A simple and green approach for the synthesis of tetrahydrobenzo[a]- xanthen-11-one derivatives using tetrabutyl ammonium fluoride in water

Article abstract of DOI:10.1055/s-0028-1088214

An efficient and simple procedure for the synthesis of 12-aryl- or 12-alkyl-8,9,10,12-tetrahydrobenzo[a]xanfhen-ll-one derivatives has been described. This one-pot multicomponent reaction involves the reaction of aldehydes, 2-naphthol, and cyclic 1,3- dik

Full text of DOI:10.1055/s-0028-1088214

LETTER
949
A Simple and Green Approach for the Synthesis of Tetrahydrobenzo[a]-
xanthen-11-one Derivatives Using Tetrabutyl Ammonium Fluoride in Water
Synthesisof
T
h
etrahydrobe
n
i
zo[
a
]x
j
anthen
a
-11-one De
y
Department of Chemistry, National Taiwan Normal University, 88 Tingchow Road, Section 4, Taipei 11677, Taiwan, Republic of China
Fax +886(2)29324249; E-mail: cheyaocf@ntnu.edu.tw
Received 18 September 2008
component reactions come close to the ideal of an ‘ideal
Abstract: An efficient and simple procedure for the synthesis of
synthesis’. Accordingly, the development of new multi-
12-aryl- or 12-alkyl-8,9,10,12-tetrahydrobenzo[a]xanthen-11-one
derivatives has been described. This one-pot multicomponent reac-
component reactions is still in demand.2
tion involves the reaction of aldehydes, 2-naphthol, and cyclic 1,3-
Over the past years, tetrabutylammonium fluoride
diketones in the presence of catalytic amount of recyclable TBAF
(TBAF) in organic synthesis has been widely used for
in water.
most fluoride-assisted reactions,3 deprotection of silyl
groups,4 desilyation,5 and fluorination.6 Tetrabutylammo-
Key words: tetrabutylammonium fluoride, recyclable, water,
tetrahydrobenzo[a]xanthen-11-one
nium fluoride has been widely recognized as a conve-
nient, organic-soluble source of naked fluoride ion. It has
also been widely used for a variety of base-catalyzed reac-
Green chemistry is the universally accepted term to de-
scribe the movement towards more environmentally ac-
ceptable chemical processes and products. The chemical
industry is a major contributor to environmental pollution
due to the ubiquitous use of hazardous organic solvents,
flammables, explosives, carcinogens, etc. The present day
challenge for chemists is to develop new products, pro-
cesses, and services that can achieve economical and en-
vironmental benefits. Solvents constitute a major factor in
deciding the efficacy of an environmental friendly tech-
nology. The ideal solvent should have a very low volatil-
ity, it should be chemically and physically stable,
recyclable and reusable, and eventually easy to handle. In
addition, solvents that allow more selective and rapid
transformations will have a significant impact. Water
emerged as a useful alternative solvent for several organic
reactions owing to many of its potential advantages such
as safety, economy, and environmental concern. Wender
et al. defined the ‘ideal synthesis’ as one in which the de-
sired product are obtained in as few steps as possible, in
quantitative yield, and environmentally compatible proce-
dure.1 The synthetic variables that have to be optimized
are time, cost, overall yield, simplicity of performance,
safety, and environmental acceptability. Multicomponent
reactions are those reactions in which three or more reac-
tants come together in a single reaction vessel to form a
new product which contains portions of all the compo-
nents. Generally, multicomponent-reaction strategy af-
fords savings in synthetic time and effort, and has
significant advantages over conventional two-component
reactions in several aspects, such as variable and high
bond-forming efficiency. With a small set of starting ma-
terials, very large libraries can be developed within a short
time. On the basis of above-mentioned advantages, multi-
tions such as alkylation, elimination, Michael addition,
and aldol condensation.7 The potential ability of the fluo-
ride ion to act as a base might be predicated on consider-
ing the strength of the H–F bond. Most ionic fluorides are
easy to prepare and use and are stable over long periods of
time. The fluoride ion is hygroscopic, but it does not react
with water and may therefore be recovered from aqueous
solution by conventional techniques. Benzoxanthene de-
rivatives are important components of biologically active
heterocycles. They also show various pharmacological
properties such as anti-inflammatory,8 antiviral,9 and anti-
bacterial activities.10 Besides this, they are well known for
their application in dyes,11 pH-sensitive fluorescent mate-
rials.12 Thus, the synthesis of a variety of xanthene hetero-
cyclic molecules is desirable. Based on the green-
chemistry approach and ideal synthesis, we have looked
into the synthesis of tetrahydrobenzo[a]xanthen-11-one
derivatives utilizing TBAF as recyclable catalyst in tap
water as economic and ecofriendly materials as catalysts
(Figure 1).
Preliminary efforts were mainly focused on the evaluation
of different additives. The yields of tetrahydroben-
zo[a]xanthen-11-one derivatives obtained by reacting al-
dehydes, 2-naphthol, and cyclic 1,3-diketones are shown
in Table 1. First, it was clearly suggested that TBAF cer-
tainly catalyzed the multicomponent reactions (compare
entries 1 and 2, Table 1). The reactions carried out by us-
ing different ammonium halide such as chloride, bromide,
and iodide showed that the fluoride ion was more active
than other halides (entries 3–5, Table 1).
The result agreed with the literature and revealed that qua-
ternary ammonium halides are known to give rise to an or-
der of nucleophilicity for the halide ions which parallels
their electronegativities, that is, fluoride > chloride > bro-
mide > iodide. We tried to explore an effective system for
multicomponent reactions by screening other fluoride
sources under the same conditions. It was found that the
SYNLETT 2009, No. 6, pp 0949–0954
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x.
x
x.
2
0
0
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Advanced online publication: 16.03.2009
DOI: 10.1055/s-0028-1088214; Art ID: W14308ST
© Georg Thieme Verlag Stuttgart · New York

950
S. Gao et al.
LETTER
Figure 1 Sketch of the procedure for the recyclable aqueous reaction system for the multicomponent reaction
fluoride ion of TBAF was the most reactive than other cycled in four times without much lost in its effectiveness.
fluoride sources (entries 6–9, Table 1). The reaction in Moreover, the recycling process and purification were op-
water was faster than in other organic solvents due to hy- erationally simple and convenient to carry out. After com-
drophobic interactions that induced a favorable aggregat- pletion of the reaction, a simple filtration afforded the
ing of the polar components in polar water. The benzoxanthene derivatives in good to excellent yield, and
observation showed the possibility of recycling TBAF the filtrate including TBAF was direct used for the next
and reusing it in the multicomponent reaction (Table 2). It cycle. On the basis of the optimization of the reaction con-
was noteworthy that the TBAF could be recovered and re- ditions, the scope of these fluoride anion catalyzed multi-
Table 1 One-Pot Synthesis of Benzo[a]xanthen Derivatives in the Presence of Various Additivesa
O
O
CHO
+
OH
additive
+
solvent
100 °C
F
O
O
1
2
3
4
F
Entry
1
Additive (equiv)
–
Solvent
H2O
Time (h)
Yield of 4 (%)b
2
2
2
2
2
2
2
2
2
2
2
2
2
2
27
90
57
58
48
24
43
16
35
48
42
62
53
55
2
TBAF (0.1)
TBACl (0.1)
TBABr (0.1)
TBAI (0.1)
NH4F (0.1)
LiF (0.1)
H2O
3
H2O
4
H2O
5
H2O
6
H2O
7
H2O
8
KF (0.1)
H2O
9
CsF (0.1)
H2O
10
11
12
13
14
TBAF (0.1)
TBAF (0.1)
TBAF (0.1)
TBAF (0.1)
TBAF (0.1)
DMF
DMSO
MeOH
MeCN
CH2Cl2
a Conditions: 1 (2 mmol), 2 (2 mmol), 3 (2 mmol), additive (10 mol%), solvent (5 mL), reflux.
b NMR yield.
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LETTER
Synthesis of Tetrahydrobenzo[a]xanthen-11-one Derivatives
951
Table 2 Recycling and Reuse of TBAF-Catalyzed Multicomponent Reaction in Watera
O
O
CHO
OH
TBAF (10 mol%)
O
+
+
O
H2O (5 mL)
reflux
O
F
O
1
2
5
6b
F
Cycle
Time (h)
Yield of 6b (%)b
1
2
3
4
5
1.5
1.5
2
99
99
82
81
45
2
2
a Conditions: 1 (2 mmol), 2 (2 mmol), and 5 (2 mmol), TBAF (10 mol%), H2O (5 mL), reflux.
b NMR yield.
Table 3 Preparation of Benzo[a]xanthen Derivatives Using TBAFa
(continued)
component reactions was explored. Not only aromatic
aldehyde, but also aliphatic aldehyde in the reactions af-
forded benzoxanthene derivatives in 60–99% yields
(Table 3). Various aromatic aldehydes with electron-
donating or electron-withdrawing group reacted success-
fully and afforded the products in good to excellent yields.
Entry
Product 413
Time (h) Yield (%)b
O
In order to extend the scope and limitations of these fluo-
ride ion catalyzed multicomponent reactions, various aro-
matic aldehydes with electron-donating or electron-
withdrawing group reacted with Meldrum’s acid and 2-
naphthol could undergo multicomponent reactions to give
the benzoxanthene derivatives in 72–94% isolated yields
(Table 4).
O
3
3.5
92
95
89
88
Cl
O
4c
Table 3 Preparation of Benzo[a]xanthen Derivatives Using TBAFa
O
4
5
6
4
Entry
Product 413
Time (h) Yield (%)b
NO2
O
O
4d
4e
4f
1
9
99
O
3
O
4a
O
OH
O
2
2
88
O
O
3
F
4b
OMe
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952
S. Gao et al.
LETTER
Table 3 Preparation of Benzo[a]xanthen Derivatives Using TBAFa
(continued)
Table 4 Preparation of Benzo[a]xanthen Derivatives Using TBAFa
Entry
Product
Product13 Time (h) Yield (%)b
Entry
Product 413
Time (h) Yield (%)b
O
O
O
1
6a
6b
6
92
99
7
6
90
O
O
O
O
O
4g
2
3
4
1.5
O
O
O
8
15
60
F
O
O
O
O
O
O
O
NH
4h
6c
3
94
9
9
99
Cl
O
4i
6d
15
72
OMe
O
10
18
96
5
6e
2
80
4j
4k
4l
O
11c
3
72
O
a Conditions: 1 (2 mmol), 2 (2 mmol), 5 (2 mmol), TBAF (10 mol%),
H2O (5 mL), reflux.
b Isolated yield.
OH
O
In conclusion, we have developed a novel, highly effi-
cient, and recyclable procedure for the synthesis of benz-
oxanthene derivative from aldehyde, 2-naphthol, and
cyclic 1,3-diketone. The procedures described here are
simple, mild, and efficient. The use of TBAF as a recycla-
ble catalyst has the advantages of being economically
viable and more efficient for multicomponent reactions in
aqueous media. The reaction system can be successfully
applied to a variety of cyclic 1,3-diketone as well as
Meldrum’s acid to synthesize a wide variety of benzox-
anthene derivatives in good to excellent yields.
12c
3
75
O
NO2
a Conditions: 1 (2 mmol), 2 (2 mmol), 3 (2 mmol), TBAF (10 mol%),
H2O (5 mL), reflux.
b Isolated yield.
c The reaction was performed by using 1,3-cyclohexanedione.
Synlett 2009, No. 6, 949–954 © Thieme Stuttgart · New York

LETTER
Synthesis of Tetrahydrobenzo[a]xanthen-11-one Derivatives
953
J = 16.3 Hz, 1 H), 2.23 (d, J = 16.3 Hz, 1 H), 1.11 (s, 3 H),
0.95 (s, 3 H). 13C NMR (100 MHz, CDCl3): d = 197.03,
164.07, 147.95, 144.94, 131.69, 131.61, 129.01, 128.62,
128.57, 128.42, 127.19, 126.42, 128.05, 123.88, 117.91,
117.23, 114.48, 51.11, 41.62, 34.90, 32.45, 29.48, 27.36.
HRMS (EI): m/z calcd. for C25H22O2 [M+]: 354.1620; found:
354.1621.
Acknowledgment
Financial support of this work by the National Science Council of
the Republic of China and Nation Taiwan Normal University (TOP
001) is gratefully acknowledged.
References and Notes
12-(4-Fluorophenyl)-9,9-dimethyl-8,9,10,12-tetrahydro-
benzo[a]xanthen-11-one (4b)
(1) Wender, P. A.; Handy, S. T.; Wrigth, D. L. Chem. Ind. 1997,
765.
White solid; mp 185–186 °C. 1H NMR (400 MHz, CDCl3):
d = 7.92 (d, J = 8.4 Hz, 1 H), 7.78–7.74 (m, 2 H), 7.44–7.40
(m, 1 H), 7.38–7.34 (m, 1 H), 7.32–7.23 (m, 3 H), 6.84 (t,
J = 8.7 Hz, 2 H), 5.69 (s, 1 H), 2.54 (s, 2 H), 2.30 (d, J = 16.3
Hz, 1 H), 2.23 (d, J = 16.3 Hz, 1 H), 1.10 (s, 3 H), 0.94 (s, 3
H). 13C NMR (100 MHz, CDCl3): d = 197.06, 164.09,
161.38 (d, J = 254 Hz), 147.93, 140.75 (d, J = 3 Hz), 131.71,
131.44, 130.08 (d, J = 8 Hz), 129.19, 128.65, 127.24,
125.16, 123.71, 117.56, 117.23, 115.22 (d, J = 21 Hz),
114.28, 51.06, 41.56, 34.17, 32.42, 29.49, 27.25. HRMS
(EI): m/z calcd for C25H21FO2 [M+]: 372.1526; found:
372.1528.
(2) (a) Nair, V.; Vinod, A. U.; Rajesh, C. J. Org. Chem. 2001,
66, 4427. (b) Bora, U.; Saikia, A.; Boruah, R. C. Org. Lett.
2003, 5, 435. (c) Demaude, T.; Knerr, L.; Pasau, P. J. Comb.
Chem. 2004, 6, 768. (d) Fayol, A.; Zhu, J. Org. Lett. 2004, 6,
115. (e) Nair, V.; Menon, R. S.; Beneesh, P. B.; Sreekumar,
V.; Bindu, S. Org. Lett. 2004, 6, 767. (f) Nair, V.; Bindu,
S.; Sreekumar, V.; Rath, N. P. Org. Lett. 2005, 5, 665.
(g) Nair, V.; Sreekumar, V.; Bindu, S.; Suresh, E. Org. Lett.
2005, 7, 2297. (h) Siamaki, A. R.; Arndtsen, B. A. J. Am.
Chem. Soc. 2006, 128, 6050. (i) Cui, S.-L.; Lin, X.-F.;
Wang, Y.-G. Org. Lett. 2006, 8, 4517. (j) Xu, X.; Cheng,
D.; Li, J.; Guo, H.; Yan, J. Org. Lett. 2007, 9, 1585.
(k) Cui, S.-L.; Wang, J.; Wang, Y.-G. Org. Lett. 2007, 9,
5023.
12-(4-Chlorophenyl)-9,9-dimethyl-8,9,10,12-tetrahydro-
benzo[a]xanthen-11-one (4c)
White solid; 182–183 °C. 1H NMR (400 MHz, CDCl3): d =
7.90 (d, J = 8.2 Hz, 1 H), 7.79 (d, J = 6.1 Hz, 1 H), 7.77 (d,
J = 8.4 Hz, 1 H), 7.45–7.42 (m, 1 H), 7.40–7.36 (m, 1 H),
7.32 (d, J = 8.9 Hz, 1 H), 7.25 (s, 2 H), 7.13 (d, J = 8.4 Hz,
2 H), 2.56 (s, 2 H) 2.31 (d, J = 16.3 Hz, 1 H), 2.24 (d,
J = 16.3 Hz, 1 H), 1.12 (s, 3 H), 0.96 (s, 3 H). 13C NMR (100
MHz, CDCl3): d = 197.07, 164.26, 147.96, 143.46, 132.14,
131.74, 131.44, 130.01, 129.31, 128.70, 128.61, 127.33,
125.24, 123.68, 117.29, 117.25, 114.05, 51.08, 41.62, 34.40,
32.47, 29.51, 27.35. HRMS (EI): m/z calcd for C25H21ClO2
[M+]: 388.1230; found: 388.1227.
(3) (a) Mori, A.; Kawashima, J.; Shimada, T.; Suguro, M.;
Hirabayashi, K.; Nishihara, Y. Org. Lett. 2000, 2, 2935.
(b) Barluenga, J.; Andina, F.; Fernandez-Rodriguez, M. A.;
Garcia-Garcia, P.; Merino, I.; Aquilar, E. J. Org. Chem.
2004, 69, 7352.
(4) Crouch, R. D. Tetrahedron 2004, 60, 5833.
(5) (a) Capperucci, A.; Degl’Innocenti, A.; Leriverend, C.;
Metzner, P. J. Org. Chem. 1996, 61, 7174. (b) Sirol, S.;
Courmarcel, J.; Mostefai, N.; Riant, O. Org. Lett. 2001, 3,
4111. (c) Denmark, S. E.; Sweis, R. F. J. Am. Chem. Soc.
2001, 123, 6439. (d) Mattson, A. E.; Zuhl, A. M.; Reynolds,
T. E.; Scheidt, K. A. J. Am. Chem. Soc. 2006, 128, 4932.
(6) (a) Albanese, D.; Landini, D.; Penso, M. J. Org. Chem.
1998, 63, 9587. (b) Shellhamer, D. F.; Horney, M. J.; Pettus,
B. J.; Pettus, T. L.; Stringer, J. M.; Heasley, V. L.; Syvert,
R. G.; Dobrolsky, J. M. Jr. J. Org. Chem. 1999, 64, 1094.
(c) Fan, R.-H.; Zhou, Y.-G.; Zhang, W.-X.; Hou, X.-L.; Dai,
L.-X. J. Org. Chem. 2004, 69, 335. (d) Yin, J.; Zarkowsky,
D. S.; Thomas, D. W.; Zhao, M. M.; Huffman, M. A. Org.
Lett. 2004, 6, 1465. (e) Sun, H.; DiMagno, S. G. J. Am.
Chem. Soc. 2005, 127, 2050.
(7) (a) Clark, J. H. Chem. Rev. 1980, 80, 429. (b) Pearson, A.
J.; Roush, W. R. Activating Agents and Protecting Groups;
J. Wiley and Sons: Chichester, 1999. (c) Ooi, T.; Maruoka,
K. Acc. Chem. Res. 2004, 37, 526. (d) Ménand, M.; Dalla,
V. Synlett 2005, 95.
(8) Poupelin, J. P.; Saint-Ruf, G.; Foussard-Blanpin, O.;
Marcisse, G.; Uchida-Ernouf, G.; Lacroix, R. Eur. J. Med.
Chem. 1978, 67.
9,9-Dimethyl-12-(4-nitrophenyl)-8,9,10,12-tetrahydro-
benzo[a]xanthen-11-one (4d)
White solid; mp 183–185 °C. 1H NMR (400 MHz, CDCl3):
d = 8.03 (d, J = 8.7 Hz, 2 H), 7.84–7.80 (m, 3 H), 7.51 (d,
J = 8.7 Hz, 2 H), 7.44–7.37 (m, 2 H), 7.36 (d, J = 9.0 Hz, 1
H), 2.60 (s, 2 H), 2.33 (d, J = 16.3 Hz, 1 H), 2.24 (d, J = 16.3
Hz, 1 H), 1.13 (s, 3 H), 0.95 (s, 3 H). 13C NMR (100 MHz,
CDCl3): d = 196.92, 164.82, 152.07, 148.00, 146.57, 131.79,
131.24, 129.84, 129.56, 128.87, 127.59, 125.45, 123.83,
123.32, 117.29, 116.25, 113.21, 51.00, 41.64, 35.08, 32.47,
29.49, 27.28. HRMS (EI): m/z calcd for C25H21NO4 [M+]:
399.1471; found: 399.1471.
12-(4-Hydroxyphenyl)-9,9-dimethyl-8,9,10,12-tetra-
hydrobenzo[a]xanthen-11-one (4e)
White solid; mp 213–214 °C. 1H NMR (400 MHz, CDCl3):
d = 7.97 (d, J = 8.3 Hz, 1 H), 7.77–7.72 (m, 2 H), 7.40 (t,
J = 8.0 Hz, 1 H), 7.35 (t, J = 7.3 Hz, 1 H), 7.30 (d, J = 8.9
Hz, 1 H), 7.14 (d, J = 8.4 Hz, 2 H), 6.73 (s, 1 H), 6.58 (d,
J = 8.4 Hz, 2 H), 5.61 (s, 1 H), 2.54 (s, 2 H), 2.30 (d, J = 16.4
Hz, 1 H), 2.24 (d, J = 16.4 Hz, 1 H), 1.08 (s, 3 H), 0.94 (s, 3
H). 13C NMR (100 MHz, CDCl3): d = 198.41, 164.73,
154.68, 147.75, 136.72, 131.73, 131.57, 129.70, 128.94,
128.56, 127.17, 125.11, 123.98, 118.07, 117.17, 115.55,
114.70, 51.03, 41.61, 34.12, 32.55, 29.38, 27.32. HRMS
(EI): m/z calcd for C25H22O3 [M+]: 370.1569; found:
370.1570.
(9) Lambert, R. W.; Martin, J. A.; Merrett, J. H.; Parkes,
K. E. B.; Thomas, G. J. WO 9706178, 1997.
(10) Hideo, T.; Teruomi, J. JP 56005480, 1981.
(11) (a) Banerjee, A.; Mukherjee, A. K. Stain Technol. 1981, 56,
83. (b) Menchen, S. M.; Benson, S. C.; Lam, J. Y. L.; Zhen,
W.; Sun, D.; Rosenblum, B. B.; Khan, S. H.; Taing, M.
US 6583168, 2003.
12-(4-Methoxyphenyl)-9,9-dimethyl-8,9,10,12-tetra-
hydrobenzo[a]xanthen-11-one (4f)
(12) Knight, C. G.; Stephens, T. Biochem. J. 1989, 258, 683.
(13) Analytical Data of Compounds 4 and 6
White solid; mp 211–212 °C. 1H NMR (400 MHz, CDCl3):
d = 7.98 (d, J = 8.4 Hz, 1 H), 7.74 (t, J = 9.3 Hz, 2 H), 7.42
(t, J = 7.4 Hz, 1 H), 7.35 (t, J = 7.3 Hz, 1 H), 7.30 (d, J = 8.9
Hz, 1 H), 7.24 (d, J = 8.6 Hz, 2 H), 6.69 (d, J = 8.6 Hz, 2 H),
5.65 (s, 1 H), 3.66 (s, 3 H), 2.54 (s, 2 H), 2.29 (d, J = 16.4
Hz, 1 H), 2.23 (d, J = 16.4 Hz, 1 H), 1.10 (s, 3 H), 0.96 (s, 3
H). 13C NMR (100 MHz, CDCl3): d = 197.11, 163.81,
9,9-Dimethyl-12-phenyl-8,9,10,12-tetrahydro-benzo[a]-
xanthen-11-one (4a)
White solid; mp 152–153 °C. 1H NMR (400 MHz, CDCl3):
d = 7.98 (d, J = 8.4 Hz, 1 H), 7.78–7.73 (m, 2H), 7.44–7.40
(m, 1H), 7.37–7.30 (m, 4 H), 7.16 (t, J = 7.6 Hz, 2 H), 7.04
(t, J = 7.3 Hz, 1 H), 5.71 (s, 1 H), 2.56 (s, 2 H), 2.30 (d,
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128.47, 126.99, 124.84, 123.29, 117.76, 117.07, 114.88,
114.82, 36.49, 33.06, 26.89, 19.97. HRMS (EI): m/z calcd
for C23H18O3 [M+]: 342.1256; found: 342.1257.
12-(4-Nitrophenyl)-8,9,10,12-tetrahydrobenzo[a]-
xanthen-11-one (4l)
157.96, 147.86, 137.34, 131.66, 129.52, 128.87, 128.54,
127.10, 125.01, 123.85, 118.06, 117.20, 114.58, 113.75,
55.21, 51.08, 41.54, 33.99, 32.40, 29.45, 27.34. HRMS (EI):
m/z calcd for C26H24O3 [M+]: 384.1725; found: 384.1726.
12-[Benzo[d][1,3]dioxol-5-yl}-9,9-dimethyl-8,9,10,12-
tetrahydrobenzo[a]xanthen-11-one (4g)
White solid; mp 246–247 °C. 1H NMR (400 MHz, CDCl3):
d = 8.03 (d, J = 8.7 Hz, 2 H), 7.82–7.79 (m, 3 H), 7.50 (d,
J = 8.7 Hz, 2 H), 7.45–7.35 (m, 3 H), 2.79–2.70 (m, 2 H),
2.48–2.36 (m, 2 H), 2.11–2.05 (m, 1 H), 2.00–1.93 (m, 1 H).
13C NMR (100 MHz, CDCl3): d = 197.08, 166.50, 152.31,
147.97, 146.55, 131.77, 131.20, 129.82, 129.62, 128.84,
127.56, 125.42, 123.84, 123.33, 117.22, 116.24, 114.45,
37.13, 35.02, 27.96, 20.42. HRMS (EI): m/z calcd for
C23H17NO4 [M+]: 371.1158; found: 371.1156.
1-Phenyl-1H-benzo[f]chromen-3 (2H)-one (6a)
White solid; mp 117–118 °C. 1H NMR (400 MHz, CDCl3):
d = 7.85 (d, J = 9.2 Hz, 2 H), 7.78 (d, J = 8.1 Hz, 1 H), 7.48–
7.40 (m, 2 H), 7.34 (d, J = 8.9 Hz, 1 H), 7.26–7.17 (m, 3 H),
7.11 (d, J = 7.1 Hz, 2 H), 4.94 (dd, J = 6.4, 2.2 Hz, 1 H),
3.22–3.12 (m, 2 H). 13C NMR (100 MHz, CDCl3): d =
167.26, 149.99, 140.74, 131.28, 131.19, 130.11, 129.41,
128.94, 127.76, 127.65, 127.12, 125.44, 123.24, 117.79,
117.74, 37.84, 37.65. HRMS (EI): m/z calcd. for C19H14O2
[M+]: 274.0994; found: 274.0986.
White solid; mp 213–214 °C. 1H NMR (400 MHz, CDCl3):
d = 7.98 (d, J = 8.4 Hz, 1 H), 7.78 (d, J = 8.5 Hz, 1 H), 7.75
(d, J = 9.0 Hz, 1 H), 7.44 (td, J = 7.0, 1.2 Hz, 1 H), 7.38 (td,
J = 7.9, 0.9 Hz, 1 H), 7.30 (d, J = 8.9 Hz, 1 H), 6.85 (dd,
J = 8.0, 1.7 Hz, 1 H), 6.78 (d, J = 1.6 Hz, 1 H) 6.61 (d,
J = 8.0 Hz, 1 H), 5.81 (dd, J = 16.9, 1.3 Hz, 1 H), 5.63 (s, 1
H), 2.56 (s, 2 H), 2.31 (d, J = 16.4 Hz, 1 H), 2.26 (d, J = 16.4
Hz, 1 H), 1.11 (s, 3 H), 0.99 (s, 3 H). 13C NMR (100 MHz,
CDCl3): d = 197.12, 163.98, 147.93, 147.69, 146.00, 139.12,
131.72, 131.60, 129.05, 128.62, 127.20, 125.13, 123.88,
121.96, 117.90, 117.27, 114.48, 109.17, 108.12, 100.95,
51.17, 41.63, 34.52, 32.47. HRMS (EI): m/z calcd for
C26H22O4 [M+]: 398.1518; found: 398.1506.
12-(1H-indol-3-yl)-9,9-dimethyl-8,9,10,12-tetrahydro-
benzo[a]xanthen-11-one (4h)
Colorless oil. 1H NMR (400 MHz, CDCl3): d = 8.13 (d,
J = 8.4 Hz, 1 H), 7.99 (s, 1 H), 7.73–7.71 (m, 2 H), 7.53 (d,
J = 8.0 Hz, 1 H), 7.37–7.29 (m, 3 H), 7.20 (dd, J = 5.2, 2.8
Hz, 2 H), 7.03 (td, J = 7.1, 0.7 Hz, 1 H), 6.95 (td, J = 7.5, 0.8
Hz, 1 H), 6.01 (s, 1 H), 2.62 (d, J = 17.2 Hz, 1 H), 2.56 (d,
J = 17.2 Hz, 1 H), 2.28 (d, J = 16.0 Hz, 1 H), 2.21 (d,
J = 16.0 Hz, 1 H), 1.10 (s, 3 H), 0.90 (s, 3 H). 13C NMR (100
MHz, CDCl3): d = 197.52, 163.96, 147.78, 136.54, 132.02,
131.71, 128.83, 128.53, 126.91, 126.19, 124.92, 123.89,
123.58, 121.68, 119.59, 119.58, 117.63, 117.14, 113.64,
111.24, 51.22, 41.59, 32.46, 29.28, 27.75, 26.78.
1-(4-Fluorophenyl)-1H-benzo[f]chromen-3 (2H)-one
(6b)
White solid; mp 138–139 °C. 1H NMR (400 MHz, CDCl3):
d = 7.88 (d, J = 9.2 Hz, 1 H), 7.87 (d, J = 9.2 Hz, 1 H), 7.75
(d, J = 8.2 Hz, 1 H), 7.51–7.43 (m, 2 H), 7.35 (d, J = 8.9 Hz,
1 H), 7.11–7.06 (m, 2 H), 6.98–6.92 (m, 2 H), 3.21 (dd,
J = 15.8, 3.2 Hz, 1 H), 3.13 (dd, J = 15.8, 2.1 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 167.07, 163.53, 161.08,
149.99, 136.45, 136.41, 131.35, 131.07, 130.34, 129.06,
128.86, 128.78, 127.79, 125.57, 123.08, 117.79, 117.61,
116.47, 116.25, 37.77, 37.14. HRMS (EI): m/z calcd for
C19H13FO2 [M+]: 292.0900; found: 292.0901.
12-Butyl-9,9-dimethyl-8,9,10,12-tetrahydrobenzo[a]-
xanthen-11-one (4i)
White solid; mp 120–122 °C. 1H NMR (400 MHz, CDCl3):
d = 8.10 (d, J = 8.4 Hz, 1 H), 7.81 (d, J = 8.0 Hz, 1 H), 7.69
(d, J = 8.8 Hz, 1 H), 7.53 (t, J = 7.7 Hz, 1 H), 7.42 (t, J = 7.8
Hz, 1 H), 7.19 (d, J = 8.9 Hz, 1 H), 4.72 (t, J = 4.5 Hz, 1 H),
2.56 (d, J = 17.6 Hz, 1 H), 2.50 (d, J = 17.6 Hz, 1 H), 2.38
(d, J = 16.4 Hz, 1 H), 2.32 (d, J = 16.4 Hz, 1 H), 1.81–1.75
(m, 2 H), 1.19 (s, 3 H), 1.14 (s, 3 H), 1.14–1.04 (m, 3 H),
0.89–0.82 (m, 1 H), 0.71 (t, J = 7.1 Hz, 3 H). 13C NMR (100
MHz, CDCl3): d = 197.72, 166.28, 148.68, 131.63, 131.44,
128.74, 128.14, 126.89, 124.97, 123.44, 118.62, 117.01,
113.02, 51.26, 41.59, 35.00, 32.34, 29.86, 28.14, 27.48,
27.29, 22.93, 14.21. HRMS (EI): m/z calcd for C23H26O2
[M+]: 334.1933; found: 334.1927.
1-(4-Chlorophenyl)-1H-benzo[f]chromen-3 (2H)-one
(6c)
Colorless oil. 1H NMR (400 MHz, CDCl3): d = 7.91–7.83
(m, 2 H), 7.73 (d, J = 8.1 Hz, 1 H), 7.52–7.41 (m, 2 H), 7.34
(d, J = 9.2 Hz, 1 H), 7.23 (d, J = 8.4 Hz, 2 H), 7.05 (d, J = 8.4
Hz, 2 H), 4.93 (d, J = 6.2 Hz, 1 H), 3.22 (dd, J = 15.7 Hz,
1 H), 3.12 (dd, J = 15.7 Hz, 1 H). 13C NMR (100 MHz,
CDCl3): d = 166.94, 150.03, 139.20, 133.72, 131.04, 130.42,
129.63, 129.07, 128.59, 127.83, 125.61, 123.02, 117.78,
117.26, 37.55, 37.26.
1-(4-Methoxyphenyl)-1H-benzo[f]chromen-3 (2H)-one
(6d)
9,9-Dimethyl-12-(naphthalen-2-yl)- 8,9,10,12-tetra-
hydrobenzo[a]xanthen-11-one (4j)
White solid; mp 132–133 °C. 1H NMR (400 MHz, CDCl3):
d = 7.85 (d, J = 8.7 Hz, 2 H), 7.78 (d, J = 8.2 Hz, 1 H), 7.48–
7.40 (m, 2 H), 7.33 (d, J = 8.9 Hz, 1 H), 7.02 (d, J = 8.6 Hz,
2 H), 6.77 (d, J = 8.7 Hz, 2 H), 4.90 (dd, J = 6.2, 2.2 Hz, 1
H), 3.71 (s, 3 H), 3.17 (dd, J = 15.8, 6.4 Hz, 1 H), 3.11 (dd,
J = 15.8, 2.6 Hz, 1 H). 13C NMR (100 MHz, CDCl3): d =
167.34, 158.92, 149.70, 132.61, 131.11, 131.02, 129.84,
128.78, 128.04, 127.74, 127.48, 125.29, 123.14, 118.10,
117.55, 114.60, 114.36, 55.20, 37.63, 36.80.
White solid; mp 231–233 °C. 1H NMR (400 MHz, CDCl3):
d = 8.04 (d, J = 8.4 Hz, 1 H), 7.81 (s, 1 H), 7.80–7.71 (m, 3
H), 7.67 (d, J = 7.7 Hz, 1 H), 7.64 (d, J = 8.8 Hz, 1 H), 7.46
(d, J = 8.4 Hz, 1 H), 7.42–7.29 (m, 5 H), 5.88 (s, 1 H), 2.58
(s, 2 H), 2.25 (q, J = 16.1 Hz, 2 H), 1.10 (s, 3 H), 0.92 (s, 3
H). 13C NMR (100 MHz, CDCl3): d = 197.08, 164.16,
148.04, 142.32, 133.51, 132.34, 131.74, 131.67, 129.16,
128.58, 128.22, 128.21, 127.62, 127.34, 127.23, 126.92,
125.91, 125.60, 125.11, 123.91, 117.76, 117.27, 114.27,
51.11, 41.66, 35.11, 32.44, 29.49, 27.41.
1-(Naphthalen-2-yl)-1H-benzo[f]chromen-3 (2H)-one
(6e)
12-(4-Hydroxyphenyl)-8,9,10,12-tetrahydrobenzo[a]-
xanthen-11-one (4k)
White solid; mp 178–180 °C. 1H NMR (400 MHz, CDCl3):
d = 7.90 (d, J = 9.0 Hz, 1 H), 7.89–7.84 (m, 1 H), 7.82–7.74
(m, 3 H), 7.65–7.63 (m, 1 H), 7.45–7.37 (m, 6 H), 7.33 (dd,
J = 8.5, 1.6 Hz, 1 H), 5.10 (dd, J = 5.9, 3.0 Hz, 1 H), 3.30–
3.21 (m, 2 H). 13C NMR (100 MHz, CDCl3): d = 167.21,
150.13, 138.15, 133.70, 132.90, 131.35, 131.26, 130.26,
129.49, 128.98, 128.08, 127.80, 127.70, 126.55, 126.29,
125.93, 125.49, 125.20, 123.28, 117.82, 117.66, 38.06,
37.61.
White solid; mp 293–296 °C. 1H NMR (400 MHz, DMSO-
d6): d = 9.17 (s, 3 H), 7.99 (d, J = 8.4 Hz, 1 H), 7.90 (d,
J = 7.4 Hz, 1 H), 7.89 (d, J = 8.9 Hz, 1 H), 7.48 (td, J = 7.0,
1.1 Hz, 1 H), 7.44–7.39 (m, 2 H), 7.05 (d, J = 8.5 Hz, 2 H),
6.55 (d, J = 8.5 Hz, 2 H), 5.48 (s, 1 H), 2.77–2.70 (m, 2 H),
2.41–2.27 (m, 2 H), 2.02–1.96 (m, 1 H), 1.90–1.79 (m, 1 H).
13C NMR (100 MHz, DMSO-d6): d = 196.18, 165.27,
155.56, 147.11, 135.70, 131.02, 130.65, 129.03, 128.76,
Synlett 2009, No. 6, 949–954 © Thieme Stuttgart · New York