Synthesis and structures of benzo[cd]furo[2,3-f]indol-4(5H)-one derivatives

Article abstract of DOI:10.1007/s11172-008-0023-x

A procedure was developed for the synthesis of derivatives of the new heterocyclic system, benzo[cd]furo[2,3-f]indole, based on the cyclodehydration of 6-acylmethyloxy-1-alkyl-benzo[cd]indol-2(1H)-ones. Either 7- or 8-aryl derivatives of benzo[cd]furo[2,3-f]indol-4(5H)-ones can be prepared depending on the reaction conditions. The molecular and crystal structures of 7- and 8-phenylbenzo[cd]furo[2,3-f]indol-4(5H)-ones were established by X-ray diffraction.

Full text of DOI:10.1007/s11172-008-0023-x

Russian Chemical Bulletin, International Edition, Vol. 57, No. 1, pp. 159—164, January, 2008
159
Synthesis and structures of benzo[cd]furo[2,3ꢀf]indolꢀ4(5H)ꢀone derivatives

I. G. Davydenko, Yu. L. Slominskii, O. I. Kalchenko, A. V. Gutov, A. N. Chernega, and A. I. Tolmachev
Institute of Organic Chemistry, National Academy of Sciences of Ukraine,
5 ul. Murmanskaya, 02660 Kiev, Ukraine.
Fax: +38 (044) 573 2643. Eꢀmail: ira_davidenko@ukr.net
A procedure was developed for the synthesis of derivatives of the new heterocyclic system,
benzo[cd]furo[2,3ꢀf]indole, based on the cyclodehydration of 6ꢀacylmethyloxyꢀ1ꢀalkylꢀ
benzo[cd]indolꢀ2(1H)ꢀones. Either 7ꢀ or 8ꢀaryl derivatives of benzo[cd]furo[2,3ꢀf]indolꢀ4(5H)ꢀ
ones can be prepared depending on the reaction conditions. The molecular and crystal structures of
7ꢀ and 8ꢀphenylbenzo[cd]furo[2,3ꢀf]indolꢀ4(5H)ꢀones were established by Xꢀray diffraction.
Key words: benzo[cd]indolꢀ2(1H)ꢀone, benzo[cd]furo[2,3ꢀf]indolꢀ4(5H)ꢀone, cyclodeꢀ
hydration, Xꢀray diffraction.
Many benzo[cd]indolꢀ2(1H)ꢀone derivatives were
found to be physiologically active compounds with a
broad spectrum of action.1—3 6,7ꢀBenzo derivatives of
this heterocyclic system, which are involved as structural
fragments in some alkaloids,4—7 are of particular interꢀ
est. At the same time, both synthetic and natural benꢀ
zo[cd]indolꢀ2(1H)ꢀone derivatives containing the
6,7ꢀfused heterocycle are virtually unknown. Earlier, we
have synthesized 7,8ꢀdihydrobenzo[cd]furo[2,3ꢀf]indolꢀ
4(5H)ꢀones as first representatives of the new heterocyclic
system, benzo[cd]furo[2,3ꢀf]indole, by the thermal or
catalytic Claisen rearrangement of 1ꢀalkylꢀ6ꢀallyloxyꢀ
benzo[cd]indolꢀ2(1H)ꢀones.8 It was of interest to deꢀ
velop an alternative procedure for the synthesis of deꢀ
rivatives of this heterocycle.
Among known methods for the construction of polyꢀ
nuclear heterocyclic systems, in particular, of benꢀ
zo[b]furans, the cyclodehydration occupies an important
place.9 We used this method for the synthesis of keto
esters 2 and 4a—e starting from 1ꢀalkylꢀ6ꢀhydroxybenꢀ
zo[cd]indolꢀ2(1H)ꢀones 1a,b (Scheme 1).
Product 2 was synthesized from compound 1a. The
heating of compound 2 in polyphosphoric acid (PPA) at
100 °C for 8 h affords 5,7ꢀdimethylbenzo[cd]furo[2,3ꢀ
f]ꢀindolꢀ4(5H)ꢀone (3) in 10% yield. The structure of the
latter compound was confirmed by 1H NMR spectroꢀ
scopy. The 1H NMR spectrum shows the following charꢀ
acteristic signals for the aromatic protons: a singlet at δ
6.94 (1 H, C(6)H), a quartet at δ 7.55 (1 H, C(8)H,
JH,H = 1.5 Hz), a doublet of doublets at δ 7.76 (1 H,
C(2)H, JH,H = 7.9 Hz), a doublet at δ 8.03 (1 H, C(3)H,
JH,H = 7.9 Hz), and a doublet at δ 8.27 (1 H, C(1)H,
JH,H = 7.9 Hz), which indicate that the cyclization proꢀ
ceeds at position 7 rather than at position 5 of the
benzo[cd]indole moiety to give the fiveꢀmembered furan
ring. The use of sulfuric, orthophosphoric, trifluoroꢀ
methanesulfonic, or Lewis acids for the condensation of
keto ester 2 did not lead to an increase in the yield of the
product because of resinification. On the contrary, the
cyclodehydration of compounds containing the aryl group
in the keto ester fragment with PPA proceeds more
smoothly. For example, the cyclodehydration of comꢀ
pounds 4a—e with PPA proceeds at 85 °C to give
5ꢀmethylꢀ and 5ꢀbutylꢀ7ꢀarylbenzo[cd]furo[2,3ꢀf]ꢀindolꢀ
4(5H)ꢀones 5a—e in higher yields (42—82%). It should
be noted that the reaction giving products 5a,b from
compounds 4a,b is regioselective and affords only
7ꢀphenylꢀsubstituted benzo[cd]furo[2,3ꢀf]indolꢀ4(5H)ꢀ
ones in 74 and 82% yields, respectively. Under these conꢀ
ditions, the reactions of compounds 4c—e produce, in
addition to 7ꢀarylꢀsubstituted benzo[cd]furo[2,3ꢀf]indolꢀ
4(5H)ꢀones, 8ꢀarylꢀsubstituted derivatives in low yields
(~20%). However, this leads to a substantial decrease in
the yield of the target products because it is difficult to
separate these isomers by preparative methods (they have
similar Rf and solubilities). In these cases, the ratios beꢀ
tween the yields of the 7ꢀ and 8ꢀisomers were determined
by HPLC of the reaction mixtures. The use of the Lewis
acid BF3•Et2O (taken as the medium) for the condensaꢀ
tion of 4e did not give the expected result. According to
the HPLC data, both isomers, 5e and 6e, were produced
in equal amounts in 43.3 and 42.3% yields, respectively.
The subsequent refluxing (10 h) did not lead to the formaꢀ
tion of exclusively the 8ꢀisomer. The heating of comꢀ
pound 4e with a tenfold excess (w/w) of PPA at 85 °C for
3 h afforded a mixture of 5e and 6e (HPLC data) in 34.3
and 39.4% yields, respectively.
The cyclodehydration of compounds 4a—d with PPA
at 135 °C gave pure 8ꢀarylbenzo[cd]furo[2,3ꢀf]indolꢀ
4(5H)ꢀones 6a—d in good yields. However, we failed to
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 154—158, January, 2008.
1066ꢀ5285/08/5701ꢀ0159 © 2008 Springer Science+Business Media, Inc.

160
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 1, January, 2008
Davydenko et al.
Scheme 1
i. Polyphosphoric acid.
R = Me (1a), Bun (1b)
R = Me, R´ = H (4a—6a), Cl (4c—6c), OMe (4e—6e); R = Bun, R´ = H (4b—6b), Cl (4d—6d)
C(10)
prepare compound 6e from 4e under these conditions;
the reaction was accompanied by resinification of the
mixture. Product 6e was isolated as an impurity in the
C(9)
C(11)
C(12)
C(5)
C(4)
synthesis of compound 5e. The heating of 7ꢀarylꢀsubstiꢀ
C(16)
C(6)
O(2)
O(1)
C(2)
tuted derivatives of arylbenzo[cd]furo[2,3ꢀf]indolꢀ
4(5H)ꢀones in the presence of polyphosphoric acid at
135 °C results in their transformation into the correꢀ
sponding 8ꢀisomers, as was exemplified by compound
5a. Earlier, this transformation has been described for
benzo[b]furan derivatives.9
C(15)
C(17)
C(18)
C(1)
C(13)
N(1)
C(14)
C(7)
C(8)
C(3)
C(20)
C(19)
Fig. 2. Molecular structure of compound 6a.
C(10)
C(9)
Table 1. Selected bond lengths (d) and bond
angles (ω) in compounds 5a and 6a
C(11)
C(12)
C(5)
C(4)
Parameter
5a
6a
O(1)
C(6)
Bond
d/Å
O(2)
C(1)—O(1)
C(4)—O(1)
C(7)—N(1)
C(13)—N(1)
C(20)—N(1)
C(13)—O(2)
Angle
1.370(6) 1.387(4)
1.368(5) 1.376(3)
1.401(5) 1.409(4)
1.401(6) 1.389(4)
1.430(6) 1.450(5)
C(1)
C(2)
C(13)
N(1)
C(3)
C(8)
C(7)
C(20)
C(15)
C(16)
C(14)
1.213(5)
—
ω/deg
C(19)
C(18)
C(2)—C(1)—O(1)
C(3)—C(4)—O(1)
C(6)—C(7)—N(1)
C(1)—О(1)—C(4)
C(7)—N(1)—C(13)
112.4(4)
110.3(4)
106.2(4)
—
—
—
—
C(17)
105.8(2)
111.2(3)
—
Fig. 1. Molecular structure of compound 5a.

Benzo[cd]furo[2,3ꢀf]indolꢀ4(5H)ꢀone derivatives
Table 2. Characteristics of compounds 2—6
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 1, January, 2008
161
Table 3. Spectroscopic characteristics of compounds 2—6 in
dichloromethane
Comꢀ Yield* M.p.
Found
Calculated
Molecular
formula
(%)
poꢀ
(%)
/°С
Compoꢀ
und
λ
max/nm
(ε•10–4/L mol–1 cm–1
)
und
С
H
N (S)
2
3
265 (3.43), 283 (1.83), 311(0.33), 326 (0.37), 393 (0.81)
282 (3.31), 341 (0.19), 359 (0.23), 388 (0.19)
254 (2.19), 283 (0.99), 326 (0.19), 340 (0.18), 396(0.42)
253 (2.17), 284 (0.95), 399 (0.39)
260 (3.27), 396 (0.4)
260 (3.49), 326 (0.33), 397 (0.52)
265 (2.68), 282 (2.39), 399 (0.37)
227 (7.79), 284 (2.98), 360 (0.27)
287 (3.13), 362 (0.38)
257 (2.48) 286 (3.62) 380 (0.30)
256 (2.45) 287(3.57) 362 (0.29)
269 (2.56) 362 (0.27)
308 (5.02) 321 (5.31)
308 (6.00) 322 (6.35) 351 (0.6)
312 (5.57) 325 (6.01)
2
83 139—140 70.57 5.10
70.58 5.13
10 162—163 76.01 4.66 5.96
75.94 4.67 5.90
69 167—168 75.75 4.76 4.53
75.70 4.76
62 142—143 76.88 5.81
5.56
5.49
С15Н13NO3
С15H11NO2
С20H15NO3
С20H15NO3
С23H21NO3
С20H14ClNO3
С21H17NO4
С20H13NO2
С23H19NO2
С20H12ClNO2
С23H18ClNO2
С21H15NO3
С20H13NO2
С23H19NO2
С20H12ClNO2
С23H18ClNO2
С21H15NO3
4a
4b
4c
4d
4e
5а
5b
5c
5d
5e
6а
6b
6c
6d
6e
3
4а
4b
4c
4d
4e
5а
5b
5c
5d
5e
6а
6b
6c
6d
6e
4.41
3.97
76.86 5.89 3.90
45 179—180 68.28 3.97 3.99
68.29 4.01
78 144—145 70.20 5.08 3.77
70.14 5.12 3.56
72 198—199 72.45 5.00 4.09
72.61 4.93 4.03
74 170—171 80.21 4.46 4.76
80.25 4.38 4.68
82 134—135 80.92 5.61
80.92 5.61
55 270—271 71.95 3.67 4.26
71.97 3.62 4.20
42 154—155 73.63 4.85 9.40
73.50 4.83 9.43
58 161—162 76.78 4.56 4.26
76.58 4.59 4.25
63 175—176 80.27 4.47
80.25 4.38 4.68
78 116—117 80.47 5.71
80.92 5.61
42 246—247 71.90 3.60 4.36
71.97 3.62 4.20
42 140—141 73.53 4.91
73.50 4.83 3.73
15** 220—221 76.76 4.42 4.35
76.58 4.59 4.25
3.98
312 (5.95) 322 (6.35) 353 (0.85)
313 (3.78) 327(4.03)
4.10
4.10
tals, molecules 5a and 6a are packed to form infinite
stacks.
To summarize, the cyclodehydration of 1ꢀalkylꢀ6ꢀ(2ꢀ
oxoꢀ2ꢀarylethoxy)ꢀ or 1ꢀalkylꢀ6ꢀ(2ꢀoxoꢀ2ꢀalkylethoꢀ
xy)benzo[cd]indolꢀ2(1H)ꢀones can be used for the synꢀ
thesis of functionalized benzo[cd]furo[2,3ꢀf]indolꢀ
4(5H)ꢀone derivatives.
4.81
4.11
4.10
Experimental
The 1H NMR spectra of solutions were recorded on a Varian
VXRꢀ300 instrument (300 MHz) with SiMe4 as the internal stanꢀ
dard. The electronic absorption spectra were measured on a
Shimadzu UVꢀ3100 spectrophotometer at a concentration of
1•10–5 mol L–1. The HPLC analysis was carried out on a Hitachi
LiChrograph highꢀpressure liquid chromatograph equipped with a
250½4.6 mm column and a LiChrosorb RP 18 column; acetoniꢀ
trile—water (80 : 20) was used as the mobile phase, the flow rate
was 1.0 mL min–1; the analytical wavelength λ = 295 nm; the
temperature was 24 °C, the volume of the samples was 20 µL. The
chromatograms were processed and the chromatographic characꢀ
teristics of the compounds were calculated on a Multispektr 3ꢀ1
integrating device (Scientific and Production Company “Analitika”).
The yields, melting points, elemental analysis data, electronic abꢀ
3.79
* The yields of the compounds isolated preparatively.
** The compound was isolated as an impurity to 5e.
The molecular and crystal structures of compounds
5a and 6a were studied by Xꢀray diffraction and are shown
in Figs 1 and 2, respectively. Selected geometric paramꢀ
eters are listed in Table 1.
In both molecules, the main cyclic O(1)N(1)C(1)—
C(13) group is approximately planar (the maximum deꢀ
viations of the atoms from the mean plane are 0.026 and
0.039 for 5a and 6a, respectively). The N(1) atom has a
trigonalꢀplanar configuration (the sum of the bond angles
at this atom in both molecules is 359.9°). The bondꢀ
length distribution in this system is indicative of a subꢀ
stantial electron density delocalization.10,11 The benzene
ring C(14)—C(19) is twisted with respect to the central
plane by only 14.7° in compound 6a; in compound 5a,
the twisting is substantially larger (by 29.5°). In the crysꢀ
1
sorption spectra, and H NMR spectra of compounds 1—6 are
given in Tables 2—4. Compounds 1a,b were synthesized according
to procedures described earlier.8,12
1ꢀMethylꢀ6ꢀ(2ꢀoxopropoxy)benzo[cd]indolꢀ2(1H)ꢀone (2).
Calcined potassium carbonate (48.3 g, 350 mmol) was added with
stirring to a solution of compound 1a (14 g, 70 mmol) in anhydrous
DMF (280 mL) warmed to 40 °C. Then chloroacetone (6.1 mL,
7.12 g, 77 mmol) was added dropwise for 30 min. The reaction
mixture was stirred for 3 h. The precipitate was filtered off, washed
on a filter with hot acetone (2×100 mL), and concentrated to 1/3 of
the initial volume. The precipitate of 2 was filtered off, the filtrate

162
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 1, January, 2008
Davydenko et al.
Table 4. 1H NMR spectra of compounds 2—6 in CDCl3
Comꢀ
pound
δ(J/Hz)
2 *
2.26 (s, 3 H, SCH3); 3.40 (s, 3 H, NCH3); 4.97 (s, 2 H, ОSH2); 6.79 (d, 1 H, S(8)H, 3JH,H = 7.8); 6.98 (d, 1 H,
S(7)H, 3JH,H = 7.8); 7.80 (dd, 1 H, S(4)H, 3JH,H = 7.2, 3JH,H = 8.1); 8.06 (d, 1 H, S(3)H, 3JH,H = 7.2);
8.27 (d, 1 H, S(5)H, 3JH,H = 8.1)
3
2.33 (s, 3 H, S(7)CH3); 3.48 (s, 3 H, NCH3); 6.94 (s, 1 H, S(6)H); 7.55 (q, 1 H, S(8)H, 3JH,H = 1.5); 7.76 (dd,
1 H, S(2)H, 3JH,H = 7.9); 8.03 (d, 1 H, S(3)H, 3JH,H = 7.9); 8.27 (d, 1 H, S(1)H, 3JH,H = 7.9)
3.40 (s, 3 H, NCH3); 5.42 (s, 2 H, ОSH2); 6.65 (d, 1 H, S(8)H, 3JH,H = 7.80); 6.70 (d, 1 H, S(7)H, 3JH,H = 7.80);
7.49—7.54 (m, 2 H, HAr); 7.61—7.67 (m, 1 H, HAr); 7.71 (dd, 1 H, S(4)H, 3JH,H = 7.2, 3JH,H = 8.1); 8.03—8.10
(m, 3 H, HAr + S(3)H); 8.32 (d, 1 H, S(5)H, 3JH,H = 8.1)
4а
4b
0.95 (t, 3 H, N(SH2)3SH3, 3JH,H = 7.5); 1.37—1.50, 1.71—1.80 (both m, 2 H each, SH2); 3.88 (t, 2 H, NCH2,
3JH,H = 7.5); 5.42 (s, 2 H, ОSH2); 6.64 (d, 1 H, S(8)H, 3JH,H = 7.8); 6.72 (d, 1 H, S(7)H, 3JH,H = 7.8); 7.48—7.54
(m, 2 H, HAr); 7.61—7.68 (m, 1 H, HAr); 7.71 (dd, 1 H, S(4)H, 3JH,H = 7.2, 3JH,H = 8.1); 8.03—8.11 (m, 3 H,
HAr + S(3)H); 8.32 (d, 1 H, S(5)H, 3JH,H = 8.1)
4c
3.41 (s, 3 H, NCH3); 5.36 (s, 2 H, ОSH2); 6.67 (d, 1 H, S(8)H, 3JH,H = 7.8); 6.71 (d, 1 H, S(7)H, 3JH,H = 7.80);
7.47—7.51 (m, 2 H, HAr); 7.72 (dd, 1 H, S(4)H, 3JH,H = 7.2, 3JH,H = 8.1); 8.00—8.03 (m, 2 H, HAr); 8.09 (d, 1 H,
S(3)H, 3JH,H = 8.1); 8.29 (d, 1 H, S(5)H, 3JH,H = 8.1)
4d *
0.90 (t, 3 H, N(SH2)3SH3, 3JH,H = 7.5); 1.30—1.40, 1.60—1.70 (both m, 2 H each, SH2); 3.86 (t, 2 H, NCH2,
3JH,H = 7.5); 5.75 (s, 2 H, ОSH2); 6.92 (d, 1 H, S(8)H, 3JH,H = 7.8); 7.03 (d, 1 H, S(7)H, 3JH,H = 7.8); 7.63—7.70
(m, 2 H, HAr); 7.80 (dd, 1 H, S(4)H, 3JH,H = 7.2, 3JH,H = 8.1); 8.05—8.11 (m, 3 H, HAr + S(3)H); 8.30 (d, 1 H,
S(5)H, 3JH,H = 8.1)
4e
5а
5b
3.41 (s, 3 H, NCH3); 3.90 (s, 3 H, ОCH3); 5.37 (s, 2 H, ОSH2); 6.67 (d, 1 H, S(8)H, 3JH,H = 7.80); 6.70 (d, 1 H,
S(7)H, 3JH,H = 7.8); 6.96—7.00 (m, 2 H, HAr); 7.72 (dd, 1 H, S(4)H, 3JH,H = 7.2, 3JH,H = 8.1); 8.03—8.09 (m, 3 H,
HAr + S(3)H); 8.33 (d, 1 H, S(5)H, 3JH,H = 8.1)
3.47 (s, 3 H, NCH3); 7.17 (s, 1 H, S(6)H); 7.42—7.48 (m, 1 H, HAr); 7.52—7.57, 7.64—7.67 (both m, 2 H each, HAr);
7.81 (dd, 1 H, S(2)H, 3JH,H = 7.2, 3JH,H = 8.1); 7.88 (s, 1 H, S(8)H); 8.06 (d, 1 H, S(3)H, 3JH,H = 7.2); 8.32
(d, 1 H, S(1)H, 3JH,H = 8.1)
0.96 (t, 3 H, N(SH2)3SH3, 3JH,H = 7.5); 1.38—1.51, 1.77—1.83 (both m, 2 H each, SH2); 3.96 (t, 2 H, NCH2,
3JH,H = 7.5); 7.18 (s, 1 H, S(6)H); 7.43—7.49 (m, 1 H, HAr); 7.51—7.57, 7.61—7.68 (both m, 2 H each, HAr); 7.82
(dd, 1 H, S(2)H, 3JH,H = 7.2, 3JH,H = 8.1); 7.88 (s, 1 H, S(8)H); 8.07 (d, 1 H, S(3)H, 3JH,H = 7.2);
8.34 (d, 1 H, S(1)H, 3JH,H = 8.1)
5c
5d
3.46 (s, 3 H, NCH3); 7.08 (s, 1 H, S(6)H); 7.49—7.61 (m, 4 H, HAr); 7.81 (dd, 1 H, S(2)H, 3JH,H = 7.2, 3JH,H = 8.1);
7.87 (s, 1 H, S(8)H); 8.06 (d, 1 H, S(3)H, 3JH,H = 7.2); 8.31 (d, 1 H, S(1)H, 3JH,H = 8.1)
0.96 (t, 3 H, N(SH2)3SH3, 3JH,H = 7.3); 1.42—1.48, 1.75—1.82 (both m, 2 H each, SH2); 3.95 (t, 2 H, NCH2,
3JH,H = 7.3); 7.08 (s, 1 H, S(6)H); 7.47—7.60 (m, 4 H, HAr); 7.81 (dd, 1 H, S(2)H, 3JH,H = 7.2, 3JH,H = 8.1);
7.86 (s, 1 H, S(8)H); 8.06 (d, 1 H, S(3)H, 3JH,H = 7.2); 8.32 (d, 1 H, S(1)H, 3JH,H = 8.1)
3.47 (s, 3 H, NCH3); 3.90 (s, 3 H, ОCH3); 7.06—7.09 (m, 2 H, HAr); 7.14 (s, 1 H, S(6)H); 7.56—7.59 (m, 2 H, HAr);
7.81 (dd, 1 H, S(2)H, 3JH,H = 7.2, 3JH,H = 8.1); 7.82 (s, 1 H, S(8)H); 8.06 (d, 1 H, S(3)H, 3JH,H = 7.2); 8.32
(d, 1 H, S(1)H, 3JH,H = 8.1)
5e
6а
6b
3.46 (s, 3 H, NCH3); 6.99 (s, 1 H, S(7)H); 7.13 (s, 1 H, S(6)H); 7.35—7.40 (m, 1 H, HAr); 7.46—7.51 (m, 2 H, HAr);
7.78 (dd, 1 H, S(2)H, 3JH,H = 7.2, 3JH,H = 8.1); 7.89—7.92 (m, 2 H, HAr); 8.03 (d, 1 H, S(3)H, 3JH,H = 7.2); 8.32
(d, 1 H, S(1)H, 3JH,H = 8.1)
0.97 (t, 3 H, N(SH2)3SH3, 3JH,H = 7.5); 1.39—1.52, 1.79—1.84 (both m, 2 H each, SH2); 3.92 (t, 2 H, NCH2,
3JH,H = 7.3); 6.98 (s, 1 H, S(7)H); 7.10 (s, 1 H, S(6)H); 7.33—7.38 (m, 1 H, HAr); 7.44—7.49 (m, 2 H, HAr); 7.77
(dd, 1 H, S(2)H, 3JH,H = 7.2, 3JH,H = 8.1); 7.87—7.91 (m, 2 H, HAr); 8.01 (d, 1 H, S(3)H, 3JH,H = 7.2); 8.30
(d, 1 H, S(1)H, 3JH,H = 8.1)
6c
6d
3.46 (s, 3 H, NCH3); 6.97 (s, 1 H, S(7)H); 7.11 (s, 1 H, S(6)H); 7.42—7.46 (m, 2 H, HAr); 7.76—7.83 (m, 3 H,
HAr + S(2)H); 8.03 (d, 1 H, S(3)H, 3JH,H = 7.2); 8.30 (d, 1 H, S(1)H, 3JH,H = 8.1)
0.98 (t, 3 H, N(SH2)3SH3, 3JH,H = 7.5); 1.42—1.48, 1.75—1.82 (both m, 2 H each, SH2); 3.96 (t, 2 H, NCH2,
3JH,H = 7.5); 7.02 (s, 1 H, S(7)H); 7.13 (s, 1 H, S(6)H); 7.43—7.47 (m, 2 H, HAr); 7.79—7.85 (m, 3 H, HAr + S(2)H);
8.05 (d, 1 H, S(3)H, 3JH,H = 7.2); 8.34 (d, 1 H, S(1)H, 3JH,H = 8.1)
6e
3.46 (s, 3 H, NCH3); 3.88 (s, 3 H, ОCH3); 6.98 (s, 1 H, S(7)H); 7.00 (s, 1 H, S(6)H); 6.98—7.02 (m, 2 H, HAr);
7.76—7.83 (m, 3 H, HAr + S(2)H); 8.01 (d, 1 H, S(3)H, 3JH,H = 7.2); 8.31 (d, 1 H, S(1)H, 3JH,H = 8.1)
* For solutions in DMSOꢀd6.

Benzo[cd]furo[2,3ꢀf]indolꢀ4(5H)ꢀone derivatives
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 1, January, 2008
163
Table 5. Crystallographic parameters and the Xꢀray data collection
and refinement statistics
methoxyphenyl)ꢀ2ꢀoxoethoxy]ꢀ1ꢀmethylbenzo[cd]indolꢀ2(1H)ꢀ
one (4e) were prepared.
Synthesis of compounds 5a—e (general procedure).
Polyphosphoric acid (tenfold excess, w/w) was added to benꢀ
zo[cd]indolꢀ2(1H)ꢀone derivatives 4a—e. The reaction mixture was
stirred at 85 °C for 3 h and cooled. Then a tenfold excess of ice water
was added. The precipitate was filtered off and washed with water to
neutral pH. The products were purified by chromatography or crysꢀ
tallization. 5ꢀMethylꢀ7ꢀphenylbenzo[cd]furo[2,3ꢀf]indolꢀ
4(5H)ꢀone (5a) (recrystallized from EtOH), 5ꢀbutylꢀ7ꢀphenylꢀ
benzo[cd]furo[2,3ꢀf]indolꢀ4(5H)ꢀone (5b) (purified by chromaꢀ
tography on a column with Silica gel Merck 100 using chloroform
as the eluent), 7ꢀ(4ꢀchlorophenyl)ꢀ5ꢀmethylbenzo[cd]furo[2,3ꢀ
f]indolꢀ4(5H)ꢀone (5c) (purified by chromatography on a column
with aluminium oxide Merck 90 using chloroform as the eluent),
5ꢀbutylꢀ7ꢀ(4ꢀchlorophenyl)benzo[cd]furo[2,3ꢀf]indolꢀ4(5H)ꢀ
one (5d) (recrystallized from toluene), and 7ꢀ(4ꢀmethoxyphenyl)ꢀ
5ꢀmethylbenzo[cd]furo[2,3ꢀf]indolꢀ4(5H)ꢀone (5e) (purified by
chromatography on a column with Merck 90 using a benzene—
ethyl acetate mixture as the eluent) were obtained.
Compound
5a
6a
a/Å
b/Å
c/Å
α/deg
11.1406(16)
7.3930(11)
34.494(5)
90
90
90
2841.0
8
1.4
8.760(5)
10.866(9)
16.013(12)
90
104.83(6)
90
1473.4
4
1.35
β/deg
γ/deg
V/Å3
Z
dcalc/g cm–3
Crystal system
Space group
µ/cm–1
Orthorhombic
Pbca
Monoclinic
P21/С
0.876
0.091
1248
F(000)
Crystal dimensions/mm
Diffractometer
624
0.21×0.11×0.43 0.19×0.40×0.52
«Bruker Smart «Enraf Nonius
ApexII»
MoꢀKα
CAD4»
MoꢀKα
Synthesis of compounds 6a—d (general procedure).
Polyphosphoric acid (15ꢀfold excess, w/w) was added to benꢀ
zo[cd]indolꢀ2(1H)ꢀone derivatives 4a—d. The reaction mixture was
stirred at 135 °C for 3 h and cooled. Then a 15ꢀfold excess of ice
water was added. The precipitate was filtered off and washed with
water to neutral pH. The product was purified by recrystallization
or chromatography. 5ꢀMethylꢀ8ꢀphenylbenzo[cd]furo[2,3ꢀ
f]indolꢀ4(5H)ꢀone (6a) (recrystallized from ethanol with an addiꢀ
tive of activated carbon) and 5ꢀbutylꢀ8ꢀphenylbenzo[cd]furo[2,3ꢀ
f]indolꢀ4(5H)ꢀone (6b) (purified by chromatography on a column
with aluminium oxide Merck 90 using chloroform as the eluent)
were obtained. In the case of product 6c, the reaction mixture was
heated for 10 h, treated with water, and extracted with chloroform.
The extract was dried with sodium sulfate and concentrated. 8ꢀ(4ꢀ
Chlorophenyl)ꢀ5ꢀmethylbenzo[cd]furo[2,3ꢀf]indolꢀ4(5H)ꢀone
(6c) was purified by chromatography on a column with aluminium
oxide Merck 90 using a benzene—ethyl acetate mixture as the eluꢀ
ent. 5ꢀButylꢀ8ꢀ(4ꢀchlorophenyl)benzo[cd]furo[2,3ꢀf]indolꢀ
4(5H)ꢀone (6d) was purified by chromatography on a column with
aluminium oxide Merck 90 using chloroform as the eluent.
Synthesis of compound 6a from 5a. Polyphosphoric acid (45 g)
was added to compound 5a (2.99 g, 10 mmol). The reaction mixꢀ
ture was stirred at 135 °C for 3 h and cooled. Then ice water
(300 mL) was added. The precipitate was filtered off and washed
with water to neutral pH. The product was chromatographed on
a column with Silica gel Merck 100 using chloroform as the eluent.
Xꢀray diffraction study of compounds 5a and 6a. Crystals were
grown by crystallization from DMF. Principal crystallographic
parameters for compounds 5a and 6a and the Xꢀray data collection
and refinement statistics are given in Table 5. Both structures were
solved by direct methods and refined by the fullꢀmatrix leastꢀsquares
method with anisotropic displacement parameters using the CRYSꢀ
TALS program package.13 All hydrogen atoms were located in
difference electron density maps and refined with fixed positional
and thermal parameters. The Chebyshev weighting scheme14 was
used in the refinement. The complete Xꢀray structural data for
compounds 5a and 6a were deposited with the Cambridge Strucꢀ
tural Database (CCDC 631876 and 632375, respectively).
Radiation
Index range
–14 ≥ h ≥ 8,
–9 ≥ k ≥ 7,
–34 ≥ l ≥ 43
26.55
0 ≥ h ≥ 10,
0 ≥ k ≥ 12,
–19 ≥ l ≥ 18
24.97
θmax/deg
Number of reflections:
measured
independent
used in refinement
with I ≥ 3σ(I)
Rmerge
8372
2935
1448
2931
2587
1118
0.034
0.038
0.038
0.032
0.037
0.04
R1(F)
Rw(F)
GOOF
Residual electron
density/e Å–3, max/min
1.125
1.194
0.16/–0.17
0.13/–0.15
was concentrated, and the residue was recrystallized from benzene.
The total yield was 14.8 g.
5,7ꢀDimethylbenzo[cd]furo[2,3ꢀf]indolꢀ4(5H)ꢀone (3).
Polyphosphoric acid (38 g) was added to compound 2 (2.55 g,
10 mmol). The reaction mixture was stirred at 100 °C for 8 h and
cooled. Then ice water (250 mL) was added. The precipitate was
filtered off and washed with water to neutral pH. The residue was
chromatographed on a silica gel column (Silica gel Merck 60) using
chloroform as the eluent.
Synthesis of compounds 4a—e (general procedure). The corꢀ
responding bromoacetophenone (20 mmol) and calcined potasꢀ
sium carbonate (13.8 g, 100 mmol) were added to a solution of
compound 1 (20 mmol) in DMF (20 mL). The reaction mixture
was stirred at 60 °C for 2 h, water (200 mL) was added, and the
precipitate was filtered off and washed with water. The product was
dried and recrystallized from an acetonitrile—DMF mixture.
1ꢀMethylꢀ6ꢀ(2ꢀoxoꢀ2ꢀphenylethoxy)benzo[cd]indolꢀ2(1H)ꢀone
(4a), 1ꢀbutylꢀ6ꢀ(2ꢀoxoꢀ2ꢀphenylethoxy)benzo[cd]indolꢀ2(1H)ꢀ
one (4b), 6ꢀ[2ꢀ(4ꢀchlorophenyl)ꢀ2ꢀoxoethoxy]ꢀ1ꢀmethylꢀ
benzo[cd]indolꢀ2(1H)ꢀone (4c), 1ꢀbutylꢀ6ꢀ[2ꢀ(4ꢀchlorophenyl)ꢀ
2ꢀoxoethoxy]benzo[cd]indolꢀ2(1H)ꢀone (4d), and 6ꢀ[2ꢀ(4ꢀ

164
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 1, January, 2008
Davydenko et al.
9. P. Cagniant, D. Cagniant, Adv. Heterocycl. Chem., Eds A. R.
Katritzky, A. J. Boulton, Academic Press, New York, 1975, 18,
337.
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