Cascade nucleophilic addition-cyclic Michael addition of arynes and phenols/anilines bearing ortho α,β-unsaturated groups: Facile synthesis of 9-functionalized xanthenes/acridines

Article abstract of DOI:10.1021/jo902311a

(Chemical Equation Presented) A facile synthesis of xanthenes and acridines based on a cascade nucleophilic addition-cyclic Michael addition process of arynes and phenols/anilines substituted with α,β-unsaturated groups at the ortho positions is described

Full text of DOI:10.1021/jo902311a

pubs.acs.org/joc
fluoresceins, rhodamines, etc., which have a xanthene
Cascade Nucleophilic Addition-Cyclic Michael
Addition of Arynes and Phenols/Anilines Bearing
Ortho r,β-Unsaturated Groups: Facile Synthesis of
9-Functionalized Xanthenes/Acridines
nucleus, exhibit essentiality in labeling proteins,2 riboses,3
and cell processes.4 Some xanthenes are good protein5 or
peptide6 receptor antagonists and potentially useful as anti-
Alzheimer drugs.7 Recently, xanthene derivatives were re-
ferred to photocatalysts in metal-free hydrogenations8 and
ligands in transition metal catalysis.9 The unit of acridines
also frequently shows up in many useful dyes which could
bond to RNA.10 Moreover, acridine derivatives such as
AcrHRs are haptens of catalytic antibody 9D911 and play
particular roles in biocatalysis12 and organic chemistry.13
Acridines are potential drugs due to their trypanocidal
activities.14 It is notable that although substituents at the 9
positions of xanthenes and acridines are essential linkers to
attach biomolecules in these examples, the linking modes
were rather limited. This is probably because of the fact that
the existing strategies to afford 9-functionalized xanthenes
or acridines are rare, most of which often include at least a
Fiedel-Craft cyclization reaction15 to construct the hetero-
cyclic nucleus and subsequent manipulation at the 9 posi-
tions of these compounds.16 So it is still desirable to develop
Xian Huang*,†,‡ and Tiexin Zhang†
†Department of Chemistry, Zhejiang University (Xixi
Campus), Hangzhou 310028, People’s Republic of China and
‡State Key Laboratory of Organometallic Chemistry,
Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, Shanghai 200032, People’s Republic of China
huangx@mail.hz.zj.cn
Received October 29, 2009
(6) Naya, A.; Sagara, Y.; Ohwaki, K.; Saeki, T.; Ichikawa, D.; Iwasawa,
Y.; Noguchi, K.; Ohtake, N. J. Med. Chem. 2001, 44, 1429.
(7) Wischik, C. M.; Edwards, P. C.; Harrington, C. R.; Roth, M.; Klug,
A. Inhibition of τ-τ association. U.S. Patent 6 953 794, 2005.
(8) Lazarides, T.; McCormick, T.; Du, P.; Luo, G.; Lindley, B.;
Eisenberg, R. J. Am. Chem. Soc. 2009, 131, 9192.
(9) Yin, J.; Buchwald, S. L. Org. Lett. 2000, 2, 1101.
A facile synthesis of xanthenes and acridines based on a
cascade nucleophilic addition-cyclic Michael addition
process of arynes and phenols/anilines substituted with
R,β-unsaturated groups at the ortho positions is de-
scribed. The reaction has also been successfully extended
to the synthesis of 9-spiro-xanthene and acridine deriva-
tives with potential biochemical interest.
(10) (a) Kuzuya, A.; Mizoguchi, R.; Sasayama, T.; Zhou, J.-M.;
Komiyama, M. J. Am. Chem. Soc. 2004, 126, 1430. (b) Carlson, C. B.; Beal,
P. A. J. Am. Chem. Soc. 2002, 124, 8510.
(11) Bensel, N.; Bahr, N.; Reymond, M. T.; Schenkels, C.; Reymond,
J.-L. Helv. Chim. Acta 1999, 82, 44.
(12) Fukuzumi, S.; Tokuda, Y.; Etano, T.; Okamoto, T.; Otera, J. J. Am.
Chem. Soc. 1993, 115, 8960.
(13) (a) Fukuzumi, S.; Okamoto, K.; Tokuda, Y.; Gros, C. P.; Guilard, R.
J. Am. Chem. Soc. 2004, 126, 17059. (b) Fukuzumi, S.; Ohkubo, K.; Tokuda,
Y.; Suenobu, T. J. Am. Chem. Soc. 2000, 122, 4286.
(14) (a) Inhoff, O.; Richards, J. M.; Brıˆet, J. W.; Lowe, G.; Krauth-Siegel,
R. L. J. Med. Chem. 2002, 45, 4524. (b) Bonse, S.; Santelli-Rouvier, C.;
Barbe, J.; Krauth-Siegel, R. L. J. Med. Chem. 1999, 42, 5448. (c) Obexer, W.;
Schmid, C.; Barbe, J.; Galy, J. P.; Brun, R. Trop. Med. Parasitol. 1995, 46, 49.
(15) For construction of xanthene nucleus, see: (a) Ishibashi, H.;
Takagaki, K.; Imada, N.; Ikeda, M. Tetrahedron 1994, 50, 10215. (b)
Ishibashi, H.; Takagaki, K.; Imada, N.; Ikeda, M. Synlett 1994, 1, 49. For
construction of acridine nucleus, see: (c) Baum, J. S.; Condon, M. E.; Shook,
D. A. J. Org. Chem. 1987, 52, 2983.
Xanthenes and acridines are of biochemical and pharma-
ceutical importance.1 A class of fluorescent dyes including
(1) (a) Wolff, M. E., Ed. Burger’s Medicinal Chemistry, 4th ed.; John Wiley
& Sons, Inc.: New York, 1981; Part III, pp 393-407. (b) Smith D. F., Ed.
Handbook of Stereoisomer: Drugs in Psychopharmacology; CRC Press; Boca
Raton, FL, 1984; pp 255-283. (c) Lednicer, D.; Metscher, L. A. Organic
Chemistry of Drug Synthesis; John Wiley & Sons, Inc.: New York, 1977;
pp 859-1067. (d) Birman, V. B.; Chopra, A.; Ogle, C. A. Tetrahedron Lett.
1996, 37, 5073. (e) Ajtai, K.; Ilich, P. J. K.; Ringler, A.; Sedarous, S. S.; Toft, D. J.;
Burghardt, T. P. Biochemistry 1992, 31, 12431.
(16) (a) Nishino, H.; Kamachi, H.; Baba, H.; Kurosawa, K. J. Org. Chem.
ꢁ
1992, 57, 3551. (b) Prashad, M.; Lu, Y.; Repic, O. J. Org. Chem. 2004, 69, 584.
(17) Himeshima, Y.; Sonoda, T.; Kobayashi, H. Chem. Lett. 1983, 1211.
(18) Gilchrist, T. L. Supplement C: The Chemistry of Triple Bonded
Functional Groups, Part 1; Patai, S., Rappaport, Z., Eds.; John Wiley &
Sons: New York, 1983.
(2) (a) Okoh, M. P.; Hunter, J. L.; Corrie, J. E. T.; Webb, M. R.
Biochemistry 2006, 45, 14764. (b) Ajtai, K.; Burghardt, T. P. Biochemistry
1995, 34, 15943. (c) Salmon-Chemin, L.; Buisine, E.; Yardley, V.; Kohler, S.;
Debreu, M.-A.; Landry, V.; Sergheraert, C.; Croft, S. L.; Krauth-Siegel,
R. L.; Davioud-Charvet, E. J. Med. Chem. 2001, 44, 548. (d) Blackman,
M. J.; Corrie, J. E. T.; Croney, J. C.; Kelly, G.; Eccleston, J. F.; Jameson,
ꢀ
D. M. Biochemistry 2002, 41, 12244. (e) Ojemyr, L.; Sanden, T.; Widengren,
J.; Brzezinski, P. Biochemistry 2009, 48, 2173.
(3) Conibear, P. B.; Jeffreys, D. S.; Seehra, C. K.; Eaton, R. J.; Bagshaw,
C. R. Biochemistry 1996, 35, 2299.
(4) Gonc-alves, M. S. T. Chem. Rev. 2009, 109, 190.
(5) (a) Sato, N.; Jitsuoka, M.; Shibata, T.; Hirohashi, T.; Nonoshita, K.;
Moriya, M.; Haga, Y.; Sakuraba, A.; Ando, M.; Ohe, T.; Iwaasa, H.;
Gomori, A.; Ishihara, A.; Kanatani, A.; Fukami, T. J. Med. Chem. 2008,
51, 4765. (b) Sato, N.; Takahashi, T.; Shibata, T.; Haga, Y.; Sakuraba, A.;
Hirose, M.; Sato, M.; Nonoshita, K.; Koike, Y.; Kitazawa, H.; Fujino, N.;
Ishii, Y.; Ishihara, A.; Kanatani, A.; Fukami, T. J. Med. Chem. 2003, 46, 666.
(19) For reviews on the cascade/tandem reactions of aryne triggered by
initial nucleophilic additions, see: (a) Sanz, R. Org. Prep. Proced. Int. 2008,
~
40, 215. (b) Rathwell, K.; Brimble, M. A. Synthesis 2007, 643. (c) Pena, D.;
ꢀ
ꢀ
Perez, D.; Guitian, E. Angew. Chem., Int. Ed. 2006, 45, 3579. (d) Dyke, A. M.;
Hester, A. J.; Lloyd-Jones, G. C. Synthesis 2006, 4093. (e) Pellissier, H.;
Santelli, M. Tetrahedron 2003, 59, 701. (f) Biehl, E. R.; Khanapure, S. P. Acc.
Chem. Res. 1989, 22, 275. (g) Kessar, S. V. Acc. Chem. Res. 1978, 11, 283. For
other cascade/tandem reactions triggered by nucleophilic additions, see:
(h) Cant, A. A.; Bertrand, G. H. V.; Henderson, J. L.; Roberts, L.; Greaney,
M. F. Angew. Chem., Int. Ed. 2009, 48, 5199. (i) Allan, K. M.; Hong, B. D.;
Stoltz, B. M. Org. Biomol. Chem. 2009, 7, 4960. (j) Giacometti, R. D.;
Ramtohul, Y. K. Synlett 2009, 2010. (k) Rogness, D. C.; Larock, R. C.
Tetrahedron Lett. 2009, 50, 4003. (l) Gilmore, C. D.; Allan, K. M.; Stoltz,
B. M. J. Am. Chem. Soc. 2008, 130, 1558. (m) Allan, K. M.; Stoltz, B. M.
J. Am. Chem. Soc. 2008, 130, 17270. (n) Soorukram, D.; Qu, T.; Barrett,
A. G. M. Org. Lett. 2008, 10, 3833. (o) Blackburn, T.; Ramtohul, Y. K.
Synlett 2008, 1159.
€
506 J. Org. Chem. 2010, 75, 506–509
Published on Web 12/18/2009
DOI: 10.1021/jo902311a
r
2009 American Chemical Society

Huang and Zhang
JOCNote
more efficient and facile methods to access 9-functionalized
xanthene and acridine derivatives.
TABLE 1. Optimization Experiments on the Synthesis of Xanthene 3aa
Since the innovation with the in situ generation of aryne
from silylaryl triflates induced by fluoride anion,17 research
on aryne chemistry sprang up again. Due to their low-lying
LUMO, arynes are highly apt to accept nucleophilic at-
tacks.18 Many cascade reactions triggered by nucleophilic
additions to arynes have been developed.19 Recently, the
scaffolds of xanthene and acridine were constructed from a
cascade nucleophilic addition-electrophilic cyclizing reac-
tion of Nu-E bifunctional reagents and arynes. As the
intramolecular Nu-E reagents, salicylaldehydes, o-hydroxyl-
phenyl ketones,20 salicylates, and their nitrogen- or sulfur-
containing analogues participated well in these processes.21
During our study on aryne chemistry,22 we envisioned that
9-functionalized xanthenes or acridines may be obtained via
a cascade nucleophilic addition-cyclic Michael addition
process if the electrophilic countpart in the Nu-E reagents
is replaced by R,β-unsaturated Michael acceptors, which
seems difficult due to the limited examples of aryl carbanions
participating in Michael addition.23 Herein, we wish to
report our results on this facile annulation using arynes
and phenols/anilines bearing ortho-substituted R,β-unsatu-
rated groups.
yield (%)b
entry equiv of CsF solvent T (°C) time (h)
3a
4a
58
61
5.6
6.3
7.0
1c
2
3
4
4
4
4
MeCN
MeCN
THF
rt
rt
36
24
29
31
84
89
92
3
4
5
rt
40
66
144
72
36
THF
THF
aThe reactions were carried out with 1a (0.6 mmol), 2a (0.9 mmol),
and a specified amount of CsF in 20 mL of solvent. bThe reactions were
monitored by TLC. Isolated yields based on 1 equiv of 1a. c0.05 equiv of
1a was recovered.
We started the investigation using 1 equiv of 4-
(2-hydroxyphenyl)but-3-(E)-en-2-one 1a, 1.5 equiv of aryne
precursor 2-(trimethylsilyl)phenyl triflate 2a, and 3.0 equiv
of CsF in MeCN. After the reaction was stirred for 36 h at
room temperature, the product 1-(9H-xanthen-9-yl)propan-
2-one 3a was obtained in a yield of 29%, and the arylation
product 4-(2-phenoxyphenyl)but-3-(E)-en-2-one 4a was also
isolated in 58% yield with 5% of 1a being recovered (Table 1,
entry 1). Increasing the amount of CsF to 4.0 equiv, the
starting materials were completely consumed in a shorter
time, but the yield of 3a was only slightly improved to
31% (Table 1, entry 2). Gratifyingly, when we used THF
as solvent, the formation of 4a was reduced to 5.6%, and the
yield of 3a was improved to 84%, although a prolonged
reaction time of 6 days was required at room temperature
(Table 1, entry 3). Furthermore, the reaction conducted
under reflux at 66 °C could furnished 3a in a yield of 92%
within 36 h (Table 1, entry 5). Therefore, the optimized
conditions for the cascade reaction utilized 1.0 equiv of 1a,
1.5 equiv of 2a, and 4 equiv of CsF in THF at 66 °C.
With the optimal experimental conditions in hand, various
ortho R,β-unsaturated phenols 1 and arynes were employed
in the cascade nucleophilic addition-cyclic Michael addition
reactions, and a variety of xanthenes were obtained in
moderate to good yields (Table 2). First, to introduce
TABLE 2. Synthesis of Xanthenes 3a
1
2
entry
E
R1
R2
product yield (%)b
1
2
3
1a MeCO
1b MeCO
1c MeCO
1d MeCO
H
5-Br
5-Cl
2a
2a
2a
H
3a
3b
3c
3d
3e
3f
92
91
84
64
72
64
73
77
H
H
H
H
H
H
4
3,5-t-Bu2 2a
5
6
1e C6H5CO
1f MeO2C
1g CN
1a MeCO
1a MeCO
H
H
H
H
H
2a
2a
2a
7
3g
8c
9d
2b 4,5-Me2 3h
2c 4-F
3ia þ 3ib 47 þ 23
aUnless otherwise specified, the reactions were conducted with 1
(0.6 mmol), 2 (0.9 mmol), and CsF (2.4 mmol) in 20 mL of THF at
66 °C for 36 h. bThe reactions were monitored by TLC. Isolated yields
based on 1. cA reaction time of 96 h was needed. dA reaction time of 54 h
was needed.
substituents into the aromatic scaffolds of xanthenes,
5-halo-substrates 1b and 1c and 3,5-dialkyl substrate 1d were
tested to react with unsubstituted aryne precursor 2a. The
incorporated halogen atoms were well tolerated, and the
reactions afforded the products 3b and 3c in 91% and
84% yields, respectively (Table 2, entries 2 and 3). How-
ever, probably due to the steric repulsive interaction of
the tert-butyl group appended at the 3-position in 1d, a
decreased yield of 3d was observed (Table 2, entry 4). Next,
we examined the reactions of aryne and substrates 1 contain-
ing other unsaturated groups at the ortho position. As
the EWG of Michael acceptors, not only the acyl group,
but also the benzoyl, methoxycarbonyl, and cyano groups
(20) Okuma, K.; Nojima, A.; Matsunaga, N.; Shioji, K. Org. Lett. 2009,
11, 169.
(21) (a) Zhao, J.; Larock, R. C. Org. Lett. 2005, 7, 4273. (b) Zhao, J.;
Larock, R. C. J. Org. Chem. 2007, 72, 583.
(22) (a) Huang, X.; Xue, J. J. Org. Chem. 2007, 72, 3965. (b) Huang, X.;
Zhang, T. Tetrahedron Lett. 2009, 50, 208. (c) Zhang, T.; Huang, X.; Xue, J.;
Sun, S. Tetrahedron Lett. 2009, 50, 1290. (d) Sha, F.; Huang, X. Angew.
Chem., Int. Ed. 2009, 48, 3458. (e) Xue, J.; Yang, Y.; Huang, X. Synlett 2007,
1533. (f) Xue, J.; Wu, L.; Huang, X. Chin. Chem. Lett. 2008, 19, 631. (g) Xue,
J.; Huang, X. Synth. Commun. 2007, 37, 2179.
(23) Only reports on conjugate addition or Michael-type addition of
phenylcarbanions of carbanion-metallic reagents could be found. For
examples of LiCuAr2, see: (a) Alexakis, A.; Berlan, J.; Besace, Y. Tetra-
hedron Lett. 1986, 27, 1047. (b) Pollock, P.; Dambacher, J.; Anness, R.;
Bergdahl, M. Tetrahedron Lett. 2002, 43, 3693. (c) Li, G.; Wei, H.-X.;
Whittlesey, B. R.; Batrice, N. N. J. Org. Chem. 1999, 64, 1061.
J. Org. Chem. Vol. 75, No. 2, 2010 507

Huang and Zhang
JOCNote
FIGURE 1. NOE experiments on 3ia and 3ib.
TABLE 3. Synthesis of Acridines 6a
FIGURE 2. NOE experiments on 6fa and 6fb.
SCHEME 1. Synthesis of 9-Spiro Xanthenes and Acridines 8a,b
5
2
entry
R3
R2
product
6a
6b
6c
6d
yield (%)b
1
2
3
5a C6H5
5b 4-ClC6H4
3-MeOC6H4 2a
2a
5b 4-ClC6H4
5b 4-ClC6H4
2a
2a
H
H
H
H
54
55
52
53
43
5c
5d Me
4
aThe reactions were conducted with 7(0.6 mmol), 2(0.9mmol), andCsF
(2.4 mmol) in 20 mL of THF at 66 °C. bThe reactions were monitored by
TLC. Isolated yields based on 7.
5c
2b 4,5-Me2 6e
2d 6-Me
6d
6fa þ 6fb 47 þ 6.2
aUnless otherwise specified, the reactions were conducted with 5 (0.6
mmol), 2 (0.9 mmol), and CsF (2.4 mmol) in 20 mL of THF at 66 °C for
36 h. bThe reactions were monitored by TLC. Isolated yields based on 5.
cA reaction time of 120 h was needed. dA reaction time of 168 h was
needed.
the reaction, a 47% yield of sterically favored product 6fa
and only a 6.2% yield of unfavored 6fb were obtained. This
regioselectivity, determined by NOE experiments (Figure 2),
might result from the steric effect of the methyl group in 2d
during the nucleophilic addition step.24
In addition, we extended this methodology to synthesize
9-spiro xanthenes and acridines. Under the established
conditions, the targeted products 8a, 8b, and 8c could be
obtained smoothly in moderate yields (Scheme 1), which
were difficult to prepare in traditional methods25 and might
be potentially worthy as drugs.25d
In conclusion, we have developed a useful methodology
to synthesize 9-functionalized xanthenes and acridines of
potential biochemical interest via cascade intermolecular
nucleophilic addition and intramolecular cyclic Michael
addition cyclization. Variations of this cascade reaction to
synthesize other meaningful structures are expected.
have all been well tolerated in the reactions, and moderate
to good yields of products were obtained (Table 2, entries
5-7).
When symmetric aryne precursor 4,5-dimethyl-
2-(trimethylsilyl)phenyl triflate 2b was employed to react
with 1a, the reaction gave the expected product 3h in 77%
yield. Nevertheless, regioisomers 3ia and 3ib were isolated in
47% and 23% yields when asymmetrical aryne precursor
4-fluoro-2-(trimethylsilyl)phenyl triflate 2c was used. The
regiochemistry of compounds 3ia and 3ib was identified by
NOE experiments (Figure 1). This result could be rationa-
lized by the electric effects in the step of nucleophilic addition
to aryne with a fluoro group.24
We then applied this method to prepare acridines. Utiliz-
ing unsubstituted aryne precursor 2a and 5a under optimal
condition, the reaction proceeded smoothly at 66 °C to give
the derived product 6a in 54% yield (Table 3, entry 1). As the
EWG of Michael acceptors of substrates 5, halogen or
alkoxy group substituted phenyl carbonyls and alkyl carbo-
nyl were tolerated by the procedure, which furnished corres-
ponding products 6b, 6c, and 6d in moderate yields (Table 3,
entries 2, 3, and 4).
Comparing with the reaction of unsubstituted aryne
precursor 2a, the reaction of symmetrically substituted
aryne precursor 2b and 5b gave a slightly lower yield
(Table 3, entry 5). When unsymmetrical aryne precursor
6-methyl-2-(trimethylsilyl)phenyl triflate 2d was applied in
Experimental Section
General Procedure for the Synthesis of 9-Substituted Xan-
thenes 3. Under an atmosphere of dry nitrogen, 1 (0.6 mmol)
and 4.0 equiv of CsF (2.4 mmol) were added to an oven-
dried Schlenk tube equipped with
a stirring bar, then
the tube was sealed with a rubber plug. After evacuating and
backfilling the Schlenk with nitrogen for three cycles, 20 mL of
anhydrous THF was added followed by the addition of 1.5 equiv
of aryne precursor 2 (0.9 mmol) by syringes. The mixture was
stirred at 66 °C. After complete consumption of the starting
materials (monitored by TLC; a reaction time of 36 h was
(25) For existing synthesis of 9-spiro xanthenes, see: (a) Pettit, G. R.;
Thomas, E. G.; Herald, C. L. J. Org. Chem. 1981, 46, 4167. (b) Pettit, G. R.;
Thomas, E. G. Can. J. Chem. 1982, 60, 629. (c) Pettit, G. R.; Thomas, E. G.
Chem. Ind. 1963, 44, 1758. For existing synthesis of 9-spiro acridines, see: (d)
Masayuki, F.; Akinori, N.; Masaru, W. Jpn. Kokai Tokkyo Koho JP 2001089457,
2001.
(24) (a) Morishita, T.; Fukushima, H.; Yoshida, H.; Ohshita, J.; Kunai,
A. J. Org. Chem. 2008, 73, 5452. (b) Yoshida, H.; Fukushima, H.; Ohshita, J.;
Kunai, A. J. Am. Chem. Soc. 2006, 128, 11040.
508 J. Org. Chem. Vol. 75, No. 2, 2010

Huang and Zhang
JOCNote
needed unless otherwise specified), the mixture was diluted with
20 mL of ethyl acetate and then filtered through a pad of silica
gel to remove the insoluble substances. After the filtrates were
concentrated in vacuo, the residue was purified by flash chro-
matography on silica gel to afford 3.
(td, J = 7.6, 1.2 Hz, 2H), 6.84 (td, J = 7.5, 1.0 Hz, 2H), 6.75 (d,
J = 7.6 Hz, 2H), 6.20 (s, 1H), 4.82 (t, J = 7.2 Hz, 1H), 3.21 (d,
J = 7.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 38.4, 47.5,
113.7, 121.1, 123.7, 127.2, 128.1, 128.3, 128.7, 132.8, 137.3,
139.8, 198.6; MS (70 eV, EI) m/z 299 [M]þ; HRMS (EI) m/z
calcd for C21H17NO [M]þ 299.1310, found 299.1308.
1-(9H-Xanthen-9-yl)propan-2-one (3a): pale white solid, mp
99-101 °C (recrystallized from petroleum ether/ethyl acetate
100:1 v/v after purification by flash chromatography (eluent:
petroleum ether/ethyl acetate 40:1 v/v)) (lit.26 mp 103 °C); Rf
Spiro[cyclohexane-1,90-xanthen]-3-one (8a): pale white solid,
mp 124-126 °C (recrystallized from petroleum ether/ethyl
acetate 100:1 v/v after purification by flash chromatography
(eluent: petroleum ether/ethyl acetate 40:1 v/v)); Rf 0.16 (TLC
1
0.52 (TLC eluent: petroleum ether/ethyl acetate 10:1 v/v); H
1
NMR (400 MHz, CDCl3) δ 7.25 (d, J = 6 Hz, 2H), 7.21 (t, J =
7.6 Hz, 2H), 7.09 (d, J = 8.0 Hz, 2H), 7.04 (t, J = 7.6 Hz, 2H),
4.61 (t, J = 6.8 Hz, 1H), 2.80 (d, J = 6.8 Hz, 2H), 1.97 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 31.1, 34.3, 54.3, 116.5, 123.4,
125.2, 127.8, 128.5, 152.1, 206.6; IR (neat) 2920, 1703, 1479,
1455, 1259, 752 cm-1; GC-MS (70 eV, EI) m/z 238 [M]þ; HRMS
(EI) m/z calcd for C16H14O2 [M]þ 238.0994, found 238.0991.
The following compounds 6 and 8 were prepared similarly.
2-(9,10-Dihydroacridin-9-yl)-1-phenylethanone (6a): yellow-
ish solid, mp 168-170 °C (recrystallized from petroleum ether
after purification by flash chromatography (eluent: petroleum
ether/ethyl acetate 40:1 v/v)) (lit.27 mp 169-171 °C); Rf 0.45
(TLC eluent: petroleum ether/ethyl acetate 10:1 v/v); 1H NMR
(400 MHz, CDCl3) δ 7.74 (d, J=7.2 Hz, 2H), 7.45 (t, J = 7.4 Hz,
1H), 7.32 (t, J = 6.8 Hz, 2H), 7.24 (d, J = 7.2 Hz, 2H), 7.08
eluent: petroleum ether/ethyl acetate 10:1 v/v); H NMR (400
MHz, CDCl3) δ 7.28-7.24 (m, 4H), 7.18-7.15 (m, 2H), 7.10 (td,
J = 7.6, 1.2 Hz, 2H), 3.10 (s, 2H), 2.49 (t, J = 6.8 Hz,
2H), 1.86-1.83 (m, 2H), 1.66-1.62 (m, 2H); 13C NMR (100
MHz, CDCl3) δ 20.6, 39.3, 41.0, 42.4, 47.7, 116.9, 123.4, 125.2,
127.8, 129.6, 152.2, 211.9; IR (neat) 2973, 2896, 1651, 1453,
1380, 1271, 1086, 1046, 880 cm-1; MS (70 eV, EI) m/z 264 [M]þ;
HRMS (EI) m/z calcd for C18H16O2 [M]þ 264.1150, found
264.1148.
Acknowledgment. We are grateful to the National Natural
Science Foundation of China (Project Nos. 20872127 and
20732005)and the National Basic ResearchProgramofChina
(973 Program, 2009CB825300) for financial support.
Supporting Information Available: General experimental
procedures and spectroscopic data for all compounds. This
material is available free of charge via the Internet at http://
pubs.acs.org.
(26) For a report of 3a, see: Krohnke, F.; Dickore, K. Chem. Ber. 1959,
92, 46.
(27) For a report on the synthesis of 6a, see: Sheppard, C. S.; Levine, R.
J. Heterocycl. Chem. 1964, 1, 67.
J. Org. Chem. Vol. 75, No. 2, 2010 509