Palladium-catalyzed intramolecular C-H activation/C-C bond formation: A straightforward synthesis of phenanthridines

Article abstract of DOI:10.1021/jo2017108

The palladium-catalyzed intramolecular C-H activation/C-C cross-coupling has been developed for a straightforward and efficient synthesis of phenanthridines. With Pd(OAc)₂ (4 mol %) as the catalyst, PCy ₃ (8 mol %) as the ligand, and

Full text of DOI:10.1021/jo2017108

Note
pubs.acs.org/joc
Palladium-Catalyzed Intramolecular C−H Activation/C−C Bond
Formation: A Straightforward Synthesis of Phenanthridines
Jinsong Peng,†,‡ Tonghui Chen,† Chunxia Chen,† and Bin Li*,†,‡
†Department of Chemistry and Chemical Engineering, College of Science, Northeast Forestry University, Harbin, 150040, P. R.
China
‡Post-doctoral Mobile Research Station of Forestry Engineering, Northeast Forestry University, Harbin, 150040, P. R. China
S
* Supporting Information
ABSTRACT: The palladium-catalyzed intramolecular C−H
activation/C−C cross-coupling has been developed for a
straightforward and efficient synthesis of phenanthridines.
With Pd(OAc)2 (4 mol %) as the catalyst, PCy3 (8 mol %) as
the ligand, and Cs2CO3 as the base, this protocol was applied
to synthesize a small library of phenanthridine derivatives in
good yields in THF.
henanthridines are frequently found in a diverse array of
compounds, including a wide range of significant natural
herein we report on palladium-catalyzed intramolecular C−H
activation/C−C cross-coupling reaction of N-(2-haloaryl)-
imines for the direct and efficient synthesis of phenanthridines.
N-(2-bromophenyl)imine (1a) derived from the addition of
2-bromobenzenamine to benzophenone was selected as a
model substrate for a palladium-catalyzed intramolecular C−H
activation/C−C cross-coupling reaction. The blank experiment
(without the catalyst and ligand) of 1a was examined in toluene
at 110 °C for 24 h using Cs2CO3 as the base, and no desired
product was obtained (entry 1, Table 1). After an initial screen
of various palladium catalysts (4 mol %) with PPh3 (8 mol %)
as the ligand, we found that the use of Pd(OAc)2 gave the best
result in 36% yield (entries 2−5, Table 1). To optimize other
reaction conditions, different ligands, solvents, bases, reaction
time, and temperature were examined using 4 mol % Pd(OAc)2
as the catalyst, as shown in Table 1. It was known that
palladium-catalyzed C−H activation/C−C bond-forming re-
actions using aryl halides as substrates are very sensitive to
catalyst structure and ligand.12b Therefore, a judicious choice of
ligands is needed to increase the yield of 2a. We then
investigated the effect of various ligands (P(o-tolyl)3, PCy3,
NHCs, bidentate phosphorus ligands such as dppm, dppb, dppf
and xantphos) on the reaction (entries 6−12, Table 1).
Pd(OAc)2 and PCy3 were found to be the combination for this
cross-coupling reaction with the best yield (entry 8, Table 1). A
survey of reaction media showed that the use of THF as solvent
provided better results than those obtained in toluene, DMSO,
and 1,2-dichloroethane (entries 8 and 13−15, Table 1).
Reactions carried out in DMF gave a comparable yield to the
reaction in THF (96 vs 98%, entries 13 and 16, Table 1).
Finally, other bases such as K2CO3, pyridine, K3PO4, and
P
products, biologically and therapeutically active compounds
such as antiviral, antiprotozoal, and antitumor agents, and
functional materials.1 Molecules containing this motif have
received considerable attention in medicinal and material
chemistry; therefore, much effort has been focused on the
synthetic methods of phenanthridine derivatives. Radical,2 one-
pot cascade,3 benzyne-mediated,4 photochemical,5 hypervalent
iodine-promoted,6 photocyclized,7 microwave-assisted,2c,8 and
transition-metal-catalyzed9 syntheses of the phenanthridine
skeleton have been reported.10
Palladium-catalyzed carbon−carbon bond-forming reactions
involving direct C−H bond activation have emerged as
powerful tools for the assembly of complex polycyclic
structures.11 The Fagnou group developed an operationally
simple catalyst system for direct intramolecular arylation
processes to form six- and five-membered ring biaryls.12
More recently, Lautens reported a palladium-catalyzed cascade
involving norbornene-mediated C−H activation/cross-coupling
for the construction of diversely substituted phenanthridine
derivatives.13 Fensterbank et al. developed a dual palladium-
catalyzed process for the efficient synthesis of phenanthridines
from benzylamines and aryl iodides by coupling a palladium/
norbornene co-catalyzed domino sequence with an oxidative
dehydrogenation.14
Although a number of useful synthetic protocols are available
for the preparation of phenanthridines, there remain many
limitations such as multistep synthetic reactions, limited
substrate scope, and, in some cases, harsh reaction conditions.
Therefore, the development of more milder, general, and
convenient processes using readily accessible building blocks
for the synthesis of the phenanthridine ring system is
imperative. In parallel with our efforts to develop more
versatile and simpler synthetic methods of heterocycles,15
Received: August 18, 2011
Published: October 12, 2011
© 2011 American Chemical Society
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The Journal of Organic Chemistry
Note
a
Table 1. Optimization of Palladium-Catalyzed Intramolecular C−C Cross-Coupling of Imine 1a
b
b
b
c
entry
catalyst
ligand
PPh3
base
solvent
yield
1
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
THF
2
Pd2(dba)3
PdCl2
trace
trace
19
3
PPh3
PPh3
PPh3
4
PdCl2(CH3CN)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
5
36
6
P(o-tolyl)3
Ipr·HCl
PCy3
39
7
19
8
48
9
xantphos
dppm
dppb
4
10
11
12
13
14
15
16
17
18
19
20
40
26
dppf
44
d
e
f
PCy3
98/92 /70 /66
PCy3
DMSO
DCE
trace
trace
96
PCy3
PCy3
DMF
PCy3
K2CO3
THF
95
PCy3
Pyridine
KOtBu
THF
61
PCy3
THF
56
PCy3
K3PO4
THF
20
a
Reaction conditions: 1.0 equiv of N-(2-bromophenyl)imine 1a (1.0 mmol), 2.0 equiv of base, 4 mol % of Pd catalyst, 8 mol % of ligand, solvent (2
b
mL). Abbreviations: dba = dibenzylideneacetone, IPr·HCl = 1,3-(2,6-diisopropylphenyl) imidazolium chloride, dppm = 1,1-bis-
(diphenylphosphino)methane, xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, dppb = 1,4-bis(diphenylphosphino) butane, dppf =
1,1′-bis(diphenylphosphino)ferrocene, DMF = dimethylformamide, DCE = 1,2-dichloroethane. Yield of isolated product after chromatography. 2
mol % of catalyst and 4 mol % of ligand were used. 1 mol % of catalyst and 2 mol % of ligand were used. Performed at 80 °C.
c
d
e
f
KOtBu were examined, Cs2CO3 and K2CO3 provided better
results (entries 17−20, Table 1).
of the aromatic motifs involved in the C−H activation process
did not seem to affect the efficiency of this transformation
(entries 1, 2, 4, and 5, Table 3). It is worth noting that C−Cl
compatible with reactions are particularly appealing because
this substituent offers great opportunities for further cross-
coupling reactions (entries 5 and 13, Table 3; entry 5, Table 2).
meta-Methyl-substituted imine substrate 1o participated in the
C−C cross-coupling reaction effectively, giving an 83% yield of
a mixture of two regioisomers (2:1, entry 14, Table 3). An
analogous substrate (Z)-1m exhibited the same trend with
sterically hindered aryl-substituted regioisomer as the main
product (2m′:2m″ = 1.5:1, entry 12, Table 3). Heteroaryl-
substituted imine substrate (Z)-1p reacted at the 2-position of
thiophene to afford the phenanthridine-like product in high
yield (entry 15, Table 3).
A proposed reaction mechanism of palladium-catalyzed
intramolecular C−C bond formation of N-aryl imines to
phenanthridines was shown in Scheme 1. Initial oxidative
addition of the aryl bromide or iodide to Pd(0) followed by
approach of the aromatic ring led to a concerted metalation-
deprotonation (CMD) transition state.12,17 Subsequent reduc-
tive elimination produced the phenanthridine product and
regenerated the active catalytic species. For aryl chloride,
oxidative addition was followed by a chloride/pivalate ligand
exchange, the latter enabling a CMD transition state to form
the palladacycle. Palladacycle intermediate underwent C−C
bond-forming reductive elimination to afford the desired
product.
Encouraged by the optimization results, we then explored the
scope and generality of the present process. The nature of the
ortho-substituted halogen on the N-aryl moiety was very
important to the reaction outcome, shown in Table 2. Both the
bromide and iodide analogues smoothly underwent the
cyclization to afford the desired product in high to excellent
yields; however, the use of aryl chloride to effect such
transformations afforded inferior results (20% yield) under
similar reaction conditions (entry 2, Table 2). The superior
reactivity of the chloride analogues can be obtained to provide
the product in 95.5% yield with the combined use of an
insoluble Cs2CO3 and a catalytic quantity of soluble carboxylate
base (in this case via deprotonation of the 20 mol % pivalic acid
in situ).16 Substitutions on the N-aryl moiety, such as Me, Cl, or
CN were applicable, affording the cyclized products in good
yields (entries 4−6, Table 2).
Imine substrates 1 with diverse substitutions on the
benzophenone moiety were examined in this process. Some
results from that study are summarized in Table 3. This method
is efficient for the synthesis of a number of phenanthridines 2 in
moderate to excellent yields. Aryl chlorides usually afforded
inferior results than their bromo analogues, even with Cs2CO3
or K2CO3/tBuCO2H as the base (entries 2 and 3, 8 and 9,
Table 3). The syntheses of hindered phenanthridines were also
facilitated by this catalyst system as demonstrated by entries 1,
8, 9, and 14 in Table 3. For aryl bromides, the electronic nature
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Note
a
Table 2. Intramolecular Cyclization of Aryl Halides
a
Reaction conditions: N-(2-halophenyl)imine 1 (1.0 equiv, 1.0 mmol), Cs2CO3 (2.0 equiv), 4 mol % of Pd(OAc)2, 8 mol % of PCy3, THF (2 mL),
b
c
110 °C, 24 h. Yield of isolated product after chromatography. 20 mol % 2,2-dimethylpropionic acid was added.
In summary, we described an efficient and simple protocol
for the synthesis of phenanthridine derivatives via palladium-
catalyzed intramolecular C−H activation/carbon−carbon bond
formation. The results presented here, together with previous
palladium-catalyzed processes, should be of considerable
interest for the valuable synthetic building blocks for medicinal
and material science.
(3 mL), and diluted with ethyl acetate (5 mL). The layers were
separated, and the aqueous layer was extracted with (2 × 5 mL)
ethyl acetate. The combined organic extracts were dried over
anhydrous sodium sulfate, filtered, and concentrated in vacuo.
The crude residue was then purified by flash chromatography
on silica gel (H) to afford the corresponding product, eluting
with 10% ethyl acetate/petroleum ether.
6-Phenylphenanthridine (2a).3c Pale yellow solid: mp
103.5−104.5 °C; IR (KBr) ν (cm−1) 3056, 3017, 2923, 2851,
1609, 1579, 1560, 1522, 1482, 1457, 1443, 1359, 1328, 1300,
EXPERIMENTAL SECTION
■
General Procedures for Palladium-Catalyzed Intra-
molecular C−C Bond-Forming Reaction of N-(o-
Halophenyl)imines. A 10 mL Schlenk tube equipped with
a magnetic stirring bar was charged with N-(o-halophenyl)-
imine substrates18 (1.0 mmol, 1.0 equiv), Pd(OAc)2 (0.04
mmol, 9.0 mg), PCy3 (0.08 mmol, 22.4 mg), PivOH (0.2
mmol, 20.4 mg, if added), and Cs2CO3 (652 mg, 2.0 mmol, 2.0
equiv), and then 2.0 mL of THF was added via syringe at room
temperature. The tube was purged with nitrogen, sealed, and
put into a preheated oil bath at 110 °C for 24 h. The reaction
mixture was cooled to room temperature, quenched with water
1
1229, 1135, 1071, 956, 782, 755, 764, 726, 700, 671; H NMR
(CDCl3, 400 MHz) δ 8.72 (m, 1H), 8.65 (d, 1H, J = 8.0 Hz),
8.28−8.30 (m, 1H), 8.13 (d, 1H, J = 8.0 Hz), 7.90−7.86 (m,
1H), 7.81−7.70 (m, 4H), 7.66−7.54 (m, 4H); 13C NMR
(CDCl3, 100 MHz) δ 161.3, 143.8, 139.8, 133.4, 130.5, 130.4,
129.7, 128.9, 128.8, 128.7, 128.4, 127.1, 126.9, 125.2, 123.7,
122.2, 121.9. HRMS-ESI (m/z): [M + Na]+ calcd for
C19H13NNa 278.0946; found 278.0949.
3-Methyl-6-phenylphenanthridine (2b).19 Yellow solid:
mp 107−108 °C; IR (KBr) ν (cm−1) 3055, 2922, 2854, 1609,
9509
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Note
a
Table 3. Variation of the Imine Derivative
a
Reaction conditions: N-(2-halophenyl)imine 1 (1.0 equiv, 1.0 mmol), Cs2CO3 (2.0 equiv), 4 mol % of Pd(OAc)2, 8 mol % of PCy3, THF (2 mL),
b
c
d
110 °C, 24 h. Yield of isolated product after chromatography. 20 mol % 2,2-dimethylpropionic acid was added as additive. The mixed (E)/(Z)
isomers were used in 3.7:1 ratios as substrates. (E)/(Z) = 1.26:1. (E)/(Z) = 1:3.4. (E)/(Z) = 1:1.34. (E)/(Z) = 1:4.65.
e
f
g
h
1558, 1541, 1474, 1457, 1444, 1362, 772, 766, 751, 727, 701,
3-Chloro-6-phenylphenanthridine (2c).2a White solid:
mp 133−134 °C; IR (KBr) ν (cm−1) 3062, 2993, 2926, 1608,
1
683; H NMR (CDCl3, 400 MHz) δ 8.66 (d, 1H, J = 8.0 Hz),
1515, 1494, 1465, 1456, 1354, 1249, 1234, 1174, 1032, 830,
8.50 (d, 1H, J = 8.0 Hz), 8.10−8.06 (m, 2H), 7.85−7.82 (m,
1H), 7.74−7.72 (m, 2H), 7.60−7.51 (m, 5H), 2.6 (s, 3H); 13C
NMR (CDCl3, 100 MHz) δ 161.2, 143.9, 139.9, 138.9, 133.5,
130.4, 129.9, 129.7, 128.8, 128.7, 128.6, 128.4, 126.6, 124.9,
122.0, 121.7, 121.4, 21.6. HRMS-ESI (m/z): [M + Na]+ calcd
for C20H15NNa 292.1102; found 292.1104.
1
735, 726; H NMR (CDCl3, 400 MHz) δ 8.64 (d, 1H, J = 8.0
Hz), 8.53 (d, 1H, J = 8.0 Hz), 8.25−8.24 (m, 1H), 8.13−8.11
(m, 1H), 7.89−7.85 (m, 1H), 7.74−7.72 (m, 2H), 7.65−7.60
(m, 2H), 7.59−7.54 (m, 3H); 13C NMR (CDCl3, 100 MHz) δ
162.4, 144.5, 139.4, 134.4, 133.1, 130.0, 129.7, 129.6, 129.1,
128.9, 128.5, 127.5, 127.4, 125.1, 123.3, 122.2, 122.1. HRMS-
9510
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Note
Scheme 1. Proposed Mechanism for the Intramolecular C−H Activation/C−C Bond Formation of N-Aryl Imines Using a
Palladium Catalyst
ESI (m/z): [M + Na]+ calcd for C19H12ClNNa 312.0556;
found 312.0553.
7.12−7.10 (m, 2H), 4.09 (s, 3H), 3.94 (s, 3H); 13C NMR
(CDCl3, 100 MHz) δ 161.2, 160.4, 160.1, 144.3, 135.6, 132.5,
131.1, 130.9, 130.2, 128.8, 126.2, 123.4, 121.9, 120.3, 117.1,
113.8, 102.9, 55.6, 55.4. HRMS-ESI (m/z): [M + Na]+ calcd
for C21H17NNaO2 338.1157; found 338.1159.
6-Phenylphenanthridine-2-carbonitrile (2d). White
solid: mp 233−234 °C; IR (KBr) ν (cm−1) 3076, 3026,
2922, 2224, 1609, 1560, 1511, 1489, 1442, 1422, 1363, 960,
903, 830, 777, 754, 689, 670, 617; H NMR (CDCl3, 400
9-Chloro-6-(4-chlorophenyl)phenanthridine (2h).9f
White solid: mp 218−219 °C; IR (KBr) ν (cm−1) 3045,
3008, 2920, 2851, 1601, 1575, 1559, 1455, 1359, 1089, 1015,
1
MHz) δ 8.95 (m, 1H), 8.66 (d, 1H, J = 8.0 Hz), 8.29 (d, 1H, J
= 8.0 Hz), 8.18 (d, 1H, J = 8.0 Hz), 7.97−7.92 (m, 2H), 7.76−
7.71 (m, 3H), 7.61−7.57 (m, 3H); 13C NMR (CDCl3, 100
MHz) δ 164.3, 145.5, 139.0, 132.4, 131.6, 131.5, 130.4, 129.7,
129.38, 129.37, 128.6, 128.5, 127.8, 125.6, 123.9, 122.2, 119.1,
110.2. HRMS-ESI (m/z): [M + Na]+ calcd for C20H12N2Na
303.0898; found 303.0896.
1
959, 825, 758, 723, 698, 668; H NMR (CDCl3, 400 MHz) δ
8.67−8.66 (m, 1H), 8.55−8.53 (m, 1H), 8.23−8.21 (m, 1H),
8.02−7.99 (m, 1H), 7.82−7.78 (m, 1H), 7.74−7.66 (m, 3H),
7.59−7.54 (m, 3H); 13C NMR (CDCl3, 100 MHz) δ 159.4,
144.1, 137.7, 137.3, 135.2, 134.8, 131.1, 130.4, 130.1, 129.6,
128.8, 127.9, 127.4, 123.3, 122.7, 122.1, 122.0. HRMS-ESI (m/
z): [M + Na]+ calcd for C19H11Cl2NNa 346.0166; found
346.0169.
5-(4-Methoxyphenyl)benzo[i]phenanthridine (2i).
White solid: mp 207−208 °C; IR (KBr) ν (cm−1) 3052,
3009, 2958, 2935, 2829, 1618, 1575, 1563, 1510, 1496, 1456,
1363, 1281, 1249, 1246, 1227, 1172, 1142, 1040, 1015, 858,
841, 828, 759, 752, 742; 1H NMR (CDCl3, 400 MHz) δ 8.69−
8.67 (m, 2H), 8.29−8.27 (m, 1H), 8.20−8.18 (m, 1H), 7.98−
7.95 (m, 2H), 7.83−7.78 (m, 1H), 7.73−7.69 (m, 1H), 7.63−
7.59 (m, 2H), 7.55−7.51 (m, 1H), 7.30−7.26 (m, 1H), 7.08−
7.06 (m, 2H), 3.94 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ
159.9, 158.9, 144.1, 137.1, 134.3, 133.2, 132.2, 130.4, 130.3,
129.8, 128.9, 128.4, 128.3, 126.6, 126.3, 125.7, 123.5, 122.4,
121.5, 119.8, 114.5, 55.4. HRMS-ESI (m/z): [M + Na]+ calcd
for C24H17NNaO 358.1208; found 358.1211.
7-Methyl-6-o-tolylphenanthridine (2e). Pale yellow
solid: mp 149−150 °C; IR (KBr) ν (cm−1) 3055, 3016,
2966, 2929, 2858, 1598, 1565, 1519, 1474, 1458, 1448, 1377,
1
1330, 1293, 1030, 955, 937, 779, 760, 742, 727; H NMR
(CDCl3, 400 MHz) δ 8.66−8.63 (m, 2H), 8.22−8.19 (m, 1H),
7.76−7.66 (m, 3H), 7.43−7.41 (m, 1H), 7.39−7.29 (m, 4H),
2.09 (s, 3H), 2.03 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ
160.7, 144.1, 142.9, 137.6, 135.4, 134.4, 131.4, 130.3, 130.2,
129.9, 128.6, 128.5, 128.2, 126.9, 125.9, 125.1, 123.9, 122.2,
120.7, 23.9, 19.7. HRMS-ESI (m/z): [M + Na]+ calcd for
C21H17NNa 306.1259; found 306.1263.
9-Methyl-6-p-tolylphenanthridine (2f). Pale yellow
solid: mp 77−78 °C; IR (KBr) ν (cm−1) 3067, 3027, 2918,
2855, 1619, 1577, 1561, 1510, 1494, 1458, 1361 1343, 1326,
1
1183, 1139, 1038, 960, 840, 828, 815, 761, 737; H NMR
(CDCl3, 400 MHz) δ 8.59 (d, 1H, J = 8.0 Hz), 8.46 (m, 1H),
8.24 (d, 1H, J = 8.0 Hz), 8.03 (d, 1H, J = 8.0 Hz), 7.76−7.72
(m, 1H), 7.67−7.63 (m, 3H), 7.43−7.37 (m, 3H), 2.64 (s, 3H),
2.49 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 161.1, 144.1,
140.8, 138.5, 137.1, 133.6, 130.2, 129.7, 129.1, 128.8, 128.7,
128.6, 126.5, 123.5, 123.4, 121.9, 121.8, 22.2, 21.4. HRMS-ESI
(m/z): [M + Na]+ calcd for C21H17NNa 306.1259; found
306.1261.
7-Methyl-6-phenylphenanthridine (2j).2c Yellow oil: IR
ν (cm−1) 3059, 3024, 2966, 2928, 1599, 1581, 1566, 1474,
1457, 1448, 1379, 1337, 1230, 1154, 1030, 955, 761, 736, 701;
1H NMR (CDCl3, 400 MHz) δ 8.63−8.61 (m, 2H), 8.24 (d,
1H, J = 8.0 Hz), 7.78−7.70 (m, 2H), 7.68−7.66 (m, 1H),
7.57−7.51 (m, 5H), 7.49−7.45 (m, 1H), 2.12 (s, 3H); 13C
NMR (CDCl3, 100 MHz) δ 160.7, 144.6, 142.8, 137.6, 134.6,
131.3, 130.1, 129.9, 128.6, 128.5, 128.4, 128.1, 126.8, 124.7,
123.8, 122.2, 120.4, 25.0. HRMS-ESI (m/z): [M + Na]+ calcd
for C20H15NNa 292.1102; found 292.1105.
9-Methoxy-6-(4-methoxyphenyl)phenanthridine
(2g). White solid: mp 148.5−149.5 °C; IR (KBr) ν (cm−1)
3051, 2958, 2935, 2828, 1615, 1509, 1455, 1362, 1280, 1227,
1171, 1014, 828, 760, 742; H NMR (CDCl3, 400 MHz) δ
Mixture of 6-(4-Methoxyphenyl)phenanthridine (2k)3c
and 9-Methoxy-6-phenyl phenanthridine (2k′).3c Insep-
arable white solid (2k:2k′ = 3.7:1): IR (KBr) ν (cm−1) 3052,
1
8.56−8.54 (m, 1H), 8.24−8.22 (m, 1H), 8.10 (d, 1H, J = 9.2
Hz), 8.03 (m, 1H), 7.78−7.65 (m, 4H), 7.25−7.23 (m, 1H),
9511
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Note
2958, 2828, 1609, 1510, 1481, 1459, 1361, 1286, 1248, 1172,
1028, 829, 760, 729. 2k (major): 1H NMR (CDCl3, 400 MHz)
δ 8.73 (d, 1H, J = 8.0 Hz), 8.64 (d, 1H, J = 8.0 Hz), 8.26 (d,
1H, J = 8.0 Hz), 8.20 (d, 1H, J = 8.0 Hz), 7.88 (t, 1H, J = 7.6
Hz), 7.80−7.69 (m, 4H), 7.67−7.63 (m, 1H), 7.13 (d, J = 8.8
ESI (m/z): [M + Na]+ calcd for C19H12ClNNa 312.0556;
found 312.0557.
Mixture of 8-Methyl-6-m-tolylphenanthridine (2o)
and 10-Methyl-6-m-tolyl phenanthridine (2o′). Insepa-
rable yellow oil (2o:2o′ = 2:1): IR ν (cm−1) 3058, 2960, 2920,
2872, 1581, 1567, 1527, 1478, 1458, 1437, 1359, 1325, 1296,
820, 789, 762, 729, 709. 2o: 1H NMR (400 MHz, CDCl3, ppm)
δ 8.86 (d, 1H, J = 8.0 Hz), 8.57 (d, 1H, J = 8.0 Hz), 8.32 (d,
1H, J = 8.0 Hz), 8.01 (d, 1H, J = 8.0 Hz), 7.69−7.65 (m, 3H),
1
Hz, 2H), 3.95 (s, 3H). 2k′ (minor): H NMR (CDCl3, 400
MHz) δ 8.57 (d, 1H, J = 8.0 Hz), 8.26 (d, 1H, J = 8.0 Hz),
8.06−8.04 (m, 2H), 7.80−7.69 (m, 3H), 7.69−7.56 (m, 4H),
7.24 (dd, 1H, J = 2.4, 7.8 Hz), 4.09 (s, 3H). HRMS-ESI (m/z):
[M + Na]+ calcd for C20H15NNaO 308.1051; found 308.1053.
Mixture of 6-p-Tolylphenanthridine (2l)3c and 9-
Methyl-6-phenylphenanthridine (2l′). Inseparable yellow
oil (2l:2l′ = 1.3:1): IR ν (cm−1) 3064, 3029, 2919, 1616, 1575,
1553, 1513, 1484, 1459, 1443, 1359, 1327, 1296, 1033, 959,
1
7.51−7.42 (m, 4H), 3.17 (s, 3H), 2.48 (s, 3H). 2o′: H NMR
(400 MHz, CDCl3, ppm) δ 8.25 (d, 1H, J = 8.0 Hz), 7.88 (m,
1H), 7.78−7.71 (m, 3H), 7.57−7.54 (m, 1H), 7.51−7.42 (m,
2H), 7.37−7.33 (m, 3H), 2.51 (s, 3H), 2.50 (s, 3H). HRMS-
ESI (m/z): [M + Na]+ calcd for C21H17NNa 306.1259; found
306.1261.
1
824, 761, 729, 703, 669. 2l: H NMR (CDCl3, 400 MHz) δ
Mixture of 9-Methoxy-6-(thiophen-2-yl)-
phenanthridine (2p) and 4-(4-Methoxy- phenyl)thieno-
[2,3-c]quinoline (2p′). Inseparable white solid (2p:2p′ =
1:4.7): IR (KBr) ν (cm−1) 3062, 2993, 2926, 1608, 1515, 1494,
1465, 1456, 1354, 1249, 1234, 1174, 1032, 830, 735, 726. 2p:
1H NMR (400 MHz, CDCl3, ppm) δ 8.52−8.45 (m, 2H), 8.16
(d, 1H, J = 8.0 Hz), 7.99 (m, 1H), 7.74−7.70 (m, 1H), 7.64−
7.60 (m, 2H), 7.56−7.54 (m, 1H), 7.27 (m, 1H), 7.24−7.21
(m, 1H), 4.06 (s, 3H). 2p′: 1H NMR (400 MHz, CDCl3, ppm)
δ 8.30−8.27 (m, 2H), 8.12 (d, 2H, J = 8.0 Hz), 8.05−8.03 (m,
1H), 7.86 (dd, 1H, J = 8.0, 3.2 Hz), 7.74−7.71 (m, 1H), 7.70−
7.64 (m, 1H), 7.13−7.10 (m, 2H), 3.92 (s, 3H). HRMS-ESI
(m/z): [M + Na]+ calcd for C18H13NNaOS 314.0616; found
314.0619.
8.72 (d, 1H, J = 8.4 Hz), 8.63 (d, 1H, J = 8.0 Hz), 8.29−8.26
(m, 1H), 8.17 (d, 1H, J = 8.0 Hz), 7.89−7.85 (m, 1H), 7.81−
7.76 (m, 1H), 7.73−7.69 (m, 3H), 7.67−7.61 (m, 1H), 7.41 (d,
2H, J = 8.0 Hz), 2.52 (s, 3H). 2l′: 1H NMR (CDCl3, 400 MHz)
δ 8.63 (d, 1H, J = 8.0 Hz), 8.51 (s, 1H), 8.29−8.26 (m, 1H),
8.02 (d, 1H, J = 8.0 Hz), 7.81−7.76 (m, 3H), 7.73−7.69 (m,
1H), 7.67−7.55 (m, 3H), 7.46 (dd, 1H, J = 0.8, 8.4 Hz), 2.68
(s, 3H). HRMS-ESI (m/z): [M + Na]+ calcd for C20H15NNa
292.1102; found 292.1105.
Mixture of 6-m-Tolylphenanthridine (2m),4d 10-Meth-
yl-6-phenylphenanthridine (2m′) and 8-Methyl-6-phe-
nylphenanthridine (2m″).3c Inseparable yellow oil
(2m:2m′:2m″ = 1:2:1.4): IR ν (cm−1) 3060, 2992, 2960,
2919, 2872, 1608, 1581, 1567, 1479, 1458, 1443, 1360, 1326,
762, 727, 702. 2m: 1H NMR (CDCl3, 400 MHz) δ 8.25 (d, 1H,
J = 8.0 Hz), 8.12 (d, 1H, J = 8.0 Hz), 7.99 (d, 1H, J = 7.6 Hz),
7.85 (m, 1H), 7.78−7.67 (m, 3H), 7.61−7.52 (m, 5H), 2.51 (s,
3H). 2m′: 1H NMR (CDCl3, 400 MHz) δ 8.87 (d, 1H, J = 8.2
Hz), 8.61−8.58 (m, 1H), 8.31−8.28 (m, 1H), 7.78−7.67 (m,
4H), 7.61−7.52 (m, 4H), 7.35 (d, 1H, J = 8.0 Hz), 3.18 (s,
3H). 2m″: 1H NMR (CDCl3, 400 MHz) δ 8.69 (d, 1H, J = 8.2
Hz), 8.60 (d, 1H, J = 8.0 Hz), 8.30 (d, 1H, J = 8.0 Hz), 7.87 (s,
1H), 7.78−7.67 (m, 5H), 7.61−7.52 (m, 3H), 2.49 (s, 3H).
HRMS-ESI (m/z): [M + Na]+ calcd for C20H15NNa 292.1102;
found 292.1105.
ASSOCIATED CONTENT
■
S
* Supporting Information
General experimental methods and 1H and 13C NMR spectra of
the products 2a−p. This material is available free of charge via
the Internet http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: libinzh62@163.com.
■
Mixture of 6-(4-Chlorophenyl)phenanthridine (2n)2a
and 9-Chloro-6-phenyl phenanthridine (2n′).2c 2n and
2n′ can be separated by column chromatography on silica gel,
eluting with 1% ethyl acetate/petroleum ether (2n:2n′ =
1:1.34). 2n: white solid; mp 148−149 °C; IR (KBr) ν (cm−1)
3070, 3046, 2956, 2923, 2852, 1609, 1592, 1559, 1482, 1395,
ACKNOWLEDGMENTS
■
We are grateful to the funds supported by the Fundamental
Research Funds for the Central Universities (DL12DB03,
DL10BB07) and by China Postdoctoral Science Foundation
(20110491013).
1
1359, 1327, 1090, 1015, 960, 829, 752, 723; H NMR (CDCl3,
REFERENCES
■
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