Synthesis and crystal structure of dimethyl-7-oxabicyclo[2.2.1]hept-5-ene exo,exo-2,3-dicarboxylate

Article abstract of DOI:10.1007/s10870-007-9206-9

Dimethyl-7-oxabicyclo[2.2.1]hept-5-ene exo,exo-2,3-dicarboxylate (1) was prepared by Fisher esterification of 7-oxabicyclo[2.2.1]-hept-5-ene exo-2,3-dicarboxylic anhydride (2) in methanol. The colorless plates obtained were characterized by FT-IR, ¹H- and ¹³C-NMR, TGA-DSC, and single crystal X-ray diffraction. The material crystallizes in space group P2₁/c, with a = 9.2375(14) A, b = 12.8757(18) A, c = 9.4608(15) A, β = 115.327(3)°, V = 1017.1(3) A³, and Z = 4. Chains of hydrogen-bonded molecules along the c-axis interact in the b direction to form layers parallel to the bc plane.

Full text of DOI:10.1007/s10870-007-9206-9

J Chem Crystallogr (2007) 37:543–548
DOI 10.1007/s10870-007-9206-9
ORIGINAL PAPER
Synthesis and Crystal Structure of Dimethyl-
7-oxabicyclo[2.2.1]hept-5-ene exo,exo-2,3-dicarboxylate
´
´
Aira Miro Vera Æ William Velasquez Æ Alexander Bricen˜o Æ
´
´
Alı Bahsas Bahsas Æ Belkis Ramırez Valero Æ
Graciela Diaz de Delgado
Received: 6 March 2007 / Accepted: 11 April 2007 / Published online: 23 June 2007
ꢀ Springer Science+Business Media, LLC 2007
Abstract Dimethyl-7-oxabicyclo[2.2.1]hept-5-ene exo,
exo-2,3-dicarboxylate (1) was prepared by Fisher esteri-
fication of 7-oxabicyclo[2.2.1]-hept-5-ene exo-2,3-dicar-
boxylic anhydride (2) in methanol. The colorless plates
obtained were characterized by FT-IR, 1H- and 13C-
NMR, TGA-DSC, and single crystal X-ray diffraction.
The material crystallizes in space group P21/c, with
to carry out projects, which involve common organic
chemistry reactions. Over the years, we have encountered
interesting results such as new polymorphs of previously
reported compounds [1].
One of these projects involved the synthesis of a 7-
oxanorbornene derivative dimethyl-7-oxabicyclo[2.2.1]
hept-5-ene exo,exo-2,3-dicarboxylate (exo-diester) (1) fol-
lowing an easy two-step procedure described in the liter-
ature [2]. Compound 1 was thus prepared by Fisher
esterification of the adduct 7-oxabicyclo[2.2.1]-hept-5-ene
exo-2,3-dicarboxylic anhydride (exo-anhydride) (2) which
was prepared as described before [3].
˚
a = 9.2375(14) A, b = 12.8757(18) A, c = 9.4608(15) A,
˚
˚
3
˚
b = 115.327(3)ꢁ, V = 1017.1(3) A , and Z = 4. Chains of
hydrogen-bonded molecules along the c-axis interact in
the b direction to form layers parallel to the bc plane.
Keywords Oxanorbornene derivatives Á 2D-NMR Á
Crystal structure Á Thermal analysis
It is interesting to note that the endo-diester is also
produced in the synthesis following the procedure of
France et al., as demonstrated by 1H-NMR. However, only
the exo-diester crystallized from the reaction mixture. A
Introduction
1
complete study by H- and 13C-NMR is being carried out
and will be published elsewhere.
As part of the undergraduate chemistry curriculum, the
students in the organic chemistry laboratories are required
These compounds, along with their endo counter-
parts, may be useful as starting materials for the syn-
thesis of diastereomerically pure compounds [4, 5], and
for the regioselective control of reactions of asym-
metrical dienes and dienophiles [6]. They may also
serve as monomers in ring-opening metathesis poly-
merizations (ROMP) [5], among other synthetic appli-
cations. In fact, the trans (exo,endo) isomer of 1
(Compound 3) was obtained as part of the synthesis of
Electronic supplementary material The online version of this
article (doi:10.1007/s10870-007-9206-9) contains supplementary
material, which is available to authorized users.
´
´
´
A. Miro Vera Á W. Velasquez Á A. Bahsas Bahsas Á
B. Ramırez Valero (&) Á G. Diaz de Delgado
´
Departamento de Quımica, Facultad de Ciencias, Laboratorio de
Cristalografıa, Universidad de Los Andes, Apdo. 40 La
´
Hechicera, Merida 5251, Venezuela
e-mail: belkis@ula.ve
1,4-anhydro-b-D-galactopyranose,
a
carbasugar ana-
logue which has been proposed as an intermediate in
the reaction catalyzed by uridine diphosphate-a-D-ga-
lactopyranose mutase (UDP-Galp mutase) [7]. This
enzyme is essential for the survival of Mycobacterium
tuberculosis and therefore is a possible target for anti-
tuberculosis agents.
G. Diaz de Delgado (&)
e-mail: diaz@ula.ve
A. Bricen˜o
Centro de Quımica, Instituto Venezolano de Investigaciones
´
Cientıficas, Caracas, Venezuela
´
123

544
J Chem Crystallogr (2007) 37:543–548
(C=O) 1748 and 1732; k (C=C tension) 1634; k (C–O ester
vibration) 1254.
The 1H-NMR spectra were obtained on a Bruker Avance
DRX 400. 1H-NMR:(400 MHz; CDCl3; dH, ppm); (2H
(Csp2), s) 6.44; (2H (C bridge head), s) 5.25; (6H (2
methoxy groups), s) 3.68; (2H (H2 and H7 ), s) 2.81.
The 13C-NMR spectra were obtained on a Bruker Avance
DRX 400. 13C-NMR: (100.13 MHz; CDCl3; dC, ppm); (2C
(C=O), s) 171.8; (C (Csp2), d) 136.5; (C (C bridge head), d)
80.3; (C (C methoxilic), q) 52.1; (C (a), d) 46.9.
Thermogravimetric analysis (TGA and DTG) and dif-
ferential scanning calorimetry measurements (DSC) were
performed in a Perkin-Elmer TGA7 thermal analyzer and a
Perkin-Elmer DSC7 cell, under a dynamic dry nitrogen
atmosphere at a heating rate of 10 ꢁC min–1. TGA (tem-
perature range 25–500 ꢁC): weight loss to only step
129.991–167.294 ꢁC; DSC (temperature range 25–
125 ꢁC): 119.2 ꢁC, endo.
Single Crystal X-ray Data Collection and Structure
Determination
Single crystal X-ray intensity data were collected on a Rigaku
AFC7S diffractometer operating at 50 kV and 30 mA, with a
Mercury CCD area detector, using MoKa radiation
˚
(k = 0.71069 A), and a graphite monochromator. A total of
235 images were collected in five sets of data with 2h =
–10.0858ꢁ, x = 0ꢁ, and //v values of 0ꢁ/0ꢁ, 0ꢁ/90ꢁ, 90ꢁ/90ꢁ,
180ꢁ/90ꢁ, and 270ꢁ/90ꢁ. The image width was 2.00ꢁ in x and
the exposure time was 40 s. The crystal to detector distance
was optimized at 41.168 mm. Unit cell parameters were
determined from 1490 reflections in the range 2.90ꢁ £ h
£ 28.10ꢁ and were refined by least-squares [8]. Absorption,
form, scale factor, among other corrections, were done by a
multi-scan technique using a form function based on spheri-
cal harmonics [8]. The structure was solved by Direct
methods with SHELXS [9]. Full matrix least-squares struc-
ture refinement was carried out with SHELXL [10]. Positions
and anisotropic thermal parameters were refined for all
non-hydrogen atoms. Hydrogen atoms were placed in cal-
culated positions and were refined using a riding model with
their Uiso equal to 1.2 times (1.3 for the methyl hydrogens)
the Ueq of the carbon atom to which they are attached.
Experimental
Synthesis and Preliminary Characterization
The compound dimethyl-7-oxabicyclo[2.2.1]hept-5-ene
exo,exo-2,3-dicarboxylate (1) was prepared in two steps.
The first step involves the Diels–Alder reaction between
furan and maleic anhydride at room temperature to yield
7-oxabicyclo[2.2.1]hept-5-ene exo-2,3-dicarboxylic anhy-
dride (2). The second step involves converting the anhy-
dride to the diester in refluxing methanol by drop wise
addition of concentrated HCl. The product was then
recrystallized in hot methanol producing colorless plates
upon cooling.
Results and Discussion
Characterization by Thermal and Spectroscopic
Techniques
The IR spectra were recorded from KBr discs, using a
PE-1600 FTIR Spectrometer with IRDM software. IR (cm–1):
k(C–H sp2 symmetric) 3098; k (C–H sp2 asymmetric)
3032; k (C–H bridge head) 2290; k (C–H sp ring) 2948; k
Compound (1) was characterized by FT-IR, 1H-NMR, 13C-
NMR, and thermogravimetric analysis (TGA-DSC). The
FT-IR spectrum (Fig. 1) showed the characteristic
123

J Chem Crystallogr (2007) 37:543–548
545
100,0
Fig. 1 FT-IR spectra (KBr
pellets) of dimethyl-7-
oxabicyclo[2.2.1]hept-5-ene
exo,exo-2,3-dicarboxylate (1)
95
90
85
80
75
70
65
60
55
50
45
40
35
30
25
20
15
10
5
%T
0,0
4400,0 4000
3000
2000
1500
1000
450,0
cm-1
Fig. 2 1H-NMR spectra of
dimethyl-7-
oxabicyclo[2.2.1]hept-5-ene
exo,exo-2,3-dicarboxylate (1)
1
absorptions for this type of material. The H-NMR exper-
iment (Fig. 2) showed only four signals, indicating that the
molecule is symmetrical in solution. There should be a
plane bisecting the molecule through O1 and the C4–C5
and C2–C7 bonds. However, from this experiment it is not
possible to determine the endo or exo conformation of the
H2 and H7 protons, attached to C2 and C7, respectively. A
NOESY (Nuclear Overhauser Effect Spectroscopy)
would show the spatial relationships between the different
protons in the molecule. The main evidence would be the
interaction between the protons a with respect to the car-
bonyl carbon and the olefinic protons. The NOESY
experiment, indeed, confirmed the exo configuration since
the signal at 2.81 ppm, which corresponds to the H2 and
H7 protons, interacts with the signal at 6.44 ppm which
corresponds to the H4 and H5 protons, attached to the
olefinic carbons C4 and C5.
From the structure of the exo-anhydride adduct (2) [3],
the average distances H2 to H4 and H5 to H7 is approxi-
˚
mately 2.97 A. These distances are analogous to the H2 to
123

546
J Chem Crystallogr (2007) 37:543–548
H4 and H5 to H7 distances in the exo-diester (1), which are
˚
in average 2.88 A. Since structural data on the related endo
Table 1 Distances between hydrogens involved in the NOESY
interactions
compounds is not available, the corresponding distances
can be calculated based on the expected geometry of the
compounds, using programs such CS ChemOffice Version
9.0 [CambridgeSoft, Cambridge, MA, USA]. The calcula-
tions are summarized in Table 1.
exo-anhydride
exo-diester
˚
exo (A)
˚
endo (A)
˚
exo (A)
˚
endo (A)
Theoretical
3.15
2.97
4.20
–
3.00
2.88
4.17
–
Experimental
From these calculations, the distances between the protons
˚
under consideration in the endo adduct differ by 1.17 A
˚
(4.17–3.00 A) with respect to the exo diastereomer. There-
The results of the TGA/DSC analysis of compound (1)
is shown in Fig. 3. As evident from Fig. 3a, the material
begins to suffer decomposition at 130 ꢁC with peak tem-
perature of 151.34 ꢁC. The DSC, Fig. 3b, shows an endo-
therm with peak temperature of 119.20 ꢁC, corresponding
to a DH of 104.48 J/g. This transition corresponds to
melting of the compound since it is not associated with a
weight loss.
˚
˚
fore, an experimental value of 4.05 A (2.88 + 1.17 A) would
be expected for the endo-diester. This is in agreement with the
NMR-NOESY experiment, where a distance of approxi-
˚
mately 3.00 A between the protons results in a medium–
˚
strong interaction whereas distances greater than 4.00 A
would produce weak interactions, which would be outside
the detection limit of the experiment.
Fig. 3 (a) TGA and (b) DSC
curves for dimethyl-7-
oxabicyclo[2.2.1]hept-5-ene
exo,exo-2,3-dicarboxylate (1)
123

J Chem Crystallogr (2007) 37:543–548
Analysis of the Crystal Structure
547
˚
Table 3 Selected bond distances (A) and angles (ꢁ) for Compound
(1)
Crystal data, experimental parameters and summary of
refinement parameters are presented in Table 2. Table 3
contains relevant bond lengths and angles. Figure 4, ob-
tained with Diamond [11], shows the molecular confor-
mation with the atom numbering scheme. In the solid state
the molecule is not completely symmetrical. The orienta-
tion of the carbonyl groups (C1–O2 and C8–O5) with re-
spect to the six-member ring is different. The torsion angle
O2–C1–C2–C3 is only –0.7(2)ꢁ while the C6–C7–C8–O5
torsion angle is 46.7(2)ꢁ. This may be due to the difference
in hydrogen bonding and contact patterns for O2 and O5.
O5 participates in only one long contact with the H6 atom
of a molecule with symmetry operation 1–x, –y, 1–z
O1–C3
1.470(2)
C1–C2
1.481(3)
1.518(3)
1.573(2)
1.499(3)
1.315(3)
1.505(3)
1.544(3)
1.491(3)
102.90(15)
102.39(13)
102.54(14)
100.97(13)
114.71(14)
109.18(14)
124.17(19)
109.10(14)
126.72(17)
111.00
O1–C6
1.432(2)
C2–C3
O2–C1
1.209(2)
C2–C7
O3–C1
1.322(2)
C3–C4
O3–C10
1.422(3)
C4–C5
O4–C8
1.335(2)
C5–C6
O4–C9
1.424(3)
C6–C7
O5–C8
1.220(2)
C7–C8
C3–O1–C6
C1–O3–C10
C8–O4–C9
O2–C1–O3
O2–C1–C2
O3–C1–C2
C1–C2–C3
C1–C2–C7
C3–C2–C7
O1–C3–C2
O1–C3–C4
C2–C3–C4
C3–C4–C5
C4–C5–C6
94.63(12)
113.29(18)
113.98(16)
123.96(19)
127.17(18)
108.87(14)
109.96(14)
114.17(15)
100.07(13)
102.34(14)
103.30(14)
104.78(14)
104.99(17)
106.61(17)
O1–C6–C5
O1–C6–C7
C5–C6–C7
C2–C7–C6
C2–C7–C8
C6–C7–C8
O4–C8-O5
O4–C8–C7
O5–C8–C7
C7–C2–H2
C5–C4–H4
C4–C5–H5
C2–C7–H7
˚
˚
[O5ÁÁÁH6–C6, O5ÁÁÁH6 2.637 A, O5ÁÁÁC6 3.603(2) A, angle
169.80ꢁ]. On the other hand, O2 participates in a chain
Table 2 Crystallographic data for Compound 1
1
128.00
CCDC deposit no.
Color/shape
CCDC 633223
Colorless/plates
127.00
111.00
Formula
C10H12O5
Formula weight
Crystal size (mm)
Crystal system
Space group
212.20
0.16 · 0.24 · 0.34
Monoclinic
P21/c
hydrogen bond with H2–C2 from a molecule at x, ½–y,
˚
˚
½+z [O2ÁÁÁH2 2.501 A, O2ÁÁÁC2 3.480(2) A, angle
178.00ꢁ]. This hydrogen bond can be described with the
first order graph set symbol N1 = C(4). The chains run
parallel to the c-axis with the molecules alternating on both
sides of the chains producing a sort of square-wave pattern
(Fig. 5). They interact along the b-axis with another chain
related by the c-glide plane to produce sheets almost par-
Unit cell dimensions
˚
a (A)
9.238(1)
12.876(2)
9.461(2)
115.327(3)
1017.1(3)
4
˚
b (A)
˚
c (A)
b (ꢁ)
3
˚
V (A )
Z
Dc (g cm–1
)
1.386
F(000)
448
T(K)
l (MoKa) (mm–1
290
)
0.112
h range (ꢁ)
Limiting indices
2.9; 28.1
–11 £ h £ 11,
–14 £ k £ 14,
–9 £ l £ 11
Absorption correction
Multi-scan
Reflections collected/unique
11518/2017
Independent reflections [I ( 2.0r(I)] 1699
Refinement method
Data/restraints/parameters
Final R indices [I ( 2.0r(I)]
R indices (all data)
GooF
Full-matrix least-squares on F2
2017/0/136
R1, 0.0546; wR2, 0.1407
R1, 0.0668; wR2, 0.1487
1.12
Fig. 4 Molecular structure of dimethyl-7-oxabicyclo[2.2.1]hept-5-
ene exo,exo-2,3-dicarboxylate (1) (Ellipsoids drawn at the 50%
probability level)
–3
)
˚
Largest diff. peak and hole (e A
0.22 and –0.22
123

548
J Chem Crystallogr (2007) 37:543–548
symbol S(5). Additionally, the bridge oxygen (O1) partic-
ipates in a long contact with the bridge-head proton H6 of a
molecule with symmetry operation –x, 1–y, –z [O1ÁÁÁH6–
˚
˚
C6, O1ÁÁÁH6 2.60 A, O1ÁÁÁC6 3.3709(17) A, angle 134ꢁ]. It
is interesting to note that the endo methyl ester group and
the endo proton (H7) do not participate in intramolecular or
intermolecular contacts of importance.
Acknowledgements The authors would like to thank CDCHT-ULA
and the support of FONACIT through grant LAB-97000821. We also
thank Dr. R. Atencio of IVIC for helpful discussions.
References
´ ´ ´ ´
1. Dıaz de Delgado G, Ramırez B, Velasquez W, Rodrıguez P
(2002) Acta Cryst E58:o501
2. France MB, Alty LT, Earl MT (1999) J Chem Educ 76:659
´
3. Ramırez BM, Dıaz de Delgado G, Velasquez WO, Perdomo G
(1998) Zeitschrift fu¨r Kristallographie–New Cryst Struct 213:1
´
´
´
4. Andres C, Nieto J, Pedrosa R, Vicente M (1998) J Org Chem
63:8570
Fig. 5 View of the structure of dimethyl-7-oxabicyclo[2.2.1]hept-5-
ene exo,exo-2,3-dicarboxylate (1) down the a axis
´
´
5. Odon Arjona AG, Csaky M, Murcia C, Plumet J (1999) J Org
Chem 64:7338
´
´
6. Odon Arjona AG, Csaky M, Murcia C, Plumet J (1999) J Org
Chem 64:9739
allel to the bc plane. These sheets stack along the a-axis
and interact only through van der Waals contacts.
7. Sadeghi-Khomami A, Blake AJ, Wilson C, Thomas NR (2005)
Org Lett 7:4891
8. CrystalClear, Rigaku/MSC (2005) MSC, 9009 New Trails Drive,
The Woodlands, TX, USA 77381-5209, Rigaku, 3-9-12 Akishi-
ma, Tokyo 196-8666, Japan
In contrast, the structure of the exo,endo isomer (3) [7]
has a different hydrogen bonding pattern. The calculations
performed using the data retrieved from the Cambridge
Structural Database, Version 5.28 [12] for 3 (REFCODE
VEBTOM) indicated that there is an intramolecular
hydrogen bond between the carbonyl oxygen of the exo
substituent (O2) and the b hydrogen atom (H3). This
9. Sheldrick GM (1997) SHELXS97. Program for crystal structure
¨
solution. University of Gottingen, Germany
10. Sheldrick GM (1997) SHELXL97. Program for crystal structure
¨
refinement. University of Gottingen, Germany
11. Brandenburg K (1998) Diamond, Version 2.1e. Crystal Impact,
Gbr, Germany
12. Allen FH (2002) Acta Cryst B58:380
˚
hydrogen bond [O2ÁÁÁH3–C3, O2ÁÁÁH3 2.43 A, O2ÁÁÁC3
˚
2.9147(16) A, angle 109ꢁ] is described by the graph set
123