Derivative of α,β-dicyanostilbene: Convenient precursor for the synthesis of diphenylmaleimide compounds, E-Z isomerization, crystal structure, and solid-state fluorescence

Article abstract of DOI:10.1021/jo049512c

A convenient and efficient procedure was developed for preparing 3,4-diaryl-substituted maleimides through the improved synthesized diaryl-substituted fumaronitrile. The synthesis of diphenyl-substituted fumaronitrile derivatives from phenylacetonitrile compounds was analyzed and improved. We found the stoichiometry of the sodium methoxide and the concentration of the starting material, phenylacetonitrile derivatives, were crucial for the high yield and easy purification of the products. Particularly, bis(4-bromophenyl)fumaronitrile, bis(3-trifluoromethylphenyl)fumaronitrile, and bis(4-methoxyphenyl)fumaronitrile were isolated in good yields of 70-90% by simple suction filtration. In addition, ¹H NMR provided compelling evidence that the E-Z isomerization was involved in the formation reaction of the maleimide compounds from either fumaronitrile or maleonitrile derivatives. Single-crystal X-ray structures of these three fumaronitrile derivatives, the first three of the kind, were obtained, revealing the nonplanar molecular structure. We ascribe the strong solid-state fluorescence of these diphenylfumaronitrile derivatives to the nonplanar structure that inhibits the close packing of the molecule aggregation and thus the fluorescence quenching.

Full text of DOI:10.1021/jo049512c

Der iva tive of r,â-Dicya n ostilben e: Con ven ien t P r ecu r sor for th e
Syn th esis of Dip h en ylm a leim id e Com p ou n d s, E-Z Isom er iza tion ,
Cr ysta l Str u ctu r e, a n d Solid -Sta te F lu or escen ce
Hsiu-Chih Yeh,† Wei-Ching Wu,† Yuh-Sheng Wen,† De-Chang Dai,† J uen-Kai Wang,*,‡,§ and
Chin-Ti Chen*,†
Institute of Chemistry, Academia Sinica, Taipei, Taiwan 11529, Center for Condensed Matter Sciences,
National Taiwan University, Taipei, Taiwan 106, and Institute of Atomic and Molecular Sciences,
Academia Sinica, Taipei, Taiwan 106
cchen@chem.sinica.edu.tw; kwang@po.iams.sinica.edu.tw
Received March 25, 2004
A convenient and efficient procedure was developed for preparing 3,4-diaryl-substituted maleimides
through the improved synthesized diaryl-substituted fumaronitrile. The synthesis of diphenyl-
substituted fumaronitrile derivatives from phenylacetonitrile compounds was analyzed and
improved. We found the stoichiometry of the sodium methoxide and the concentration of the starting
material, phenylacetonitrile derivatives, were crucial for the high yield and easy purification of
the products. Particularly, bis(4-bromophenyl)fumaronitrile, bis(3-trifluoromethylphenyl)fuma-
ronitrile, and bis(4-methoxyphenyl)fumaronitrile were isolated in good yields of 70-90% by simple
1
suction filtration. In addition, H NMR provided compelling evidence that the E-Z isomerization
was involved in the formation reaction of the maleimide compounds from either fumaronitrile or
maleonitrile derivatives. Single-crystal X-ray structures of these three fumaronitrile derivatives,
the first three of the kind, were obtained, revealing the nonplanar molecular structure. We ascribe
the strong solid-state fluorescence of these diphenylfumaronitrile derivatives to the nonplanar
structure that inhibits the close packing of the molecule aggregation and thus the fluorescence
quenching.
1. In tr od u ction
illusive and yet to be developed. A systematic study of
the reaction is thus needed to provide insightful informa-
tion on the reaction, which is valuable for the efficient
preparation of NPAMLMe, an unusual, nondoped, host
emitter for red organic light-emitting diodes (OLEDs).3
In addition, bis(4-bromophenyl)fumaronitrile is also a
synthetic precursor for another efficient and bright host
emitter, bis(4-(N-(1-naphthyl)phenylamino)phenyl)fuma-
ronitrile (NPAFN), for nondoped red OLEDs.4 Accord-
ingly, we feel that the synthetic chemistry about R,â-
Recently, we reported an improved synthetic procedure
in preparing N-methyl-3,4-bis(4-(N-(1-naphthyl)pheny-
lamino)phenyl)maleimide (NPAMLMe) via the easily
isolated intermediate bis(4-bromophenyl)fumaronitrile
(or trans-4,4′-dibromo-R,â-dicyanostilbene) from (4-bro-
mophenyl)acetonitrile (route B, Scheme 1).1 Preparing
diphenyl-substituted fumaronitrile compounds from phen-
yl-substituted acetonitrile derivatives by oxidative cou-
pling reaction, in either Br2- or I2-containing alcoholic
alkoxide or aqueous hydroxide, has been known to
chemists and can be traced back to the late 19th century.2
However, surveying the literature reveals that the reac-
tion has been performed somewhat differently in many
cases and the reaction yields varied even for the same
parent compound, trans-R,â-dicyanostilbene. Considering
trans-R,â-dicyanostilbene bearing different substituents,
the synthetic yields differ widely and range from less
than 20% to more than 80%.2 This indicates that the
reaction is sensitive to the reaction conditions and
chemical structure. The essence of the synthesis seems
(2) For examples see (a) Chalanay, L.; Knoevenagel, E. Chem. Ber.
1892, 25, 285. (b) Heller, G. J ustus Liebigs Ann. Chem. 1904, 332, 247.
(c) Cook, A. H.; Linstead, R. P. J . Chem. Soc. 1937, 929. (d) Koelsch,
C. F.; Wawzonek, S. J . Org. Chem. 1941, 6, 684. (e) Niederl, J .; Ziering,
A. J . Am. Chem. Soc. 1942, 64, 2486. (f) Weizman, M.; Patai, S. J .
Am. Chem. Soc. 1949, 71, 2587. (g) Coe, D. G.; Gale, M. M.; Linstead,
R. P.; Timmons, C. J . J . Chem. Soc. 1957, 123 and refs 1-11 cited
therein for the synthesis of dipehenylfumaronitrile in the late 19th
and early 20th centuries. (h) Marinina, L. E.; Mikhalenko, S. A.;
Luk’yanets, E. A. J . Gen. Chem. USSR 1974, 43, 2010. (i) Irie, M.;
Mohri, M. J . Org. Chem. 1988, 53, 803. (j) Fields, E. K.; Behrend, J .;
Meyerson, S.; Winzenburg, M. L.; Ortega, B. R.; Hall, H. K., J r. J . Org.
Chem. 1990, 55, 5156. (k) Hanack, M.; Renz, G. Chem. Ber. 1990, 123,
1105. (l) Baumann, T. F.; Barrett, A. G. M.; Hoffman, B. M. Inorg.
Chem. 1997, 36, 5661. (m) Anderson, M. E.; Barrett, A. G. M.; Hoffman,
B. M. Inorg. Chem. 1999, 38, 6143. (n) Meyers, M. J .; Sun, J .; Carlson,
K. E.; Marriner, G. A.; Katzenellenbogen, B. S.; Katzenellenbogen, J .
A. J . Med. Chem. 2001, 44, 4230. (o) Vagin, S. I.; Hanack, M. Eur. J .
Org. Chem. 2002, 2859. (p) Vagtin, S.; Barthel, M.; Dini, D.; Hanack,
M. Inorg. Chem. 2003, 42, 2683.
* To whom correspondence should be addressed. Fax: +886-2-
27831237.
† Institute of Chemistry, Academia Sinica.
‡ National Taiwan University.
§ Institute of Atomic and Molecular Sciences, Academia Sinica.
(1) Yeh, H.-C.; Chan, L.-H.; Wu, W.-C.; Chen, C. T. J . Mater. Chem.
2004, 14, 1293.
(3) Wu, W.-C.; Yeh, H.-C.; Chan, L.-H.; Chen, C.-T. Adv. Mater.
2002, 14, 1072.
(4) Yeh, H.-C.; Yeh, S.-J .; Chen, C.-T. Chem. Commun. 2003, 2632.
10.1021/jo049512c CCC: $27.50 © 2004 American Chemical Society
Published on Web 08/25/2004
J . Org. Chem. 2004, 69, 6455-6462
6455

Yeh et al.
SCHEME 1
SCHEME 2
dicyanostilbene, either the E-isomer (diphenylfumaroni-
trile) or the Z-isomer (diphenylmaleonitrile), and diphe-
nylmaleimide derivatives is vital for the development of
potent materials such as NPAMLMe or NPAFN for
nondoped red OLEDs. Here we present the analysis of
the reaction conditions in depth to improve the synthesis
and the purification process. We also provide a logical
explanation for the unusually strong fluorescence ob-
served for NPAFN in the solid state4 by the X-ray
structure determination of three diphenylfumaronitrile
derivatives.
2. Resu lts a n d Discu ssion
2.1. Op im iza tion of th e Syn th esis of F u m a r on i-
tr iles. On the basis of the scattered evidence found in
the literature,2 conceivable reactions involved in the
synthesis can be divided into steps 1-9 as shown in
Scheme 2. They are the deprotonation of a benzylic
carbon (reactions 1, 3, and 5), halogenation of benzylic
carbon (reaction 2), nucleophilic substitution with sub-
sequent elimination reaction in forming diphenylfuma-
ronitrile (trans-R,â-dicyanostilbene) or diphenylmaleoni-
trile (cis-R,â-dicyanostilbene) (reactions 4 and 5), meth-
oxide-initiated intramolecular cyclization (reactions 6 and
7), and the next two hydrolysis steps leading to the
maleimide ring (reactions 8 and 9). Although it is easy
to perform (at room temperature requiring no heating
or cooling) and has the advantage of a wide range of
available phenylacetonitriles as the staring materials,5
the one-step synthesis suffers from low to modest reaction
yields. Furthermore, the purification often requires care-
ful column chromatography that greatly limits the syn-
thesis only suitable for small-scale preparation. Before
the N-methylation of maleimide, the relatively high
polarity of maleimide compounds is quite close to that of
several other unidentified color species and makes the
separation by chromatography rather difficult. Consider-
(5) Yeh, H.-C.; Wu, W.-C.; Chen, C.-T. Chem. Commun. 2003, 404.
6456 J . Org. Chem., Vol. 69, No. 19, 2004

Fumaronitrile as a Precursor for Maleimide
SCHEME 3
ing the large amount of the material demanded in the
fabrication of OLEDs, an improved synthesis of maleim-
ide compounds, which is convenient to perform and
suitable for large-scale preparation, becomes a quest.
In our recent process of improving the reaction yield
of one-step synthesis of 3,4-bis(4-bromophenyl)maleimide,
we frequently encountered better results (higher reaction
yield and cleaner reaction product) by performing the
reaction first at low temperature and then warming to
room temperature (-78 f +25 °C) and controlling the
stoichiometric amount of sodium methoxide base to no
more than 3 equiv in the reaction.5 However, the further
reduction of the amount of sodium methoxide base often
dramatically decreases the reaction yield. More recently,
we have found that what we obtained is mainly bis(4-
bromophenyl)fumaronitrile instead of 3,4-bis(4-bromophe-
nyl)maleimide from those unsatisfactory synthetic ex-
periments.1 We deduced that an insufficient amount of
sodium methoxide (e3 equiv) will bring the reaction to
fumaronitrile instead of maleimide because it needs 2.0
equiv of sodium methoxide to generate the former and
2.0 equiv or more of sodium methoxide to obtain the
latter. This is quite consistent with the stoichiometry of
sodium methoxide in Scheme 2. On the other hand,
lowering the temperature in the early stage of the
reaction can statistically reduce the chance of generating
downstream product of maleimide even in the circum-
stance of insufficient sodium methoxide. Here, another
key issue is that we switch the solvent from THF to
diethyl ether. We have found that diethyl ether is a better
solvent than THF in obtaining cleaner product. This is
partially due to the diaryl-substituted fumaronitriles
usually having a lower solubility in ether than in THF,
which facilitates the precipitation of the desired product
for easy isolation (by filtration) and prevents the fuma-
ronitrile from further reacting with sodium methoxide
in solution.
ronitrile products. The product often can be easily
obtained with good to high yields by simple filtration of
the reaction solution if the reaction concentration is set
above the saturation point of the product. For instance,
0.25 M is the optimum concentration for bis(4-bromophe-
nyl)fumaronitrile, and a higher concentration of 1.0-2.0
M is necessary for the high-yield synthesis of diphenyl-
fumaronitrile, bis(3-trifluoromethylphenyl)fumaronitrile,
and bis(4-methoxyphenyl)fumaronitrile due to the higher
solubility of the products. Following our improved
reaction conditions and the simple isolation method, bis-
(4-bromophenyl)fumaronitrile, diphenylfumaronitrile,
bis(3-trifluoromethylphenyl)fumaronitrile, and bis(4-
methoxyphenyl)fumaronitrile can be obtained directly in
pure form from the reaction with good to high yields of
90%, 86%, 67%, and 69%, respectively.
2.2. Syn th esis of N-Meth yla ted Ma leim id e fr om
F u m a r on itr ile. With readily available fumaronitrile
derivatives in pure form, a one-step synthesis procedure
becomes possible for the preparation of N-methyl-3,4-
diaryl-substituted maleimides. For the sake of easy
column chromatography in the later step of the synthesis,
the N-methylation of maleimide with iodimethane was
performed without the isolation of the pure maleimide
product from the previous reaction. However, removal of
the ionic species (by extraction) generated from the acidic
hydrolysis procedure is necessary to increase the reaction
yield. We were able to prepare N-methyl-3,4-diaryl-
substituted maleimides in reasonable yields of 52-73%
after the column chromatography purification. Such
results are satisfactory considering the moderate purity
of the maleimide reactants. It is worth noting that the
column chromatography performed at this stage on
N-methylated maleimide is significantly easier than that
before N-methylation due to the relatively low polarity
of the N-methylated maleimide and the distant separa-
tion from other side products during column chromatog-
raphy.
Regarding the product purification, we have found that
the concentration of the reaction is critical for a quick
and easy isolation of the product and should be adjusted
accordingly on the basis of the solubility of the fuma-
The advantage of the new synthesis (route B in Scheme
3) is its relatively high yield and the ease of purification,
namely, chromatography once instead of twice including
J . Org. Chem, Vol. 69, No. 19, 2004 6457

Yeh et al.
1
F IGURE 1. Aromatic region of H NMR spectra (in CDCl3)
of bis(4-methoxyphenyl)fumaronitrile (top), bis(4-methoxyphe-
nyl)maleonitrile (middle), and bis(4-methoxyphenyl)maleimide
(bottom).
a difficult one. The overall yield of the preparation of the
N-methylated maleimide compounds (from acetonitrile
derivatives) is around 35-63%, a substantial improve-
ment from those of route A in Scheme 3. More impor-
tantly, the most desired compound N-methyl-3,4-bis(4-
bromophenyl)maleimide, the precursor for synthesizing
NPAMLMe, is particularly beneficial to the improved
synthetic procedure with an overall isolated yield of
∼63%, the highest among all N-methyl-3,4-diarylmale-
imide compounds reported so far. The overall yield of the
synthesis of N-methyl-3,4-bis(4-bromophenyl)maleimide
has never been over 45% through route A of Scheme 3.
F IGURE 2. 1H NMR spectrum (in CDCl3) of the reaction
products (from the reaction shown above) providing evidence
of possible E-Z isomerization under the reaction conditions
(see the text for details).
We first tried to isolate the Z-isomer of 4-methoxy-
substituted R,â-dicyanostilbene, i.e., bis(4-methoxyphe-
nyl)maleonitrile, from the reaction with an E-isomer
reactant. We quenched the reaction (by acidic hydrolysis)
of maleimide formation halfway toward completion (cut
the reaction time in half). After the removal of ionic
species by extraction, the crude reaction mixture was
taken for 1H NMR examination for the presence of the
Z-isomer in the reaction mixture. From several attempts,
all we found in the 1H NMR spectra were the signals
caused by the reactant bis(4-methoxyphenyl)fumaroni-
trile and the product bis(4-methoxyphenyl)maleimide.
There was no detectable signal of bis(4-methoxyphenyl)-
maleonitrile. After several failed attempts, we changed
the reactant to the Z-isomer and looked for the signals
of the E-isomer instead in 1H NMR spectra (Figure 2).
In addition to the unreacted Z-isomer reactant and the
maleimide product, we saw the signals due to the
E-isomer of 4-methoxy-substituted R,â-dicyanostilbene.
This is alternative evidence of the E-Z isomerization
between malenitrile and fumaronitrile under the reaction
conditions (diethyl ether in the presence of sodium
methoxide and modest heating).6c In addition, we noticed
that the reaction of forming bis(4-methoxyphenyl)male-
imide, in fact, ran much faster than that using the
E-isomer as the reactant. Such an observation is also in
1
2.3. H NMR Ch a r a cter iza tion of F u m a r on itr ile,
Ma leon itr ile, a n d Ma leim id e. Due to the relatively
large size of the single crystal, we were able to take the
1H NMR spectra of the individual crystals in solution.
This helps in the spectroscopic differentiation of two
isomers (fumaronitrile and maleonitrile) in addition to
maleimide derivative. The 4-methoxy-substituted com-
pounds turned out to be the ideal case in our synthesis,
generating a sufficient amount of the Z-isomer in con-
junction with the E-isomer, and they were separable by
column chromatography. Figure 1 shows the 1H NMR
spectra in the aromatic region of the three species. It is
evident that the E-isomer has a more pronounced differ-
ence in chemical shifts of phenyl ring signals than the
other two compounds. This is quite consistent with the
maleimide structurally resembling the Z-isomer than the
E-isomer. Another characteristic feature of the maleimide
compound is the humplike signal due to the imide
hydrogen around 7.35 ppm (Figure 1), which is unique
among the three compounds. Similar 1H NMR spectral
patterns were also observed for the other three sets of
the compound and thus can be used as a common
identification marker.
Synthetically, the E-isomers of R,â-dicyanostilbene
derivatives were the compounds we adopted in the
synthesis of maleimide compounds. With the geometry
concern, it is intriguing to ask how it could be possible
to form the maleimide compound with the E-isomer
(fumaronitrile) that has nitrile groups on the opposite
side of the C-C double bond. It is possible unless an E-Z
isomerization process takes place before the intramo-
lecular cyclization reaction. This has been supposed to
be the case, a long-time postulation.2g,6a,b With the
complete 1H NMR data of the three species, we attempted
to offer the spectroscopic evidence to support the case.
(6) (a) Baguley, M. E.; France, H.; Linstead, R. P.; Whalley, M. J .
Chem. Soc. 1955, 3521. (b) Fitzgerald, J .; Tayloer, W.; Owen, H.
Synthesis 1991, 686. (c) The base sensitivity of the isomerization of
fumaronitrile and maleonitrile has been noted again recently (Huisgen,
R.; Li, X.; Giera, H.; Langhals E. Helv. Chim. Acta 2001, 84, 981). The
central C-C double bond of either fumaronitrile or maleonitrile is
susceptible to base, such as fluoride, alkoxide, or even a polar solvent
molecule such as acetonitrile. It is conceivable that the base acts as a
nucluophile in transforming the double bond to a rotary C-C single
bond. The C-C double bond can thus be recovered after the elimination
of the substituted base but with alternative isomer structure (from
cis to trans form or from trans to cis form).
6458 J . Org. Chem., Vol. 69, No. 19, 2004

Fumaronitrile as a Precursor for Maleimide
F IGURE 3. X-ray crystal structure of bis(4-bromophenyl)-
fumaronitrile with a 30% thermal ellipsoid.
FIGURE 6. Fluorescence image of NPAFN in dichloromethane
solution (in vial) and as a solid powder (on glass slide).
F IGURE 4. X-ray crystal structure of bis(3-trifluorometh-
ylphenyl)fumaronitrile with a 50% thermal ellipsoid.
F IGURE 7. Fluorescence images of the single crystal of bis-
(3-trifluoromethylphenyl)fumaronitrile (top left), bis(4-bro-
mophenyl)fumaronitrile (top right), and bis(4-methoxyphenyl)-
fumaronitrile (bottom).
molecule is generated through a crystallographic center
of inversion because of the symmetrical configuration
imposed by the occupation of the special position in the
monoclinic crystal. Consequently, there is no doubt about
the E-configuration (fumaronitrile), instead of the Z-
configuration (maleonitrile), of the three structures re-
ported here.
F IGURE 5. X-ray crystal structure of bis(4-methoxyphenyl)-
fumaronitrile with a 30% thermal ellipsoid.
The bond lengths of the central C-C double bond are
1.341(5), 1.344(7), and 1.360(3) Å for bromo, trifluoro-
methyl, and methoxy, respectively. The 1.341(5) Å bond
length of bis(4-bromophenyl)fumaronirile and bis(3-tri-
fluoromethylphenyl)fumaronitrile and 1.344(7) Å bond
length of bis(3-trifluoromethylphenyl)fumaronitrile are
rather similar to the 1.338 Å bond length of the central
C-C double bond of the unsubstituted parent trans-
stilbene.9 On the other hand, the bond distance 1.360(3)
Å of bis(4-methoxyphenyl)fumaronitrile is rather close to
the bond distance 1.362(2) Å of the central C-C double
bond of 2,3-bis(4-methylphenyl)maleonitrile (a Z-form
isomer).10 We tried to connect the difference in chemical
reactivity of the diphenylfumaronitrile bearing a different
substituent to the bond length of the central C-C double
bond. Chemically, we have noticed that NPAFN is the
one among five diphenylfumaronitrile derivatives (the
parent and 4-bromo, 3-CF3, 4-methoxy, and 4-(1-naph-
thyl)phenylamino derivatives) most susceptible to the
accord with the requirement of E-Z isomerization if the
E-isomer is the reactant.
2.4. X-r a y Cr ysta l Str u ctu r e a n d Solid -Sta te F lu o-
r escen ce. The single-crystal X-ray structures were
obtained for verifying the E-isomer configuration of bis-
(4-bromophenyl)fumaronitrile, bis(3-trifluoromethylphe-
nyl)fumaronitrile, and bis(4-methoxyphenyl)fumaroni-
trile (Figures 3-5). We note that there has been only one
preceding report on the crystal structure of the parent
compound, diphenylfumaronitrile, in the early 1960s.7
However, this crystal structure was poorly refined.
For instance, the C-C double bond of the central
CNsHCdCHsCN unit was determined to be 1.46 Å,
which is way too long for a typical sp2-sp2-connected
C-C double bond (i.e., 1.34 Å for ethylene).8 Interestingly
enough, except the bromo-substituted compound, these
crystals belong to the same symmetrical subgroup (2/m
point group) of the monoclinic system, two independent
half-molecules are in the asymmetric unit, and each full
(9) Hoekstra, A.; Meertens, P.; Vos, A. Acta Crystallogr., Sect. B
1975, 31, 2813.
(7) Wallwork, S. C. Acta Crystallogr. 1961, 14, 375.
(8) Costain, C. C.; Stoicheff, B. P. J . Chem. Phys. 1959, 30, 777.
(10) Faulmann, C.; Cassoux, P.; Pullen, A. E. Acta Crystallogr., Sect.
B 2000, 56, 384.
J . Org. Chem, Vol. 69, No. 19, 2004 6459

Yeh et al.
F IGURE 8. Crystal packing diagrams of bis(4-methoxyphenyl)fumaronitrile viewing along the a-axis, (a) b-axis (b), and c-axis
(d) (three or four layers of the stacking molecules are included in the diagrams). A perspective view of the nonplanar molecule (c).
E-Z isomerization in solution (such as chloroform). Bis-
(4-methoxyphenyl)fumaronitrile shows such isomeriza-
tion as well but to a much less extent. There is no sign
of E-Z isomerization of bis(4-bromophenyl)fumaritrile
and bis(3-trifluoromethylphenyl)fumaronitrile by 1H NMR
spectroscopy (see section 2.3). The bond distance seems
to follow the trend of the susceptibility of E-Z isomer-
ization. The long central C-C double bond of bis(4-
methoxyphenyl)fumaronitrile may be due to the electron-
donating effect of the methoxy substituent. Such an effect
is supposed to be much stronger for NPAFN, an amino-
donor-bearing diphenylfumaronitrile derivative. Never-
theless, the crystal structure of NPAFN is needed to
confirm our speculation.
Fluorescencewise, previously we have reported that
NPAFN is unusual because it is brightly fluorescent but
only in the solid state (Figure 6).4 Unfortunately, we were
not able to obtain a single crystal suitable for X-ray
structure determination probably due to the amorphous
nature of NPAFN.4 However, the nonplanar structure
observed here (see below) for diphenylfumaronitrile-type
molecules is quite inspiring in the explanation of the
unusual fluorescence of NPAFN. Similar to that of
NAPNF, Figure 7 shows the conspicuous fluorescence of
bis(3-trifluoromethylphenyl)fumaronitrile, bis(4-bromophe-
nyl)fumaronitrile, and bis(4-methoxyphenyl)fumaroni-
trile in the solid state. Recent measurements showed the
solid-state fluorescence quantum yields are 19%, 22%,
32%, and 49% for NPAFN and 3-trifluoromethylphenyl-,
4-bromophenyl-, and 4-methoxyphenyl-substituted diphe-
nylfumaronitrile fluorophores, respectively.
In fact, all three molecules do not have a flat confor-
mation (neither does diphenylfumaronitrile despite its
poor X-ray data). There are considerable deviations from
planarity: 40° and 44° (bromo compound), 42° (triflu-
oromethyl compound), and 66° (methoxy compound) were
determined for the torsion angle between the plane of
the phenyl ring and the central CNsHCdCHsCN unit.
We believe such nonplanarity is due to the necessity of
avoiding close contacts between the ortho hydrogen of the
benzene ring and the adjacent CN group. This is ac-
cordant with the small torsion angle of 3-7° observed
for nearly flat trans-stilbene.9 It is interesting to note that
whereas a parallel orientation was found for bis(4-
methoxyphenyl)fumaronitrile as well as bis(3-trifluorom-
ethylphenyl)fumaronitrile, the pair of the phenyl rings
of each bis(4-bromophenyl)fumaritrile were nearly per-
pendicular to each other, forming an edge-to-face (or
T-shaped) contact between the molecules (see the Sup-
porting Information).
6460 J . Org. Chem., Vol. 69, No. 19, 2004

Fumaronitrile as a Precursor for Maleimide
by de Mello et al. on vacuum-deposited thin films.12 Whereas
the improved synthesis and characterization of bis(4-bro-
mophenyl)fumaronitrile and N-methyl-3,4-bis(4-bromophenyl)-
maleimide have been described before,1 those of the corre-
sponding parent diphenylfumaronitrile and N-methyl-3,4-
diphenylmaleimide together with their 3-trifluoromethyl and
4-methoxy derivatives are reported here.
Due to the prominent nonplanarity, the crystal struc-
ture of bis(4-methoxyphenyl)fumaronitrile is the best
among the three crystals illustrating a stacking feature
of this type of the molecules and the influence on the
molecular contact. The stacking structure of molecules
of bis(4-methoxyphenyl)fumaronitrile is clearly seen, and
it is along the a axis of the unit cell (Figure 8a,b).
However, the spacing (repeating distance) in each mol-
ecule stack is large, 3.907(1) Å, which is equivalent to
the length of the a axis of the unit cell (Figure 8d). The
large spacing is due to the erection of the CN group in a
large angle out of the plane of parallel phenyl rings
(Figure 8b-d). Quantitatively, the closest contact hap-
pens to be the oxygen atom of the methoxy group and
the hydrogen atom of the methoxy group of the neighbor-
ing molecule (2.87 Å), although it is unlikely relevant to
the fluorescence quenching. The closest interatomic
interaction keen to the fluorescence quenching is found
between the C5 carbon and the hydrogen atom on C3 in
Figure 5, which is 3.54 Å in distance. The shortest
distance considered for direct π-π interaction is 3.60 Å
between the C2 carbon in Figure 5 and the vicinal C3
carbon of the nearest neighboring molecules. Both dis-
tances are considered to be too long for an effective
distance of π-π interaction, 3.36 Å, a nonbonded inter-
planar spacing of graphite.11 Therefore, we can conclude
that there is no intimate π-π interaction between the
molecules in the solid state and hence there is only
limited fluorescence quenching in the solid state.
3.1. Gen er a l P r oced u r e for th e Syn th esis of Dip h en yl-
Su bstitu ted F u m a r on itr ile Der iva tives. The following
procedure was applied to the reaction with a solvent volume
of 100 mL for phenylacetonitrile (1 M), 400 mL for 4-bro-
mophenylacetonitrile (0.25 M), and 50 mL for both 3-trifluo-
romethylphenylacetonitrile and 4-methoxyphenylacetonitrile
(2 M). Acetonitrile derivatives and 1 equiv of iodine were
dissolved in dry diethyl ether. Sodium methoxide (2-2.2
equiv)-methanol solution was added slowly (over a period of
30 min) into the reaction solution at dry ice temperature under
a nitrogen atmosphere. The reaction solution was allowed to
warm by replacing the dry ice bath with an ice-water bath
before the temperature rose above 0 °C. During this time, more
and more precipitation was formed in the solution. The
reaction solution was stirred for another 3-4 h, and then the
reaction was quenched with 3-6% hydrochloric acid at less
than 10 °C. The solution was filtered to isolate the solid, which
was rinsed with cold methanol-water solution to wash away
ionic substances. A second crop of the pure product could often
be isolated by filtration of the original filtrate after further
concentration. The reported reaction yields of the following
fumaronitrile derivatives do not include the product isolated
from the filtrate.
3.1.1. Dip h en ylfu m a r on itr ile. An off-white solid. Yield:
1
86% (9.9 g). H NMR (400 MHz, CDCl3): δ (ppm) 7.80-7.84
(m, 4H), 7.50-7.56 (m, 6H). 13C NMR (100 MHz, CDCl3): δ
(ppm) 131.9, 131.6, 129.1, 128.6, 125.5, 116.5. FAB-MS: calcd
MW ) 230.08, m/e ) 230.10 (M+). Anal. Found (Calcd) for
The nonplanar molecular structure of three fumaroni-
trile compounds in conjunction with their solid-state
fluorescence strongly implies that NPAFN may possess
a similar nonplanar structure. The nonplanar structure
greatly prevents π-conjugated molecules from close stack-
ing, which induces the fluorescence quenching in the solid
state. In the case of NPAFN, the nonplanar 1-naphth-
ylphenylamino groups can further push the molecules
away from tight stacking.
C
16H10 N2: C, 83.19 (83.46); H, 4.47 (4.38); N, 12.14 (12.17).
3.1.2. Bis(3-t r iflu or om et h ylp h en yl)fu m a r on it r ile. A
1
white solid. Yield: 67% (12.3 g). H NMR (400 MHz, CDCl3):
δ (ppm) 8.07 (s, 2H), 8.03 (d, 2H, J ) 7.9 Hz), 7.84 (d, 2H, J )
7.9 Hz), 7.71 (t, 2H, J ) 7.9 Hz). 13C NMR (100 MHz, CDCl3):
2
δ (ppm) 132.3, 132.1 (q, J CF ) 33.2 Hz), 131.8, 130.1, 128.6
3
3
1
(q, J CF ) 3.6 Hz), 125.6 (q, J CF ) 3.5 Hz), 123.2 (q, J CF
)
271.2 Hz), 115.6. FAB-MS: calcd MW ) 366.06, m/e ) 365.99
(M-). Anal. Found (Calcd) for C18H8F6N2: C, 58.94 (59.03); H,
2.29 (2.20); N, 7.55 (7.65).
In summary, we have analyzed the reaction of forming
3,4-diphenylmaleimide from phenylacetonitrile reactants.
We can perform the reaction in one step or in two steps,
which is more favorable via the formation of diphenyl-
fumaronitrile. The stoichiometry of the sodium methoxide
base is the key controlling factor in addition to the near-
saturation concentration of the reactant, which facilitates
the handy isolation of pure diphenylfumaronitrile deriva-
tives. The successful synthesis and characterization of
four 3,4-diphenylmaleimide and four diphenylfumaroni-
trile compounds illustrate our points. The E-Z (or
fumaronitrile-maleonitrile) isomerization process in the
synthesis of maleimide from phenylacetonitrile was
3.1.3. Bis(4-m eth oxyp h en yl)fu m a r on itr ile. Unlike the
other three fumaronitrile compounds isolated from the reaction
solution, the product was found to be a mixture of fumaroni-
trile and maleonitrile with
a molar ratio of about 19:1
determined by 1H NMR. A lemon yellow solid. Yield: 69% (10.0
1
g). H NMR (400 MHz, CDCl3): δ (ppm) 7.78 (d, 4H, J ) 8.9
Hz), 6.99 (d, 4H, J ) 8.9 Hz), 3.87 (s, 3H). 13C NMR (CDCl3):
δ (ppm) 162.0, 130.4, 124.6, 122.7, 117.3, 114.6, 55.5. FAB-
MS: calcd MW ) 290.11, m/e ) 290.10 (M+). Anal. Found
(Calcd) for C18H14N2O2: C, 74.08 (74.47); H, 4.83 (4.86); N, 9.15
(9.65). A pure sample of bis(4-methoxyphenyl)maleonitrile was
isolated by column chromatography. 1H NMR (400 MHz,
CDCl3): δ (ppm) 7.28 (d, 4H, J ) 9.0 Hz), 6.80 (d, 4H, J )
9.0 Hz), 3.80 (s, 3H). 13C NMR (100 MHz, CDCl3): δ (ppm)
161.4, 130.9, 123.2, 122.9, 117.3, 114.5, 55.3. FAB-MS: calcd
MW ) 290.11, m/e ) 290.10 (M+). Anal. Found (Calcd) for
1
implied by the H NMR evidence. The nonplanar molec-
ular structure of diphenylfumaronitrile derivatives was
revealed by X-ray structure determination and was
ascribed to be the reason for strong fluorescence observed
in the solid state.
C
18H14N2O2: C, 74.13 (74.47); H, 4.78 (4.86); N, 9.45 (9.65).
3.2. Gen er a l P r oced u r e for th e Syn th esis of N-Meth y-
la ted Dip h en ylm a leim id e Der iva tives. The following pro-
cedure was applied to the reaction proceeding in toluene (50
mL) containing fumaronitrile compounds (0.2 M). Sodium
methoxide (3 equiv)-methanol solution was added to the
reaction solution. The solution mixture was then stirred for
another 1-3 h depending on the substituent of the fumaroni-
3. Exp er im en ta l Section
The quantum yields of red emitting fluorene derivatives
were determined by the integrating-sphere method described
(11) Gluster, J . P.; Lewis, M.; Rossi, M. Crystal Structure Analysis
for Chemists and Biologists; VCH: Weinheim, Germany, 1994.
(12) de Mello, J . C.; Wittmann, H. F.; Friend, R. H. Adv. Mater. 1997,
9, 230.
J . Org. Chem, Vol. 69, No. 19, 2004 6461

Yeh et al.
triles. We found electron-donating substituents, such as meth-
oxy, required a longer time (i.e., 3 h) and a higher temperature
(i.e., 50 °C) to drive the reaction toward completion. On the
other hand, room temperature and a short period of reaction
time (i.e., 1 h) were enough for an electron-withdrawing-
substituent-containing fumaronitrile, such as bis(3-trifluoro-
methylphenyl)fumaronitrile. The reaction was quenched by
water and then extracted by dichloromethane. After the
removal of the solvent, the solid residue was treated at 0 °C
with 2.0 equiv of potassium tert-butoxide in DMF. After 1-2
h of stirring, 2.5 equiv of iodomethane was added to the
solution. The solution was then stirred at room temperature
for about 10 h. After the removal of volatiles under reduced
pressure, the residue was redissolved in dichloromethane and
extracted with water. The desired product in dichloromethane
was isolated by column chromatography (silica gel, ethyl
acetate/hexanes).
(M+ + 1). Anal. Found (Calcd) for C19H11F6NO2: C 57.13
(57.15), H 2.67 (2.78), N 3.33 (3.51).
3.2.3. N-Meth yl-3,4-bis(4-m eth oxyp h en yl)m a leim id e. A
golden yellow solid. Yield: 73% (2.4 g). 1H NMR (400 MHz,
CDCl3): δ (ppm) 7.45 (d, 4H, J ) 9.0 Hz), 6.85 (d, 4H, J ) 9.0
Hz), 3.81 (s, 6H), 3.09 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
(ppm) 184.3, 180.6, 171.4, 160.7, 134.3, 131.4, 121.4, 114.1,
55.2, 39.6, 24.1. FAB-MS: calcd MW ) 323.12, m/e ) 324.2
(M+ + 1). Anal. Found (Calcd) for C19H17NO4: C 70.19 (70.58),
H 5.14 (5.30), N 4.20 (4.33).
Ack n ow led gm en t. We are grateful to the National
Science Council of Taiwan (Grant No. NSC 92-2113-M-
001-064) and Academia Sinica for financial support. In
addition, acknowledgment is made to Mr. Gene-Hsiang
Lee of the Instrument Center, National Taiwan Uni-
versity, for collecting data and solving the single-crystal
X-ray structure of bis(3-trifluoromethylphenyl)fuma-
ronitrile.
3.2.1. N-Meth yl-3,4-d ip h en ylm a leim id e. An apple green
solid. Yield: 68% (1.8 g). 1H NMR (300 MHz, CDCl3): δ (ppm)
7.43-7.46 (m, 4H), 7.30-7.36 (m, 6H), 3.14 (s, 3H). 13C NMR
(100 MHz, CDCl3): δ (ppm) 170.8, 136.3, 129.8, 129.7, 128.7,
128.5, 24.2. FAB-MS: calcd MW ) 263.09, m/e ) 264.3 (M+
+
Su p p or tin g In for m a tion Ava ila ble: CIF files for bis(4-
bromohenyl)fumaronitrile, bis(3-trifluoromethylphenyl)fuma-
ronitrile, and bis(4-methoxyphenyl)fumaronitrile and X-ray
crystal strucure data and crystal packing diagrams of bis-
(4-bromophenyl)fumaronitrile and bis(3-trifluoromethylphe-
nyl)fumaronitrile (PDF). This material is available free of
charge via the Internet at http://pubs.acs.org.
1). Anal. Found (Calcd) for C17H13NO2: C 77.79 (77.55), H 5.11
(4.98), N 4.93 (5.32).
3.2.2. N-Meth yl-3,4-bis(3-tr iflu or om eth ylp h en yl)m a le-
im id e. A green-yellow solid. Yield: 52% (2.1 g). 1H NMR (300
MHz, CDCl3): δ (ppm) 7.71 (s, 2H), 7.64 (t, 4H, J ) 9.0 Hz),
7.49 (t, 2H, J ) 7.80 Hz), 3.17 (s, 3H). 13C NMR (75 MHz,
CDCl3): δ (ppm) 169.7, 135.6, 132.5, 131.2, 129.1, 128.1, 126.8,
126.7, 123.2, 24.5. FAB-MS: calcd MW ) 399.07, m/e ) 400.3
J O049512C
6462 J . Org. Chem., Vol. 69, No. 19, 2004