2182
The Journal of Physical Chemistry, Vol. 83, No. 16, 1979
B. A. Soltz, J. Y. Corey, and D. W. Larsen
Molecular Motion in Chlorpromazine and Chlorpromazine Hydrochloride Barbara A.
Soltr, Joyce Y.
Corey, and David W. Larsen"
Department of Chemistry, University of Missouri-Sf.
Louis, Sf. Louis, Missouri 63121 (Received February 5, 1979)
Chlorpromazine, I, and chlorpromazine hydrochloride, 11,have been studied in the solid state with pulsed NMR techniques. The relaxation times, T1, TI,, and TID, and second moments, AI2, have been measured from 98 K to the melting point of the solid. Methyl reorientation was observed in both compounds with activation barriers of 2.5 and 2.0 kcal/mol, respectively. The onset of a second motion in I is observed in the high temperature region with an activation barrier of 3.9 kcal/mol. The AI2 transition associated with this motion is very large, which suggests that it involves motion of the aminopropyl chain. The motion is attributed to the fact that the chain configuration is trans-gauche and a model for the motion is discussed. A phase transition occurs in I1 in the high temperature region.
Introduction Since 1950 there have been a myriad of studies for determining the clinical effectiveness of tricyclic compounds in the treatment of various psychiatric di~0rders.l~ The parent compound for 6,6,6 systems is phenothiazine, which is known to be biologically i n a ~ t i v e .Modification ~ of the basic structure by changing the nitrogen substituent to a dimethylaminopropyl side chain that is meta to a chlorine atom in the tricyclic nucleus produces chlorpromazine, I. This compound is a widely prescribed
a:nc, I
Y
I, Y = CH,CH,CH,NMe, 11, Y = CH,CH,CH,NMe,.HCl
tranquilizer and the model to which all other antipsychotic reagents are compared.6 The success with chlorpromazine produced a variety of studies on structural modifications with the aim of enhancing activity or at least to gain an insight into the mechanism by which these drugs interact at the biological site. For exampleY7 the length of the side chain has been varied, as well as the amino substituents on the terminal N. In addition, the skeletal substituents have been placed a t various positions relative to the side chain and the central ring heteroatoms varied as has the size of the central ring. For psychotropic activity it was found that a three carbon side chain is necessary but the terminal amino substituents may vary from alkyl to aromatic with little effect. In general, the skeletal substituent is an electron-withdrawinggroup which must be meta to the side chain. The central ring heteroatoms that appear to enhance activity are those which possess a lone pair of electrons. Chlorpromazine is nonplanar in the solid state,8 as well as in solution: with the central six-membered ring existing in a boat conformation. The solid state structures also indicates that the dimethylaminopropyl side chain is not symmetrically placed with respect to the two benzo rings due possibly to a van der Waals interaction between the amino N and the C1 substituent.1° A relationship between the solid state structure of chlorpromazine and that of the biogenic amine, dopamine, has been suggested.'l It was postulated that chlorpromazine adopts a conformation similar to dopamine at the biological site, blocking the uptake of dopamine by the receptor, but not activating the receptor site itself.12 0022-365417912083-2 162$01.OOlO
One important implication from these studies is that chlorpromazine may adopt a preferred conformation which is probably related to motional processes in the molecule. Previous studies to observe molecular motion in solid^'^-'^ by using pulsed NMR relaxation have been reported by us. We now wish to report results for chlorpromazine, I, and chlorpromazine hydrochloride, 11. Anticipated motions to be detected in these compounds from NMR relaxation data include motional processes associated with the side chain, pyramidal inversion at nitrogen, and ring inversion or flexing in addition to reorientation of methyl groups. These motions are rapid even at low temperature, and they are impossible or extremely difficult to study by NMR line shape analysis13J7in solution. We also find that a comparison of results for I and I1 is of use in characterizing these motions.
Experimental Section Compounds I and I1 were prepared according to a published synthetic route.18 Chlorpromazine was isolated as a dark yellow oil which slowly crystallized. Recrystallization from aqueous ethanol afforded pale yellow crystals, mp = 53 OC. Spectroscopic properties were consistent with those published for I. Chlorpromazine hydrochloride, 11, was obtained by bubbling anhydrous HC1 into a solution of the free base, dissolved in anhydrous ether. The salt was recrystallized from xylene-chloroform mixtures, mp = 190-192 "C. Samples were dried by pumping over Drierite for 24 h at 0.1 mmHg prior to enclosure in glass tubes for the pulsed NMR studies. Proton NMR measurements of the Zeeman spin-lattice relaxation time ( T J , the rotating frame spin-lattice relaxation time (T1,,),the dipolar relaxation time (TID),and the second moment ( M J were obtained with a Polaron NMR spectrometer operating at 60 MHz.13J9 The techniques have been described prev i o u ~ l y .The ~ ~ bloch decays were found to be Gaussian within experimental error for these samples. H1= 26.8 G for the TI, measurements. No hysteresis effects were observed in these studies; the relaxation times were reproducible with respect to temperature change once thermal equilibrium was established in the sample. This suggests that the phases present were stable at the given temperatures. The computer calculations were performed on an IBM 370/168 computer. Results Chlorpromazine (I). The experimentally determined relaxation times, T1 and TID,are plotted on a log scale as 0 1979 American Chemical Society
The Journal of Physical Chemistry, Vol. 83,
Molecular Motion in Chlorpromazine
I
No. 16, 1979 2163
\
h
a.y \ \
7 5
-2
-3 -
100 I
10
e
I
I
6
4
-
1
200
TEMPERATURE
1
2
la3/1
300 (
K1
Figure 2. Second monent vs. temperature for chlorpromazine (I). Dashed line is drawn arbitrarily through the data points.
Figure 1. log relaxation times vs. reciprocal temperature for chlorpromazine (I). Solid line is calculated by use of eq 1. Dashed lines are drawn arbitrarily through the data points.
a function of reciprocal temperature in Figure 1. T1 appears to be controlled by a single relaxation process over the entire temperature range shown in Figure 1. The well-defined minimum in T1 at 103/T = 5.15 (194 K) is attributable to methyl group reorientation about its C3 axis; the assignment is discussed below. Activation parameters for the motion were obtained by fitting the minimum with a BPI? type expressionz0in which y is the 1
3
gyromagnetic ratio, MZmod is that portion of the second moment that is modulated by the motion, wo is the Larmor frequency (60 MHz), and T , is the correlation time of the motion. The solid line for TI in Figure 1 has been calculated by assuming that T~ follows an Arrhenius expression: T , = (2.9 X exp(2.45 X 103/RT)s, with M21pod = 4.7 G2. It can be seen that the fit of data is satisfactory. The temperature dependence of TIDfor lo3/ T > 6 is in general accord with theoretical prediction and the gradient corresponds to E A = 2.4 kcal/mol. Thus, it appears that Ti, is also controlled by methyl reorientation in this region. The experimental M 2 values are plotted against temperature in Figure 2. M z exhibits a transition below -180 K. A plateau is observed between these two temperatures (12C-180 K). The transition below 120 K is associated with methyl reorientation and the plateau corresponds to MzCnigbI, the limiting value of M 2 when the motion is rapid enough to partially narrow the line. In the high temperature region of Figure 1, TIDdecreases with increasing temperature, which indicates the presence of a second motion. The M2 transition in Figure 2 above 180 K is also attributable to this motion. The gradient of T I D for IO3/ T < 6 corresponds to an activation barrier of 3.9 kcal/mol for the process. It is anticipated that contributions to Tl from this motion would be observable only at much higher temperatures than shown in Figure 1. The assignment of the second motional process is discussed below.
T,
O" U'
/
-4
i
I
10
I
a
1
II
I
6
4
2
103/~
Figure 3. log relaxation times vs. reciprocal temperature for chlorpromazine hydrochloride (11). Solid line is calculated by use of eq 1. Dashed lines are drawn arbitrarily through the data points.
Chlorpromazine Hydrochloride ( I n . The experimental relaxation times, TI, TIP, and TID, are plotted against reciprocal temperature in Figure 3, and the M 2 data are presented in Figure 4. A minimum in TI is observed at 103/T = 6.2 (161 K) in Figure 3. The minimum is attributed to methyl group reorientation. The solid line for T1 in Figure 3 is calculated from eq i with 7, = (3.7 X exp(1.96 X 103/RT) s, and Marnod = 4.0 G2. The M 2 transition below about 100 K in Figure 4 is also associated wit,h methyl reorientation and the plateau corresponding to M2(high) extends from -100 to -300 K. The behavior of T1, and T1D for 103/T> 4 does not correspond to that of T,. The gradients of T1, and T I D yield an activation barrier of -1.4 kcal/mol. In addition, the apparent T1 minimum at 10"T N 10 is too shallow by roughly an order of magnitude, based on the T1
2164
The Journal of Physical Chemistry, Vol. 83,
No. 16, 1979
B. A.
Soltz, J. Y. Corey, and D. W. Larsen
C(3) C(2)
Figure 5. Solid state structure of chlorpromazine (I) as determined crystallographically (ref 8).
100
200
300
TEMPERATURE (K)
Flgure 4. Second moment vs. temperature for chlorpromazine hydrochloride (11). Dashed line is drawn arbhrarily through the data points.
TABLE I: Activation Parameters for Molecular Motions in Chlorpromazine (I) and Chlorpromazine Hydrochloride (111 EA,
compd
motion
I I I1
methyl reorient chain motion methyl reorient
I1
kcall mol
M2tnpd, TalS
2.4 2.9 x 10-l2 3.9 1.9 3.7 X lo-'* (-1.4)
G
4.7 4.0
rninimum.l3 These facts suggest that there are contributions to T1, and TID from a second motional process, and the shallow T1,minimum suggests that the motion modulates a very small portion of the second moment, M2. If this is the case, then a contribution to T1 would be anticipated, but only at very high temperature, e.g., lo3/ T e 2. There are discontinuities in Tlp,TID,and M 2 at approximately 290 K. We attribute these effects to a phase transition. The motion controlling T1, methyl reorientation, is apparently unaffected by the phase transition. The activation parameters for I and I1 are summarized in Table I.
Discussion Crystallographic evidence demonstrates that phenothiazine derivatives are nonplanar (the dihedral angle between benzo-group planes is 139 and 137" in I8and 11,22 respectively). For both compounds the sum of the angles about the nitrogen atoms is approximately 355' and the side chain substituent may be viewed as occupying a quasi-equatorial position. The side chain is tilted away from the plane which bisects the framework of the molecule in halves, but in the opposite sense in the two molecules (toward the C1 substituent in I and in the opposite direction in IIZ2).The approximate conformations of the side chain are trans-gauche for I (torsion angles for C,-C, and C,-C, are -164 and 75O, respectively22) and trans-eclipsed for I1 (torsion angles for C,-C, and Co-C, are -152 and -127O, respectively22). In addition, there is a hydrogen bonding interaction, N-H-Cl, in II.23 A sketch of the crystallographic structure for I8 is shown in Figure 5. In the subsequent paragraphs the probable motions observed in the solid as reflected in the observed T1 and T 1measurements ~ are described and assigned.
It is probable that the main motion controlling T I in the two compounds is methyl group reorientation. In order to confirm this assignment, the rigid lattice value of M 2 has been determined for each compound and reduction factors applied to account for the effects of molecular m o t i o n ~ . l ~We - ~ thus ~ obtain values that can be compared with the observed M2. The Van Vleck equation24for the rigid lattice second moment M2(rl)is given by 715.9 (2) M2(rl) = T i f i k r , k - ' where M2(rl)in G 2 is the value when all motion is sufficiently slow so that the NMR line is not motionally narrowed, n is the number of protons in the sample, and rjk is the distance between protons j and k in A. In favorable cases, r,k may be evaluated directly from the crystallographic data, as has been previously described.13J4 However, in this case, crystal structures have been reported for Is and 11,21but the proton positions have not been determined for either compound. Thus, it was necessary to estimate25M2(+ In Figure 2, the M 2 transition lies below 100 K, and a plateau corresponding to M2( h) is observed between 120 and -180 K. It is anticipate2that the rigid lattice M z will be observed only at temperatures well below 100 K. We estimate M2(rl)= 26.9 f 2 G2 for I. This value is then corrected for molecular motion by use of reduction factors. Assuming rapid methyl group reorientation, we obtain M2 = 15.8 f 2 G2,which is compared with M2(high) = 14.3 f 0.5 G2. We conclude that, within the uncertainty, the calculated M 2 agrees with the observed M2,and the motion may be assigned to methyl reorientation. We note that in Figure 2, the largest observed value of M 2 is -20 G2, and that this value is less than the calculated M261). Thus, only a portion of the M 2 transition associated with methyl reorientation is shown in Figure 2. The M 2 transition above 180 K in Figure 2 lowers M z by 1 9 G2,and the activation barrier for the process was found to be 3.9 kcal/mol. Inspection of the various intraand intermolecular contributions to M 2 indicates that a decrease of 1 9 G2 (which is about 213 of M2 at the plateau below 180 K) can be accounted for only by a motion involving the aminopropyl chain. Below we consider a model for the chain motion. If the chain is taken to be in an idealized trans-gauche configuration, then a simultaneous rotation about the C(13)-C(14) bond and the C(14)-C(15) bond carries the chain from the trans-gauche configuration to a gauchegauche configuration without substantially altering the distance between the two N atoms (as determined from Dreiding models). These rotations change the positions of C(14) and C(15) and to a lesser extent N(2), C(16), and C(17). This motion would decrease M 2 by -5 G2which is a substantial decrease but is not enough to account for the decrease as demonstrated in Figure 4. In order to
-
Molecular Motion in Chlorpromazine
decrease M 2 by -9 G2all CH2 groups in the chain must move. If the previously described rotations about C(13)-C(14) and C(14)-C(15) are accompanied by a simultaneous swing about N(l)-C(13) and rotation about C(15)-N(2) a decrease in M2 of -9 G2 is calculated. Although in the solid state the bond angles along the chain deviate from the tetrahedral value and the torsion angles do not correspond to the idealized trans (*180') or gauche (f 60') conformations, motion along the chain through angles of 90' as described will reduce M 2 by -9 G2. In such a model the phenothiazine framework is essentially stationary and the predominant motion involves the internal portion of the chain and possibly a small involvement of the NMe2 terminus. Such a motion could be accomodated within the solid lattice. The motion is in contrast to that observed in long chain hydrocarbons26just below the melting point. In this case, a molecular rotation about the long axes of the chains is proposed, and the motion decreases M2 by 10-14 G2. For a motion to occur in the solid, there is presumably the requirement that the structure be relatively open at the site of the motion. Nitrogen inversion in I could be possible but the sum of the bond angles about N(1) is about 354' (357' in 7hydroxychlorpromazine27)which indicates that the local structure is almost planar and thus the barrier to inversion would be expected to be very small. The sum of the angles about N(2) is 331', close to the idealized pyramidal nitrogen and this raises the possibility of 180' rotation about N(2)-C(15) with inversion N(2). This would exchange C(16) and C(17); however, the M2 reduction from such a process is = 1 G2,and thus no conclusion about such a motion is possible. Inversion of the phenothiazine ring would contribute very little to M2 reduction; however, ring inversion may be ruled out in this case since it can occur only with reorientation of the entire molecule, and thus the anticipated activation barrier is much greater than the observed 4 kcal/mol. For chlorpromazine hydrochloride, 11, there is an M2 plateau between -110 and 290 K (see Figure 4). The M2 value for this region is observed to be 11.6 f 0.5 G2and is much lower than M2(rl) which is estimated to be 25.5 G2. Reduction of this value by assuming, as before, rapid methyl group reorientation gives 14.9 G2 which is 3.3 G2 larger than the observed result. In light of the procedure used, the agreement is satisfactory. As with I above, for 11, only a portion of the M2 transition associated with methyl reorientation is observed in Figure 4. There is a discontinuity in M2 occurring just under 300 K which we associate with a phase transition. The result is that M 2 is lowered by approximately 3 G2. The relaxation and second moment data for I and I1 indicate that methyl group reorientation occurs for both compounds, and that the activation barrier is slightly larger for I. The difference may be due to the fact that the bond angles about the amino N are not exactly tetrahedral in either compound. The CH,-N-CH, angle is 109.9' in I8 and 110.8' in 11,21and this is consistent with a higher activation energy for I. In general, the CH3-N-CH3 angle is observed to be larger in amine hydrochlorides than in the corresponding free amine^.^^,^^ The second motion for I is observed in the high temperature region, and the motion must be associated with the side chain as discussed above. A phase transition is observed for I1 in the temperature region in which side chain motion is observed for I. This phase transition may be associated with a discontinuous change in the rate of chain motion, but the effect is much smaller than that
The Journal of Physical Chemistry, Vol. 83, No. 16, 1979
2165
observed for I, and thus a different model would be required to explain any proposed chain motion in 11. It is likely, however, that changes of the N-H-C1 hydrogen bond must preceed any motion of the side chain in the hydrochloride salt. Motional processes in the solid salts of imipramine and desipramine have been examined.16 There are two molecules of imipramine hydrochloride in the asymmetric unit which differ primarily in the conformation of the side chainsz8 One molecule has a trans-trans configuration for the CH2CH2CH2N+Me2H side chain and the second a trans-gauche configuration. Both molecules are hydrogen bonded to the chloride ion (NH-Cl = 3.035 and 3.047 A). The solid state structure of desipramine hydrochloride which contains the side chain, CH2CH2CH2N+H2Me...C1, is unknown but it is reasonable to assume an interaction similar to imipramine hydrochloride. We have observed and described a substantial M2 decrease for side chain motion only for I, a free base. The absence of motion in I1 (and the other hydrochloride salts studied) may be attributed to the presence of the hydrogen bond which effectively anchors the end of the chain. Conformational preference of the side chain for imipramine hydrochloride in CDC13 solution has been reported but no conformational preference was observed for the free bases of imipramine1' or c h l o r p r o m a ~ i n e . ~ ~
Acknowledgment. J.Y.C. gratefully acknowledges the support of this work by the National Institute of Neurological Diseases and Stroke, NIH research grant number ROlNS10903. B.A.S. also acknowledges support from a Summer Research Grant awarded by the Graduate School, University of Missouri-St. Louis. We also thank McDonnel Douglas Astronautics Corp. for providing a storage oscilloscope for use in this study. D.W.L. thanks J. Wright (University of Kent) for several helpful discussions.
References and Notes (1) J. Courvoisier, J. Fournel, R. Ducrot, M. Kolsky, and P. Koetchet, Arch. Int. Pharmacodyn.,92, 305 (1952). (2) J. Delay, T. Deniker, and J. M. Hoel, Ann. Med. Psycho/.,110, 112 (1952). (3) H. E. Lehmann and G. E. Hanrahan, AMA Arch. Neural. Psychiatry, 71, 227 (1954). (4) E. F. Domino, R. D. Hudson, and G. Zografi, "Drugs Affecting the Central Nervous System", Vol. 2, A. Burger, Ed., Marcel Dekker, New York, 1968. (5) E. Schenker and H. Herbst, "Progress in Drug Research", Vol. 5, E. Jucker, Ed., Berkhauser, Basel and Stuttgart, 1963, p 269. (6) C. L. Zirkel and C. Kaiser, "Medicinal Chemistry", 3rd ed,pari 2, 1970, p 1410. (7) M. H. Bickel and B. B. Brodle, Int. J. Neurophamcol., 3, 61 1 (1964). (8) J. J. H. McDowell, Acta Crystallogr., Sect. B , 25, 2175 (1969). (9) L. S.Isbrandt, R. K. Jensen, and L. Petrakis, J. Mag. Reson., 12, 143 (1973). A. Feinberg and S. H. Snyder, Proc. Natl. Acad. U.S.A.,72, 1899 (1975). A. S. Horn, M. L. Post, and 0. Kennard, J. Pharm. Pharmacol.,27, 553 (1975). A. S. Horn and S. H. Snyder, Proc. Acad. Sci. U.S.A., 88, 2325 (1974). D. W. Larsen and J. Y. Corey, J. Am. Chem. Soc., 99, 1740 (1977). D. W. Larsen and T. A. Smentkowskl, J. Mag. Reson., 28, 171 (1977). D. W. Larsen, J. Y. Corey, T. A. Smekowski, and F. E. Stary, J. Organomet. Chem., 135, 161 (1977). D. W. Larsen, T. A. Smentkowski, B. A. Soltz, and F. E. Stary, J. Am. Chem. Soc., 100, 4982 (1978). R. J. Abraham, L. J. Kricka, and A. Ledwith, J . Chem. Soc., Perkin Trans. 2 , 1648 (1974). F. M. Moracci and F. Liberatore, J. Med. Chem., 11, 398 (1974). T. C. Farrar and E. D. Becker, "Pulse and Fourier Transform NMR", Academic Press, New York, 1971. N. Bloembergen, E. M. Purcell, and R. V. Pound, Phys. Rev., 73, 679 (1948). M.k.'Cor&ac-Calas and P. Marsau, C . R . Acad. Sci. Paris, Ser. C , 274, 1806 (1972). Parameters were computed from the data published in ref 21 and reported in J. R. Rodgers, A. S. Horn, and 0. Kennard, J . Pharm. pharmacal., 28, 246 (1976); E. R. Corey, J. Y. Cwey, and M. D. Glick,
2166
The Journal of Physical Chemistry, Vol. 83, No. 16, 1979
V. Subramanian and K. Seff
Acta Crystallogr., Sect. 5 , 32, 2025 (1976). (23) A N 4 I distance of 2.93 A was computed from the atomic parameters publlshed in ref 21. We thank E. R. Corey for performing this calculation. (24) J. H. Van Vleck, Phys. Rev., 74, 1168 (1948). (25) Since proton positions were not reported for I' and 11'' the initial for I and I1 was to first estimate method used to calculate M2(r,) idealized proton positions based on the reported skeletons and then to calculate Maimfrom these positions. This procedure gave impossibly large contributions for I1 from several very close proton pairs. We,
(26) (27) (28) (29) (30)
therefore, estimated M2(r,) for I1 by using proton positions calculated from the data for I* but corrected for the different number of protons. E. R. Andrew, J . Chem. Phys., 18, 607 (1950); Physica, 17, 405 (1951). J. J. H. McDowell, Acta Crysfa//ogr., Sect. 5 , 33, 771 (1977). M. L. Post, 0. Kennard, and A. S. Horn, Acfa Crysta//ogr., Sect. 5 , 31, 1008 (1975). M. L. Post and A. S. Horn, Acta Crysfa//ogr.,Sect. 6,33,2590 (1977). J. Barbe and A. M. Chauvet-Monges, C. R. Acad. Sci. Paris, Ser. C , 279, 935 (1974).
Crystal Structure of Dehydrated Cesium- and Thallium-Exchanged Zeolite A V. Subramanian
and Karl Seff"
Chemistry Department, University of Hawaii, Honolulu, Hawaii 96822 (Received February 23, 1979) Publication costs assisted by the National Science Foundation
The crystal structure of vacuum-dehydrated Cs9Tl3SiI2All2048, zeolite A with all Na+ ions replaced by Cs+ ions and Tl' ions as indicated, has been determined by single-crystal X-ray diffraction experiments in the cubic space group Pm3m (a = 12.312(3) A). The final weighted R index is 0.067. The nine Cs+ ions are distributed over four crystallographically distinct sites. Six of these are located on threefold axes in the large cavity: two are 2.08 A from the planes of 6-ring oxide ions, and the remaining four are 1.39 A, substantially closer, from their corresponding planes. Three other Cs+ ions occupy 8-ring sites: one is at the center of an oxygen 8-ring, and the two others are located off the planes of their &rings. Two T1' ions occupy threefold-axis positions inside the sodalite unit, and the third is in the large cavity opposite a 4-ring. The Cs+ and Tl' content of the crystal whose structure was determined is supported by X-ray fluorescence analysis.
Introduction Complete exchange of the relatively large cations Ag+,l K+,2and Tl+ for Na+ ions in zeolite A is readily achieved. Yet only a maximum of seven Cs+ ions could be exchanged into Na12-A4v5or K12-Aa6This work was undertaken with the hope that complete exchange of Cs+ for T1+ would be possible. Because the relatively large T1+ions do not fit well into the 6-ring and 8-ring sites of the zeolite, they might be expected to be readily exchangeable. The structure of dehydrated Cs12-A would be of interest because of the large total volume of its exchangeable cations and because one or more Cs+ ions might be in a state of extreme coordinative unsaturation, perhaps zero coordinate. If the complete exchange of Cs+ for T1+ were not achieved, a structural basis for the lesser exchange limit could be learned. In addition, the relative preferences of the cations for the coordination sites available within the zeolite would be seen. Experimental Section Crystals of zeolite 4A were prepared by a modification of Charnell's m e t h ~ dincluding ,~ a second crystallization with seed crystals from the first synthesis. A single crystal, approximately 0.085 mm on an edge, was lodged in a fine glass capillary. The crystal was exchanged with aqueous 0.05 M TlOH by flow methods (0.5 cm/s) a t 25(1) "C for 7 days. After being transferred to a new capillary, it was similarly exchanged with aqueous 0.05 M CsOH for 7 days. The crystal was then dehydrated at 350 "C under vacuum (1 X torr) for 2 days. After cooling to 24(1) "C, the crystal was sealed in its capillary and removed from the vacuum line by torch. Microscopic examination indicated that the crystal had not been damaged by these exchange 0022-3654/79/2083-2166$01 .OO/O
and dehydration procedures, and had remained colorless.
X-Ray Data Collection The space group Pm3m (no systematic absences) was used throughout this work for reasons discussed previously.8 Preliminary crystallographic experiments and subsequent data collection were performed with an automated, four-circle Syntex PI diffractometer, equipped with a graphite monochromator and a pulse-height analyzer. Molybdenum radiation was used for all experiments ( K q , h = 0.70930 A; Ka2, h = 0.71359 A). The cubic unit cell constant, as determined by least-squares refinement of 15 intense reflections (20" < 20 < 24"), is a = 12.312(3)
A.
Reflections from two intensity-equivalent regions of reciprocal space (hkl,h Ik 5 1, and hlk, h I1 Ik ) were examined by 6-20 scans at a constant rate of 1.0 deg m i d from 1.0" (in 20) below the calculated Kal peak to 1.0" above the Ka2 maximum. Background intensity was counted a t each end of a scan range for a time equal to half the scan time. The intensities of three reflections, (0,4,4), (4,0,4),and (4,4,0),were recorded after every 100 reflections to monitor crystal and instrument stability. Only small, random fluctuations of these check reflections were noted during the course of data collection. Other details of the data collection were the same as previously r e p ~ r t e d . ~ The raw data for each region were corrected for Lorentz and polarization effects. An absorption correction ( p = 113.1 cm-') was applied and the reduced data were merged by use of the computer program COMPARE.' Of the 890 unique reflections which were examined, 284 had intensities which exceeded three times their respective standard deviations, and only these were used in structure solution and refinement.
0 1979 American Chemical Society
