First example of a synthesis of the tetracyclic 2,4-di(tert-butyl)- 6,7-dihydrofuro[2',3':3,4]cyclohepta- [1,2-b]indole system

Full text of DOI:10.1007/s10593-010-0477-2

Chemistry of Heterocyclic Compounds, Vol. 46, No. 1, 2010
LETTERS TO THE EDITOR
FIRST EXAMPLE OF A SYNTHESIS
OF THE TETRACYCLIC 2,4-DI(tert-BUTYL)-
6,7-DIHYDROFURO[2',3':3,4]CYCLOHEPTA-
[1,2-b]INDOLE SYSTEM
A. V. Butin1*, N. O. Kostyukova1, F. A. Tsiunchik1,
S. A. Lysenko1, and I. V. Trushkov1
Keywords: aryldifurylmethanes, indoles, recyclization, cyclization.
We have recently studied the acid-catalyzed recyclization of ortho-substituted benzylfurans. In these
reactions, the furan ring acts as a formal equivalent of a 1,4-diketone: one carbonyl group participates in the
formation of a new heterocycle, while the other is liberated. In the case of arylbis(5-methyl-2-furyl)methanes,
the recyclization may be accompanied by a secondary cyclization involving the liberated carbonyl group [1-5],
which leads to fused tetracyclic heterocycles. In contrast, the secondary cyclization does not occur when a bulky
tert-butyl group is present at C-5. [6].
R
R
R
O
O
O
NH
N
POCl3
H2O
N
O
+
Bu-t
O
Bu-t
Bu-t
O
O
O
t-Bu
t-Bu
2a,b
t-Bu
3a
1–3 a R = NO2, 1, 2 b R = Br
1a,b
_______
* To whom correspondence should be addressed, e-mail: alexander_butin@mail.ru.
1Research Institute of Heterocyclic Compounds Chemistry, Kuban State Technological University, Krasnodar
350072, Russia.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 137-139, January, 2010. Original
article submitted November 11, 2009.
0009-3122/10/4601-0117©2010 Springer Science+Business Media, Inc.
117

In a continuation of a study of the behavior of (2-benzoylaminoaryl)bis(5-tert-butyl-2-furyl)methanes in
the presence of acids [7, 8], we found that the action of POCl3 and a drop of water on benzene solutions of 1a
and 1b at room temperature leads to tetracyclic derivatives 2a and 2b. The reaction proceeds through the
intermediate formation of ketones 3. Ketone 3a was isolated from the reaction mixture and characterized, while
ketone 3b could not be isolated due to its low concentration.
1
The IR spectra were taken on a Shimadzu IR Prestige-21 spectrometer for KBr pellets. The H and
13C NMR spectra were taken on a Bruker DPX 300 spectrometer at 300 and 75 MHz, respectively, in CDCl3.
The shifts were measured related to the solvent signal (1H: δ = 7.25, 13C: δ = 77.13 ppm).
Synthesis of Compounds 2 and 3 (General Method). A sample of 10 ml POCl3 and one drop of water was
added to a solution of compound 1 (2 mmol) in benzene (40 ml). The reaction mixture was maintained for 24 h at
room temperature. Then, the mixture was poured into 200 ml water, neutralized by adding a solution of 20 g NaOH
in 150 ml water, and extracted with three 50-ml portions of methylene chloride. The combined organic fractions were
dried over anhydrous sodium sulfate. The solvent was evaporated in vacuum. The residue was separated on a column
packed with Sorbpolimer KSK silica gel (fraction 5-40 µm) using 1:8 benzene–petroleum ether as the eluent.
2,4-Di(tert-butyl)-7-(4-nitrobenzoyl)-6,7-dihydrofuro[2',4':3,4]cyclohepta[1,2-b]indole (2a) was
obtained in 21% yield (0.20 g) as an orange powder, mp 191-192°C (CH2Cl2-hexane). IR spectrum, ν, cm-1:
2964, 1680, 1524, 1452, 1346, 1324, 1206. 1H NMR spectrum, δ, ppm (J, Hz): 1.20 (9H, s, t-C4H9); 1.43 (9H, s,
t-C4H9); 2.83 (2H, d, J = 7.2, CH2); 5.17 (1H, t, J = 7.2, =CH); 6.46 (1H, s, H Fur); 7.19-7.24 (1H, m, H Ar);
7.31-7.37 (1H, m, H Ar); 7.47-7.51 (1H, m, H Ar); 7.97-8.01 (1H, m, H Ar); 7.98 (2H, d, J = 9.0, H Ar); 8.39
13
(2H, d, J = 9.0, H Ar). C NMR spectrum, δ, ppm: 25.8, 29.1 (3C), 30.8 (3C), 32.7, 35.9, 104.1, 112.2, 113.7,
114.9, 120.3, 122.9, 124.0 (2C), 124.1, 124.3, 126.6, 130.7 (2C), 131.0, 136.8, 141.0, 144.6, 146.8, 150.2,
162.3, 166.8. Found, %: C 74.61; H 6.57; N 5.92. C30H30N2O4. Calculated,%: C 74.67; H 6.27; N 5.80.
7-(4-Bromobenzoyl)-2,4-di(tert-butyl)-6,7-dihydrofuro[2',3':3,4]cyclohepta[1,2-b]indole (2b) was
obtained in 41% yield (0.42 g) as yellow needles, mp 206-207°C (CH2Cl2–hexane). IR spectrum, ν, cm-1: 2952,
1680, 1592, 1448, 1324, 756. 1H NMR spectrum, δ, ppm (J, Hz): 0.79 (9H, s, t-C4H9); 1.34 (9H, s, t-C4H9); 3.82
(3H, s, CH3); 6.13 (1H, d, J = 3.3, H Fur); 6.38 (1H, d, J = 12.0, =CH); 6.48 (1H, d, J = 3.3, H Fur); 6.89 (2H, d,
J = 8.7, H Ar); 7.19 (1H, d, J = 12.0, =CH); 7.44-7.50 (1H, m, H Ar); 7.52 (2H, d, J = 8.7, H Ar); 7.63-7.68
(1H, m, H Ar); 8.04-8.07 (1H, m, H Ar); 8.11-8.13 (H Ar). 13C NMR spectrum, δ, ppm: 25.7, 29.1 (3C), 30.8
(3C), 32.7, 35.9, 104.1, 112.5, 112.9, 114.8, 120.1, 122.4, 123.6, 123.9, 126.3, 128.1, 131.4 (2C), 131.8,
132.1 (2C), 134.2, 137.0, 144.3, 147.1, 162.0, 168.0. Found, %: C 69.53; H 5.96; N 2.44. C30H30BrNO2.
Calculated, %: C 69.77; H 5.85; N 2.71.
1-{3-[5-tert-Butyl-2-furyl]-1-(4-nitrobenzoyl)-1H-indol-2-yl}-4,4-dimethyl-3-pentanone (3a) was
obtained in 35% yield (0.35 g) as a red powder, mp 126-127°C (CH2Cl2–hexane). IR spectrum, ν, cm-1: 2968, 1696,
1604, 1520, 1408, 1344, 1304, 1208, 1180. 1H NMR spectrum, δ, ppm (J, Hz): 1.12 (9H, s, t-Bu); 1.35 (9H, s, t-Bu);
3.06-3.11 (1H, m, CH2); 3.28-3.37 (2H, m, CH2); 6.14 (1H, d, J = 3.3, H Fur); 6.55 (1H, d, J = 9.0, H Fur); 6.57-6.59
(1H, m, H Ar); 6.99-7.05 (1H, m, H Ar); 7.20-7.26 (1H, m, H Ar); 7.87-7.89 (1H, m, H Ar); 7.94 (2H, d, J = 9.0,
H Ar); 8.35 (2H, d, J = 9.0, H Ar). 13C NMR spectrum, δ, ppm: 22.2, 26.4 (3C), 29.1 (3C), 32.7, 36.9, 44.0, 103.8,
108.4, 112.8, 113.8, 120.5, 123.3, 123.6, 124.0 (2C), 127.5, 131.0 (2C), 135.9, 137.5, 140.7, 146.0, 150.3, 163.7,
167.4, 214.7. Found, %: C 71.85; H 6.68; N 5.36. C30H32N2O5. Calculated, %: C 71.98; H 6.44; N 5.60.
This work was carried out with the financial support of the Russian Basic Research Fund
(Grant No. 2.1.1/4628 RNPVSh).
REFERENCES
1.
A. V. Butin, A. V. Gutnov, V. T. Abaev, and G. D. Krapivin, Khim. Geterotsikl. Soedin., 883 (1998).
[Chem. Heterocycl. Comp., 762 (1998)].
118

2.
3.
A. V. Butin, S. K. Smirnov, and T. A. Stroganova, J. Heterocycl. Chem., 43, 623 (2006).
V. T. Abaev, A. S. Dmitriev, A. V. Gutnov, S. A. Podelyakin, and A. V. Butin, J. Heterocycl. Chem., 43,
1195 (2006).
4.
5.
A. S. Dmitriev, V. T. Abaev, W. Bender, and A. V. Butin, Tetrahedron, 63, 9437 (2007).
A. V. Butin, V. T. Abaev, V. V. Mel'chin, A. S. Dmitriev, A. S. Pilipenko, and A. S. Shashkov,
Synthesis, 1798 (2008).
6.
A. S. Dmitriev, S. A. Podelyakin, V. T. Abaev, and A. V. Butin, Khim. Geterotsikl. Soedin., 1400
(2005). [Chem. Heterocycl. Comp., 1194 (2005)].
7.
8.
A. V. Butin, S. K. Smirnov, and I. V. Trushkov, Tetrahedron Lett., 49, 20 (2008).
A. V. Butin, S. K. Smirnov, F. A. Tsiunchik, M. G. Uschuskin, and I. V. Trushkov, Synthesis, 2943
(2008).
119