Synthesis of N-substituted 2,3-dichlorobicyclo[2.2.2]oct-5-ene-2,3- dicarboxylic acid imides

Full text of DOI:10.1134/S1070428012030256

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 3, pp. 469–472. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © Ya.M. Nagiev, 2012, published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48, No. 3, pp. 467–469.
SHORT
COMMUNICATIONS
Synthesis of N-Substituted 2,3-Dichlorobicyclo[2.2.2]oct-
5-ene-2,3-dicarboxylic Acid Imides
Ya. M. Nagiev
Nagiev Institute of Chemical Problems, National Academy of Sciences of Azerbaijan,
pr. G. Dzhavida 29, Baku, Az-1143 Azerbaijan
e-mail: yaqubnaghiyev@yahoo.com
Received December 27, 2010
DOI: 10.1134/S1070428012030256
Compounds of the norbornene series containing
side-chain functional groups possess various useful
properties, in particular biological and physiological
activity [1–4]. Norbornene derivatives have become
more accessible as a result of improvement of proce-
dures for Diels–Alder reaction.
1630, 985–900, 835–760, and 755–730 cm–1, which
are typical of stretching and bending vibrations of
C=O, C–N, C=C, C6H4, and C–Cl groups.
Molecules IIIa–IIIl possess four electron-with-
drawing groups at the double bond, which make them
highly reactive as dienophiles toward electron-donor
1,3-cyclohexadiene. The reactions were carried out at
50–100°C (7–12 h) at a diene-to-dienophile ratio of
1 :(1–2). The effect of temperature on the yield of
Diels–Alder adducts was studied in the reaction with
imide IIId as an example. The yield of IVd increased
from 65 to 90% as the temperature rose from 50 to
80°C. Further raising the temperature to 100°C led to
reduced yield. Thus the optimal conditions were reac-
tant ratio 1:1, temperature 80°C, and reaction time 5 h.
We previously studied the Diels–Alder reaction of
N-substituted dichloromaleimides with cyclopenta-
diene [2, 5–7], which led to the formation of bicyclic
adducts, and examined the structure and properties of
the products, as well as some general relations holding
in this reaction. In continuation of studies in this line,
the present communication reports on the Diels–Alder
reaction of N-substituted dichloromaleimides with
1,3-cyclohexadiene.
N-Substituted dichloromaleimides IIIa–IIIl were
synthesized by reaction of dichloromaleic anhydride
with primary amines in glacial acetic acid on heating.
The reaction occurred in two steps with initial forma-
tion of amido acid A [8] which then underwent cy-
clization to imide III.
Under these conditions, [4+2]-cycloaddition of
1,3-cyclohexadiene to other N-substituted dichloro-
maleimides IIIa–IIIl gave norbornene imides IVa–
IVl. Compounds IVa–IVl were isolated as crystalline
substances in 70–95% yield; the highest yield was
observed for imide IVj (95%), and the lowest, for
2,3-dichloro-N-(4-methylphenyl)bicyclo[2.2.2]oct-5-
ene-2,3-dicarboximide (IVl) (71%).
The structure of imides IIIa–IIIl was confirmed by
1
elemental analysis and IR and H NMR spectroscopy.
The IR spectra of IIIa–IIIl contained strong absorp-
Compounds IVa–IVl in the IR spectra displayed
tion bands in the regions 1750–1705, 1380–1330,
absorption bands in the regions 2955–2885 (=CH),
O
O
O
Cl
O
NHR
Cl
Cl
Cl
Cl
Cl
O
O
+ RNH2
N
R
N
R
–H2O
HO
Cl
Cl
O
O
O
I
IIa–IIl
A
IIIa–IIIl
IVa–IVl
R = H (ą), Ph (b), cyclo-C6H11 (c), 3-O2NC6H4 (d), 4-O2NC6H4 (e), 3,4-Cl2C6H3 (f), 4-BrC6H4 (g), 3-BrC6H4 (h), 4-MeOC6H4 (i),
ClC(O)CH2 (j), 2,5-Cl2C6H3 (k), 4-MeC6H4 (l).
469

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470
1790–1730 (C=O), and 745–745 cm–1 (C–Cl); the
presence of absorption bands in the regions 3040–3020
and 720–690 cm–1 [ν(=C–H)] indicated that molecules
C 41.85; H 1.42; Cl 24.77; N 9.81. C10H4Cl2N2O4. Cal-
culated, %: C 41.81; H 1.39; Cl 24.74; N 9.76.
2,3-Dichloro-N-(3,4-dichlorophenyl)maleimide
(IIIf). Yield 80%, mp 202–204°C. IR spectrum, ν,
cm–1: 1750–1705 (C=O), 1640 (C=C), 1330 (C–N),
835 (C6H3), 733 (C–Cl). Found, %: C 38.52; H 0.89;
Cl 45.59; N 4.58. C10H3Cl4NO2. Calculated, %:
C 38.59; H 0.97; Cl 45.66; N 4.50.
1
IV contained a strained double bond. In the H NMR
spectrum of imide IVa, protons in the six-membered
ring of the norbornene fragment appeared as an AA′XX′
spin system, δ 3.17 (1-H, 4-H) and 6.34 ppm (5-H,
6-H). Protons in the ethylene bridge gave rise to
an AA′BB′ spin system, δ 1.42, 2.14 ppm, 2JAB = 2JA′B′
=
N-(4-Bromophenyl)-2,3-dichloromaleimide
(IIIg). Yield 90%, mp 230–232°C. IR spectrum, ν,
cm–1: 1750–1705 (C=O), 1640 (C=C), 1335 (C–N), 830
(C6H4), 735 (C–Cl), 640 (C–Br). Found, %: C 37.47;
H 1.29; N 4.42. C10H4BrCl2NO2. Calculated, %:
C 37.38; H 1.25; N 4.36.
10.1 Hz. The NH proton resonated at δ 2.99 ppm. The
13C NMR spectrum of adduct IVa [δC, ppm: 163.35
(C=O), 133.80 (C5, C6), 70.94 (C2, C3), 40.72 (C1, C4),
18.65 (C7, C8)] also confirmed the assumed structure.
N-Substituted 2,3-dichloromaleimides IIIa–IIIl
(general procedure). 2,3-Dichloromaleic anhydride,
16.7 g (0.1 mol), was dispersed in 60 g of glacial acetic
acid, 0.1 mol of the corresponding amine was added
dropwise, and the mixture was stirred for 30 min at
85°C and for 90 min at 108°C. The mixture was then
cooled to 10°C under stirring, and the precipitate was
filtered off, washed with water, and dried under
reduced pressure at 60°C.
N-(3-Bromophenyl)-2,3-dichloromaleimide
(IIIh). Yield 88%, mp 167–169°C. IR spectrum, ν,
cm–1: 1750–1705 (C=O), 1642 (C=C), 1330 (C–N),
835 (C6H4), 734 (C–Cl), 638 (C–Br). Found, %:
C 37.15; H 1.22; N 4.31. C10H4BrCl2NO2. Calculated,
%: C 37.38; H 1.25; N 4.36.
2,3-Dichloro-N-(4-methoxyphenyl)maleimide
(IIIi). Yield 77%, mp 209–210°C. IR spectrum, ν,
cm–1: 1755 (C=O), 1650 (C=C), 1340 (C–N), 1150
(C–O), 834 (C6H4), 735 (C–Cl). Found, %: C 48.49;
H 2.61; Cl 26.19; N 5.11. C11H7Cl2NO3. Calculated,
%: C 48.53; H 2.57; Cl 26.10; N 5.15.
2,3-Dichloromaleimide (IIIa). Yield 20%, mp 180–
182°C. IR spectrum, ν, cm–1: 1745–1700 (C=O), 1640,
820 (C=C), 1380 (C–N), 738 (C–Cl). Found, %:
C 28.53; H 0.71; Cl 42.75; N 8.41. C4HCl2NO2. Cal-
culated, %: C 28.92; H 0.6; Cl 42.77; N 8.43.
(3,4-Dichloro-2,5-dioxo-2,5-dihydro-1H-pyrrol-
1-yl)acetyl chloride (IIIj). Yield 50%, mp 93–95°C.
IR spectrum, ν, cm–1: 1750–1705 (C=O), 1640 (C=C),
1400 (C–H), 1380 (C–N), 737 (C–Cl). Found, %:
C 29.73; H 0.79; Cl 43.96; N 5.81. C6H2Cl3NO3. Cal-
culated, %: C 26.69; H 0.83; Cl 43.92; N 5.77.
2,3-Dichloro-N-phenylmaleimide (IIIb). Yield
80%, mp 205–206°C. IR spectrum, ν, cm–1: 1750–
1705 (C=O), 1640 (C=C), 1380–1330 (C–N), 1536
(C=Carom), 738 (C–Cl). Found, %: C 49.62; H 2.10;
Cl 29.26; N 5.85. C10H5Cl2NO2. Calculated, %:
C 49.59; H 2.07; Cl 29.34; N 5.79.
2,3-Dichloro-N-(2,5-dichlorophenyl)maleimide
(IIIk). Yield 83%, mp 205–206°C. IR spectrum, ν,
cm–1: 1755–1710 (C=O), 1642 (C=C), 1340 (C–N),
835 (C6H3), 739 (C–Cl). Found, %: C 38.57; H 0.91;
Cl 45.79; N 4.56. C10H3Cl4NO2. Calculated, %:
C 38.59; H 0.97; Cl 45.66; N 4.50.
2,3-Dichloro-N-cyclohexylmaleimide (IIIc). Yield
42%, mp 139–140°C. IR spectrum, ν, cm–1: 1755–
1710 (C=O), 1645 (C=C), 1630 (C6H11), 1380–1330
(C–N), 738 (C–Cl). Found, %: C 48.36; H 4.40;
Cl 28.67; N 5.69. C10H11Cl2NO2. Calculated, %:
C 48.39; H 4.44; Cl 22.63; N 5.65.
2,3-Dichloro-N-(4-methylphenyl)maleimide
(IIIl). Yield 70%, mp 191–192°C. IR spectrum, ν,
cm–1: 1750–1703 (C=O), 1640 (C=C), 1338 (C–N),
840 (C6H4), 735 (C–Cl). Found, %: C 51.51; H 2.77;
Cl 27.69; N 5.41. C11H7Cl2NO2. Calculated, %:
C 51.66; H 2.73; Cl 27.73; N 5.47.
2,3-Dichloro-N-(3-nitrophenyl)maleimide (IIId).
Yield 90%, mp 203–205°C. IR spectrum, ν, cm–1:
1750–1710 (C=O), 1640, 820 (C=C), 1358–1330
(C–N), 1150 (NO2), 835 (C6H4), 740 (C–Cl). Found,
%: C 41.82; H 1.36; Cl 24.80; N 9.69. C10H4Cl2N2O4.
Calculated, %: C 41.81; H 1.39; Cl 24.74; N 9.76.
2,3-Dichloro-N-phenylbicyclo[2.2.2]oct-5-ene-
2,3-dicarboximide (IVb). A solution of 0.484 g
(2 mmol) of imide IIIb in 10 ml of toluene was heated
to 80°C, a solution of 0.16 g (2 mmol) of cyclohexa-
1,3-diene in 5 ml of toluene was added dropwise over
2,3-Dichloro-N-(4-nitrophenyl)maleimide (IIIe).
Yield 92%, mp 193–194°C. IR spectrum, ν, cm–1:
1750–1720 (C=O), 1645, 830 (C=C), 1358 (C–N),
1150–1120 (NO2), 840 (C6H4), 742 (C–Cl). Found, %:
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 3 2012

SYNTHESIS OF N-SUBSTITUTED 2,3-DICHLOROBICYCLO[2.2.2]OCT-5-ENE-...
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1
a period of 10 min, and the mixture was heated for
5.5 h at 80°C and evaporated on a water bath. The
residue was recrystallized from benzene–hexane (1:1)
and dried at 80°C. Yield 0.579 g (90%), white crystals,
mp 189–191°C; compound IVb is readily soluble in
(88%), mp 178–180°C. H NMR spectrum, δ, ppm:
1.32–1.88 m (2H, 7-H, 8-H), 2.81 m (2H, 1-H, 4-H),
5.51 m (2H, 5-H, 6-H), 6.55–7.50 m (4H, C6H4).
Found, %: C 47.95; H 3.01; Cl 17.87; N 3.36.
C16H12BrCl2NO2. Calculated, %: C 47.88; H 2.99;
Cl 17.76; N 3.49.
1
toluene, benzene, and DMF. H NMR spectrum, δ,
ppm: 1.30–2.88 m (2H, 7-H, 8-H), 2.80 m (2H, 1-H,
4-H), 5.55 m (2H, 5-H, 6-H), 6.88 m (5H, Ph). Found,
%: C 59.59; H 4.05; Cl 22.08; N 4.39. C16H13Cl2NO2.
Calculated, %: C 59.62; H 4.04; Cl 22.05; N 4.35.
N-(3-Bromophenyl)-2,3-dichlorobicyclo[2.2.2]-
oct-5-ene-2,3-dicarboximide (IVh). Yield 32.48 g
(81%), mp 174–176°C. H NMR spectrum, δ, ppm:
1.28–1.91 m (2H, 7-H, 8-H), 2.85 m (2H, 1-H, 4-H),
5.54 m (2H, 5-H, 6-H), 6.55–7.51 m (4H, C6H4).
Found, %: C 47.97; H 3.04; Cl 17.82; N 3.42.
C16H12BrCl2NO2. Calculated, %: C 47.88; H 2.99;
Cl 17.76; N 3.49.
1
Compounds IVa and IVc–IVl were synthesized in
a similar way.
2,3-Dichlorobicyclo[2.2.2]oct-5-ene-2,3-dicarbox-
imide (IVa). Yield 0.344 g (70%), mp 148–150°C. The
spectral parameters of compound IVa are given in text.
Found, %: C 48.79; H 3.62; Cl 28.88; N 5.66.
C10H9Cl2NO2. Calculated, %: C 48.78; H 3.66;
Cl 28.96; N 5.69.
2,3-Dichloro-N-(4-methoxyphenyl)bicyclo[2.2.2]-
oct-5-ene-2,3-dicarboximide (IVi). Yield 26.05 g
1
(74%), mp 167–169°C. H NMR spectrum, δ, ppm:
1.44–1.98 m (2H, 7-H, 8-H), 2.84 m (2H, 1-H, 4-H),
5.51 m (2H, 5-H, 6-H), 3.07 m (3H, OCH3), 6.54–
6.78 m (4H, C6H4). Found, %: C 58.02; H 4.13;
Cl 20.32; N 3.82. C16H15Cl2NO3. Calculated, %:
C 57.95; H 4.26; Cl 20.17; N 3.98.
2,3-Dichloro-N-cyclohexylbicyclo[2.2.2]oct-5-
ene-2,3-dicarboximide (IVc). Yield 23.54 g (72%),
1
mp 118–120°C. H NMR spectrum, δ, ppm: 1.31–
1.91 m (2H, 7-H, 8-H), 2.79 m (2H, 1-H, 4-H), 5.57 m
(2H, 5-H, 6-H), 1.25 m (11H, cyclo-C6H11). Found, %:
C 58.71; H 5.52; Cl 21.77; N 4.24. C16H19Cl2NO2.
Calculated, %: C 58.72; H 5.50; Cl 21.71; N 4.28.
(3a,7a-Dichloro-1,3-dioxo-1,3,3a,4,7,7a-hexahy-
dro-2H-4,7-ethanoisoindol-2-yl)acetyl chloride
(IVj). Yield 30.64 g (95%), mp 220°C (decomp.).
1H NMR spectrum, δ, ppm: 2.11–2.40 m (2H, 7-H,
8-H), 3.31 m (2H, 1-H, 4-H), 6.45 m (2H, 5-H, 6-H),
4.14 m (2H, CH2). Found, %: C 44.72; H 3.29;
Cl 33.19; N 4.22. C12H10Cl3NO3. Calculated, %:
C 44.65; H 3.10; Cl 33.02; N 4.34.
2,3-Dichloro-N-(3-nitrophenyl)bicyclo[2.2.2]oct-
5-ene-2,3-dicarboximide (IVd). Yield 33.03 g (90%),
1
mp 179–181°C. NMR spectrum N, δ, ppm: 1.31–
1.90 m (2H, 7-H, 8-H), 2.81 m (2H, 1-H, 4-H), 5.51 m
(2H, 5-H, 6-H), 6.54–7.40 m (4H, C6H4). Found, %:
C 52.29; H 3.30; Cl 19.42; N 7.65. C16H12Cl2N2O4.
Calculated, %: C 52.32; H 3.27; Cl 19.35; N 7.63.
2,3-Dichloro-N-(2,5-dichlorophenyl)bicyclo-
[2.2.2]oct-5-ene-2,3-dicarboximide (IVk). Yield
1
34.01 g (87%), mp 150–152°C. H NMR spectrum, δ,
2,3-Dichloro-N-(4-nitrophenyl)bicyclo[2.2.2]oct-
5-ene-2,3-dicarboximide (IVe). Yield 33.76 g (92%),
ppm: 1.31–2.05 m (2H, 7-H, 8-H), 2.72 m (2H, 1-H,
4-H), 5.57 m (2H, 5-H, 6-H), 6.57–7.38 m (3H, C6H3).
Found, %: C 49.71; H 2.92; Cl 36.84; N 3.61.
C16H11Cl4NO2. Calculated, %: C 49.10; H 2.81;
Cl 36.84; N 3.58.
1
mp 185–187°C. H NMR spectrum, δ, ppm: 1.35–
1.87 m (2H, 7-H, 8-H), 2.76 m (2H, 1-H, 4-H), 5.42 m
(2H, 5-H, 6-H), 6.54–7.51 m (4H, C6H4). Found, %:
C 52.42; H 3.18; Cl 19.29; N 7.87. C16H12Cl2N2O4.
Calculated, %: C 52.32; H 3.27; Cl 19.35; N 7.63.
2,3-Dichloro-N-(4-methylphenyl)bicyclo[2.2.2]-
oct-5-ene-2,3-dicarboximide (IVl). Yield 23.86 g
1
2,3-Dichloro-N-(3,4-dichlorophenyl)bicyclo-
[2.2.2]oct-5-ene-2,3-dicarboximide (IVf). Yield
(71%), mp 169–171°C. H NMR spectrum, δ, ppm:
1.37–1.94 m (2H, 7-H, 8-H), 2.83 m (2H, 1-H, 4-H),
5.49 m (2H, 5-H, 6-H), 1.89 m (3H, CH3), 6.79–
7.04 m (4H, C6H4). Found, %: C 61.11; H 4.44;
Cl 21.32; N 4.23. C17H15Cl2NO2. Calculated, %:
C 60.71; H 4.46; Cl 21.13; N 4.17.
1
34.4 g (88%), mp 167–169°C. H NMR spectrum, δ,
ppm: 1.05–1.97 m (2H, 7-H, 8-H), 2.79 m (2H, 1-H,
4-H), 5.64 m (2H, 5-H, 6-H), 6.31–6.72 m (3H, C6H3).
Found, %: C 49.76; H 2.98; Cl 36.85; N 3.59.
C16H11Cl4NO2. Calculated, %: C 49.10; H 2.81;
Cl 36.72; N 3.58.
The IR spectra were recorded in KBr on a Specord
M-80 spectrometer. The NMR spectra were measured
1
N-(4-Bromophenyl)-2,3-dichlorobicyclo[2.2.2]-
oct-5-ene-2,3-dicarboximide (IVg). Yield 33.28 g
on Tesla BS-487 (80 MHz, H) and Bruker WM-400
1
spectrometers (400 MHz for H and 100.6 MHz for
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 3 2012

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13C) from solutions in C6D6 and (CD3)2C=O using
TMS and HMDS as internal references. The initial
reagents and solvents were prepared according to the
procedures described in [2, 9].
4. Motsarev, G.V. and Moskovtsev, V.V., Khim. Promst.,
1981, p. 465.
5. Nagiev, Ya.M., Farzaliev, V.M., Bagirov, Sh.T., Orud-
zheva, A.A., and Faradzhov, G.M., Azerb. Khim. Zh.,
2006, no. 3, p. 38.
6. Nagiev, Ya.M. and Adigezalov, V.A., Khim. Probl., 2007,
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