Synthesis of polybenzoquinazolines via an intramolecular dehydration of photocyclization

Article abstract of DOI:10.1016/j.tet.2016.04.080

Benzo[h]-naphth[1,2-f]quinazolines and benzo[h]-phenanthren[9,10-f]quinazoines were synthesized from intermediates 4-(2-hydroxyphenyl)-5-(naphthalen-1-yl)pyrimidines and 4-(2-hydroxyphenyl)-5-(phenanthren-1-yl) pyrimidines by the intramolecular dehydration of photocyclization. The intermediates were obtained by the condensation of 3-arylchromone with formamidine, acetamidine or guanidine refluxing in ethanol, respectively. Irradiation of the corresponding intermediates by a high-pressure mercury lamp in 19:1 (v/v) [Formula presented]₂O or 18:1:1 (v/v) [Formula presented]₂O-Dioxane lead to target products. This photocyclization showed advantages including catalyst-free and mild reaction condition. Moreover, water was the only by-product of this reaction. The crystal structure of 2-amino-12-methoxy-benzo[h]-naphth[1,2-f]quinazoline was determined and the fluorescence properties of these polybenzoquinazolines were also investigated.

Full text of DOI:10.1016/j.tet.2016.04.080

Tetrahedron 72 (2016) 5037e5046
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of polybenzoquinazolines via an intramolecular
dehydration of photocyclization
,
b
,
,
b
,
,
b
,
,
b
,
,b,c,
*
Wei Wei a c, Chenchen Li a c, Tao Wang a c, Dian Liu a c, Zunting Zhang a
a Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, People’s Republic of China
b National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, People’s Republic of China
c School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi’an 710062, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
Benzo[h]-naphth[1,2-f]quinazolines and benzo[h]-phenanthren[9,10-f]quinazoines were synthesized
from intermediates 4-(2-hydroxyphenyl)-5-(naphthalen-1-yl)pyrimidines and 4-(2-hydroxyphenyl)-5-
(phenanthren-1-yl) pyrimidines by the intramolecular dehydration of photocyclization. The in-
termediates were obtained by the condensation of 3-arylchromone with formamidine, acetamidine or
guanidine refluxing in ethanol, respectively. Irradiation of the corresponding intermediates by a high-
pressure mercury lamp in 19:1 (v/v) EtOHeH2O or 18:1:1 (v/v) EtOHeH2O-Dioxane lead to target
products. This photocyclization showed advantages including catalyst-free and mild reaction condition.
Moreover, water was the only by-product of this reaction. The crystal structure of 2-amino-12-methoxy-
benzo[h]-naphth[1,2-f]quinazoline was determined and the fluorescence properties of these poly-
benzoquinazolines were also investigated.
Received 19 March 2016
Received in revised form 26 April 2016
Accepted 29 April 2016
Available online 11 June 2016
Keywords:
Photocyclization
Intramolecular dehydration
Benzo[h]-naphth[1,2-f ]quinazolines
Benzo[h]-phenanthren[9,10-f]quinazoines
Ó 2016 Published by Elsevier Ltd.
1. Introduction
solution at 140 ꢀC.7a In 1999, the same group synthesized dibenzo
[f,h]quinazolines by the PIFA (phenyliodine(III) bis(tri-
The quinazoline skeleton is a key structural element due to its
wide applications, for example, they have been reported to possess
pharmaceutical activities1 such as antidepressant, anti-cancer, en-
zymatic inhibitors, and antiviral. In addition, fused quinazolines
belong to heterocyclic aromatic compounds (HACs),2 which contain
one or more nitrogen, sulfur, or oxygen atoms and are present along
with polycyclic aromatic hydrocarbons (PAHs). As we known, PAHs
can be used as functional organic materials such as electronic de-
vices and optoelectronic devices,3 because they are affinitive with
fluoroacetate)) mediated regioselective oxidative coupling of 4,5-
diarylpyrimidines.7b Furthermore, dibenzo[f,h]quinazolines were
also obtained from 4-(2-chlorophenyl)-2,6-dimethoxy-5-(2,5-
dimethoxyphenyl)pyrimidine with tri(cyclohexyl)phosphine as li-
gand, in the presence of palladium(II) acetate as a transition-metal
catalyst and cesium carbonate as a base.7c These methods required
metal catalysts, or special oxidant. As for the polybenzoquinazo-
lines, only dibenzo[f,h]quinazolines were reported, and three or
more benzene rings fused quinazoline had not been disclosed to
date. Herein, an efficient methodology for the synthesis of benzo
[h]-naphth[1,2-f]quinazolines and benzo[h]-phenanthren[9,10-f]
quinazoines 5 via the photocyclization of 4-(2-hydroxyph-enyl)-5-
(naphthalen-1-yl) pyrimidines and 4-(2-hydroxyphenyl)-5-(phe-
nanthren-9-yl)pyrimidines 4 (Scheme 1) was reported.
their molecular, electronic and
p-conjugated structures. Mean-
while, the scientific community is always interested in HACs mainly
due to the unique properties and potential applications of some of
them in the field of materials science.4 HACs are also applied in the
synthetic chemistry as a catalyst.5 Specially, the aromatic ring
framework of HACs are contributed by the lone pair of electrons of
nitrogen atoms, which can lead to fabulous physical and chemical
properties, for instance, fluorescence and higher carrier mobility.6
In recent years, the syntheses of dibenzo[f,h]quinazolines have
been developed.7 Dibenzo[f,h]quinazolines were achieved by the
reaction of 4,5-o,o-dihaloarylpyrimidines with Me6Sn2 as the or-
ganometallic reagent and Pd(PPh3)4 as the catalyst in dioxane
Encouraged by our previous work, 2H-phenanthro[9,10-c]pyr-
azoles8a and dibenzo[f,h][1,2,4]triazolo[3,4-b]quinazolines8b were
prepared by the dehydration of photocyclization of 3,4-diaryl-1H-
pyrazoles and 6-phenyl-7-(2-hydroxyphenyl)- 1,2,4-triazolo[4,3-a]
pyrimidines. In order to synthesize larger
p-conjugated system of
fused quinazolines and explore their distinctive properties, we hy-
pothesized that benzo[h]-naphth[1,2-f]quinazolines and benzo[h]-
phenanthren[9,10-f]quinazoines 5 would be given from 4-(2-
hydroxyphenyl)-5-(naphthalen-1-yl)pyrimidines
and
4-(2-
* Corresponding author. E-mail address: zhangzunting@sina.com (Z. Zhang).
http://dx.doi.org/10.1016/j.tet.2016.04.080
0040-4020/Ó 2016 Published by Elsevier Ltd.

5038
W. Wei et al. / Tetrahedron 72 (2016) 5037e5046
Scheme 1. Reported Approachs and Our Strategy.
hydroxyphenyl)-5-(phenanthren-9-yl)pyrimidines 4 through the
intramolecular dehydration of photocyclization.
15 h (Table 1, entry 1). Then, the reaction conditions were opti-
mized (Table 1). When tert-butanol or methanol was used as sol-
vent, 5a was afforded in lower yields (entries 2 and 3, 15% and 13%).
Only a trace amount of 5a was observed in acetonitrile (entry 4).
Ethanol-water (19:1 v/v) was used as solvent resulted in 33% yield
of 5a (entry 5), the reason was that the addition of water was fa-
vorable to excited state intramolecular proton transfer (ESIPT).13
While ethanolewater (2:1 v/v) was used as solvent, the yield of
5a decreased to 25% (entry 6). Only a trace amount of 5a was
detected when a mixture of ethanol and 1% HCl (1:1 v/v) was used
as solvent (entry 7). The irradiation time was increased to 25 and
35 h, the yield of 5a separately increased to 47% and 68% (entries 8
and 9). Subsequently, continue to increase the irradiation time to
40 h, the yield decreased to 65% (entry 10). Due to poor solubility,
the corresponding intermediates 4 (1 mmol) could not be dissolved
in ethanolewater (100 mL, 19:1 v/v). We could not attempt higher
concentration of 4 (10ꢁ2 M). In addition, the corresponding in-
termediates 4meo (0.1 mmol) were irradiated in ethanol-dioxane-
water (100 mL, 18:1:1 v/v) because of the poor solubility in etha-
nolewater (100 mL, 19:1 v/v).
2. Results and discussion
2.1. Synthesis of the intermediates (4)
Following the literature procedure,9,10 3-iodochromones 2 were
got via a two-step procedure: condensation reaction of o-hydrox-
yacetophenones 1 with DMF/DMA in DMF, subsequently cyclization
reaction with I2. Negishi cross-coupling reactions were used for
synthesis 3-(1-naphthyl)chromones 3aed in 63e85% yields with
Nickel(II) chloride and triphenylphosphine.10
A methodology
namely Suzuki coupling11 was used to obtain 3-(9-phenanthrenyl)
chromones 3eeg in 45e76% yields. Based on our previous work of
the condensation of isoflavones and guanidine,12 the corresponding
intermediates
4-(2-hydroxyphenyl)-5-(naphthalen-1-yl)pyrimi-
dines 4ael and 4-(2-hydroxyphenyl)-5-(phenanthren-9-yl)pyrim-
idines 4meo were obtained in 55e97% yields by the condensation
of 3 with formamidine acetate, acetamidine hydrochloride or
guanidine hydrochloride in ethanol at 78 ꢀC (Scheme 2).
2.3. Scope of substrates
2.2. Optimization of the solvents in photocyclization reaction
With the optimized reaction conditions in hand, we commenced
to explore the substrate scope, and the results were depicted in
Table 2. Generally, the corresponding intermediates 4-(2-
In our initial investigation, 5a was obtained in 18% yield by the
irradiation of 4a (0.1 mmol) with a high-pressure mercury lamp
(500 W) in ethanol (100 mL) under an argon atmosphere for
hydroxyphenyl)-5-(naphthalen-1-yl)pyrimidines
and
4-(2-

W. Wei et al. / Tetrahedron 72 (2016) 5037e5046
5039
Scheme 2. Preparation of Intermediates 4aeo.
Table 1
benzo[h]-naphth[1,2-f] quinazolines 5ael and benzo[h]-phe-
nanthren[9,10-f]quinazoines 5meo. Fortunately, 5d was recrys-
tallized from ethyl acetate and the structure was further confirmed
by single-crystal X-ray diffraction.
Optimization of the photocyclization reaction of 4aa
Based on previous work of photocyclization reactions,13 a rea-
sonable mechanism for the preparation of polybenzoquinazolines 5
can be formulated. It is illustrated in Scheme 3. Firstly, under UV
light, compound 4 undergoes excited state from the phenolic form
to the keto form 6 by intramolecular proton transfer. Secondly,
intermediate 7 is then formed under UV irradiation, the subsequent
dehydration of which delivered 5 as the product.
Entry
Solvent
Time (h)
Yieldb/%
1
2
3
4
5
6
7
8
9
EtOH
MeOH
t-BuOH
MeCN
EtOHeH2O(19:1)
EtOHeH2O(2:1)
EtOHꢁ1% HCl (1:1)
EtOHeH2O(19:1)
EtOHeH2O(19:1)
EtOHeH2O(19:1)
15
15
15
15
15
15
15
25
35
40
18
15
13
Trace
33
25
Trace
47
68
65
2.4. Fluorescence properties of products
The fluorescent properties of compounds 5 were subsequently
investigated in ethanol and in the solid state. The emission spectra
of 5 showed blue-purple fluorescence (lEm max¼405e459 nm) in
Table 3. The emissions maxima of 5a, 5b, 5c and 5d, bearing an
amino-group in the 2-position of pyrimidine ring, were
431e438 nm. Compounds 5eel, carrying a methyl group or H atom
in the 2-position of pyrimidine ring, had emission maxima at
405e423 nm. The bathochromic shift of emissions was in close
contact with the substituents (H, Me, NH2) on pyrimidine ring,
whereas was unrelated to the substituents (H, F, OMe, t-Bu) on
aromatic ring. For 5m, 5n and 5o, the emission maxima had
10
The optimization condition was in bold.
a
Reaction conditions: The intermediate 4a (0.1 mmol, 10ꢁ3 M) was dissolved in
different solvents (100 mL) and irradiated with a high pressure mercury lamp
(500 W) under an argon atmosphere in quartz tubes.
b
Yield of isolated product after column chromatography based on 4a.
a bathochromic shift due to the expanded
p
conjugated.15 In ad-
hydroxyphenyl)-5-(phenanthren-9-yl)pyrimidines
4
carrying
dition, these compounds also fluoresced in the solid state and
showed in Table 3 (solid). The emission maxima of 5c and 5o were
593 and 597 nm. The majority of product 5 were at the range from
406 to 484 nm.
electron-donating substituents gave the corresponding products in
higher yields than those with electron-withdrawing groups.
For example, 5h was obtained in 51% yield and it beared
a methoxy group. Nevertheless, the fluoro containing product 5f
was obtained in only 30% yield (Table 2). As we know, the solubility
of these compounds was poor in chloroform and dichloromethane,
3. Conclusion
due to their larger
p
-conjugated system.14 When tert-butyl group
was introduced into the desired products, the solubility was nota-
bly improved. We provided an efficient method for the synthesis of
In summary, an efficient tactic for synthesis of benzo[h]-naphth
[1,2-f] quinazolines and benzo[h]-phenanthren[9,10-f]quinazoines

5040
W. Wei et al. / Tetrahedron 72 (2016) 5037e5046
Table 2
Synthesis of polybenzoquinazolines 5 via intramolecular dehydration of Photocyclizationa
a
Reaction condition: The intermediate 4 (0.1 mmol, 10ꢁ3 M) was dissolved in di erent solvents (100 mL) and
irradiated with a high pressure mercury lamp (500 W) under an argon atmosphere in quartz tubes.
b Reaction solvent was 18:1:1 (v/v/v) EtOH-dioxane-H2O for 5m, 5n and 5o.
c Yield of isolated product after column chromatography based on 4.
by intramolecular photocyclization of 4-(2-hydroxyphenyl)-5-
(naphthalen-1-yl)pyrimidines and 4-(2-hydroxyphenyl)-5-(phe-
nanthren-9-yl)pyrimidines was developed. Compared with the
cyclizations of metal catalysts and oxidant reaction, the intra-
molecular dehydration of photocyclization was mild, catalyst-free
and good yields. In addition, only water was formed and utilized
the light as an ideal clean reagent.16 The target products showed
blue-purple fluorescence (lEm
possessed larger Stokes shift. In the solid state, the majority of
¼405e459 nm) in ethanol and
max
products also had blue-purple fluorescence and the minority of
Scheme 3. Plausible Mechanism for the Photocyclization Reaction.

W. Wei et al. / Tetrahedron 72 (2016) 5037e5046
5041
Table 3
Spectroscopic properties of target products
Compd
lex [nm]
(Solution) lem [nm]
Stokes shift [cmꢁ1
]
lex [nm]
(Solid) lem [nm]
Stokes shift [cmꢁ1
]
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
281
280
277
279
261
260
267
271
259
258
267
272
292
294
294
435
438
432
431
413
420
410
406
415
423
414
405
457
459
452
12,598
12,883
12,952
12,640
14,101
14,652
13,062
12,270
14,514
15,119
13,299
12,073
12,364
12,227
11,890
370
366
370
369
370
368
382
366
368
367
367
366
367
378
372
443
445
593
570
423
440
406
438
441
448
404
439
484
468
597
4454
4850
10,164
9556
3386
4447
1547
4491
4498
4927
2495
4543
5794
5088
10,131
products (5c and 5o) possessed yellow-orange fluorescence. The
molecular structure of target compounds was slightly tilted from
planarity. This method as well provided facile construction of HACs
that were applicable for screening of fundational organic materials.
iodide (0.55 mmol) was added and stirred at 65 ꢀC for 1 h. The
reaction mixture was quenched with 10% HCl (2 mL), and extracted
with CH2Cl2 (2ꢂ15 mL). The combined CH2Cl2 extract was washed
with 10% HCl (5 mL), brine (5 mL), and dried over MgSO4. The or-
ganic layer was concentrated under vacuo to give the crude prod-
uct. The crude product was purified over silica gel using petroleum
ether: ethyl acetate as eluent to give substituted 3-(1-naphthyl)
chromones 3aed.
4. Experimental section
4.1. General remarks
4.2.1. 3-(Naphthalen-1-yl)chromone (3a). Colorless powder. Yield
115.6 mg (85%). Mp 124e126 ꢀC. IR (KBr) 3043, 1642, 1609, 1564,
Unless otherwise noted, all reagents were purchased from
commercial suppliers and used without purification. Thin-layer
chromatography was performed on precoated silica gel 60 GF254
plates. Silica gel (200e300 mesh) was used for column chroma-
tography. 1H NMR spectra were recorded on 300 MHz, 400 or
600 MHz spectrometer. Spectra were referenced internally to the
1506, 1460, 1348, 1282, 1162, 1112, 776, 751 cmꢁ1 1H NMR
.
(400 MHz, CDCl3)
d
8.32 (d, J¼8.0 Hz, 1H), 7.98 (s, 1H), 7.87 (t,
J¼8.0 Hz, 2H), 7.73e7.66 (m, 2H), 7.51e7.39 (m, 6H); 13C NMR
(100 MHz, CDCl3):
d 176.6, 156.5, 154.3, 133.8, 133.7, 132.5, 129.9,
129.3, 128.5, 128.3, 126.5, 126.4, 126.0, 125.7, 125.4, 125.4, 125.4,
124.5, 118.2. HRMS (ESI-TOF) m/z [MþNa]þ calcd for C19H12O2Na
295.0735, found 295.0741.
residual proton resonance in CDCl3
2.50 ppm). Chemical shifts ( ) were reported as part per million
(ppm) in
scale downfield from TMS. 13C NMR spectra were
recorded on 75 MHz, 100 or 150 MHz spectrometer and the spectra
were referenced to CDCl3 ( 77.0 ppm, the middle peak) or DMSO-
d6 39.5 ppm, the middle peak). Coupling constants (J) are re-
ported in hertz (Hz). High-resolution mass spectrometry (HRMS)
was recorded using the electron-spray ionization (ESI) technique.
The absorbance and fluorescence spectra were measured in etha-
nol. Melting points were measured with a X-5 micro-melting point
apparatus and were uncorrected. IR spectra were recorded with
a Nicollet 170SX FTIR spectrophotometer with KBr pellets. The
excitation wavelength and fluorescence spectra were measured in
ethanol.
(d 7.26 ppm) or DMSO-d6 (d
d
d
4.2.2. 6-Fluoro-3-(naphthalen-1-yl)chromone (3b). Colorless pow-
der. Yield 102.9 mg (71%). Mp 176e178 ꢀC. IR (KBr) 3051, 1651, 1613,
d
(d
1564, 1477, 1315, 1269, 1244, 1108, 772, 727 cmꢁ1 1H NMR
.
(400 MHz, CDCl3)
d 8.04 (m, 2H), 7.98e7.89 (m, 3H), 7.73e7.70 (m,
1H), 7.57e7.43 (m, 5H); 13C NMR (100 MHz, CDCl3)
d 175.8, 159.7(d,
1JCeF¼245.31 Hz), 154.4, 152.8, 133.7, 132.4, 129.4, 129.4, 128.5,
128.3,126.4,126.1, 125.6 (d, 3JCeF¼7.48 Hz), 125.5,125.4,124.8,122.1
2
3
(d, JCeF¼25.48 Hz), 120.4 (d, JCeF¼7.98 Hz), 111.2 (d,
2JCeF¼23.41 Hz). HRMS (ESI-TOF) m/z [MþNa]þ calcd for
C19H11FO2Na 313.0641, found 313.0638.
4.2.3. 7-tert-Butyl-3-(naphthalen-1-yl)chromone
powder. Yield 103.3 mg (63%). Mp 173e175 ꢀC. IR (KBr) 3049, 2952,
2875, 1629, 1560, 1419, 1346, 1280, 1174, 1120, 900, 779, 702 cmꢁ1
1H NMR (400 MHz, CDCl3)
8.29 (d, J¼8.6 Hz, 1H), 8.02 (s, 1H), 7.92
(t, J¼8.0 Hz, 2H), 7.76 (d, J¼8.2 Hz, 1H), 7.58e7.41 (m, 6H), 1.44 (s,
9H). 13C NMR (100 MHz, CDCl3)
176.3, 158.3, 156.6, 154.1, 133.6,
(3c). Colorless
4.2. Preparation of 3-arylchromones 3aed
.
Preparation of the 1-naphthylzinc Iodide: A dried 25 mL flask
was charged with acetonitrile (5 mL), cobalt bromide (219 mg,
1 mmol), zinc dust (877.5 mg, 13.5 mmol), allylchloride (1.95 mmol,
d
d
0.15 mL)and 50 mL of trifluoroacetic acid, the mixture was stirred for
132.4, 130.0, 129.1, 128.3, 128.2, 126.0, 125.9, 125.7, 125.3, 123.3,
5 min at room temperature. Then 1-iodonaphthalene (5 mmol,
0.73 mL) was added and the reaction mixture was stirred for 1 h at
room temperature.
122.0, 114.4, 35.4, 31.0. HRMS (ESI-TOF) m/z [MþH]þ calcd for
C23H21O2 329.1542, found 329.1535.
Preparation of the 3-(1-naphthyl)chromones 3aed: These
reactions carried out as referred in the literature.10 After tetrahy-
drofuran (THF) drying with Na/benzophenone, daretilled under N2
atmosphere to use. A hot-oven dried Schlenk tube was charged
with substituted 3-iodochromone 2 (0.5 mmol), NiCl2 (1.9 mg,
0.015 mmol), PPh3 (7.9 mg, 0.03 mmol), LiCl (31.5 mg, 0.75 mmol)
followed by THF (3 mL) solvent under an argon atmosphere. The
reaction mixture was stirred at 65 ꢀC for 5 min, 1-naphthylzinc
4.2.4. 7-Methoxy-3-(naphthalene-1-yl)chromone
(3d). Colorless
powder. Yield 128.4 mg (85%). Mp 193e194.0 ꢀC. IR (KBr) 3073, 2924,
2854,1641, 1570,1493, 1464, 1385, 1361, 1268,1219, 1161, 1110, 1076,
991, 906, 852, 789, 759, 698 cmꢁ1 1H NMR (300 MHz, DMSO-d6)
.
d
8.43 (s, 1H), 8.06e7.99 (m, 3H), 7.67e7.46 (m, 5H), 7.24 (s, 1H),
7.15e7.12 (m, 1H), 3.94 (s, 3H). 13C NMR (75 MHz, DMSO-d6)
175.4,
164.4,158.4,155.3,133.6,132.9,132.6,130.8,129.1,128.8,128.6,127.4,
d

5042
W. Wei et al. / Tetrahedron 72 (2016) 5037e5046
126.6,126.4,125.9,124.7,118.0,115.4,101.3, 56.7. HRMS(ESI-TOF)m/z
[MþNa]þ calcd for C20H14O3Na 325.0841, found 325.0841.
purified by flash column chromatography (ethyl aceta-
teepetroleum ether) on silica gel (200e300 mesh) to afford the
desired product.
4.3. Preparation of 3-arylchromones 3eeg11
4.4.1. 2-Amino-4-(2-hydroxyphenyl)-5-(naphthalen-1-yl)pyrimidine
(4a). Yellow powder. Yield 588.4 mg (94%). Mp 241e243 ꢀC. IR
(KBr) 3383, 3329, 3155, 3055, 1659, 1575, 1527, 1448, 1386, 1340,
1215, 1165, 1109, 935, 840, 752 cmꢁ1. 1H NMR (600 MHz, DMSO-
A
mixture of substrated 3-iodochromone (2 mmol), 9-
phenanthracenylboronic acid (488.4 mg, 2.2 mmol) and K2CO3
(552 mg, 4 mmol) in THF (20 mL) and water (5 mL) was added with
Pd(PPh3)4 (46.2 mg, 0.04 mmol) under an argon atmosphere. The
reaction mixture was stirred at 60e65 ꢀC and monitored by TLC.
After the reaction was completed, the reaction mixture was diluted
with ethyl acetate (100 mL) and water (50 mL). The organic layer
was washed with water (50 mL) and brine (50 mL) and then dried
by MgSO4. Upon removal of the solvent, the corresponding 3-(9-
Phenanthryl)chromones 3eeg was obtained after chromatogra-
phy on silica gel (petrol ethereethyl acetate).
d6)
d
11.72 (s, 1H), 8.21 (s, 1H), 7.92 (d, J¼8.1 Hz, 1H), 7.89 (d,
J¼8.2 Hz, 1H), 7.59 (d, J¼8.4 Hz, 1H), 7.47 (dd, J¼14.9, 7.1 Hz, 2H),
7.39 (t, J¼7.3 Hz, 1H), 7.34 (d, J¼6.6 Hz, 1H), 7.12 (s, 2H),
7.01e6.96 (m, 1H), 6.75 (dd, J¼7.9, 1.3 Hz, 1H), 6.72 (d, J¼8.0 Hz,
1H), 6.28 (t, J¼7.3 Hz, 1H). 13C NMR (150 MHz, DMSO-d6)
d 163.0,
161.5, 161.3, 157.4, 135.2, 133.3, 131.6, 130.7, 129.6, 128.2, 127.9,
127.8, 126.3, 125.9, 125.6, 125.1, 121.4, 119.7, 117.7, 116.9. HRMS
(ESI-TOF) m/z [MþH]þ calcd for C20H16N3O 314.1293, found
314.1286.
4.3.1. 3-(Phenanthren-9-yl)chromone (3e). Brown powder. Yield
489.4 mg (76%). Mp 192e194 ꢀC. IR (KBr) 3051, 1638, 1609, 1564,
4.4.2. 2-Amino-4-(2-hydroxy-5-fluorophenyl)-5-(naphthalen-1-yl)
pyrimidine (4b). Yellow powder. Yield 536.2 mg (81%). Mp
271e273 ꢀC. IR (KBr) 3386, 3334, 3165, 2924, 2854,1658,1564,1519,
1436, 1342, 1257, 1205, 1110, 931, 871, 813, 767, 657 cmꢁ1. 1H NMR
1493, 1464, 1369, 1344, 1302, 1128, 851, 756, 718 cmꢁ1 1H NMR
.
(400 MHz, CDCl3)
d
8.77 (dd, J¼13.4, 8.3 Hz, 2H), 8.39 (dd, J¼8.0,
1.3 Hz, 1H), 8.13 (s, 1H), 7.91 (d, J¼7.8 Hz, 1H), 7.83e7.49 (m, 9H). 13
C
NMR (100 MHz, CDCl3)
d
176.7, 157.1, 156.6, 154.2, 133.9, 131.4, 131.3,
(600 MHz, DMSO-d6)
d
11.31 (s, 1H), 8.26 (s, 1H), 7.94 (d, J¼8.1 Hz,
130.9, 130.6, 129.4, 129.0, 128.8, 127.2, 126.8, 126.6, 126.5, 126.3,
125.7,125.4,124.5,123.0,122.7,118.2. HRMS (ESI-TOF) m/z [MþNa]þ
calcd for C23H14O2Na 345.0891, found 345.0897.
1H), 7.91 (d, J¼8.2 Hz, 1H), 7.61 (d, J¼8.4 Hz, 1H), 7.49 (dd, J¼14.8,
6.9 Hz, 2H), 7.42 (t, J¼7.5 Hz, 1H), 7.38 (d, J¼6.9 Hz, 1H), 7.15 (s, 2H),
6.86 (td, J¼8.5, 3.2 Hz, 1H), 6.70 (dd, J¼8.9, 4.9 Hz, 1H), 6.55 (dd,
J¼10.1, 3.1 Hz, 1H). 13C NMR (150 MHz, DMSO-d6)
d 162.0, 161.7,
1
4.3.2. 6-Fluoro-3-(phenanthren-9-yl)chromone
(3f). Colorless
161.1, 154.7, 153.9 (d, JCeF¼231.9 Hz), 134.7, 133.3, 131.5, 128.2,
3
powder. Yield 380.8 mg (56%). Mp 209e211 ꢀC. IR (KBr) 3070, 1629,
127.9, 126.3, 126.0, 125.6, 125.1, 122.5 (d, JCeF¼7.5 Hz), 119.90,
1579, 1467, 1344, 1298, 1245, 1141, 939, 881, 823, 727 cmꢁ1. 1H NMR
117.68 (d, JCeF¼7.9 Hz), 117.2 (d, JCeF¼22.6 Hz), 115.3 (d,
2JCeF¼24.6 Hz). HRMS (ESI-TOF) m/z [MþH]þ calcd for C20H15FN3O
332.1199, found 332.1190.
3
2
(400 MHz, CDCl3)
d
8.74 (dd, J¼14.3, 8.3 Hz, 2H), 8.10 (s, 1H), 7.99
(dd, J¼8.0, 2.8 Hz,1H), 7.88 (d, J¼7.7 Hz,1H), 7.83e7.55 (m, 7H), 7.48
(m, 1H). 13C NMR (100 MHz, CDCl3)
d 176.0, 159.7 (d,
1JCeF¼245.6 Hz), 154.3, 152.7, 131.2, 131.0, 130.8, 130.5, 129.4, 128.7,
4.4.3. 2-Amino-4-(2-hydroxy-4-tert-butylphenyl)-5-(naphthalen-1-
yl)pyrimidine (4c). Colorless powder. Yield 715.9 mg (97%). Mp
216e218 ꢀC. IR (KBr) 3473, 3300, 3140, 2957, 2864, 1637, 1562,
128.5, 127.2, 126.8, 126.4, 125.4 (d, 3JCeF¼7.1 Hz), 125.0, 123.0, 122.0,
2
3
122.1 (d, JCeF¼25.4 Hz), 120.3 (d, JCeF¼8.0 Hz), 111.2 (d,
2JCeF¼23.39 Hz). HRMS (ESI-TOF) m/z [MþH]þ calcd for C23H14FO2
341.0978, found 341.0965.
1481, 1425, 1380, 1205, 1099, 1024, 952, 786, 675 cmꢁ1 1H NMR
.
(400 MHz, CDCl3)
d
13.27 (s, 1H), 8.28 (s, 1H), 7.91 (d, J¼8.2 Hz,
2H), 7.64 (d, J¼8.4 Hz, 1H), 7.50 (m, 2H), 7.40 (t, J¼7.6 Hz, 1H), 7.34
(d, J¼6.9 Hz, 1H), 6.94 (s, 1H), 6.63 (d, J¼8.5 Hz, 1H), 6.20 (d,
J¼9.0 Hz, 1H), 5.34 (s, 2H), 1.15 (s, 9H). 13C NMR (100 MHz, CDCl3)
4.3.3. 7-tert-Butyl-3-(phenanthren-9-yl)chromone (3g). Colorless
powder. Yield 340.2 mg (45%). Mp 221e223 ꢀC. IR (KBr) 3059, 2954,
2871, 1633, 1558, 1423, 1357, 1296, 1201, 1136, 887, 842, 732 cmꢁ1
.
d 163.3, 162.6, 159.8, 159.7, 156.1, 131.3, 133.8, 132.0, 130.1, 128.4,
1H NMR (400 MHz, CDCl3)
d
8.75 (dd, J¼13.1, 8.3 Hz, 2H), 8.30 (d,
128.0, 126.7, 126.2, 125.8, 125.3, 120.7, 115.7, 115.4, 115.0, 34.6, 30.7.
HRMS (ESI-TOF) m/z [MþH]þ calcd for C24H24N3O 370.1919, found
370.1916.
J¼8.5 Hz, 1H), 8.08 (s, 1H), 7.89 (d, J¼7.7 Hz, 1H), 7.80 (d, J¼8.1 Hz,
1H), 7.74e7.53 (m, 7H), 1.45 (s, 9H). 13C NMR (100 MHz, CDCl3)
d
176.5, 158.3, 156.7, 154.0, 131.3, 131.2, 130.7, 130.3, 129.1, 129.0,
128.6, 127.0, 126.7, 126.6, 126.5, 126.0, 125.6, 123.3, 122.8, 122.5,
4.4.4. 2-Amino-4-(2-hydroxy-4-methoxyphenyl)-5-(naphthalen-1-
yl)pyrimidine (4d). Colorless powder. Yield 651.7 mg (95%). Mp
215e217 ꢀC. IR (KBr) 3417, 3304, 3142, 2926, 2839, 1625, 1552, 1487,
1437, 1375, 1285, 1207, 1151, 1031, 962, 842, 783, 729 cmꢁ1. 1H NMR
122.0, 114.4, 35.4, 31.0. HRMS (ESI-TOF) m/z [MþH]þ calcd for
C
27H23O2 379.1698, found 379.1688.
4.4. Preparation for the synthesis of 4-(2-hydroxyphenyl)-5-
(naphthalene-1-yl) pyrimidines 4ael and 4-(2-
hydroxyphenyl)-5-(phenanthren-9-yl)pyrimidines 4meo
(600 MHz, DMSO-d6)
d
13.43 (s, 1H), 8.15 (s, 1H), 7.96 (d, J¼4.9 Hz,
1H), 7.95 (d, J¼5.0 Hz, 1H), 7.56e7.52 (m, 2H), 7.49 (t, J¼7.3 Hz, 1H),
7.41e7.38 (m, 2H), 7.22 (s, 2H), 6.57 (d, J¼9.0 Hz, 1H), 6.32 (d,
J¼2.6 Hz, 1H), 5.76 (dd, J¼9.0, 2.6 Hz, 1H), 3.59 (s, 3H). 13C NMR
Based on the literature procedure.12 Formamidine acetate,
acetamidine hydrochloride or guanidine hydrochloride
(6 mmol) was added to an EtOH (150 mL) solution of the
substrated 3-arylchromones 3 (2 mmol). The mixture was stir-
red at 78 ꢀC and NaOH (1M, EtOH) was added dropwise to make
the pH of the mixture between 8 and 9. The progress of the
reaction was monitored by TLC. After completion of the re-
action, the mixture was concentrated by rotary evaporation to
give crude compounds 4. It was dissolved with CH2Cl2 (150 mL)
and water (50 mL) and adjusted to neutral. The organic layer
was separated and dried over MgSO4. The filtrate was concen-
trated under reduced pressure. The crude products were
(150 MHz, DMSO-d6) d 162.0, 161.8, 161.6, 161.2, 160.7, 135.7, 133.4,
131.5, 130.8,128.4,128.0,127.8, 126.5,126.1,125.9,125.0,118.0, 112.1,
104.8, 101.8, 55.0. HRMS (ESI-TOF) m/z [MþH]þ calcd for
C21H18N3O2 344.1399, found 344.1391.
4.4.5. 2-Methyl-4-(2-hydroxyphenyl)-5-(naphthalen-1-yl)pyrimi-
dine (4e). Colorless powder. Yield 524.2 mg (84%). Mp 146e148 ꢀC.
IR (KBr) 3182, 3057, 2925, 2852, 1556, 1500, 1442, 1390, 1299, 1247,
1166, 1043, 962, 750 cmꢁ1. 1H NMR (400 MHz, DMSO-d6)
d 10.48 (s,
1H), 8.67 (s, 1H), 7.91 (t, J¼8.6 Hz, 2H), 7.64 (d, J¼8.2 Hz, 1H), 7.44
(m, 3H), 7.36 (d, J¼6.9 Hz, 1H), 7.03 (t, J¼8.1 Hz, 2H), 6.74 (d,
J¼8.0 Hz, 1H), 6.50 (t, J¼7.4 Hz, 1H), 2.80 (s, 3H). 13C NMR (150 MHz,

W. Wei et al. / Tetrahedron 72 (2016) 5037e5046
5043
DMSO-d6)
d
165.6,163.3,159.0,155.9,133.9,133.1,131.1,130.5,129.9,
3.0 Hz, 1H). 13C NMR (150 MHz, CDCl3)
d
161.5, 161.2, 155.4, 155.3,
1
129.3, 128.3, 128.2, 127.8, 126.3, 125.9, 125.3, 125.1, 123.5, 118.2,
116.2, 25.4. HRMS (ESI-TOF) m/z [MþNa]þ calcd for C21H16N2ONa
335.1160, found 335.1152.
155.0 (d, JCeF¼233.9 Hz), 133.8, 133.5, 131.2, 130.8, 129.7, 128.8,
2
127.5, 127.3, 126.7, 125.7, 124.5, 119.9 (d, JCeF¼23.5 Hz), 119.5 (d,
3
2
3JCeF¼7.7 Hz), 117.7 (d, JCeF¼8.0 Hz), 115.6 (d, JCeF¼25.8 Hz).
HRMS (ESI-TOF) m/z [MþH]þ calcd for C20H14FN2O 317.1090, found
317.1079.
4.4.6. 2-Methyl-4-(2-hydroxy-5-fluorophenyl)-5-(naphthalen-1-yl)
pyrimidine (4f). Yellow powder. Yield 633.6 mg (96%). Mp
146e148 ꢀC. IR (KBr) 3113, 3045, 2924, 2852, 1558, 1498, 1437,
4.4.11. 4-(2-Hydroxy-4-tert-butylphenyl)-5-(naphthalen-1-yl)pyrim-
idine (4k). Colorless powder. Yield 531.1 mg (75%). Mp 175e177 ꢀC.
IR (KBr) 3193, 3039, 2958, 2869, 1622, 1562, 1510, 1438, 1384, 1284,
1384, 1253, 1180, 1122, 1049, 952, 871, 771, 709, 655 cmꢁ1 1H
.
NMR (600 MHz, DMSO-d6)
d 13.34 (s, 1H), 8.68 (s, 1H), 7.98 (d,
J¼8.3 Hz, 1H), 7.93 (d, J¼8.2 Hz, 1H), 7.57 (dd, J¼8.1, 7.2 Hz, 1H),
7.50 (t, J¼7.5 Hz, 1H), 7.44 (d, J¼8.4 Hz, 1H), 7.41e7.36 (m, 2H),
6.71 (dd, J¼9.0, 5.0 Hz, 1H), 6.82 (m, 1H), 6.40 (dd, J¼10.7,
1222, 1022, 935, 869, 786 cmꢁ1. 1H NMR (400 MHz, CDCl3)
d 13.44
(s, 1H), 9.22 (s, 1H), 8.68 (s, 1H), 8.01e7.93 (m, 2H), 7.58e7.49 (m,
3H), 7.42 (d, J¼7.2 Hz,1H), 7.38 (d, J¼6.9 Hz,1H), 7.00 (s,1H), 6.68 (d,
J¼8.5 Hz, 1H), 6.23 (d, J¼8.6 Hz, 1H), 1.16 (s, 9H). 13C NMR (100 MHz,
3.0 Hz, 1H), 2.90 (s, 3H). 13C NMR (150 MHz, DMSO-d6)
d 165.0
(s, 2H), 161.5, 161.4(d, 4JCeF¼2.4 Hz), 156.3, 154.6 (d,
1JCeF¼234.8 Hz), 133.9, 133.8, 131.1, 129.5, 128.8, 127.9, 127.6,
127.2, 126.6, 125.8, 124.7, 119.7 (d, 2J¼23.3 Hz), 119.4 (d,
3JCeF¼7.7 Hz), 117.8 (d, 3JCeF¼7.7 Hz, 2H), 115.7 (d,
2JCeF¼25.4 Hz), 25.5. HRMS (ESI-TOF) m/z [MþH]þ calcd for
CDCl3) d 162.5, 160.8, 160.4, 156.9, 155.0, 134.5, 133.8, 131.2, 130.5,
129.9,129.2,128.6,127.5,127.1,126.5,125.8,125.0,116.0,115.5,114.8,
34.7, 30.7. HRMS (ESI-TOF) m/z [MþH]þ calcd for C24H23N2O
355.1810, found 355.1801.
C
21H16FN2O 331.1247, found 331.1239.
4.4.12. 4-(2-Hydroxy-4-methoxyphenyl)-5-(naphthalen-1-yl)pyrimi-
dine (4l). Colorless powder. Yield 400.2 mg (61%). Mp 122e124 ꢀC.
IR (KBr) 3188, 3062, 2932, 2844, 1606, 1558, 1434, 1382, 1259, 1201,
4.4.7. 2-Methyl-4-(2-hydroxy-4-tert-butylphenyl)-5-(naphthalen-1-
yl)pyrimidine (4g). Yellow powder. Yield 404.8 mg (55%). Mp
130e132 ꢀC. IR(KBr): 3209, 3055, 2963, 2877,1616,1554,1433,1367,
1309, 1215, 1105, 1047, 945, 864, 783, 684 cmꢁ1. 1H NMR (400 MHz,
1159, 1037, 962, 783 cmꢁ1 1H NMR (600 MHz, CDCl3)
. d 13.89 (s,
1H), 9.17 (s, 1H), 8.64 (s, 1H), 7.97 (d, J¼8.3 Hz, 1H), 7.93 (d,
J¼8.2 Hz, 1H), 7.58e7.54 (m, 1H), 7.53e7.47 (m, 2H), 7.42e7.38 (m,
2H), 6.65 (d, J¼9.2 Hz, 1H), 6.46 (d, J¼2.6 Hz, 1H), 5.77 (dd, J¼9.2,
CDCl3)
(m, 2H), 6.98 (s, 1H), 6.66 (d, J¼8.1 Hz, 1H), 6.23 (d, J¼7.7 Hz, 1H),
2.89 (s, 3H), 1.16 (s, 9H). 13C NMR (100 MHz, CDCl3)
164.6, 163.4,
d 13.86 (s, 1H), 8.58 (s, 1H), 7.95 (m, 2H), 7.53 (m, 3H), 7.39
2.7 Hz, 1H), 3.68 (s, 3H). 13C NMR (150 MHz, DMSO-d6)
d 163.1,
d
162.9, 162.4, 160.6, 154.9, 134.7, 133.9, 131.6, 131.2, 129.9, 129.2,
128.6, 127.4, 127.1, 126.6, 125.8, 125.0, 110.6, 106.4, 102.1, 55.1.
HRMS (ESI-TOF) m/z [MþH]þ calcd for C21H17N2O2 329.1290, found
329.1291.
161.0, 160.4,156.6,134.7,133.8,131.4, 130.0,128.9,128.5,127.5, 127.1,
126.9, 126.4, 125.7, 125.1, 115.7, 115.4, 114.9, 34.7, 30.7, 25.5. HRMS
(ESI-TOF) m/z [MþH]þ calcd for C25H25N2O 369.1967, found
369.1960.
4.4.13. 2-Amino-4-(2-hydroxyphenyl)-5-(phenanthren-9-yl)pyrimi-
dine (4m). Yellow powder. Yield 682.4 mg (94%). Mp >300 ꢀC. IR
(KBr) 3402, 3323, 3161, 3066, 1651, 1571, 1494, 1446, 1383, 1207,
4.4.8. 2-Methyl-4-(2-hydroxy-4-methoxyphenyl)-5-(naphthalen-1-
yl)pyrimidine (4h). Yellow powder. Yield 489.1 mg (75%). Mp
147e149 ꢀC. IR (KBr) 3182, 3051, 2927, 2841, 1581, 1527, 1440, 1382,
1276, 1157, 1029, 962, 839, 779, 713 cmꢁ1. 1H NMR (600 MHz, CDCl)
1039, 948, 821, 744 cmꢁ1. 1H NMR (600 MHz, DMSO-d6)
d 11.92 (s,
1H), 8.83 (m, 2H), 8.29 (s, 1H), 7.92 (d, J¼7.7 Hz, 1H), 7.75 (s, 1H),
7.69 (t, J¼7.4 Hz, 1H), 7.64 (m, 3H), 7.50 (t, J¼7.4 Hz, 1H), 7.17 (s, 2H),
6.96 (t, J¼7.4 Hz, 1H), 6.92 (d, J¼7.8 Hz, 1H), 6.71 (d, J¼8.0 Hz, 1H),
d
14.36 (s, 1H), 8.54 (s, 1H), 7.94 (d, J¼8.3 Hz, 1H), 7.92 (d, J¼8.1 Hz,
1H), 7.54 (t, J¼7.6 Hz, 1H), 7.49 (t, J¼7.9 Hz, 2H), 7.38 (t, J¼6.8 Hz,
2H), 6.65 (d, J¼9.1 Hz, 1H), 6.45 (s, 1H), 5.75 (d, J¼9.0 Hz, 1H), 3.67
6.23 (t, J¼7.4 Hz, 1H). 13C NMR (150 MHz, DMSO-d6)
d 163.1, 161.6,
(s, 3H), 2.86 (s, 3H). 13C NMR (150 MHz, CDCl3)
d
164.3, 163.1, 163.0,
157.6, 134.0, 131.2, 131.0, 137.1, 130.1, 129.6, 129.5, 128.7, 128.4, 127.1,
127.1, 127.0, 126.9, 126.2, 123.3, 122.9, 121.4, 119.6, 117.8, 117.1. HRMS
(ESI-TOF) m/z [MþNa]þ calcd for C24H17N3ONa 386.1269, found
386.1255.
162.2, 160.7, 134.9, 133.8, 131.6, 131.2, 129.0, 128.5, 127.4, 126.9,
126.5, 126.4, 125.8, 125.1, 110.6, 106.1, 102.0, 55.09, 25.40. HRMS
(ESI-TOF) m/z [MþH]þ calcd for C22H19N2O2 343.1447, found
343.1440.
4.4.14. 2-Amino-4-(2-hydroxy-5-fluorophenyl)-5-(phenanthren-9-
yl)pyrimidine (4n). Yellow powder. Yield 617.2 mg (81%). Mp
294.5e296.5 ꢀC. IR (KBr) 3410, 3336, 3178, 3068, 1656, 1566, 1504,
1442, 1359, 1253, 1205, 1112, 1033, 964, 885, 817, 767, 723 cmꢁ1. 1H
4.4.9. 4-(2-Hydroxyphenyl)-5-(naphthalen-1-yl)pyrimidine
(4i). Yellow powder. Yield 518.5 mg (87%). Mp 120e122 ꢀC. IR
(KBr) 3205, 3053, 1608, 1560, 1500, 1448, 1386, 1249, 1161, 1035,
956, 854, 759 cmꢁ1. 1H NMR (600 MHz, DMSO-d6)
d
13.08 (s, 1H),
NMR (400 MHz, DMSO-d6)
d
11.46 (s,1H), 8.84 (t, J¼8.3 Hz, 2H), 8.32
9.25 (s, 1H), 8.75 (s, 1H), 7.96 (d, J¼8.3 Hz, 1H), 7.93 (d, J¼8.2 Hz,
1H), 7.54 (t, J¼7.6 Hz, 1H), 7.50 (dd, J¼13.1, 7.8 Hz, 2H), 7.39 (t,
J¼7.2 Hz, 2H), 7.10 (t, J¼7.7 Hz, 1H), 6.98 (d, J¼8.2 Hz, 1H), 6.75 (d,
J¼8.2 Hz, 1H), 6.19 (t, J¼7.7 Hz, 1H). 13C NMR (150 MHz, DMSO-d6)
(d, J¼2.8 Hz, 1H), 7.92 (d, J¼7.4 Hz, 1H), 7.77 (s, 1H), 7.73e7.61 (m,
4H), 7.52 (t, J¼7.5 Hz, 1H), 7.17 (s, 2H), 6.80 (t, J¼8.5 Hz, 1H),
6.75e6.62 (m, 2H). 13C NMR (151 MHz, DMSO-d6)
d 162.2, 161.8,
1
161.3, 154.6 (d, JCeF¼231.8 Hz), 153.5, 133.4, 133.1, 130.7, 130.0,
d
162.7, 161.2, 160.0, 155.3, 134.3, 133.8, 132.7, 131.0, 130.9, 130.3,
129.5, 128.6, 128.5, 127.1, 127.0, 126.9 (d, 3JCeF¼8.0 Hz), 126.1, 123.2,
3
129.3, 128.7, 127.6, 127.2, 126.6, 125.8, 124.9, 118.6, 118.4, 117.7.
HRMS (ESI-TOF) m/z [MþH]þ calcd for C20H15N2O 299.1184, found
299.1183.
122.8, 122.7, 122.7, 119.9, 117.7(d, JCeF¼7.9 Hz), 117.2(d,
2JCeF¼22.7 Hz), 115.3(d, JCeF¼24.4 Hz). HRMS (ESI-TOF) m/z
2
[MþH]þ calcd for C24H17FN3O 382.1356, found 382.1338.
4.4.10. 4-(2-Hydroxy-5-fluorophenyl)-5-(naphthalen-1-yl)pyrimi-
dine (4j). Yellow powder. Yield 556.1 mg (88%). Mp 123e125 ꢀC. IR
(KBr) 3107, 3053, 1624, 1550, 1446, 1371, 1256, 1191, 1109, 1047, 966,
4.4.15. 2-Amino-4-(2-hydroxy-4-tert-butylphenyl)-5-(phenanthren-
9-yl)pyrimidine (4o). Colorless powder. Yield 695.5 mg (83%). Mp
282.5e284.5 ꢀC. IR (KBr) 3475, 3278, 3141, 3063, 2960, 2869, 1624,
1581, 1545, 1481,1425, 1369, 1207,1107, 1035, 947, 808, 740 cmꢁ1. 1H
873, 773, 653 cmꢁ1. 1H NMR (600 MHz, CDCl3)
d 12.87 (s, 1H), 9.27
(s, 1H), 8.79 (s, 1H), 8.00 (d, J¼8.3 Hz, 1H), 7.94 (d, J¼8.2 Hz, 1H),
7.60e7.55 (m, 1H), 7.51 (t, J¼7.3 Hz,1H), 7.45e7.35 (m, 3H), 6.92 (dd,
J¼9.0, 5.0 Hz, 1H), 6.82 (ddd, J¼9.1, 7.6, 3.0 Hz, 1H), 6.41 (dd, J¼10.6,
NMR (400 MHz, CDCl3)
1H), 7.85 (d, J¼7.9 Hz, 1H), 7.75e7.58 (m, 5H), 7.51e7.44 (m, 1H),
6.96 (d, J¼2.0 Hz, 1H), 6.90 (d, J¼8.6 Hz, 1H), 6.16 (dd, J¼8.6, 2.1 Hz,
d
13.50 (s, 1H), 8.76 (t, J¼8.3 Hz, 2H), 8.32 (s,

5044
W. Wei et al. / Tetrahedron 72 (2016) 5037e5046
1H), 5.48 (s, 2H), 1.11 (s, 9H). 13C NMR (150 MHz, CDCl3)
d
162.1,
(KBr) 3492, 3290, 3136, 2952, 2864, 1631, 1566, 1471, 1421, 1315,
1251, 933, 842, 792, 750, 688 cmꢁ1. 1H NMR (400 MHz, CDCl3)
9.75
162.1, 160.9, 159.0, 154.6, 134.4, 131.3, 130.9, 130.1, 129.6, 129.2,
128.6, 128.2, 127.15, 127.14, 127.1, 127.0, 126.1, 123.4, 122.9, 118.4,
116.6, 115.0, 114.4, 34.2, 30.5. HRMS (ESI-TOF) m/z [MþH]þ calcd for
d
(s, 1H), 9.09 (d, J¼8.5 Hz, 1H), 8.67 (d, J¼8.2 Hz, 1H), 8.60 (d,
J¼8.6 Hz, 2H), 8.01 (d, J¼7.7 Hz, 1H), 7.96 (d, J¼8.8 Hz, 1H), 7.79 (d,
J¼8.5 Hz, 1H), 7.67e7.58 (m, 2H), 5.49 (s, 2H), 1.53 (s, 9H). 13C NMR
C
28H26N3O 420.2076, found 420.2057.
(100 MHz, CDCl3)
d (ppm) 160.0, 159.7, 153.8, 153.4, 133.5, 133.0,
129.9, 128.4, 127.8, 126.9, 126.5, 126.4, 126.3, 126.1, 125.5, 125.3,
125.1, 120.7, 119.0, 114.7, 35.5, 31.4. HRMS (ESI-TOF) m/z [MþH]þ
calcd for C24H22N3 352.1814, found 352.1805.
4.5. General procedure for the synthesis of benzo[h]-naphth
[1,2-f] quinazolines and benzo[h]-phenanthren[9,10-f]quina-
zoines 5
4.5.4. 2-Amino-12-methoxy-benzo[h]-naphth[1,2-f ]quinazoline
(5d). Yellow powder. Yield 136.5 mg (71%). Mp 233e234.0 ꢀC. IR
(KBr) 3396, 3311, 3182, 2933, 2835, 1645, 1564, 1465, 1294, 1231,
1155,1036, 939, 866, 796, 744, 669 cmꢁ1. 1H NMR (600 MHz, DMSO-
4-(2-hydroxyphenyl)-5-(naphthalen-1-yl)pyrimidines
4ael
(0.1 mmol) was added to a EtOH-water (19:1) solution (100 mL), the
solution was contained in 100 mL quartz tubes, deaerated by bub-
bling argon for 30 min and irradiated with a high pressure mercury
lamp (500 W) for 35 h at 20 ꢀC. Then, the solvent was removed under
reduced pressure, and the residue was purified by column chro-
matography on silica gel using petrol ether: ethyl acetate (or petrol
ether: diethyl ether: dichloromethane) as eluent to give the corre-
sponding products 5ael. Due to the poor solubility of 4meo, we
used EtOH-dioxane-water (18:1:1) solution as solvent. The other
procedure for the synthesis of 5meo was same with that of 5ael and
5ae5o characterized by 1H NMR, 13C NMR, IR and HRMS.
d6),
d
4.02 (s, 3H), 7.10 (s, 2H), 7.36 (d, 1H, J¼8.9 Hz), 7.64 (t, 1H,
J¼7.3 Hz), 7.68 (t, 1H, J¼7.2 Hz), 7.99 (d, 1H, J¼8.8 Hz), 8.07 (d, 1H,
J¼7.8 Hz), 8.13 (d, 1H, J¼1.8 Hz), 8.64 (d, 1H, J¼8.3 Hz) 8.70 (d, 1H,
J¼9.0 Hz), 9.00 (d, 1H, J¼8.9 Hz), 9.57 (s, 1H); 13C NMR (100 MHz,
DMSO-d6),
d 161.4, 160.7, 159.2, 152.5, 134.6, 133.4, 128.3, 128.2,
127.8, 126.6, 126.4, 125.7, 124.5,122.3, 121.4, 116.4, 112.2, 105.5, 55.6;
HRMS (ESI-TOF) m/z [MþH]þ calcd for C21H16N3O 326.1293, found
326.1290.
In order to further investigation of product structures, the
crystal structure of 5d was determined (Fig. 1). The average dis-
tance of atoms C2 to C21, N1 and N2 from the least square plane
4.5.1. 2-Amino-benzo[h]-naphth[1,2-f]quinazoline
(5a). Yellow
powder. Yield 120.4 mg (68%). Mp 230e232 ꢀC. IR (KBr) 3452, 3298,
ꢀ
(C2eC21, N1, N2) was 0.2129 A. The distances of atoms N2, C21 and
3190, 3053, 2924, 2858, 1730, 1624, 1560, 1460, 1390, 1232, 1126,
1045, 954, 808, 748 cmꢁ1. 1H NMR (600 MHz, DMSO-d6),
d 7.20 (s,
ꢀ
C14 from the least square plane (C2eC21, N1, N2) were 0.4914 A,
ꢀ
0.5488 and ꢁ0.5354 A, respectively. The dihedral angle between
2H), 7.64 (t, J¼7.3 Hz,1H), 7.69 (t, J¼7.3 Hz,1H), 7.76 (t, J¼7.4 Hz,1H),
7.99 (d, J¼8.8 Hz, 1H), 8.07 (d, J¼7.8 Hz,1H), 8.66 (dd, J¼15.6, 8.7 Hz,
2H), 8.75 (d, J¼8.3 Hz, 1H), 9.11 (d, J¼7.9 Hz, 1H), 9.63 (s, 1H); 13C
ring E (C11eC16) and A (C18eC21, N1, N2) was 29.6ꢀ (Fig. 1). Owing
the reason of the repulsion between contiguous H15 and H21
atoms in space (Fig. 1a), the molecular structure of polycyclic ring
system of 5d was slightly tilted from planarity (Fig. 1 b). It in-
dicated that the atoms of polycyclic ring system for 5ae5o were
also slightly tilted from planarity. The crystallographic data and
selected bond length, angles and torsion angles were summarized
in Tables 3 and 4, respectively. Crystallographic data were de-
posited in CSD under CCDC-1449149 registration number and
were available free of charge upon request to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK (fax: þ44-1223-336033, e-mail:
deposit@ccdc.cam.ac.uk).
NMR (100 MHz, DMSO-d6),
d 113.1, 121.0, 123.6, 124.7, 124.8, 125.1,
126.4, 126.6, 127.2, 127.6, 128.2, 128.3, 128.4, 130.6, 132.6, 133.2,
152.5, 159.4, 160.7; HRMS (ESI-TOF) m/z [MþH]þ calcd for C20H14N3
296.1188, found 296.1183.
4.5.2. 2-Amino-13-fluoro-benzo[h]-naphth[1,2-f ]quinazoline
(5b). Colorless powder. Yield 116.4 mg (62%). Mp 237e239 ꢀC. IR
(KBr) 3384, 3289, 3068, 2925, 2864, 1726, 1618, 1570, 1518, 1454,
1380, 1265, 1176, 1085, 1043, 952, 877, 786, 727, 671 cmꢁ1. 1H NMR
(400 MHz, DMSO-d6)
d
9.58 (s, 1H), 8.77 (dd, J¼9.2, 5.3 Hz, 1H), 8.65
(dd, J¼10.3, 2.9 Hz, 1H), 8.60 (t, J¼7.9 Hz, 2H), 8.05 (d, J¼7.3 Hz, 1H),
7.95 (d, J¼8.9 Hz, 1H), 7.73e7.60 (m, 3H), 7.23 (s, 2H). 13C NMR
4.5.5. 2-Methyl-benzo[h]-naphth[1,2-f]quinazoline
(5e). Yellow
powder. Yield 88.2 mg (50%). Mp 185e187 ꢀC. IR (KBr) 3037, 2922,
(100 MHz, DMSO-d6)
d
162.4 (d, 1JCeF¼243.9 Hz), 160.6, 159.9, 159.5,
4
3
2852, 1921, 1562, 1508, 1429, 1371, 1242, 1039, 956, 866, 806,
151.4 (d, JCeF¼3.5 Hz), 133.0, 130.2 (d, JCeF¼8.2 Hz), 129.3, 128.3,
746 cmꢁ1. 1H NMR (400 MHz, CDCl3)
1H), 8.69 (d, J¼8.0 Hz, 1H), 8.58 (d, J¼8.1 Hz, 1H), 8.52 (d, J¼8.8 Hz,
1H), 8.00 (t, J¼7.5 Hz, 2H), 7.84 (t, J¼7.3 Hz, 1H), 7.75 (t, J¼7.3 Hz,
1H), 7.70e7.54 (m, 2H), 3.01 (s, 3H). 13C NMR (150 MHz, CDCl3)
d
9.97 (s, 1H), 9.32 (d, J¼7.8 Hz,
3
128.0, 127.5, 126.7 (d, JCeF¼6.5 Hz), 126.3, 124.4, 124.3, 120.9,
118.9(d, 2JCeF¼23.0 Hz), 113.4, 109.3, 109.1 (d, 2JCeF¼22.5 Hz). HRMS
(ESI-TOF) m/z [MþH]þ calcd for C20H13FN3 314.1094, found 314.1093.
d
163.9, 157.5, 151.3, 133.5, 132.9, 130.7, 129.4, 129.1, 128.7, 128.6,
4.5.3. 2-Amino-12-tert-butyl-benzo[h]-naphth[1,2-f ]quinazoline
(5c). Yellow powder. Yield 210.6 mg (63%). Mp 228e229 ꢀC. IR
128.1, 127.6, 127.5, 127.1, 126.5, 125.5, 124.2, 123.1, 120.7, 118.6, 26.1.
Fig. 1. Molecular structure of compound 5d (recrystallized from ethyl acetate). (a) From vertical direction of the molecular plane; (b) From parallel direction of the molecular plane.

W. Wei et al. / Tetrahedron 72 (2016) 5037e5046
5045
Table 4
126.5, 124.8, 123.2, 120.7, 117.5, 116.4, 105.4, 55.5, 26.1; HRMS (ESI-
TOF) m/z [MþH]þ calcd for C22H17N2O 325.1341, found 325.1339.
Crystallographic data for compound 5d
Empirical formula
Formula weight
Temperature (K)
Wavelength (A)
Crystal system, space group
Unit cell dimensions
C21H15N3O
325.36
296(2)
0.71073
4.5.9. Benzo[h]-naphth[1,2-f]quinazoline (5i). Colorless powder.
Yield 90.7 mg (54%). Mp 179e181 ꢀC. IR (KBr) 3045,1944,1739,1606,
1566, 1512, 1456, 1413, 1336, 1230, 1161, 1103, 1039, 950, 873, 800,
ꢀ
Monoclinic, C2/c
740 cmꢁ1. 1H NMR (400 MHz, CDCl3)
d 10.02 (s, 1H), 9.39 (s, 1H), 9.26
ꢀ
a¼18.237(10) A
ꢀ
b¼13.871(8) A
(d, J¼7.9 Hz,1H), 8.64 (d, J¼8.0 Hz,1H), 8.53 (d, J¼8.1 Hz,1H), 8.46 (d,
ꢀ
c¼14.473(9) A
J¼8.7 Hz, 1H), 7.97 (t, J¼7.5 Hz, 2H), 7.83 (t, J¼7.4 Hz, 1H), 7.74 (t,
alpha¼90.00 deg.
beta¼121.706(9) deg.
gamma¼90.00 deg.
3115(3)
J¼7.5 Hz, 1H), 7.69e7.58 (m, 2H). 13C NMR (150 MHz, CDCl3)
d 157.4,
154.7, 151.1, 133.5, 132.9, 131.0, 129.4, 129.3, 129.1, 128.7, 128.6, 127.8,
127.5, 127.3, 126.7, 125.5, 123.8, 123.2, 121.1, 120.7, 58.4. HRMS (ESI-
TOF) m/z [MþH]þ calcd for C20H13N2 281.1079, found 281.1077.
3
ꢀ
Volume (A )
Z, Calculated density (g cmꢁ3
)
)
8, 1.388
0.088
1360
Absorption coefficient (mmꢁ1
F(000)
4.5.10. 13-Fluoro-benzo[h]-naphth[1,2-f]quinazoline (5j). Colorless
powder. Yield 41.1 mg (23%). Mp 254e256 ꢀC. IR (KBr) 3055, 1612,
Crystal size, mm
Theta range for data collection
Limiting indices
0.36ꢂ0.31ꢂ0.22
1.97e25.10 deg.
ꢁ21ꢃhꢃ21,
1564, 1517, 1462, 1411, 1255, 1176, 1096, 1026, 800 cmꢁ1 1H NMR
.
ꢁ14ꢃkꢃ16,
(600 MHz, CDCl3)
d
10.19 (s, 1H), 9.45 (s, 1H), 8.99 (dd, J¼9.7, 2.8 Hz,
ꢁ17ꢃlꢃ17
1H), 8.77 (d, J¼8.4 Hz, 1H), 8.67 (dd, J¼9.0, 5.1 Hz, 1H), 8.57 (d,
J¼8.9 Hz, 1H), 8.11 (d, J¼8.8 Hz, 1H), 8.07 (d, J¼7.9 Hz, 1H), 7.75 (t,
Reflections collected/unique
Completeness to theta
Max. and min. transmission
Refinement method
7714/2771 [R(int)¼0.0442]
99.8%
J¼7.5Hz,1H), 7.69(t,J¼7.2Hz,1H), 7.63(td, J¼9.0,2.8Hz,1H).13CNMR
0.9808 and 0.9694
Full-matrix least-squares on F2
2771/0/228
1
(150 MHz, CDCl3)
d
162.3 (d, JCeF¼247.5 Hz), 157.7, 154.7, 150.4(d,
4JCeF¼3.9 Hz), 133.4, 131.3(d, 3JCeF¼8.3 Hz), 129.6, 129.5, 129.4, 128.7,
Data/restraints/parameters
Goodness-of-fit on F2
1.072
3
128.3, 127.5, 127.4, 126.7, 125.7 (d, JCeF¼8.6 Hz), 123.3, 121.6, 120.6,
Final R indices [I>2sigma(I)]
R indices (all data)
Largest diff. peak and hole
R1¼0.0543, wR2¼0.1542
119.7 (d, 2JCeF¼23.3 Hz),110.7 (d, 2JCeF¼22.6 Hz). HRMS (ESI-TOF) m/z
[MþH]þ calcd for C20H12FN2 299.0985, found 299.0983.
R1¼0.0843, wR2¼0.1738
ꢀꢁ3
0.227 and ꢁ0.181 e. A
4.5.11. 12-tert-Butyl-benzo[h]-naphth[1,2-f]quinazoline (5k). Yellow
powder. Yield 70.6 mg (35%). Mp 166e168 ꢀC. IR (KBr) 3049, 2958,
2924, 2862, 1612, 1560, 1504, 1458, 1415, 1369, 1259, 1107, 1026,920,
HRMS (ESI-TOF) m/z [MþH]þ calcd for C21H15N2 295.1235, found
295.1228.
842, 798, 734 cmꢁ1. 1H NMR (400 MHz, CDCl3)
d 10.08 (s, 1H), 9.40
4.5.6. 2-Methyl-13-fluoro-benzo[h]-naphth[1,2-f ]quinazoline
(5f). White powder. Yield 56.2 mg (30%). Mp 240e242 ꢀC. IR (KBr)
3028, 2954,1934,1894,1562,1510,1423,1361,1251,1178,1116,1016,
(s, 1H), 9.23 (d, J¼8.6 Hz, 1H), 8.72 (d, J¼8.3 Hz, 1H), 8.66e8.62 (m,
2H), 8.06e8.02 (m, 2H), 7.87 (d, J¼8.3 Hz, 0H), 7.66 (m, 2H), 1.55 (s,
9H). 13C NMR (101 MHz, CDCl3)
d 157.3, 154.7, 154.3, 151.1, 133.4,
939, 894, 852, 804, 744 cmꢁ1. 1H NMR (600 MHz, CDCl3)
d
10.05 (s,
132.6, 129.5, 129.1, 128.9, 128.6, 127.5, 127.1, 126.8, 126.4, 126.0,
125.2, 123.9, 120.7, 120.6, 119.1, 35.6, 31.4. HRMS (ESI-TOF) m/z
[MþH]þ calcd for C24H21N2 337.1705, found 337.1701.
1H), 8.99 (dd, J¼9.8, 2.8 Hz, 1H), 8.74 (d, J¼8.4 Hz, 1H), 8.62 (dd,
J¼9.0, 5.1 Hz, 1H), 8.53 (d, J¼8.9 Hz, 1H), 8.06 (d, J¼4.4 Hz, 1H), 8.05
(d, J¼3.0 Hz, 1H), 7.74e7.69 (m, 1H), 7.66 (t, J¼7.1 Hz, 1H), 7.59 (td,
J¼9.0, 2.8 Hz, 1H), 3.01 (s, 3H). 13C NMR (150 MHz, CDCl3)
d
163.0,
4.5.12. 12-Methoxy-benzo[h]-naphth[1,2-f ]quinazoline
(5l). Colorless powder. Yield 102.3 mg (55%). Mp 227e228.5 ꢀC. IR
(KBr) 3047, 2983, 2916, 2844, 1614, 1570, 1513, 1419, 1342, 1285,
1227,1170,1053, 926, 844, 787, 697 cmꢁ1. 1H NMR (400 MHz, CDCl3)
162.7 (d, 1JCeF¼274.7 Hz), 157.8, 150.5 (d, 4JCeF¼4.0 Hz), 133.4, 131.3
(d, 3JCeF¼8.5 Hz), 129.5 (d, 2JCeF¼15.1 Hz), 129.0, 128.7, 127.8, 127.5,
127.3, 126.86, 125.7 (d, 3JCeF¼8.0 Hz), 123.7, 120.6, 119.4, 119.3, 119.1,
110.6(d, 2JCeF¼22.8 Hz), 26.1. HRMS (ESI-TOF) m/z [MþH]þ calcd for
d
10.06 (s, 1H), 9.37 (s, 1H), 9.25 (d, J¼8.9 Hz, 1H), 8.76 (d, J¼8.2 Hz,
C
21H14FN2 313.1141, found 313.1134.
1H), 8.51 (d, J¼8.9 Hz, 1H), 8.04 (d, J¼8.5 Hz, 2H), 7.98 (s, 1H),
7.72e7.69 (m, 1H), 7.69e7.63 (m, 1H), 7.39 (d, J¼8.8 Hz, 1H), 4.07 (s,
4.5.7. 2-Methyl-12-tert-butyl-benzo[h]-naphth[1,2-f]quinazoline
(5g). Yellow powder. Yield 115.5 mg (55%). Mp 196e198 ꢀC. IR (KBr)
3063, 2958, 2866, 1566, 1497, 1433, 1367, 1269, 1230, 1035, 927, 840,
3H). 13C NMR (150 MHz, CDCl3)
d 162.1, 157.3, 154.8, 151.2, 134.9,
133.6, 129.6, 129.1, 128.7, 128.3, 127.7, 127.5, 127.3, 126.8, 124.6,
123.2, 120.8, 120.1, 116.6, 105.7, 55.6. HRMS (ESI-TOF) m/z [MþH]þ
calcd for C21H14N2O 311.1184, found 311.1181.
796, 758, 686 cmꢁ1. 1H NMR (400 MHz, CDCl3)
d 10.00 (s, 1H), 9.27
(d, J¼8.7 Hz, 1H), 8.74 (d, J¼8.2 Hz, 1H), 8.67e8.62 (m, 2H), 8.05 (d,
J¼4.5 Hz, 1H), 8.03 (s, 1H), 7.85 (d, J¼8.5 Hz, 1H), 7.66 (dt, J¼14.5,
7.0 Hz, 2H), 3.01 (s, 3H), 1.54 (s, 9H). 13C NMR (100 MHz, CDCl3)
4.5.13. 2-Amino-benzo[h]-phenanthren[9,10-f ]quinazoline
(5m). Yellow powder. Yield 78.7 mg (38%). Mp 186e188 ꢀC. IR (KBr)
3462, 3311, 3190, 2353, 1728, 1641, 1591, 1489, 1423, 1375, 1286,
d
163.9, 157.4, 154.0, 151.3, 133.4, 132.6, 129.4, 128.5, 128.4, 128.3,
127.6, 126.9, 126.8, 126.3, 125.7, 125.2, 124.3, 120.6, 119.0, 118.3, 35.5,
31.4, 26.1. HRMS (ESI-TOF) m/z [MþH]þ calcd for C25H23N2 351.1861,
found 351.1852.
1217, 1149, 1064, 738 cmꢁ1. 1H NMR (400 MHz, DMSO-d6)
d 9.48 (s,
1H), 9.09 (d, J¼7.7 Hz, 1H), 8.81 (s, 2H), 8.59 (d, J¼7.7 Hz, 2H), 8.40
(d, J¼4.7 Hz, 1H), 7.81 (t, J¼6.8Hz, 1H), 7.71 (m, 5H), 7.20 (s, 2H)$13C
NMR (150 MHz, DMSO-d6)
d 161.0, 159.8, 152.4, 131.5, 130.3, 129.8,
4.5.8. 2-Methyl-12-methoxy-benzo[h]-naphth[1,2-f ]quinazoline
(5h). Colorless powder. Yield 99.1 mg (62%). Mp 198e200 ꢀC. IR
(KBr) 3039, 2931, 2842, 1614, 1570, 1497, 1429, 1371, 1286, 1225,
129.6,128.9,128.8,128.4,128.0,127.7,127.3,127.2,127.1,127.0,126.5,
126.4, 125.6, 124.9, 123.9, 123.0, 112.7. HRMS (ESI-TOF) m/z [MþH]þ
calcd for C24H16N3 346.1344, found 346.1337.
1186, 1128, 1064, 1043, 960, 926, 781, 839, 688 cmꢁ1 1H NMR
.
(400 MHz, CDCl3)
d
9.92 (s, 1H), 9.22 (d, J¼8.9 Hz, 1H), 8.71 (d,
4.5.14. 2-Amino-5-fluoro-benzo[h]-phenanthren[9,10-f]quinazoline
(5n). Yellow powder. Yield 76.2 mg (35%). Mp 284e286 ꢀC. IR (KBr)
3502, 3286, 3159, 1618, 1583, 1440, 1379, 1211, 1114, 1047, 974, 916,
J¼8.1 Hz, 1H), 8.43 (d, J¼8.9 Hz, 1H), 8.00 (dd, J¼13.2, 8.3 Hz, 2H),
7.91 (d, J¼1.8 Hz, 1H), 7.73e7.57 (m, 2H), 7.33 (dd, J¼8.9, 2.1 Hz, 1H),
4.04 (s, 3H), 2.97 (s, 3H)$13C NMR (150 MHz, CDCl3)
d
163.9, 161.8,
819, 738 cmꢁ1
.
1H NMR (600 MHz, CDCl3)
d
9.46 (s, 1H), 8.82 (t,
157.3, 151.3, 134.7, 133.5, 129.4, 128.5, 128.4, 127.7, 127.6, 127.4, 127.0,
J¼7.0 Hz, 2H), 8.68 (dd, J¼10.1, 2.9 Hz, 1H), 8.61 (dd, J¼9.0, 5.4 Hz,

5046
W. Wei et al. / Tetrahedron 72 (2016) 5037e5046
Nosulenko, I. S.; Katsev, A. M.; Shandrovskaya, O. S. Eur. J. Med. Chem. 2011, 46,
6066e6074.
1H), 8.50 (d, J¼8.0 Hz, 1H), 8.34 (d, J¼7.9 Hz, 1H), 7.70 (m, 5H), 7.24
(s, 2H)$13C NMR (150 MHz, DMSO-d6)
d 161.0, 160.5(d,
2. Xue, W. L.; Warshawsky, D. Toxicol. Appl. Pharmacol. 2005, 206, 73e93.
3. (a) Kundu, P. K.; Samanta, D.; Leizrowice, R.; Margulis, B.; Zhao, H.; Borner, M.;
Udayabhaskararao, T.; Manna, D.; Klajn, R. Nat. Chem. 2015, 7, 646e652; (b)
Larock, R. C.; Doty, M. J.; Tian, Q. P.; Zenner, J. M. J. Org. Chem. 1997, 62,
7536e7537; (c) Goldfinger, M. B.; Crawford, K. B.; Swager, T. M. J. Am. Chem. Soc.
1997, 119, 4578e4593.
4. (a) Bae, J. S.; Lee, D. H.; Lee, D. W.; Jang, J. G.; Jeon, S. Y. U. S. Patent 20 070
131 929, 2007; (b) Cai, Y. S.; Guo, Z. Q.; Chen, J. M.; Li, W. L.; Zhong, L. B.; Gao,
Y.; Jiang, L.; Chi, L. F.; Tian, H.; Zhu, W. H. http://dx.doi.org/10.1021/jacs.
5b11580.
4
1JCeF¼244.5 Hz), 160.0, 151.4(d, JCeF¼3.6 Hz),130.9, 130.9, 130.8,
130.2, 129.6,128.8,128.3,128.1, 127.6,127.3, 127.2, 127.1, 127.0, 126.5,
125.0, 123.8(d, 3JCeF¼10.9 Hz), 122.5, 118.0(d, 2JCeF¼23.1 Hz), 112.9,
2
109.3(d, JCeF¼22.5 Hz). HRMS (ESI-TOF) m/z [MþNa]þ calcd for
C
24H15FN3 386.1069, found 346.1059.
4.5.15. 2-Amino-12-tert-butyl-benzo[h]-phenanthren[9,10-f]quina-
zoline (5o). Yellow powder. Yield 139.5 mg (58%). Mp 232e234 ꢀC.
IR (KBr) 3496, 3302, 3186, 2922, 2858, 1722, 1622, 1571, 1485, 1440,
5. (a) Pan, X.; Fang, C.; Fantin, M.; Malhotra, N.; So, W. Y.; Peteanu, L. A.; Isse,
A. A.; Gennaro, A.; Liu, P.; Matyjaszewski, K. J. Am. Chem. Soc. 2016, 138,
2411e2425; (b) Pan, X.; Curran, D. P. Org. Lett. 2014, 16, 2728e2731; (c) Pan,
1373, 1273, 1227, 1165, 1114, 736 cmꢁ1 1H NMR (400 MHz, CDCl3)
.
^
ꢁ
X.; Lacote, E.; Lalevee, J.; Curran, D. P. J. Am. Chem. Soc. 2012, 134,
5669e5674.
d
9.61 (s, 1H), 9.09 (d, J¼8.6 Hz, 1H), 8.71 (m, 4H), 8.41 (d, J¼7.5 Hz,
1H), 7.77 (d, J¼8.5 Hz, 1H), 7.66 (m, 4H), 5.51 (s, 2H), 1.47 (s, 9H). 13
C
6. (a) Ionkin, A. S.; Marshall, W. J.; Fish, B. M.; Bryman, L. M.; Wang, Y. Chem.
Commun. 2008, 2319; (b) Koji, T.; Akiko, H..; Kunihiro I.; Kenichi, A. Japan.
Patent 2 010 024 388, 2010; (c) Lim, J. O.; Hwang, S. H.; Kim, Y. K. Jung, H. J.;
Han, S. H.; Kwak, Y. H.; Lee, S. Y.; Lee, C. H.; Ko, H. J.; Lee, J. H. U. S. 20 120 267
613, 2012; (d) Balaban, A. T.; Gutman, I.; Stankovic, S. Polycycl. Aromat. Compd.
2004, 24, 173e193.
7. (a) Olivera, R.; Pascual, S.; Herrero, M.; SanMartin, R.; Dominguez, E. Tetrahe-
dron Lett. 1998, 39, 7155e7158; (b) Olivera, R.; SanMartin, R.; Pascual, S.; Her-
rero, M.; Dominguez, E. Tetrahedron Lett. 1999, 40, 3479e3480; (c) Kadiyala, R.
R.; Tilly, D.; Nagaradja, E.; Roisnel, T.; Matulis, V. E.; Ivashkevich, O. A.; Halauko,
Y. S.; Chevallier, F.; Gros, P. C.; Mongin, F. Chem.dEur. J. 2013, 19, 7944e7960; (d)
Mahmoodi, N. O.; Khodaee, Z. Mendeleev Commun. 2004, 304e306.
8. (a) Xue, P. P.; Du, Z. C.; Wang, T.; Zhang, Z. T. Synthesis 2015, 47, 3385e3391; (b)
Wang, Q. Y.; Zhang, Z. T.; Du, Z. C.; Hua, H. L.; Chen, S. S. Green Chem. 2013, 15,
1048e1054.
NMR (150 MHz, CDCl3) d 160.3, 160.1, 153.2, 152.8, 132.4, 130.9, 130.5,
129.3, 128.9, 128.2, 128.0, 127.2, 127.0, 126.8, 126.6, 126.4, 125.7, 125.4,
125.1, 124.8, 124.6, 123.7, 123.7, 114.5, 35.4, 31.3. HRMS (ESI-TOF) m/z
[MþH]þ calcd for C28H24N3 402.1970, found 402.1948.
Acknowledgements
We are grateful for financial support from the National Natural
Science Foundation of China (No: 21372150, 21542002) and the
Fundamental Funds Research for the Central Universities (No:
GK201503034).
9. Biegasiewicz, K. F.; St. Denis, J. D.; Carroll, V. M.; Priefer, R. Tetrahedron Lett.
2010, 51, 4408.
10. Wang, D. S. M. Dissertation, Shaanxi Normal University, 2012.
11. Xie, F. C.; Cheng, G.; Hu, Y. H. J. Comb. Chem. 2006, 8, 286e288.
12. Gao, M. X.; He, Q.; Han, W. Y.; Zhang, Z. T. Acta Pharm. Sin. 2010, 45, 1123.
13. (a) Manoj, K. N.; Peter, W. Photochem. Photobiol. Sci. 2008, 7, 1544; (b) Sato, T.;
Shimada, S.; Hata, K. Bull. Chem. Soc. Jpn. 1971, 44, 2484e2490.
14. Zhang, Q.; Peng, H. Q.; Zhang, G. S.; Lu, Q. ,Q.; Chang, J.; Dong, Y. Y.; Shi, X. Y.;
Wei, J. F. J. Am. Chem. Soc. 2014, 136, 5057.
15. (a) Maciej, K.; Daniel, T. G. J. Org. Chem. 2015, 80, 2893e2899; (b) Masaki, S.;
Yoshinori, Y.; Tomonori, M.; Takashi, K.; Eiji, N.; Akari, H.; Kunihisa, S.; Hiroshi,
H. J. Am. Chem. Soc. 2015, 137, 1024; (c) Hayashi, Y.; Obata, N.; Tamaru, M.;
Yamaguchi, S.; Matsuo, Y.; Saeki, A.; Seki, S.; Kureishi, Y.; Saito, S.; Yamaguchi,
S.; Shinokubo, H. Org. Lett. 2012, 14, 866e869; (d) Chai, Y.; Yang, E. Q.; Zhang, Y.
L.; Xie, A. L.; Cao, X. P. Synthesis 2012, 44, 439e445.
Supplementary data
Supplementary data related to this article can be found, in the
online version at http://dx.doi.org/10.1016/j.tet.2016.04.080.
References and notes
1. (a) Rewcastle, G. W.; Palmer, B. D.; Bridges, A. J.; Showalter, H. D. H.; Sun, L.;
Nelson, J.; McMichael, A.; Kraker, A. J.; Fry, D. W.; Denny, W. A. J. Med. Chem.1996,
39, 918e928; (b) Onoda, Y.; Nomoto, Y.; Ohno, T.; Yamada, K.; Ichimura, M.
WO Patent 9 808 848, 1998; (c) Ashvar, C. S.; Chiang, S. M.; Emerson, D. L.; Hu, N.;
Jensen, G. M. WO 2 001095 884, A2, 2001.12.20; (d) Berger, D. M.; Birnberg, G. H.;
Wang, Y. N. WO Patent 2 002 053 528, 2002; (e) Widler, L.. WO Patent 2 008 089
933, 2008; (f) Berest, G. G.; Voskoboynik, O. Y.; Kovalenko, S. I.; Antypenko, O. M.;
16. Protti, S.; Manzini, S.; Fagnoni, M.; Albini, A. RSC Green Chem. Ser. 2009, 3 (Eco-
Friendly Synthesis of Fine Chemicals), 80e111.