 4379(6) - 1327(6)

3139(3) 2828(4) 1431 (4) 435(3) -968(4) - 1920(3) - 1536(3) - 123(3) 72(4) 1481(4) 2469(3) 3876(4) 4839(4) 4568(3) 2246(3) 774(3) - 1138(4) - 1320(4) - 1844(4) 4208(4) 4069(4) 5018(4)

-2121(2) -921(3) - 984(3) - 1671(2) - 1719(3) -2488(3) -3683(3) -3542(2) -3061(3) -3119(3) -2423(2) -2412(3) - 1757(3) -2104(3) - 2818(3) - 2862 (3) -2147(4) - 464(3) -4624(3) - 3664 (4) - 1711 (4) -3256(4)

2.9(1) 3.1(1) 3.4(1) 2.7(1) 3.1(1) 3.2(1) 3.0(1) 2.7(1) 3.1(1) 3.4(1) 2.7(1 ) 3.1(1) 3.4(1) 3.3(1) 2.5(1 ) 2.4( 1) 3.9(1) 4.0(1) 3.7(1 ) 4.0(1 ) 4.0(1) 4.2(1)

aCalculated from refined anisotropic thermal parameters terminant of the Uij matrix.

as

Beq =

87r2DuI/3, where Dv

is the de-

278

Gluzifiski et al. Table 3. Anisotropic thermal motion coefficients (• 10 3) for nonhydrogen atoms"

Atom N(I) C(2) C(3) N(4) C(5) C(6) C(7) N(8) C(9) C(10) N(ll) C(12) C(13) C(14) C(15) C(16) C(17) C(18) C(19) C(20) C(21) C(22)

U~i

Uzz

U33

UIz

UI3

U23

47(2) 55(3) 58(3) 41(2) 48(3) 46(3) 49(3) 41(2) 39(3) 44(3) 36(2) 46(2) 51(3) 59(3) 38(2) 35(2) 42(3) 78(3) 54(3) 69(3) 44(3) 70(3)

36(2) 44(2) 49(2) 37(2) 41(2) 36(2) 34(2) 35(2) 44(2) 47(2) 37(2) 40(2) 36(2) 35(2) 35(2) 36(2) 53(2) 56(3) 50(2) 50(2) 51(2) 44(2)

34(2) 33(2) 39(2) 30(1) 39(2) 48(2) 38(2) 33(1) 47(2) 48(2) 34(1) 38(2) 45(2) 42(2) 27(2) 27(2) 62(3) 44(2) 39(2) 48(2) 58(3) 66(3)

15(1) 16(2) 17(2) 11(1) 11(2) 12(2) 11(2) 11(1) 17(2) 12(2) 9(1) 6(2) 5(2) 14(2) 10(2) 13(2) 6(2) 18(2) 6(2) 5(2) 2(2) 22(2)

9(1) 14(2) 21(2) 9(1) 12(2) 10(2) 7(2) 8(1) 13(2) 16(2) 10(1) 11(2) 9(2) 9(2) 6(2) 6(2) 17(2) 18(2) -3(2) 19(2) 7(2) 9(2)

4(t) 0(1) 9(2) 7(1) 13(2) 11(2) 1(1) 2(1) 2(2) 5(2) 5(1) 7(2) 3(2) 3(2) 6(1) 6(1) 12(2) 23(2) 1(2) 15(2) 6(2) t7(2)

~The temperaturefactor is in the form exp [--271.2 (Ut

l hZ a .2 +

"

"

"

+ 2 Ui2hka * b * + 9 "

")].

and angles (Table 4 and 5, respectively) reveals no peculiarities in the molecular geometry. As expected, the molecule of I has an almost exact C2 point group symmetry. The equation of this noncrystallographic two-fold axis was calculated from atomic coordinates as one of the main axes of inertia of the molecule. It may be shown that the average deviation from C2 symmetry calculated for nonhydrogen, symmetrical atom pairs (0.006 A , defined as the average displacement of interatomic centers with respect to the two-fold symmetry axis) is within twice the average standard deviation (0.004 ,~) calculated for atomic Cartesian coordinates in I. The two hexahydropyrimidine and the two piperazine rings fused into a cis-perhydrotetraazapyrene system have slightly deformed chair conformations. Similarly, as in I I and other c i s - P T A P derivatives, four main least-squares planes can be distinguished in the skeleton of I: (1)--through C(7), N(8), C(16), C(15), N(1), and C(14); (2)--C(2), C(3), N(4), C(5), C(6), C(9), C(10), N(11), C(12), and C(13); (3)--N(1), C(2), C(16), N(4), C(7), and C(6); (4)--N(8), C(9), C(15), N ( l l ) , C(14), and C(13). The planes (1) and (2) are almost parallel to each other [dihedral angle 0.7(1)~ with a distance between them of 1.107(2) A. The planes (3) and (4) form almost equal dihedral angles with (1) and (2), of average 132.0(1) ~ Thus, the geometries of the moleculal skeleton in I and I I are very close to each other.

Structure of CIsH34N4

279

CI8

C5 C6

~ , ~

C 17

C3

C2 C7

C9 N8

C19

~ H16

Nll C10

N1

:14

C21 C13 C12

HI5 C22

Fig. 2. ORTEP(Johnson, 1965) diagram of a single molecule of I oriented at optimal viewing. The thermal motion ellipsoids are set at a 40% probability level. Methyl and methylene hydrogen atoms have been omitted for clarity. Table 4. Bond lengths (,~) in I, excluding hydrogen atoms N(1)-C(2) N(1)-C(14) N(1)-C(15) C(2)-C(3) C(3)-N(4) N(4)-C(5) N(4)-C(16) C(5)-C(6) C(15)-C(16)

1.471(5) 1.475(4) 1.453(5) 1.507(5) 1.473(6) 1.505(4) 1.487(4) 1.524(6) 1.552(4)

C(5)-C(17) C(5)-C(18) C(6)-C(7) C(7)-N(8) C(7)-C(19) N(8)-C(9) N(8)-C(16) C(9)-C(10)

1.552(6) 1.548(6) 1.529(6) 1.470(4) 1.528(5) 1.464(5) 1.449(5) 1.503(5)

C(10)-N(11) N(11)-C(12) N(11)-C(15) C(12)-C(13) C(12)-C(20) C(12)-C(21) C(13)-C(14) C(14)-C(22)

1.469(6) 1.495(4) 1.471(5) 1.522(6) 1.559(6) 1.541(6) 1.535(6) 1.532(6)

280

Gluzifiski et ai.

~,,~=, z ~ z z ~ z z z z

"6 .-4

~o

;>

Structure of C18H34N4

281

Acknowledgment The authors are indebted to Dr. R. A. Kolifiski for supplying the crystals of I and for valuable discussions, and to Dr. K. L. Loening, The Nomenclature Director of Chemical Abstracts Service, for his kind suggestions concerning the nomenclature problems in cis-PTAP derivatives. This work was supported by grant No. MR-I.9 of the Polish Academy of Sciences.

References Alcock, N. W., Moore, P., and Mok, K. F. (1980) J. Chem. Soc. Perkin Trans. 2, 1186-1190. Allinger, N. L., Sprague, J. T., and Yuh, Y. A. (1975) MM1. Program for Molecular Mechanics Calculations (University of Georgia). Caulkett, P. W. R., Greatbanks, D., Turner, R. W., and Jarvis, J. A. J. (1977) J. Chem. Soc. Chem. Commun., 150-151. Caulkett, P. W. R., Greatbanks, D., Turner, R. W., and Jarvis, J. A. J. (1978) Heterocycles 9, 1003-1008. Choifiski, W. M. (1974) PhD Thesis, Institute of Organic Chemistry, Polish Academy of Sciences, Warsaw, Poland. Choifiski, W. M., and Kolifiski, R. A. (1980) Polish Patent No. 101,075; Chem. Abstr. 92, 94444x. Choifiski, W. M., Koliriski, R. A., and Zbie6, M. A. (1985), in preparation. Gluzifiski, P., Krajewski, J. W., and Urbaficzyk-Lipkowska, Z. (1980) Acta Crystallogr. B 36, 2182-2184. Gluzifiski, P., Krajewski, J. W., Urbaficzyk-Lipkowska, Z., Bleidelis, J., and Kemme, A. (1982) Acta Crystallogr. B 38, 3038-3041. International Tables for X-Ray Crystallography (1974). Vol. IV (Kynoch Press, Birmingham, England). Johnson, C. K. (1965) ORTEP. Report ORNL-3794, Oak Ridge National Laboratory, Tennessee. Krajewski, J. W., Urbaficzyk-Lipkowska, Z., Bleidelis, J., and Kemme, A. (1977) Cryst. Struct. Commun. 6, 853-858. Main, P. (1978) MULTAN78. Program for Crystal Structure Determination (University of York, Great Britain). Motherwell, S. (1974) EEN'~. Potential Energy Program (University of Cambridge, England), a conversational version modified by L. Gluzifiski (1982), Institute of Physical Chemistry, Polish Academy of Sciences, Warsaw, Poland. Riddell, F. G., Murray-Rust, P., Kolifiski, R., and Gluzifiski, P. (1982) Tetrahedron 38, 673678. Sheldrick, G. M. (1976) SHELX76. Program for Crystal Structure Determination (University of Cambridge, England). Stewart, J. M., Kundell, F. A., and Baldwin, J. C. (1970) The X-RAY70 System (Computer Science Center, University of Maryland, College Park, Maryland). Zbie6, M. A. (1980). PhD Thesis, Institute of Organic Chemistry, Polish Academy of Sciences, Warsaw, Poland.

British Library Lending Division Supplementary Publication No. 60483 contains 22 pages of structure factor tables.