Haval-Argade contrathermodynamic rearrangement of alkylidenesuccinimides to alkylmaleimides via the corresponding isoimides: A general approach to alkyl and dialkyl substituted maleimides

Article abstract of DOI:10.1016/j.tet.2006.01.091

A simple and efficient access to alkyl and dialkyl substituted maleimides has been demonstrated via the new contrathermodynamic rearrangement of (E)-alkylidenesuccinimides to alkylmaleimides. The (E)-alkylidenesuccinimides obtained from the Wittig-condens

Full text of DOI:10.1016/j.tet.2006.01.091

Tetrahedron 62 (2006) 3557–3563
Haval–Argade contrathermodynamic rearrangement of
alkylidenesuccinimides to alkylmaleimides via the corresponding
isoimides: a general approach to alkyl and dialkyl
substituted maleimides*
*
Kishan P. Haval and Narshinha P. Argade
Division of Organic Chemistry (Synthesis), National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411 008, India
Received 26 November 2005; revised 6 January 2006; accepted 26 January 2006
Available online 24 February 2006
Abstract—A simple and efficient access to alkyl and dialkyl substituted maleimides has been demonstrated via the new
contrathermodynamic rearrangement of (E)-alkylidenesuccinimides to alkylmaleimides. The (E)-alkylidenesuccinimides obtained from
the Wittig-condensation of N-arylmaleimide with aliphatic aldehydes on regioselective hydrolysis furnished the corresponding
(E)-alkylidenesuccinanilic acids in 95–98% yields. The b-alkylidenesuccinanilic acids on treatment with cyanuric chloride in the presence
of triethylamine gave the corresponding b-alkylisomaleimides in 78–80% yields via the b-alkylideneisosuccinimides with the exocyclic to
endocyclic carbon–carbon double bond migration. The kinetically controlled products alkylisomaleimides in refluxing acetic acid furnished
the thermodynamically controlled alkylmaleimides in 98% yield. The Wittig condensation of alkyl substituted isomaleimides/maleimides
with aliphatic aldehydes gave the desired dialkyl substituted maleimides in high yields. A conversion of a-methylenesuccinanilic acids to
a-methylisomaleimides has also been described, with 90% yield.
q 2006 Elsevier Ltd. All rights reserved.
1. Introduction
known in the literature5,6 as bioactive natural products and
one can surmise that nature might be designing them by
employing the condensation of pyruvic acid with the other
respective carboxylic acids. Several elegant routes to
alkylmethylmaleic anhydrides have been reported in the
past decade.6 To the best of our knowledge, to date no
natural product with a simple monoalkyl or dialkyl
substituted maleic anhydride moiety is known in the
literature. Only one method for the synthesis of monoalkyl
substituted maleic anhydrides is known—by the Heck
reaction using palladium-catalyzed dicarbonylation of
terminal acetylenes.7 The use of poisonous carbon
monoxide is a drawback of this simple one-step approach.
The dialkyl substituted maleic anhydrides have been
designed using the Grignard coupling reactions with
dimethyl acetylenedicarboxylate at K78 8C followed by
The cyclic anhydrides and imides are the compounds of
choice for all chemists from both the basic and applied point
of view for multiple purposes. The vast array of nucleophilic
reactions undergone by symmetrical and unsymmetrical
maleic anhydrides and maleimides confer on them a high
synthetic potential. As such, a large number of maleic
anhydrides and maleimides have been extensively used in
the synthesis of natural and unnatural bioactive heterocyclic
compounds,1 structurally interesting compounds highlight-
ing regiochemical dichotomy2 and several types of
polymers with tailored material characteristics.3 Maleic
anhydrides and maleimides bearing both hydrophilic groups
and hydrophobic parts are very important for their
bioactivities and material properties4 (Fig. 1). Several
alkylmethyl substituted maleic anhydrides such as chaeto-
mellic acids A and B, aspergillus acids A–D, maleic
anhydride segment of tautomycin and tyromycin A are
* NCL Communication no. 6691.
Keywords: Maleimides; Wittig coupling; Isomaleimides; Contrathermo-
dynamic rearrangement; Alkyl and dialkylmaleimides.
*
Corresponding author. Tel.: C91 20 25902333; fax: C91 20 25893153;
e-mail: np.argade@ncl.res.in
Figure 1. Alkyl and dialkyl substituted maleic anhydrides and imides.
0040–4020/$ - see front matter q 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.01.091

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K. P. Haval, N. P. Argade / Tetrahedron 62 (2006) 3557–3563
150–200 8C, tetralin reflux) and under the transition metal
catalyzed isomerization conditions [RuCl3, HRuCl(PPh3)3,
RhCl3, HRhCl(PPh3)3] were fruitless. We learnt from these
experiments that such type of (E)-alkylidenesuccinimides 2
to alkylmaleimides 6 conversion is a difficult process. The
compounds 2a–c could be thermodynamically more stable
due to the extra stability of carbon–carbon double bond with
(E)-geometry, than the corresponding compounds 6a–c. We
planned with reason and decided to alter the imide
dicarbonyl symmetry of 2 for such type of double bond
migrations. The amic/anilic acids under kinetically con-
trolled dehydration conditions are known to furnish the
corresponding isoimides.13 We felt that preparation of
isoimides would be helpful for such a carbon–carbon double
bond migration as the isomaleimides are expected to be
more stable than the corresponding alkylidineisosuccin-
imides due to the extension of p-cloud conjugation from the
aryl ring to the butyroiminolide carbonyl group. The highly
regioselective aqueous lithium hydroxide induced hydro-
lysis of 2 exclusively furnished the b-alkylidenesuccinanilic
acids 3 in 95–98% yields.
Figure 2. Triphenylphosphine and maleimide adducts (Wittig adducts).
trapping the cis-enolate with alkyl halides.8 The low
temperature reactions, lower reactivities of cis-enolates at
that temperature and contamination of trans-enolates are the
limitations of this approach. Hence, development of a new
practical approach to the alkyl and dialkyl substituted
maleic anhydrides and maleimides is still a useful and
challenging task of current interest. In continuation of our
studies on cyclic anhydrides chemistry,9 now we herein
report an easy approach to monoalkyl and dialkyl
substituted maleimides via the contrathermodynamic
(E)-alkylidenesuccinimides to alkylmaleimides rearrange-
ment as a key reaction.
Cyanuric chloride is a decent dehydrating agent for such
type of kinetic dehydrations13 and the treatment of acids 3
with cyanuric chloride in the presence of triethyl amine as a
base at room temperature directly furnished the expected
anti-b-alkylisomaleimides 5 in 78–80% yields. Both the
dehydrative cyclizations of acids 3 to form the intermediates
b-alkylideneisosuccinimides 4 (which could not be isolated)
and the abstraction of the a-methylene proton on
intermediate 4 to form the b-alkyl isomaleimides 5 took
place in one-pot. Our hypothesis turned out to be correct and
to the best of our knowledge this is the first example of
carbanion generation on an isoimide skeleton, though
in situ, and its application for the facile carbon framework
rearrangement. The structures of isomaleimides 5a–c were
unambiguously established on the basis of lactone carbonyl
(1794–1798 cmK1) and imine (1676–1678 cmK1) stretch-
ing frequencies in IR-spectra, appropriate 1H NMR data and
the presence of imine carbon atom (d 140.9–141.0) in 13C
NMR spectra. We could very easily convert these
kinetically controlled alkylisomaleimides 5a–c to the
2. Results and discussion
The formation of maleimide–triphenylphosphine adduct is
well known10 (Fig. 2) and we felt that the stepwise
activation of two vinylic protons in maleimide as Wittig
adducts would provide an efficient approach to alkylmale-
imides and dialkylmaleimides. In this context, starting from
N-p-tolylmaleimide (1), we prepared the (E)-alkylidene-
succinimides 2a–c in 89–91% yield11 (Scheme 1). We
thought that trisubstituted exocyclic carbon–carbon double
bond in compounds 2 will migrate easily to form the
trisubstituted endocyclic compounds 6 for the two reasons,
viz. (i) exocyclic to endocyclic carbon–carbon double bond
migrations are generally more easy and (ii) the endocyclic
trisubstituted carbon–carbon double bond will be in
conjugation with two imide carbonyls.12 We tried several
reagents and reaction conditions for the conversion of 2–6,
but all our attempts met with failure. The conversion of 2–6
under basic conditions (Et3N, Pyridine, DBU, NaH,
t-BuOKKC, t-BuLi), under the thermal conditions (heat
Scheme 1. Reagents, conditions and yields: (i) PPh3, THF, RCHO, reflux, 10 h (89–91%); (ii) aq 2 N LiOH, THF, 0 8C to rt, 5 h, (95–98%); (iii) cyanuric
chloride, NEt3, DCM, 0 8C to rt, 8 h (78–80%); (iv) AcOH, reflux, 5 h (98%); (v) PPh3, AcOH, RCHO, reflux, 18 h (77–80%); (vi) NEt3CTHF (1:1), reflux,
48 h (95–96%).

K. P. Haval, N. P. Argade / Tetrahedron 62 (2006) 3557–3563
3559
Scheme 2. Reagents, conditions and yields: (i) Et2O, ArNH2, rt, 1 h (98%); (ii) cyanuric chloride, NEt3, DCM, 0 8C to rt, 8 h (90%).
desired corresponding thermodynamically more stable
alkylmaleimides 6a–c in 98% yield, by just refluxing them
in glacial acetic acid for five hours. Both the opening of
iminobutenolides 5 with acetic acid to form the mix
anhydride intermediates and the intramolecular cyclization
via the amide nitrogen lone pair to form the compounds 6
took place in one-pot. We feel that these monoalkyl
substituted maleimides 6 will be potential precursors for
several bioactive natural products containing butenolide/
butyrolactone and butyrolactam core with fatty alkyl chain
substituents.14 Both the alkylisomaleimides 5 and alkyl-
maleimides 6 on treatment with refluxing acetic acid–
sodium acetate mixture or on treatment with triethylamine
in THF reverted to the more stable (E)-alkylidenesuccin-
imides 2 in quantitative yield, proving that in these systems
the endocyclic to exocyclic carbon–carbon double bond
migrations are more facile. These observations revealed and
confirmed that the order of thermodynamic stability for
these imides and isoimides is 2O6O5O4 and what we have
accomplished was the contrathermodynamic rearrangement
of exoimides 2 to endoimides 6 via the isoimides 4 and 5.
Finally, with the application of our earlier developed
synthetic protocol6f for the synthesis of chaetomellic acid
A, we could very easily transform the alkyl substituted
maleimides to the symmetrically dialkyl substituted
maleimides 8 via the intermediates 7 in very good yields.
As expected the alkylisomaleimides on triphenylphosphine
induced Wittig condensation with aliphatic aldehydes in
refluxing acetic acid also furnished the imides 8 via the
intermediates 6 and 7 in 77–80% yield. In the present 4-step
approach the alkylmaleimides were obtained in 65–70%
overall yields, while in the 5-step approach, the dialkylsub-
stituted maleimides were obtained in 48–55% overall yields.
In the present synthetic sequence, the stepwise use of two
different aliphatic aldehydes would provide a way to the
unsymmetrically dialkylsubstituted maleimides. The
hydrolysis of alkylsubstituted maleimides 6 under acidic
conditions followed by the dehydration to the corresponding
alkylmaleic anhydrides and the hydrolysis of dialkylmale-
imides to the corresponding dialkylmaleic anhydrides is
well known in the literature.6f,7,9i
of triethylamine also gave a-methylisomaleimide 12 in 90%
yield via the intermediate a-methyleneisosuccinimide 11,
proving that b-methylene protons can also be abstracted in a
similar fashion for such type of exo–endo framework
rearrangements.
3. Conclusion
In summary, we have demonstrated a simple and efficient
approach to alkylmaleimides and dialkylmaleimides via the
two Wittig coupling reactions, taking advantage for the first
time of kinetically controlled isoimides as intermediates to
enforce the difficult migration of exocyclic carbon–carbon
double bonds to the endocyclic position (2a–c to 6a–c). We
have also demonstrated that in the present strategy, both the
a- and b-methylene protons on isosuccinimide skeleton are
accessible for such type of exocyclic to endocyclic carbon–
carbon double bond migrations. The present Haval–Argade
contrathermodynamic rearrangement is noteworthy and lots
of new chemistry will be possible from this important
isoimide functionality. The present practical approach with
scale up potential is general in nature and it will be useful to
design a large number of analogs and congeners of
alkylmaleimides and dialkylmaleimides of interest, to a
large section of the chemists’ community. We also feel that
the present approach will be useful to design carbocyclic
compounds like byssochlamic acid and its analogs. The
present results will also be of interest to chemists studying
such type of exo–endo carbon–carbon double bond
isomerization reactions.
4. Experimental
4.1. General
Commercially available cyclic anhydrides, aromatic
amines, aliphatic aldehydes and triphenylphosphine were
used. Freshly recrystallized cyanuric chloride (CCl4) was
used. Melting points are uncorrected. Column chromato-
graphic separations were carried out on ACME silica gel
(60–120 mesh). FT-IR spectra were recorded on a FT-IR-
8300 Shimadzu spectrometer. 1H NMR spectra were
recorded in CDCl3 using TMS as internal standard and in
DMSO-d6 on a Bruker AC 200, MSL 300 and Bruker DRX
500 NMR spectrometers (200, 300 and 500 MHz, respect-
ively). 13C NMR spectra were recorded on a Bruker AC 200,
MSL 300 and Bruker DRX 500 NMR spectrometers (50, 75
and 125 MHz, respectively).
In the above mentioned strategy, we have proved that the
a-protons on the inisolable intermediate alkylideneisosuc-
cinimides 4 are accessible for such type of rearrangements.
We planned to verify the accessibility of the corresponding
b-protons in a-alkylideneisosuccinimides. In this context,
we performed the regioselective ring opening of itaconic
anhydride (9) with p-toluidine and obtained the a-methyl-
enesuccinanilic acid 10 in 98% yield (Scheme 2). The
treatment of acid 10 with cyanuric chloride in the presence

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K. P. Haval, N. P. Argade / Tetrahedron 62 (2006) 3557–3563
4.2. General procedure for N-p-tolyl-3(E)-alkylidene-
succinimides 2a–c
4.3.1. 3-p-Tolylcarbamoyl-non-3-enoic acid (3a). White
solid (11.33 g, 98%), mp 143–145 8C (petroleum etherC
ethyl acetate); H NMR (CDCl3, 200 MHz) d 0.87 (t, JZ
1
A solution of N-p-tolylmaleimide (1, 50 mmol) and
triphenylphosphine (50 mmol) in THF (125 mL) was stirred
at room temperature for 30 min. To the reaction mixture was
added aliphatic aldehyde (75 mmol) and it was refluxed for
10 h. The THF was distilled off in vacuo at 50 8C and the
residue was purified by silica gel column chromatography
using a mixture of petroleum ether and ethyl acetate (9:1) to
obtain the alkylidenesuccinimides 2a/b/c in 89–91% yields.
6 Hz, 3H), 1.20–1.40 (m, 4H), 1.47 (quintet, JZ6 Hz, 2H),
2.27 (s, 3H), 2.37 (q, JZ6 Hz, 2H), 3.38 (s, 2H), 7.06 (d,
JZ8 Hz, 2H), 7.16 (t, JZ6 Hz, 1H), 7.33 (d, JZ8 Hz, 2H),
8.01 (bs, 1H); 13C NMR (DMSO-d6, 50 MHz) d 14.0, 20.6,
22.1, 28.0, 28.5, 31.1, 34.1, 119.0, 119.1, 129.2, 131.9,
137.0, 137.1, 168.3, 168.4; IR (Nujol) nmax 2383, 2700–
2500, 1682, 1657, 1597 cmK1. Anal. Calcd for C17H23NO3:
C, 70.56; H, 8.01; N, 4.84. Found: C, 70.43; H, 7.96; N,
4.85.
4.2.1. 3-Hexylidene-1-p-tolyl-pyrrolidine-2,5-dione (2a).
White solid (12.34 g, 91%), mp 112–113 8C (petroleum
ether); 1H NMR (CDCl3, 200 MHz) d 0.90 (t, JZ6 Hz, 3H),
1.22–1.45 (m, 4H), 1.53 (quintet, JZ6 Hz, 2H), 2.23 (q, JZ
6 Hz, 2H), 2.37 (s, 3H), 3.37 (d, JZ2 Hz, 2H), 6.93 (tt, JZ
8, 2 Hz, 1H), 7.18 (d, JZ8 Hz, 2H), 7.27 (d, JZ8 Hz, 2H);
13C NMR (CDCl3, 50 MHz) d 13.7, 20.9, 22.2, 27.5, 29.6,
31.2, 31.8, 125.1, 126.0, 129.2, 129.4, 138.1, 139.6, 168.7,
173.0; MS (m/e) 271, 242, 228, 214, 200, 189, 172, 133,
107, 95, 81, 67, 53; IR (Nujol) nmax 1771, 1749, 1712, 1691,
1676 cmK1. Anal. Calcd for C17H21NO2: C, 75.24; H, 7.80;
N, 5.16. Found: C, 75.11; H, 7.92; N, 5.07.
4.3.2. 3-p-Tolylcarbamoyl-tridec-3-enoic acid (3b).
White solid (13.24 g, 96%), mp 138–140 8C (petroleum
etherCethyl acetate); H NMR (CDCl3, 200 MHz) d 0.87
1
(t, JZ6 Hz, 3H), 1.24 (bs, 12H), 1.47 (quintet, JZ6 Hz,
2H), 2.28 (s, 3H), 2.39 (q, JZ6 Hz, 2H), 3.38 (s, 2H), 7.07
(d, JZ8 Hz, 2H), 7.18 (t, JZ6 Hz, 1H), 7.34 (d, JZ8 Hz,
2H), 7.96 (bs, 1H); 13C NMR (DMSO-d6, 50 MHz) d 14.2,
20.6, 22.3, 28.3, 28.5, 28.6, 28.7, 28.9, 29.1, 29.2, 31.5,
119.0, 119.1, 129.2, 131.9, 137.0, 137.1, 168.4, 168.5; IR
(Nujol) nmax 3420, 2700–2500, 1682, 1661, 1597 cmK1
.
Anal. Calcd for C21H31NO3: C, 73.00; H, 9.04; N, 4.05.
Found: C, 73.12; H, 9.13; N, 4.16.
4.2.2. 3-Decylidene-1-p-tolyl-pyrrolidine-2,5-dione (2b).
White solid (14.54 g, 89%), mp 106–108 8C (petroleum
ether); 1H NMR (CDCl3, 200 MHz) d 0.88 (t, JZ6 Hz, 3H),
1.27 (bs, 12H), 1.52 (quintet, JZ6 Hz, 2H), 2.23 (q, JZ
6 Hz, 2H), 2.37 (s, 3H), 3.37 (d, JZ2 Hz, 2H), 6.93 (tt, JZ
8, 2 Hz, 1H), 7.18 (d, JZ8 Hz, 2H), 7.27 (d, JZ8 Hz, 2H);
13C NMR (CDCl3, 50 MHz) d 14.0, 21.1, 22.6, 28.0, 29.18,
29.24, 29.31, 29.37, 29.9, 31.8, 32.0, 125.2, 126.2, 129.3,
129.7, 138.4, 140.0, 169.0, 173.2; IR (Nujol) nmax 1771,
1709, 1676, 1466 cmK1. Anal. Calcd for C21H29NO2: C,
77.02; H, 8.93; N, 4.28. Found: C, 76.89; H, 9.02; N, 4.16.
4.3.3. 3-p-Tolylcarbamoyl-heptadec-3-enoic acid (3c).
White solid (15.21 g, 95%), mp 126–128 8C (petroleum
ether); 1H NMR (CDCl3, 200 MHz) d 0.87 (t, JZ6 Hz, 3H),
1.24 (bs, 20H), 1.47 (quintet, JZ6 Hz, 2H), 2.28 (s, 3H),
2.38 (q, JZ6 Hz, 2H), 3.38 (s, 2H), 7.07 (d, JZ8 Hz, 2H),
7.17 (t, JZ6 Hz, 1H), 7.33 (d, JZ8 Hz, 2H), 7.94 (bs, 1H);
13C NMR (CDCl3CDMSO-d6, 50 MHz) d 12.6, 19.2, 20.9,
27.0, 27.3, 27.5, 27.6, 27.7, 27.9 (5!CH2), 30.2, 33.1,
117.8, 125.4, 127.5, 130.7, 135.2, 143.6, 167.0, 167.4; IR
(Nujol) nmax 3411, 2700–2500, 1688, 1660, 1599 cmK1
.
Anal. Calcd for C25H39NO3: C, 74.77; H, 9.79; N, 3.49.
Found: C, 74.69; H, 9.82; N, 3.51.
4.2.3. 3-Tetradecylidene-1-p-tolyl-pyrrolidine-2,5-dione
(2c). White solid (17.06 g, 89%), mp 58–60 8C (petroleum
ether); 1H NMR (CDCl3, 200 MHz) d 0.88 (t, JZ6 Hz, 3H),
1.25 (bs, 20H), 1.55 (quintet, JZ6 Hz, 2H), 2.25 (q, JZ
6 Hz, 2H), 2.39 (s, 3H), 3.38 (d, JZ2 Hz, 2H), 6.95 (tt, JZ
8, 2 Hz, 1H), 7.20 (d, JZ8 Hz, 2H), 7.28 (d, JZ8 Hz, 2H);
13C NMR (CDCl3, 75 MHz) d 13.7, 20.8, 22.3, 27.9, 29.1,
29.2, 29.3 (7!CH2), 29.5, 31.8, 125.4, 125.9, 129.2, 129.5,
137.8, 139.1, 168.5, 172.6; MS (m/e) 383, 355, 257, 228,
215, 202, 189, 172, 108, 95, 81; IR (Nujol) nmax 1785, 1720,
1695, 1470 cmK1. Anal. Calcd for C25H37NO2: C, 78.28; H,
9.72; N, 3.65. Found: C, 78.19; H, 9.64; N, 3.60.
4.4. General procedure for N-p-tolylalkylisomaleimides
5a–c
To a slurry of alkylidenesuccinanilic acids (3a–c, 30 mmol)
in DCM (50 mL) was added triethylamine (90 mmol) in a
dropwise fashion with constant stirring at 0 8C. To the
resulting reaction mixture was added a solution of cyanuric
chloride (33 mmol) in DCM (50 mL) and the reaction
mixture was further stirred under argon atmosphere for 8 h
at room temperature. The reaction mixture was concentrated
in vacuo and residue was dissolved in ethyl acetate (50 mL).
The organic layer was washed with water, 5% aqueous
sodium bicarbonate, brine and dried over Na2SO4. The ethyl
acetate layer was concentrated in vacuo and the crude
product was purified by silica gel column chromatography
using a mixture of petroleum ether and ethyl acetate (9:1) to
obtain pure N-p-tolylalkylisomaleimides 5a–c in 78–80%
yields.
4.3. General procedure for N-p-tolyl-3(E)-alkylidene-
succinanilic acids 3a–c
To a solution of alkylidenesuccinimides (2a–c, 40 mmol) in
THF (50 mL) was added 2 N aqueous LiOH (50 mL) in a
dropwise fashion at 0 8C and the reaction mixture was
stirred for 5 h at room temperature. THF was distilled off in
vacuo and the aqueous layer was acidified with 2 N HCl and
extracted with ethyl acetate (3!50 mL). The combined
organic layer was washed with water, brine and dried over
Na2SO4. Concentration of the organic layer in vacuo gave
the desired alkylidenesuccinanilic acids 3a–c in 95–98%
yields.
4.4.1. 4-Hexyl-5-p-tolylimino-5H-furan-2-one (5a). Thick
oil (6.50 g, 80%), 1H NMR (CDCl3, 200 MHz) d 0.90 (t, JZ
6 Hz, 3H), 1.35 (bs, 6H), 1.69 (quintet, JZ6 Hz, 2H), 2.35
(s, 3H), 2.64 (t, JZ6 Hz, 2H), 6.29 (s, 1H), 7.17 (d, JZ
8 Hz, 2H), 7.33 (d, JZ8 Hz, 2H); 13C NMR (CDCl3,

K. P. Haval, N. P. Argade / Tetrahedron 62 (2006) 3557–3563
3561
50 MHz) d 13.9, 21.0, 22.4, 26.2, 27.3, 28.8, 31.3, 121.0,
125.3, 129.4, 137.1, 140.9, 150.1, 159.7, 167.1; IR (neat)
nmax 1798, 1678, 1622, 1506 cmK1. Anal. Calcd for
C17H21NO2: C, 75.24; H, 7.80; N, 5.16. Found: C, 75.12;
H, 7.93; N, 5.02.
1638, 1516 cmK1. Anal. Calcd for C17H21NO2: C, 75.24; H,
7.80; N, 5.16. Found: C, 75.20; H, 7.73; N, 5.11.
4.5.2. 3-Decyl-1-p-tolyl-pyrrole-2,5-dione (6b). White
solid (6.40 g, 98%), mp 58–60 8C (petroleum etherCethyl
1
acetate); H NMR (CDCl3, 200 MHz) d 0.87 (t, JZ6 Hz,
4.4.2. 4-Decyl-5-p-tolylimino-5H-furan-2-one (5b). White
solid (7.67 g, 78%), mp 53–55 8C (petroleum ether); H
3H), 1.26 (bs, 14H), 1.64 (quintet, JZ6 Hz, 2H), 2.36 (s,
3H), 2.50 (dt, JZ6, 2 Hz, 2H), 6.40 (t, JZ2 Hz, 1H), 7.10–
7.30 (m, 4H); 13C NMR (CDCl3, 50 MHz) d 14.1, 21.1,
22.6, 25.5, 27.0, 29.2, 29.3, 29.4, 29.5, 30.1, 31.9, 125.8,
126.2, 128.9, 129.7, 137.6, 150.3, 170.0, 170.6; IR (CHCl3)
nmax 1773, 1713, 1638, 1516 cmK1. Anal. Calcd for
C21H29NO2: C, 77.02; H, 8.93; N, 4.28. Found: C, 76.95;
H, 8.88; N, 4.21.
1
NMR (CDCl3, 200 MHz) d 0.87 (t, JZ6 Hz, 3H), 1.25 (bs,
14H), 1.68 (quintet, JZ6 Hz, 2H), 2.35 (s, 3H), 2.64 (t, JZ
6 Hz, 2H), 6.29 (s, 1H), 7.17 (d, JZ8 Hz, 2H), 7.33 (d, JZ
8 Hz, 2H); 13C NMR (CDCl3, 50 MHz) d 14.1, 21.1, 22.7,
26.3, 27.4, 29.1, 29.2, 29.3, 29.4, 29.6, 31.9, 121.1, 125.4,
129.5, 137.1, 141.0, 150.2, 159.8, 167.2; IR (CHCl3) nmax
1798, 1678, 1622, 1506 cmK1. Anal. Calcd for C21H29NO2:
C, 77.02; H, 8.93; N, 4.28. Found: C, 77.11; H, 9.04; N,
4.33.
4.5.3. 3-Tetradecyl-1-p-tolyl-pyrrole-2,5-dione (6c).
White solid (7.52 g, 98%), mp 72–74 8C (petroleum
etherCethyl acetate); H NMR (CDCl3, 200 MHz) d 0.87
1
4.4.3. 4-Tetradecyl-5-p-tolylimino-5H-furan-2-one (5c).
White solid (8.96 g, 78%), mp 58–60 8C (petroleum ether);
1H NMR (CDCl3, 200 MHz) d 0.87 (t, JZ6 Hz, 3H), 1.25
(bs, 22H), 1.68 (quintet, JZ6 Hz, 2H), 2.35 (s, 3H), 2.64 (t,
JZ6 Hz, 2H), 6.29 (s, 1H), 7.17 (d, JZ8 Hz, 2H), 7.33 (d,
JZ8 Hz, 2H); 13C NMR (CDCl3, 50 MHz) d 14.1, 21.1,
22.7, 26.3, 27.4, 29.1, 29.2, 29.3, 29.4, 29.6 (5!CH2), 31.9,
121.1, 125.4, 129.5, 137.1, 141.0, 150.2, 159.8, 167.2; IR
(CHCl3) nmax 1794, 1676, 1620, 1506 cmK1. Anal. Calcd
for C25H37NO2: C, 78.28; H, 9.72; N, 3.65. Found: C, 78.33;
H, 9.59; N, 3.60.
(t, JZ6 Hz, 3H), 1.25 (bs, 22H), 1.64 (quintet, JZ6 Hz,
2H), 2.36 (s, 3H), 2.50 (dt, JZ6, 2 Hz, 2H), 6.40 (t, JZ
2 Hz, 1H), 7.10–7.30 (m, 4H); 13C NMR (CDCl3, 50 MHz)
d 14.1, 21.1, 22.7, 25.5, 27.1, 29.2, 29.3, 29.5, 29.6 (6!
CH2), 31.9, 125.9, 126.2, 128.9, 129.7, 137.7, 150.3, 169.9,
170.6; IR (CHCl3) nmax 1773, 1713, 1638, 1516 cmK1
.
Anal. Calcd for C25H37NO2: C, 78.28; H, 9.72; N, 3.65.
Found: C, 78.22; H, 9.81; N, 3.54.
4.6. General procedure for N-p-tolyl-2-alkylidene-3-
alkylsuccinimides 7a–c
4.4.4. 3-Methyl-5-p-tolylimino-5H-furan-2-one (12). This
compound was obtained in 90% yield by using the same
procedure as used for the synthesis of compounds 5a–c; off
A solution of N-p-tolylalkylmaleimides (6a–c, 10 mmol),
triphenylphosphine (10 mmol) and aliphatic aldehyde
(15 mmol) in glacial acetic acid (30 mL) was refluxed for
18 h with constant stirring. Acetic acid was distilled off in
vacuo at 50 8C and the residue was dissolved in ethyl acetate
(100 mL). The organic layer was washed with water, brine
and dried over Na2SO4. Concentration of the organic layer
in vacuo followed by silica gel column chromatographic
purification of the residue using petroleum ether and ethyl
acetate (9:1) gave N-p-tolyl-2-alkylidene-3-alkylsuccin-
imides 7a–c in 77–80% yields.
1
white solid; mp 115–116 8C (petroleum ether); H NMR
(CDCl3, 300 MHz) d 2.15 (s, 3H), 2.36 (s, 3H), 7.02 (s, 1H),
7.19 (d, JZ9 Hz, 2H), 7.32 (d, JZ9 Hz, 2H); 13C NMR
(CDCl3, 75 MHz) d 10.7, 21.0, 125.0, 129.4, 136.5, 136.9,
138.7, 141.2, 148.9, 168.7; IR (Nujol) nmax 1778, 1674,
1599, 1462 cmK1. Anal. Calcd for C12H11NO2: C, 71.62; H,
5.51; N, 6.96. Found: C, 71.77; H, 5.48; N, 6.93.
4.5. General procedure for N-p-tolylalkylmaleimides
6a–c
The above compounds were also obtained from N-p-
tolylalkylisomaleimides 5a–c using the same procedure.
A solution of N-p-tolylalkylisomaleimides (5a–c, 20 mmol)
in glacial acetic acid (50 mL) was refluxed for 5 h. Acetic
acid was distilled off in vacuo at 50 8C and the residue was
dissolved in ethyl acetate. The organic layer was washed
with water, aqueous sodium bicarbonate, brine and dried
over Na2SO4. The organic layer was concentrated in vacuo
and the obtained residue, on silica gel column chromato-
graphic purification using petroleum ether and ethyl acetate
(9.5:0.5), gave N-p-tolylalkylmaleimides 6a–c in 98%
yields.
4.6.1. 3-Hexyl-4-hexylidene-1-p-tolyl-pyrrolidine-2,5-
dione (7a). Off white solid (2.85 g, 80%), mp 69–70 8C
(petroleum etherCethyl acetate); 1H NMR (CDCl3,
200 MHz) d 0.86 (t, JZ6 Hz, 3H), 0.91 (t, JZ6 Hz, 3H),
1.15–1.45 (m, 12H), 1.53 (quintet, JZ6 Hz, 2H), 1.75–1.98
(m, 1H), 1.98–2.15 (m, 1H), 2.28 (q, JZ8 Hz, 2H), 2.38 (s,
3H), 3.51 (unresolved multiplet, 1H), 6.93 (dt, JZ8, 2 Hz,
1H), 7.17 (d, JZ8 Hz, 2H), 7.27 (d, JZ8 Hz, 2H); 13C
NMR (CDCl3, 50 MHz) d 13.9, 14.0, 21.2, 22.4, 22.5, 24.6,
28.1, 29.2, 29.3, 30.7, 31.5, 31.6, 42.5, 126.2, 129.0, 129.3,
129.7, 138.4, 140.3, 169.3, 176.9; IR (CHCl3) nmax 1767,
1709, 1670, 1516 cmK1. Anal. Calcd for C23H33NO2: C,
77.70; H, 9.36; N, 3.94. Found: C, 77.79; H, 9.43; N, 3.72.
4.5.1. 3-Hexyl-1-p-tolyl-pyrrole-2,5-dione (6a). White
solid (5.31 g, 98%), mp 70–72 8C (petroleum etherCethyl
1
acetate); H NMR (CDCl3, 200 MHz) d 0.89 (t, JZ6 Hz,
3H), 1.15–1.50 (m, 6H), 1.64 (quintet, JZ6 Hz, 2H), 2.36
(s, 3H), 2.50 (dt, JZ6, 2 Hz, 2H), 6.40 (t, JZ2 Hz, 1H),
7.10–7.30 (m, 4H); 13C NMR (CDCl3, 50 MHz) d 14.0,
21.1, 22.4, 25.4, 27.0, 28.8, 31.4, 125.8, 126.2, 128.9, 129.6,
137.6, 150.3, 169.9, 170.5; IR (CHCl3) nmax 1773, 1713,
4.6.2. 3-Decyl-4-decylidene-1-p-tolyl-pyrrolidine-2,5-
dione (7b). Off white solid (3.62 g, 78%), mp 71–73 8C
(petroleum etherCethyl acetate); 1H NMR (CDCl3,
200 MHz) d 0.87 (t, JZ6 Hz, 6H), 1.25 (bs, 28H),

3562
K. P. Haval, N. P. Argade / Tetrahedron 62 (2006) 3557–3563
1.40–1.60 (m, 2H), 1.75–2.15 (m, 2H), 2.27 (q, JZ8 Hz,
2H), 2.37 (s, 3H), 3.50 (unresolved multiplet, 1H), 6.92 (dt,
JZ8, 2 Hz, 1H), 7.17 (d, JZ8 Hz, 2H), 7.27 (d, JZ8 Hz,
2H); 13C NMR (CDCl3, 50 MHz) d 14.1, 21.2, 22.6, 24.7,
28.5, 29.3, 29.4, 29.5 (11!CH2), 30.7, 31.9, 42.5, 126.2,
129.0, 129.4, 129.7, 138.4, 140.3, 169.2, 176.8; IR (Nujol)
nmax 1769, 1719, 1670, 1516 cmK1. Anal. Calcd for
C31H49NO2: C, 79.60; H, 10.56; N, 2.99. Found: C, 79.52;
H, 10.44; N, 3.07.
141.1, 170.9; IR (CHCl3) nmax 1707, 1516, 1394 cmK1
.
Anal. Calcd for C39H65NO2: C, 80.77; H, 11.30; N, 2.42.
Found: C, 80.81; H, 11.42; N, 2.37.
4.8. 2-Methylene-N-p-tolyl-succinamic acid (10)
To a stirred solution of itaconic anhydride (2.00 g,
17.8 mmol) in ether (10 mL) at room temperature was
added a solution of p-toluidine (1.90 g, 17.8 mmol) in ether
(10 mL) in a dropwise fashion over a period of 10 min. The
reaction mixture was stirred at room temperature for 50 min.
and the precipitated product was filtered, washed with ether
(2!10 mL) and dried under vacuum to obtain 2-methylene-
N-p-tolyl-succinamic acid 10 (4.00 g, 98% yield); White
4.6.3. 3-Tetradecyl-4-tetradecylidene-1-p-tolyl-pyrroli-
dine-2,5-dione (7c). Off white solid (4.48 g, 77%), mp
73–75 8C (petroleum etherCethyl acetate); 1H NMR
(CDCl3, 500 MHz) d 0.80–0.90 (m, 6H), 1.10–1.40 (m,
44H), 1.45–1.55 (m, 2H), 1.80–1.95 (m, 1H), 1.95–2.10 (m,
1H), 2.20–2.33 (m, 2H), 2.37 (s, 3H), 3.50 (unresolved
multiplet, 1H), 6.91 (dt, JZ8, 2 Hz, 1H), 7.17 (d, JZ10 Hz,
2H), 7.26 (d, JZ10 Hz, 2H); 13C NMR (CDCl3, 125 MHz)
d 14.1, 21.2, 22.7, 24.7, 28.5, 29.3–29.6 (21!CH2), 30.8,
31.9, 42.5, 126.2, 129.1, 129.4, 129.7, 138.5, 140.4, 169.3,
1
solid; mp 188–190 8C (ethyl acetateCethanol); H NMR
(CDCl3CDMSO-d6, 200 MHz) d 2.20 (s, 3H), 3.28 (s, 2H),
5.69 (s, 1H) 6.21 (s, 1H), 6.98 (d, JZ8 Hz, 2H), 7.39 (d, JZ
8 Hz, 2H), 9.48 (bs, 1H); 13C NMR (DMSO-d6, 50 MHz) d
20.7, 39.8, 119.3, 127.8, 129.4, 132.2, 136.2, 137.1, 168.0,
168.6; IR (Nujol) nmax 3292, 2700–2500, 1676, 1655, 1630,
1462 cmK1. Anal. Calcd for C12H13NO3: C, 65.74; H, 5.98;
N, 6.39. Found: C, 65.62; H, 6.05; N, 6.24.
176.9; IR (CHCl3) nmax 1769, 1705, 1670, 1518 cmK1
.
Anal. Calcd for C39H65NO2: C, 80.77; H, 11.30; N, 2.42.
Found: C, 80.67; H, 11.16; N, 2.53.
4.7. General procedure for N-p-tolyldialkylmaleimides
8a–c
Acknowledgements
K.P.H. thanks CSIR, New Delhi, for the award of a research
fellowship. We thank Dr. S. Mangaleswaran from our
research group for a couple of early experiments related to
this work.
To a stirred solution of N-p-tolyl-2-alkylidene-3-alkyl-
succinimides (7a–c, 5 mmol) in THF (20 mL) was added
triethylamine (20 mL) and the reaction mixture was refluxed
for 48 h and then it was concentrated in vacuo. The residue
was dissolved in ethyl acetate and the organic layer was
washed with water, brine and dried over Na2SO4.
Concentration of the organic layer in vacuo followed by
silica gel column chromatographic purification of the
residue using petroleum ether and ethyl acetate (9.5:0.5)
gave N-p-tolyldialkylmaleimides 8a–c in 95–96% yields.
References and notes
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4.7.1. 3,4-Dihexyl-1-p-tolyl-pyrrole-2,5-dione (8a). Thick
oil (1.70 g, 96%), 1H NMR (CDCl3, 200 MHz) d 0.89 (t, JZ
6 Hz, 6H), 1.15–1.45 (m, 12H), 1.57 (quintet, JZ6 Hz, 4H),
2.36 (s, 3H), 2.44 (t, JZ8 Hz, 4H), 7.22 (s, 4H); 13C NMR
(CDCl3, 50 MHz) d 14.0, 21.1, 22.5, 23.9, 28.6, 29.3, 31.4,
125.7, 129.3, 129.5, 137.2, 141.1, 170.9; IR (CHCl3) nmax
1707, 1516, 1395 cmK1. Anal. Calcd for C23H33NO2: C,
77.70; H, 9.36; N, 3.94. Found: C, 77.79; H, 9.45; N, 3.99.
4.7.2. 3,4-Bis-decyl-1-p-tolyl-pyrrole-2,5-dione (8b).
Thick oil (2.22 g, 95%), H NMR (CDCl3, 200 MHz) d
1
0.87 (t, JZ6 Hz, 6H), 1.25 (bs, 28H), 1.57 (quintet, JZ
6 Hz, 4H), 2.36 (s, 3H), 2.44 (t, JZ6 Hz, 4H), 7.22 (s, 4H);
13C NMR (CDCl3, 75 MHz) d 14.0, 21.0, 22.6, 23.9, 28.6,
29.3, 29.5, 29.6 (3!CH2), 31.9, 125.7, 129.3, 129.5, 137.1,
141.1, 170.9; IR (neat) nmax 1711, 1516, 1389 cmK1. Anal.
Calcd for C31H49NO2: C, 79.60; H, 10.56; N, 2.99. Found:
C, 79.66; H, 10.47; N, 3.03.
4.7.3. 3,4-Ditetradecyl-1-p-tolyl-pyrrole-2,5-dione (8c).
Thick oil (2.76 g, 95%), H NMR (CDCl3, 200 MHz) d
1
0.87 (t, JZ6 Hz, 6H), 1.25 (bs, 44H), 1.57 (quintet, JZ
6 Hz, 4H), 2.36 (s, 3H), 2.44 (t, JZ6 Hz, 4H), 7.22 (s, 4H);
13C NMR (CDCl3, 50 MHz) d 14.1, 21.1, 22.7, 23.9, 28.6,
29.3, 29.5, 29.6 (7!CH2), 31.9, 125.7, 129.3, 129.5, 137.2,

K. P. Haval, N. P. Argade / Tetrahedron 62 (2006) 3557–3563
3563
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