One-pot preparation of fluorinated polyhydrobenzoacridine-1-one derivatives under microwave irradiation and solvent-free conditions

Article abstract of DOI:10.1002/cjoc.201090211

A facile and efficient synthesis of fluorine-containing polyhydrobenzoacridines was accomplished by a three-component coupling of fluorinated aldehyde, α-naphthylamine, and 1,3-cyclohexanedione or dimedone under microwave irradiation and solvent-free cond

Full text of DOI:10.1002/cjoc.201090211

FULL PAPER
One-pot Preparation of Fluorinated Polyhydrobenzoacridine-
1-one Derivatives under Microwave Irradiation
and Solvent-free Conditions
Jin, Jianana(金见安)
Zhang, Jianmin*,a,b(章建民)
Xin, Yongb(信勇)
Liu, Fengruia(刘凤瑞)
Shang, Wenlia(商文丽)
Zhu, Shizheng*,b(朱仕正)
a Department of Chemistry, School of Science, Shanghai University, Shanghai 200444, China
b Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy
of Sciences, Shanghai 200032, China
A facile and efficient synthesis of fluorine-containing polyhydrobenzoacridines was accomplished by a
three-component coupling of fluorinated aldehyde, α-naphthylamine, and 1,3-cyclohexanedione or dimedone under
microwave irradiation and solvent-free conditions without catalyst. All new compounds were obtained in moderate
to good yields and characterized by standard spectroscopic methods.
Keywords
fluorinated polyhydrobenzoacridines, condensation reaction, microwave irradiation, one-pot,
three-component coupling
Introduction
hyde, amine and diketone (A3 coupling) transformed to
polyhydrobenzoacridines can be finished by microwave
irradiation.9 To our best knowledge, the preparation of
poly- or perfluorinated polyhydrobenzoacridines has not
been reported.
As a part of our current work connected the micro-
wave-promoted reactions with the organofluorine
chemistry, we describe an efficient and clean one-pot
procedure for the preparation of fluorinated polyhydro-
benzoacridines under microwave irradiation and sol-
vent-free conditions without catalyst.
The acridine derivatives have been known first to be
used as pigments and dyes.1 Then they are considered to
be important chemotherapeutics for the bactericidal and
antimalarial activities.2 In addition, polyhydroacridine
derivatives have high fluorescence efficiency and have
been reported to be used as fluorescent molecular
probes for monitoring of polymerization process.3 They
are also increasingly receiving attention due to their
likeness in properties with those of 1,4-dihydropyridines,
which have similarities in structure to the biologically
important compounds such as NADH and NADPH.4 As
a consequence, the interest of organic chemists in the
synthesis or structure modifications of acridinedione
derivatives remains high.
Recently, microwave-promoted reactions, especially
those run in water or solvent-free conditions have been
attracting increasing research interest from chemists, not
only because these reactions exhibit some particular or
unexpected reactivities in some cases but also because
they are significantly useful for green chemistry.5
Meanwhile, a one-pot multi-component reaction (MCR),
as a versatile strategy in organic synthesis, has been
caught much attention. In our corresponding investiga-
tions, we have reported a series of microwave-promoted
synthesis, such as 2-pentafluorophenylquinoline deriva-
tives,6 α-aminoalkyl phosphonates7 and fluorinated
propargylamines,8 etc.
Results and discussion
The microwave-promoted three-component coupling
experiment was performed by irradiation of a mixture
with equimolecular amounts of fluorinated benzoalde-
hyde, α-naphthylamine, and diketone in a flask under
solvent-free conditions without catalyst to afford the
desired 9-fluorinated phenyl substituted 1,2,3,4,9,10-
hexahydrobenzo[c]acridine-1-one derivates (Table 1).
The chemical synthesis procedure was easy to oper-
ate. Compared with the traditional heating methodology
which was carried out in the C6H6, EtOH, or H2O for
several hours, in our case, the reaction time was short-
ened to several minutes, and without any catalyst and
solvent. In a word, this synthetic method was fit for the
philosophy of green chemistry.
All the new products were fully characterized by IR,
1H NMR, 19F NMR, MS and elemental analysis. For
Furthermore, the three-component coupling of alde-
*
E-mail: zhusz@mail.sioc.ac.cn; Tel.: 0086-021-54925184; Fax: 0086-021-64166128
Received January 31, 2010; revised March 9, 2010; accepted April 1, 2010.
Project supported by the National Natural Science Foundation of China (No. 20972092).
Chin. J. Chem. 2010, 28, 1217— 1222
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1217

Jin et al.
FULL PAPER
Table 1 Synthesis of the fluorinated polyhydrobenzoacridines
Entry
1
Aldehyde (1)
α-Naphthylamine (2)
Diketone (3)
Product (4)
Time/min
8
Yield/%
59
4aa
2
3
4ba
4ca
6
5
68
76
4
5
6
4da
4ea
4fa
5
6
8
74
83
51
7
8
4ab
4bb
7
6
64
71
9
4cb
5
79
1218
www.cjc.wiley-vch.de
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2010, 28, 1217— 1222

One-pot Preparation of Fluorinated Polyhydrobenzoacridine-1-one Derivatives
Continued
Yield/%
Entry
10
Aldehyde (1)
α-Naphthylamine (2)
Diketone (3)
Product (4)
Time/min
6
4db
81
75
48
11
12
4eb
4fb
5
8
example, the FT-IR of 4aa spectrum showed single
－1
acutely middle intension signal at about 3307 cm－ for
the vibration of NH, and a strong band at 1587 cm 1 for
its carbonyl group. Its 1H NMR spectrum appeared mul-
tiplet at δ 2.97—1.92 for three CH2 protons, a singlet at
δ 5.54 for C(7)-H, multiplet in the region δ 7.00—7.59
for aromatic protons, doublet at δ 7.80, 8.47 for C(9)-H,
C(10)-H, and a singlet at δ 9.35 for NH proton. The 19F
NMR spectrum was very similar to the starting
fluorinated aldehyde, showed multiplet at δ －118.73
for a fluorine atom. The mass spectrum exhibited a mo-
lecular ion peak at m/z ＋343 ([M]＋) and its base peak at
m/z 248 ([M－FC6H4] ). The spectra of compounds
4ab—4fb were similar to the compounds 4aa—4fa ex-
cept another two singlets at about δ 1.00 for two CH3
protons.
The molecular structure of 4cb was further deter-
mined by X-ray crystal diffraction analysis. Its molecu-
lar structure and the packing map are shown in Figure 1.
The selected bond lengths (Å) and bond angles (°) for
compound 4cb are listed in Table 1. This compound
showed strong intermolecular hydrogen bonding be-
tween N—H…O (dN— O＝2.127 Å; ∠N—H…O＝
H…
163.23°), and the weak intermolecular hydrogen bond-
ing between C—H…F (dC— F＝2.666 Å; ∠C—H…
H…
F＝165.29°) and C—H…O (dC— O＝2.436 Å; ∠C—
H…
H…O＝168.44°) (Figure 2).
On the basis of the experimental results above, to-
gether with some literature reports,10 two tentative reac-
tion pathways are proposed as shown in Scheme 1. In
path a, fluorinated benzoaldehyde 1 reacted with dike-
tone 2 to form intermediate A, which was attacked by
α-naphthylamine 3 to the C＝C double bond and trans-
formed to B. Finally, the target product 4 was obtained
after losing H2O. Another pathway was that
α-naphthylamine 3 attacked the carbonyl group of A to
give intermediate C. Then the product 4 was obtained
after electrocyclic reaction and followed by a [1,3]-
H-shift.
Figure 1 Crystal structure and the packing map of compound
4cb.
Conclusion
In summary, we have developed an efficient green
three-component reaction for the preparation of poly-
and perfluorinated polyhydrobenzoacridines under mi-
crowave irradiation and solvent-free conditions. The
notable advantages of this procedure, such as environ-
Chin. J. Chem. 2010, 28, 1217— 1222
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
1219

Jin et al.
FULL PAPER
tion crystal structure analysis was obtained on Bruker
SMART P4 instrument.
Synthesis of polyhydrobenzoacridines
Fluorinated benzoaldehyde (2 mmol), α-naphthyla-
mine (2 mmol), 1,3-cyclohexanedione or dimedone (2
mmol) were mixed and put into a 50 mL flask, then it
was exposed to microwave irradiation at 800 W using a
microwave oven for an appropriate time as checked by
TLC (Table 2). After completion of the reaction, the
reaction mixture was diluted with water. Then the pre-
cipitate formed and filtered to obtain the crude material,
which was further purified by flash column chromatog-
raphy [using V(petroleum ether)∶V(ethylacetate)＝4∶
1 as eluant] to afford pure products.
Figure 2 The intermolecular hydrogen bonds of compound 4cb.
3,3-Dihydro-9-(2-fluorophenyl)-1,2,3,4,9,10-hexa-
mental friendly, simple workup procedure, short route
and reaction time, make this method attractive and use-
ful in synthesis fields. Further chemical transformation
and the potential performances of these products are still
under investigation in our laboratory.
hydrobenzo[c]acridine-1-one (4aa)
Yellow solid;
1
m.p. 258—259 ℃; H NMR (DMSO-d6, 500 MHz) δ:
9.35 (s, 1H, NH), 8.47 (d, J＝8.5 Hz, 1H, ArH), 7.80 (d,
J＝8.0 Hz, 1H, ArH), 7.59—7.44 (m, 3H, ArH), 7.24—
7.21 (m, 2H, ArH), 7.12—7.00 (m, 3H, ArH), 5.54 (s,
1H, CH), 2.97—2.92 (m, 1H, CH), 2.77—2.70 (m, 1H,
CH), 2.30—2.20 (m, 2H, CH2), 2.04—1.92 (m, 2H,
CH2); 19F NMR (DMSO-d6, 470 MHz) δ: －118.70—
－118.75 (m, 1F); IR (KBr) ν: 3307, 3059, 2949, 1586,
1517, 1498, 1389, 1267, 1183, 1139＋, 1023, 821, 756
Experimental
General experimental techniques and apparatus
All reactions were performed in an improved do-
mestic Sanyo, EM-551S/550S, microwave oven (2450
MHz, 80—800 W). TLC was performed on precoated
silica gel F-254 plates (0.25 mm; E. Merck), and prod-
uct(s) and starting material(s) were detected by viewing
under UV light. Column chromatography was per-
formed on silica gel (200—300 mesh). Melting points
were determined in open capillaries and were uncor-
rected. Infrared spectra were recorded on an AVA-
TAR370 FT spectrophotometer (Perkin Elmer, USA).
NMR spectra were determined with DRX500MHz
spectrometer (Bruker, Germany), using solutions in
deuterated dimethylsulfoxide with Me4Si and CFCl3 as
the internal and external standards for 1H and 19F nuclei,
respectively. Low resolution mass spectrum was ob-
tained on Finnigan GC-MS 4021 instrument using the
electron impact ionization technique (70 eV). Elemental
analyses were performed in this Institute. X-ray diffrac-
－1
cm ; MS (70 eV) m/z (%): 343 ([M] , 46), 248 ([M－
C6H4F]＋, 100). Anal. calcd for C23H18FNO: C 80.45, H
5.28, N 4.08; found C 80.18, H 5.41, N 4.07.
3,3-Dihydro-9-(3-fluorophenyl)-1,2,3,4,9,10-hexa-
hydrobenzo[c]acridine-1-one (4ba) Yellow solid;
1
m.p. 252—253 ℃; H NMR (DMSO-d6, 500 MHz) δ:
9.38 (s, 1H, NH), 8.49 (d, J＝8.5 Hz, 1H, ArH), 7.83 (d,
J＝8.0 Hz, 1H, ArH), 7.60—7.47 (m, 3H, ArH), 7.34 (d,
J＝8 Hz, 1H, ArH), 7.23—7.19 (m, 1H, ArH), 7.05—
6.86 (m, 3H, ArH), 5.29 (s, 1H, CH), 2.96—2.91 (m,
1H, CH), 2.74—2.68 (m, 1H, CH), 2.32—2.23 (m, 2H,
CH2), 2.02—1.88 (m, 2H, CH2); 19F NMR (DMSO-d6,
470 MHz) δ: －113.75—－113.81 (m, 1F); IR (KBr) ν:
3290, 3059, 2946, 1586, 1515, 1492, 1385, 1267, 1180,
－1
1139＋, 1021, 795, 768 cm ; MS (70 eV) m/z (%): 343
([M] , 31), 248 ([M－C6H4F]＋, 100). Anal. calcd for
Scheme 1 Tentative reaction pathways for the three-component coupling reaction
1220
www.cjc.wiley-vch.de
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2010, 28, 1217— 1222

One-pot Preparation of Fluorinated Polyhydrobenzoacridine-1-one Derivatives
C23H18FNO: C 80.45, H 5.28, N 4.08; found C 80.41, H
5.27, N 3.98.
m/z (%): 415 ([M]＋, 11), 248 ([M－C6F5]＋, 24), 190
([M－C9H6F5O]＋, 100). Anal. calcd for C23H14F5NO: C
66.51, H 3.40, N 3.37; found C 66.43, H 3.52, N 3.35.
3,3-Dimethyl-9-(2-fluorophenyl)-1,2,3,4,9,10-hexa-
hydrobenzo[c]acridine-1-one (4ab) Yellow solid;
3,3-Dihydro-9-(4-fluorophenyl)-1,2,3,4,9,10-hexa-
hydrobenzo[c]acridine-1-one (4ca)
Yellow solid;
1
m.p. 260—261 ℃; H NMR (DMSO-d6, 500 MHz) δ:
9.35 (s, 1H, NH), 8.48 (d, J＝8.5 Hz, 1H, ArH), 7.82 (d,
J＝7.5 Hz, 1H, ArH), 7.59—7.46 (m, 3H, ArH), 7.29 (d,
J＝8.5 Hz, 1H, ArH), 7.25—7.21 (m, 2H, ArH), 7.01—
6.97 (m, 2H, ArH), 5.27 (s, 1H, CH), 2.94—2.87 (m,
1H, CH), 2.74—2.67 (m, 1H, CH), 2.31—2.22 (m, 2H,
CH2), 2.01—1.86 (m, 2H, CH2); 19F NMR (DMSO-d6,
470 MHz) δ: －117.45—－117.81 (m, 1F); IR (KBr) ν:
3283, 3058, 2940, 1584, 1516, 1491, 1386, 1268, 1181,
1
m.p. 280—281 ℃; H NMR (DMSO-d6, 500 MHz) δ:
9.29 (s, 1H, NH), 8.46 (d, J＝8.5 Hz, 1H, ArH), 7.80 (d,
J＝8.5 Hz, 1H, ArH), 7.59—7.44 (m, 3H, ArH), 7.26—
7.23 (m, 1H, ArH), 7.19 (d, J＝8.5 Hz, 1H, ArH),
7.12—7.00 (m, 3H, ArH), 5.51 (s, 1H, CH), 2.77 (d, J＝
17.5 Hz, 1H, CH), 2.68 (d, J＝17 Hz, 1H, CH), 2.24 (d,
J＝16.5 Hz, 1H, CH), 2.03 (d, J＝16 Hz, 1H, CH), 1.09
(s, 3H, CH3), 1.04 (s, 3H, CH3); 19F NMR (DMSO-d6,
470 MHz) δ: －119.01—－119.06 (m, 1F); IR (KBr) ν:
3271, 3053, 2959, 1583, －1517, 1491, 1386, 1257, 1152,
－1
1139＋, 1021, 816, 756 cm ; M＋S (70 eV) m/z (%): 343
([M] , 42), 248 ([M－C6H4F] , 100). Anal. calcd for
C23H18FNO: C 80.45, H 5.28, N 4.08; found C 80.32, H
5.29, N 3.98.
1
1057＋, 824, 756, 646 cm ; M＋S (70 eV) m/z (%): 371
([M] , 47), 276 ([M－C6H4F] , 100). Anal. calcd for
C25H22FNO: C 80.84, H 5.97, N 3.77; found C 80.64, H
6.01, N 3.69.
3,3-Dihydro-9-(3,4-difluorophenyl)-1,2,3,4,9,10-
hexahydrobenzo[c]acridine-1-one (4da)
Yellow
1
solid; m.p. 257—258 ℃; H NMR (DMSO-d6, 500
MHz) δ: 9.39 (s, 1H, NH), 8.49 (d, J＝8.5 Hz, 1H, ArH),
7.83 (d, J＝7.5 Hz, 1H, ArH), 7.60—7.48 (m, 3H, ArH),
7.34 (d, J＝8.5 Hz, 1H, ArH), 7.26—7.19 (m, 2H, ArH),
7.02—6.99 (m, 1H, ArH), 5.29 (s, 1H, CH), 2.95—2.90
(m, 1H, CH), 2.74—2.68 (m, 1H, CH), 2.30—2.23 (m,
2H, CH2), 2.02 —1.89 (m, 2H, CH2); 19F NMR
(DMSO-d6, 470 MHz) δ: －139.16—－139.25 (m, 1F),
3,3-Dimethyl-9-(3-fluorophenyl)-1,2,3,4,9,10-hexa-
hydrobenzo[c]acridine-1-one (4bb) Yellow solid;
1
m.p. 233—234 ℃; H NMR (500 MHz, DMSO-d6) δ:
9.29 (s, 1H, NH), 8.46 (d, J＝8.5 Hz, 1H, ArH), 7.80 (d,
J＝8.5 Hz, 1H, ArH), 7.59—7.44 (m, 3H, ArH), 7.26—
7.23 (m, 1H, ArH), 7.19 (d, J＝8.5 Hz, 1H, ArH),
7.12—7.00 (m, 3H, ArH), 5.51 (s, 1H, CH), 2.77 (d, J＝
17.5 Hz, 1H, CH), 2.68 (d, J＝17 Hz, 1H, CH), 2.24 (d,
－142.65—－142.74 (m, 1F); IR (KBr) ν: 3285, 3056,
J＝16.5 Hz, 1H, CH), 2.03 (d, J＝16 Hz, 1H, CH), 1.09
(s, 3H, CH3), 1.04 (s, 3H, CH3); 19F NMR (470 MHz,
DMSO-d6) δ: －113.57—－113.62 (m, 1F); IR (KBr) ν:
3299, 3056, 2955, 1589, －1520, 1500, 1388, 1263, 1152,
2956, 1589, －1517, 1498, 1388, 1265, 1184, 1139, 1025,
＋
1
796, 759 cm ; MS (70 eV) m/z (%): 361 ([M] ,20), 248
([M－C6H3F2]＋, 100). Anal. calcd for C23H17F2NO: C
76.44, H 4.74, N 3.88; found C 76.65, H 4.71, N 3.76.
3,3-Dihydro-9-(3,5-difluorophenyl)-1,2,3,4,9,10-
1
1060＋, 874, 765, 614 cm ; MS (70 eV) m/z (%): 371
([M] , 26), 276 ([M－C6H4F]＋, 100). Anal. calcd for
C25H22FNO: C 80.84, H 5.97, N 3.77; found C 80.99, H
6.03, N 3.78.
hexahydrobenzo[c]acridine-1-one (4ea)
Yellow
1
solid; m.p. 257—258 ℃; H NMR (DMSO-d6, 500
MHz) δ: 9.41 (s, 1H, NH), 8.49 (d, J＝8.5 Hz, 1H, ArH),
7.84 (d, J＝8.0 Hz, 1H, ArH), 7.60—7.50 (m, 3H, ArH),
7.38 (d, J＝8.5 Hz, 1H, ArH), 6.95—6.88 (m, 3H, ArH),
5.33 (s, 1H, CH), 2.97—2.92 (m, 1H, CH), 2.75—2.69
(m, 1H, CH), 2.33—2.25 (m, 2H, CH2), 2.03—1.90 (m,
2H, CH2); 19F NMR (DMSO-d6, 470 MHz) δ:
－110.29—－110.33 (m, 2F); IR (KBr) ν: 3304, 3060,
2940, 1621, 1591, 1518, 1502, 1392, 1262, 1187, 1112,
3,3-Dimethyl-9-(4-fluorophenyl)-1,2,3,4,9,10-hexa-
hydrobenzo[c]acridine-1-one (4cb)10a Yellow solid;
1
m.p. 256—258 ℃; H NMR (DMSO-d6, 500 MHz) δ:
9.32 (s, 1H, NH), 8.48 (d, J＝8.5 Hz, 1H, ArH), 7.83 (d,
J＝8 Hz, 1H, ArH), 7.60—7.47 (m, 3H, ArH), 7.31 (d,
J＝8.5 Hz, 1H, ArH), 7.24—7.19 (m, 1H, ArH), 7.05—
6.87 (m, 3H, ArH), 5.26 (s, 1H, CH), 2.75 (d, J＝17 Hz,
1H, CH), 2.66 (d, J＝17 Hz, 1H, CH), 2.25 (d, J＝16
Hz, 1H, CH), 2.07 (d, J＝16 Hz, 1H, CH), 1.08 (s, 3H,
CH3), 0.99 (s, 3H, CH3); 19F NMR (DMSO-d6, 470
MHz) δ: －117.41—－117.47 (m, 1F); IR (KBr) ν:
3289, 3044, 2959, 1579, 1517,－1493, 1388, 1265, 1222,
＋
－1
826, 758 cm ; M＋S (70 eV) m/z (%): 361 ([M] , 27),
248 ([M－C6H3F2] , 100). Anal. calcd for C23H17F2NO:
C 76.44, H 4.74, N 3.88; found C 76.26, H 4.75, N 3.91.
3,3-Dihydro-9-(pentafluorophenyl)-1,2,3,4,9,10-
1
hexahydrobenzo[c]acridine-1-one (4fa)
Yellow
1154, 1057, 852, 813, 642 cm ; MS (70 eV) m/z (%):
solid; m.p.＞300 ℃; 1H NMR (DMSO-d6, 500 MHz) δ:
9.51 (s, 1H, NH), 8.49 (d, J＝8.5 Hz, 1H, ArH), 7.85 (d,
J＝8.0 Hz, 1H, ArH), 7.63—7.48 (m, 3H, ArH), 7.06 (d,
J＝8.5 Hz, 1H, ArH), 5.75 (s, 1H, CH), 2.87—2.81 (m,
1H, CH), 2.74—2.68 (m, 1H, CH), 2.32—2.18 (m, 2H,
CH2), 2.00—1.88 (m, 2H, CH2); 19F NMR (DMSO-d6,
470 MHz) δ: －144.46—－144.50 (m, 2F), －157.88—
－157.97 (m, 1F), －163.64—－163.75 (m, 2F); IR
(KBr) ν: 3309, 3061, 2949, 1590, 1519, 1500, 1393,
371 ([M]＋, 41), 276 ([M－C6H4F]＋, 100). Anal. calcd
for C25H22FNO: C 80.84, H 5.97, N 3.77; found C 80.50,
H 6.17, N 3.54.
Crystal data for 4cb, C25H22FNO: MW＝371.14, or-
thorhombic, space group: Pbca, a＝8.511(3) Å, α＝90°;
b＝13.007(4) Å, β＝90°; c＝35.121(12) Å, γ＝90°; V＝
3888(2) Å3, Z＝8, Dc＝1.269 Mg/m3, F(000)＝1568,
crystal size: 0.15 mm×0.12 mm×0.10 mm, theta range
for data collection 2.32° —27.01°, limiting indices
－10≤h≤9, －16≤k≤16, －34≤l≤44, reflections
－1
1266, 1188, 1104, 1024, 801, 740 cm ; MS (70 eV)
Chin. J. Chem. 2010, 28, 1217— 1222
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
1221

Jin et al.
FULL PAPER
collected/unique 17561/4198 [R(int)＝0.0610], com-
pleteness to theta＝27.01, 99.0%, max. and min. trans-
mission 0.9917 and 0.9876, refinement method
full-matrix least-squares on F2, data/restraints/para-
meters ＝4198/0/260, goodness-of-fit on F2 ＝0.937,
final R indices [I＞2sigma(I)] R1＝0.0468, wR2＝0.1124,
R indices (all data) R1＝0.1002, wR2＝0.1306, extinc-
tion coefficient＝0.0012(4), largest diff. peak and hole
(d, J＝16 Hz, 1H, CH), 2.04 (d, J＝16 Hz, 1H, CH),
1.08 (s, 3H, CH3), 0.97 (s, 3H, CH3); 19F NMR
(DMSO-d6, 470 MHz) δ: －144.64—－144.70 (m, 2F),
－157.73—－157.82 (m, 1F), －163.69—－163.78 (m,
2F); IR (KBr) ν: 3292, 3053, 2962, 1587, 1518－, 1501,
1
1391, 1264, 1149, 1102, 991, 885, 793, 620 cm ; MS
(70 eV) m/z (%): 443 ([M]＋, 44), 276 ([M－C6F5]＋, 64),
＋
80 ([M － C20H14F5N] , 100). Anal. calcd for
－3
＝0.143 and －0.120 e•Å . CCDC number is 760560.
C25H18F5NO: C 67.72, H 4.09, N 3.16; found C 67.70,
H 3.85, N 3.29.
3,3-Dimethyl-9-(3,4-difluorophenyl)-1,2,3,4,9,10-
hexahydrobenzo[c]acridine-1-one (4db) Yellow solid;
1
m.p. 259—261 ℃; H NMR (DMSO-d6, 500 MHz) δ:
References
9.33 (s, 1H, NH), 8.48 (d, J＝8.5 Hz, 1H, ArH), 7.83 (d,
J＝8 Hz, 1H, ArH), 7.60—7.48 (m, 3H, ArH), 7.31 (d,
J＝8.5 Hz, 1H, ArH), 7.26—7.20 (m, 2H, ArH), 7.00 (d,
J＝5 Hz, 1H, ArH), 5.26 (s, 1H, CH), 2.75 (d, J＝16.5
Hz, 1H, CH), 2.66 (d, J＝17 Hz, 1H, CH), 2.25 (d, J＝
16 Hz, 1H, CH), 2.07 (d, J＝16 Hz, 1H, CH), 1.07 (s,
3H, CH3), 0.99 (s, 3H, CH3); 19F NMR (DMSO-d6, 470
MHz) δ: －139.27—－139.36 (m, 1F), －142.63— －
142.73 (m, 1F); IR (KBr) ν: 3311, 3056, 2955, 1592,
1519, 1500, 1389, 1262, 1151, 105＋9, 874, 768, 608
1
2
3
4
Albert, A. The Acridines, 2nd ed., Edward Arnold Ltd,
London, 1996.
Spalding, D. P.; Chapin, E. C.; Mosher, H. S. J. Org. Chem.
1954, 19, 357.
Popielarz, R.; Hu, S. K.; Neckers, D. C. J. Photochem.
Photobiol. A: Chem. 1997, 110.
Srividya, N.; Ramamurthy, P.; Shanmugasundaram, P.;
Ramakrishnan, V. T. J. Org. Chem. 1996, 61, 5083.
Dallinger, D.; Kappe, C. O. Chem. Rev. 2007, 107, 2563.
(a) Zhu, S. Z.; Xu, B.; Zhang, J.; Qin, C. Y.; Huang, Q. C.;
Qu, C. X. Phosphorus, Sulfur Silicon Relat. Elem. 1996,
112, 219.
5
6
－1
cm ; MS (70 eV) m/z (%): 389 ([M] , 32), 276 ([M－
C6H3F2]＋, 100). Anal. calcd for C25H21F2NO: C 77.10,
H 5.44, N 3.60; found C 76.87, H 5.63, N 3.57.
(b) Zhu, S. Z.; Jin, X. L. J. Fluorine Chem. 1995, 72, 19.
(c) Zhang, J. M.; Yang, W.; Song, L. P.; Cai, X.; Zhu, S. Z.
Tetrahedron Lett. 2004, 45, 5771.
3,3-Dimethyl-9-(3,5-difluorophenyl)-1,2,3,4,9,10-
hexahydrobenzo[c]acridine-1-one (4eb)
Yellow
1
solid; m.p. 244—245 ℃; H NMR (DMSO-d6, 500
MHz) δ: 9.37 (s, 1H, NH), 8.48 (d, J＝8.5 Hz, 1H, ArH),
7.84 (d, J＝7.5 Hz, 1H, ArH), 7.61—7.49 (m, 3H, ArH),
7.35 (d, J＝8.5 Hz, 1H, ArH), 6.95—6.88 (m, 3H, ArH),
5.23 (s, 1H, CH), 2.77 (d, J＝17 Hz, 1H, CH), 2.67 (d,
J＝16.5 Hz, 1H, CH), 2.25 (d, J＝16 Hz, 1H, CH), 2.09
(d, J＝15.5 Hz, 1H, CH), 1.08 (s, 3H, CH3), 1.00 (s, 3H,
CH3); 19F NMR (DMSO-d6, 470 MHz) δ: －110.33—
－110.40 (m, 2F); IR (KBr) ν: 3305, 3058, 2957, 1594,
1520, 1499, 1387, 1260, 1152, 1114, 1060, 988, 861,
7
8
9
Lv, X. Y.; Zhang, J. M.; Xing, C. H.; Du, W. Q.; Zhu, S. Z.
Synth. Commun. 2007, 37, 743.
Du, W. Q.; Zhang, J. M.; Wu, R.; Liang, Q.; Zhu, S. Z. J.
Fluorine Chem. 2008, 129, 695.
(a) Kidwai, M.; Rastogi, S. Heteroat. Chem. 2005, 16, 138.
(b) Tu, S. J.; Jia, R. H.; Jiang, B.; Zhang, Y.; Zhang, J. Y. J.
Heterocycl. Chem. 2006, 43, 1621.
(c) Nadaraj, V.; Selvi, S. T.; Mohan, S. Eur. J. Med. Chem.
2009, 44, 976.
(d) Tu, S. J.; Wu, S. S.; Yan, S.; Hao, W. J.; Zhang, X. H.;
Cao, X. D.; Han, Z. G.; Jiang, B.; Shi, F.; Xia, M.; Zhou, J.
F. J. Comb. Chem. 2009, 11, 239.
＋
－1
759, 612 cm ; MS (70 eV) m/z (%): 389 ([M＋] , 30),
276 ([M－C6H3F2]＋, 95), 80 ([M－C20H17F2N] , 100).
Anal. calcd for C25H21F2NO: C 77.10, H 5.44, N 3.60;
found C 76.90, H 5.45, N 3.50.
10 (a) Wang, X. S.; Zhang, M. M.; Zeng, Z. S.; Shi, D. Q.; Tu,
S. J.; Wei, X. Y.; Zong, Z. M. Tetrahedron Lett. 2005, 46,
7169.
3,3-Dimethyl-9-(pentafluorophenyl)-1,2,3,4,9,10-
hexahydrobenzo[c]acridine-1-one (4fb)
Yellow
1
(b) Skatetskii, V. V.; Kozlov, N. G.; Dikusar, E. A. Russ. J.
Org. Chem. 2007, 43, 1481.
(c) Cortes, E.; Martinez, R.; Gustavo Avila, J.; Alfredo
Toscano, R. J. Heterocycl. Chem. 1988, 25, 895.
solid; m.p. 214—215 ℃; H NMR (DMSO-d6, 500
MHz) δ: 9.46 (s, 1H, NH), 8.48 (d, J＝8.5 Hz, 1H, ArH),
7.84 (d, J＝8 Hz, 1H, ArH), 7.63—7.49 (m, 3H, ArH),
7.06 (d, J＝8.5 Hz, 1H, ArH), 5.75 (s, 1H, CH), 2.68 (d,
J＝17 Hz, 1H, CH), 2.64 (d, J＝16.5 Hz, 1H, CH), 2.24
(E1001311 Cheng, B.; Dong, H.)
1222
www.cjc.wiley-vch.de
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2010, 28, 1217— 1222