Preparation of Substituted Phenanthridines from the Coupling of Aryldiazonium Salts with Nitriles: A Metal Free Approach

Article abstract of DOI:10.1021/acs.joc.5b00579

A transition metal free approach for the synthesis of substituted phenanthridines from the coupling reaction of aryldiazonium tetrafluoroborates with nitriles has been developed. This operationally simple protocol proceeds through a substitution of aryldiazonium with nitriles followed by an intramolecular arylation to provide the corresponding phenanthridines in moderate to excellent yields. (Chemical Equation Presented).

Full text of DOI:10.1021/acs.joc.5b00579

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Note
Preparation of Substituted Phenanthridines From The Coupling
of Aryldiazonium Salts With Nitriles-A Metal Free Approach
Mani Ramanathan, and Shiuh Tzung Liu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b00579 • Publication Date (Web): 29 Apr 2015
Downloaded from http://pubs.acs.org on May 3, 2015
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Preparation of Substituted Phenanthridines From
The Coupling of Aryldiazonium Salts With Nitrilesꢀ
A Metal Free Approach
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Mani Ramanathan and Shiuh-Tzung Liu*
Department of Chemistry, National Taiwan University, Taipei 106, Taiwan
Corresponding author. Eꢀmail: stliu@ntu.edu.tw
RECEIVED DATE
TITLE RUNNING HEAD: Preparation of Phenanthridines
ABSTRACT. A transition metal free approach for the synthesis of substituted phenanthridines
from the coupling reaction of aryldiazonium tetrafluoroboates with nitriles has been developed.
This operationally simple protocol proceeds through a substitution of aryldiazonium with nitriles
followed by an intramolecular arylation to provide the corresponding phenanthridines in
moderate to excellent yields.
KEYWORDS. Phenanthridine, Diazonium, Nitrile, Coupling
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Phenanthridines are an important class of Nꢀheteroaryl compounds with a wide range of
applications in material1 and medicinal chemistry,2 Substituted phenanthridines are versatile
scaffolds and building blocks in pharmaceuticals with potential therapeutic utility.3 Drugs with
this ubiquitous framework possess broad spectrum of biological activities ranging from
antibacterial,4 antituberculosis,5a to antitumoral activity.5bꢀc Owing to these applications,
synthesis of substituted phenanthridine motif has spurred vigorous researches for the
development of new methodologies.
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The PictetꢀHubert reaction is a classical method leading to phenanthridine, which involved the
zinc chloride promoted dehydration of Nꢀacylꢀ2ꢀbiphenylamine followed by cyclization at
elevated temperatures (>200oC).6a Later, the dehydration agent in this reaction was replaced by
phosphorus oxychloride.6b However, these reactions require harsh conditions to facilitate the
cyclization. In recent years, quite a number of approaches have developed including transition
metal catalyzed approaches,7 radical promoted cyclization,8 addition of a nitrile to 2ꢀfluoroꢀ2’ꢀ
lithiobiphenyl,9aꢀb cycloaddition,9cꢀf insertion9gꢀk and hypervalent iodine promoted cyclization.10
Some approaches from orthoꢀfunctionalized biaryls to phenanthridines were summarized in
Figure 1.11 Despite the demonstrated advantages, there are limitations to exclude the transition
metal catalysts and complicated preꢀfunctionalized sites. Thus, appealing alternatives with easily
accessible precursors are in demand rather than pursuing a sequence of strict conditions.
Aryl diazonium salts have been served as reactive aryl halide surrogates in Pdꢀcatalyzed cross
coupling reactions for CꢀC bond formation.12 The inherent electrophilicity of dizonium salts
comes from N2 being an excellent leaving group and offers a pathway to introduce various
groups into an aromatic ring to yield a wide range of compounds. In addition, the interest in
using aryl diazonium salts lies in their ease of preparation and large choice of functional groups.
In this context, Barba and coworkers have made a research to synthesis of anilides from
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aryldiazonium salts and nitriles under microwave irradiation.13 Encouraged by this report, we
sought to make a subtle approach for pheananthridine core by modification of this protocol.
Herein, we report an efficient strategy for the synthesis of substituted phenanthridines from a
reaction of 2ꢀaryldiazonium tetrafluroborates with a variety of nitriles under a transition metal
catalystꢀfree condition.
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CN
O
R
H
N
R
O
N
O
F
Ph
Ph
(c)
POCl3
(a)
RLi(b)
hv or Fe(III)
R
N
H2N
RCHO
Ph
RMgX
[Cu]
(i)
(d)
Ph
CN
RCN,Cu(II)
(e,f)
)
I
I
I
[Ru]
(g)
(
(h)
n
Ph
M
,
)
2
H
O
(
B
R
R
NC
N3
I
Ar
(a) ref. 6a; (b~i) ref.11a-11i, respectively.
Figure 1 Synthetic approaches leading to phenanthridines from ortho functionalized biaryls.
First, the reaction of phenyldiazonium salt 1 with acetonitrile was carried out to find the
optimum reaction conditions (Table 1). With 20 mol% of Cu(I)Br as the catalyst at refluxing
temperature in the air, the reaction proceeded to yield 6ꢀmethyl phenanthridine 3a and the amide
derivative 2 as a separable mixture (Eq. 1). Similar results were obtained under metal or acidꢀ
catalyzed conditions (Table 1. entries 1, 3, 4). Carrying out the reaction in various solvents
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provided poor results (Entries 2, 5, 6). Performing the reaction at elevated temperature both
under conventional and microwave heating resulted the mixture of the products without
appreciable increment in the formation of 3a (Entries 7~8). Presumably, the formation of 2
comes from hydrolysis of the resulting carbocation I via the nucleophilic substitution of nitrile
toward diazonium salt (Scheme 1, path a). Thus, we investigated the reaction under anhydrous
conditions in a seal reaction vessel. To our delight, the reaction proceeded efficiently to afford
the desired pheanthridine in 88% isolated yield as a sole product (Table 1, entry 9). Apparently,
under the anhydrous condition, the direct electrophilic aromatic substitution took place on the
adjacent ring to give the product (Scheme 1, path b). Although this is resemble to the classical
PictetꢀHubert reaction, the reaction conditions developed in this work appeared to be much
milder.
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O
5
4
N
N2 BF4
Ph
NH
3
2
6
+
(1)
7
1
8
10
9
2
3a
1
Table 1 Reaction Optimizationa
entry
additive
CuBr
Temp(oC) Time(h) Conv. 2/3ab
1
2
80
85
12
12
12
12
12
15
8
100%
1:1
ꢀ
Cu(OTf)2/DCEc
3
Sc(OTf)3
80
100%
100%
1:1
1:2
ꢀ
4
CF3COOH
THF(solvent)c
Toluene(solvent)c
ꢀ
80
5
67
6
110
170
ꢀ
7d
100%
1:1
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8d
9e
ꢀ
ꢀ
ꢀ
135
120
120
1
3
3
100%
100% 88: 0f
65% 65:0
1:1
3
4
5
6
7
8
10g
9
a
b
Reaction conditions: 1a (0.3 mmol) and additive in acetonitrile (0.3 mL) in open air.
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c
d
determined by NMR. Solvent used (0.3 mL); DCE = 1,2ꢀdichloroethane. microwave
irradiation in air. e in a sealed tube under anhydrous conditions. isolated yield . g in a sealed
f
tube under anhydrous conditions but with 0.1 mL CH3CN.
Scheme 1 Reaction Pathway for 2 and 3a
Me
2
C
Me
a
N2
Ph
N
path a
N
OH2
b
path b
3a
N2
I
Under the optimized reaction conditions, the generality and the limitations of this protocol
were examined with varieties of nitriles including aliphatic, aryl, heteroꢀaryl, and benzyl nitriles.
The results are summarized in Table 2. As illustrated, all the reactions proceeded cleanly and
provided the corresponding 6ꢀsubstituted phenanthridines in moderate to excellent yields. We
are pleased to find that various functionalized nitriles do proceed the reaction even with the
bromoꢀsubstituted one (Table2, entry 4).
Table 2 Reaction of diazonium salt 1 with various nitrilesa
N
R
1
+
RCN
3
entry nitrile
Product (yield)b
1
2
3
4
CH3CN
3a, R = Me (88%)
3b, R = nPr (86%)
CH3(CH2)2CN
(CH3)2CHCN
CH3CH(Br)CN
3c, R = iPr (76%)
3d, R = CH3CH(Br)ꢀ (73%)
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5
PhCH2CN
3e, R = PhCH2ꢀ (73%)
3f, R = Ph (76%)
6
PhCN
7
8
9
7
p-MeC6H4CN
p-BrC6H4CN
o-BrC6H4CN
m-MeOC6H4CN
3g, R = p-MeC6H4ꢀ (68%)
3h, R = p-BrC6H4ꢀ (54%)
3i, R = o-BrC6H4ꢀ (58%)
3j, R = m-MeOC6H4ꢀ (52%)
3k, R = 3ꢀthienyl (78%)
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9
10
11
CN
S
a 1 (0.3 mmol) and nitrile (0.3 mL) in a sealed tube at 120oC for 3h. Isolated yield after
b
column chromatography.
With the use of the percent yield of the phenanthridines within the first two hours as a
measurement of kX, a Hammett plot analysis of the formation of 6ꢀaryl substituted products
(logkX/kH) against σ+ values gives a line with a slope (ρ+) of ꢀ 0.54. This observation clearly
suggests the involvement of an intermediate with a developing positive charge in the reaction,
consistent with the proposed species I (scheme 1).
Having established the reaction conditions, this protocol was then applied to a variety of
substituted diazonium salts. Thus, 2ꢀ(substituted phenyl)benzenediazonium tetrafluoroborate 4~6
and
substituted 2ꢀphenylbenzenediazonium tetrafluoroborate 7 were subjected for this
investigation. Table 3 summarizes the preparation of phenanthridines from 4~6. Reaction of 2ꢀ
(oꢀmethylphenyl)benzenediazonium tetrafluoroborate 4 with various nitrile yielded 6,10ꢀ
substituted
phenanthridines
8a~8d
in
good isolated yields, whereas 2ꢀ(pꢀ
methoxyphenyl)benzenediazonium tetrafluoroborate 5 gave 6,8ꢀsubstituted phenanthridines
9a~9d in good yields. The fluoroꢀsubstituted substrate, 2ꢀ(pꢀfluorophenyl)benzenediazonium
tetrafluoroborate 6, reacted with benzonitrile and acetonitrile to give 8ꢀfluorophenanthridines 9e
(43%) and 9f (58%), respectively.
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Y
BF4
BF4
N2
N2
5
4
3
Y
2'
4'
3'
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4, Y = 2'-CH3
5, Y = 4'-CH3O
6, Y = 4'-F
7a, Y = 4-CF3
7b, Y = 4-Cl
7c, Y = 4-CH3
7d, Y = 5-CH3
O
7e, Y = 4-
N
O
Table 3 Phenanthridines from 2ꢀ(substituted phenyl)benzenediazonium salts 4a,b
N
R
N
R
R1
R1
8a, R = Me, R1 = Me (81%)
8b, R = nPr, R1 = Me (78%)
8c, R = iPr, R1 = Me (74%)
8d, R = Ph, R1 = Me (71%)
9a, R = Me, R1 = MeO (86%)
9b, R = nPr, R1 = MeO (83%)
9c, R = iPr, R1 = MeO (74%)
9d, R = Ph, R1 = MeO (77%)
9e, R = Ph, R1 = F (43%)
9f, R = Me, R1 = F (58%)
asubstrate (0.3 mmol) and RCN (0.3 mL) in a sealed tube at 120oC for 3h. Isolated yield given
b
in parentheses.
It is noticed that reaction of benzonitrile with 2ꢀ(oꢀmethoxyphenyl)benzenediazonium
tetrafluoroborate 10 did not provide the corresponding phenanthridine, but dibenzofuran was
obtained the major product (Scheme 2a).14 Apparently the oxygen atom of the methoxy group
acts as a nucleophile to undergo the displacement followed by the elimination of methyl group.
For the metaꢀ analog 11, the diazonium coupling reaction took place directly, instead of the
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nucleophilic attack by the nitrile, to give benzo[c]cinnoline in 85 % yield, presumably due to the
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double activation of the substituents (Scheme 2b).15
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Scheme 2.
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(a)
Me
BF4
O
N2
O
ꢀ
100%
MeO
10
(b)
BF4
Ν
Ν
N2
ꢀ
OMe
OMe
85%
11
To further diversify the scope of the reaction, we next sought to investigate the substituent
effect on the arene ring possessing the diazonium functionality (Table 4). It was found that
reaction of 4ꢀCF3 substituted diazonium salt 7a provided the desired product in moderate yields
(12a-b), whereas 4ꢀCl and 4ꢀMe substituted 2ꢀphenyl benzenediazonium tetrafluoroborates
furnished the corresponding phenanthridines in excellent yields (12c-12h). Preparation of other
regioꢀisomers 13a-b and 2ꢀphenanthridinecarboxamides14a-b can be also achieved from 7d and
7e, respectively.
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Table 4 Phenanthridines from substituted 2ꢀphenylbenzeneꢀdiazonium salts 6a,b
5
6
7
8
9
N
R
RCN
X
7a-e
ꢀ
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11
12
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12a R = Me, R2 = CF3 (66%)
12b R = nꢀPr, R2 = CF3 (61%)
12c R = Me, R2 = Cl (84%)
12d R = nꢀPr, R2 = Cl (81%)
12e R = iꢀPr, R2 = Cl (73%)
12f R = Ph, R2 = Cl (76%)
12g R = Me, R2 = Me (82%)
12h R = Ph, R2 = Me (76%)
13a R = Me, R3 = Me (88%)
13b R = Ph, R3= Me (79%)
N
R
R2
R3
N
R
N
R
14a R = Me (76%)
14b R = Ph (68%)
O
N
O
asubstrate (0.3 mmol) and RCN (0.3 mL) in a sealed tube at 120oC for 3h. Isolated yield given
b
in parentheses.
Other substituted phenanthridines can be prepared as well. Typically, preparation of a 2,6,8ꢀ
trisubstitued phenanthridine was achieved as illustrated in Scheme 3. Suzukiꢀcoupling of 2ꢀ
bromoꢀp-toluidine with p-methoxyphenylꢀboronic acid gave the desired biarylamine 15.
Diazotization of 15 yielded the diazonium salt 16, which was heated in acetonitrile to give 17 in
86% yield.
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Scheme 3 Preparation of triꢀsubstituted phenanthridine 17
5
6
7
8
9
+
Ν
N2
-
NH2
Br
BF4 iii
i
86%
ii
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OMe
OMe
17
16
i. p-MeOC6H4B(OH)2, PdCl2(PPh3)2; ii NaNO2, HBF4; iii CH3CN, ꢀ
Finally, we studied the cyclization with 1ꢀnaphthalenylbenzenediazonium tetrafluoroborate
18. Surprisingly, using 18, acetonitrile, and the conditions optimized in Table 1 afforded a
mixture of fluoranthene 19 and 6ꢀmethylbenzo[k]phenanthridine 20 in a ratio of 71%:11%
(scheme 4), indicating that the electrophilic aromatic substitution took place majorly at α’ꢀ
position of the naphthylenyl ring.
Scheme 4 Reaction of 1ꢀnaphthalenylbenzenediazonium tetrafluoroborate.
N
BF4
N2
CH3CN
+
ꢀ
18
19 (71%)
20 (11%)
In summary,
a
thermalꢀcyclization to construct phenanthridines from 2ꢀ
phenylbenzenediazonium salt and nitriles under anhydrous conditions was developed. The scope
of the method was examined using a variety of nitriles and 2ꢀphenylbenzenediazonium
tetrafluoroborate. It is noteworthy that the purification of solid products can be accomplished by
a simple filtration. This strategy allows convenient and easy access to a wide range of
functionality. Compared to the PictetꢀHubert reaction, experimental simplicity, mild reaction
conditions and easy access to various substituents in the molecules are delivered by this
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methodology. Further studies on the development of this methodology to construct complicated
molecules are ongoing in this laboratory.
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Experimental Section
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13
General information. H and C NMR were recorded in a 400 MHZ spectrometer in CDCl3
and CD3CN referenced to TMS. All the nitriles were dried over activated 4Ao Molecular sieves
and solid nitriles were purchased and used without any further drying. Other chemnicals were
used as purchased. Flash chromatography was performed using silica gel 230ꢀ400 mesh. In cases
of known compounds, their 1H and 13C NMR values were compared with the literature values. 2ꢀ
Aminobiaryls were synthesized by SuzukiꢀMiyaura coupling of arylboronic acids and 2ꢀbromo
anilines. Unless otherwise noted, all the reactions were performed without any special
precautions.
General procedure for preparing 2-aminobiaryls:
All the 2ꢀaminobiaryls were synthesized by following the reported methods. Spectral data of
the compounds are in agreement with those reported in the literature. A typical procedure for
preparing 2ꢀ(oꢀtolyl)ꢀaniline is shown below.16
2ꢀbromoaniline (2.90 mmol, 1 equiv.), 2ꢀmethylphenylboronic acid (3.78 mmol, 1.3 equiv.),
PdCl2(PPh3)2 (0.29 mmol, 0.1 equiv.), and potassium carbonate (8.72 mmol, 3 equiv.) were
suspended in DMF (15 mL) and water (3 mL) in a 50 mL Schlenk bottle. The flask was equipped
with a reflux condenser and heated to 80oC for 24h under nitrogen atmosphere. Upon
completion, reaction mixture was cooled to room temperature and diluted with ethyl acetate (50
mL). After passing through a short celite pad, the filtrate was washed with saturated aqueous
sodium bicarbonate (2 X 20 mL) and brine (20 mL). Combined organic layer was dried over
anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by
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column chromatography (SiO2, 2ꢀ10% EAꢀhexane) to give 2(2ꢀmethylphenyl)ꢀaniline in (430
5
6
1
mg, 2.34 mmol, 80% yield). H NMR (400 MHz, CDCl3) δ 7.05ꢀ7.21 (m, 5H), 6.92 (d, J = 7.2
7
8
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Hz, 1H), 6.71 (t, J = 7.2 Hz, 1H), 6.66 (d, J = 8.0 Hz, 1H), 3.34 (bs, 2H), 2.08 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 143.5, 138.5, 136.9, 130.2, 130.04, 130.02, 128.3, 127.6, 127.4, 126.1,
118.2, 115.0, 19.6.
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4'-methoxy-5-methyl-[1,1'-biphenyl]-2-amine (15).16b 2ꢀbromoꢀ4ꢀmethylaniline (1.88 mmol, 1
equiv.), 4ꢀmethoxyphenylboronic acid (2.44 mmol, 1.3 equiv.), PdCl2(PPh3)2 (0.18 mmol, 0.1
equiv.), and potassium carbonate (5.64 mmol, 3 equiv.) were suspended in DMF (10 mL) and
water (2 mL) in a 50 mL schlenk bottle. The flask was equipped with a reflux condenser and
heated to 80oC for 24h under nitrogen atmosphere. Upon completion, reaction mixture was
cooled to room temperature and diluted with ethyl acetate (30 mL). After passing through a short
celite pad, the filtrate was washed with saturated aqueous sodium bicarbonate (2 X 15 mL) and
brine (15 mL). Combined organic layer was dried over anhydrous sodium sulfate and
concentrated under reduced pressure. The residue was purified by column chromatography (SiO2,
2ꢀ10% EAꢀhexane) to give 4'ꢀmethoxyꢀ5ꢀmethylꢀ[1,1'ꢀbiphenyl]ꢀ2ꢀamine (280 mg, 1.31 mmol,
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71% yield) as a viscous oil. H NMR (400 MHz, CDCl3) δ 7.37 (d, J = 8.8 Hz, 2H), 6.94ꢀ6.99
(m, 4H), 6.68 (d, J = 7.6 Hz, 1H), 3.84 (s, 3H), 3.52 (bs, 2H), 2.27 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 158.6, 140.9, 131.8, 130.9, 130.1, 128.6, 127.8, 127.4, 115.7, 114.1, 55.2, 20.3. HRMS
(ESI) m/z = 214.1232 calcd. for C14H16NO (M+H)+, found; 214.1236.
General procedure for preparing biaryldiazonium tetrafluoroborates.17
Corresponding aniline (10 mmole) was dissolved in a mixture of water (4 mL) and 50%
aqueous hydrofluroboric acid (19.3 mmol, 1.92 equiv.). The mixture was cooled to 0oC and a
solution of NaNO2 (10 mmol in 1.5 mL of water) was added slowly. The resulting reaction
mixture was stirred at 0oC for 30 minutes and the precipitate was collected by filtration. The
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solid product was dissolved in minimum acetone and reꢀprecipitated using diethyl ether to yield
aryldiazonium tetrafluroborate which was dried under vacuum.
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2-biphenyldiazonium tetrafluoroborate (1).17b 633 mg, 80%, pale green solid. H NMR (400
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MHz, CD3CN) δ; 8.60 (d, J = 8.4 Hz, 1H), 8.31 (t, J = 7.6 Hz, 1H), 7.91ꢀ7.97 (m, 2H), 7.68ꢀ7.69
(m, 5H); 13C NMR (100 MHz, CD3CN) δ 147.7, 143.1, 134.5, 133.7, 132.4, 131.7, 131.0, 131.0,
129.7, 114.1. HRMS(ESI) calcd. for C12H9 (MꢀBF4ꢀN2)+ m/z = 153.0705, found; 153.0669.
2’ꢀMethylꢀ(1,1’ꢀbiphenyl)ꢀ2ꢀdiazonium tetrafluoroborate (4).17a 654 mg, 85%, offꢀwhite solid.
1H NMR (400 MHz, CD3CN) δ 8.61 (bs, 1H), 8.29 (t, J = 7.6 Hz, 1H), 7.95 (t, J = 7.6 Hz, 1H),
7.88 (d, J = 8.0 Hz, 1H), 7.42ꢀ7.57 (m, 4H), 2.25 (s, 3H); 13C NMR (100 MHz, CD3CN) δ 147.0,
142.6, 137.8, 134.5, 134.2, 132.8, 132.6, 132.2, 131.8, 130.2, 127.9, 115.7, 20.0.
4’-Methoxy-(1,1’-biphenyl)-2-diazonium tetrafluoroborate (5).17a 601 mg, 80%, yellow
powder. 1H NMR (400 MHz, CD3CN) δ 8.55 (d, J = 8.4 Hz, 1H), 8.25 (t, J = 8.0 Hz, 1H), 7.92
(d, J = 8.0 Hz, 1H), 7.85 (t, J = 8.0 Hz, 1H), 7.64 (d, J = 8.4 Hz, 2H), 7.19 (d, J = 8.4 Hz, 2H),
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3.89 (s, 3H); C NMR (100 MHz, CD3CN) δ 163.2, 147.2, 142.8, 134.3, 133.3, 131.4, 131.0,
125.8, 116.4, 113.4, 56.4. HRMS(ESI) calcd. for C13H11N2O (MꢀBF4)+ m/z = 211.0871, found:
211.0873.
4’-Fluoro-(1,1’-biphenyl)-2-diazonium tetrafluoroborate (6). 450 mg, 69%, yellow powder. 1H
NMR (400 MHz, CD3CN) δ 8.61 (d, J = 8.0 Hz, 1H), 8.29 (t, J = 7.6 Hz, 1H), 7.93 (d, J = 8.0
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Hz, 1H), 7.90ꢀ7.92 (m, 1H), 7.71ꢀ7.74 (m, 2H), 7.41 (t, J = 8.8 Hz, 2H); C NMR (100 MHz,
CD3CN) δ 165.3 (d, J = 249 Hz), 145.9, 143.0, 134.5, 133.7, 132.3 (d, J = 10.0 Hz), 131.7, 130.1
(d, J = 10.0 Hz), 118.0 (d, J = 22.0 Hz), 114.3. HRMS(ESI) calcd. for C12H8F (MꢀBF4ꢀN2)+ m/z
= 171.0610, found: 171.0609.
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2’-Methoxy-(1,1’-biphenyl)-2-diazonium tetrafluoroborate (10). 448 mg, 83%, yellow powder.
1H NMR (400 MHz, CD3CN) δ 8.56 (d, J = 7.6 Hz, 1H), 8.28 (d, J = 7.6 Hz, 1H), 7.89 (t, J = 7.6
Hz, 2H), 7.65 (t, J = 7.6 Hz, 1H), 7.50 (d, J = 7.2 Hz, 1H), 7.25 (t, J = 7.6 Hz, 2H), 3.92 (s, 3H).
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HRMS(ESI) calcd. for C13H11N2O (MꢀBF4)+ m/z = 211.0871, found: 211.0873. Pure C NMR
could not be obtained due to the simultaneous formation of dibenzofuran.
3’-Methoxy-(1,1’-biphenyl)-2-diazonium tetrafluoroborate (11). 474 mg, 80%, yellow powder.
1H NMR (400 MHz, CD3CN) δ 8.60 (d, J = 8.3 Hz, 1H), 8.27 (m, 1H), 9.50 (m, 2H), 7.57 (m,
1H), 7.22 (m, 3H). Pure 13C NMR could not be obtained due to the simultaneous formation of 2ꢀ
methoxybenzo[c]cinnoline.
5ꢀTrifluoromethylꢀ(1,1’ꢀbiphenyl)ꢀ2ꢀdiazonium tetrafluoroborate (7a) 454 mg, 71%, pale
yellow solid. 1H NMR (400 MHz, CD3CN) δ 8.82 (d, J = 8.8 Hz, 1H), 8.27 (s, 1H), 8.20 (d, J =
8.8 Hz, 1H), 7.70ꢀ7.76 (m, 5H); 13C NMR (100 MHz, CD3CN) δ 147.9, 141.3 (q, J = 136.8 Hz),
135.6, 132.9, 132.7, 131.1, 130.8, 129.9, 128.3, 124.5, 121.8. HRMS(ESI) calcd. for C13H8F3N2
(MꢀBF4)+ m/z = 249.0640, found: 249.0638.
5-Chloro-(1,1’-biphenyl)-2-diazonium tetrafluoroborate (7b). 511 mg, 76%, offꢀwhite
powder. 1H NMR (400 MHz, CD3CN) δ 8.60 (d, J = 8.8 Hz, 1H), 8.0 (s, 1H), 7.92 (d, J = 8.8 Hz,
1H), 7.68 (bs, 5H); 13C NMR (100 MHz, CD3CN) δ 150.0, 148.4, 135.8, 133.9, 132.8, 132.7,
132.0, 131.0, 129.7, 112.4. HRMS(ESI) calcd. for C12H8Cl (MꢀBF4ꢀN2)+ m/z = 187.0314, found:
187.0301.
5ꢀMethylꢀ(1,1’ꢀbiphenyl)ꢀ2ꢀdiazonium tetrafluoroborate (7c).17a 422 mg, 55%, pale yellow
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powder. H NMR (400 MHz, CD3CN) δ 8.48 (d, J = 8.6 Hz, 1H), 7.79 (s, 1H), 7.73 (d, J = 8.6
Hz, 1H), 7.66 (bs, 5H), 2.65 (s, 3H); 13C NMR (100 MHz, CD3CN) δ 157.3, 146.9, 134.4, 134.3,
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133.8, 132.5, 132.2, 130.9, 129.6, 109.9, 23.2 HRMS(ESI) calcd. for C13H11 (MꢀBF4ꢀN2)+ m/z =
167.0861, found: 167.0857
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4-methyl-[1,1'-biphenyl]-2-diazonium tetrafluoroborate (7d). 498 mg, 86%, pale yellow
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powder. H NMR (400 MHz, CD3CN) δ 8.37 (s, 1H), 8.11ꢀ8.14 (m, 1H), 7.85 (d, J = 8.1 Hz,
1H), 7.66 (bs, 5H), 2.57 (s, 3H). 13C NMR (100 MHz, CD3CN) δ 144.6, 144.2, 143.2, 133.7,
133.6, 133.3, 132.2, 131.0, 129.7, 113.6, 21.0. HRMS(ESI) calcd. for C13H11 (MꢀBF4ꢀN2)+ m/z =
167.0861, found: 167.0848.
[1,1'-biphenyl]-3-yl)(morpholino)methanone-6-diazonium tetrafluoroborate (7e). 430 mg,
81%, pale yellow powder. 1H NMR (400 MHz, CD3CN) δ 8.65 (d, J = 8.4 Hz, 1H), 7.90 (d, J =
1.2 Hz, 1H), 7.85 (dd, J = 8.4, 1.2 Hz, 1H), 7.66ꢀ7.71 (m, 5H), 3.70 (d, J = 2.4 Hz, 4H), 3.58 (d,
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J = 4.4 Hz, 2H), 3.32 (d, J = 4.4 Hz, 2H); C NMR (100 MHz, CD3CN) δ 166.5, 149.6, 147.8,
135.2, 133.3, 132.6, 131.5, 131.0, 129.8, 129.7, 114.5, 67.0, 66.9, 48.4, 43.1. HRMS(ESI) calcd.
for C17H16N3O2 (MꢀBF4)+ m/z = 294.1243, found: 294.1232.
4'-methoxy-5-methyl-[1,1'-biphenyl]-2-diazonium tetrafluoroborate (16). 270 mg, 66%,
orange solid. 1H NMR (400 MHz, CD3CN) δ 8.42 (d, J = 8.8 Hz, 1H), 7.75 (s, 1H), 7.66 (d, J =
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8.4 Hz, 1H), 7.62 (d, J = 8.8 Hz, 2H), 7.18 (d, J = 9.2 Hz, 2H), 3.88 (s, 3H), 2.63 (s, 3H); C
NMR (100 MHz, CD3CN) δ 163.1, 157.1, 147.1, 134.2, 133.9, 131.9, 131.3, 125.9, 116.4, 109.3,
56.4, 23.2. HRMS(ESI) calcd. for C14H13N2O (MꢀBF4)+ m/z = 225.1022, found: 225.1039.
2ꢀ(1ꢀnaphthalenyl)ꢀbenzenediazonium tetrafluoroborate (18). 430 mg, 86%, orange powder. 1H
NMR (400 MHz, CD3CN) δ 8.68 (d, J = 7.5 Hz, 1H), 8.37 (t, J = 7.8 Hz, 1H), 8.20 (dd, J = 5.8,
3.2 Hz, 1H), 8.10 (d, J = 7.8 Hz, 1H), 8.04 (t, J = 7.5 Hz, 2H), 7.61ꢀ7.75 (m, 5H). HRMS(ESI)
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calcd. for C16H11 (MꢀBF4ꢀN2)+ m/z = 203.0855, found; 203.0787. Pure 13C NMR could not be
obtained due to the simultaneous formation of fluoroanthene.
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General procedure for the preparation of phenanthridines.
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In a dry 10 mL glass sealed tube, aryldiazonium salt (0.3 mmol) was suspended in 0.3 mL of
appropriate anhydrous nitrile. The tube was sealed with a Teflon screw cap and stirred in a
preheated oil bath (120oC) for 3 hours. After cooling to room temperature, solvents were
removed under reduced pressure and purified by silica gel column chromatography (SiO2,
DCM/MeOH, 99:1) to get the desired compounds.
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6-methylphenanthridine (3a).11f 49 mg, 88%, viscous oil. H NMR (400 MHz, CDCl3): δ 8.60
(d, J = 8.2 Hz, 1H), 8.51 (dd, J = 8.0, 1.0 Hz, 1H), 8.20 (d, J = 8.2 Hz, 1H), 8.10 (dd, J = 8.2, 0.8
Hz, 1H), 7.82 (td, J = 7.6, 1.2 Hz, 1H), 7.65ꢀ7.71 (m, 2H), 7.60 (td, J = 7.6, 1.2 Hz, 1H), 3.03 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 158.9, 143.5, 132.5, 130.5, 129.2, 128.6, 127.3, 126.5,
126.3, 125.8, 123.7, 122.3, 121.9, 23.3. HRMS(ESI) calcd. for C14H12N (M+H)+ m/z = 194.0970,
found: 194.0976.
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6-propylphenanthridine (3b).7a 57 mg, 86%, viscous oil. H NMR (400 MHz, CDCl3): δ 8.61
(d, J = 8.2 Hz, 1H), 8.51 (d, J = 8.2 Hz, 1H), 8.23 (d, J = 8.2 Hz, 1H), 8.10 (d, J = 8.2 Hz, 1H),
7.80 (td, J = 5.9, 1.3 Hz, 1H), 7.64ꢀ7.71 (m, 2H), 7.59 (td, J = 5.9, 1.3 Hz, 1H), 3.31ꢀ3.35 (m,
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2H), 1.95 (sex, J = 7.6 Hz, 2H), 1.11 (t, J = 7.6 Hz, 3H); C NMR (100 MHz, CDCl3) δ 162.2,
143.7, 132.9, 130.2, 129.5, 128.5, 127.1, 126.3, 126.2, 125.2, 123.6, 122.4, 121.8, 38.3, 22.8,
14.4. HRMS(ESI) calcd. for C16H16N (M+H)+ m/z = 222.1282, found: 222.1285.
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6-isopropylphenanthridine (3c).11g 51 mg, 76%, viscous oil. H NMR (400 MHz, CDCl3): δ
8.58 (d, J = 8.2 Hz, 1H), 8.46 (d, J = 8.2 Hz, 1H), 8.24 (d, J = 8.2 Hz, 1H), 8.06 (d, J = 8.0 Hz,
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1H), 7.74 (t, J = 7.3 Hz, 1H), 7.59ꢀ7.64 (m, 2H), 7.50ꢀ7.54 (m, 1H), 3.92 (sept, J = 6.7 Hz, 1H),
1.44 (d, J = 6.7 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 165.8, 143.8, 133.0, 129.9, 129.9,
128.4, 127.0, 126.1, 125.6, 124.7, 123.4, 122.5, 121.8, 31.5, 21.9. HRMS(ESI) calcd. for
C16H16N (M+H)+ m/z = 222.1282, found: 222.1289.
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6-(1-bromoethyl)phenanthridine (3d). 51 mg, 73%, viscous oil. H NMR (400 MHz, CDCl3):
δ 8.64 (d, J = 8.2 Hz, 1H), 8.53 (dd, J = 8.1, 1.4 Hz, 1H), 8.40 (d, J = 8.2 Hz, 1H), 8.18 (dd, J =
8.1, 1.2 Hz, 1H), 7.83 (ddd, J = 15.3, 7.6, 1.2 Hz, 1H), 7.70 (m, 2H), 7.65 (ddd, J = 15.0, 7.6, 1.4
Hz, 1H), 6.00 (q, J = 6.7 Hz, 1H), 2.37 (d, J = 6.7 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
158.0, 143.2, 133.4, 130.5 (2C), 128.7, 127.4, 127.2, 125.6, 124.1, 123.7, 122.6, 121.9, 44.8,
22.9. HRMS(ESI) calcd. for C15H13BrN (M+H)+ m/z = 286.0231, found: 286.0237.
6-benzylphenanthridine (3e).18a 64 mg, 73%, pale yellow solid, mp 105ꢀ107oC. 1H NMR (400
MHz, CDCl3): δ 8.60 (dd, J = 8.2, 0.6 Hz, 1H), 8.53 (dd, J = 8.0, 0.7 Hz, 1H), 8.18 (ddd, J = 8.9,
5.2, 1.2 Hz, 2 H), 7.71ꢀ7.74 (m, 2H), 7.63 (ddd, J = 8.2, 7.0, 1.3 Hz, 1H), 7.55 (m, 1H), 7.31 (d, J
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= 7.6 Hz, 2H), 7.21ꢀ7.24 (m, 2H), 7.15 (t, J = 7.3 Hz, 1H), 4.75 (s, 2H); C NMR (100 MHz,
CDCl3) δ 160.1, 143.7, 139.1, 133.2, 130.3, 129.8, 128.6, 128.5, 128.4, 127.2, 127.0, 126.6,
126.3, 125.3, 123.9, 122.4, 121.9, 43.0. HRMS(ESI) calcd. for C20H16N (M+H)+ m/z = 270.1283,
found: 270.1280.
6-phenylphenanthridine (3f).8i 58 mg, 76%, white solid, mp 103ꢀ105 oC. 1H NMR (400 MHz,
CDCl3): δ 8.68 (d, J = 8.3 Hz, 1H), 8.60 (dd, J = 8.1, 1.3 Hz, 1H), 8.24 (dd, J = 8.1, 1.0 Hz, 1H),
8.09 (dd, J = 8.3, 0.6 Hz, 1H), 7.83 (td, J = 8.3, 1.3 Hz, 1H), 7.71ꢀ7.76 (m, 3H), 7.67 (td, J = 8.3,
1.3 Hz, 1H), 7.49ꢀ7.61 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 161.2, 143.7, 139.7, 133.4,
130.5, 130.3, 129.7, 128.9, 128.8, 128.7, 128.4, 127.1, 126.9, 125.2, 123.7, 122.1, 121.9.
HRMS(ESI) calcd. for C19H14N (M+H)+ m/z = 256.1126, found: 256.1124.
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6-(p-tolyl)phenanthridine (3g).11h 57 mg, 68%, white solid, mp 104ꢀ105oC. H NMR (400
MHz, CDCl3): δ 8.71 (d, J = 8.2 Hz, 1H), 8.62 (d, J = 8.0 Hz, 1H), 8.25 (d, J = 8.0 Hz, 1H), 8.15
(d, J = 8.2 Hz, 1H), 7.86 (t, J = 8.0 Hz, 1H), 7.76 (t, J = 7.8 Hz, 1H), 7.70ꢀ7.60 (m, 4H), 7.37 (d,
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J = 7.8 Hz, 2H), 2.49 (s, 3H); C NMR (100 MHz, CDCl3) δ 161.2, 143.7, 138.5, 136.8, 133.4,
130.4, 130.2, 129.6, 129.0, 128.9, 128.7, 127.0, 126.7, 125.3, 123.6, 122.1, 121.8, 21.3. ).
HRMS(ESI) calcd. for C20H16N (M+H)+ m/z = 270.1283, found: 270.1275.
6-(4-bromophenyl)phenanthridine (3h)11i 48 mg, 54%, white solid, mp 152ꢀ154oC. H NMR
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(400 MHz, CDCl3): δ 8.69 (d, J = 8.3 Hz, 1H), 8.60 (dd, J = 8.2, 1.2 Hz, 1H), 8.20 (dd, J = 8.2 ,
1.2 Hz, 1H), 8.01ꢀ8.05 (m, 1H), 7.85 (ddd, J = 8.3, 7.0, 1.3 Hz, 1H), 7.75 (ddd, J = 8.3, 7.0, 1.5
Hz, 1H), 7.66ꢀ7.70 (m, 3H), 7.59ꢀ7.62 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 159.9, 143.7,
138.6, 133.5, 131.6, 131.4, 130.7, 130.3, 128.9, 128.4, 127.2, 127.1, 124.9, 123.7, 123.1, 122.3,
121.9. HRMS(ESI) calcd. for C19H13BrN (M+H)+ m/z = 334.0231, found: 334.0228.
6-(2-bromophenyl)phenanthridine (3i)18b 63 mg, 58%, viscous oil. H NMR (400 MHz,
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7.84 (ddd, J = 8.3, 7.0, 1.3 Hz, 1H), 7.65ꢀ7.78 (m, 4H), 7.58 (ddd, J = 8.3, 7.0, 1.3 Hz, 1H), 7.46ꢀ
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7.51 (m, 2H), 7.37 (ddd, J = 9.2, 6.3, 2.8 Hz, 1H); C NMR (100 MHz, CDCl3) δ 160.5, 143.6,
140.5, 132.9, 132.8, 131.0, 130.7, 130.4, 130.0, 128.8, 128.4, 127.5, 127.3, 127.2, 125.2, 124.0,
122.8, 122.1, 122.0. HRMS(ESI) calcd. for C19H13BrN (M+H)+ m/z = 334.0231, found:
334.0229.
6-(3-methoxyphenyl)phenanthridine (3j). 44 mg, 52%, white solid; mp 115ꢀ116oC; H NMR
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(400 MHz, CDCl3): δ 8.67 (d, J = 8.2 Hz, 1H), 8.59 (d, J = 8.1 Hz, 1H), 8.24 (dd, J = 8.1, 1.2 Hz,
1H), 8.11 (d, J = 8.2 Hz, 1H), 7.83 (ddd, J = 8.2, 7.1, 1.1 Hz, 1H), 7.74 (ddd, J = 8.2, 7.1, 1.2 Hz,
1H), 7.64ꢀ7.69 (m, 1H), 7.59 (t, J = 8.1 Hz, 1H), 7.45 (t, J = 8.2 Hz, 1H), 7.27 (d, J = 7.4 Hz,
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2H), 7.04ꢀ7.07 (m, 1H), 3.87 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 161.0, 159.6, 143.7, 141.0,
133.4, 130.5, 130.3, 129.4, 128.9, 128.8, 127.1, 126.9, 125.2, 123.7, 122.2, 122.1, 121.9, 114.9,
114.7, 55.4. ). HRMS(ESI) calcd. for C20H16NO (M+H)+ m/z = 286.1232, found: 286.1221.
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6-(thiophen-3-yl)phenanthridine (3k). 66 mg, 78%, viscous oil. H NMR (400 MHz, CDCl3):
δ 8.66 (d, J = 8.2 Hz,1H), 8.57 (dd, J = 8.2, 0.7 Hz, 1H), 8.27 (dd, J = 8.2, 0.7 Hz, 1H), 8.19ꢀ8.21
(m, 1H), 7.81ꢀ7.85 (m, 1H), 7.71ꢀ7.77 (m, 2H), 7.61ꢀ7.67 (m, 2H), 7.55ꢀ7.57 (m, 1H), 7.49 (ddd,
J = 5.0, 2.9, 0.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 156.4, 143.8, 140.8, 133.4, 130.5,
130.2, 129.2, 128.8, 128.4, 127.2, 126.8, 126.3, 125.7, 125.4, 123.6, 122.2, 121.9. HRMS(ESI)
calcd. for C17H12NS (M+H)+ m/z = 262.0690, found; 262.0682.
6,10-dimethylphenanthridine (8a).19 53 mg, 81%, white solid, mp 85ꢀ86oC. H NMR (400
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MHz, CDCl3): δ 8.74 (d, J = 8.4 Hz, 1H), 8.12 (dd, J = 7.2, 5.2 Hz, 2H), 7.58ꢀ7.59 (m, 2H), 7.61ꢀ
7.70 (m, 2H), 3.10 (s, 3H), 3.02 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.1, 144.7, 135.4,
134.7, 132.0, 129.5, 127.8, 127.3, 126.6, 126.5, 125.4, 125.2, 125.0, 26.8, 24.1. HRMS(ESI)
calcd. for C15H14N (M+H)+ m/z = 208.1126, found; 208.1125.
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10-methyl-6-propylphenanthridine (8b). 52 mg, 78%, viscous oil. H NMR (400 MHz,
CDCl3): δ 8.75 (d, J = 8.4 Hz, 1H), 8.15ꢀ8.18 (m, 2H), 7.64ꢀ7.71 (m, 2H), 7.55ꢀ7.59 (m, 2H),
3.32ꢀ3.36 (m, 2H), 3.10 (s, 3H), 1.89ꢀ1.99 (m, 2H), 1.10 (t, J = 7.4 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 162.5, 144.7, 135.6, 134.5, 132.5, 129.7, 127.8, 126.7, 126.6, 126.5, 125.4,
125.0, 124.8, 38.9, 26.9, 22.9, 14.4. HRMS(ESI) calcd. for C17H18N (M+H)+ m/z = 236.1439,
found: 236.1438.
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6-isopropyl-10-methylphenanthridine (8c). 51 mg, 74%, viscous oil. H NMR (400 MHz,
CDCl3): δ 8.75 (d, J = 8.4 Hz, 1H), 8.25 (d, J = 8.1 Hz, 1H), 8.17 (d, J = 6.5 Hz, 1H), 7.63ꢀ7.70
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(m, 2H), 7.54ꢀ7.59 (m, 2H), 3.98 (sept, J = 6.7 Hz, 1H), 3.11 (s, 3H), 1.50 (d, J = 6.7 Hz, 6H);
13C NMR (100 MHz, CDCl3) δ 166.0, 144.9, 135.7, 134.2, 132.6, 130.1, 127.6, 127.6, 126.4,
126.2, 125.2, 124.8, 124.1, 31.8, 27.0, 22.0. HRMS(ESI) calcd. for C17H18N (M+H)+ m/z =
236.1439, found: 236.1441.
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10-methyl-6-phenylphenanthridine (8d).7d 54 mg, 71%, white solid, mp 105ꢀ106 C. H NMR
(400 MHz, CDCl3): δ 8.84 (d, J = 8.4 Hz, 1H), 8.28 (d, J = 8.4 Hz, 1H), 7.96 (d, J = 8.4 Hz, 1H),
7.72ꢀ7.76 (m, 1H), 7.63ꢀ7.68 (m, 4H), 7.46ꢀ7.55 (m, 4H), 3.16 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 161.9, 144.8, 140.4, 135.2, 134.8, 132.8, 130.5, 129.6, 128.5, 128.3, 128.0, 127.7,
126.8, 126.5, 126.4, 126.0, 125.1, 26.8. HRMS(ESI) calcd. for C20H16N (M+H)+ m/z = 270.1283,
found; 270.1287.
8-methoxy-6-methylphenanthridine (9a).20a 54 mg, 66%, pale yellow solid, mp 109ꢀ111oC. H
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NMR (400 MHz, CD3CN): δ 8.50 (d, J = 9.0 Hz, 1H), 8.45 (dd, J = 7.7, 1.1 Hz, 1H), 7.93 (dd, J
= 7.7, 1.1 Hz, 1H), 7.58ꢀ7.67 (m, 2H), 7.47 (td, J = 9.0, 2.5 Hz, 2H), 3.95 (s, 3H), 2.91 (s, 3H);
13C NMR (100 MHz, CD3CN) δ 160.0, 159.4, 142.0, 128.9, 128.7, 127.8, 127.7, 127.6, 125.2,
124.7, 122.9, 122.7, 108.1, 56.4, 23.2. HRMS(ESI) calcd. for C15H14NO (M+H)+ m/z =
224.1075, found: 224.1080.
8-methoxy-6-propylphenanthridine (9b). 57 mg, 83%, pale yellow solid, mp 75ꢀ76oC. H
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NMR (400 MHz, CD3CN): δ 8.60 (d, J = 9.0 Hz, 1H), 8.52 (dd, J = 7.9, 1.1 Hz, 1H), 7.96ꢀ7.98
(m, 1H) 7.57ꢀ7.66 (m, 3H), 7.48 (dd, J = 9.0, 2.6 Hz, 1H), 3.97 (s, 3H), 3.28 (t, J = 7.6 Hz, 2H),
1.92ꢀ1.95 (m, 2H), 1.09 (t, J = 7.3 Hz, 3H); 13C NMR (100 MHz, CD3CN) δ 162.2, 159.9, 143.9,
130.3, 128.5, 127.8, 127.6, 127.4, 125.3, 124.6, 122.8, 121.5, 107.7, 56.4, 38.5, 22.6, 14.6.
HRMS(ESI) calcd. for C17H18NO (M+H)+ m/z = 252.1388, found: 252.1396.
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6-isopropyl-8-methoxyphenanthridine (9c). 54 mg, 74%, pale yellow solid, mp 92ꢀ94oC. H
NMR (400 MHz, CD3CN): δ 8.64 (d, J = 9.0 Hz, 1H), 8.54 (dd, J = 8.0, 1.5 Hz, 1H), 7.98ꢀ8.00
(m, 1H), 7.71 (d, J = 2.6 Hz, 1H), 7.58ꢀ7.67 (m, 2H), 7.50 (dd, J = 9.0, 2.6 Hz, 1H), 3.96 (s, 3H),
3.97ꢀ4.06 (m, 1H), 1.45 (d, J = 6.7 Hz, 6H); 13C NMR (100 MHz, CD3CN) δ 166.2, 160.0,
143.8, 130.4, 128.5, 128.0, 127.4, 127.0, 125.5, 125.5, 122.8, 121.4, 107.4, 56.4, 32.1, 22.2.
HRMS(ESI) calcd. for C17H18NO (M+H)+ m/z = 252.1388, found: 252.1380.
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8-methoxy-6-phenylphenanthridine (9d).20b 65 mg, 77%, pale yellow solid, mp 127ꢀ129oC. 1H
NMR (400 MHz, CD3CN): δ 8.68 (d, J = 9.0 Hz, 1H), 8.59ꢀ8.61 (m, 1H), 8.06ꢀ8.08 (m, 1H),
7.65ꢀ7.74 (m, 4H), 7.55ꢀ7.61 (m, 3H), 7.51 (dd, J = 9.0, 2.7 Hz, 1H), 7.44 (d, J = 2.7 Hz, 1H),
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3.79 (s, 3H); C NMR (100 MHz, CD3CN) δ 161.1, 159.7, 144.0, 141.0, 130.9, 130.5, 129.7,
129.3, 128.9, 128.5, 128.1, 127.4, 125.3, 124.7, 122.9, 122.0, 109.6, 56.1. HRMS(ESI) calcd. for
C20H16NO (M+H)+ m/z = 286.1232, found; 286.1230.
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8-fluoro-6-phenylphenanthridine (9e).11i 32 mg, 43%, pale yellow solid, mp 128ꢀ129oC. H
NMR (400 MHz, CDCl3): δ 8.68 (dd, J = 9.2 Hz, 1H), 8.54 (dd, J = 8.0, 0.8 Hz, 1H), 8.24 (d, J =
8.0 Hz, 1H), 7.66ꢀ7.76 (m, 5H), 7.50ꢀ7.61 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 161.2 (d, J =
247 Hz), 160.38, 143.4, 139.2, 130.4, 130.1, 129.5, 128.9, 128.7, 128.6, 127.3, 126.5 (d, J = 8.0
Hz), 124.7 (d, J = 8.4 Hz), 123.3, 121.7, 119.7 (d, J = 23 Hz), 113.2 (d, J = 22 Hz). HRMS(ESI)
calcd. for C19H13FN (M+H)+ m/z = 274.1032, found; 274.1040.
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8-fluoro-6-methylphenanthridine (9f).20c 34 mg, 58%, pale yellow solid, mp 89ꢀ90oC. H
NMR (400 MHz, CDCl3): δ 8.56 (dd, J = 9.0, 5.3 Hz, 1H), 8.42 (d, J = 8.1 Hz, 1H), 8.07 (d, J =
8.1 Hz, 1H), 7.78 (dd, J = 9.6, 2.6 Hz, 1H), 7.67 (td, J = 8.2, 1.2 Hz, 1H), 7.52ꢀ7.61 (m, 2H),
2.96 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 162.5, 158.0 (d, J = 222.7 Hz), 143.3, 129.4, 129.2,
128.5, 127.0 (d, J = 7.4 Hz), 126.7, 124.8 (d, J = 33.2 Hz), 123.2, 121.6, 119.4 (d, J = 29.6 Hz),
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111.1 (d, J = 21.2 Hz), 23.3. HRMS(ESI) calcd. for C14H11FN (M+H)+ m/z = 212.0876, found:
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6-methyl-2-(trifluoromethyl)phenanthridine (12a).11d 44 mg, 66%, white solid, mp 107ꢀ109oC.
1H NMR (400 MHz, CDCl3): δ 8.77 (s, 1H), 8.61 (d, J = 8.2 Hz, 1H), 8.23 (d, J = 8.2 Hz, 1H),
8.16 (d, J = 8.5 Hz, 1H), 7.86ꢀ7.90 (m, 2H), 7.74 (td, J = 8.2, 1.0 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 161.4, 145.0, 132.1, 131.1, 130.1, 128.2, 126.7, 126.1, 125.7, 124.6, 123.4, 123.0,
122.3, 119.8 (d, J = 3.9 Hz), 22.3. HRMS(ESI) calcd. for C15H11F3N (M+H)+ m/z = 262.0844,
found: 262.0849.
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6-propyl-2-(trifluoromethyl)phenanthridine (12b). 45 mg, 61%, white solid, mp 59ꢀ60oC. H
NMR (400 MHz, CDCl3): δ 8.71 (s, 1H), 8.56 (d, J = 8.2 Hz, 1H), 8.20 (d, J = 8.2 Hz, 1H), 8.13
(d, J = 8.5 Hz, 1H), 7.77ꢀ7.83 (m, 2H), 7.66 (td, J = 8.2, 1.1 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 164.7, 145.1, 132.1, 130.9, 130.3, 128.1, 126.5, 125.7, 125.5, 124.5, 123.2, 123.0,
122.4, 119.7 (d, J = 3.9 Hz), 38.2, 22.6, 14.3. HRMS(ESI) calcd. for C17H15F3N (M+H)+ m/z =
290.1157, found: 290.1160.
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2-chloro-6-methylphenanthridine (12c).21 54 mg, 84%, white solid, mp 120ꢀ121oC. H NMR
(400 MHz, CD3CN): δ 8.61 (d, J = 8.2 Hz, 1H), 8.58 (d, J = 2.2 Hz, 1H), 8.26 (d, J = 8.2 Hz,
1H), 7.93 (d, J = 8.7 Hz, 1H), 7.87 (td, J = 8.2, 1.0 Hz, 1H), 7.76 (td, J = 8.2, 1.0 Hz, 1H), 7.65
(td, J = 8.7, 2.2 Hz, 1H), 2.94 (s, 3H); 13C NMR (100 MHz, CD3CN) δ 159.4, 142.0, 131.4,
131.1, 130.8, 130.7, 128.6, 128.1, 126.6, 125.7, 124.7, 122.4, 121.7, 22.5. HRMS(ESI) calcd. for
C14H11ClN (M+H)+ m/z = 228.0580, found: 228.0589.
2-chloro-6-propylphenanthridine (12d). 60 mg, 81%, white solid, mp 97ꢀ98oC. 1H NMR (400
MHz, CD3CN): δ 8.64 (d, J = 8.2 Hz, 1H), 8.59 (d, J = 2.1 Hz, 1H), 8.32 (d, J = 8.2 Hz, 1H),
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MHz, CD3CN) δ 163.9, 143.6, 132.9, 132.9, 132.4, 132.1, 130.1, 129.6, 127.8, 126.7, 126.1,
124.1, 123.3, 38.8, 23.2, 14.9. HRMS(ESI) calcd. for C16H15ClN (M+H)+ m/z = 256.0893,
found: 256.0893.
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2-Chloro-6-isopropylphenanthridine (12e). 53 mg, 73%, white solid, mp 128ꢀ130oC. 1H NMR
(400 MHz, CD3CN): δ 8.69 (d, J = 8.0 Hz, 1H), 8.64 (d, J =2.4 Hz, 1H), 8.41 (d, J = 8.4 Hz, 1H),
7.99 (d, J = 8.8 Hz, 1H), 7.89 (td, J = 8.4, 1.2 Hz, 1H), 7.79 (td, J = 8.4, 1.2 Hz, 1H), 7.68 (dd, J
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= 8.8, 2.4 Hz, 1H), 4.04 (sept, J = 6.8 Hz, 1H), 1.44 (d, J = 6.8 Hz, 6H); C NMR (100 MHz,
CD3CN) δ 167.6, 143.2, 132.8, 132.6, 132.2, 131.7, 129.8, 129.3, 126.9, 125.7, 125.6, 123.9,
122.9, 32.1, 22.3. HRMS(ESI) calcd. for C16H15ClN (M+H)+ m/z = 256.0888, found: 256.0897.
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2-chloro-6-phenylphenanthridine (12f).8e 62 mg, 76%, white solid, mp 143ꢀ145oC. H NMR
(400 MHz, CD3CN): δ 8.73 (d, J = 8.4 Hz, 1H), 8.71 (d, J = 2.0 Hz, 1H), 8.07 (dd, J = 8.0, 3.2
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Hz, 1H), 7.92 (t, J = 8.0 Hz, 2H), 7.69ꢀ7.74 (m, 4H), 7.57ꢀ7.61 (m, 3H); C NMR (100 MHz,
CD3CN) δ 162.4, 143.3, 140.6, 133.4, 133.3, 132.7, 132.0, 130.7, 130.2, 129.8, 129.6, 129.3,
129.2, 126.2, 125.8, 123.7, 123.0. HRMS(ESI) calcd. for C19H13ClN (M+H)+ m/z = 290.0737,
found; 290.0735.
2,6-Dimethylphenanthridine (12g).18a 49 mg, 82%, viscous oil. 1H NMR (400 MHz, CDCl3): δ
8.51 (d, J = 8.2 Hz, 1H), 8.22 (s, 1H), 8.10 (d, J = 8.2 Hz, 1H), 7.91 (d, J = 8.2 Hz, 1H), 7.72 (td,
J = 8.2, 1.2 Hz, 1H), 7.58 (td, J = 8.2, 1.0 Hz, 1H), 7.44 (dd, J = 8.3, 1.5 Hz, 1H), 2.94 (s, 3H),
2.52 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 157.7, 141.8, 136.0, 132.3, 130.2, 130.2, 128.9,
127.1, 126.4, 125.9, 123.5, 122.2, 121.5, 23.2, 21.8. HRMS(ESI) calcd. for C15H14N (M+H)+ m/z
= 208.1126, found: 208.1135.
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2-methyl-6-phenylphenanthridine (12h).21c 61 mg, 76%, white solid, mp 73ꢀ75oC. H NMR
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NMR (100 MHz, CDCl3) δ 160.2, 142.0, 139.7, 136.8, 133.1, 130.5, 130.3, 129.9, 129.7, 128.8,
128.5, 128.3, 126.9, 125.2, 123.5, 122.1, 121.5, 21.9. HRMS(ESI) calcd. for C20H16N (M+H)+
m/z = 270.1283, found; 270.1278.
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MHz, CDCl3): δ 8.55 (dd, J = 8.3, 0.4 Hz, 1H), 8.39 (d, J = 8.3 Hz, 1H), 8.17 (dd, J = 8.3, 0.4
Hz, 1H), 7.88 (s, 1H), 7.77ꢀ7.81 (m, 1H), 7.61ꢀ7.65 (m, 1H), 7.42 (dd, J = 8.3, 1.4 Hz, 1H), 3.01
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(s, 3H); C NMR (100 MHz, CDCl3) δ 158.8, 143.6, 138.7, 132.6, 130.4, 128.8, 128.0, 126.8,
126.5, 125.5, 122.1, 121.7, 121.4, 23.2, 21.5. HRMS(ESI) calcd. for C15H14N (M+H)+ m/z =
208.1126, found: 208.1120.
3-methyl-6-phenylphenanthridine (13b).7d 58 mg, 79%. White solid. mp: 108ꢀ110oC. 1H NMR
(400 MHz, CDCl3): δ 8.62 (d, J = 8.3 Hz, 1H), 8.46 (d, J = 8.3 Hz, 1H), 8.06 (d, J = 8.3 Hz, 1H),
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(100 MHz, CDCl3) δ 161.2, 143.8, 139.8, 138.9, 133.4, 130.4, 129.8, 129.7, 128.8, 128.6, 128.5,
128.3, 126.6, 124.9, 121.9, 121.7, 121.3, 21.5. HRMS(ESI) calcd. for C20H16N (M+H)+ m/z =
270.1283, found; 270.1291.
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(6-methylphenanthridin-2-yl)(morpholino)methanone (14a). 51 mg, 76%, viscous oil. H
NMR (400 MHz, CDCl3): δ 8.61 (d, J = 1.5 Hz, 1H), 8.59 (d, J = 8.2 Hz, 1H), 8.22 (d, J = 8.2
Hz, 1H), 8.11 (d, J = 8.3 Hz, 1H), 7.83ꢀ7.87 (m, 1H), 7.69ꢀ7.73 (m, 1H), 7.67 (dd, J = 8.3, 1.5
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Hz, 1H), 3.73 (bs, 8H), 3.04 (s, 3H); C NMR (100 MHz, CDCl3) δ 170.3, 160.4, 143.9, 132.9,
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132.2, 131.0, 129.3, 127.9, 126.8, 126.7, 126.0, 123.8, 122.3, 121.7, 66.9, 23.3. HRMS(ESI)
calcd. for C19H19N2O2 (M+H)+ m/z = 307.1446, found; 307.1447.
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(6-phenylphenanthridin-2-yl)(morpholino)methanone (14b). 52mg, 68%. white solid. mp: 206ꢀ
208oC. 1H NMR (400 MHz, CDCl3): δ 8.65 (d, J = 1.6 Hz, 1H), 8.62 (d, J = 8.3 Hz, 1H), 8.20 (d,
J = 8.3 Hz, 1H), 8.06 (d, J = 8.2 Hz, 1H), 7.80ꢀ7.84 (m, 1H), 7.65ꢀ7.68 (m, 3H), 7.57ꢀ7.61 (m,
1H), 7.45ꢀ7.52 (m, 3H), 3.65 (bs, 8H); 13C NMR (100 MHz, CDCl3) δ 170.2, 162.5, 144.2,
139.3, 133.4, 133.2, 131.0, 130.4, 129.6, 129.1, 128.8, 128.4, 127.7, 127.0, 125.4, 123.7, 122.2,
121.7, 66.9. HRMS(ESI) calcd. for C24H21N2O2 (M+H)+ m/z = 369.1603, found; 369.1593.
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8ꢀmethoxyꢀ2,6ꢀdimethylphenanthridine (17).8c 59 mg, 86%, pale yellow solid 124ꢀ126oC. H
NMR (400 MHz, CD3CN) δ 8.53 (d, J = 9.2 Hz, 1H), 8.29 (s, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.52
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(d, J = 2.4 Hz, 1H), 7.42ꢀ7.47 (m, 2H), 3.95 (s, 3H), 2.89 (s, 3H), 2.56 (s, 3H); C NMR (100
MHz, CD3CN) δ 159.7, 158.0, 142.1, 137.2, 130.1, 129.8, 128.1, 127.2, 125.0, 124.5, 122.3,
121.4, 107.9, 56.3, 23.7, 21.8. HRMS (ESI) calcd. for C16H16NO (M+H)+ m/z = 238.1232, found;
238.1237.
Dibenzo[b,d]furan.22a Biaryldiazonium salt 10 (0.23 mmol) was dissolved in 0.5 mL of
anhydrous acetonitrile in a 10 mL round bottomed flask and stirred at room temperature for 15 h
under nitrogen atmosphere. Removal of solvents under reduced pressure and purification by flash
column chromatography (EA/Hexane, 1:0.1) afforded the title compound (39 mg, quantitative) as
a white solid. 1H NMR (400 MHz, CDCl3): δ 7.94 (dd, J = 7.6, 0.6 Hz, 2H), 7.56 (d, J = 8.2 Hz,
2H), 7.44 (dt, J = 8.5, 1.3 Hz, 2H), 7.33 (dt, J = 8.3, 1.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ
156.1, 127.1, 124.2, 122.6, 120.6, 111.6. These data are in agreement with the reported data.
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2-methoxybenzo[c]cinnoline.22b Biaryldiazonium salt 11 (0.26 mmol) was suspended in 0.26
mL of anhydrous acetonitrile in a sealed tube and heated to 120oC for 3h. Purification by flash
chromatography (MeOH/DCM, 0.1:10) afforded the title compound (47 mg, 85%) as a viscous
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oil. H NMR (400 MHz, CDCl3): δ 8.66ꢀ8.68 (m, 1H), 8.62 (d, J = 9.2 Hz, 1H), 8.47ꢀ8.50 (m,
1H), 7.83ꢀ7.89 (m, 2H), 7.79 (d, J = 2.4 Hz, 1H), 7.47 (dd, J = 8.8, 2.4 Hz, 1H), 4.06 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 161.8, 145.1, 142.0, 133.2, 131.1, 130.7, 129.2, 123.1, 121.4, 120.9,
120.2, 100.5, 55.8. HRMS(ESI) calcd. for C13H11N2O (M+H)+ m/z = 211.0871, found; 211.0867.
Fluoroanthene (19).22c 45mg, 71%, white solid. mp 106ꢀ107oC. 1H NMR (400 MHz, CDCl3):
δ 7.93 (d, J = 7.0 Hz, 2H), 7.91 (dd, 5.5, 3.1 Hz, 2H), 7.83 (d, J = 8.2 Hz, 2H), 7.63 (dd, J = 8.2,
7.0 Hz, 2H), 7.37 (dd, 5.5, 3.1 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 139.4, 136.9, 132.3,
129.9, 127.9, 127.5, 126.6, 121.4, 120.0. These data are in agreement with the reported data.
6-Methylbenzo[k]phenanthridine (20).19 6.7 mg, 11%, white solid, H NMR (400 MHz,
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CDCl3): δ 9.12ꢀ9.14 (m, 1H), 8.97 (d, J = 8.4 Hz, 1H), 8.23 (d, J = 8.1 Hz, 1H), 8.12 (d, J = 8.8
Hz, 1H), 8.02ꢀ8.06 (m, 1H), 7.99 (d, J = 8.8 Hz, 1H), 7.71ꢀ7.77 (m, 3H), 7.65 (td, J = 8.4, 1.4
Hz, 1H), 3.12 (s, 3H). HRMS (ESI) m/z = 244.1126 calcd. for C18H14N (M+H)+, found;
244.1116.
ASSOCIATED CONTENT
Supporting Information
Spectra for all new compounds. This material is available free of charge via the Internet at
http://pubs.acs.org
AUTHOR INFORMATION
Corresponding Author
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*Eꢀmail: stliu@ntu.edu.tw
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Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENT
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We thank the National Science Council, Taiwan (Grant No. MOST103ꢀ2113ꢀMꢀ002 ꢀ002ꢀ
MY3) for the financial support. We also thank “National Taiwan University Mass Spectrometryꢀ
based Proteomics Core Facility” for the measurement of ESI mass data.
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