Synthesis, characterisation and crystal structure of a co-crystal of two components: 1,2-bis(6-methylpyridin-2-yl)ethane-1,2-dione and 1-(pyridin-2-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione

Article abstract of DOI:10.3184/030823407X200434

A condensation reaction of an equimolar ratio of 2-pyridinecarboxaldehyde and (6-methylpyridin-2-yl)methanol without a catalyst in a solvent-free reaction at 140°C was expected to yield 2-hydroxy-[1,2-bis(6-methylpyridin-2-yl)] ethan-1-one. FT-IR spectroscopy of the yellow-brown solid reaction product indicated the presence of a -CO-COH- group. The solid compound was treated with cyclohexane and green crystals were produced. The crystals were characterised by FT-IR, ¹H NMR, El mass spectrometry and single-crystal X-ray diffraction. The molecular and crystal structure determined by single-crystal X-ray diffraction resolved one crystal showing two molecular components [C ₁₃H₁₀N₂O₂ and C₁₄H ₁₂N₂O₂] at a ratio of 60.4:39.6 [C _13.40H_10.79N₂O₂]. Both compounds co-crystallise in the triclinic space group P-1, with a = 7.859(5), b = 8.021(14), c = 9.060(5) A, α = 101.36(2)°, β= 90.06(3)°, γ = 90.92(3)°, V = 559.8(5) A³, Z= 2. The compounds were 1,2-bis(6-methylpyridin-2-yl)ethane-1,2-dione and 1-(pyridin-2-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione. These results are important because they confirm that condensation in a solvent- and catalyst-free reaction yielded precursors that were converted into α-diketone compounds by the action of solvent and oxygen.

Full text of DOI:10.3184/030823407X200434

JOURNAL OF CHEMICAL RESEARCH 2007
MARCH, 185–189
RESEARCH PAPER 185
Synthesis, characterisation and crystal structure of a co-crystal of two
components: 1,2-bis(6-methylpyridin-2-yl)ethane-1,2-dione and
1-(pyridin-2-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione
M. Judith Percinoa*, Víctor M. Chapelaa, Omar Urzúaa, Héctor Toribioa and
Cecilia Rodríguez-Barbarínb
aCentro de Química, Instituto de Ciencias, Universidad Autónoma de Puebla, Complejo de Ciencias, ICUAP, Edif. 76, 22 Sur y San.
Claudio, C.P. 72570, Puebla, Puebla, México
bDivisión de Estudios de Posgrado, Facultad de Ciencias Químicas, U.A.N.L., Guerrero y Progreso S/N, Col. Treviño, C.P. 64570
Monterrey, N.L., México
A condensation reaction of an equimolar ratio of 2-pyridinecarboxaldehyde and (6-methylpyridin-2-yl)methanol
without a catalyst in a solvent-free reaction at 140°C was expected to yield 2-hydroxy-[1,2-bis(6-methylpyridin-2-
yl)]ethan-1-one. FT-IR spectroscopy of the yellow-brown solid reaction product indicated the presence of a –CO–
COH– group. The solid compound was treated with cyclohexane and green crystals were produced. The crystals
1
were characterised by FT-IR, H NMR, EI mass spectrometry and single-crystal X-ray diffraction. The molecular
and crystal structure determined by single-crystal X-ray diffraction resolved one crystal showing two molecular
components [C13H10N2O2 and C14H12N2O2] at a ratio of 60.4:39.6 [C13.40H10.79N2O2]. Both compounds co-crystallise in
the triclinic space group P-1, with a = 7.859(5), b = 8.021(14), c = 9.060(5) Å, a = 101.36(2)°, b = 90.06(3)°, g = 90.92(3)°,
V = 559.8(5) Å3, Z = 2. The compounds were 1,2-bis(6-methylpyridin-2-yl)ethane-1,2-dione and 1-(pyridin-2-yl)-2-
(6-methylpyridin-2-yl)ethane-1,2-dione. These results are important because they confirm that condensation in a
solvent- and catalyst-free reaction yielded precursors that were converted into a-diketone compounds by the action
of solvent and oxygen.
Keywords: 1,2-diketones, 2-hydroxy-[1,2-bis(6-methylpyridin-2-yl)]ethan-1-one, 1,2-bis(6-methylpyridin-2-yl)ethane-1,2-di-
one, 1-(pyridin-2-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione, co-crystal structure
In organic chemistry, one of the oldest known reactions is the
cyanide-catalysed benzoin condensation.1 The remarkably
specific cyanide ion catalysis of the reaction was first studied
by Lapworth2 in 1903. Benzoins contain a –COCHOH–
group and can be oxidised to the a-diketone (benzil) very
efficiently by several reagents such as nitric acid3, Fehlings
solution3 and thallium nitrate.4-7 It is also known that 2-
pyridinecarboxaldehyde undergoes benzoin condensation,8-9 in
the presence of KCN or glacial acetic acid as catalyst but yields
trans-1,2-di-(2-pyridyl)-1,2-ethenediol instead of the benzoin
derivative (a-pyridoin). On the other hand, it is known that
weak forces, especially hydrogen bonding, considerably affect
the structures of crystals and liquids.10 It has been suggested
that a-pyridoin may be completely dominated by the enediol
isomer because of intramolecular interactions taking place
in the latter.11 Butane-2,3-dione is in tautomeric equilibrium
with but-1-en-2-ol-3-one and buta-1,3-diene-2,3-diol, which
are expected to be stabilised by –OH…O =C< and –OH…
OH– intramolecular hydrogen bonds. Osmialowski et al.11
showed that in chloroform solution (1Z,3Z)-1,4-di(pyridin-2-
yl)buta-1,3-diene-2,3-diol is in ca 9:1 equilibrium with (3Z)-
3-hydroxy-1,4-di(pyridin-2-yl)but-3-en-2-one, while no 1,4-
di(pyridin-2-yl)butane-2,3-dione was detected. Theoretical
calculations showed that –CO–COH–, especially the highly
conjugated –HOC =COH– forms, are preferred in tautomeric
mixtures in both vacuum and chloroform solution, due to one
or two O–H…N interactions.
Accordingtoarecentstudyofcondensationreactionswithout
catalyst and solvent of different aldehydes and methylpyridines
to obtain precursor or intermediary compounds,12 it was
proposed that the reaction of 2-pyridinecarboxaldehyde and
2-pyridinemethanol at 140°C without a catalyst or solvent
yielded the compound 2-hydroxy-1,2-di(pyridin-2-yl)ethan-
1-one.13 In addition, it has been reported that reaction of (6-
methylpyridin-2-yl)methanol and 2-pyrdinecarboxaldehyde
without solvent and catalyst yielded the compound 1,2-bis(6-
methylpyridin-2-yl)ethene-1,2-diol, with single-crystal X-ray
diffraction showing that it is a symmetrical molecule with two
intramolecular hydrogen bonds.14
As a result, it was proposed to isolate the precursor 2-
hydroxy-[1,2-bis(6-methylpyridin-2-yl)]ethan-1-one (1) from
the reaction of (6-methylpyridin-2-yl)methanol and 2-
pyridincarboxaldehyde according to Scheme 1 and justify
the proposal that the compounds with a –CO–COH– group
could be oxidised to –CO–CO– in solution in the presence of
oxygen. However, the reaction results were more interesting,
as proposed in Scheme 2. Crystal structure determination
of the co-crystal is important because, to the best of our
O
O
H
Me
N
N
Me
N
N
Me
H
OH
140°C
5 h
+
OH
2-pyridinecarboxaldehyde
1
(6-methyl-2-pyridine)methanol
Scheme 1
* Correspondent. E-mail: jpercino@siu.buap.mx
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186 JOURNAL OF CHEMICAL RESEARCH 2007
O
H
Me
N
N
Me
O
OH
N
Me
N
C
140°C
5 h
H2
H
OH
+
1
O
H
Me
N
(6-methyl-2-pyridine)methanol
2-pyridinecarboxaldehyde
N
O
OH
2
O2
solvent
N
O
Me
N
N
Me
N
Me
+
O
O
4
3
green crystals
Scheme 2
the w-scan method. A total of 1968 independent reflections (out of
7836 measured) for which |F|/s(|F|)>4.0 were corrected for Lorentz
and polarisation effects, but not for X-ray absorption. The structure
was solved using direct methods and refined15 on F2 by full-matrix
least-squares analysis with anisotropic displacement parameters
for the non-hydrogen atoms. Hydrogen atoms were placed in the
calculated positions.
knowledge, the synthesis conditions and crystal structure of
the title compounds have not been reported.
Experimental
Materials and instruments
2-Pyridinecarboxaldehyde and (6-methylpyridin-2-yl)methanol were
supplied by Aldrich Chemical Co. and were distilled before use.
IR spectra of reaction products were recorded on a Vertex model 70
Bruker 750 FT-IR spectrophotometer by ATR. 1H NMR spectra were
obtained on a Varian 300-MHz NMR spectrometer in D2O. Melting
points were measured using an SEV (0–300°C) apparatus and are
uncorrected. The crystal structure data were measured with a Bruker
P4/Pc diffractometer with a graphite monochromator and Mo–Ka
radiation (l = 0.71073 Å).
Results and discussion
The results from condensation reaction at an equimolar
ratio of 2-pyridinecarboxaldehyde and (6-methylpyridin-
2-yl)methanol at 140°C without catalyst or solvent were
unexpected. Only the new compound 2-hydroxy-[1,2-bis(6-
methylpyridin-2-yl)]ethan-1-one (1) was expected according
to the recently reported conditions for the reaction of 2-
pyridinecarboxaldehyde and (pyridin-2-yl)methanol.13
Figure 1 shows the IR spectrum for the yellow-brown powder
from the condensation reaction of 2-pyridinecarboxaldehyde
and (6-methylpyridin-2-yl)methanol. The spectrum shows
an intense band at 1709 cm–1 assigned16,17 to C=O stretching
vibrations, which is weaker than in the starting material
(2-pyridinecarboxaldehyde), and bands at 3472 and 1183
cm–1 assigned to nO–H vibration stretching and νC–OH,
respectively, indicating the presence of a –C(O)–COH–
group, but the results did not indicate that it was a mixture
of compounds. The green crystals obtained after the yellow-
brown powder was treated with cyclohexane gave the IR
spectrum in Fig. 2. It clearly shows two bands at 1710 and
1694 cm–1 due to the two C=O groups characteristic of an a-
diketone.
Synthesis of 2-hydroxy-[1,2-bis(6-methylpyridin-2-yl)]ethan-1-one
(1) and 2-hydroxy-1-(pyridin-2-yl)-2-(6-methylpyridin-2-yl)ethan-
1-one (2): Initially the reaction was expected to form only
the compound 2-hydroxy-[1,2-bis(6-methylpyridin-2-yl)]ethan-1-
one (1) (Scheme 1). A mixture of (6-methylpyridin-2-yl)methanol
(0.008 mol) and 2-pyridinecarboxaldehyde (0.008 mol) was heated
at 140°C with no solvent or catalyst. The reaction mixture was
magnetically stirred for 5 h. The appearance of the mixture changed
from colourless to a red-brown oily liquid. Immediately, without
allowing it to cool, the mixture was precipitated by adding 2 M
NaOH solution dropwise with agitation. After adding the required
amount to obtain a precipitate (4.0 ml of NaOH solution), the yellow-
brown powder was filtered using vacuum. The yield was 27% and the
m.p. of the powder was 95–100°C.
Synthesis of a co-crystal of two components: 1,2-bis(6-methyl-
pyridin-2-yl)ethane-1,2-dione (3) and 1-(pyridin-2-yl)-2-(6-methyl-
pyridin-2-yl)ethane-1,2-dione (4): The powder obtained from the
first procedure was dissolved in cyclohexane and filtered, producing
a green-yellow solution that was poured into a precipitation vessel
and kept at room temperature for a week. At the end of that time,
small green crystals were formed, with m.p. 115–120°C, and a small
portion of yellow powder on the glass wall, with m.p. 84–89°C. Both
compounds were dissolved again in cyclohexane to obtain only green
crystals with m.p. 120–123°C.
1H NMR spectra clearly indicated that the green crystals
are two compounds (Fig. 3), since the spectrum presented two
signals at 2.41 and 1.56 ppm, which are due to two different –
CH3 groups. In addition, the signal at 8.59 ppm indicated that
a proton is present in the ortho-position of the pyridine ring,
which might be due to the co-compound 1-(pyridin-2-yl)-2-(6-
methylpyridin-2-yl)ethane-1,2-dione, whereas the spectrum
should only present signals for the compound 1,2-bis(6-
methylpyridin-2-yl)ethane-1,2-dione. The signals between
8.59 and 7.24 ppm were assigned to aromatic protons.
X-Ray experiments
The title mixture crystallises from cyclohexane as green prismatic
crystals. A single crystal with approximate dimensions 0.50 ¥ 0.40 ¥
0.30 mm3 was selected for X-ray structure determination.
Three-dimensional room-temperature X-ray data were collected
in the range 3.0°<2q<50.0° on a Bruker P4 diffractometer with a
graphite monochromator and Mo–Ka radiation (l = 0.71073 Å) using
The characterisation by EI mass fragmentation was
decisive.18 The EI spectrum gave molecular ions at m/z 240
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JOURNAL OF CHEMICAL RESEARCH 2007 187
Fig. 1 IR spectrum of compounds 1 and 2.
Fig. 2 IR spectrum of compounds 3 and 4.
Fig. 3 1H NMR of the green crystals in CDCl3.
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188 JOURNAL OF CHEMICAL RESEARCH 2007
for the 1,2-bis(6-methylpyridin-2-yl)ethane-1,2-dione (3)
and m/z 226 for 1-(pyridin-2-yl)-2-(6-methylpyridin-2-yl)
ethane-1,2-dione (4). Mass spectrometry confirmed the
presence of both compounds based on molecular ions at
m/z 240 and 226.
experimental crystal data, structure determination and
refinement are shown in Table 1. Selected bond lengths are
given in Table 2. The solid sample is a co-crystal formed by
two molecules present in different proportions: C13H10N2O2
(Fig. 4A) with 60.4% occupancy and C14H12N2O2 (Fig. 4B)
with 39.6% occupancy. These molecules are present in
solution and crystallised together.
The spectroscopy data were corroborated by X-ray
diffraction. The crystal data and pertinent details of the
Table 1 Crystal data and structure determination of the title
compounds
Empirical formula
Color, habit
C13.40H10.79N2O2
Green, prismatic
0.5 ¥ 0.4 ¥ 0.3 mm3
Triclinic
Crystal size
Crystal system
Space group
Unit cell dimensions
P-1
a = 7.859(5) b = 8.021(4)
c = 9.060(5) Å
a = 101.36(2)° b = 90.60(3)°
g = 90.92(3)°
Volume
559.8(5) Å3
Z
2
Formula weight
Density (calc.)
Absorption coefficient
F(000)
Diffractometer used
System used
Radiation
Voltage and tube current
Temperature
Monochromator
2q range
231.77
1.375 g cm–3
0.095 mm–1
242
Bruker P4
XSCAnS,21 release 2.31
Mo–Ka (l=0.71073 Å)
50 kV, 25 mA
(A)
297(2) K
Highly oriented graphite crystal
3.0–50.0°
Scan type
Scan speed
w
Variable speed, 1.75–17.5° min–1
in w
Scan range (w)
1.86° + separation between the
Ka1 and Ka2 positions
Stationary crystal and stationary
counter at the beginning and
end of a scan, each for 25% of
the total scan time
3 measured every 97
reflections: 1 0 2; 1 2 0; 2 0 1
min 0.942, max 1.022
–9£h£9, –9£k£ 9, –10£l£10
7836
1968 (Rint=6.95%)
99.2% to 2q =50.0°
1103
8.07
None
Background measurement
Standard reflections
Correction from standards
Index ranges
Reflections collected
Independent reflections
Completeness
Reflections with Fo>4s(Fo)
I/s(I) (all data)
<
>
Absorption correction
System used15,22
SHELXTL 5.03 and SHELXL-Plus
5.10
Wilson’s statistics
Solution
|E2–1| = 1.036
<
>
(B)
Direct methods and difference
Fourier maps
Fig. 4 (A) Molecule A, C13H10N2O2 with 60.42% occupancy
in the co-crystal. (B) Molecule B, C14H12N2O2 with 39.58%
occupancy in the co-crystal.
Refinement method
Quantity minimised
Hydrogen atoms
Restraints, constraints
Weighting scheme
Full matrix least-squares
2 2
S[w(Fo2–Fc ) ]
Riding model, fixed isotropic U
1, 0
w = [s2(Fo2) + (0.1283 P)2 +
0.0584 P]–1, where
2
P = (max[Fo2,0] + 2Fc )/3
Final R indices (I > 2 s(I))
Final R indices (all data)
Goodness-of-fit
Largest and mean D/s
Data-to-parameters ratio
Largest difference peak
Largest difference hole
R1 = 6.60 %, wR2 = 19.41 %
R1 = 11.18%, wR2 = 23.26%
S = 1.042
0.000, 0.000
1968/166
0.223 e Å–3
–0.275 e Å–3
Table 2 Selected bond lengths/Å
O(1)–C(7)
O(2)–C(8)
C(6)–C(7)
C(7)–C(8)
1.196(4)
1.188(4)
1.449(5)
1.524(5)
C(8)–C(9)
C(1)–C(2)
C(13)–C(14)
1.465(4)
1.464(5)
1.481(5)
Fig.
5
Molecular representation of the composite title
compound, C13.40H10.79N2O2, with the atom labelling scheme
shown; thermal ellipsoids are at the 30% probability level.
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JOURNAL OF CHEMICAL RESEARCH 2007 189
Å; C10–H10A…O2, 165.98°]. There is a π…π interaction
between equivalent symmetry related pyridine rings [N1, C2
to C6; symmetry code: 1–x, 1–y, 1–z], with a separation of
3.673 Å (3.35 Å in graphite);21 these interactions stabilise
the solid structure (Fig. 6). The results open the opportunity
to obtain precursor compounds that could then yield novel
compounds without a catalyst in a solvent-free reaction.
CCDC 644649 contains the supplementary crystallographic
data for this paper. The data can be obtained free of charge
from the Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request.cif.
The authors acknowledge CONACYT for financial support
(Project numbers 44237 and 46360).
Received 23 October 2006; accepted 25 March 2007
Paper 06/4273
doi: 10.3184/030823407X200434
References
1
2
3
4
F. Wöhler and J. Liebig, Ann. Pharm., 1832, 3, 249.
A. Lapworth, J. Chem. Soc., 1903, 83, 995.
J.S. Buck and S.S. Jenkins, J. Am. Chem. Soc., 1929, 51, 2163.
A. McKillop, B. Swann, M.E. Frod and E.C Taylor, J. Am. Chem. Soc.,
1973, 95, 3641.
5
6
M. Weiss and M. Appel, J. Am. Chem. Soc., 1948, 70, 3666.
G.-S. Zhang, Q.-Z. Shi, M.-F. Chen and K.Cai, Synth. Commun., 1997,
27, 953.
7
S.A. Tymonko, B.A. Nattier and R.S. Mohan, Tetrahedron Lett., 1999, 40,
7657.
C. Harries and G.H. Lenart, Liebigs Ann., 1915, 410, 95.
H. Hensel, Angew. Chem., 1953, 65, 491.
Fig.
6
View of the molecular packing structure of
C13.40H10.79N2O2, showing H-bonding and p···p interaction at
3.673 Å between equivalent symmetry related pyridin rings
(N1, C2 to C6; symmetry code: 1-x, 1-y, 1-z).
8
9
10 K. Müller-Dethlefts and P. Hobza, Chem. Rev., 2000, 100, 143.
11 B. Osmialowski, E. Kolehmainen, M. Nissinen, T.M. Krygowski and
R.Gawinecki, J. Org. Chem., 2002, 67, 3339.
All atoms occupy general positions in the unit cell and a
representation of the composition of the two molecules in
the crystal is given in Fig. 5. The pyridine rings in the title
compound are nearly perpendicular to each other, with a
dihedral angle of 85.9°. Related compounds show similar
dihedral geometry: 1,2-di-2-pyridylethanedione19 with 82.1°
and 1-(6-methylpyridin-2-yl)-2-phenylethanedione20 with
86.1°. The torsion angle for the dione moiety, O=C–C=O, is
73.5° for the title compound, and –78.6° and 75.8° for the
related compounds mentioned above. The C7–C8 distance
of 1.524(5) Å is significantly longer than the value of 1.48
Å expected for a C sp2–C sp2 bond. Elongation of the
corresponding bond in the related compounds is also evident,
which could be due to repulsion between the two ketonic
oxygen atoms.
12 M.J. Percino, V.M. Chapela, A. Sánchez and J.L. Maldonado-Rivera,
Chem. Indian J., 2006, 3, 262.
13 J. Percino, V.M. Chapela, H. Toribio, C. Rodriguez-Barbarin and
F. Melendez-Bustamante, International Chemical Congress of Pacific
Basin Societies, Pacifichem 2005 Congress, Honolulu, Hawaii, USA,
2005.
14 M.J. Percino, V.M. Chapela, C. Rodríguez-Barbarín, J. Chem. Res., 2005,
12, 757.
15 G.M. Sheldrick, SHELXTL-Plus 5.10. Bruker AXS Inc., Madison,
Wisconsin, USA. 1997.
16 L.J. Bellamy, The Infra-red Spectra of Complex Molecules, 3rd edn.,
John Wiley and Sons, Inc., New York, 1975.
17 K. Nakanishi and P.H. Solomon, Infrared Absorption Spectroscopy,
2nd edn., Holden-Day, Inc., Oakland, 1977.
18 M.J. Percino, V.M. Chapela, O. Urzúa and H. Toribio, Int. J. Mass
Spectrom., 2007, 262, 122.
19 S. Hirokawa, T. Ashida, Acta Crystallogr., 1961, 14, 774; T. Ashida and
S. Hirokawa, Acta Crystallogr., 1970, B26, 454.
20 Y.Li, A.Usman, Y.Zhang, H.Fun and J. Xu, Acta Crystallogr., E, 2002, 58,
1400.
21 R.W.G. Wyckoff, Geometrical Structure, Interscience Publishers,
New York, USA, 1963 p 83.
22 Siemens. XSCAnS User’s Manual. Version 2.31. Siemens, Analytical
X-ray Instruments Inc., Madison, WI, USA, 1999
23 G.M. Sheldrick, SHELXTL. Release 5.03. Siemens Analytical, X-ray
Instruments Inc., Madison, WI, USA, 1995
The crystal packing presents intermolecular H-bonding
contacts between one of the O atoms [O2] and two hydrogens,
H1B of the CH3 group of a symmetry related molecule (B)
[O2…H1B, 2.199 Å; C1–H1B…O2, 173.93°] and H10A
of the other ring of the same molecule [O2…H10A, 2.512
PAPER: 06/4273