Cyanuric chloride: Decent dehydrating agent for an exclusive and efficient synthesis of kinetically controlled isomaleimides

Article abstract of DOI:10.1016/j.tet.2005.10.027

Starting from maleanilic and maleamic acids, a facile general approach to kinetically controlled isomaleimides has been described for the first time using cyanuric chloride as a dehydrating agent with 85-98% yields. The effect of a variety of substituents

Full text of DOI:10.1016/j.tet.2005.10.027

Tetrahedron 62 (2006) 937–942
Cyanuric chloride: decent dehydrating agent for an exclusive and
efficient synthesis of kinetically controlled isomaleimides*
*
Kishan P. Haval, Santosh B. Mhaske and Narshinha P. Argade
*
Division of Organic Chemistry (Synthesis), National Chemical Laboratory, Pune 411 008, India
Received 5 August 2005; revised 28 September 2005; accepted 13 October 2005
Available online 4 November 2005
Abstract—Starting from maleanilic and maleamic acids, a facile general approach to kinetically controlled isomaleimides has been
described for the first time using cyanuric chloride as a dehydrating agent with 85–98% yields. The effect of a variety of substituents
present on the aromatic ring in amine and maleic anhydride moiety, on these kinetic/thermodynamic dehydration processes of anilic
acids has been also described. Under the same set of reaction conditions the phthalanilic acid gave kinetically controlled product,
isophtalimide in 91% yield, while the corresponding succinanilic acid furnished the thermodynamically more stable succinimide in
high yield.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
mixtures of imides and isoimides in varying proportions,
(e) addition of liberated hydrochloric acid to the carbon–
carbon double bond and (f) 2C2 cycloaddition reactions of
formed imine with ketenes, chlorsulfonylisocyanates,
chloroacetyl or 2-chlorophenoxyacetyl chlorides.10
Recently isoimides have found applications in preparation
of surfmers,11 novel polyimides,12 novel polyisoimides,5d,13
agro-chemicals,9a pharmaceuticals,9a spiro b-lactams,6,10a,b
resins,14 polyhydrazides,15 herbicidal anti-dotes,16 mem-
branes,13b adhesives,13b diagnosis and cancer treatment and
in vivo photodynamic therapy.4d,17 Isoimides are useful in
the detection and measurement of biological materials
such as bacteria, enzymes and hormones.7b To focus on
the unique butiminolide functional moiety and to explore
the chemistry of this important functional group, a search
for readily available, cheap, efficient and general
quantized reagent is a task of significant challenge.1–9
Cyanuric chloride has been used earlier as dehydrating
agent on several type of organic compounds.18 The
predominance of deprotonation of the amide groups or
conversion of carboxylic hydroxyl group into good
leaving groups results in predominant formation of the
imides or isoimides, respectively.19 In this context, we
reasoned that in comparison with acid anhydrides, acid
chlorides, ketenes and carbodiimides, the optimum
reactive chloroimines will be soft and the best dehydrating
agents to obtain these kinetically controlled isomaleimide
products. We chose cyanuric chloride with three
inherently present chloro-imine units for this kinetic
dehydrative cyclization purpose and now we herein report
first simple and efficient method for the synthesis of
isoimides (Schemes 2–6).
Anilic acids on dehydration under kinetically controlled
conditions form isoimides while under thermodynamically
controlled conditions they furnish the corresponding imides
(Scheme 1).1,2 A large number of applications of imides
are known and plenty of methods to design them are well
established.2 The first isomaleimide synthesis was reported in
1955 by Tsou et al.1a using trifluroacetic anhydride as
a dehydrating agent and to the best of our knowledge a natural
product with an isoimide moiety is not known. In comparison
with imide, the isoimide chemistry is less explored and only
limited isoimide chemistry is known, as a general and efficient
method to exclusively design isoimides is still elusive.
Presently isomaleimides have been synthesized from the
corresponding maleamic acids by using (i) COCl2/Et3N,3
(ii) DCC,4 (iii) Ac2O/NaOAc,5 (iv) CH3COCl/Et3N,6 (v)
EtOCOCl/Et3N,6 (vi) (CF3CO)2O/Et3N,7 (vii) ketenes8 and
(viii) 2-chloro-1,3-dimethylimidazolinium chloride9 in
pyridine as dehydrating agents. In the synthesis of isomale-
imides,3–9 the use of above mentioned dehydrating reagents
have the following limitations (a) large excess amount of
reagent is required, (b) tedious workup and purification
procedures are involved, (c) low yields of isoimides with
decomposition of anilic acids, (d) formation of inseparable
* NCL Communication no. 6687.
Keywords: Maleamic acids; Cyanuric chloride; Dehydration; Kinetic
products; Isomaleimides.
Corresponding authors. Fax: C91 20 25893153;
e-mail addresses: np.argade@ncl.res.in; sb.mhaske@ncl.res.in
*
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.10.027

938
K. P. Haval et al. / Tetrahedron 62 (2006) 937–942
Z
XY
NHCOCH = CHCOOH
i
N
O
O
OH
O
N
N
O
H
O
O
-H2O
NHCOCH = CHCOOH
Bismaleamic acid 9
-H2O
Anilic acids 1
Bisisomaleimide 10
X/Y = H, Me, Cl, OMe, CO2Me, NO2
Z = -CH2CH2-, -CH=CH-, -o-C6H4-
(i) Cyanuric chloride, NEt3, DCM, 0 oC to rt, 8 h (85%)
O
O
N
Scheme 4.
O
N
O
Z
O
Z
Cyanuric chloride
R
N
O
R
NEt3, DCM, 0 oC to rt,
8 h (85-96%)
OH
O
N
O
XY
H
XY
11a-c
12a-c
Isoimides 2 (kinetically
controlled products)
Imides 3 (thermodynamically
controlled products)
Scheme 5.
Table 2
Scheme 1.
Sr. no.
Acid
R
Product (%)
X
1
2
3
11a
11b
11c
CH3
p-H3CO–C6H4–CH2
(R)-PhC(H3)CH2
12a (87)
12b (85)
12c (96)
R'
R''
O
R''
R'
O
Cyanuric chloride
N
O
X
NEt3, DCM, 0 oC to rt,
8 h (90-98%)
O
OH
N
H
4a-j
5a-j
H3C
Z
O
Cl
N
O
R''
O
OH
H
N
NH
Cl
N
N
i
i
R'
O
-
13a: Z = -o-C6H4-
Cl
N
Cl
N
Cl
X
13b: Z = -CH2-CH2-
O
N
N
O
N
N
O
N
Cl
H
..
H3C
Et3N
H3C
N
O
Cl
2,4-Dichlorotriazanoylmaleate
O
O
14 (91%)
15 (92%)
Scheme 2.
(i) Cyanuric chloride, NEt3, DCM, 0 oC to rt, 8 h
Table 1
Scheme 6.
R0
R00
Sr. no.
Acid
X
Product (%)
2. Results and discussion
1
2
3
4
5
6
7
8
9
10
4a
4b
4c
4d
4e
4f
4g
4h
4i
H
H
H
H
H
H
H
H
H
H
Ph
H
H
H
H
H
H
H
CH3
CH3
H
5a (90)
5b (98)
5c (93)
5d (90)
5e (91)
5f (93)
5g (94)
5h (97)
5i (90)
5j (95)
o-CH3
p-CH3
o-OCH3
p-OCH3
p-Cl
o-CO2CH3
H
p-CH3
p-CH3
In our research group we have been using cyclic anhydrides
as potential precursors for the synthesis of recently isolated
bioactive natural and unnatural products20 and the reactions
of cyclic anhydrides with a variety of aromatic and aliphatic
amines are known to furnish the corresponding anilic and
amic acids in high yields.20f In accordance with our aim, we
performed the reaction of N-phenylmaleanilic acid (4a) in
DCM with cyanuric chloride (1.1 equiv) in the presence of
triethylamine (3.0 equiv) at room temperature and exclu-
sively obtained the corresponding N-phenylisomaleimide
(5a) in 90% yield (Scheme 2). We believe that the present
kinetic dehydration must be proceeding via the formation of
intermediate 2,4-dichlorotriazinoylmaleate and both the
leaving group ability of 2,4-dichlorotrazine-2-ol and the
stability of the formed 4,6-dichlorotriazin-2-one must be
responsible for this quantitative and exclusive formation of
isoimide. In the same conversion, use of half an equivalent
of cyanuric chloride also furnished the isoimide 5a but in
less than 50% yield, revealing that 1.1 equiv of cyanuric
chloride is necessary for the quantitative conversion of
maleanilic acid to the corresponding isoimide, indicating
that the in situ generated 4,6-dichlorotriazin-2-one does not
further act as a dehydrating agent with same reactivity.
To establish the generality of this new set of reaction
conditions, we prepared several maleanilic acids 4b–g and
4j
O
O
O2N
..
OH
O
OH
N
N
H
O
+
N
H
O
O
6b-c
6a
-
i
i
O
N
O
O
N
O2N
NO2
7a (94%)
O
8b,c (97%, 95%)
a: -ortho, b: -meta, c: -para
(i) Cyanuric chloride, NEt3, DCM, 0 oC to rt, 8 h
Scheme 3.

K. P. Haval et al. / Tetrahedron 62 (2006) 937–942
939
all of them on treatment with cyanuric chloride furnished
exclusively the corresponding desired N-arylisomaleimides
5b–g in 90–98% yields (Table 1). The structures of these
butiminolides 5a–g were established from the characteristic
lactone carbonyl and imine double bond stretching
frequencies in infra-red spectra, presence of two doublet
succinimide. In our hands reaction of dichloromaleanilic
acid 16 with cyanuric chloride also gave the corresponding
dichloromaleimide 17 in 97% yield23 (Scheme 7). We feel
that the present imide formation could be due to the extra
thermodynamic stability of disubstitued maleimides,
indicating that the present conditions are also useful to
design the corresponding succinimides and disubstituted
maleimides. The conversion of kinetically controlled
isoimides to the corresponding thermodynamically more
stable imides is known in the literature.24
1
peaks for the vinylic protons in H NMR spectra and 13C
NMR data. The presence of syn and anti isomerism was
observed in H NMR spectra of some of the isoimides.
1
We prepared the mono-substituted methyl and phenyl
maleanilic acids 4i and 4j from the reactions of p-toluidine
with methylmaleic and phenylmaleic anhydrides, respect-
ively.21 These acids 4h–j on treatment with cyanuric
chloride also gave the corresponding mono-substituted
isomaleimides 5h–j in 90–97% yields.
Cl
O
Cl
Cl
H3C
Cl
O
i
H3C
N
OH
N
O
H
O
16
17
(i) Cyanuric chloride, NEt3, DCM, 0 oC to rt, 8 h (97%)
Generally, the isomaleimides with a nitro group on aromatic
ring are prepared directly from the corresponding diacid-
chlorides and nitro anilines.22 We planned to study the effect
of electron withdrawing o-/m-/p-nitro groups on these
cyanuric chloride induced dehydration reactions and
prepared the corresponding o-/m-/p-nitromaleanilic acids
6a–c. The treatment of o-nitromaleanilic acid (6a) with
cyanuric acid chloride exclusively gave the corresponding
o-nitroisomaleimide 7a in 94% yield, while m-nitro-
maleanilic acid (6b) and p-nitromaleanilic acid (6c) under
the same set of reaction conditions gave only the
corresponding nitromaleimides 8b,c in quantitative yields
(Scheme 3). Herein, we were unable to obtain the
corresponding isomaleimides from acids 6b,c even after
carrying out the addition of cyanuric chloride at K20 or
K78 8C and we always ended-up with formation of
maleimides 8b,c. We reason that the o-nitromaleanilic
acid 6a exclusively provides isoimide 7a due to the
intramolecular hydrogen bonding of –NH proton with the
o-nitro group forming a stable six-membered cyclic
structure. This makes the –NH proton less accessible to
the base and isoimide formation takes place via the
participation of lone pair of electrons on the nitrogen
atom. The diacid 9 on treatment with cyanuric chloride
(2.2 equiv) also smoothly furnished the bis-isomaleimide 10
in 85% yield (Scheme 4). It appears that the bisisoimide 10
will be a potential substrate to attempt novel 2C2
intramolecular cycloaddition reaction.
Scheme 7.
3. Conclusions
In summary, we have demonstrated an elegant general
approach to exclusively design kinetically controlled
N-aryl/N-alkyl isomaleimides and isophthalimides using
readily available cyanuric chloride as a dehydrating agent
and the present approach has several advantages over earlier
approaches. We feel that the present new clean and efficient
route to isoimides will be highly useful to further explore
the important field of isoimide chemistry as they are
dissymmetric in nature, nucleophilic ring openings under
neutral conditions are feasible and both carbonyl and imine
functionalities will be accessible. Our further studies on
isoimide synthesis and the first intramolecular cyclization
on isomaleimide skeleton to design the heterocyclic systems
via the Michael additions, by taking the advantage of
syn-anti equilibrium are in progress.
4. Experimental
4.1. General
Commercially available cyclic anhydrides and aromatic/
aliphatic amines were used. Freshly recrystallized cyanuric
chloride (CCl4) was used. Column chromatographic
separations were carried out on ACME silica gel (60–120
mesh/100–200 mesh). Melting points are uncorrected.
FT-IR spectra were recorded on a FT-IR-8300 Shimadzu
The reaction of cyanuric chloride with maleamic acids
11a–c also gave the corresponding N-alkylisomaleimides
12a–c in 85–96% yields (Scheme 5, Table 2) indicating that
the present kinetic dehydration condition works equally
well with maleamic acids to design N-alkylisomaleimides
in very good yields.
1
spectrometer. H NMR spectra were recorded in CDCl3
using TMS as an internal standard on a Brucker AC 200 and
MSL 300 NMR spectrometers (200 and 300 MHz,
respectively). 13C NMR spectra were recorded on a Brucker
AC 200, MSL 300 and Brucker AV 400 NMR spectrometers
(50, 75 and 100 MHz, respectively). The presence of syn
We studied the dehydration reactions of phthalanilic acid
13a and succinanilic acid 13b using cyanuric chloride as a
dehydrating agent under the same set of reaction conditions.
The acid 13a furnished the desired isophthalimide 14 in
91% yield, while the acid 13b gave exclusively the
corresponding succinimide 15 in 92% yield (Scheme 6).
Here we surmise that for isolation of these kinetically
controlled butiminolides, a strong carbon–carbon double
bond support to the backbone is essential. Alternatively,
the formed relatively less stable isosuccinimide might be
undergoing an in situ isomerization to the corresponding
1
and anti isomerism was observed in H NMR spectra of
some of the isoimides.
4.2. General procedure for preparation of isoimides
To a slurry of amic acid (10 mmol) in DCM (30 mL) was
added Et3N (30 mmol) in a drop-wise fashion with constant
stirring at 0 8C. To the resulting reaction mixture was added
a solution of cyanuric chloride (11 mmol) in DCM (20 mL)

940
K. P. Haval et al. / Tetrahedron 62 (2006) 937–942
and the reaction mixture was further stirred for 8 h at room
temperature. The reaction mixture was concentrated in
vacuo and the residue was dissolved in ethyl acetate
(50 mL). The organic layer was washed with water, 5%
aqueous bicarbonate, brine and dried over Na2SO4. The
organic layer was concentrated in vacuo and the obtained
product was purified by silica gel column chromatography
using a mixture of petroleum ether and ethyl acetate (9:1) to
4.2.7. Methyl 2-(5-oxo-5H-furan-2-ylideneamino)-
benzoate (5g). Yellow thick oil (2.17 g, 94%); H NMR
1
(CDCl3, 200 MHz) d 3.83 (s, 3H), 6.73 (d, JZ6 Hz, 1H),
7.02 (d, JZ8 Hz, 1H), 7.24 (t, JZ8 Hz, 1H), 7.44–7.57 (m,
2H), 7.98 (d, JZ8 Hz, 1H); 13C NMR (CDCl3, 50 MHz) d
51.8, 121.3, 121.7, 124.8, 129.2, 130.5, 132.5, 141.7, 145.3,
151.3, 165.7, 166.1; IR (neat) nmax 1801, 1720, 1713 cmK1
.
Anal. Calcd for C12H9NO4: C, 62.34; H, 3.92; N, 6.06.
Found: C, 62.43; H, 3.81; N, 5.97.
1
obtain pure isoimide (85–98% yields). Satisfactory IR, H
and 13C NMR and elemental analysis data were obtained for
all the newly synthesized compounds.
4.2.8. 3-Methyl-5-phenylimino-5H-furan-2-one (5h). Off
white solid (1.81 g, 97%), mp 110–112 8C (pet. ether); H
1
4.2.1. 5-Phenylimino-5H-furan-2-one (5a). Pale yellow
solid (1.56 g, 90%), mp 65–67 8C (pet. ether); H NMR
(CDCl3, 200 MHz) d 6.70 (d, JZ8 Hz, 0.95H), 6.80 (d,
JZ8 Hz, 0.05H), 7.20–7.60 (m, 6H); IR (nujol) nmax 1819,
1798, 1724, 1678 cmK1. Anal. Calcd for C10H7NO2: C,
69.36; H, 4.08; N, 8.09. Found: C, 69.29; H, 3.97; N, 8.11.
NMR (CDCl3, 300 MHz) d 2.16 (s, 3H), 7.04 (s, 1H),
7.15–7.45 (m, 5H); 13C NMR (CDCl3, 50 MHz) d 10.9,
124.5, 126.7, 128.8, 136.4, 139.3, 143.8, 149.6, 168.6; IR
(nujol) nmax 1780, 1674 cmK1. Anal. Calcd for C11H9NO2:
C, 70.58; H, 4.85; N, 7.48. Found: C, 70.43; H, 4.66;
N, 7.59.
1
4.2.2. 5-o-Tolylimino-5H-furan-2-one (5b). Yellow thick
oil (1.83 g, 98%); H NMR (CDCl3, 200 MHz) d 2.31 (s,
4.2.9. 3-Methyl-5-p-tolylimino-5H-furan-2-one (5i). Off
white solid (1.81 g, 90%), mp 115–116 8C (pet. ether); H
1
1
3H), 6.71 (d, JZ6 Hz, 0.96H), 6.83 (d, JZ6 Hz, 0.04H),
7.05–7.44 (m, 4H), 7.44 (d, JZ6 Hz, 1H); 13C NMR
(CDCl3, 50 MHz) d 17.7, 121.7, 125.9, 126.2, 128.0, 130.2,
132.0, 142.3, 142.6, 149.7, 166.9; IR (neat) nmax 1801, 1794,
1688 cmK1. Anal. Calcd for C11H9NO2: C, 70.58; H, 4.85;
N, 7.48. Found: C, 70.42; H, 4.81; N, 7.53.
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, 20.9, 125.0, 129.4, 136.5,
136.9, 138.7, 141.2, 148.9, 168.7; IR (nujol) nmax 1778,
1674 cmK1. Anal. Calcd for C12H11NO2: C, 71.62; H, 5.51;
N, 6.96. Found: C, 71.70; H, 5.63; N, 7.07.
4.2.3. 5-p-Tolylimino-5H-furan-2-one (5c). Pale yellow
solid (1.74 g, 93%), mp 76–78 8C (pet. ether); H NMR
4.2.10. 4-Phenyl-5-p-tolylimino-5H-furan-2-one (5j).
Yellow solid (2.50 g, 95%), mp 174–176 8C (pet. etherC
ethyl acetate); H NMR (CDCl3, 200 MHz) d 2.37 (s, 3H),
7.15–7.30 (m, 2H), 7.35–7.55 (m, 6H), 7.85–8.05 (m, 2H);
13C NMR (CDCl3, 50 MHz) d 21.2, 125.6, 127.9, 128.1,
129.0, 129.6, 130.9, 133.0, 137.5, 137.8, 141.3, 148.7,
166.7; IR (nujol) nmax 1771, 1657 cmK1. Anal. Calcd for
C17H13NO2: C, 75.55; H, 4.98; N, 5.32. Found: C, 75.71; H,
5.06; N, 5.38.
1
1
(CDCl3, 300 MHz) d 2.37 (s, 3H), 6.66 (d, JZ6 Hz, 0.9H),
6.74 (d, JZ6 Hz, 0.1H), 7.20 (d, JZ6 Hz, 2H), 7.35–7.40
(m, 3H); 13C NMR (CDCl3, 50 MHz) d 21.0, 125.5, 127.2,
129.5, 137.6, 140.7, 143.1, 149.4, 167.2; IR (nujol) nmax
1796, 1763, 1676 cmK1. Anal. Calcd for C11H9NO2: C,
70.58; H, 4.85; N, 7.48. Found: C, 70.43; H, 4.92; N, 7.36.
4.2.4. 5-(2-Methoxy-phenylimino)-5H-furan-2-one (5d).
Yellow thick oil (1.83 g, 90%); 1H NMR (CDCl3, 200 MHz)
d 3.87 (s, 3H), 6.66 (d, JZ6 Hz, 1H), 6.90–7.00 (m, 2H),
7.19 (dd, JZ8, 2 Hz, 1H), 7.33 (dd, JZ8, 2 Hz, 1H), 7.47
4.2.11. 5-(2-Nitro-phenylimino)-5H-furan-2-one (7a).
Pale yellow solid (2.05 g, 94%), mp 113–115 8C (pet.
etherCethyl acetate); H NMR (CDCl3, 200 MHz) d 6.80
(d, JZ6 Hz, 1H), 7.17 (d, JZ8 Hz, 1H), 7.34 (t, JZ8 Hz,
1H), 7.50 (d, JZ6 Hz, 1H), 7.62 (t, JZ8 Hz, 1H), 8.06 (d,
JZ8 Hz, 1H); 13C NMR (CDCl3, 50 MHz) d 123.4, 124.9,
125.8, 129.9, 133.7, 139.3, 141.4, 141.8, 152.8, 165.6; IR
(nujol) nmax 1817, 1801, 1702, 1527, 1377 cmK1. Anal.
Calcd for C10H6N2O4: C, 55.05; H, 2.77; N, 12.84. Found:
C, 54.97; H, 2.88; N, 12.97.
1
(d, JZ6 Hz, 1H); IR (neat) nmax 1807, 1794, 1690 cmK1
.
Anal. Calcd for C11H9NO3: C, 65.01; H, 4.46; N, 6.89.
Found: C, 64.94; H, 4.51; N, 6.92.
4.2.5. 5-(4-Methoxy-phenylimino)-5H-furan-2-one (5e).
Pale yellow solid (1.85 g, 91%), mp 75 8C (pet. etherCethyl
acetate); H NMR (CDCl3, 200 MHz) d 3.84 (s, 3H), 6.62
1
(d, JZ6 Hz, 0.96H), 6.74 (d, JZ6 Hz, 0.04H), 6.92 (d,
JZ8 Hz, 2H), 7.38 (d, JZ6 Hz, 1H), 7.56 (d, JZ8 Hz, 2H);
IR (nujol) nmax 1796, 1665 cmK1. Anal. Calcd for
C11H9NO3: C, 65.01; H, 4.46; N, 6.89. Found: C, 64.92;
H, 4.32; N, 6.97.
4.2.12. 1-(3-Nitro-phenyl)-pyrrole-2,5-dione (8b). Off
white solid (2.12 g, 97%), mp 132–134 8C (pet. etherC
ethyl acetate); H NMR (CDCl3, 200 MHz) d 6.94 (s, 2H),
7.66 (t, JZ8 Hz, 1H), 7.80 (d, JZ8 Hz, 1H), 8.24 (d,
JZ8 Hz, 1H), 8.34 (t, JZ2 Hz, 1H); IR (nujol) nmax 1724,
1533, 1346 cmK1. Anal. Calcd for C10H6N2O4: C, 55.05; H,
2.77; N, 12.84. Found: C, 55.09; H, 2.82; N, 12.90.
1
4.2.6. 5-(4-Chloro-phenylimino)-5H-furan-2-one (5f).
Pale yellow solid (1.93 g, 93%), mp 100–102 8C (pet.
etherCethyl acetate); H NMR (CDCl3, 200 MHz) d 6.71
1
(d, JZ6 Hz, 0.94H), 6.78 (d, JZ6 Hz, 0.06H), 7.37 (s, 4H),
7.40 (d, JZ6 Hz, 1H); 13C NMR (CDCl3, 100 MHz) d
126.7, 128.0, 129.2, 133.2, 141.9, 143.2, 150.4, 166.8; IR
(nujol) nmax 1825, 1801, 1759, 1678 cmK1. Anal. Calcd for
C10H6NO2Cl: C, 57.85; H, 2.91; N, 6.75. Found: C, 58.01;
H, 3.01; N, 6.66.
4.2.13. 1-(4-Nitro-phenyl)-pyrrole-2,5-dione (8c). Golden
yellow solid (2.07 g, 95%), mp 173–175 8C (pet. etherC
1
ethyl acetate); H NMR (CDCl3, 200 MHz) d 6.94 (s, 2H),
7.68 (d, JZ10 Hz, 2H), 8.33 (d, JZ10 Hz, 2H); 13C NMR
(CDCl3, 50 MHz) d 124.4, 125.4, 134.6, 137.1, 146.2,
168.5; IR (nujol) nmax 1780, 1715, 1521, 1348 cmK1. Anal.

K. P. Haval et al. / Tetrahedron 62 (2006) 937–942
941
Calcd for C10H6N2O4: C, 55.05; H, 2.77; N, 12.84. Found:
C, 55.17; H, 2.87; N, 12.92.
nmax 1730 cmK1. Anal. Calcd for C11H7NO2Cl2: C, 51.59;
H, 2.76; N, 5.47. Found: C, 51.62; H, 2.81; N, 5.55.
4.2.14. N,N0-Bis-(5-imino-5H-furan-2-one)-benzene-1,2-
diamine (10). Golden yellow solid (2.28 g, 85%), mp
143–145 8C (benzene); 1H NMR (CDCl3, 200 MHz) d 6.70
(d, JZ8 Hz, 1.92H), 6.80 (d, JZ8 Hz, 0.08H), 7.10–7.55
(m, 6H); 13C NMR (CDCl3, 75 MHz) d 121.8, 127.0, 128.5,
137.2, 142.5, 151.4, 166.6; MS (m/e) 268, 207, 170, 142,
115, 102, 90, 82, 64, 54. IR (CHCl3) nmax 1813, 1796, 1720,
1686, 1678 cmK1. Anal. Calcd for C14H8N2O4: C, 62.69; H,
3.00; N, 10.44. Found: C, 62.82; H, 3.11; N, 10.57.
Acknowledgements
K.P.H. and S.B.M. thank CSIR, New Delhi, for the award of
research fellowship. N.P.A. thanks Department of Science
and Technology, New Delhi, for financial support.
4.2.15. 5-Methylimino-5H-furan-2-one (12a). Yellow
thick oil (0.97 g, 87%); 1H NMR (CDCl3, 200 MHz) d
2.88 (s, 3H), 6.21 (d, JZ12 Hz, 1H), 7.01 (d, JZ12 Hz,
1H); IR (nujol) nmax 1711, 1618 cmK1. Anal. Calcd for
C5H5NO2: C, 54.05; H, 4.54; N, 12.61. Found: C, 54.11; H,
4.60; N, 12.49.
References and notes
1. (a) Tsou, K. C.; Barnett, R. J.; Seligman, A. M. J. Am. Chem.
Soc. 1955, 77, 4613. (b) Sauers, C. K.; Cotter, R. J. J. Org.
Chem. 1961, 26, 6. (c) Cotter, R. J.; Sauers, C. K.;
Whelan, J. M. J. Org. Chem. 1961, 26, 10. (d) Curtin, D. Y.;
Miller, L. L. Tetrahedron Lett. 1965, 1869. (e) Hedaya, E.;
Hinman, R. L.; Theodoropulos, S. J. Org. Chem. 1966, 31,
1311. (f) Hedaya, E.; Hinman, R. L.; Theodoropulos, S. J. Org.
Chem. 1966, 31, 1317. (g) Ernst, M. L.; Schmir, G. L. J. Am.
Chem. Soc. 1966, 88, 5001. (h) Curtin, D. Y.; Miller, L. L.
J. Am. Chem. Soc. 1967, 89, 637. (i) Barratt, M. D.;
Davies, A. P.; Evans, M. T. A. Eur. J. Biochem. 1971, 24,
280. (j) Anderson, N. H.; Ollis, W. D.; Thorpe, J. E.;
Ward, A. D. J. Chem. Soc., Perkin Trans. 1 1975, 825. (k)
Boyd, G. V.; Monteil, R. L. J. Chem. Soc., Perkin Trans. 1
1978, 1338. (l) Mazurkiewicz, R. Wiad. Chem. 1987, 41, 755.
(m) Nielsen, O.; Buchardt, O. Synthesis 1991, 819.
(n) Ezzell, S. A.; Hansen, R. G.; Anderson, G. J. PCT Int.
Appl. WO 9720832 A1, 1997, 51; Chem. Abstr. 1997, 127,
109325. (o) Fruk, L.; Graham, D. Heterocycles 2003, 60, 2305.
(p) Conley, N. R.; Hung, R. J.; Willson, C. G. J. Org. Chem.
2005, 70, 4553 and references cited therein 1a–p.
4.2.16. 5-(4-Methoxy-benzylimino)-5H-furan-2-one
(12b). Thick oil (1.85 g, 85%); 1H NMR (CDCl3,
200 MHz) d 3.80 (s, 3H), 4.76 (s, 2H), 6.64 (d, JZ6 Hz,
1H), 6.90 (d, JZ8 Hz, 2H), 7.15–7.35 (m, 3H); 13C NMR
(CDCl3, 50 MHz) d 52.7, 55.0, 113.8, 128.4, 129.0, 130.1,
142.1, 151.9, 158.6, 166.5; IR (CHCl3) nmax 1773, 1709,
1630 cmK1 Anal. Calcd for C12H11NO3: C, 66.35; H, 5.11;
N, 6.45. Found: C, 66.24; H, 5.09; N, 6.42.
4.2.17. 5-(1-Phenyl-ethylimino)-5H-furan-2-one (12c).
Yellow thick oil (1.93 g, 96%); 1H NMR (CDCl3,
200 MHz) d 1.55 (d, JZ6 Hz, 3H), 5.19 (q, JZ6 Hz, 1H),
6.62 (d, JZ6 Hz, 0.95H), 6.73 (d, JZ6 Hz, 0.05H),
7.15–7.60 (m, 6H); 13C NMR (CDCl3, 75 MHz) d 24.0,
58.4, 126.5, 127.2, 128.5, 128.8, 142.5, 143.7, 150.9, 166.7;
IR (nujol) nmax 1711, 1634 cmK1. Anal. Calcd for
C12H11NO2: C, 71.62; H, 5.11; N, 6.96. Found: C, 71.77;
H, 5.03; N, 7.06.
2. (a) Searle, N. E. U.S. Patent 2,444,536, 1948; Chem. Abstr.
1948, 42, 7340. (b) Mehta, N. B.; Phillips, A. P.; Lui, F. F.;
Brooks, R. E. J. Org. Chem. 1960, 25, 1012. (c) Braish, T. F.;
Fox, D. E. Synlett 1992, 979. (d) Reddy, P. Y.; Kondo, S.;
Toru, T.; Ueno, Y. J. Org. Chem. 1997, 62, 2652. (e) Le, Z.-G.;
Chen, Z.-C.; Hu, Y.; Zheng, Q.-G. Synthesis 2004, 995 and
references cited therein 2a–e.
4.2.18. 3-p-Tolylimino-3H-isobenzofuran-1-one (14). Off
white solid (2.16 g, 91%), mp 125–127 8C (pet. ether); H
1
NMR (CDCl3, 200 MHz) d 2.39 (s, 3H), 7.23 (d, JZ8 Hz,
2H), 7.41 (d, JZ8 Hz, 2H), 7.79 (t, JZ8 Hz, 1H), 7.85 (t,
JZ6 Hz, 1H), 7.99 (d, JZ6 Hz, 1H), 8.10 (d, JZ8 Hz, 1H);
13C NMR (CDCl3, 50 MHz) d 21.0, 123.4, 124.9, 125.1,
127.4, 129.4, 132.7, 135.2, 136.4, 137.1, 140.9, 146.1,
164.9; IR (nujol) nmax 1811, 1792, 1705 cmK1. Anal. Calcd
for C15H11NO2: C, 75.93; H, 4.67; N, 5.90. Found: C, 76.06;
H, 4.71; N, 5.85.
3. Nagata, T.; Tamaoki, A.; Kajimoto, N.; Wada, M. Jpn. Kokai
Tokkyo Koho JP 61022074 A2 4, 1986; Chem. Abstr. 1986,
105, 24175.
4. (a) Awad, W. I.; Wasfi, A. S.; Ewad, M. J. S. J. Iraqi Chem.
Soc. 1977, 2, 5. (b) Harris, F. W.; Karnavas, A. J.;
Cucuras, C. N.; Das, S. Polym. Prepr. 1985, 26, 287.
(c) Oishi, T.; Fujimoto, M.; Yoshimoto, N.; Kimura, T.
Polym. J. 1989, 21, 655. (d) Pandey, R. K.; Kozyrev, A. N.;
Dougherty, T. J. PCT Int. Appl. WO 9732885 A1 47, 1997;
Chem. Abstr. 1997, 127, 247962.
4.2.19. 1-p-Tolyl-pyrrolidine-2,5-dione (15). White solid
(1.74 g, 92%), mp 158–160 8C (pet. ether); 1H NMR
(CDCl3, 200 MHz) d 2.38 (s, 3H), 2.88 (s, 4H), 7.16 (d,
JZ8 Hz, 2H), 7.28 (d, JZ8 Hz, 2H); IR (nujol) nmax 1770,
1705, 1600 cmK1. Anal. Calcd for C11H11NO2: C, 69.82; H,
5.86; N, 7.40. Found: C, 69.99; H, 5.72; N, 7.33.
5. (a) Baumann, M. Eur. Pat. Appl. EP 38303 A2 16, 1981;
Chem. Abstr. 1982, 96, 52172. (b) Raetzsch, M.; Krahl, K.
Acta Polym. 1984, 36, 91. (c) Kurimoto, I.; Yoshimura, M.;
Inoue, K. Yamaguchi, T. Jpn. Kokai Tokkyo Koho JP
01056670 A2 8, 1989; Chem. Abstr. 1989, 111, 175922. (d)
Kurita, K.; Suzuki, Y.; Enari, T.; Kikuchi, M.; Nishimura, S.;
Ishii, S. J. Polym. Sci., Part A: Polym. Chem. 1994, 32, 393. (e)
Corrie, J. E. T.; Moore, M. H.; Wilson, G. D. J. Chem. Soc.,
Perkin Trans. 1 1996, 777.
4.2.20. 3,4-Dichloro-1-p-tolyl-pyrrole-2,5-dione (17).
White solid (2.48 g, 97%), mp 152–154 8C (pet. ether); H
1
NMR (CDCl3, 200 MHz) d 2.40 (s, 3H), 7.22 (d, JZ8 Hz,
2H), 7.30 (d, JZ8 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d
21.2, 125.9, 127.8, 130.0, 133.5, 138.6, 162.1; IR (nujol)

942
K. P. Haval et al. / Tetrahedron 62 (2006) 937–942
6. Capraro, H. G.; Winkler, T.; Martin, P. Helv. Chim. Acta 1983,
66, 362.
17. Kozyrev, A. N.; Zheng, G.; Lazarou, E.; Dougherty, T. J.;
Smith, K. M.; Pandey, R. K. Tetrahedron Lett. 1997, 38, 3335.
18. (a) De Luca, L.; Giacomelli, G.; Porcheddu, A. Org. Lett.
2001, 3, 1519. (b) De Luca, L.; Giacomelli, G.; Porcheddu, A.
Org. Lett. 2002, 4, 553. (c) Porcheddu, A.; Giacomelli, G.;
Salaris, M. J. Org. Chem. 2005, 70, 2361 and references cited
therein 18a–c.
7. (a) Aziz, T.; Shubber, A. Iraqi J. Sci. 1981, 22, 340.
(b) Theodoropulos, S. U.S. US 4789742 A6 7, 1988; Chem.
Abstr. 1989, 111, 97063.
8. Roth, M. Ger. Offen. DE 2705186 18, 1977; Chem. Abstr.
1977, 87, 167864.
9. (a) Ikeda, K.; Yamashita, W.; Tamai, S. Eur. Pat. Appl. EP
846714 A1 36, 1998; Chem. Abstr. 1998, 129, 68137.
(b) Ikeda, K.; Yamashita, W.; Tamai, S. U.S. US 5892061
A6 24, 1999; Chem. Abstr. 1999, 130, 281980.
10. (a) Capraro, H. G.; Rhis, G.; Martin, P. Helv. Chim. Acta 1983,
66, 633. (b) Barba, V.; Hernandez, C.; Rojas-Lima, S.;
Fartin, N.; Norberto, S. R. Can. J. Chem. 1999, 77, 2025.
11. Klimenkovs, I.; Zicmanis, A.; Uzulina, I.; Graillat, C.; Guyot, A.
J. Dispersion Sci. Technol. 2004, 25, 119.
19. Koton, M. M.; Kudryavtsev, V. V.; Zubkov, V. A.;
Yakimanskii, A. V.; Meleshko, T. K.; Bogorad, N. N.
Vysokomol. Soedin., Ser. A 1984, 26, 2534.
20. (a) Kar, A.; Gogoi, S.; Argade, N. P. Tetrahedron 2005, 61,
5297. (b) Mondal, M.; Argade, N. P. Tetrahedron Lett. 2004,
45, 5693. (c) Kar, A.; Argade, N. P. Tetrahedron 2003, 59,
2991. (d) Kar, A.; Argade, N. P. J. Org. Chem. 2002, 67, 7131.
(e) Mhaske, S. B.; Argade, N. P. J. Org. Chem. 2001, 66, 9038.
(f) Argade, N. P.; Balasubramaniyan, V. Hetereocycles 2000,
53, 475 and references cited therein.
12. Marasco, J.-P.; Garapon, J.; Sillion, B. Polym. Bull. 1995,
35, 285.
21. Balasubramaniyan, V.; Argade, N. P. Tetrahedron 1989, 45,
835 and references cited therein.
13. (a) Mochizuki, A.; Teranishi, T.; Ueda, M. Polym. Prepr.
1994, 35, 371. (b) Kasai, T. Jpn. Kokai Tokkyo Koho JP A2 7,
1994; Chem. Abstr. 1995, 122, 163013.
22. Ganin, E. V. Chem. Heterocycl. Compd. 1998, 33, 1092.
23. Ganin, E. V. Ukr. Khim. Zh. 1997, 63, 39.
14. Domeier, L. A.; Clark, E. M. Eur. Pat. Appl. Ep 277013 A1 6,
1988; Chem. Abstr. 1989, 110, 76676.
24. (a) McCormack, M. T.; Hegarty, A. F. J. Chem. Soc., Perkin
Trans. 2 1976, 1701. (b) Kehrbach, W.; Alexandrou, N. E.
J. Heterocycl. Chem. 1978, 15, 1255. (c) Hegarty, A. F.;
Tynan, N. M.; Fergus, S. J. Chem. Soc., Perkin Trans. 2 2002,
1328 and references cited therein 24a–c.
15. Nagarathinam, R.; Viswanathan, S. Polym. Bull. 1986, 16, 147.
16. Kirino, O.; Rubin, B.; Casida, J. E. Agric. Biol. Chem. 1985,
49, 267.