2-(2-Furyl)-5,6-dihydro-1(3)H-acenaphtho[4,5-d]imidazole. Synthesis and electrophilic substitution reactions

Article abstract of DOI:10.1134/S1070428012070135

2-(2-Furyl)-5,6-dihydro-1(3)H-acenaphtho[4,5-d]imidazole was synthesized by the Weidenhagen reaction of acenaphthene-4,5-diamine with furfural. Alkylation of the title compound with methyl iodide in KOH-DMSO gave isomeric 1- and 3-methyl derivative, the l

Full text of DOI:10.1134/S1070428012070135

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 7, pp. 968–971. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © E.V. Illenzeer, A.A. Aleksandrov, M.M. El’chaninov, 2012, published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48, No. 7,
pp. 972–975.
2-(2-Furyl)-5,6-dihydro-1(3)H-acenaphtho[4,5-d]imidazole.
Synthesis and Electrophilic Substitution Reactions
E. V. Illenzeer, A. A. Aleksandrov, and M. M. El’chaninov
South Russian State Technical University (Novocherkassk Polytechnic Institute),
ul. Prosveshcheniya 132, Novocherkassk, 346428 Russia
e-mail: aaanet1@yandex.ru
Received January 31, 2012
Abstract—2-(2-Furyl)-5,6-dihydro-1(3)H-acenaphtho[4,5-d]imidazole was synthesized by the Weidenhagen
reaction of acenaphthene-4,5-diamine with furfural. Alkylation of the title compound with methyl iodide in
KOH–DMSO gave isomeric 1- and 3-methyl derivative, the latter being the major product. 2-(2-Furyl)-3-
methyl-5,6-dihydro-3H-acenaphtho[4,5-d]imidazole was subjected to electrophilic substitution reactions
(bromination, nitration, formylation, acylation, and sulfonation. Depending on the conditions, electrophilic
attack was directed at the furan ring or acenaphthene fragment or both these.
DOI: 10.1134/S1070428012070135
There are almost no published data on the synthesis
and properties of acenaphtho[4,5-d]imidazole having
a furyl substituent. On the other hand, such hetero-
cyclic compounds attract interest as potential biologi-
cally active substances and organic luminophores [1].
The synthesis and chemical behavior of 2-(2-furyl)-
1H-acenaphtho[9,10-d]imidazole were reported in [2].
The goal of the present work was to develop a con-
venient procedure for the synthesis of 2-(2-furyl)-5,6-
dihydro-1(3)H-acenaphtho[4,5-d]imidazole (I) and
study its transformations in reactions with electrophilic
and radical reagents. Compound I was synthesized by
us for the first time by reaction of acenaphthene-4,5-
diamine with furfural according to Weidenhagen [3]
(yield 64%). Alkylation of I with an equimolar amount
of methyl iodide was performed in the system KOH–
DMSO, and the yield was nearly quantitative. As
unsymmetrical heterocyclic systems studied previously
[4], the reaction gave a mixture of two N-methyl deriv-
atives, 2-(2-furyl)-1-methyl-5,6-dihydro-1H-acenaph-
tho[4,5-d]imidazole (II) and 2-(2-furyl)-3-methyl-
5,6-dihydro-3H-acenaphtho[4,5-d]imidazole (III)
(Scheme 1), due to fast annular tautomerism. Accord-
ing to the 1H NMR data, the major product was isomer
III; its fraction was about 79%. The NCH3 group in III
gave rise to a singlet at δ 4.06 ppm, whereas the
corresponding signal of II was located at δ 4.44 ppm.
Obviously, the downfield position of the NCH3 signal
of II is determined by diamagnetic constituent of the
ring current in the acenaphthene system.
Pure 3-methyl isomer III was isolated by column
chromatography and was brought into reactions with
some electrophilic reagents, in particular with bromine
in 1,2-dichloroethane, acetyl nitrate, hexamethylene-
tetramine in polyphosphoric acid (PPA), and sulfuric
and carboxylic acids in PPA, In addition, compound
III was nitrated with dilute nitric acid (d = 1.42 g/cm3)
(Scheme 2). As we showed previously [4], various
2-hetarylimidazole systems stabilize π-excessive five-
membered heterocycles directly conjugated with the
imidazole fragment. It was found that the character of
stabilization in acid medium does not change appreci-
Scheme 1.
Me
N
N
N
N
MeI, KOH–DMSO
+
N
H
O
O
N
O
Me
I
II
III
968

2-(2-FURYL)-5,6-DIHYDRO-1(3)H-ACENAPHTHO[4,5-d]IMIDAZOLE.
969
Scheme 2.
Me
Me
N
N
HNO3
or Br2–C2H4Cl2
or H2SO4–PPA
RCOOH–PPA
or (CH2)6N4–PPA
N
O
N
O
X
R'
III
R
O
IVa–IVc
IVd–IVg
X = O2N (a), Br (b), HOSO2 (c); R = H, R′ = H (d), CHO (e); R = Me, R′ = H (f); R = Ph, R′ = H (g).
ably in going from quinoline to naphthalene and then
to acenaphthene.
Our results may be rationalized in terms of leveling
of the reactivities of the acenaphtho[4,5-d]imidazole
system and deactivated furan ring toward medium-
strength electrophiles in polyphosphoric acid.
The nitration of III was performed using the com-
plex of copper(II) nitrate and acetic anhydride at 20°C
[5]. The reaction involved the furan ring, and the yield
of 2-(5-nitrofuran-2-yl) derivative IVa was ~67%.
Radical nitration of III with dilute nitric acid on
heating was not selective, and we failed to isolate or
identify nitration product. Unlike acenaphtho[9,10-d]-
imidazole analog [2], the bromination of III in
dichloroethane, as well as in PPA, afforded exclusively
2-(5-bromofuran-2-yl) derivative IVb in 63% yield.
5-Sulfo derivative IVc was obtained by sulfonation of
III with 2 equiv of sulfuric acid in PPA at 110–120°C.
EXPERIMENTAL
The IR spectra were recorded on a Specord IR-75
spectrometer from compounds dissolved in chloroform
1
or dispersed in mineral oil. The H NMR spectra were
recorded on a Varian Unity-300 instrument (300 MHz)
using the residual proton signals of the deuterated
solvents as reference (CHCl3, δ 7.26 ppm; DMSO-d5,
δ 2.50 ppm). The elemental compositions were deter-
mined on a Perkin Elmer 2400 analyzer. The melting
points were measured in capillaries using a PTP melt-
ing point apparatus. The progress of reactions was
monitored, and the purity of products was checked, by
TLC on Al2O3 plates (Brockmann activity grade II;
development with iodine vapor) or Silufol UV-254
plates (eluent methylene chloride).
Unlike 2-(2-furyl)-1-methyl-1H-acenaphtho-
[9,10-d]imidazole studied previously, Vilsmeier
formylation of 2-(2-furyl)-3-methyl-5,6-dihydro-3H-
acenaphtho[4,5-d]imidazole (III) occurred at 60–70°C;
1
however, according to the H NMR data, the aldehyde
group entered position 9 in the acenaphthene fragment
(compound IVd). By heating compound III with hexa-
methylenetetramine in PPA at 70–80°C we obtained
5,9-dialdehyde IVe as a result of formylation at both
furan and acenaphthene fragments.
2-(2-Furyl)-5,6-dihydro-1(3)H-acenaphtho-
[4,5-d]imidazole (I). A mixture of 7.37 g (40 mmol) of
acenaphthene-4,5-diamine in 75 ml of isopropyl al-
cohol, 16 g of copper acetate in 200 ml of water, and
3.85 g (40 mmol) of furfural was heated for 2 h at 80–
90°C. The mixture was cooled, the precipitate of cop-
per salt was filtered off and dispersed in 100 ml of
isopropyl alcohol, and gaseous hydrogen sulfide was
passed through the suspension over a period of 1 h.
The precipitate of copper sulfide was filtered off, the
filtrate was evaporated by half and diluted with 100 ml
of water, and the precipitate was filtered off and re-
crystallized from ethanol. Yield 6.66 g (64%), mp 188–
Despite deactivating effect of the imidazoacenaph-
thene fragment, compound III underwent acetylation
with acetic acid in PPA at 110–120°C much more
readily as compared to acenaphtho[9,10-d]imidazole
analog. The product was 9-acetyl derivative IVf. In the
1H NMR spectrum of IVf, methyl protons in the acetyl
group resonated as a singlet at δ 2.98 ppm, whereas the
corresponding signal of furylacenaphtho[9,10-d]imid-
azole was observed at δ 2.52 ppm; the downfield
position of the former is determined by the effect of
the pyridine-type nitrogen atom. Benzoylation of III
with benzoic acid in PPA was carried out at higher
temperature (140–150°C); likewise, 9-benzoyl deriva-
tive IVg was formed in ~56% yield.
1
189°C. H NMR spectrum, δ, ppm: 3.43 s (4H, CH2),
6.60–6.62 m (1H, 4′-H), 7.10 d (1H, 3′-H, J = 3.6 Hz),
7.23 s (1H, 4-H), 7.33 d (1H, 7-H, J = 6.5 Hz), 7.55 t
(1H, 8-H, J = 7.5 Hz), 7.65 d (1H, 5′-H, J = 1.8 Hz),
8.30 d (1H, 9-H, J = 8.0 Hz), 12.73 br.s (1H, NH).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 7 2012

ILLENZEER et al.
970
tography on aluminum oxide (15 × 2.5 cm) using
methylene chloride as eluent. Yield 0.21 g (67%).
Found, %: C 78.69; H 4.52; N 10.39. C17H12N2O. Cal-
culated, %: C 78.44; H 4.65; N 10.76.
b. Sodium nitrite, 0.21 g (3 mmol), was added in
portions to a solution of 0.35 g (1 mmol) of compound
IVb in 5 ml of acetic acid, and the mixture was heated
for 1 h under reflux, cooled, poured into 20 ml of
water, and treated as described above in a. The prod-
ucts obtained by the two methods were identical in the
melting point (no depression was observed on mixing).
Yield 0.17 g (53%), mp 222–223°C (from ethanol). IR
spectrum, ν, cm–1: 1560 (NO2, asym.), 1380 (NO2,
2-(2-Furyl)-1-methyl-5,6-dihydro-1H-acenaph-
tho[4,5-d]imidazole (II) and 2-(2-furyl)-3-methyl-
5,6-dihydro-3H-acenaphtho[4,5-d]imidazole (III).
Methyl iodide, 3.12 g (22 mmol), was added dropwise
under vigorous stirring at 15–20°C to a solution of
5.21 g (20 mmol) of compound I in 20 ml of DMSO
containing 1.24 g (22 mmol) of powdered potassium
hydroxide. The mixture was stirred for 2 h, poured into
200 ml of water, and extracted with chloroform (2×
50 ml). The combined extracts were evaporated to
a volume of 20 ml, dried over sodium sulfate, filtered,
and evaporated to isolate 4.00 g (73%) of isomer mix-
ture II/III. Pure compounds II and III were isolated
by column chromatography on Al2O3 (70×3.5 cm)
using chloroform as eluent.
1
sym.). H NMR spectrum, δ, ppm: 3.44 s (4H, CH2),
4.12 s (3H, NCH3), 7.25 s (1H, 4-H), 7.28 d (1H, 3′-H,
J = 3.6 Hz), 7.30 d (1H, 7-H, J 7.0 Hz), 7.48 d (1H,
4′-H, J = 3.6 Hz), 7.57 t (1H, 8-H, J = 7.8 Hz), 8.25 d
(1H, 9-H, J = 8.1 Hz). Found, %: C 67.87; H 3.89;
N 12.93. C18H13N3O3. Calculated, %: C 67.71; H 4.10;
N 13.16.
Isomer II. Yield 0.56 g (14%), mp 137–138°C
1
2-(5-Bromofuran-2-yl)-3-methyl-5,6-dihydro-
3H-acenaphtho[4,5-d]imidazole (IVb). Bromine,
0.21 ml (4 mmol), was added to a solution of 0.55 g
(2 mmol) of compound III in 10 ml of 1,2-dichloro-
ethane, and the mixture was heated for 2 h under
reflux. The mixture was treated with water and neutral-
ized with a solution of ammonia, and the bottom layer
was separated and subjected to chromatography in
a column charged with Al2O3 using methylene chloride
as eluent. Yield 0.44 g (63%), mp 127–128°C. 1H NMR
spectrum, δ, ppm: 3.45 s (4H, CH2), 4.06 s (3H,
NCH3), 6.51 d (1H, 4′-H, J = 3.6 Hz), 7.09 d (1H,
3′-H, J = 3.6 Hz), 7.25 s (1H, 4-H), 7.30 d (1H, 7-H,
J = 7.2 Hz), 7.56 t (1H, 8-H, J = 7.8 Hz), 8.24 d (1H,
9-H, J = 8.1 Hz). Found, %: C 60.93; H 3.58;
Br 23.00. C18H13BrN2O. Calculated, %: C 61.21;
H 3.71; Br 22.62.
5-(3-Methyl-5,6-dihydro-3H-acenaphtho[4,5-d]-
imidazol-2-yl)furan-2-sulfonic acid (IVc). A mixture
of 0.55 g (2 mmol) of compound III, 0.39 g (4 mmol)
of sulfuric acid (d = 1.84 g/cm3), and 8 g of PPA was
heated for 1 h at 100°C. The mixture was cooled and
diluted with 50 ml of water, and the precipitate was
filtered off. The product was dissolved in 5% aqueous
sodium hydroxide, and the solution was treated with
activated charcoal on heating at the boiling point,
filtered, and neutralized with hydrochloric acid until
weakly acidic reaction. Yield 0.40 g (57%), mp 302–
303°C (from water). IR spectrum: ν 1280 cm–1 (SO2).
1H NMR spectrum, δ, ppm: 3.50 s (4H, CH2), 4.12 s
(3H, NCH3), 7.10 d (1H, 4′-H, J = 3.3 Hz), 7.27 s (1H,
4-H), 7.29 d (1H, 3′-H, J = 3.3 Hz), 7.32 d (1H, 7-H,
J = 7.5 Hz), 7.58 t (1H, 8-H, J = 8.0 Hz), 8.26 d (1H,
(from benzene). H NMR spectrum, δ, ppm: 3.45 s
(4H, CH2), 4.44 s (3H, NCH3), 6.58–6.60 m (1H,
4′-H), 7.08 d (1H, 3′-H, J = 3.6 Hz), 7.25 d (1H, 7-H,
J = 6.3 Hz), 7.50 t (1H, 8-H, J = 7.2 Hz), 7.61 d (1H,
5′-H, J = 1.8 Hz), 7.62 s (1H, 4-H), 8.03 d (1H, 9-H,
J = 8.1 Hz). Found, %: C 78.66; H 5.22. C18H14N2O.
Calculated, %: C 78.81; H 5.14.
Isomer III. Yield 2.88 g (72%), mp 168–169°C
(from ethanol). 1H NMR spectrum, δ, ppm: 3.45 s (4H,
CH2), 4.06 s (3H, NCH3), 6.58–6.60 m (1H, 4′-H),
7.08 d (1H, 3′-H, J = 3.6 Hz), 7.25 s (1H, 4-H), 7.30 d
(1H, 7-H, J = 6.3 Hz), 7.56 t (1H, 8-H, J = 7.2 Hz),
7.61 d (1H, 5′-H, J = 1.8 Hz), 8.27 d (1H, 9-H, J =
8.1 Hz). Found, %: C 79.12; H 4.87; N 10.44.
C18H14N2O. Calculated, %: C 78.81; H 5.14; N 10.21.
3-Methyl-2-(5-nitrofuran-2-yl)-5,6-dihydro-3H-
acenaphtho[4,5-d]imidazole (IVa). Acetic anhydride,
15 ml, was added in small portions on cooling to
4.48 g (20 mmol) of copper nitrate, maintaining the
temperature below 30–40°C. When the exothermic re-
action was over, the mixture was kept for 24 h at room
temperature, the precipitate of copper(II) nitrate was
filtered off, and the filtrate was used in the nitration of
compound III.
a. Compound III, 0.27 g (1 mmol), was dissolved
in 2 ml of freshly prepared acetic anhydride, and
0.28 ml of the nitrating mixture (see above) was added
under stirring at room temperature. The reaction time
was 30–40 min. The mixture was then treated with
10 ml of cold water and neutralized with 25% aqueous
ammonia. The precipitate was filtered off, thoroughly
washed with water, and subjected to column chroma-
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2-(2-FURYL)-5,6-DIHYDRO-1(3)H-ACENAPHTHO[4,5-d]IMIDAZOLE.
971
9-H, J = 8.2 Hz). Found, %: C 60.73; H 4.17; N 8.22.
ture of 0.55 g (2 mmol) of compound III and 0.36 g
(6 mmol) of acetic acid in 8 g of PPA was stirred for
6 h at 110–120°C. The mixture was diluted with 25 ml
of water, carefully neutralized with a solution of am-
monia, and extracted with methylene chloride. The
product was isolated by column chromatography using
CH2Cl2 as eluent. Yield 0.30 g (30%), mp 163–164°C
(from ethanol). IR spectrum: ν 1680 cm–1 (C=O).
1H NMR spectrum, δ, ppm: 2.98 s (3H, CH3), 3.47 s
(4H, CH2), 4.11 s (3H, NCH3), 6.59–6.61 m (1H,
4′-H), 7.14 d (1H, 3′-H, J = 3.3 Hz), 7.29 d (1H, 7-H,
J = 6.9 Hz), 7.34 s (1H, 4-H), 7.58 d (1H, 8-H, J =
7.5 Hz), 7.60 d (1H, 5′-H, J = 1.8 Hz). Found, %:
C 76.24; H 4.87; N 9.13. C20H16N2O2. Calculated, %:
C 75.93; H 5.10; N 8.85.
[2-(2-Furyl)-3-methyl-5,6-dihydro-3H-acenaph-
tho[4,5-d]imidazol-9-yl]phenylmethanone (IVg).
A mixture of 0.55 g (2 mmol) of compound III and
1.22 g (10 mmol) of benzoic acid in 8 g of PPA was
stirred for 6 h at 140–150°C. The product was isolated
as described above for IVf. Yield 0.42 g (56%),
mp 155–156°C (from ethanol). IR spectrum:
ν 1660 cm–1 (C=O). 1H NMR spectrum, δ, ppm: 3.49 s
(4H, CH2), 4.10 s (3H, NCH3), 6.59–6.62 m (1H,
4′-H), 7.14 d (1H, 3′-H, J = 3.5 Hz), 7.28 d (1H, 7-H,
J = 7.0 Hz), 7.34 s (1H, 4-H), 7.51–7.54 m (3H, m-H,
p-H), 7.58 d (1H, 5′-H, J = 1.8 Hz), 7.62 d (1H, 8-H,
J = 7.5 Hz), 8.00 d (2H, o-H, J = 8.2 Hz). Found, %:
C 79.57; H 5.03; N 7.69. C25H18N2O2. Calculated, %:
C 79.35; H 4.79; N 7.40.
C18H14N2O4S. Calculated, %: C 61.01; H 3.98; N 7.90.
2-(2-Furyl)-3-methyl-5,6-dihydro-3H-acenaph-
tho[4,5-d]imidazole-9-carbaldehyde (IVd). A solu-
tion of 0.55 g (2 mmol) of compound III in 4.75 g
(65 mmol) of dimethylformamide was cooled to 0–
5°C, 4.6 g (30 mmol) of phosphoryl chloride was
added dropwise under stirring, and the mixture was
stirred for 10 min at 0–5°C and for 1 h at 60°C. The
mixture was cooled, neutralized with a concentrated
solution of ammonia to pH 7, and extracted with 25 ml
of chloroform. The extract was dried over anhydrous
sodium sulfate and subjected to chromatography on
a column charged with Al2O3 using chloroform as
eluent. Yield 0.26 (43%), mp 180–181°C (from hep-
tane). IR spectrum: ν 1690 cm–1 (C=O). 1H NMR spec-
trum, δ, ppm: 3.48 s (4H, CH2), 4.12 s (3H, NCH3),
6.59–6.61 m (1H, 4′-H), 7.12 d (1H, 3′-H, J = 3.4 Hz),
7.30 d (1H, 7-H, J = 6.9 Hz), 7.35 s (1H, 4-H), 7.60 d
(1H, 8-H, J = 7.5 Hz), 7.62 d (1H, 5′-H, J = 1.8 Hz),
10.29 s (1H, CHO). Found, %: C 75.67; H 4.92;
N 8.98. C19H14N2O2. Calculated, %: C 75.48; H 4.67;
N 9.27.
2-(5-Formylfuran-2-yl)-3-methyl-5,6-dihydro-
3H-acenaphtho[4,5-d]imidazole-9-carbaldehyde
(IVe). A mixture of 0.55 g (2 mmol) of compound III
and 0.84 g (6 mmol) of hexamethylenetetramine in 8 g
of PPA was stirred for 4 h on heating at 80–90°C. The
mixture was diluted with 50 ml of water and neutral-
ized with a solution of ammonia, and the product was
extracted into methylene chloride and isolated as
described above for IVd. Yield 0.48 g (73%), mp 192–
193°C (from ethanol). IR spectrum, ν, cm–1: 1690,
REFERENCES
1. Pechkin, A.A., El’chaninov, M.M., Luk’yanov, B.S., and
Alekseenko, Yu.S., Khim. Geterotsikl. Soedin., 2004,
p. 711.
1
1670 (C=O). H NMR spectrum, δ, ppm: 3.48 s (4H,
CH2), 4.10 s (3H, NCH3), 7.30 d (1H, 7-H, J = 7.0 Hz),
7.32 d (1H, 3′-H, J = 3.6 Hz), 7.35 s (1H, 4-H), 7.40 d
(1H, 4′-H, J = 3.6 Hz), 7.62 d (1H, 8-H, J = 7.5 Hz),
9.73 s (1H, CHO), 10.30 s (1H, CHO). Found, %:
C 73.09; H 4.43; N 8.57. C20H14N2O3. Calculated, %:
C 72.72; H 4.27; N 8.48.
2. Achkasova, A.A. and El’chaninov, M.M., Khim. Getero-
tsikl. Soedin., 2006, p. 191.
3. Weidenhagen, R., Ber., 1936, vol. 69, p. 2263.
4. El’chaninov, M.M., Doctoral (Chem.) Dissertation,
Rostov-on-Don, 2006.
1-[2-(2-Furyl)-3-methyl-5,6-dihydro-3H-ace-
naphtho[4,5-d]imidazol-9-yl]ethanone (IVf). A mix-
5. Churkin, Yu.S. and Savin, V.I., Khim. Geterotsikl.
Soedin., 1968, p. 369.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 7 2012