C-H...π and C=O...π intermolecular interactions in dibenzyl-3,6-dimethylpyrazine-2,5-dicarboxylate

Article abstract of DOI:10.1007/s10870-007-9307-5

A new pyrazine compound, has been synthesised and characterised by single-crystal X-ray diffraction: monoclinic, P2₁/c with a = 11.0707(3) A, b = 5.23700(10) A, c = 16.6997(5) A, β = 103.5385(16)°, Mr = 376.40, V = 941.30(4) A³, Z =

Full text of DOI:10.1007/s10870-007-9307-5

J Chem Crystallogr (2008) 38:301–303
DOI 10.1007/s10870-007-9307-5
ORIGINAL PAPER
C–HÁÁÁp and C=OÁÁÁp Intermolecular Interactions in Dibenzyl-3,6-
dimethylpyrazine-2,5-dicarboxylate
Joana A. Silva Æ Ana C. Santos Æ Ana T. Marques Æ Manuela Ramos Silva Æ
´
Ana Matos Beja Æ Abılio J. F. N. Sobral
Received: 7 September 2007 / Accepted: 5 November 2007 / Published online: 28 November 2007
Ó Springer Science+Business Media, LLC 2007
Abstract A new pyrazine compound, has been synthe-
sised and characterised by single-crystal X-ray diffraction:
˚
monoclinic, P21/c with a = 11.0707(3) A, b = 5.23700
have been used as anti-diabetics, nutrition supplement,
insecticides and fungicites [7]. Pyrazine ring is important
for antimycobacterial activity of some drugs used in the
treatment of tuberculosis. One example is pyrazinamine,
one of the frontline agents prescribed for the treatment of
Mycrobacterium tuberculosis. New drugs and/or new der-
ivates of old drugs, such as pyrazinamide, have been
prepared and studied in the last years and the quest for new
pyrazines is intense [8–11].
˚
˚
(10) A, c = 16.6997(5) A, b = 103.5385(16)°, Mr =
3
376.40, V = 941.30(4) A , Z = 2. Each molecule pos-
˚
sesses Ci symmetry with the two halves of the molecule
related by an inversion centre. C–HÁÁÁp and C=OÁÁÁp
interactions held the molecules together.
Keywords Pyrazine Á Antituberculotic activity Á
We have synthesised the title compound as a potential
antituberculotic agent. Preliminary biological assays in
HT-29 cells showed that the dibenzyl-3,6-dimethylpyr-
azine-2,5-dicarboxylate is not cytotoxic and in vitro
antituberculosis activity tests are currently being done.
Intermolecular interactions
Introduction
Pyrazines are important compounds in supramolecular
chemistry namely in the design of polynuclear metal
complexes. Such complexes provide the opportunity for the
study of magnetic exchange mechanisms [1–3]. They are
also present in the volatiles responsible for the roasted
aromas of cooked food such as roasted coffee beans and
roasted peanuts [4–6]. Pyrazines play also important roles
as intermediates for perfumes, pharmaceuticals and agri-
cultural chemicals. Amides and sulfonamides of pyrazines
Experimental
Preparation of Dibenzyl-3,6-dimethylpyrazine-2,5-
dicarboxylate
The title compound was prepared through the general
conditions of the Knorr reaction for pyrroles but using a
open flask to allow a large presence of air in the reaction
medium to permit an easier auto-condensation of the
2-imino derivatives of the benzyl 3-oxobutanoate [12]. In a
typical experiment, to a solution of 2 mL (10 mmol) of
methyl 4-acetyl-5-oxohexanoate in 100 mL of acetic acid
are added 2 mL (10 mmol) of benzyl 3-oxobutanoate in
50 mL of aqueous sodium nitrite 1 M. After 1 h 10 g of
granular Zn are added drop wise at 50 °C. After 2 h
500 mL of water are added to precipitate the crude material
that was filtrated, dried under vacuum and crystallized. The
first crystallization from dichloromethane/hexane affords
the benzyl 4-(3-methoxy-3-oxopropyl)-3,5-dimethyl-1
Electronic supplementary material The online version of this
article (doi: 10.1007/s10870-007-9307-5) contains supplementary
material, which is available to authorized users.
J. A. Silva Á A. C. Santos Á A. T. Marques Á A. J. F. N. Sobral
Chemistry Department, University of Coimbra, 3004-516
Coimbra, Portugal
M. R. Silva (&) Á A. M. Beja
CEMDRX, Physics Department, University of Coimbra,
3004-516 Coimbra, Portugal
e-mail: manuela@pollux.fis.uc.pt
123

302
J Chem Crystallogr (2008) 38:301–303
H-pyrrole-2-carboxylate (0.47 g, 15% yield). The filtrate
was then dried and the remaining material was crystallized
from ethanol to give 0.94 g of pale yellow crystals of
dibenzyl 3,6-dimethylpyrazine-2,5-dicarboxylate (25%
yield), that were collected and dried under vacuum before
X-ray analysis.
Table 1 Summary of crystallographic results
Temperature (K)
Empirical formula
Formula weight
293(2)
22H20N2O4
C
376.40
˚
Wavelength (A)
0.71073
Crystal system
Space group
monoclinic
P21/c
˚
a (A)
11.0707(3)
5.2370(10)
16.6997(5)
103.5385(16)
941.30(4)
2
˚
b (A)
Crystal structure determination
˚
c (A)
A crystal of the title compound with prismatic shape and
pale yellow colour and having approximate dimensions of
0.37 9 0.17 9 0.10 mm was glued on a glass fiber and
mounted on a Bruker Apex II difractometer. Diffraction
data were collected at room temperature 293(2) K using
b (°)
Volume (A )
3
˚
Z
Calculated density (g/cm3)
Absorption coefficient (mm-1
F(000)
1.328
)
0.092
˚
graphite monochromated Mo Ka (k = 0.71073 A). Data
396
Crystal size (mm3)
h range for data collection (°)
Index ranges
0.37 9 0.17 9 0.10
1.89–37.24
were processed using PLATON and an absorption correc-
tion (using SADABS) was applied which resulted in
transmission factors ranging from 0.973 to 0.991 [13, 14].
Data were corrected for Lorentz and Polarization effects.
Reflections with 2h B 74° were used for structure solution
and refinement.
-18 B h B 18, -8 B k B 8,
-28 B l B 28
Reflections collected/unique
45317/4778
99.9%
Completeness to h = 51°
The structure was solved by direct methods using
SHELXS-97 [15]. It was refined by full-matrix least-
squares on F2 using the SHELXL-97 program [15]. All the
hydrogen atoms were placed at calculated positions and
allowed to ride on their parent atoms using SHELXL-97
defaults. The final least-squares cycle was based on 1654
observed reflections [I [ 2r(I)] and 128 variable parame-
ters, converged with R = 0.0345 and wR = 0.1358 for
room temperature. Crystallographic details, selected inter-
atomic distances and angles and geometric details of
H-bonds are given in Tables 1, 2 and 3 respectively.
Transmission factors (min/max)
Data/restraints/parameters
Goodness-of-fit on F2
0.973/0.991
1654/0/128
1.150
Final R indices [I [ 2r(I)]
R indices (all data)
0.0345 /0.1069
0.0506/0.1358
-0.230 /0.186
CCDC 656082
-3
˚
Largest diff. peak and hole (e A
)
CCDC Number
˚
Table 2 Selected bond lengths (A) and angles (°)
N1–C1
1.334(2)
1.339(2)
1.198(2)
1.3220(18)
114.29(13)
79.4(2)
N1–C2
C4–O1
Results and Discussion
C4–O2
C4–O2–C5
C7–C6–C5–O2
Crystal Structure of the Title Compound
The structure of the title compound together with the atom-
numbering scheme, is illustrated in Fig. 1. The packing
diagram and the formation of chains is shown on Fig. 2.
Selected bond lengths and angles are listed in Table 2.
Dibenzyl 3,6-dimethylpyrazine-2,5-dicarboxylate crys-
tallizes in space group P21/c with two molecules per unit
cell. Each molecule possesses Ci symmetry with the two
halves of the molecule related by an inversion center
(Fig. 1). The pyrazine ring is therefore planar. The car-
boxylate group and C3 and C5 are also in the main
molecular plane. The outer phenyl rings are twisted out of
this plane making a dihedral angle of 74.58(8)°, with the
pyrazine ring plane.
Table 3 Geometric details of the C–HÁÁÁp and C=OÁÁÁp intermolec-
˚
ular interactions (A, °)
H, OÁÁÁp
2.94
CÁÁÁp
3.659(2)
Angle
135
C10–H10ÁÁÁpa
C4–O1ÁÁÁpb
3.4469(16)
3.8093(16)
98.32(11)
ap system of the phenyl ring with symmetry operator 1-x, -1/2 + y,
1/2 - z
b
p system of the pyrazine ring with symmetry operator x, -1 + y, z
123

J Chem Crystallogr (2008) 38:301–303
303
observed in the molecular assembling: carbonylÁÁÁp inter-
actions (Fig. 2, Table 3). The carboxylate carbonyl group
is almost parallel to the pyrazine ring giving rise to the
interaction of the lone pair of atom O1 to the pyrazine ring.
The C4=O1ÁÁÁCentroid angle is 98.32(11)° and the oxygen
˚
atom and the p system are separated by 3.4469(16) A. This
interaction joins the molecules in chains along the c axis.
Fig. 1 ORTEPII plot of the title compound. Displacement ellipsoids
are drawn at the 50% level
Supplementary Material
Crystallographic data for structural analysis have been
deposited with the Cambridge Crystallographic Data Center,
CCDC 656082. Copies of this information may be obtained
free of charge on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK (fax: +44 1223 336 033; e-mail:
deposit@ccdc.cam.ac.uk or http://www.ccdc.cam.ac.uk).
Acknowledgement This work was supported by Fundac¸a˜o para a
ˆ
Ciencia e a Tecnologia under project POCI/AMB/55281/2004.
References
1. Zhang K-L, Wang Z, Huang H, Zhu Y, You X-Z (2004) J Mol
Struct 693:193
2. Wang F-Q, Zhuang W-J, Jin L-P (2007) J Mol Struct 832:48
ˇ
ˇ ˇ
3. Govindaswamy P, Therrien B, Su¨ss-Fink G, Stepnicka P, Ludvık J
´
(2007) J Organomet Chem 692:1661
4. Oliveira AL, Cruz PM, Eberlin M.N, Cabral FA (2005) Cienc
Tecnol Aliment Campinas 25:677
ˆ
5. Hashim L, Chaveron H (1995) Food Res Int 28:619
6. Bondarovich HA, Friedel P, Krampl V, Renner JA, Shephard FW,
Gianturco MA (1967) J Agr Food Chem 15(6):1093
7. Higashio Y, Shoji T (2004) Appl Cat A: General 260:251
8. Bonde CG, Gaikwad (2004) Bioorg Med Chem 12:2151
9. Sriam D, Yoggeswari P, Reddy SP (2006) Bioorg Med Chem Lett
16:2113
Fig. 2 Partial content of the unit cell of the title compound showing
the chain formation via the carbonylÁÁÁp interactions (depicted as
dashed lines)
10. Seitz LE, Suling WJ, Reynolds RC (2002) J Med Chem 45:5604
´
ˇ
11. Krinkova J, Dolleza M, Hartl J, Buchta V, Pour M (2002)
Farmaco 57:71
Although there are not conventional hydrogen bonding
donors in this compound, there are intermolecular inter-
actions promoting the crystal cohesion. C10 carbon shares
its attached hydrogen atom with the aromatic p system of a
neighbouring phenyl ring. In this interaction the
C10ÁÁÁCentroid (1 - x, -1/2 + y, 1/2 - z) distance is
12. Bean GP (1990) The chemistry of heterocyclic compounds,
Chapter 2, vol 48. John Wiley & Sons
13. Spek AL (2003) J Appl Cryst 36:7
¨
14. Sheldrick GM (2001) SADABS. University of Gottingen,
Germany
15. Sheldrick GM (1997) SHELXS97 and SHELXL-97. University
of Gottingen, Germany
16. Malone JF, Murray CM, Charlton MH, Docherty R, Lavery AJ
(1997) J Chem Soc Faraday Trans 93:3429
˚
3.659(2) A and the bond angle is 135°, configuring a type
V interaction according to the classification of Malone et
al. with the hydrogen atom interacting with the ring edge
carbon atoms [16]. Other less usual interactions are
123