Synthesis of 1,2-dimethoxy-1,2-di(pyridin-2-yl)-1,2-ethanediol: Crystal and molecular structure determination

Article abstract of DOI:10.1007/s10870-005-9064-2

The compound, 2-hydroxy-[1,2-di(pyridin-2-yl)]ethane-1-one, 1, was isolated from the reaction of 2-pyridinecarboxaldehyde and 2-pyridinemethanol at 140°C without catalyst or solvent and characterized by¹H-NMR and IR spectral data. The compound 1 was treated with ethyl acetate to produce the 1,2-di(pyridin-2-yl)ethane-1,2-dione, 2. When 2 was dissolved in an excess of CH₃OH, crystals of 1,2-dimethoxy-1,2-di(pyridin-2-yl)-1,2-ethanediol, 3, were obtained. The molecular and crystal structure of 3 was determined by single crystal X-ray diffraction. The compound crystallizes in the monoclinic system belonging to the P2₁/n space group with a = 6.867(2) A, b=9.546(4) A, c=10.522(5) A, α=90°, β=98.48(4)°, γ=90°. The asymmetric unit comprises two molecules of 3. Although the di-hemiketal was obtained in crystal form, it was found to be unstable, because its IR spectrum changed after a short time, indicating that it had been converted back to the original diketone, 2. The IR showed signals at 1713, and 1690 due to νC =O assigned to di-ketone group.

Full text of DOI:10.1007/s10870-005-9064-2

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Journal of Chemical Crystallography, Vol. 36, No. 5, May 2006 ( 2006)
DOI: 10.1007/s10870-005-9064-2
Synthesis of 1,2-dimethoxy-1,2-di(pyridin-2-yl)-1,2-
ethanediol: Crystal and molecular structure determination
M. Judith Percino,(1)∗ V´ıctor M. Chapela,(1) Silvia Romero,(1)
Cecilia Rodr´ıguez-Barbar´ın,(2) and Francisco J. Melendez-Bustamante(3)
Received July 21, 2005; accepted December 20, 2005
Published Online February 14, 2006
The compound, 2-hydroxy-[1,2-di(pyridin-2-yl)]ethane-1-one, 1, was isolated from the
reaction of 2-pyridinecarboxaldehyde and 2-pyridinemethanol at 140◦C without catalyst or
solvent and characterized by1H-NMR and IR spectral data. The compound 1 was treated
with ethyl acetate to produce the 1,2-di(pyridin-2-yl)ethane-1,2-dione, 2. When 2 was
dissolved in an excess of CH3OH, crystals of 1,2-dimethoxy-1,2-di(pyridin-2-yl)-1,2-
ethanediol, 3, were obtained. The molecular and crystal structure of 3 was determined
by single crystal X-ray diffraction. The compound crystallizes in the monoclinic system
˚
˚
˚
belonging to the P21/n space group with a = 6.867(2) A, b = 9.546(4) A, c = 10.522(5) A,
α = 90◦, β = 98.48(4)◦, γ = 90◦. The asymmetric unit comprises two molecules of 3. Al-
though the di-hemiketal was obtained in crystal form, it was found to be unstable, because
its IR spectrum changed after a short time, indicating that it had been converted back to the
original diketone, 2. The IR showed signals at 1713, and 1690 due to νC = O assigned to
di-ketone group.
KEY WORDS: Hemiketal; 2-hydroxy-[1,2-di(pyridin-2-yl)]ethane-1-one; 1,2-di(pyridin-2-yl)ethane-1,2-
dione; crystal structure; 2,2ꢁ-pyridil.
Introduction
In organic chemistry, one of the oldest
ion catalysis of the reaction was first studied
by Lapworth2 in 1903. Benzoins contain the
–
–
group COCHOH and can be oxidized to the
α-diketone (benzil) very efficiently by several
reagents such as nitric acid,3 Fehlings solu-
tion,3 thalium nitrate.4–7 Also it is known that
2-pyridinecarboxaldehyde by benzoin condensa-
tion8,9 in the presence of KCN or glacial acetic
acid as catalyst gave trans-1,2-di-(2-pyridyl)-1,2-
ethenediol instead of α-pyridoin. The crystal
structure of the ethenediol was reported.10 The
molecule possesses a center of symmetry, has
known reactions is the cyanide-catalyzed benzoin
condensation.1 The remarkably specific cyanide
(1) Centro de Qu´ımica, Instituto de Ciencias, Universidad Auto´noma
de Puebla, Complejo de Ciencias, ICUAP, Edif. 76, 22 Sur y San.
Claudio, C. P. 72570, Puebla, Mexico.
(2) Divisio´n de Estudios de Posgrado, Facultad de Ciencias Qu´ımicas,
U.A.N.L., Guerrero y Progreso S/N, Col. Trevin˜o, C. P. 64570,
Monterrey, N.L. Mexico.
(3) Facultad de Ciencias Qu´ımicas, Beneme´rita Universidad Auto´n-
oma de Puebla Edif. 140, Ciudad Universitaria, C.P. 72570,
Puebla, Mexico.
–
a trans configuration around the central C C
bonds, and is planar. There are two intramolec-
∗
To whom correspondence should be addressed; e-mail: at 1215-
–
ular O H · · · N hydrogen bonds giving stability to
San Dario Avenue Suite G 48-126, Laredo, Texas 78040; e-mail:
jpercino@siu.buap.mx.
the compound.
303
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1074-1542/06/0500-0303/0 2006 Springer Science+Business Media, Inc.

304
Percino, Chapela, Romero, Rodr´ıguez-Barbar´ın, and Melendez-Bustamante
It was proposed11–13 that trans-1,2-di-(2-
yl)-buta-1,3-diene-2,3-diol is in ca. 9:1 equi-
librium with (3Z)-3-hydroxy-1,4-di(pyridin-2-
yl)but-3-en-2-one, while no 1,4-di(pyridin-2-
yl)2,3-butanedione was detected. Theoretically
pyridyl)-1,2-ethenediol is not stable in air and
is easily oxidized to 1,2-di(pyridin-2-yl)]ethane-
1,2-dione, 2, [2,2ꢁ-pyridil, 1,2-di(2-pyridyl)-1,2-
ethanedione, di-2-pyridilglioxal]. The crystal
structure of 2 was reported for the first time in
1961 by Hirokawa and Ashida.14 They showed
that the structure is rather unusual as it exhibits
a plane-to-plane stacking made by four almost
parallel pyridine rings.
–
–
–
calculations showed that CO COH and es-
–
=
–
pecially the highly conjugated HOC COH
forms are preferred in the tautomeric mix-
tures, both in vacuum and in chloroform so-
–
lution, because of one or two O H · · · N
interactions.16
On the other hand, it is known that
the weak forces, especially hydrogen bond-
ing, affect considerably the structures of crys-
tals and liquids.15 It has been suggested that
α-pyridoin may be completely dominated by
the enediol isomer, because of intramolecu-
lar interactions taking place in the latter.16
Butane-2,3-dione is in tautomeric equilibrium
with 1-buten-2-ol-3-one and 1,3-butanediene-2,3-
diol which are expected to be stabilized by
In the present work, our main aim was to iso-
late 1 (also known as α-pyridoin) and then convert
it to 2. We proposed that 2 in methanol solution
would produce 3 (Scheme 1). The crystal structure
determination of 3 is important because, to the
best of our knowledge, the synthesis conditions
and crystal structure of the title compound have
not been reported.
Despite the di-hemiketal being obtained in
crystal form, it was found to be unstable, because
its IR spectrum changed after some time indicat-
ing that it had been converted back to the original
diketone.
–
=
–
–
OH · · · O C< and OH · · · OH intramolecular
hydrogen bonds. Osmialowski et al.16 showed that
in chloroform solution (1Z,3Z)-1,4-di(pyridin-2-
Scheme 1.

1,2-dimethoxy-1,2-di(pyridin-2-yl)-1,2-ethanediol
305
Experimental
Synthesis of 1,2-di(pyridin-2-yl)-
ethane-1,2-dione (2)
Materials and instruments
The powder obtained from synthesis of 1 was
dissolved in ethyl acetate and filtered, producing
a yellow solution which was poured into a closed
vessel and kept at room temperature for a week.
At the end of that time, green little crystals were
formed, with melting point 155–157◦C. The IR
spectrum was compared with the one already re-
ported17 and it was found to be identical. IR(KBr):
2-Pyridinecarboxaldehyde and 2-pyridin-
emethanol were supplied by Aldrich Chem. Co.
and they were distilled before use. The IR spec-
tra were recorded on a Bruker Vertex 70 model
FT-IR spectrophotometer. Melting points were
measured using a Fisher–Johns (0–300◦C) appa-
ratus. Values obtained were not corrected. The
UV-Vis spectra were recorded on a Beckman
DU 7500 spectrophotometer. The1H-NMR spec-
tra were obtained on a Jeol Eclipse 400 MHz
NMR-spectrometer.
3056 cm−1 νC H (Py); 1713 and 1690 νC O
–
=
−1
–
–
–
=
ketone ( CO CO ); 1583 cm C C (Py); 902,
760 cm−1 δCH. UV-Vis λmax = 202, 205, 238,
272, 370 nm.
Synthesis of the 2-hydroxy-[1,2-di(pyridin-
2-yl)] ethane-1-one (1)
Formation of 1,2-dimethoxy-1,2-
di(pyridin-2-yl)- 1,2-ethanediol (3)
A
mixture
of
2-pyridinemethanol
A saturated solution, with the powder ob-
tained from the synthesis of 1 and methanol, was
prepared. This solution was kept at a tempera-
ture of 4◦C for 4 weeks. After that time uncol-
ored crystals were formed, melting point 146–
(0.008 mmol) and 0.008 mmol of the 2-
pyridinecarboxaldehyde was heated at 140◦C
with no solvent or catalyst. The reaction mixture
was magnetically stirred during 5 h. The
mixture’s appearance changed from colorless to a
brown oily liquid. Immediately, without allowing
it to cool, the mixture was precipitated by adding
dropwise 2 N HCl solution with agitation. If
too much HCl is added, the precipitate formed
may dissolve and only an oily solution obtained.
After adding the required amount to obtain
the precipitate (3.25 mL of HCl solution), the
yellow brown powder was filtered using vacuum.
The melting point of this compound was 134–
136◦C.
150◦C. IR (KBr): 3446 cm−1 νO H (low inte−n1-
–
sity and sharp); 1597 cm−1 (νC N), 1574 cm−1
=
=
–
–
(νC C); 1469 (δC H, CH3 O group); 1212 cm
−1
–
–
– –
(νC OH); 1124 cm (δO H); 1074 (νC O C).
IR(KBr): 3500 cm−1, νO H (broad);
2853 cm , νC H (w); 1713 cm , νC O ke-
tone (low intensity band); 1591νC N (pyri-
–
−1
−1
–
=
=
−1
=
dine grou−p)1; 1581 cm , νC C (phenyl group);
–
1182 cm ,−ν1 C O (s and sharp band); 783
1
–
and 732 cm , δC H (out of plane). H-NMR
(CD3Cl): δ = 8.5–8.44 ppm (d, 2H, J = 5.13 Hz);
δ = 8.045–8.00 ppm (4H, J = 7.70, 1.47 Hz);
δ = 7.82–7.80 ppm (d, 2H, J = 8.07 Hz). UV-Vis
λmax = 202, 247, 378, 465 nm.
Fig. 1. The molecular structure of the title compound. Ther-
mal ellipsoids for all atoms different to H are at 50% proba-
bility level.

306
Percino, Chapela, Romero, Rodr´ıguez-Barbar´ın, and Melendez-Bustamante
X-ray experimental section
rameters for the nonhydrogen atoms. Hydrogen
atoms were placed in calculated positions. The
crystal data and pertinent details of the experi-
mental conditions are summarized in Table 1.
Crystals of title compound (C14H16N2O4)
were obtained when 1 was dissolved in an excess
of CH3OH. A suitable green prismatic crystal with
0.70 mm × 0.70 mm × 0.60 mm dimensions was
used for data collection.
Results and discussion
Three-dimensional, room-temperature X-
ray data were collected in the range of 3.5◦ <
2θ < 60.0◦ on a Siemens P4 diffractometer with
a graphite monochromator and a Mo Kα radia-
The reaction conditions used, no catalyst and
no solvent, allowed us to isolate 2-hydroxy-1,2-
di(pyridin-2-yl)]ethane-1-one, 1. Conventional
conditions8,9 give only trans-1,2-di(pyridin-2-
yl)ethenediol. Oxidation of 1 in solution al-
lowed 1,2-di(pyridin-2-yl)ethane-1,2-dione (2) to
be obtained. Characterization data of the com-
pounds have confirmed their structures. The IR
results show that the band intensity at 1713 cm−1
˚
tion (λ = 0.71073 A) by the ω-scan method. The
1902 independent reflections (of 2561 measured)
for which |F|/σ(|F|) > 3.0 were corrected for
Lorentz and polarization effects, but not for X-
rays absorption. The structure was solved using
direct methods and refined18 on F2 by full-matrix
least-squares with anisotropic displacement pa-
=
assigned to the stretching vibration C O for
compound 1 is weaker than in the starting ma-
–
terial, 2-pyridinecarboxaldehyde, and O H vibra-
Table 1. Crystallographic Data for 1,2-Dimethoxy-1,2-di(pyridin-
tion stretching appeared. In the IR spectrum of
2, the structure was proven by the two bands
2-yl)-1,2-ethanediol
=
Empirical formula
CCDC deposit no.
Color, habit
C14H16N2O4
253718
Green, prismatic
0.70 × 0.70 × 0.60
Monoclinic
P21/n
6.867(2)
9.246(4)
10.522(5)
90
98.48(4)
90
660.8(5)
2
1.389
0.103
292
5.90–59.96
2561
assigned to the two C O groups. The UV-
Vis results also gave evidence of the formation
of all compounds. Formation of 1,2-dimethoxy-
1,2-di(pyridin-2-yl)-1,2-ethanediol (3) was unex-
pected. It is known19 that, with a few exceptions,
hemiketals are too unstable to be isolated even
though the alcohol was used in excess. Never-
theless, in a related case, Moll et al.20 reported
the formation of 1,2-diethoxy-1,2-dihydroxy-1,2-
di(2-pyridyl)ethane dihydrochloride by treating 2
with ethanolic hydrogen chloride.
Crystal size (mm3)
Crystal system
Space group
˚
a (A)
˚
b (A)
˚
c (A)
α (◦)
β (◦)
γ (◦)
3
˚
Volume (A )
Z
Dcalc (g/cm3)
In our case, the formation of 1,2-dimethoxy-
1,2-di(pyridin-2-yl)-1,2-ethanediol (3) from 2
might be due to steric hindrance by the pyridyl
groups of the carbonyls, because it was found
that addition of a catalyst was not necessary.
The molecular structure of 3 is shown in Fig. 1.
The pyridyl rings are located anti to each
Absorption coefficient (mm−1
F(0 0 0)
)
2θ range (◦)
Reflections collected
Independent reflectionsa
Reflections with Fo > 4σ(Fo)
Final R indices (I > 2σ(I))a
Final R indices (all data)a
1902 (Rint = 2.9%)
1663
R1 = 4.90, wR2 = 14.04
R1 = 5.52, wR2 = 15.27
0.991
0.294
− 0.210
Goodness-of-fita
Largest difference peak (e/A )
Largest difference hole (e/A )
–
other relative to the single bond C(6) C(6A).
3
˚
˚
The crystal data and pertinent details of the
experimental conditions are summarized in
Table 1. Bond lengths and angles are listed in
Table 2. Since the crystal belongs to P21/n and
the number of molecules in a unit cell is two, each
3
ꢀ
ꢀ
2
2
o
|F −ꢂF ꢃ|
||
|
|
||
F
− F
o
c
aRint
wR2
=
=
,
R1
=
,
o
ꢀ
ꢀ
2
|F |
o
F
o
ꢁ ꢀ
ꢂꢀ
2
2
2
2
2
c
2
w(F −F
)
w(F −F
)
o
c
o
ꢀ
, S =
.
2
2
m−n
w(F
)
o

1,2-dimethoxy-1,2-di(pyridin-2-yl)-1,2-ethanediol
307
Fig. 2. A perspective view of the crystal package across of the crystallographic axis b
for the 1,2-dimethoxy-1,2-di(pyridin-2-yl)-1,2-ethanediol showing the hydrogen bonds.
molecule possesses an inversion center localized
There are two intramolecular hydrogen
bonds between two symmetry related hydro-
gen atoms of the alcohol groups and the ni-
–
at the center of C(6) C(6A) bond.
–
trogen atoms of pyridine rings, O H · · · N. The
◦
˚
Table 2.
Bond Lengths (A) and Bond Angles ( ) for 1,2-
Dimethoxy-1,2-di(pyridin-2-yl)-1,2-ethanediol
length of the intramolecular hydrogen bond
is 2.679(2) A, shorter distance than a normal
distance for O H. . .N typical of hydrogen bonds
with (2.8 A) value. The Fig. 2 shows a perspective
˚
˚
Bond lengths (A)
–
–
O(1) C(6)
1.3919(14)
1.4148(14)
1.4223(17)
1.3346(18)
1.3415(16)
1.378(2)
1.375(2)
1.388(2)
1.3823(16)
1.5295(16)
1.567(2)
˚
–
O(2) C(6)
–
O(2) C(7)
of crystal package of 3.
–
N(1) C(1)
–
–
The angle between the atoms O(1) H(1A)
–
N(1) C(5)
N(1) is of 146.06◦. The structure shows a bond
–
C(1) C(2)
˚
–
C(6) C(6A) with a length of 1.567(5)A, a value
–
C(2) C(3)
–
C(3) C(4)
–
that is larger than the normal distance for C C
–
C(4) C(5)
with sp3 hybridization (1.542 0.005 A). The
˚
–
C(5) C(6)
˚
–
C(6) O(1) bond distance (1.3919 0.0014 A)
found in the present crystal is shorter than a typi-
cal single bond (1.43 A), which may be due to the
–
C(6) C(6)
Bond angles (◦)
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
C(6) O(2) C(7)
115.19(10)
118.19(11)
123.10(13)
118.73(14)
118.88(13)
118.95(13)
122.15(12)
115.87 (9)
121.97(10)
111.84 (9)
107.72 (9)
110.98 (9)
111.64(12)
103.31(10)
111.38(11)
˚
–
C(1) N(1) C(5)
–
hydrogen bond of the O H group. On the contrary,
–
N(1) C(1) C(2)
˚
–
C(3) C(2) C(1)
–
–
the C(6) O(2) bond distance (1.4148 0.0014 A)
–
C(2) C(3) C(4)
˚
and C(7) O(2) (1.4223 0.0017 A) are typical
–
C(5) C(4) C(3)
single bonds.
–
N(1) C(5) C(4)
–
The double bond values for aromatic C C
and C N of the pyridine ring are 1.394(5) and
1.339(5)A, respectively. The molecular confor-
mation geometry, within the accuracy of the re-
sults, shows the methoxy and hydroxyl groups in
anti position and are not planar to each other. Also,
it is interesting that although the hemiketal shows
–
N(1) C(5) C(6)
–
C(4) C(5) C(6)
–
–
O(1) C(6) O(2)
˚
–
O(1) C(6) C(5)
–
O(2) C(6) C(5)
–
O(1) C(6) C(6)
–
O(2) C(6) C(6)
–
C(5) C(6) C(6)

308
Percino, Chapela, Romero, Rodr´ıguez-Barbar´ın, and Melendez-Bustamante
◦
˚
Table 3. Hydrogen Bonds (A and ) for 1,2-Dimethoxy-1,2-di(pyridin-2-yl)-1,2-ethanediol
–
D H
–
D
H
A
Symmetry for A
H · · · A
D · · · A
D H · · · A
O1
H1A
N1 −x, −y, −z
0.884
1.888
–
2.679(2)
148.06
◦
˚
˚
Note. Hydrogen bonds with H · · · A < r (A) + 2.000 A and D H · · · A>110 . D: donor atom;
A: acceptor atom.
5. Weiss, M.; Appel, M. J. Am. Chem. Soc. 1948, 70, 3666.
6. Zhang, G.-S.; Shi, Q.-Z.; Chen, M.-F.; Cai, K. Synth. Commun.
1997, 27, 953.
7. Tymonko, S.A.; Nattier, B.A.; Mohan, R.S. Tetrahedron Lett.
1999, 7657, 7659.
8. Harries, C.; Lenart, G.H. Liebigs Ann. 1915, 410, 95.
9. Hensel, H. Angew. Chem. 1953, 65, 491.
good stability, we found that after few months,
it was converted to 2, and this was confirmed by
IR. The molecule is symmetrical and it could be
said that its stability is due to the hydrogen bonds,
˚
D · · · A = 2.679 A (Table 3).
10. Ashida, T.; Hirokawa, S.; Okaya, Y. Acta Cryst. 1965, 18,
122.
Supplementary material Crystallographic data (excluding struc-
ture factors) reported in this paper have been deposited with the
Cambridge Crystallographic Data Centre as supplementary publi-
cation no. CCDC 253718. Copies of available material can be ob-
tained, free of charge, on application to the CCDC, 12 Union Road,
Cambridge CB2 IEZ, UK (fax: + 44-(0)1223-336033 or e-mail:
deposit@ccdc.cam.ac.uk).
11. Buehler, C.A.; Harris, J.O. J. Am. Chem. Soc. 1950, 72, 5051.
12. Buehler, C.A.; Addleburg, J.W.; Glenn, D.M. J. Org. Chem.
1955, 20, 1350.
13. Buehler, C.A.; Edwards, S.P. J. Am. Chem. Soc. 1952, 20, 977.
14. Hirokawa, S.; Ashida, T., Acta Cryst. 1961, 14, 774. Ashida, T.;
Hirokawa, S. Acta Cryst. 1970, B26, 454.
15. Mu¨ller-Dethlefts, K.; Hobza, P. Chem. Rev. 2000, 100, 143.
16. Osmialowski, B.; Kolehmainen, E.; Nissinen, M.; Krygowski,
T.M.; Gawinecki, R. J. Org. Chem. 2002, 67, 3339.
17. The Aldrich Library of Infrared Spectra, Vol. 1, 3rd ed.; C.J.
Aldrich Chemical: Milwaukee, WI, 1981; p 850.
18. Sheldrick, G.M. SHELX97 Users Manual; University of
Go¨ttingen, Germany, 1997.
References
1. Wo¨hler, F.; Liebig, J. Ann. Pharm. 1832, 3, 249.
2. Lapworth, A. J. Chem. Soc. 1903, 83, 995.
3. Buck, J.S.; Jenkins, S.S. J. Am. Chem. Soc. 1929, 51, 2163.
4. Mckillop, A.; Swann, B.; Frod, M.E.; Taylor, E.C. J. Am. Chem.
Soc. 1973, 95, 3641.
19. Morrison, R.T.; Boyd, R.N. Organic Chemistry, 2nd ed., Allyn
and Bacon, Boston, 1967; p 642.
20. Moll, R.B.; Poziomek, E.J.; Mosher, W.A. J. Org. Chem. 1971,
36(8), 1056.