Nitroimidazoles part 7. Synthesis and Anti-HIV activity of new 4-Nitroimidazole derivatives

Article abstract of DOI:10.5560/ZNB.2012-0122

Reverse transcriptase enzyme (RT) is an attractive target for the development of new drugs useful in AIDS therapy and HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs), and offers the possibility of generating structures of increased potency. On this basis, a series of 4-oxo-3-phenyl-2- (phenylimino)thiazolidin-5-ylidene, 3-hydroxypropyl, 3-azidopropyl, and 3-aminopropyl derivatives of 1-benzyl-2-ethyl-4-nitroimidazoles 6-8, as well as the substituted 1,2,3-triazolo analogs 12-14, the diazepam 15 and carboxamide derivatives 16 and 17 were synthesized. All compounds have been evaluated for their anti-HIV activity.

Full text of DOI:10.5560/ZNB.2012-0122

Preparation, Crystal Structures and Properties of Two
Modifications of UCr6P4
Wolfgang Jeitschko* and Reinhold Brink
Anorganisch-Chemisches Institut der Universität Münster,
Wilhelm-Klemm-Straße , D-W-4400 Münster
8
Z. Naturforsch. 47b, 192-196(1992); received September 5, 1991
Tin Flux, Crystal Structure, Magnetic Properties, Structural Relationships
UCr
(880 °C and 1000 °C), respectively. The crystal structures o f both modifications were deter-
mined from single-crystal data. a-UCr P4: P6m2 (No. 187), a = 698.5(3) pm, c = 350.8(1) pm,
Z = 1, R = 0.052 for 18 variable parameters and 410 structure factors; /?-UCr P4: Pmmn (No.
6
P4
was prepared from a tin flux in two forms at low (a) and high (ß) temperatures
6
6
59), a = 698.6(1) pm, b = 350.85(4) pm, c = 1196.1(2) pm, Z = 2, R = 0.047 for 21 variables
and 656 structure factors. Although the lattice constants of both modifications are closely re-
lated, the two forms can be transformed into each other only by a very sluggish, reconstructive
phase transformation. Nevertheless, both structures have very similar coordination polyhedra.
The U atoms have
6
P neighbours in trigonal prismatic arrangement. H alf of the Cr atoms
have tetrahedral, the other half square pyramidal P coordinations. As is typical for phosphides
with high metal content, all metal atoms additionally have many metal neighbours. The P at-
oms are located in trigonal prisms of metal atoms with two or three additional metal atoms
outside the rectangular faces of the prisms. Both modifications of UCr
6
P4 show relatively high,
almost temperature independent paramagnetism, as is frequently observerd for intermetallic
phases of uranium.
During the investigations of ternary systems
lanthanoid(Ln)-transition metal(T)-phosphorus
numerous phosphides were found with a metal:
phosphorus ratio close to or at exactly 2:1. Exam-
ples are the series Ln2Fe12P7, Ln2Co12P7 [1, 2],
Ln2N i12P7 [3], Ln2R h12P7 [4]~LnFe5P3 [5]", LnCo5P3
[6 - 8], LnNi5P3 [9, 10], LnCo8P5 [11, 12], Ln6Ni20P13
[13], LnCo3P2 [8, 14, 15], Ln5Co19P]2 [8, 16],
Ln5R u19P12 [17], LnNi4P2 [18], and Ln3Ni7P5 [19],
A few corresponding actionoid transition metal
phosphides have also been reported: Th6Co20P13
[20], U 6Rh20P]3 [21] and UMn4P2[22], Here we give
a detailed account of our work on two modifica-
tions of UCr6P4. Preliminary reports about their
crystal structures were given before [23, 24],
del-de Haen, “reinst”). The best results were
achieved by preparing first UP2 (with about 10%
excess of phosphorus) by reaction of the compo-
nents in evacuated silica tubes for 20 h at 450 °C.
The excess (white) phosphorus was separated from
the main product by a temperature gradient in the
furnace. The resulting UP2 sample was crushed to
a powder under argon and not allowed to contact
air prior to the reactions. Appropriate amounts of
UP2were then reacted with chromium powder and
red phosphorus in a tin flux. The atomic ratios
U :C r:P :S n varied between 4:19:9:68 and
5:17:8:70. The samples were placed in alumina
containers, which were sealed in evacuated silica
tubes and slowly heated (50 °C/h) to 450 °C, where
they were held for about 10 h to allow reaction of
the excess phosphorus. They were then annealed
for ten days at temperatures between 880 and
1000 °C. The tin-rich matrix of the samples was
dissolved in moderately diluted (1 : 1) hydrochloric
acid. The Guinier powder patterns showed the
samples annealed at 1000 °C to be single phase
/?-UCr6P4. The samples annealed at 880 °C consist-
ed of the a modification with minor amounts of
the ß modification.
Sample Preparation and Properties
Both modifications of UCr6P4 were prepared
from the elemental components using tin as a flux
[25, 26], Starting materials were small platelets of
uranium (Merck, “nuklearrein”), chromium pow-
der (150 mesh, nominal purity 99.99%), red phos-
phorus in the form of small pieces (Höchst AG,
Knapsack, “ultrapure”), and granules of tin (Rie-
Both modifications crystallize in the form of
black needles with metallic lustre. They are stable
in air and only very slowly attacked by hot concen-
trated hydrochloric acid.
Magnetic susceptibility measurements were
made with a Faraday balance between liquid ni-
* Reprint requests to W. Jeitschko.
Verlag der Zeitschrift für Naturforschung,
D-W-7400 Tübingen
0932 - 0776/92/0200- 0192/$ 01.00/0
- 10.1515/znb-1992-0208
Downloaded from De Gruyter Online at 09/12/2016 06:58:54AM
via free access

W. Jeitschko-R . Brink • Two M odifications of U C rfiP4
193
collected with a four-circle diffractometer. The po-
sitions of the uranium atoms were obtained from
the Patterson syntheses; those of the other atoms
were found on difference Fourier maps. For the
full-matrix least-squares refinements atomic scat-
tering factors [30] were used, corrected for anomal-
ous dispersion [31], Weights reflected the counting
statistics. Parameters accounting for isotropic sec-
ondary extinction were refined and applied to the
calculated structure factors. To check for devia-
tions from the ideal compositions, we refined oc-
cupancy parameters together with the thermal pa-
rameters, while the scale factors were held con-
stant. No significant deviations from the ideal
occupancies were observed. In the final cycles the
ideal occupancies were assumed. The correct
handedness of the crystal used to determine the
structure of the hexagonal crystal was found by re-
fining both enantiomorphic settings. The residual
trogen and room temperature as described earlier
[21]. Both modifications show almost tempera-
ture-independent paramagnetism. At room tem-
perature the susceptibility of the /^-modifications is
X = 4.3(±0.1)x 10~3 cm3/mol; it increases to / =
4 .7(± 0.1)x 10“3 cm3/mol at 77 K. The values for
the low temperature modification are about 10%
higher, but could not be determined accurately be-
cause the sample contained the high temperature
modification as a second phase. The magnitude of
these susceptibilities is considerably higher than
the Pauli paramagnetism of ordinary metals and
similar to that of “heavy fermion systems” [28],
Structure Determinations
Indices for the interpretation of the Guinier
powder data could be assigned on the basis of the
single-crystal data and the intensities calculated
[29] from the refined structure. Lattice constants
were refined by least-squares fits using a-quartz
(a = 491.30 pm, c = 540.46 pm) as standard. They value for the correct setting was lower by 4 relative
are listed in Table I together with other data of the
structure determination.
% (0.052 V5. 0.054). The final residuals, positional
parameters and interatomic distances are given in
Tables I-III. The anisotropic thermal parameters
and structure factor tables are available [32, 33]*.
Needle-shaped single-crystals of both UCr6P4
modifications were investigated in Weissenberg
cameras. In both cases the needle axes turned out
to be the short axes, as is usually the case. The
crystals had the Laue symmetries 6/mmm and
mmm and the structures were eventually deter-
mined in the space groups P6m2 (No. 187) and
Pmmn (No. 59), respectively. Intensity data were
* Further details may be obtained from: Fachinforma-
tionszentrum Karlsruhe, Gesellschaft für wissen-
schaftliche Information mbH, D-7514 Eggenstein-
Leopoldshafen 2, by quoting the Registry No. CSD
55861, the names of the authors and the journal
citation.
Table I. Crystallographic data for
the low {a)- and high (/^-temperatu-
/?-UCr
6
P
4
a-U Cr
6
P
4
re modification of UCrT\.
P6m2 (No. 187)
Pmmn (No. 59)
a = 698.6(1)
b = 350.85(4)
Space group
Cell-constants (pm)
a
= 698.5(3)
c
= 350.8(1)
c
= 1196.1(2)
= 0.2932
= 2
c/a = 0.5022
V
Z
V
Z
=0.1482
= 1
Cell volume (nm3)
Formula units per cell
Formula weight
Calculated density (g/cm3)
Crystal size (//m)
Radiation
673.90
673.90
^ ca lc —7.55
0 calc =
7
'
3
10x 13x 6100
13* 18* 150
graphite monochromated M oK a
scintillation counter, pulse height discriminator
Detector
0/20
Scan type
Scan range (2 0)
±h, ±k, ±1
Absorption corr. from
Total no. of data
Data after averaging
Data with I > 3er(I)
Residual (on F values)
Weighted residual
No. of variables
0/20
80°
1
0
0
°
±
1
2
, ±
6
,
± 2 1
±13, ±13, ±7
psi scan data
6123
648
410
R = 0.052
/?w= 0.060
18
psi scan data
7239
1108
654
R = 0.039
/?w= 0.047
40
- 10.1515/znb-1992-0208
Downloaded from De Gruyter Online at 09/12/2016 06:58:54AM
via free access

194
W. Jeitsch k o -R . Brink • Two Modifications of U C r6P4
Table II. Atomic parameters for a- and /?-UCr P4. The
6
Table III. Interatomic distances (pm) in a- and
/?-UCr P4. All m etal-m etal and metal-phosphorus di-
stances shorter than 360 pm are listed. The shortest P -P
distances are all greater than 300 pm. Standard devia-
tions are all less than 0.5 pm in the a- and less than 0.6
pm in the /^-modification.
last column lists the equivalent isotropic thermal pa-
rameter Bea(x 100 in units of nm2). Standard deviations
in the positions of the last listed digit are given in paran-
theses throughout this paper.
6
Atom
z
X
y
Bec
a-U Cr
U:
6
P
4
y?-UCr
U:
6
P
4
a-UCr
6
P
4
P6m2 (No. 187)
285.6
299.9
350.8
352.2
4P(3)
2P(1)
283.5
287.0
299.5
304.8
333.5
347.8
350.8
352.0
6
P( )
Cr(l)
1
1
a
0
0
0
0
1
0
1
0
0.423(6)
1.47(6)
0.55(3)
0.78(5)
U
6
3k
3j
.
2
0
1
1
/
/
2
2
Cr(l)
Cr(2)
P(l)
P(2)
0.7989(3)
0.4624(3)
2
Cr(l)
2U
Cr( )
0.5376
0.8137
1/3
6
2
4Cr(4)
2Cr(4)
2Cr(3)
2U
3k 0.1863(5)
2/3
1
.
2
( 1 )
1
e
Cr(l):
Cr(2):
234.8
237.4
277.2
279.1
299.9
350.8
2P(1)
2
/?-UCr
6
P
4
Pmmn (No. 59)
P(
Cr(l)
2
)
2
2
Cr(
2
)
1/4
1/4
1/4
U
2
2
2
b
a
a
0.68048(6) 0.359(7)
3/4
1/4
1/4
4Cr(2)
2U
2Cr
0.70(4)
0.43(4)
0.38(2)
0.72(3)
0.63(7)
0.51(6)
0.41(4)
Cr(l)
Cr(2)
Cr(3)
Cr(4)
P(D
P(2)
P(3)
0.8834(2)
0.2830(2)
0.0897(2)
0.5746(2)
0.4906(4)
0.0107(4)
0.7715(3)
Cr(l):
Cr(2):
Cr(3):
2
P(
2
)
232.3
235.9
277.9
281.9
299.5
350.8
2P(3)
4 f 0.0550(3) 1/4
4 f 0.5574(3) 1/4
4Cr(3)
2Cr(3)
2U
242.9
247.1
270.4
279.1
350.8
352.2
4P(1)
1P(2)
1/4
1/4
3/4
1/4
2
a
1/4
2
b
2
Cr(
2
)
2Cr(l)
4 f
0.5281(5)
4C r(l)
2
2
Cr(
U
2
)
243.0
248.3
268.4
279.1
350.8
352.0
4P(3)
1
P( )
1
2Cr(3)
4Cr(4)
Discussion
2
Cr(l)
234.8
242.9
285.6
Pd):
P(2):
4Cr(2)
2U
2
Cr(
2
)
The structures and coordination polyhedra of
the two modification of UCr6P4 are shown in
Fig. 1. Both represent new structure types, and al-
though both structures have much in common, the
phase transformation taking place somewhere be-
tween 880 and 1000 °C must be of the sluggish, re-
constructive type as opposed to the displacive, fer-
roic type, because the connectivity of the atoms is
different. The high-temperature (/?) modification
for a given composition can usually be described
with a smaller number of positional parameters.
UCr6P4 represents one of the few exceptions from
this rule.
In both modifications of UCr6P4 all atoms are
placed on mirror planes, which extend perpendicu-
lar to the short axes. In both structures the U at-
oms have six P neighbours forming trigonal prisms
at (average) distances of 285.6 pm and 284.7 pm in
the a- and /^-modification, respectively. These
coordination polyhedra are augmented by twelve
Cr atoms at average distances of 326.0 pm and
323.7 pm. Two U atoms a translation period
above and below at (the same distances in both
structures of) 350.8 pm complete these coordina-
tion polyhedra, although these interactions can
hardly be considered as bonding. Two types of dif-
ferent coordinations for the Cr atoms occur in
2U
6
Cr(l)
237.4
247.1
2
P(
2
)
241.4
242.3
244.6
268.4
272.5
277.9
281.9
287.6
347.8
350.8
3 Cr(2)
2P(3)
1P(2)
1Cr(2)
1Cr(3)
2Cr(l)
lC r(l)
2Cr(3)
1U
2Cr(3)
234.4
236.4
237.1
262.8
269.1
279.1
304.8
333.5
350.8
Cr(4):
2P(1)
1P(3)
1
P( )
1
2 Cr(4)
lCr(4)
2
Cr( )
2
2U
1U
2Cr(4)
234.4
237.1
248.3
287.0
4Cr(4)
2Cr(4)
1Cr(2)
2U
P(D:
2Cr(l)
4Cr(3)
2Cr(3)
232.3
241.4
244.6
P(2):
P(3):
235.9
236.4
242.3
243.0
283.5
lC r(l)
lCr(4)
2Cr(3)
2
Cr(
2
)
2U
- 10.1515/znb-1992-0208
Downloaded from De Gruyter Online at 09/12/2016 06:58:54AM
via free access

195
W. Jeitschko-R . Brink • Two M odifications of U C r6P4
these neighbouring atoms ar “needed”, however,
to complete the coordination polyhedra.
As is usually observed for phosphides with high
metal content the phosphorus atoms have six met-
al neighbours forming trigonal prisms (Fig. 2). In
phosphides with a m etal:phosphorus ratio of ex-
actly 2:1 the phosphorus atoms have three addi-
tional metal neighbours outside the rectangular
faces of the prisms, thus increasing the coordina-
tion number to nine. In UCr6P4 the metal p h o s-
phorus ratio is slightly lower and therefore in both
modifications one quarter of the P atoms is coordi-
nated to nine metal atoms, while the others have
only eight close metal neighbours.
oc-UCr6F2
Fig. 1. Crystal structures and coordination polyhedra of
the low (a)- and high (/?)-temperature modifications of
UCr P4. Atoms connected by thick and thin lines are
6
separated from each other by half a translation period of
the projection direction.
both structures. Half of the Cr atoms (the Cr(l) at-
oms in the a- and the Cr(l) and Cr(4) atoms in the
/^-modification) have four P neighbours forming a
distorted tetrahedron (at average distances of
236.1 pm, 234.1 pm and 235.4 pm), the other half
has five P neighbours forming a distorted square
pyramid (with average distances of 243.7 pm,
244.1 pm, and 242.4 pm for the Cr(2) atoms of the
a- and the Cr(2) and Cr(3) atoms of the
^-modification, respectively). The average C r-P
distances are larger for the Cr atoms with five P
neighbours than the average C r-P distances of the
Cr atoms with four P neighbours, as it should be
for these strong interactions. In addition both
types of Cr atoms have ten metal neighbours with
C r-C r distances ranging between 262.8 pm and
350.8 pm and C r-U distances between 299.5 pm
and 352.2 pm. The larger ones of these distances
can hardly be counted as bonding interactions,
/3-UCr6P4
Fig. 2. Arrangement of the trigonal metal prisms around
the phosphorus atoms in the two modifications of
UCr P4. Atoms connected by thick and thin lines are
separated from each other by half a translation period of
the projection direction. Large and small circles: U and
Cr; filled circles: P.
6
We thank Dipl.-Ing. U. Rodewald and Dr.
M. H. Möller for the collection of the single-crys-
tal diffractometer data. The magnetic susceptibili-
ties were determined by Dipl.-Phys. T. Vomhof
and Dr. M. Reehuis. We are also grateful for gen-
erous gifts of ultrapure red phosphorus (Hoechst
AG, Werk Knapsack) and silica tubes (Dr. G. Hö-
fer, Heraeus Quarzschmelze). This work was sup-
ported by the Deutsche Forschungsgemeinschaft
and the Fonds der Chemischen Industrie.
- 10.1515/znb-1992-0208
Downloaded from De Gruyter Online at 09/12/2016 06:58:54AM
via free access

196
[1] W. Jeitschko, D. J. Braun, R. H. Ashcraft, and R.
Marchand, J. Solid State Chem. 25, 309 (1978).
[2] M. Reehuis and W. Jeitschko, J. Phys. Chem. Solids
50, 563(1989).
W. Jeitsch k o -R . Brink • Two M odifications of U Cr6P4
[16] W. Jeitschko and E. J. Reinbold, Z. Naturforsch.
40b, 900(1985).
[17] V. Ghetta, P. Chaudouet, R. Madar, J. P. Senateur,
and B. Lambert-Andron, J. Less-Common Met.
146,299(1989).
[3] W. Jeitschko and B. Jaberg, Z. Anorg. Allg. Chem.
[18] S. I. Chikhrii, S. V. Orishchin, and Yu. B. Kuz’ma,
Dopov. Akad. Nauk. Ukr. RSR, Ser. A 1986, 81.
[19] S. I. Chikhrii, S. V. Orishchin, Yu. B. Kuz’ma, and
T. Glovyak, Sov. Phys. Crystallogr. 34,681 (1989).
[20] E. Ganglberger, Z. Kristallogr. 128,438 (1969).
[21] V. Ghetta, P. Chaudouet, R. Madar, J. P. Senateur,
and B. Lambert-Andron, Mater. Res. Bull. 22, 483
(1987).
467,95(1980).
[4] J.-Y. Pivan, R. Guerin and M. Sergent, C. R. Acad.
Sei. Ser. 11299,533(1984).
[5] W. Jeitschko, U. Meisen, and U. D. Scholz, J. Solid
State Chem. 55, 331(1984).
] V. N. Davydov and Yu. B. Kuz'ma, Dopov. Akad.
Nauk. Ukr. RSR Ser. A: Fiz. Mat. Tekh. Nauk.
1981,81 (1981).
[6
[22] W. Jeitschko, L. J. Terbüchte, E. J. Reinbold, P. G.
Pollmeier, and V. Vomhof, J. Less-Common Met.
161, 125(1990).
[7] U. Meisen and W. Jeitschko, J. Less-Common Met.
102, 127(1984).
[
8
] U. Jakubowski-Ripke and W. Jeitschko, J. Less-
Common Met. 136,261 (1988).
[23] R. Brink and W. Jeitschko, Z. Kristallogr. 174, 27
(1986).
[9] W. K. Hofmann and W. Jeitschko, J. Solid State
Chem. 51, 152(1984).
[10] J. V. Badding and A. M. Stacy, J. Solid State Chem.
67,354(1987).
[11] U. Meisen and W. Jeitschko, Z. Kristallogr. 167,
135(1984).
[24] R. Brink and W. Jeitschko, Z. Kristallogr. 178, 34
(1987).
[25] P. Jolibois, C. R. Acad. Sei. 150, 106 (1910).
[26] R. Rühl and W. Jeitschko, Inorg. Chem. 21, 1886
(1982).
[27] W. Jeitschko and M. Reehuis, J. Phys. Chem. Solids
[12] M. Reehuis, W. Jeitschko, E. Mörsen, and W. Mül-
ler-Warmuth, J. Less-Common Met. 139,359 (1988).
[13] R. Madar, P. Chaudouet, E. Dhari, J. P. Senateur,
R. Fruchart, and B. Lambert, J. Solid State Chem.
56,335(1985).
48,667(1987).
[28] F. Steglich, J. Phys. Chem. Solids 50,225 (1989).
[29] K. Yvon, W. Jeitschko, and E. Parthe, J. Appl.
Crystallogr. 10,73(1977).
[30] D. T. Cromer and J. B. Mann, Acta Crystallogr.
[14] W. Jeitschko and U. Jakubowski, J. Less-Common
Met. 110,339(1985).
A 24, 321 (1968).
[31] D. T. Cromer and D. Libermann, J. Chem. Phys.
53, 1891 (1970).
[32] R. Brink, Diplomarbeit, Univ. Münster (1985).
[15] S. I. Chikhrii, S. V. Orishchin, and Yu. B. Kuz’ma,
Izv. Akad. Nauk SSSR, Neorg. Mater. 25, 1380
(1989).
[33] R. Brink, Dissertation, Univ. Münster (1989).
- 10.1515/znb-1992-0208
Downloaded from De Gruyter Online at 09/12/2016 06:58:54AM
via free access