Synthesis of 2-(3-indolyl)-1,4-naphthoquinones using 3-iodoindoles

Article abstract of DOI:10.1002/jhet.5570420625

The usefulness of 3-iodoindoles available for introduction of an indole unit is presented. The reaction of various halo-3-iodoindoles with 1,4-naphthoquinone gave the corresponding 2-(3-indolyl)-1,4-naphthoquinones in moderate yields. The 3-iodoindole was used for synthesis of a compound containing both naphthazarin and indole skeletons.

Full text of DOI:10.1002/jhet.5570420625

Sep-Oct 2005
1195
Synthesis of 2-(3-Indolyl)-1,4-naphthoquinones Using 3-Iodoindoles
Yasuhiro Tanoue*, Moritsugu Hamada and Norihisa Kai
Department of Food Science and Technology, National Fisheries
University, Nagatahonmachi, Shimonoseki 759-6595, Japan
Kazunori Sakata and Mamoru Hashimoto
Department of Applied Chemistry, Faculty of Engineering, Kyushu Institute of Technology, Tobata-ku,
Kitakyushu 804-8550, Japan
Takeshi Nagai
Department of Food Science and Technology, Tokyo University of Agriculture, Abashiri,
Hokkaido 099-2493, Japan
Received December 1, 2004
The usefulness of 3-iodoindoles available for introduction of an indole unit is presented. The reaction of
various halo-3-iodoindoles with 1,4-naphthoquinone gave the corresponding 2-(3-indolyl)-1,4-naphtho-
quinones in moderate yields. The 3-iodoindole was used for synthesis of a compound containing both naph-
thazarin and indole skeletons.
J. Heterocyclic Chem., 42, 1195 (2005).
An indole unit occurs naturally in indole alkaloids and
many of the naturally occurring compounds have physio-
logically important activity [1]. In previous papers [2,3]
we have reported syntheses of Tyrian purple [4] and its
related compounds using 3-iodoindoles. 3-Iodoindole
compounds are labile, and so are not commercially avail-
able. However, the compounds are easily synthesized
from the corresponding indoles.
Some reports have appeared concerning the reaction of
indoles with 1,4-naphthoquinones. For example, Bu’Lock
and Mason [5] reported that the reaction of indole (1) with
1,4-naphthoquinone (2) gave 2-(3-indolyl)-1,4-naphtho-
quinone (3) in acetic acid at room temperature for 7 days
without describing the yield. Prota et al. [6] found that the
reaction of 1 with 2 afforded 3 in acidic ethanol at room
temperature for an hour in moderate yield. In the course of

1196
Y. Tanoue, M. Hamada and N. Kai, K. Sakata and M. Hashimoto and T. Nagai
Vol. 42
our synthetic study of natural products containing an
indole moiety, we have found that 3-iodoindole is a favor-
able reagent for introduction of the indole unit into 2. The
present paper describes syntheses of 2-(3-indolyl)-1,4-
naphthoquinones and a compound having both naphtha-
zarin and indole skeletons using 3-iodoindoles.
In our hands the reported procedure [5] gave 3 in only 16
% yield. Therefore, we have investigated a difference of
reactivity in 1 and 3-iodoindole (4). The reaction of 4 with
2 in acetic acid at 90 °C for 40 minutes gave 3 in 74 %
yield. On the other hand, treatment of 1 with 2 afforded 3
under the same reaction conditions in only 11 % yield
(Scheme 1). The results seem to indicate that 4 is very
favorable for introduction of an indole unit in comparison
with 1. The reactions of 4 with 2 are shown in Table 1
under various conditions. Further refluxing time
decreased the yield in acetic acid because of decomposi-
tion of 4 (entry 5). Interestingly the product 3 was also
obtained in moderate yield in case of acetonitrile as solvent
(entry 6). On the basis of the results, the reaction of vari-
ous halo-3-iodoindoles (5) with 2 was run (Table 2). Since
compounds 5 were somewhat stable to heat relative to 4,
the reaction was kept under reflux in acetic acid.
naphthoquinone) moiety. On the other hand, aster-
riquinones [8], which exhibit a range of biological activi-
ties, have both indole and benzoquinone moieties.
Accordingly, we next have synthesized a compound 9,
which contains both moieties (Scheme 2).
Treatment of 4 with 5,8-dimethoxy-1,4-naphthoquinone
(7a) [9] gave 2-(3-indolyl)-5,8-dimethoxy-1,4-naphtho-
quinone (8a) in acetic acid at 90 °C for 20 minutes in 51 %
yield. Attempts to do demethylation [10] of 8a using
The structural determination of 6e is described as a typi-
1
cal example. The H NMR spectrum shows the signals at δ
7.26 (singlet) and 8.22 (doublet) due to 3-H and 2’-H,
respectively. The mass spectrum clearly exhibits the mol-
ecular ion peak at m/z 291. The data as well as the elemen-
tal analysis indicate the structure of 6e.
AlCl , BBr etc. were unsuccessful. Thus, the starting
3
3
Naturally occurring shikonin [7], which is a potent phar-
maceutical substance with a wide spectrum of biological
properties, contains a naphthazarin (5,8-dihydroxy-1,4-
material 7a was replaced by 5,8-diacetoxy-1,4-naphtho-
quinone (7b) [11]. The reaction of 4 with 7b gave 5,8-
diacetoxy-2-(3-indolyl)-1,4-naphthoquinone (8b) in

Sep-Oct 2005
Synthesis of 2-(3-Indolyl)-1,4-naphthoquinones Using 3-Iodoindoles
1197
2-(3-Indolyl)-1,4-naphthoquinone (3).
refluxing acetic acid for 5 minutes in 40 % yield with a by-
product, 5/8-acetoxy-5/8-hydroxy-2-(3-indolyl)-1,4-naph-
thoquinone (8c). The structure of 8c was mainly deter-
This compound was obtained as blackish-purple needles (ethyl
acetate), mp 206.5 –208 °C (lit [6], 175 °C); ir (KBr): NH 3245,
1
-1
1
mined by its H NMR spectrum, which shows the hydroxy
CO 1667, 1630 cm ; H nmr (dimethyl sulfoxide–d ): δ 7.02
6
–7.25 (m, 2H, 5'- and 6'-H), 7.26 (s, 1H, 3-H), 7.54 (dd, 1H, 7'-H,
J=1.2, 7.0 Hz), 7.84 – 7.86 (m, 2H, 6- and 7-H), 7.88 (d, 1H, 4'-
H, J=7.6 Hz), 8.00 (m, 1H, 5-H), 8.08 (m, 1H, 8-H), 8.25 (d, 1H,
(s, 1H) at δ 12.79 and the methyl protons (s, 3H) at δ 2.47.
Hydrolysis of 8b was carried out in aqueous ethanol
including sodium hydroxide to give our desired product,
5,8-dihydroxy-2-(3-indolyl)-1,4-naphthoquinone (9) in 65
% yield. The structural assignment of 9 was based on its
H NMR spectrum, which shows the quinone (s, 1H) at δ
7.30, the amine (s, 1H) at δ 12.14, and the two hydroxy
protons at δ 12.61 and 12.82.
In summary, we found that 3-iodoindoles are favorable
reagents for introduction of an indole unit. Compound 9,
which contains both naphthazarin and indole skeletons
was synthesized using this approach.
13
2'-H, J=2.7 Hz), 12.04 ppm (s, 1H, NH); C nmr (dimethyl sul-
foxide– d ): δ 107.33 (3'-C), 112.58 (7'-C), 119.97 (6'-C), 121.24
6
(5'-C), 125.12 (5'- and 8'-C), 126.48 (8-C), 127.64 (3-C), 131.64,
132.45 (9-C, 10-C), 132.51 (2'-C), 133.52, 133.99 (6- and 7-C),
136.70 (9'-C), 142.06 (2-C), 184.09 (C=O), 184.95 ppm(C=O);
1
+
ms: m/z (relative intensity) 273 (M , 100 %), 245 (22), 217 (36),
189 (13), 104 (22).
Anal. Calcd for C
H NO : C, 79.11; H, 4.06; N, 5.13.
18 11 2
Found: C, 78.69; H, 4.52; N, 5.10.
2-(6-Bromo-3-indolyl)-1,4-naphthoquinone (6a).
This compound was obtained as blackish-purple needles (ethyl
-1 1
EXPERIMENTAL
acetate), mp 276 - 278 °C; ir: NH 3160, CO 1666, 1628 cm ; H
nmr (dimetyl sulfoxide-d ): δ 7.24 (s, 1H, 3-H), 7.33 (dd, 1H, 5'-
6
1
13
H, J=1.8, 8.6 Hz), 7.71 (d, 1H, 7'-H, J=1.8 Hz), 7.83 (d, 1H, 4'-H,
J=8.6 Hz), 7.86 - 8.00 (m, 2H, 6- and 7-H), 8.02 (m, 1H, 5-H),
8.10 (m, 1H, 8-H), 8.23 (d, 1H, 2'-H, J=3.1 Hz), 12.10 ppm (s,
H NMR and C NMR spectra were taken on a JEOL JNM-
EX90A (90 MHz) and JEOL JNM-A500 (500 MHz) spectrom-
eters in chloroform-d and dimethyl sulfoxide-d at room tem-
6
13
1H, NH); C nmr (dimethyl sulfoxide -d ): δ 107.60, 115.06,
perature. Chemical shifts are given in ppm relative to tetram-
ethylsilane as an internal reference standard. EI mass spectra
were perforrmed with a JEOL JMS-SX 102A mass spectrome-
ter. Infrared spectra were recorded on a Shimadzu IR 470 spec-
tophotormeter as potassium bromide pellets. Melting points
were observed with a Yanaco MS-S3 micro melting point appa-
ratus (hot-plate type). Elemental analyses were determined
with a Yanaco CHN Corder MT-3. For preparative column
chromatography, Wakogel C-200 silica gel was employed.
Thin- layer chromatography (TLC) was accomplished on pre-
6
115.09, 121.87, 123.91, 124.27, 125.24, 126.58, 128.59, 131.64,
132.43, 133.00, 133.74, 134.14, 137.62, 141.72, 184.21 (C=O),
184.73 ppm (C=O); ms: m/z (relative intensity) 353 (M+2, 100
+
%), 351 (M , 98), 272 (12), 216 (21), 104 (29).
Anal. Calcd for C H BrNO : C, 61.39; H, 2.86; N, 3.98.
18 10
2
Found: C, 61.32; H, 2.92; N, 3.88.
2-(5-Bromo-3-indolyl)-1,4-naphthoquinone (6b).
This compound was obtained as reddish-purple grains (ethyl
acetate:hexane = 1:1), mp 237 - 238 °C; ir: NH 3240, CO 1667,
coated plates of silica gel 60F
Haloindoles were purchased from Tokyo Kasei Kogyo Co. Ltd
(Tokyo, Japan).
(Merck). 5- and 6-
254+365
-1
1
1629 cm ; H nmr (chloroform-d): δ 7.34 (d, 1H, 7'-H, J=8.5
Hz), 7.37 (s, 1H, 3-H), 7.39 (dd, 1H, 6'-H, J=1.8, 8.5 Hz), 7.74 -
7.79 (m, 2H, 6- and 7-H), 8.10 (d, 1H, 4'-H, J=1.8 Hz), 8.14 (m,
1H, 5-H), 8.17 (m, 1H, 8-H), 8.22 (d, 1H, 2'-H, J=3.1 Hz), 8.76
General Procedure for Iodination of Indoles.
13
ppm (s, 1H, NH); C nmr (chloroform-d): δ 108.65, 113.22,
Iodination of 6-bromoindole is described as a typical example.
To a solution of 6-bromoindole (100 mg, 0.51 mmol) in methanol
(10 ml) was added sodium hydroxide (20 mg, 0.51 mmol). After
the mixture was stirred at room temperature for 10 minutes, iodine
(129 mg, 0.51 mmol) and an aqueous solution (1 ml) of potassium
iodide (59 mg, 0.51 mmol) were added. The mixture was further
stirred at room temperature for 3 h, and then water was added.
The resulting precipitate was collected by filtration, washed with
water, and dried in vacuo to obtain 6-bromo-3-iodoindole (5a, 134
mg), which was used for the following reaction without purifica-
tion because of its lability.
115.35, 122.98, 125.90, 126.34, 126.94, 127.23, 130.21, 131.54,
132.16, 132.74, 133.45, 133.87, 134.90, 141.51, 185.17 (C=O),
185.22 ppm (C=O); ms: m/z (relative intensity) 353 (M+2, 91.8
+
%), 351 (M , 91.4 %), 274 (78), 273 (100), 272 (97), 245 (47),
244 (42), 217 (86), 216 (75), 189 (79).
Anal. Calcd for C H BrNO : C, 61.39; H, 2.86; N, 3.98.
18 10
2
Found: C, 61.59; H, 3.18; N, 3.82.
2-(6-Chloro-3-indolyl)-1,4-naphthoquinone (6c).
This compound was obtained as blackish-purple needles (ethyl
-1
1
acetate), mp 272 -274 °C; ir: NH 3170, CO 1666, 1628 cm ; H
General Procedure for Synthesis of 2-(3-Indolyl)-1,4-naphtho-
quinones.
nmr (dimethyl sulfoxide-d ): δ 7.21 (dd, 1H, 5'-H, J=1.8, 8.6 Hz),
6
7.25 (s, 1H, 3-H), 7.57 (d, 1H, 7'-H, J=1.8 Hz), 7.86 - 7.90 (m,
3H, 4'-, 6-, and 7-H), 8.02 (m, 1H, 5-H), 8.10 (m, 1H, 8-H), 8.25
Synthesis of 2-(6-bromo-3-indolyl)-1,4-naphthoquinone (6a)
is described as a typical example. A solution of 1,4-naphtho-
quinone (66 mg, 0.42 mmol) and 6-bromo-3-iodoindole (134 mg,
0.42 mol) in acetic acid (10 ml) was refluxed for 70 minutes.
After the mixture was concentrated under reduced pressure, the
residue was chromatographed on silica gel with chloroform to
give 6a (110 mg, 75 %).
13
(d, 1H, 2'-H, J=2.4 Hz), 12.10 ppm (s, 1H, NH); C nmr
(dimethyl sulfoxide-d ): δ 107.58, 112.16, 121.33, 121.51,
6
124.00, 125.24, 126.58, 127.07, 128.55, 131.65, 132.43, 133.10,
133.74, 134.14, 137.19, 141.74, 184.22 (C=O), 184.74 ppm
+
(C=O); ms: m/z (relative intensity) 309 (M+2, 35 %), 307 (M ,
100), 279 (28), 216 (40), 175 (28), 113 (29), 104 (83).

1198
Y. Tanoue, M. Hamada and N. Kai, K. Sakata and M. Hashimoto and T. Nagai
Vol. 42
Anal. Calcd for C H ClNO : C, 70.25; H, 3.28; N, 4.55.
Found: C, 70.33; H, 3.35; N, 4.47.
122.25, 125.12, 127.58, 131.41, 136.62, 142.27, 152.33, 152.81,
183.40 (C=O), 184.81 ppm (C=O); ms: m/z (relative intensity)
333 (M , 100 %), 316 (23), 304 (42), 290 (22), 163 (28), 141
18 10
2
+
2-(5-Chloro-3-indolyl)-1,4-naphthoquinone (6d).
This compound was obtained as blackish-purple needles (ethyl
(23), 130 (36), 117 (38).
Anal. Calcd for C
H NO : C, 72.06; H, 4.54; N, 4.20.
20 15 4
-1 1
acetate), mp 221 - 222 °C; ir: NH 3230, CO 1659, 1630 cm ; H
Found: C, 71.78; H, 4.51; N, 4.04.
nmr (dimeththyl sulfoxide - d ): δ 7.21 (s, 1H, 3-H), 7.24 (dd,
6
5,8-Diacetoxy-2-(3-indolyl)-1,4-naphthoquinone (8b).
1H, 6'-H, J=1.8, 8.6 Hz), 7.54 (d, 1H, 7'-H, J=8.6 Hz), 7.84 (d,
1H, 4'-H, J=1.8 Hz), 7.86 - 7.90 (m, 2H, 6- and 7-H), 8.02 (m,
1H, 5-H), 8.10 (m, 1H, 8-H), 8.23 (d, 1H, 2'-H, J=2.7 Hz), 12.16
This compound was obtained as blackish-purple grains (ethyl
acetate:hexane = 5:1), mp 235 - 237 °C; ir: NH 3375, CO 1760,
-1
1
13
1665, 1633 cm ; H nmr (chloroform-d): δ 7.19 (s, 1H, 3-H),
7.22 - 7.27 (m, 2H, 5'- and 6'-H), 7.35 (d, 1H, 6/7-H, J=8.9 Hz),
7.39 (d, 1H, 6/7-H, J=8.9 Hz), 7.40 (dd, 1H, 7'-H, J=1.8, 7.0 Hz),
7.83 (dd, 1H, 4'-H, J=1.8, 8.9 Hz), 8.06 (d, 1H, 2'-H, J=2.7 Hz),
(s, 1H, NH); C nmr (dimethyl sulfoxide - d ): δ 107.35, 114.02,
6
119.35, 122.48, 125.24, 125.75, 126.38, 126.38, 126.57, 128.78,
131.65, 132.38, 133.28, 133.72, 134.13, 135.20, 141.74, 184.22
(C=O), 184.67 ppm (C=O); ms: m/z (relative intensity) 309
13
+
8.73 ppm (s, 1H, NH); C nmr (chloroform-d): δ 21.19 (2CH ),
(M+2, 36 %), 307 (M , 100), 221 (25), 216 (14), 147 (12), 104
3
108.39, 111.91,120.30,121.90, 123.38, 124.55, 125.39, 125.60,
129.50, 130.19, 130.49, 130.94, 136.27, 142.11, 146.99, 147.58,
169.51 (CH CO), 169.66 (CH CO), 183.21 (C=O), 183.88 ppm
(20).
Anal. Calcd for C H ClNO : C, 70.25; H, 3.28; N, 4.55.
18 10
2
Found: C, 70.01; H, 3.50; N, 4.90.
3
3
+
(C=O); ms: m/z (relative intensity) 389 (M , 31 %), 347 (37),
305 (100), 276 (17), 141 (16).
2-(6-Fluoro-3-indolyl)-1,4-naphthoquinone (6e).
This compound was obtained as blackish-purple needles (ethyl
acetate:hexane = 2:1), mp 254 - 256 °C; ir: NH 3165, CO 1665,
Anal. Calcd for C
Found: C, 67.63; H, 4.00; N, 3.51.
H NO : C, 67.87; H, 3.88; N, 3.60.
22 15 6
-1
1
1620 cm ; H nmr (dimethyl sulfoxide - d ): δ 7.04 - 7.08 (m,
6
5/8-Acetoxy-5/8-hydroxy-2-(3-indolyl)-1,4-naphthoquinone
(8c).
1H, 5'-H), 7.26 (s, 1H, 3-H), 7.31 (dd, 1H, 7'-H, J=2.4, 9.5 Hz),
7.86 - 7.90 (m, 3H, 4'-, 6-, and 7-H), 8.02 (m, 1H, 5-H), 8.10 (m,
1H, 8-H), 8.22 (d, 1H, 2'-H, J=2.4 Hz), 12.05 ppm (s, 1H, NH);
This compound was obtained as blackish-purple needles (ethyl
acetate:hexane = 5:1), mp 177 - 179 °C; ir: NH 3355, CO 1756,
13
C nmr (dimethyl sulfoxide-d ): δ 98.69 (d, 7'-C, J=25.9 Hz),
6
-1
1
1616 cm ; H nmr (chloroform-d): δ 2.47 (s, 3H, CH ), 7.25 -
107.57 (3'-C), 109.41 (d, 5'-C, J=23.8 Hz), 121.34 (d, 4'-C,
J=10.3 Hz), 121.93, 125.23, 126.58, 128.20, 131.66, 132.47,
132.88, 133.72, 134.13, 136.85 (d, 8'-C, J=12.4 Hz), 141.85,
159.08 (d, 6'-C, J=237 Hz), 184.22 (C=O), 184.81 ppm (C=O);
3
7.31 (m, 5H, 3-, 5'-, 6'-, 6-, and 7-H), 7.38 (m, 1H, 7'-H), 7.90 (m,
1H, 4'-H), 8.13 (d, 1H, 2'-H, J=3.1 Hz), 8.77 (broad, 1H, NH),
13
12.79 ppm (s, 1H, OH); C nmr (chloroform-d): δ 21.21 (CH ),
108.92, 112.00, 114.84, 120.40, 122.14, 122.85, 123.57, 125.42,
125.70, 127.83, 131.85, 132.11, 136.24, 142.74, 143.81, 159.52
3
+
ms, m/z (relative intensity) 291 (M , 100 %), 263 (56), 235 (79),
207 (23), 104 (67).
(C-OH), 169.89 (COCH ), 183.64 (C=O), 189.75 ppm (C=O);
ms: m/z (relative intensity) 347 (M , 44 %), 306 (62), 305 (100),
277 (21), 276 (21), 220 (15).
Anal. Calcd for C
Found: C, 74.33; H, 3.56; N, 4.57.
H FNO : C, 74.22; H, 3.46; N, 4.81.
18 10 2
3
+
2-(5-Fluoro-3-indolyl)-1,4-naphthoquinone (6f).
Anal. Calcd for C
H NO : C, 69.16; H, 3.77; N, 4.03.
20 13 5
This compound was obtained as blackish-purple needles (ethyl
acetate:hexane = 5:1), mp 223 - 225 °C; ir: NH 3370, CO 1658,
Found: C, 68.87; H, 3.88; N, 3.96.
Hydrolysis of 5,8-Diacetoxy-2-(3-indolyl)-1,4-naphthoquinone
(8b).
-1
1
1640 cm ; H nmr (chloroform-d): δ 6.99 - 7.03 (m, 1H, 6'-H),
7.31 (s, 1H, 3-H), 7.35 (dd, 1H, 7'-H, J=4.6, 8.9 Hz), 7.60 (dd,
1H, 4'-H, J=2.1, 10.1 Hz), 7.73 -7.75 (m, 2H, 6- and 7-H), 8.12
(m, 1H, 5-H), 8.14 (m, 1H, 8-H), 8.22 (s, 1H, 2'-H), 9.60 ppm (s,
-2
To a solution of 8b (31 mg, 7.96×10 mmol) in ethanol (5 ml)
was added aqueous 1 M sodium hydroxide (10 ml). After the mix-
ture was stirred at room temperature for 2 h, acetic acid (1.5 ml)
and water (10 ml) were added. The resulting precipitate was col-
lected by filtration, washed with water, and dried. The crude prod-
uct was purified by thin - layer chromatography on silica gel to
give 9 (15.8 mg, 65 %). Recrystallization from acetonitrile gave
blackish-purple needles, mp 246 - 248 °C; ir: NH 3180, CO 1591
13
1H, NH); C nmr (chloroform-d): δ 105.9 (d, 4'-C, J=24.8 Hz),
111.5 (d, 6'-C, J=26.9 Hz), 112.7 (d, 9'-C, J=10.3 Hz), 112.8 (d,
7'-C, J=10.4 Hz), 125.8, 126.9, 129.3, 132.2, 132.6, 132.7, 132.8,
133.0, 133.4, 133.8, 142.0, 159.1 (d, 5'-C, J=238 Hz), 185.3
+
(C=O), 185.5 (C=O); ms: m/z (relative intensity) 291 (M , 100
%), 263 (54), 235 (72), 207 (20), 104 (49).
-1 1
cm ; H nmr (dimethyl sulfoxide-d ): δ 7.22 -7.27 (m, 2H, 5'- and
Anal. Calcd for C
H FNO : C, 74.22; H, 3.46; N, 4.81.
6
18 10 2
6'-H), 7.30 (s, 1H, 3-H), 7.36 (d, 1H, 6/7-H, J=9.5 Hz), 7.40 (d,
1H, 6/7-H, J=9.5 Hz), 7.55 (dd, 1H, 7'-H, J=1.4, 6.6 Hz), 7.90 (dd,
1H, 4'-H, J=1.3, 7.0 Hz), 8.33 (d, 1H, 2'-H, J=3.1 Hz), 12.14 (s,
Found: C, 74.01; H, 3.54; N, 4.79.
2-(3-Indolyl)-5,8-dimethoxy-1,4-naphthoquinone (8a).
13
1H, NH), 12.61 (s, 1H, OH), 12.82 ppm (s, 1H, OH); C nmr
This compound was obtained as reddish-orange needles (chlo-
roform:ethanol = 10:1), mp 285–287 °C; ir: NH 3325, CO 1641
(dimethyl sulfoxide-d ): δ 107.22, 111.43, 112.60, 112.70, 120.04,
6
-1
1
121.52, 122.78, 125.05, 127.43, 129.06, 130.01, 133.07, 136.69,
142.98, 157.23 (C-OH), 158.51 (C-OH), 185.97 (C=O), 186.67
cm ; H nmr (dimethyl sulfoxide - d ): δ 3.87 (s, 3H, OCH ),
6
3
3.89 (s, 3H, OCH ), 7.02 (s, 1H, 3-H), 7.17 -7.23 (m, 2H, 5'- and
3
+
ppm (C=O); ms: m/z (relative intensity) 305 (M , 100 %), 277
6'-H), 7.50 - 7.52 (m, 3H, 6-, 7-, and 7'-H), 7.80 (d, 1H, 4'-H,
J=7.3 Hz), 8.12 (d, 1H, 2'-H, J=2.8 Hz), 11.90 ppm (s, 1H, NH);
(18), 260 (11), 220 (13), 153 (14), 141 (16), 108 (19).
13
Anal. Calcd for C
H NO : C, 70.82; H, 3.63; N, 4.59.
C nmr (dimethyl sulfoxide-d ): δ 56.56 (CH ), 56.67 (CH ),
18 11 4
6
3
3
106.88, 112.41, 119.85, 120.35, 120.49, 120.85, 120.91, 122.07,
Found: C, 71.10; H, 4.16; N, 4.60.

Sep-Oct 2005
Synthesis of 2-(3-Indolyl)-1,4-naphthoquinones Using 3-Iodoindoles
1199
[5] J. D. Bu'Lock and J. Harley – Mason, J. Chem. Soc., 703
(1951).
[6] M. G. Corradini, C. Costantini, G. Prota and T. M. Schultz,
Gazz. Chim. Ital., 119, 153 (1989).
[7a] R. H. Thomson, Naturally Occurring Quinones III, Chapman
& Hall, London, 1987, pp 219 – 223; [b] A. Terada, Y. Tanoue, A.
Hatada and H. Sakamoto, J. Chem. Soc., Chem. Commun., 987 (1983);
[c] For a review, see: V. P. Papageorgiou, A. N. Assimopoulou, E. A.
Couladouros, D. Hepworth and K. C. Nicolaou, Angew. Chem. Int. Ed.
38, 270 (1999).
Acknowledgement.
We are grateful to Mr. Nobuhiko Akabane, Mr. Jun Endo, and
Mr. Takashi Teraoka for their technical assistance. We are also
thankful to the Center for Instrumental Analysis, Kyushu
Institute of Technology for elemental analyses, mass spectra and
NMR (500 MHz) spectra.
REFERENCES AND NOTES
[8] R. H. Thomson, Naturally Occurring Quinones III, Chapman
& Hall, London, 1987, pp 108–113.
[9a] D. B. Bruce and R. H. Thomson, J. Chem. Soc., 1089 (1955);
[b] Y. Tanoue and A. Terada, Bull. Chem. Soc. Jpn., 61, 2039 (1988).
[10] For a review on cleavage of ethers, see: V. M. Bhatt and S. U.
Kulkarni, Synthesis, 249 (1983).
[11] Y. Tanoue, K. Sakata, M. Hashimoto, M. Hamada, N. Kai and
T. Nagai, Nippon Kagaku Kaishi, 67 (1999); Chem. Abstr., 130, 182238s
(1999).
[1] For a review, see: M. Toyota and N. Ihara, Nat. Prod. Rep., 15,
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[2] Y. Tanoue, A. Terada, K. Sakata, M. Hashimoto, S. Morishita,
M. Hamada, N. Kai and T. Nagai, Fisheries Sci., 67, 726 (2001).
[3] Y. Tanoue, K. Sakata, M. Hashimoto, M. Hamada, N. Kai and
T. Nagai, Dyes and Pigments, 62, 101 (2004).
[4] For a review, see: P. E. McGovern and R. H. Michel, Acc.
Chem. Res., 23, 152 (1990).