The diastereoisomers methyl 5-(S)-[2-(R)/(S)-methoxycarbonyl)-2,3,4,5- tetrahydropyrrol-1-ylcarbonyl]-1-(4-methylphenyl)-4,5-dihydropyrazole-3- carboxylate

Article abstract of DOI:10.1107/S0108270101021552

The title diastereoisomers, methyl 5-(S)-[2-(S)-methoxy-carbonyl)- 2,3,4,5-tetrahydropyrrol-1-ylcarbonyl]-1-(4-methyl-phenyl)-4,5-dihydropyrazole- 3-carboxylate and methyl 5-(S)-[2-(R)-methoxycarbonyl)-2,3,4,5-tetrahydropyrrol- 1-ylcarbonyl]-1-(4-methylphenyl)-4,5-dihydropyrazole-3-carboxylate, both C₁₉H₂₃N₃O₅, have been studied in two crystalline forms. The first form, methyl 5-(S)-[2-(S)-methoxycarbonyl)-2,3,4, 5-tetrahydropyrrol-1-ylcarbonyl]-1-(4-methylphenyl)-4,5-dihydropyrazole-3- carboxylate-methyl 5-(S)-[2-(R)-methoxycarbonyl)-2,3,4,5-tetrahydropyrrol- 1-ylcarbonyl]-1-(4-methylphenyl)-4,5-dihydropyrazole-3-carboxylate(1/1), 2(S),-5(S)-C₁₉H₂₃N₃O₅·2(R), 5(S)-C₁₉H₂₃N₃O₅, contains both S,S and S,R isomers, while the second, methyl 5-(S)-[2-(S)-methoxycarbonyl)-2,3,4,5- tetrahydropyrrol-1-ylcarbonyl]-1-(4-methylphenyl)-4,5-dihydropyrazole-3- carboxylate, 2(S),-5(S)-C₁₉H₂₃N₃O₅, is the pure S,S isomer. The S,S isomers in the two structures show very similar geometries, the maximum difference being about 15° on one torsion angle. The differences between the S,S and S,R isomers, apart from those due to the inversion of one chiral centre, are more remarkable, and are partially due to a possible rotational disorder of the 2-(methoxycarbonyl)tetrahydropyrrole group.

Full text of DOI:10.1107/S0108270101021552

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
mixture directly by diffusion of hexane into a CH2Cl2 solution
at 297±298 K. Initially, small amorphous or microcrystalline
spheres (about 1 mm in diameter) were obtained, while in the
ISSN 0108-2701
The diastereoisomers methyl 5-(S)-
[2-(R)/(S)-methoxycarbonyl)-2,3,4,5-
tetrahydropyrrol-1-ylcarbonyl]-1-(4-
methylphenyl)-4,5-dihydropyrazole-3-
carboxylate
end, good crystals were obtained in the form of long thin
blades suitable for X-ray analysis. Quite surprisingly, the
structure of these blades [hereinafter (I)] shows the presence
of both isomers, i.e. the S,S compound (molecule A) and the
S,R compound (molecule B). Molecule A is ordered, while the
2-methoxycarbonyltetrahydropyrrole group of B shows quite
large displacement parameters, indicating a partial rotational
disorder. For this reason, we may deduce that, in solution, a
pre-organized AB adduct exists which is more soluble than the
single diastereoisomer A. This is quite unusual since, to our
knowledge, very few cocrystallized diastereoisomers have
been reported in the crystallographic literature, especially
ones which are ordered and in a 1:1 ratio. Two rare examples
Tullio Pilati* and Gianluigi Casalone
Á
CNR±Centro per lo Studio delle Relazioni fra Struttura e Reattivita Chimica,
Á
c/o Dipartimento di Chimica±Fisica ed Elettrochimica, Universita degli Studi di
Milano, Via Golgi 19, 20133 Milano, Italy
Correspondence e-mail: pila@csrsrc.mi.cnr.it
Received 9 November 2001
Accepted 17 December 2001
Online 28 February 2002
The title diastereoisomers, methyl 5-(S)-[2-(S)-methoxy-
carbonyl)-2,3,4,5-tetrahydropyrrol-1-ylcarbonyl]-1-(4-methyl-
phenyl)-4,5-dihydropyrazole-3-carboxylate and methyl 5-(S)-
[2-(R)-methoxycarbonyl)-2,3,4,5-tetrahydropyrrol-1-ylcar-
bonyl]-1-(4-methylphenyl)-4,5-dihydropyrazole-3-carboxyl-
ate, both C19H23N3O5, have been studied in two crystalline
forms. The ®rst form, methyl 5-(S)-[2-(S)-methoxycarbonyl)-
2,3,4,5-tetrahydropyrrol-1-ylcarbonyl]-1-(4-methylphenyl)-
4,5-dihydropyrazole-3-carboxylate±methyl 5-(S)-[2-(R)-me-
thoxycarbonyl)-2,3,4,5-tetrahydropyrrol-1-ylcarbonyl]-1-(4-
methylphenyl)-4,5-dihydropyrazole-3-carboxylate (1/1), 2(S),-
5(S)-C19H23N3O5Á2(R),5(S)-C19H23N3O5, contains both S,S
and S,R isomers, while the second, methyl 5-(S)-[2-(S)-
methoxycarbonyl)-2,3,4,5-tetrahydropyrrol-1-ylcarbonyl]-
1-(4-methylphenyl)-4,5-dihydropyrazole-3-carboxylate, 2(S),-
5(S)-C19H23N3O5, is the pure S,S isomer. The S,S isomers in
the two structures show very similar geometries, the maximum
difference being about 15ꢀ on one torsion angle. The
differences between the S,S and S,R isomers, apart from those
due to the inversion of one chiral centre, are more remarkable,
and are partially due to a possible rotational disorder of the
2-(methoxycarbonyl)tetrahydropyrrole group.
Â
are given by Soriano-Garcõa et al. (1990) and Bligh et al.
(1993).
The microspheres obtained from the ®rst crystallization
were separated by hand from the crystals containing both
diastereoisomers. The material of these microspheres was
shown by NMR spectroscopy to be the pure major component
of the mixture. It was recrystallized using the same solvents
but at a lower temperature (292 K) in an air-conditioned
Comment
The title diastereoisomers were synthesized (Garanti & Mol-
teni, 2002) by 1,3-dipolar cycloaddition of N-4-methylphenyl-
C-methoxycarbonylnitrilimine to 1-(1-oxoprop-2-enyl)-2-(S)-
methoxycarbonyl-2,3,4,5-tetrahydropyrazole. A 67:33 ratio of
the diastereoisomers was observed by NMR spectroscopy, and
a crystal structure determination was suggested in order to
establish the con®guration of the major component.
Figure 1
A view of the pure S,S isomer from (II) (molecule C) with the atom-
numbering scheme. Displacement ellipsoids are drawn at the 50%
probability level and H atoms are shown as small spheres of arbitrary
radii.
Since separation of the isomers by standard chromato-
graphic methods failed, an attempt was made to crystallize the
o178 # 2002 International Union of Crystallography
DOI: 10.1107/S0108270101021552
Acta Cryst. (2002). C58, o178±o180

organic compounds
1
2
Ê
1.177 (4) A] and in the short contact C13BÁ Á ÁO25B( x, y
,
Ê
z) [2.946 (6) A].
The packing of (I) is characterized by the antiparallel
coupling of the 1-(4-methylphenyl)dihydropyrazole moieties
of molecules A and B; the angle between the lines joining N1A
to C12A and N1B to C12B is 164.1 (1)ꢀ, while the angle
between the mean planes through the ring atoms N1/C6±C12
in molecules A and B is 157.5 (1)ꢀ.
Three weak and approximately linear CÐHÁ Á ÁO hydrogen
bonds help to stabilize the crystal of (I), together with other,
less linear, hydrogen bonds. In the packing of (II), molecules
are linked by a CÐHÁ Á ÁO hydrogen bond.
Experimental
The title diastereoisomers were synthesized according to the method
of Garanti & Molteni (2002) by 1,3-dipolar cycloaddition of
N-4-methylphenyl-C-methoxycarbonylnitrilimine to 1-(1-oxoprop-2-
enyl)-2-(S)-methoxycarbonyl-2,3,4,5-tetrahydropyrazole. A ratio of
67:33 the diastereoisomers was observed by NMR spectroscopy.
Crystals were obtained by diffusion of hexane into a CH2Cl2 solution
at 297±298 K.
Figure 2
A view of molecule B (the S,R isomer) from (I) with the atom-numbering
scheme. Displacement ellipsoids are drawn at the 30% probability level
and H atoms are shown as small spheres of arbitrary radii. The large
anisotropy of the ellipsoids of the methoxycarbonylpyrrole group
indicates a possible rotational disorder. Atom H5B is wholly obscured
behind C5B.
Compound (I)
Crystal data
3
room. The crystals obtained were, in general, multiply
twinned, but suf®ciently large to allow a wedge large enough
for X-ray analysis to be cut. This material, (II) (molecule C,
Fig. 1), is the S,S molecule.
C19H23N3O5ÁC19H23N3O5
Dx = 1.300 Mg m
Mo Kꢁ radiation
Cell parameters from 4420
re¯ections
Mr = 746.81
Monoclinic, P21
a = 12.5056 (14) A
Ê
Ê
b = 13.3082 (16) A
ꢂ = 2.3±20.7ꢀ
ꢃ = 0.10 mm
T = 293 (2) K
1
Ê
c = 12.9491 (14) A
The chemically equivalent bond distances in molecules A
and C do not differ by more than 3 s.u.'s from their mean
values, while equivalent angles in some cases reach this limit,
the largest difference occurring for N19ÐC23ÐC24 [110.5 (2)
and 108.3 (3)ꢀ for molecules C and A, respectively]. The
differences in the torsion angles are sometimes greater than
10ꢀ, in particular around the bonds N1ÐC6, N1ÐC5 and
C23ÐC24, the maximum difference being for the torsion
angle C5ÐN1ÐC6ÐC7 [168.5 (3) and 176.7 (2)ꢀ in mol-
ecules A and C, respectively]. In consequence, the confor-
mation of the pyrazole ring is more planar in molecule C than
in molecule A, with the total puckering coordinates q2 being
ꢀ = 117.695 (2)ꢀ
Ê
V = 1908.2 (4) A
Z = 2
3
Rhombic prism, yellow
0.42 Â 0.34 Â 0.12 mm
Data collection
Bruker SMART CCD area-detector
diffractometer
! and ' scans
21 406 measured re¯ections
3524 independent re¯ections
2789 re¯ections with I > 2ꢄ(I)
Rint = 0.034
ꢂmax = 25ꢀ
h = 14 ! 14
k = 15 ! 15
l = 15 ! 15
Re®nement
Ê
Re®nement on F2
R[F2 > 2ꢄ(F2)] = 0.039
wR(F2) = 0.101
S = 0.94
3524 re¯ections
503 parameters
H-atoms parameters constrained
2
0.036 (3) and 0.133 (3) A, respectively [Cremer & Pople
(1975), calculated after Nardelli (1983)].
w = 1/ꢄ2(Fo
)
(Á/ꢄ)max = 0.001
Apart from the different con®guration at C5, with obvious
changes in the torsion angles around all bonds to C5, mol-
ecules A and B show greater deviations of other chemically
equivalent parameters. For example, the con®guration of the
3
Ê
Áꢅmax = 0.20 e A
3
Ê
0.12 e A
Áꢅmin
=
Ê
pyrazole ring is more deformed in B, with q2 = 0.219 (7) A, but
Compound (II)
with opposite phase ['2 is 136 (2) and 40 (2)ꢀ in A and B,
respectively].
Crystal data
3
The possible partial disorder affecting molecule B is
re¯ected not only in the large displacement parameters of the
2-methoxycarbonyltetrahydropyrrole group of molecule B
(Fig. 2), but also in the apparent shortening of some distances,
C19H23N3O5
Mr = 373.40
Monoclinic, P21
Dx = 1.344 Mg m
Mo Kꢁ radiation
Cell parameters from 5921
re¯ections
Ê
a = 6.9782 (9) A
b = 17.56 (2) A
ꢂ = 2.3±26.5ꢀ
Ê
1
Ê
c = 7.7576 (10) A
ꢃ = 0.10 mm
T = 293 (2) K
Ê
such as C20ÐC21 [1.458 (7) and 1.509 (6) A in B and A,
ꢀ = 103.884 (5)ꢀ
Ê
respectively], C21ÐC22 [1.467 (9) and 1.510 (7) A], C22Ð
Ê
C23 [1.488 (7) and 1.523 (5) A], C24ÐO25 [1.148 (6) and
3
Ê
V = 922.7 (11) A
Z = 2
Wedge, yellow
0.40 Â 0.30 Â 0.22 mm
ꢁ
Acta Cryst. (2002). C58, o178±o180
Pilati and Casalone C19H23N3O5ÁC19H23N3O5 and C19H23N3O5 o179

organic compounds
Data collection
For both compounds, data collection: SMART (Bruker, 1999); cell
re®nement: SMART; data reduction: SAINT (Bruker, 1999);
program(s) used to solve structure: SIR92 (Altomare et al., 1994);
program(s) used to re®ne structure: SHELXL97 (Sheldrick, 1997);
molecular graphics: ORTEPIII (Burnett & Johnson, 1996); software
used to prepare material for publication: SHELXL97.
Bruker SMART CCD area-detector
diffractometer
! and ' scans
21 391 measured re¯ections
2188 independent re¯ections
1649 re¯ections with I > 2ꢄ(I)
Rint = 0.028
max = 27.5ꢀ
ꢂ
h = 9 ! 9
k = 22 ! 22
l = 10 ! 10
We thank Professor L. Garanti and Dr G. Molteni for
suggesting this study, and for the gift of suitable crystals.
Re®nement
Re®nement on F2
R[F2 > 2ꢄ(F2)] = 0.029
wR(F2) = 0.061
S = 0.84
2188 re¯ections
300 parameters
H-atoms parameters constrained
w = 1/[ꢄ2(Fo2) + (0.0161P)2]
where P = (Fo2 + 2Fc2)/3
(Á/ꢄ)max = 0.002
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: BM1481). Services for accessing these data are
described at the back of the journal.
3
Ê
Áꢅmax = 0.12 e A
3
Ê
0.11 e A
Áꢅmin
=
References
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atoms of methyl groups attached to sp2 and sp3 centres were located
from difference Fourier syntheses and were re®ned as part of a rigid
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Polidori, G. & Camalli, M. (1994). J. Appl. Cryst. 27, 435.
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Ê
rotating group, with CÐH = 0.96 A and Uiso(H) = 1.5Ueq(C) for both
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to the low ratio of observations to parameters for (I), all H atoms in
this structure were introduced at calculated positions as riding atoms,
Ê
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È
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Â
Â
Â
Â
Â
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ꢁ
o180 Pilati and Casalone
C19H23N3O5ÁC19H23N3O5 and C19H23N3O5
Acta Cryst. (2002). C58, o178±o180