Stereoselective Stobbe condensation of ethyl methyl diphenylmethylenesuccinate with aromatic aldehydes

Article abstract of DOI:10.1021/ol026668v

(matrix presented) The E configuration of benzylidene(diphenylmethylene)succinic anhydride (R = H), obtained by the Stobbe condensation of ethyl methyl diphenylmethylenesuccinate with benzaldehyde, was determined by single-crystal X-ray diffraction. Nonco

Full text of DOI:10.1021/ol026668v

ORGANIC
LETTERS
2002
Vol. 4, No. 20
3521-3524
Stereoselective Stobbe Condensation of
Ethyl Methyl
Diphenylmethylenesuccinate with
Aromatic Aldehydes
,†
Jin Liu* and Neil R. Brooks‡
Department of Chemistry, Murray State UniVersity, Murray, Kentucky 42071,
and X-ray Crystallographic Laboratory, Department of Chemistry,
UniVersity of Minnesota, Minneapolis, Minnesota 55455
jin.liu@murraystate.edu
Received August 5, 2002
ABSTRACT
The E configuration of benzylidene(diphenylmethylene)succinic anhydride (R ) H), obtained by the Stobbe condensation of ethyl methyl
diphenylmethylenesuccinate with benzaldehyde, was determined by single-crystal X-ray diffraction. Noncovalent π stacking interaction between
two stacked phenyl groups is suggested as a stabilizing energy for the highly crowded molecule. The nature and the position of substituents
(R) on the aromatic rings of substituted benzaldehydes showed no effect on the E stereoselectivity in the condensation.
In the course of our studies of noncovalent π stacking
interaction between stacked phenyl groups,1 we examined
benzylidene(diphenylmethylene)succinic anhydride (1), a
derivative of succinic anhydride. Some of these anhydride
derivatives first discovered by Stobbe were known as
thermally irreversible photochromic compounds (fulgides).2
During the past few years, many research groups reported
potential applications of new generations of fulgides.3-5
* To whom correspondence should be addressed. Fax: 270-762-6474.
† Murray State University.
‡ University of Minnesota.
(1) Liu, J.; Liu, R. S. H.; Simmons, C. J. Tetrahedron Lett. 1997, 38,
3999-4002.
Compound 1 prepared by the Stobbe condensation of
diethyl diphenylmethylenesuccinate (2) with benzaldehyde
(2) Johnson, W. S.; Daub, G. H. In Organic Reactions, Vol. 6; John
Wiley and Sons: New York, 1951; pp 2-73.
(3) Yokoyama, Y. Chem. ReV. 2000, 100, 1717-1739.
(4) Heller, H.; Ottaway, M. J. J. Chem. Soc., Chem. Commun. 1995,
479-480.
(5) Janicki, S. Z.; Schuster, G. B. J. Am. Chem. Soc. 1995, 117, 8524-
8527.
10.1021/ol026668v CCC: $22.00 © 2002 American Chemical Society
Published on Web 08/30/2002

Scheme 1
was known (Scheme 1).2 A literature survey has shown that
room temperature, the product was recrystallized from
methanol to afford an orange crystal, which was analyzed
by single-crystal X-ray diffraction. The E configuration of
the product was determined (Figure 1).8 The crystal structure
the configuration of compound 1 was believed to be Z for
many years, considering severe steric interaction existing in
the E isomer. In 1972, Hart and Heller reported NMR data
and assigned the E configuration of compound 1, on the basis
of deshielding of the olefinic proton and shielding of the
aromatic protons in the E isomer.6 However, the structure
of compound 1 was not fully characterized. Moreover, it was
uncertain whether the E stereoselectivity of this type of
Stobbe condensation depended on the nature and the position
of substituents on the aromatic ring of benzaldehyde.
To fully understand the stereoselectivity in the Stobbe
condensation of diphenylmethylenesuccinate with aromatic
aldehydes, we first decided to determine the configuration
of compound 1 by way of single-crystal X-ray diffraction.
Next, we planned to carry out similar condensations of
diphenylmethylenesuccinate with substituted benzaldehydes
containing different kinds of substituents at different positions
on the aromatic rings, to investigate substituent effects on
the stereoselectivity. Herein, we describe the results of our
recent studies.
We chose ethyl methyl diphenylmethylenesuccinate (5)2,7
instead of diethyl diphenylmethylenesuccinate (2) to prepare
compound 1 and used sodium hydride as a base (Scheme
1). The diacid (4) was afforded directly from the Stobbe
condensation, followed by an acidic workup. The second
approach eliminated the base hydrolysis of the half ester (3)
that was usually carried out at a high temperature, thus
avoiding thermal isomerization during the process. Com-
pound 1, an orange powder, was afforded after dehydration
of the diacid (4) using acetyl chloride.
Figure 1. X-ray structure of compound 1 at 173 K (displacement
ellipsoids shown at the 50% probability level).
reveals that the diene unit is highly twisted with a torsional
angle (∼25°).9 The two phenyl groups connected to the same
carbon (C7 in Figure 1) are not coplanar because of a large
torsion angle (∼42°). The phenyl group, which is closer to
the carbonyl group (C5 in Figure 1), is almost coplanar with
the conjugated 1,3-butadiene unit. The other phenyl group
nearly stacks onto the remaining phenyl group that gives the
E configuration of the CdC bond. Also, the crystal-packing
diagram (Figure 2) shows that the stacked phenyl groups
tend to face each other in the crystal form.
Under the normal lab lights, the orange product (1) was
stable in its solid form and in common organic solvents. At
(6) Hart, R. J.; Heller, H. G. J. Chem. Soc., Perkin Trans. 1 1972, 1321-
1324.
(7) Compound 5 was prepared by Stobbe condensation of benzophenone
with diethyl succinate, followed by esterification using methanol and a
catalytic amount of concentrated H2SO4.
3522
Org. Lett., Vol. 4, No. 20, 2002

Figure 2. Crystal-packing diagram of compound 1.
Although the formation of the Z configuration allowed
compound 1 to maintain maximum conjugation across the
1,3-butadiene unit and to gain the stabilizing resonance
energy, the experimental result indicated that the molecule
preferred to form the highly crowded E configuration.
Noncovalent π stacking interactions play an important role
in many areas of chemistry.10 In organic chemistry, the effects
of noncovalent π stacking interactions on photodimerization,
photopolymerization,11 and asymmetric synthesis12 have been
observed. Noncovalent π stacking interactions have been
known to assemble various types of biological supramol-
ecules, for example, DNA and RNA, and to provide the
stabilizing energy for them.13 Based on the stacking orienta-
tion and the distance of two phenyl groups (∼3.26 Å) in
compound 1, a noncovalent π stacking interaction between
the stacked phenyl groups is suggested as an important
stabilizing energy for the crowded structure. The observed
noncovalent interaction is an intramolecular force that occurs
between two phenyl groups.
A closer examination of 1H NMR of compound 1 revealed
that the signals of 10 aromatic protons were more upfield-
shifted than those of the five remaining protons. Because
the formation of a π-π complex caused electron shielding,14
the upfield chemical shifts were assigned to the aromatic
protons on the stacked phenyl rings. This method can also
be applied to determine the configurations of some related
anhydrides.
To examine the effects of different substituents on the
stereoselectivity of the Stobbe condensation, diester 5 was
condensed under the same reaction conditions with p-
methoxybenzaldehyde, p-methylbenzaldehyde, p-chloro-
benzaldehyde, and p-nitrobenzaldehyde, respectively, to
afford four dicarboxylic acids.15 The anhydride products
(8) Data for compound 1: C24H16O3, monoclinic space group: P21/c;
cell dimensions: a ) 8.1438(11) Å, b ) 11.5962(16) Å, c ) 18.591(3) Å,
â ) 95.066(2)°, V ) 1748.8(4) Å3, Z ) 4, Dcalc ) 1.338 Mg/m3, F(000) )
736, µ ) 0.088 mm-1. X-ray diffraction data were collected on an orange
block crystal (0.40 × 0.20 × 0.20 mm3) at 173(2) K using a Bruker SMART
area diffractometer, λ (Mo Ka) ) 0.71073 Å. Data integration was carried
out with SAINT V6.1 (Bruker Analytical X-ray Systems, Madison, WI),
corrections for absorption and decay were applied using SADABS. The
structure was solved, by direct methods, and refined using the SHELXTL-
Plus V5.10. All non-hydrogen atoms were refined with anisotropic thermal
parameters. Hydrogen atoms were placed with ideal positions and refined
with isotropic thermal parameters related to the parent carbon atom. R1 )
0.0367 for 2732 data [I>2_(I)] and ) 0.0418 for all 3093 data.
(9) Selected bond lengths: C(3)-C(4) ) 1.4671(17); C(3)-C(6) )
1.3519(18); C(4)-C(7) ) 1.3751(18); C(6)-C(8) ) 1.4586(18); C(7)-
C(14) ) 1.4803(17); C(7)-C(20) ) 1.4808(17) Å. Selected bond angles:
C(6)-C(3)-C(4) ) 137.02(12)°; C(7)-C(4)-C(3) ) 132.07(11)°; C(3)-
C(6)-C(8) ) 131.31(12)°; C(4)-C(7)-C(14) ) 122.78(11)°; C(4)-C(7)-
C(20) ) 121.37(11)°. Selected torsion angles: C(4)-C(3)-C(6)-C(8) )
-4.6(2)°; C(3)-C(4)-C(7)-C(14) ) -12.8(2)°; C(3)-C(4)-C(7)-C(20)
) 168.14(12)°; C(6)-C(3)-C(4)-C(7) ) -25.4(2)°.
(14) Viel, S.; Mannina, L.; Segre, A. Tetrahedron Lett. 2002, 43, 2515-
2519.
(15) General Procedure. With nitrogen flowing, aromatic aldehyde (1.4
mmol), the diester 5 (1.23 mmol), benzene (3.0 mL), and 60% sodium
hydride in mineral oil (1.6 mmol) were added into a flame-dried flask (150
mL). The flow of nitrogen was stopped, and a drop of methanol was added
carefully into the stirred mixture at room temperature to initiate the
condensation. After the initial reaction had subsided, the reaction mixture
was stirred at room temperature for 30 min. The reaction was quenched by
slow addition of water (3.0 mL) and was acidified by addition of
concentrated HCl. The resulting mixture was extracted with ethyl ether three
times. The combined ethereal solutions were extracted with ammonia (1.0
N, 15 mL). The alkaline solution, cooled in an ice-water bath, was acidified
using concentrated HCl. The precipitated oil was collected by ether
extraction. The ethereal solution was washed with brine and dried over
MgSO4. Removal of ether in vacuo afforded the diacid as an oil. In dim
red light, the diacid was dissolved in acetyl chloride (1.5-2.0 mL) and left
at room temperature for 30 min. The extra acetyl chloride was removed in
vacuo to give a residue, which was dissolved into a small amount of ethyl
acetate (1.0-2.0 mL). The anhydride product was precipitated by addition
of hexane.
(10) Hunter, C. A.; Lawson, K. R.; Perkins, J.; Urch, C. J. J. Chem.
Soc., Perkin Trans. 2 2001, 651-669.
(11) Coates, G. W.; Dunn, A. R.; Henling, L. M.; Ziller, J. W.;
Lobkovsky, E. B.; Grubbs, R. H. J. Am. Chem. Soc. 1998, 120, 3641-
3649.
(12) Jones, G. B.; Chapmam, B. J. Synthesis 1995, 475-497.
(13) Guckian, K. M.; Schweitzer, B. A.; Ren, R. X.-F.; Sheils, C. J.;
Tahmassebi, D. C.; Kool, E. T. J. Am. Chem. Soc. 2000, 122, 2213-2222.
Org. Lett., Vol. 4, No. 20, 2002
3523

1
Table 1. Yields, UV-Vis Absorption Maxima (nm) in Methanol, and Partial H NMR Data (ppm, CDCl3, 200 MHz) of the Products
a
aromatic aldehyde
yield (%)
λmax
δ1
o-Hc
m-Hc
o-Hd
m-Hd
p-Hd
benzaldehyde
p-methoxybenzaldehyde
p-methylbenzaldehyde
p-chlorobenzaldehyde
p-nitrobenzaldehyde
1 (70)
6 (80)
7 (53)
8 (59)
9 (53)
10 (50)
11 (58)
388, 297
412, 316
394, 304
391, 299
397, 304
384, 285
428, 324
7.63b
7.62
7.61
7.55
7.57
7.54
7.84
6.90
6.86
6.91
6.91
6.93
6.94
6.70
6.98
6.94
6.91
6.91
6.93
6.94
6.80
7.12
7.06
6.99
7.06
7.00
7.04
6.98
6.91
6.85
6.96
7.11
7.23
6.45
6.74
6.86
7.80
3,5-bis(trifluoromethyl)-benzaldehyde
2,4,6-trimethoxybenzaldehyde
5.60
a Chemical shifts of the olefinic protons. b The chemical shift of the olefinic proton of the Z isomer is 6.85 ppm (ref 6). c Chemical shifts of the ortho/
meta protons on the stacked and substituted phenyl rings. d Chemical shifts of the ortho/meta/para protons on the stacked and unsubstituted phenyl rings.
(6-9) were precipitated as orange solids immediately after
dehydration.
The E configuration of these orange solids (6-9) was
confirmed by their 1H NMR and 13C NMR spectra, MS, and
and 2,4,6-trimethoxyphenyl groups shifted upfield. The
UV-vis data and by comparing to those of compound 1
(Table 1). The upfield chemical shifts of the protons on the
stacked and unsubstituted aromatic rings, as well as the
downfield shifts of the olefinic protons, were observed. No
other isomers were found from the above reactions.
Moreover, 3,5-bis(trifluoromethyl)benzaldehyde and 2,4,6-
trimethoxybenzaldehyde were reacted with the ester (5),
respectively, to afford compound 10 as an orange solid and
compound 11 as a red solid. The E configuration of these
two products was also confirmed by the spectral data (Table
1).
singlet at 5.60 ppm assigned for the m,m′-Hs on the 2,4,6-
trimethoxyphenyl group indicated two equivalent protons,
which was caused by fast rotation of the two stacking phenyl
rings in solution at room temperature.1 The preparation of
six anhydrides (6-11) indicated that the number and the
nature (electron-withdrawing or electron-donating) of sub-
stituents on the aromatic rings of substituted benzaldehydes
have no effect on the E seteroselectivity of this type of the
Stobbe condensation.16
In summary, we have determined the E configuration of
the Stobbe condensation of compound 5 with the substituted
benzaldehydes. The effort to study noncovalent π stacking
interaction possibly existing in these anhydrides is currently
ongoing in the author’s lab.
Acknowledgment. This work was supported by grants
from Kentucky NSF EPSCoR and Howard Hughes Medical
Institution.
Supporting Information Available: Crystallographic
data for compound 1 in CIF format. This material is available
free of charge via the Internet at http://pubs.acs.org.
OL026668V
Figure 3. 1H NMR spectrum (200 MHz, CDCl3) of compound
11.
(16) The conclusion was also supported by our recent preparation of
(E,E)-bis(2,4,6-trimethoxybenzylidene)succinic anhydride. Spectral data: 1H
NMR (200 MHz, CDCl3) δ 8.03 (s, 2H), 5.60 (s, 4H), 3.71 (s, 6H), 3.54
(s, 12H); 13C NMR (50.1 MHz, CDCl3) δ 163.96, 158.36, 131.45, 121.53,
111.75, 107.80, 88.37, 55.16, 54.92; UV-vis λmax ) 560, 408 nm, in
acetone; MS (M+1)+, 457.
The 1H NMR spectrum (Figure 3) of compound 11 showed
the signals of the aromatic protons of the stacked phenyl
3524
Org. Lett., Vol. 4, No. 20, 2002