L. Liu et al.
6-Chloro-3-(9H-xanthen-9-yl)-1H-indole 3i: m.p. 145–147 ꢀC;
1H NMR (400 MHz, CDCl3): dppm 5.48 (s, 1H, CH), 6.88–7.27 (m, 12H),
7.90 (br, s, 1H, NH); 13 C NMR (100 MHz, CDCl3): dppm 151.3
(C–Oarom), 137.2 (C–Narom), 129.4 (Carom), 128.2 (Carom), 127.9
(Carom), 124.4 (Carom), 124.1 (Carom), 123.3 (Carom), 123.2 (Carom),
120.6 (Carom), 120.5 (Carom), 116.5 (Carom), 111.2 (Carom), 35.5
(CH); anal. calcd for C21H14ClNO: C 76.02, H 4.25, N 4.22; found
C 75.79, H 3.97, N 4.10.
To evaluate the generality of this reaction, using an optimized
protocol, we performed the direct substitution of xanthen-9-ol 1
with various indoles 2a-l (Table 2) in CH2Cl2 at room temperature
promoted by 1 mol% 1,3-dichloro-tetra-n-butyl-distannoxane.
As can be seen from the summarized results, except for indolin-
2-one, all other substituted indoles could smoothly proceed to
give the corresponding 3-(9-H-xanthen-9-yl)-1H-indole derivatives
with high or excellent yield. Not only 4-substituted or 5-substituted
indoles but also 6- or 7-substituted indoles showed high reactiv-
ity in our methodology (entries 3–11). Moreover, whether these
substituents are electronic-withdrawing groups or electronic-
donating groups, high yields of substituted products could be
obtained. Upon closer inspection of the data in Table 2, we
noticed that 4-chloroindole (Table 2, entry 4) gave a slightly lower
yield than those of 5- and 6-chloroindoles (Table 2, entries 6 and
9). This may be ascribed to the indole 4-position steric hindrance
and electronic-withdrawing effect for the electrophilic substitu-
tion in the place of the indole 3-position. Surprisingly, for the
4-acetoxy substituted indole, excellent yield could be afforded
in this reaction system (Table 2, entry 3). Furthermore, almost
quantitatively, product 3b was obtained when using the 2-methyl
indole (Table 2, entry 2). Nevertheless, for the indolin-2-one, two
by-products – 9H-xanthen-9-one and 9H-xanthene, were obtained
under this reaction condition with 13% and 42% yield (5 mg and
15 mg), respectively.
6-Bromo-3-(9H-xanthen-9-yl)-1H-indole 3j: m.p. 155–158 ꢀC;
1H NMR (400 MHz, CDCl3): dppm 5.47 (s, 1H, CH), 6.87–7.41 (m, 12H),
7.89 (br, s, 1H, NH); 13 C NMR (100 MHz, CDCl3): dppm 151.3 (C–Oarom),
137.7 (C–Narom), 129.4 (Carom), 128.0 (Carom), 124.7 (Carom), 124.1
(Carom), 123.2 (Carom), 123.1 (Carom), 121.0 (Carom), 120.6 (Carom),
116.5 (Carom), 115.9 (Carom), 114.2 (Carom), 100.0 (Carom), 35.5 (CH);
anal. calcd for C21H14BrNO: C 67.04, H 3.75, N 3.72; found C 66.85,
H 3.40, N 3.51.
1
7-Methyl-3-(9H-xanthen-9-yl)-1H-indole 3k: m.p. 185–187 ꢀC; H
NMR (400 MHz, CDCl3): dppm 2.41 (s, 3H, CH3), 5.52 (s, 1H, CH),
6.86–7.22 (m, 12H), 7.85 (br, s, 1H, NH); 13 C NMR (100MHz, CDCl3):
dppm 151.4 (C–Oarom), 136.3 (C–Narom), 129.5 (Carom), 127.7 (Carom),
125.5 (Carom), 124.5 (Carom), 123.1 (Carom), 122.7 (Carom), 122.6 (Carom),
121.0 (Carom), 120.4 (Carom), 119.9 (Carom), 117.5 (Carom), 116.3 (Carom),
35.7 (CH), 16.6 (CH3); anal. calcd for C22H17NO: C 84.86, H 5.50, N
4.50; found C 84.61, H 5.29, N 4.39.
1
2-(9H-Xanthen-9-yl)-1H-pyrrole 3m: m.p. 109–111 ꢀC; H NMR
1
(400 MHz, CDCl3): dppm 5.23 (s, 1H, CH), 5.99–6.05 (m, 2H),
6.46–6.48 (m, 1H), 6.84–7.14 (m, 8H), 7.52 (br, s, 1H, NH); 13 C
NMR (100 MHz, CDCl3): dppm 150.3 (C–Oarom), 150.2 (C–Oarom),
133.1 (C–N pyrrole), 128.4 (Carom), 127.9 (Carom), 127.1 (Carom),
127.0 (Carom), 122.3 (Carom), 122.1 (Carom), 122.0 (Carom), 121.8
(Carom), 117.1 (CH–N pyrrole), 115.6 (Carom), 115.4 (Carom), 106.9
(C pyrrole), 106.3 (C pyrrole), 36.2 (CH); anal. calcd for C17H13NO:
C 82.57, H 5.30, N 5.66; found C 82.15, H 4.80, N 5.06.
3-(9H-Xanthen-9-yl)pentane-2,4-dione 3n: m.p. 139–141 ꢀC;
1H NMR (400 MHz, CDCl3): dppm 1.87 (s, 6H), 4.08–4.11 (d, 1H, CH,
J =12Hz), 4.83–4.86 (d, 1H, CH, J = 12 Hz), 7.02–7.27 (m, 8H); 13 C
NMR (100 MHz, CDCl3): dppm 201.7 (CH3–C=O), 153.3 (C–Oarom),
129.1 (Carom), 128.40 (Carom), 123.7 (Carom), 123.4 (Carom), 116.8
(Carom), 73.8 (O=C–C–C=O), 40.2 (CH), 31.8 (CH3); anal. calcd for
C18H16O3: C 77.12, H 5.75; found C 76.90, H 5.69.
9H-Xanthen-9-one: 5 mg, yield 13%; H NMR (400 MHz, CDCl3):
d
ppm 7.39–7.42 (m, 2H, Ph), 7.51–7.53 (d, 2H, Ph), 7.73–7.77 (m, 2H,
Ph), 8.36–8.38 (m, 2H, Ph); 13 C NMR (100 MHz, CDCl3): dppm 177.3
(C=O), 156.2 (C–Oarom), 134.9 (Carom), 126.8 (Carom), 124.0 (Carom),
121.9 (Carom), 118.0 (Carom); anal. calcd for C13H8O2: C 79.58, H 4.11;
found C 79.67, H 4.16; ESI-MS calcd for C13H8O: 197.20 ([M + H]+),
found 197.27 ([M + H]+). 9H-Xanthene: 15 mg, yield 42%; H NMR
1
(400 MHz, CDCl3): dppm 4.06 (s, 2H, CH2), 7.01–7.07 (m, 4H, Ph),
7.17–7.22 (m, 4H, Ph); 13 C NMR (100 MHz, CDCl3): dppm 150.6
(C&bond;Oarom), 127.5 (Carom), 126.2 (Carom), 121.5 (Carom), 119.2
(Carom), 115.0 (Carom), 26.5 (CH2); ESI-MS calcd for C13H10O: 183.22
([M + H]+), found 183.07 ([M + H]+).
The reason for this remains unclear at present. Previous articles
have ever reported that Bu2SnO can oxidize alcohols into their
corresponding ketones.[34–36] Moreover, xanthen-9-ol 1 is easily ox-
idized in air. Thus, in our reaction system, the oxidative product was
also obtained due to the co-action of the stannoxane catalyst and
oxygen gas from air.
Results and Discussion
Next, we also examined the substitution of xanthen-9-ol with
other nucleophiles in our protocol (Fig. 2). The results are summa-
rized in Table 3. It was found that the high active nucleophiles,
such as 2 m and 2n, could be smoothly substituted by xanthen-
9-ol with high yields (Table 3, entries 1 and 2). However, in the
case of diethyl malonate, no corresponding substituted product
was obtained but resulted in the oxidative by-product 9H-
xanthen-9-one (Table 3, entry 3). To test our protocol efficiency,
we used the lower reactive furan, thiophene and imidazole
nucleophiles. As a result, only trace amounts of corresponding
substituted products were obtained, with a large amount of
9H-xanthen-9-ol left in these three cases catalyzed by 1,3-
dichloro-tetra-n-butyl-distannoxane after 10 h (Table 3, entries
4–6). Unfortunately, the reaction could not proceed in our pro-
tocol, even with a prolonged reaction time, when using the
N-methyl imidazole as a nucleophile (Table 3, entry 7). In addition,
the low activity of benzhydrol was also examined and no product
was obtained. This may be due to the very weak Lewis acidity of
1,3-dichloro- tetra-n-butyl-distannoxane catalyst.
In our initial study, we investigated the direct nucleophilic substitu-
tion of xanthen-9-ol 1 with indole 2a by using the various reaction
conditions (Table 1). As shown in Table 1, in the absence of catalyst,
the reaction could not proceed in water at room temperature even
prolonging reaction time to 96h, but it could take place in organic
solvent (THF or CH2Cl2) with low yield (entries 1–3, Table 1). When
using organotin compound, because of the poor solubility of
Bu2SnO in CH2Cl2, the reaction could only afford the corresponding
substituted product in more than the moderate level yield (entry 4).
And changing the Bu2SnO to the Bu2SnCl2, slightly better but not
best result was obtained (entry 5). In order to improve the reaction
yield further, we applied the high lipophilic 1,3-dichloro-tetra-n-
butyl-distannoxane to catalyze this reaction. As a result, excellent
reaction yield was obtained (entry 6). Nevertheless, this reaction
was sluggish in aqueous media in the presence of 1 mol%
1,3-dichloro-tetra-n-butyl- distannoxane (entry 7). This may be
due to its heterogeneous reaction.
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Copyright © 2012 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2012, 26, 9–15