2-Phenylmalonpiperadide and 2-phenylmalonmorpholide

Article abstract of DOI:10.1107/S0108270103021310

The structures of 2-phenylmalonpiperadide (I) and 2-phenylmalonmorpholide (II) was analyzed. The molecular conformations and the packing arrangements of both the compounds were compared. Although chemically similar, the compounds exhibited different molecular conformations. The only conformational similarities were that their respective carbonyl groups were oriented in the same direction and the heterocyclic rings existed in the chair arrangement. The similarities arose due to the same space group and a similar alignment of their phenyl-substituted backbone with respect to the c axis.

Full text of DOI:10.1107/S0108270103021310

organic compounds
Acta Crystallographica Section C
Crystal Structure
Communications
1-oxo-1H-pyrazolo[1,2-a]pyrazol-4-ylium-3-olate. We decided
to continue investigating the nucleophilic cleavage of this
compound using a variety of nucleophiles, including both
piperidine and morpholine, with all resultant products being
2-phenylmalonamide derivatives. Interestingly, a search of the
April 2003 release of the Cambridge Structural Database
(Allen, 2002) reveals that there are 37 reported structures of
malonamides, including both symmetrical and unsymmetrical
analogues, yet of these there is only one 2-phenylmalonamide
derivative, that being the amide itself (Sakamoto et al., 2000).
Reported here are the crystal structures of both 2-phenyl-
malonpiperadide, (I), and 2-phenylmalonmorpholide, (II).
ISSN 0108-2701
2-Phenylmalonpiperadide and
2-phenylmalonmorpholide
Daniel E. Lynch,a* Gillian E. Spicera and Ian
McClenaghanb
aSchool of Science and the Environment, Coventry University, Coventry CV1 5FB,
England, and bKey Organics Ltd, Highfield Industrial Estate, Camelford, Cornwall
PL32 9QZ, England
Correspondence e-mail: apx106@coventry.ac.uk
Received 3 September 2003
Accepted 25 September 2003
Online 30 November 2003
The structures of 2-phenylmalonpiperadide [systematic name:
2-phenyl-1,3-bis(piperidin-1-yl)propane-1,3-dione, C19H26N2-
O2, (I)] and 2-phenylmalonmorpholide [systematic name: 1,3-
dimorpholino-2-phenylpropane-1,3-dione, C17H22N2O4, (II)],
have been determined and both their molecular conforma-
tions and packing arrangements compared. Although chemi-
cally similar, compounds (I) and (II) exhibit different
molecular conformations. The only general conformational
similarities are that their respective carbonyl groups are
orientated in the same direction and the heterocyclic rings
exist in the chair arrangement. General similarities in the
packing arrangements arise due to both compounds having
the same space group (P212121) and a similar alignment of
their phenyl-substituted backbone with respect to the c axis.
Similar CÐHÁ Á ÁO hydrogen-bonding associations are listed
for the carbonyl O atoms, while only one of the morpholine O
atoms is involved in any such association.
Compounds (I) and (II) share crystallographic similarities
by both packing in the same non-centrosymmetric space group
and sharing similar cell dimensions and cell volumes. The only
chemical difference between the two compounds is the
substitution of the piperidyl 4-position CH2 groups in (I) for
3
Ê
the morpholine O atoms in (II), with the loss of ca 104 A in
cell volume. However, these two O atoms have the potential to
cause a difference in the solid-state packing of (II), as opposed
to (I), because exposed O atoms can act as hydrogen-bond
acceptors, in addition to the two malonamide carbonyl O
atoms. Comparative molecular conformations for (I) and (II)
are shown in Figs. 1 and 2, respectively, while selected torsion
angles are listed in Tables 1 and 3.
Comment
Symmetrical malonamides can be prepared by two classical
methods (Burgada, 1964), with both involving the reaction of
two molar equivalents of an amine with either diethyl
malonate or malonyl dichloride. A third, more modern but less
ef®cient, synthesis involves the reaction of two molar
equivalents of a base or amine with 3-oxopyrazolo[1,2-a]-
pyrazol-8-ylium-1-olate (Zvilichovsky & David, 1982), a
compound also derived from either diethyl malonate or
malonyl dichloride. The nucleophilic cleavage of derivatives
of 3-oxopyrazolo[1,2-a]pyrazol-8-ylium-1-olate to produce
symmetrical malonamides was also investigated by Potts et al.
(1988), who studied the decomposition of these compounds
using morpholine, aniline or water. Experimental runs were
performed in tetrahydrofuran at 298 K and took from a few
seconds to several days for a complete reaction, depending on
the substituents of the initial pyrazolo[1,2-a]pyrazole, with one
of the slowest reactions being seen for 5,7-dimethyl-2-phenyl-
Figure 1
The molecular con®guration and atom-numbering scheme for (I).
Displacement ellipsoids are drawn at the 50% probability level.
Acta Cryst. (2003). C59, o715±o718
DOI: 10.1107/S0108270103021310
# 2003 International Union of Crystallography o715

organic compounds
With both saturated heterocyclic ring systems in the chair
conformation and the carbonyl groups orientated in the same
direction for both molecules, the important torsion angles
become those containing the C16ÐC2 bond, speci®cally N4Ð
C1ÐC2ÐC16 and C16ÐC2ÐC3ÐN10, because the back-
bone torsion angles for the two compounds, viz. N4ÐC1Ð
C2ÐC3 and C1ÐC2ÐC3ÐN10, are inversely similar. The
conformation of 2-phenylmalonamide itself differs from both
(I) and (II) by having the carbonyl groups arranged in
opposing directions and the backbone chain much ¯atter.
Comparative torsion angles are 98.15 (N1ÐC1ÐC2ÐC4),
101.16 (C4ÐC2ÐC3ÐN2), 26.26 (N1ÐC1ÐC2ÐC3) and
134.11ꢁ (C1ÐC2ÐC3ÐN4) (note that in 2-phenylmalon-
amide, atom C4 = C16).
The CÐHÁ Á ÁO hydrogen-bonding associations for com-
pounds (I) and (II) are listed in Tables 2 and 4, respectively,
and although both compounds are arranged very differently,
the malonamide carbonyl O atoms in each are involved in the
same number of intermolecular CÐHÁ Á ÁO associations. In
Figure 4
Packing diagram of (II), viewed down the a axis.
addition, there is only one listed association to a morpholine O
atom (O13), indicating that the morpholine O atoms do not
have much effect on the difference in the molecular packing.
The unit cells for (I) and (II), both viewed down the a axis, are
shown in Figs. 3 and 4. Interestingly, the phenyl rings in both
compounds are arranged almost perpendicular to the c axis,
orientating the main length of the backbone in the same
direction as the c axis. However, apart from these general
packing similarities, the two structures remain considerably
different. The occurrence of crystallographic differences
between chemically similar compounds, such as (I) and (II), is
interesting and in the structures discussed in this paper have
no apparent cause. Additional comparative compounds would
be those containing thiomorpholine, piperazine or any minor
4-position derivative of piperidine or piperazine.
Experimental
For (I), a 2:1 molar ratio of piperidine (0.71 g, 8.33 mmol) and 5,7-
dimethyl-2-phenyl-1-oxo-1H-pyrazolo[1,2-a]pyrazol-4-ylium-3-olate
(1.00 g, 4.20 mmol) was re¯uxed in tetrahydrofuran (THF, 100 ml) for
48 h. Upon cooling the reaction, the solvent was removed under
reduced pressure. The crude product was redissolved in minimal THF
and precipitated by pouring into cool deionized water (100 ml).
Collection in vacuo yielded an off-white powder (0.94 g, 72%; m.p.
416±419 K). Spectroscopic analysis, IR (ꢀmax, KBr, cm 1): 1647 (s)
Figure 2
The molecular con®guration and atom-numbering scheme for (II).
Displacement ellipsoids are drawn at the 50% probability level.
1
and 1626 (s) (CO); H NMR (400 MHz, d6-DMSO, Me4Si, p.p.m.):
1.40 (m, 12H, CH2), 3.40 (m, 8H, NCH2), 5.40 (s, 1H), 7.30 (m, 5H,
ArH); m/z (ES): 315 (MH+, 15%), 337 (M + Na, 39%), 651 (2M + Na,
100%). Compound (II) was produced using a method analogous to
that used for (I), using morpholine (1.45 g, 1.67 mmol) and 5,7-di-
methyl-2-phenyl-1-oxo-1H-pyrazolo[1,2-a]pyrazol-4-ylium-3-olate
(2.00 g, 8.33 mmol). The ®nal product was collected in vacuo as a
white powder (2.33 g, 88%, m.p. 459±461 K). Spectroscopic analysis,
IR (ꢀmax, KBr, cm 1): 1658 (s) and 1633 (s) (CO); 1H NMR
(400 MHz, d6-DMSO, Me4Si, p.p.m.): 3.27±3.63 (br m, 16H, NCH2
and OCH2), 5.51 (s, 1H), 7.21±7.39 (m, 5H, ArH); m/z (ES): 319
(MH+, 30%), 341 (M + Na, 100%), 659 (2M + Na, 73%). Crystals of
both compounds were grown from CHCl3 solutions.
Figure 3
Packing diagram of (I), viewed down the a axis. Note that atom O3 is
obsured by atom C3.
ꢀ
o716 Daniel E. Lynch et al.
C19H26N2O2 and C17H22N2O4
Acta Cryst. (2003). C59, o715±o718

organic compounds
Data collection
Compound (I)
Bruker±Nonius KappaCCD area-
detector diffractometer
' and ! scans
Absorption correction: multi-scan
(SORTAV; Blessing, 1995)
Tmin = 0.944, Tmax = 0.975
9999 measured re¯ections
2032 independent re¯ections
1909 re¯ections with I > 2ꢄ(I)
Rint = 0.066
Crystal data
C19H26N2O2
Mr = 314.42
Orthorhombic, P212121
Ê
a = 6.1652 (3) A
Ê
b = 10.2718 (5) A
c = 26.1962 (17) A
Ê
V = 1658.95 (16) A
Z = 4
Dx = 1.259 Mg m
Mo Kꢁ radiation
Cell parameters from 6419
re¯ections
ꢂmax = 27.5ꢁ
h = 9 ! 10
ꢂ = 2.9±27.5ꢁ
k = 11 ! 14
1
l = 18 ! 22
ꢃ = 0.08 mm
T = 120 (2) K
Ê
3
Plate, colourless
0.15 Â 0.10 Â 0.04 mm
Re®nement
3
Re®nement on F2
R[F2 > 2ꢄ(F2)] = 0.039
wR(F2) = 0.103
S = 1.12
2032 re¯ections
209 parameters
(Á/ꢄ)max < 0.001
3
Ê
Áꢅmax = 0.38 e A
3
Ê
0.35 e A
Áꢅmin
Extinction correction: SHELXL07
=
Data collection
Extinction coef®cient: 0.067 (7)
Bruker±Nonius KappaCCD area-
detector diffractometer
' and ! scans
Absorption correction: multi-scan
(SORTAV; Blessing, 1995)
Tmin = 0.988, Tmax = 0.997
6936 measured re¯ections
2177 independent re¯ections
1013 re¯ections with I > 2ꢄ(I)
Rint = 0.176
ꢂ
max = 27.5ꢁ
h = 7 ! 7
k = 9 ! 13
l = 34 ! 25
H-atom parameters constrained
w = 1/[ꢄ2(Fo2) + (0.0639P)2
+ 0.2187P]
2
2
where P = (Fo + 2Fc )/3
Table 3
Selected torsion angles (ꢁ) for (II).
Re®nement
Re®nement on F2
R[F2 > 2ꢄ(F2)] = 0.069
wR(F2) = 0.177
S = 0.94
2177 re¯ections
(Á/ꢄ)max < 0.001
Áꢅmax = 0.34 e A
3
Ê
O1ÐC1ÐC2ÐC16
N4ÐC1ÐC2ÐC16
O1ÐC1ÐC2ÐC3
N4ÐC1ÐC2ÐC3
106.91 (18)
71.0 (2)
13.8 (2)
C16ÐC2ÐC3ÐO3
C1ÐC2ÐC3ÐO3
C16ÐC2ÐC3ÐN10
C1ÐC2ÐC3ÐN10
20.3 (2)
100.5 (2)
158.25 (16)
81.0 (2)
3
Ê
0.34 e A
Extinction correction: SHELXL97
Áꢅmin
=
168.29 (15)
Extinction coef®cient: 0.012 (3)
209 parameters
H-atom parameters constrained
w = 1/[ꢄ2(Fo2) + (0.0705P)2]
Table 4
Hydrogen-bonding and short_contact geometry (A, ) for (II).
2
where P = (Fo + 2Fc2)/3
ꢁ
Ê
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
C2ÐH2Á Á ÁO1i
1.00
0.95
0.99
0.99
0.99
0.99
2.41
2.50
2.32
2.51
2.31
2.43
3.344 (2)
3.361 (2)
2.747 (2)
3.275 (2)
2.738 (3)
3.305 (2)
155
150
105
134
105
148
Table 1
Selected torsion angles (ꢁ) for (I).
C17ÐH17Á Á ÁO1i
C5ÐH52Á Á ÁO1
C9ÐH92Á Á ÁO13ii
C11ÐH112Á Á ÁO3
C12ÐH122Á Á ÁO3iii
O1ÐC1ÐC2ÐC16
N4ÐC1ÐC2ÐC16
O1ÐC1ÐC2ÐC3
N4ÐC1ÐC2ÐC3
19.1 (7)
159.0 (5)
102.6 (6)
79.3 (5)
C16ÐC2ÐC3ÐO3
C1ÐC2ÐC3ÐO3
C16ÐC2ÐC3ÐN10
C1ÐC2ÐC3ÐN10
96.3 (6)
24.2 (7)
83.4 (6)
156.1 (5)
Symmetry codes: (i) 2 x; 12 ‡ y; 23 z; (ii) 25 x; 1 y; 21 ‡ z; (iii) ‡ x; 21 y; 1 z.
1
2
Table 2
Hydrogen-bonding and short-contact geometry (A, ) for (I).
All H atoms were included in the re®nement at calculated posi-
tions in the riding-model approximation, with CÐH distances set at
ꢁ
Ê
Ê
0.95 (aryl H), 0.99 (CH2) and 1.00 A (CÐH), and isotropic displa-
DÐHÁ Á ÁA
DÐH
HÁ Á ÁA
DÁ Á ÁA
DÐHÁ Á ÁA
cement parameters set equal to 1.25Ueq of the carrier atom. The high
Rint value for (I) was the result of weak high-angle data. The numbers
of Friedel pairs for (I) and (II) were 1386 and 1195, respectively. In
the absence of large atoms in both structures or strong anomalous
dispersion effects, the Friedel opposites were merged prior to
re®nement.
C5ÐH51Á Á ÁO1
0.99
0.99
0.99
0.99
0.95
2.34
2.52
2.32
2.43
2.59
2.757 (7)
3.436 (7)
2.735 (7)
3.177 (7)
3.340 (7)
104
153
104
132
136
C9ÐH91Á Á ÁO1i
C11ÐH112Á Á ÁO3
C15ÐH151Á Á ÁO3ii
C17ÐH17Á Á ÁO1ii
1
1
2
Symmetry codes: (i) 2 x; y
;
z; (ii) 1 ‡ x; y; z.
2
For both compounds, data collection: DENZO (Otwinowski &
Minor, 1997) and COLLECT (Nonius, 1998); cell re®nement:
DENZO and COLLECT; data reduction: DENZO and COLLECT;
program(s) used to solve structure: SHELXS97 (Sheldrick, 1997);
program(s) used to re®ne structure: SHELXL97 (Sheldrick, 1997);
molecular graphics: PLUTON94 (Spek, 1994) and PLATON97
(Spek, 1997); software used to prepare material for publication:
SHELXL97.
Compound (II)
Crystal data
C17H22N2O4
Mr = 318.37
Mo Kꢁ radiation
Cell parameters from 6411
re¯ections
Orthorhombic, P212121
Ê
a = 8.3900 (1) A
ꢂ = 1.0±30.5ꢁ
ꢃ = 0.10 mm
T = 120 (2) K
1
Ê
b = 10.8464 (2) A
The authors thank the EPSRC National Crystallography
Service (Southampton) and the EPSRC Chemical Database
Service at Daresbury Laboratory, England (Fletcher et al.,
1996).
Ê
c = 17.0838 (4) A
Ê
V = 1554.65 (5) A
3
Block, colourless
0.60 Â 0.40 Â 0.26 mm
Z = 4
Dx = 1.360 Mg m
3
ꢀ
Acta Cryst. (2003). C59, o715±o718
Daniel E. Lynch et al. C19H26N2O2 and C17H22N2O4 o717

organic compounds
Nonius (1998). COLLECT. Nonius BV, Delft, The Netherlands.
Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276,
Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M.
Sweet, pp. 307±326. New York: Academic Press.
Supplementary data for this paper are available from the IUCr electronic
archives (Reference: GG1184). Services for accessing these data are
described at the back of the journal.
Potts, K. T., Murphy, P. M., DeLuca, M. R. & Kuehnling, W. R. (1988). J. Org.
Chem. 53, 2898±2910.
Sakamoto, J., Nakagawa, T., Kanehisa, N., Kai, Y. & Katsura, M. (2000). Acta
Cryst. C56, e485±e486.
Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of
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ꢀ
o718 Daniel E. Lynch et al.
C19H26N2O2 and C17H22N2O4
Acta Cryst. (2003). C59, o715±o718