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
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
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