Synthesis of N-substituted imides of 2,3-dichlorobicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic Acid

Full text of DOI:10.1134/S1070428015080217

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2015, Vol. 51, No. 8, pp. 1183–1186. © Pleiades Publishing, Ltd., 2015.
Original Russian Text © Ya.M. Nagiev, 2015, published in Zhurnal Organicheskoi Khimii, 2015, Vol. 51, No. 8, pp. 1202–1205.
SHORT
COMMUNICATIONS
Synthesis of N-Substituted Imides
of 2,3-Dichlorobicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic Acid
Ya. M. Nagiev
Nagiev Institute of Chemical Problems, National Academy of Sciences of Azerbaijan,
pr. G. Dzhavida 29, Baku, Az1143 Azerbaijan
e-mail: yaqub56@mail.ru
Received January 30, 2013
DOI: 10.1134/S1070428015080217
Compounds of bicyclo[2.2.1]hept- and -[2.2.2]oct-
5-ene series containing functional groups in the side
chain possess various biological and physiological activi-
ty [1–6]. Accessibility of norbornene derivatives increased
as a result of improvement of Diels-Adler reactions and
the preparation from cyclopentadiene. Previously we
investigated the diene condensation of N-substituted
imides of dichloromaleic acid with cyclopentadiene and
1,3-cyclohexadiene [7–11] resulting in generation of
bicyclic adducts. The composition and properties of ob-
tained compounds, as well as some pattern of the reac-
tion course, were investigated. In this study the research
in this direction is extended and the results of the inves-
tigation of diene condensation of dichloromaleic acid N-
substituted imides with cyclopentadiene are reported.
In IR spectrum of compounds 3а–3k strong
absorption bands of stretching and bending vibrations
are present at 1750–1705, 1380–1330, 1630, 985–900,
835–760, 755–730 cm–1, typical of С=О, С–N, C=C,
C6H4, C–Cl groups. Dichloromaleimides contain at the
double bond four electrophilic groups having therefore
a high reactivity in the diene synthesis with electron-
donor cyclopentadiene which results in the formation
of norbornene imides 5а–5k.
Using cyclopentadiene in diene reactions allows
attenuating the strain in the obtained bicycloalkenes
and hence changing the activity of double carbon-
carbon bond in adducts. Reactions of cyclopentadiene
with imides of dichloromaleic acid proceed according
to Scheme 2.
N-Substituted imides of dichloromaleic acid were
synthesized from primary amines and dichloromaleic
anhydride in glacial acetic acid at heating. Reactions
occur in two stages with generation of amidoacid A
[12, 13] in the first stage followed by its cyclization in
imide under the reaction conditions (Scheme 1).
The obtained compounds 5а–5k are solid crystal-
line substances. Their composition and structure were
confirmed by IR, 1Н NMR spectroscopy and elemental
analysis data.
Adducts 5а–5k contain a multiple carbon-carbon
bond С=С capable to react with electrophilic reagents;
by changing the structure of diene component it is
possible to control the reactivity of this double bond.
Composition and structure of the synthesized
1
imides were confirmed by IR and Н NMR spectro-
scopy and the data of elemental analysis.
Scheme 1.
O
O
Cl
Cl
Cl
Cl
Cl
C
C
COOH
Δ
_H2O
N
O
R
+
H2N
R
O
O
C
O
N
H
R
Cl
2a_2k
A
1
3a_3k
R = Ph (a), m-ClC6H4 (b), p-ClC6H4 (c), CH2COОН (d), m-NO2C6H4 (e), Н (f), CH2COCl (g), cyclo-C6H11 (h),
СН2СН(СN)СН3 (i), m-МeC6H4 (j), 2,4-(NO2)2С6Н3 (k).
1183

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the downfield area (7.19, 7.46 ppm) of the spectrum
1184
Scheme 2.
O
N
there are multiplet resonance signals corresponding the
Cl
O
Cl
Cl
five-spin АА'/ВВ'С system of aromatic protons.
R
+
N
O
R
13С NMR spectrum of adduct 5а [δ 170.38 (С8,9),
136.90 (2Cm), 129.80 (С11), 126.34 (Со), 73.32 (С2,3),
55.75 (С1,4), 50.39 (С7) ppm] also confirms its struc-
ture С15H11Cl2NO2.
Cl
O
3a_3k
4
5a_5k
N-Substituted imides of dichloromaleic acid (3e–
3h) [10]. To suspension of 16.7 g (0.1 mol) of dichlo-
romaleic anhydride in 60 g of glacial acetic acid was
added dropwise 0.1 mol of the corresponding amine.
The mixture was stirred for 30 min at 85°С and for 90
min at 108°С. Then the mixture was cooled while
stirred to 10°С, the precipitate was filtered off, washed
with water, and dried in a vacuum at 60°С.
For example, in the reactions of cyclopentadiene with
imides of dichloromaleic acid the formed bicycle-
heptene structure is more strained and the reactivity of
carbon-carbon bond in this system is higher [14, 15].
Reactions were carried out at 10–50°С during 3–5 h
at molar ratio of diene–dienophile 1 : 0.25–1 : 1.75.
Effect of the temperature on the yield was investigated
by an example of adduct 5e. At raising temperature
from 10 to 40°С the yield grew from 57 to 94%.
Raising the temperature further to 50°С results in
lowering of the adduct 5e yield due to the growing
yield of cyclopentadiene dimer.
N-Phenylimide of dichloromaleic acid (3a). Yield
81%, mp 205–206°С. IR spectrum, ν, cm–1: 1750–
1705 (С=О), 1640 (С=С), 1380–1330 (=N–), 1536
(С6Н5), 735 (С–Cl). Found, %: С 49.62; Н 2.10; Cl
29.26; N 5.85. С15H11Cl2NO2. Calculated, %: С 49.59;
Н 2.07; Сl 29.34; N 5.79.
Optimal temperature for preparation of adduct 5e is
40°С, time of the reaction 4 h, ratio diene–dienophile
1 : 1.25.
N-(m-Chlorophenyl)imide of dichloromaleic acid
(3b). Yield 90%, mp 179–191°С. IR spectrum, ν, cm–1:
1750–1705 (С=О), 1641 (С=С), 1330 (=N–), 835
(С6Н5), 735 (С–Cl). Found, %: С 43.42; Н 1.29; Cl
38.49; N 5.11. С10H4Cl3NO2. Calculated, %: С 43.40;
Н 1.45; Сl 38.52; N 5.06.
In similar conditions the reaction of [4+2]-cyclo-
addition of cyclopentadiene to the other substituted
imides of dichloromaleic acid 3а–3k was carried out.
Yield of adducts 5а–5k varies in the limits 78–97%,
where the highest yield is observed for compound 5g
(97%), and the lowest, for m-methylphenylimide of
2,3-dichlorobicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic
acid 5j (78%). By physicochemical characteristics
compounds 5а–5k are similar to each other, their
molecules have endo-configuration [16].
N-(p-Chlorophenyl)imide of dichloromaleic acid
(3c). Yield 92%, mp 207–209°С. IR spectrum, ν, cm–1:
1745–1705 (С=О), 1642 (С=С), 1336 (=N–), 832
(С6Н5), 737 (С–Cl). Found, %: С 43.45; Н 1.48; Cl
38.57; N 5.09. С10H4Cl3NO2. Calculated, %: С 43.40;
Н 1.45; Сl 38.52; N 5.06.
In the IR spectra of compounds 5а–5k there are
absorption bands in the region 2955–2885 (=СН),
1790–1730 (С=О), and 745–735 cm–1 (С–Cl). The
absorption bands in the region 3040–3020 (=C–H) and
720–690 cm–1 (=C–H) show the presence of a strained
double bond in the molecules.
(2,5-Dioxo-3,4-dichloro-2,5-dihydro-1Н-pyrrol-
1-yl)acetic acid (N-carboxymethylimide of dichloro-
maleic acid) (3d). Yield 75%, mp 195–196°С. IR
spectrum, ν, cm–1: 1750–1700 (С=О), 1643 (С=С),
1339 (=N–), 735 (С–Cl). Found, %: С 32.21; Н 1.39;
Cl 31.75; N 6.28. С6H3Cl2NO4. Calculated, %: С
32.14; Н 1.34; Сl 31.70; N 6.25.
1
In the Н NMR spectrum of imide 5а protons of
six-membered cycle of the norbornene fragment form
the spin system АА'ХХ', where А and А' are protons Н1,4
(δ 3.55 ppm), and Х and Х' are protons Н5,6 (δ 6.39 ppm).
Bridging methylene protons are nonequivalent and
appear in 1Н NMR as an АВ system, δ(НА) 2.23, δ(НВ)
3-(2,5-Dioxo-3,4-dichloro-2,5-dihydro-1Н-pyr-
rol-1-yl)-2-methylpropionitrile [N-(2-cyanopropyl)
imide of dichloromaleic acid] (3i). Yield 85%, mp
110–111°С. IR spectrum, ν, cm–1: 2250 (СN), 1735
2
1
2.59 ppm, JАВ 9.6 Hz. Each component of АВ spec-
(С=О), 1644 (С=С), 1340 (=N–), 732 (С–Cl). Н
trum has additional fine structure due to the spin-spin
NMR spectrum, δ, ppm: 1.25 m (3Н), 2.65 m (2Н),
2.20 m (1Н). Found, %: С 41.34; Н 2.46; Cl 30.52; N
coupling of the bridging protons with protons Н1,4–6. In
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 8 2015

SYNTHESIS OF N-SUBSTITUTED IMIDES OF 2,3-DICHLOROBICYCLO[2.2.1]HEPT...
1185
12.19. С8H6Cl2N2O2. Calculated, %: С 41.21; Н 2.57;
Сl 30.47; N 12.02.
(3,5-Dioxo-2,6-dichloro-4-azatricyclo-[5.2.1.02,6]-
dec-8-en-4-yl)acetic acid (N-carboxymethylimide of
2,3-dichlorobicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic
acid) (5d). Yield 0.557 g (96%), mp 173–175°С. 1Н NMR
spectrum, δ, ppm: 2.08 m (1Н, НА), 2.40 m (1Н, НВ),
3.50 m (2Н, Н1,4), 6.18 m (2Н, Н5,6), 4.12 m (2Н, СН2).
Found, %: С 45.54; Н 3.08; Cl 24.46; N 4.81. C11Н9Сl2·
NO4. Calculated, %: С 45.52; Н 3.10; Cl 24.48; N 4.83.
N-(m-Methylphenyl)imide of dichloromaleic acid
(3j). Yield 78%, mp 87–89°С. IR spectrum, ν, cm–1:
1750–1709 (С=О), 1642 (С=С), 1339 (=N–), 842
(С6Н5), 736 (С–Cl). Found, %: С 42.51; Н 1.22; Cl
22.96; N 4.61. С11H7Cl2NO2. Calculated, %: С 42.58;
Н 1.29; Сl 22.90; N 4.52.
N-(m-Nitrophenyl)imide of 2,3-dichlorobicyclo-
[2.2.1]hept-5-ene-2,3-dicarboxylic acid (5e). Yield
N-(2,4-Dinitrophenyl)imide of dichloromaleic
acid (3k). Yield 93%, mp 188–190°С. IR spectrum, ν,
cm–1: 1751–1712 (С=О), 1645, 825 (С=С), 1354 (=N–),
1
0.788 g (94%), mp 197–199°С. Н NMR spectrum, δ,
ppm: 1.31 m (1Н, НА), 2.04 m (1Н, НВ), 2.84 m (2Н,
Н1,4), 5.41 m (2Н, Н5,6), 6.54–7.41 m (4Н, С6Н4). Found,
%: С 51.52; Н 2.93; Cl 19.89; N 7.99. C15Н10Сl2N2O4.
Calculated, %: С 50.99; Н 2.83; Cl 20.93; N 7.99.
1
1150–1120 (N=O), 838 (С6Н4), 743 (С–Cl). Н NMR
spectrum, δ, ppm: 1.25 m (3Н), 2.65 m (2Н), 2.20 m
(1Н). Found, %: С 36.19; Н 0.88; Cl 21.45; N 12.61.
С10H3Cl2N3O6. Calculated, %: С 36.14; Н 0.91; Сl
21.39; N 12.65.
Imide of 2,3-dichlorobicyclo[2.2.1]hept-5-ene-
2,3-dicarboxylic acid (5f). Yield 0.371 g (80%), mp
N-Phenylimide of 2,3-dichlorobicyclo[2.2.1]hept-
5-ene-2,3-dicarboxylic acid (5а). To a solution of
0.484 g (2 mmol) of imide 3а in 10 mL of benzene at
40°С during 15 min was added dropwise a solution of
0.165 g (2.5 mmol) of just distilled cyclopentadiene in
3 mL of benzene, the mixture was maintained for 4 h
and evaporated on a water bath. The precipitate was
recrystallized from a mixture benzene–hexane, 1 : 1,
dried at 90°С. Yield 0.524 g (85%). Colorless powder,
stable, nonhygroscopic, nonexplosive, well soluble in
dimethylformamide, dioxane, benzene, toluene, N-
methylpyrrolidine, acetone, mp 204–206°С. IR spec-
trum, ν, cm–1: 3060, 740, 705 (С–Н); 2950, 2880 (С–Н);
2875, 2745 (=N–); 1790, 1730 (С=О); 1640 (С=С);
1600, 1495 (С6Н4); 745 (С–Cl). Found, %: С 49.62; Н
2.10; Cl 29.26; N 5.85. С15H11Cl2NO2. Calculated, %:
С 49.59; Н 2.07; Сl 29.34; N 5.79.
1
167–169°С. Н NMR spectrum, δ, ppm: 2.10 m (1Н,
НА), 2.41 m (1Н, НВ), 3.48 m (2Н, Н1,4), 6.45 m (2Н,
Н5,6), 3.01 m (1Н, NН). Found, %: С 46.49; Н 3.07; Cl
30.55; N 6.22. C9Н7Сl2NO2. Calculated, %: С 45.56; Н
3.02; Cl 30.60; N 6.04.
(3,5-Dioxo-2,6-dichloro-4-azatricyclo-[5.2.1.02,6]-
dec-8-en-4-yl)acetylchloride (N-chlorocarbonylme-
thylimide of 2,3-dichlorobicyclo[2.2.1]-hept-5-ene-
2,3-dicarboxylic acid) (5g). Yield 0.63 g (97%), mp
1
230°С (decomp.). Н NMR spectrum, δ, ppm: 2.09 m
(1Н, НА), 2.43 m (1Н, НВ), 3.35 m (2Н, Н1,4), 6.43 m
(2Н, Н5,6), 4.15 m (2Н, СН2). Found, %: С 42.54; Н
2.66; Cl 34.42; N 4.72. C11Н8Сl3NO3. Calculated, %:
С 42.79; Н 2.59; Cl 34.62; N 4.54.
N-Cyclohexylimide of 2,3-dichlorobicyclo[2.2.1]-
hept-5-ene-2,3-dicarboxylic acid (5h). Yield 0.496 g
1
N-(m-Chlorophenyl)imide of 2,3-dichlorobicyc-
lo-[2.2.1]hept-5-ene-2,3-dicarboxylic acid (5b).
(79%), mp 182–184°С. Н NMR spectrum, δ, ppm:
1.30 m (1Н, НА), 2.01 m (1Н, НВ), 2.90 m (2Н, Н1,4),
5.54 m (2Н, Н5,6), 1.24 m (11Н, С6Н11). Found, %: С
57.26; Н 4.99; Cl 22.73; N 4.22. C15Н17Сl2NO2.
Calculated, %: С 57.33; Н 5.41; Cl 22.61; N 4.46.
1
Yield 0.594 g (87%), mp 197–199°С. Н NMR spec-
trum, δ, ppm: 1.31 m (1Н, НА), 2.02 m (1Н, НВ), 2.87
m (2Н, Н1,4), 5.49 m (2Н, Н5,6), 6.56–7.43 m (4Н,
С6Н4). Found, %: С 52.59; Н 2.99; Cl 31.01; N 4.06.
C15Н10Сl3NO2. Calculated, %: С 52.63; Н 2.92; Cl
31.10; N 4.09.
3-(3,5-Dioxo-2,6-dichloro-4-azatricyclo-[5.2.1.02,6]-
dec-8-en-4-yl)-2-methylpropionitrile [N-(2-cyano-
propyl)imide of 2,3-dichlorobicyclo-[2.2.1]hept-5-
ene-2,3-dicarboxylic acid] (5i). Yield 0.538 g (90%),
N-(p-Chlorophenyl)imide of 2,3-dichlorobicyclo-
[2.2.1]hept-5-ene-2,3-dicarboxylic acid (5c). Yield
0.61 g (89%), mp 199–201°С. 1Н NMR spectrum, δ, ppm:
1.32 m (1Н, НА), 2.04 m (1Н, НВ), 2.85 m (2Н, Н1,4),
5.47 m (2Н, Н5,6), 6.58–7.44 m (4Н, С6Н4). Found, %:
С 52.55; Н 2.97; Cl 31.04; N 4.03. C15Н10Сl3NO2.
Calculated, %: С 52.63; Н 2.92; Cl 31.10; N 4.09.
1
mp 130–131°С. Н NMR spectrum, δ, ppm: 2.05 m
(1Н, НА), 2.45 m (1Н, НВ), 3.32 m (2Н, Н1,4), 6.32 m
(2Н, Н5,6), 1.25 m (3Н, СН3), 2.20 m (1Н, СН), 2.61 m
(2Н, СН2). Found, %: С 52.23; Н 4.32; Cl 23.59; N
9.46. C13Н12Сl2N2O2. Calculated, %: С 52.17; Н 4.01;
Cl 23.74; N 9.36.
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NAGIEV
1186
4. Mamedov, E.G., Ayubov, I.G., Mamedova, G.F.,
N-(m-Methylphenyl)imide of 2,3-dichlorobicyclo-
Gadzhiev, O.B., and Nagiev, A.V., Azerb. Khim. Zh.,
2006, p. 52.
5. Mamedbeili (Mamedov), E.G., Kyazimova, T.G.,
Nagiev, Z.M., Abdiev, O.B., and Aliev, K.A., Russ.
J. Org. Chem., 2009, vol. 45, p. 74.
6. Motsarev, G.V. and Moskovtsev, V.V., Khim. Prom.,
1981, vol. 8, p. 465.
7. Nagiev, Ya.M., Azerb. Khim. Zh., 2011, p. 129.
[2.2.1]hept-5-ene-2,3-dicarboxylic acid (5j). Yield
1
0.499 g (78%), mp 156–160°С. Н NMR spectrum, δ,
ppm: 1.32 m (1Н, НА), 2.11 m (1Н, НВ), 2.92 m (2Н,
Н1,4), 5.51 m (2Н, Н5,6), 1.86 m (3Н, СН3), 6.72–7.03
m (4Н, С6Н4). Found, %: С 59.69; Н 4.12; Cl 22.17; N
4.28. C16Н13Сl2NO2. Calculated, %: С 59.62; Н 4.04;
Cl 22.05; N 4.35.
N-(2,4-Dinitrophenyl)imide of 2,3-dichlorobicyclo-
[2.2.1]hept-5-ene-2,3-dicarboxylic acid (5k). Yield
8. Nagiev, Ya.M., Farzaliev, V.M., Bagirov, Sh.T.,
Orudzheva, A.A., and Faradzhov, G.M., Azerb. Khim.
Zh., 2006, p. 38.
1
0.756 g (95%), mp 178–180°С. Н NMR spectrum, δ,
ppm: 1.35 m (1Н, НА), 2.22 m (1Н, НВ), 2.89 m (2Н,
Н1,4), 5.51 m (2Н, Н5,6), 6.51–7.51 m (3Н, С6Н3).
Found, %: С 36.26; Н 0.87; Cl 21.52; N 12.83.
C15Н9Сl3N3O6. Calculated, %: С 36.15; H 0.90; Cl
21.38; N 12.65.
9. Nagiev, Ya.M., Russ. J. Org. Chem., 2012, vol. 48,
p. 301.
10. Nagiev, Ya.M., Azerb. Khim. Zh., 2010, p. 152.
11. Nagiev, Ya.M., Russ. J. Org. Chem., 2012, vol. 48,
p. 469.
12. Shakhtakhtinskii, T.N., Nagiev, Ya.M., Bagirov, Sh.T.,
Adigezalov, V.A., and Andreeva, E.I., USSR Inventor’s
Certificate no. 1702561, 1991, Byull. Izobret., 1991,
no. 48.
13. Nagiev, Ya.M., Bagirov, Sh.T., Adigezalov, V.A.,
Valitov, R.B., Shagas, G.G., Sapozhnikov, Yu.E., and
Nasibov, Sh.S., Azerb. Khim. Zh., 1986, p. 80.
IR spectra were recorded on a Specord M-80
spectrometer in KBr pellets, NMR spectra were
registered on Tesla BS-487 (80 (1H) МHz) and Bruker
WM [400 (1H) and 100.6 (13C) МHz] spectrometers in
С6D6 and (СD3)СO applying TMS and Dynasylan
HMDS as internal references. Initial reagents and
solvents were prepared by methods [17].
14. Zefirov, N.S. and Sokolov, V.I., Russ. Chem. Rev.,
1967, vol. 36, p. 87.
REFERENCES
15. Nagiev, Ya.M., Samuilov, Ya.D., Bagirov, Sh.T.,
Shnulin, A.N., Adigezalov, V.A., Nasibov, Sh.S.,
Pashaev, B.K., and Shakhtakhtinskii, T.N., Zh. Org.
Khim., 1992, vol. 28, p. 1643.
1. Chinchilla, R., Farvello, R.L., Galindo, N., and Najera, C.,
Tetrahedron: Asymmetry, 1999, vol. 10, p. 821.
2. Tarabara, I.N., Kas’yan, A.O., Krishchik, O.V.,
Shishkina, S.V., Shishkin, O.V., and Kas’yan, L.I.,
Russ. J. Org. Chem., 2002, vol. 38, p. 1299.
16. Nagiev, Ya.M., Shnulin, A.N., Bagirov, Sh.T.,
Adigezalov, V.A., Shil’nikov, V.I., and Mamedov, I.M.,
Kristallografiya, 1989, vol. 34, p. 96.
3. Nagiev, Ya.M., Akhmedov, R.M., Farzaliev, V.M., and
17. Gordon, A.J. and Ford, R.A., The Chemist’s
Companion, New York: Willey, 1972.
Gasanov, A.I., Azerb. Khim. Zh., 2005, p. 58.
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