Direct conversion of 1-(2-bromobenzoyl)isoquinolines to dibenzo[ de,g ]quinolin-7-ones via reductive photocyclization

Article abstract of DOI:10.1021/jo400645g

A series of A/D-ring substituted dibenzo[de,g]quinolin-7-ones was produced from the corresponding isoquinolinones and (2-bromophenyl)acetonitriles in four steps. This represents a convenient approach toward the synthesis of tetracyclic alkaloids. A direct conversion of 1-(2-bromobenzoyl)isoquinolines to dibenzo[de,g]quinolin-7-ones is the key step in the total synthesis. The yield of the reductive photocyclization depends on the position of the substituents at the isoquinolyl ring and the phenyl group. The mechanism of the reductive photocyclization is also discussed.

Full text of DOI:10.1021/jo400645g

Article
pubs.acs.org/joc
Direct Conversion of 1‑(2-Bromobenzoyl)isoquinolines to
Dibenzo[de,g]quinolin-7-ones via Reductive Photocyclization
Ta-Hsien Chuang,* Chien-Fu Li, Hong-Zin Lee, and Yu-Chia Wen
School of Pharmacy, China Medical University, No. 91, Hsueh-Shih Road, Taichung, 40402 Taiwan, Republic of China
S
* Supporting Information
ABSTRACT: A series of A/D-ring substituted dibenzo[de,g]quinolin-7-ones was produced from the corresponding
isoquinolinones and (2-bromophenyl)acetonitriles in four steps. This represents a convenient approach toward the synthesis
of tetracyclic alkaloids. A direct conversion of 1-(2-bromobenzoyl)isoquinolines to dibenzo[de,g]quinolin-7-ones is the key step
in the total synthesis. The yield of the reductive photocyclization depends on the position of the substituents at the isoquinolyl
ring and the phenyl group. The mechanism of the reductive photocyclization is also discussed.
INTRODUCTION
■
Since the first isolation of liriodenine from Atherosperma
moschatum Labill. in 1956,1 dibenzo[de,g]quinolin-7-one
alkaloids have been the focus of study in medicinal and
synthetic chemistry. Some of the dibenzo[de,g]quinolin-7-one
alkaloids have shown extensive pharmacological activities, such
as antileishmanial,2 antimicrobial,3,4 antivirus,5−7 antioxidative,8
vasorelaxing,8,9 antiplatelet aggregation,10−12 antiflammatory,13
and cytotoxic13−19 activities. Moreover, previous structure−
activity relationship (SAR) studies have indicated that removal
of the oxo function sharply reduces the cytotoxic activities
against human lung carcinoma A-549 and colon HCT-8 tumor
cells.20 This finding suggests that the oxo function may
contribute to anticancer activity by extending the conjugation
of the aporphine ring system.20,21 However, dibenzo[de,g]-
quinolin-7-one alkaloids are present in minor amounts in
method involving the intermolecular [4 + 2] cycloaddition of
protected 1-methylene-isoquinoline 5 with benzyne33 or 10-
plants, even though they may be widely distributed in many
plant families (e.g., Annonaceae, Magnoliaceae).22−26 These
tetracyclic alkaloids are most likely derived in the plants
through the oxidation of the corresponding aporphines.27,28
The wide range of pharmacological properties exhibited by
dibenzo[de,g]quinolin-7-one alkaloids has attracted the atten-
tion of chemists. Over the past several decades, the following
methodologies have allowed access to dibenzo[de,g]quinolin-7-
one alkaloids: (a) Coupling of rings A/D: using the Pschorr
cyclization of 1-(2-amionbenzoyl)isoquinoline 1, the first total
synthesis of dibenzo[de,g]quinolin-7-ones was disclosed by
Taylor in 1961,29 and other methods are photocyclization30 or
Bu3SnH-induced aryl radical cyclization31 of the bromides 2 or
3. (b) Ring closure between rings B and D: intramolecular
Friedel−Crafts acylation of 8-phenyl-3,4-dihydroisoquinolines
4 in polyphosphoric acid has been utilized.32 (c) A convergent
(methoxyimino)phenanthren-9-one 6 with dimethyl acetylene-
dicaboxylate (DMAD)34 to provide the tetracyclic skeleton.
However, there are some inherent limitations in the above
methodologies. For example, the symmetrical species benzyne
and DMAD were used. Moreover, the precursors of the Pschorr
and radical cyclizations, obtained via alkylation of Reissert
compounds, resulted in 1-cyanoisoquinoline byproducts that
were difficult to separate from the products.35 Furthermore, an
attempt to prepare the aporphine skeleton by photocyclization
of the bromo ketone 7, as reported by Kessar et al.,36 was
unsuccessful. In this paper, we disclose a convenient one-pot
methodology to produce a variety of A/D-ring substituted
dibenzo[de,g]quinolin-7-ones 8 via photocyclization of 1-(2-
Received: March 27, 2013
Published: April 23, 2013
© 2013 American Chemical Society
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a
Scheme 1. Synthesis of 1-(2-Bromobenzoyl)isoquinolines 13
a
Reagents and conditions: (a) (i) Tf2O, py, CH3CN, rt, 2 h; (ii) NaI, TfOH, rt, overnight; (b) NaNH2, THF, reflux, overnight; (c) NaH, O2, THF,
rt, 3 h.
Table 1. Formation of 12 and 13 from 1-Iodoisoquinolines 10 and (2-Bromophenyl)acetonitriles 11
a
products (%)
entry
1-iodoisoquinoline (10), R =
(2-bromophenyl)acetonitrile (11), R =
12
13
1
10A, R = H
11A, R = H
12a (97)
12b (72)
12c (76)
12d (89)
12e (76)
12f (85)
12g (95)
12h (75)
12i (91)
12j (100)
12k (97)
12l (93)
12m (74)
12n (100)
12o (84)
12p (80)
12q (92)
12r (87)
12s (97)
12t (91)
13a (95)
13b (96)
13c (81)
13d (59)
13e (94)
13f (84)
13g (67)
13h (55)
13i (89)
13j (91)
13k (94)
2
10A, R = H
11B, R = 4,5-dimethoxy
11C, R = 4,5-methylenedioxy
11D, R = 5-trifluoromethyl
11A, R = H
3
10A, R = H
b
b
4
10A, R = H
5
10B, R = 5-methoxy
10B, R = 5-methoxy
10B, R = 5-methoxy
10B, R = 5-methoxy
10C, R = 5,6-dimethoxy
10C, R = 5,6-dimethoxy
10C, R = 5,6-dimethoxy
10C, R = 5,6-dimethoxy
10D, R =7-methoxy
10D, R = 7-methoxy
10D, R = 7-methoxy
10D, R = 7-methoxy
10E, R = 6,7-methylenedioxy
10E, R = 6,7-methylenedioxy
10E, R = 6,7-methylenedioxy
10E, R = 6,7-methylenedioxy
6
11B, R = 4,5-dimethoxy
11C, R = 4,5-methylenedioxy
11D, R = 5-trifluoromethyl
11A, R = H
7
8
9
10
11
12
13
14
15
16
17
18
19
20
11B, R = 4,5-dimethoxy
11C, R = 4,5-methylenedioxy
11D, R = 5-trifluoromethyl
11A, R = H
b
13l (65)
13m (88)
13n (96)
13o (88)
11B, R = 4,5-dimethoxy
11C, R = 4,5-methylenedioxy
11D, R = 5-trifluoromethyl
11A, R = H
b
13p (74)
13q (92)
13r (79)
13s (94)
11B, R = 4,5-dimethoxy
11C, R = 4,5-methylenedioxy
11D, R = 5-trifluoromethyl
b
13t (53)
a
b
Isolated yields. Recovered starting materials 12d, 12h, 12l, 12p, and 12t in 24%, 25%, 30%, 12%, and 30% yields, respectively.
bromobenzoyl)isoquinolines 13 in the presence of sodium
borohydride (NaBH4). In addition, a systematic investigation of
substituent effects on the reductive photocyclization is also
discussed.
thermal cyclization of the corresponding styryl isocyanates, as
previously reported.37 Subsequently, the reaction of com-
pounds 9 with trifluoromethanesulfonic anhydride (Tf2O) in
the presence of pyridine led to the isoquinolyl triflates.
Treatment of the intermediate triflates with sodium iodide
and TfOH at room temperature in acetonitrile produced the
desired iodides 10. The one-pot iodination of isoquinolinones 9
gave the 1-iodoisoquinolines 10 in high yields.
RESULTS AND DISCUSSION
■
The strategy for the preparation of 1-(2-bromobenzoyl)-
isoquinolines 13, the photocyclization precursors, is shown in
Scheme 1. First, a series of isoquinolinones 9 was obtained via
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We originally planned to synthesize the photocyclization
precursor 13a via the Cu(I)-catalyzed acylation of 1-
isoquinolylzinc iodide generated from the direct insertion of
zinc into iodoisoquinoline 10a in the presence of LiCl using 2-
bromobenzoyl chloride.38 Unfortunately, only the hydrolysis
product isoquinoline was obtained despite the use of flame-
dried glass vessels and standard Schlenk techniques. Therefore,
we developed a two-step approach to synthesize the
intermediates 13 via (2-bromophenyl)isoquinolin-1-ylacetoni-
triles 12. The 1-iodoisoquinolines 10 reacted with commercially
available (2-bromophenyl)acetonitriles 11 to give the adducts
12 in yields ranging from 72 to 100% (Table 1).39 Then, the
key photocyclization precursors 13 were readily produced in
moderate to excellent yields (53 to 96%, Table 1) through
oxidative decyanation of the corresponding nitriles 12 with
oxygen in the presence of sodium hydride.40 It should be
mentioned here that some of the starting materials (12d, 12h,
12l, 12p, and 12t) were recovered from the oxidative
decyanation reaction (Table 1, entries 4, 8, 12, 16, and 20).
However, the conversion could not be completed by extending
the reaction time to 6 h, most likely because the α-carbanions
of the acetonitriles 12 were stabilized by the inductive effect of
the electron-withdrawing substituent −CF3.
With the series of 1-(2-bromobenzoyl)isoquinolines 13 in
hand, the key cyclization reaction was investigated. The
unsubstituted dibenzo[de,g]quinolin-7-one 8a was chosen as
our initial target because its simplicity would allow us to test the
feasibility of the cyclization. First, the bromo ketone 13a was
subjected to Bu3SnH-induced aryl radical cyclization according
to the method of Orito et al.31 and a somewhat modified
version of this method to give the cyclization adduct 8a in a low
yield. Additionally, we attempted to synthesize dibenzo[de,g]-
quinolin-7-one 8a by photocyclization of bromo ketone 13a in
MeOH, which resulted in a complicated reaction mixture. This
result is similar to Kessar’s observation that the photoinduced
cyclization of bromo ketone 7 in dilute aqueous HCl solution
was unsuccessful.36 Intriguingly, we found that dibenzo[de,g]-
quinolin-7-one 8a could be obtained in 55% yield by irradiation
of a solution of the bromo ketone 13a and 1.5 equiv of NaBH4
in MeOH (eq 1). Thus, the direct conversion of 1-(2-
bromobenzoyl)isoquinolines to dibenzo[de,g]quinolin-7-ones
using one-pot reductive photocyclization was accomplished.
the reductive photocyclization of 1-(2-bromobenzoyl)-isoqui-
nolines 13a−t are shown in Table 2. First, with the bromo
ketones 13b and 13c, which have vicinal dimethoxy or
methylenedioxy groups at the 4,5-positions of the benzoyl
group, the yields of dibenzo[de,g]quinolin-7-ones 8b and 8c
slightly increased (compare entry 1 with entries 2 and 3).
However, the photocyclization of bromo ketone 13d, which has
a strong electron-withdrawing group (−CF3) at the 5-position
of the phenyl group, was complete after a short period of time
(9 h) and led to the production of the corresponding
dibenzo[de,g]quinolin-7-one 8d in 33% yield along with several
complicated inseparable products (entry 4). We hypothesized
that a shorter reaction time was needed because the
photoinduced electron transfer from isoquinolyl ring to phenyl
ring could be enhanced by the electron-withdrawing substituent
−CF3 on the phenyl ring. Second, bromo ketones 13e, 13f,
13g, and 13h bearing the electron-donating group 5-OCH3 on
the isoquinolyl ring produced the corresponding dibenzo[de,g]-
quinolin-7-ones 8e, 8f, 8g, and 8h in higher yields (86%, 95%,
80%, and 99%, respectively). Similarly, when bromo ketones
13m, 13n, 13o, and 13p, which have a methoxy group at the 7-
positions of the isoquinolyl ring, were utilized the photo-
cyclizations provided higher yields of dibenzo[de,g]quinolin-7-
ones 8m, 8n, 8o, and 8p (63%, 95%, 81%, and 80%,
respectively). The results revealed that the reactivity of the
photocyclization of 1-(2-bromobenzoyl)isoquinolines could be
increased by the presence of 5-OCH3 and 7-OCH3 substituents
(compare entry 1 with entries 5 and 13, entry 2 with entries 6
and 14, entry 3 with entries 7 and 15, and entry 4 with entries 8
and 16). Third, when the bromo ketones 13i, 13j, 13k, and 13l,
which have vicinal 5,6-dimethoxy groups on the isoquinolyl
ring, were subjected to the same conditions, formation of the
dibenzo[de,g]quinolin-7-ones was disfavored (compare entry 5
with entry 9, entry 6 with entry 10, entry 7 with entry 11, and
entry 8 with entry 12). The lower yields were also observed
when the bromo ketones 13q, 13r, 13s, and 13t, which have a
6,7-methylenedioxy group on the isoquinolyl ring, were used
(compare entry 13 with entry 17, entry 14 with entry 18, entry
15 with entry 19, and entry 16 with entry 20). We hypothesized
that the yields of dibenzo[de,g]quinolin-7-ones decreased
because the photoinduced electron transfer from isoquinolyl
ring to phenyl ring could be retarded by the inductive effect of
the oxygen atom at the 6-position of the isoquinolyl ring.
Clearly, the reductive photocyclization was promoted by
methoxy groups at the 5- or 7-positions of the isoquinolyl
ring or the trifluoromethyl group at the 5-position of the phenyl
group. In contrast, the reactivity of the reductive photo-
cyclization was decreased by a methoxy group on the 6-position
of the isoquinolyl ring.
Mechanistic study. On the basis of the above results, a
complete mechanistic route for the formation of dibenzo[de,g]-
quinolin-7-ones 8 through a reductive photocyclization of 1-(2-
bromobenzoyl)isoquinolines 13 with NaBH4 is proposed and
depicted in Scheme 2. First, NaBH4 apparently plays a role in
reducing bromo ketones 13 into the corresponding α-hydroxy-
(2-bromobenzyl)isoquinolines 14 prior to photocyclization
because irradiation of bromo ketone 13a in MeOH in the
absence of NaBH4 led to a complicated reaction mixture.
Subsequently, the photoreaction of intermediates 14 might be
initiated by photoinduced electron transfer, and gave diradical-
ions 15 with a radical-cation on the isoquinolyl ring and a
radical-anion on the phenyl ring.41 The carbocation of the
intermediates 15 could be stabilized by the resonance effect of
Based on the results of the model study, we anticipated that a
series of dibenzo[de,g]quinolin-7-ones 8b−t would be readily
produced using the reductive photocyclization method (eq 1).
The substituent effects on the reaction time and the yields from
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Table 2. Reductive Photocyclization of Bromo Ketone Precursors 13a−t with NaBH4 (1.5 equiv) in MeOH (2.5 mM) To
Provide Dibenzo[de,g]quinolin-7-ones 8a−t
substituent
entry
reactant
time (h)
R1
R2
R3
R4
R5
product 8 (%)
1
13a
13b
13c
13d
13e
13f
15
24
15
9
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
8a (55)
8b (77)
8c (69)
8d (33)
8e (86)
8f (95)
8g (80)
8h (99)
8i (61)
8j (70)
8k (78)
8l (80)
8m (63)
8n (95)
8o (81)
8p (80)
8q (45)
8r (81)
8s (53)
8t (72)
2
OCH3
OCH3
3
−OCH2O−
−OCH2O−
−OCH2O−
−OCH2O−
−OCH2O−
4
H
H
CF3
H
5
15
20
15
10
48
24
24
24
15
20
15
10
13
18
18
5
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
H
6
OCH3
OCH3
7
13g
13h
13i
8
H
H
CF3
H
9
OCH3
OCH3
OCH3
OCH3
H
10
11
12
13
14
15
16
17
18
19
20
13j
OCH3
OCH3
13k
13l
H
H
CF3
H
13m
13n
13o
13p
13q
13r
13s
13t
OCH3
OCH3
OCH3
OCH3
H
H
OCH3
OCH3
H
H
H
H
H
H
CF3
H
H
−OCH2O−
−OCH2O−
−OCH2O−
−OCH2O−
H
OCH3
OCH3
H
H
H
CF3
yellow) observed during the workup. The auto-oxidation of
intermediates 16 with air resulted in the formation of the
desired dibenzo[de,g]quinolin-7-ones 8 after thorough removal
of the reducing reagent during the workup procedure.42
Scheme 2. Mechanism of the Reductive Photocyclization of
1-(2-Bromobenzoyl)isoquinolines 13 with NaBH4
CONCLUSION
■
To our knowledge, this paper is the first to describe the
reductive photocyclization of 1-(2-bromobenzoyl)isoquinolines
13 to give dibenzo[de,g]quinolin-7-ones 8 using NaBH4 as a
reducing agent. A series of substituted dibenzo[de,g]quinolin-7-
ones 8 was synthesized from the corresponding bromo ketones
13 in a one-pot reaction. The substituent effects on the
subsequent reductive photocyclization are shown. When
−OCH3 is at the 5- or 7-positions of the isoquinolyl ring or
−CF3 at the 5-position of the phenyl group, the photo-
cyclization can be enhanced. Hence, 9-trifluoromethyl-3-
methoxy-dibenzo[de,g]quinolin-7-one (8h) could be obtained
in the highest yield.
EXPERIMENTAL SECTION
■
General Methods. All reagents were purchased and used without
further purification. Column chromatography was carried out using a
230−400 mesh silica gel. Nuclear magnetic resonance spectra were
recorded on 500 and 600 MHz FT-NMR spectrometers; all chemical
shifts were reported in ppm from tetramethylsilane as an internal
standard. Melting points are uncorrected. FT-IR, MS, and elemental
analysis were measured with conventional spectrometers. High-
resolution electron ionization mass spectra (HREI-MS) were recorded
on a high-resolution E/B mass spectrometer using a double-focusing
magnetic-sector mass analyzer and orbitrap mass analyzer used for
HRESI-MS measurements.
the methoxy groups at the 5- or 7-positions of the isoquinolyl
ring, and the carbanion of the intermediates 15 could also be
stabilized by the inductive effect of the trifluoromethyl group
on the phenyl ring. Hence, the reductive photocyclization of (2-
bromo-5-trifluoromethylphenyl)-(5-methoxyisoquinolin-1-yl)-
methanone (13h) was obtained in the highest yield. In contrast,
the reductive photocyclization of bromo ketones with a
methoxy group at the 6-position of the isoquinolyl ring was
retarded because the inductive effect of oxygen made the
carbocation on the isoquinolyl ring less stable. The facts
supported the existence of the diradical-ions 15. After
elimination of the bromide as well as radical recombination, a
loss of proton from the isoquinolyl ring would lead to the
formation of 7-hydroxyaporphines 16. No further oxidation
occurred before workup due to the presence of NaBH4, and
this is supported by the obvious color change (from orange to
General Procedure for the Preparation of 1-Iodoisoquino-
line 10. Trifluoromethanesulfonic anhydride (11.0 mmol) was slowly
added to a mixture of the isoquinolinones 937 (10.0 mmol) and
pyridine (11.5 mmol) in acetonitrile (20 mL) cooled in an ice bath.
The reaction mixture was stirred for 2 h at room temperature under
N2. Without purification, sodium iodide (50.0 mmol) was added in
one portion at room temperature, and trifluoromethanesulfonic acid
(11.0 mmol) was then added dropwise via syringe. The reaction
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mixture was stirred at room temperature overnight. After the reaction
was complete, the resulting solution was diluted with water (35 mL)
and toluene (45 mL). Then, the mixture was quenched with 10 M
sodium hydroxide to reach a pH of ca. 10 while being cooled in an ice
bath. The organic layer was separated and washed with 5% sodium
thiosulfate (2 × 10 mL), 1 M sodium hydroxide (10 mL), and water (3
× 10 mL). The organic extract was dried with anhydrous MgSO4,
filtered, and evaporated under reduced pressure. The residue was
purified by column chromatography over silica gel eluting with
hexane−EtOAc (10:1) to give the pure 1-iodoisoquinolines 10. The
full spectral data of 10A−E are described as follows.
7.41 (1H, dd, J = 7.8, 1.7 Hz), 7.60−7.63 (1H, m), 7.65 (1H, dd, J =
7.8, 1.7 Hz), 7.69−7.72 (2H, m), 7.89 (1H, d, J = 8.2 Hz), 7.97 (1H, d,
J = 8.2 Hz), 8.61 (1H, d, J = 5.7 Hz); 13C NMR (125 MHz, CDCl3) δ
42.2, 177.7, 121.5, 123.4, 123.7, 125.5, 127.7, 128.2, 128.3, 130.2,
130.3, 130.4, 133.1, 134.2, 136.6, 141.9, 153.0; IR (KBr) 2249 cm−1;
ESIMS m/z (rel int) 323 (100, [M + 1]+), 323 (100, [M + 3]+). Anal.
Calcd for C17H11BrN2: C, 63.18; H, 3.43; N, 8.67. Found: C, 63.17; H,
3.20; N, 8.51.
(2-Bromo-4,5-dimethoxyphenyl)isoquinolin-1-yl-acetonitrile
(12b): yield 72% (1.93 g, 5.0 mmol); white granule; mp 146−147 °C
1
(hexane−EtOAc); H NMR (500 MHz, CDCl3) δ 3.69 (3H, s), 3.86
(3H, s), 6.45 (1H, s), 6.91 (1H, s), 7.07 (1H, s), 7.62 (1H, t, J = 8.3
Hz), 7.69−7.72 (2H, m), 7.88 (1H, d, J = 8.3 Hz), 8.02 (1H, d, J = 8.3
Hz), 8.63 (1H, d, J = 8.3 Hz); 13C NMR (125 MHz, CDCl3) δ 41.8,
55.9, 56.1, 112.4, 113.5, 115.3, 118.1, 121.5, 123.9, 125.6, 126.0, 127.7,
128.3, 130.5, 136.7, 141.9, 149.1, 149.9, 153.5; IR (KBr) 2243 cm−1;
ESIMS m/z (rel int) 383 (100, [M + 1]+), 385 (97, [M + 3]+). Anal.
Calcd for C19H15BrN2O2: C, 59.55; H, 3.95; N, 7.31. Found: C, 59.64;
H, 4.07; N, 7.07.
1-Iodoisoquinoline (10A): yield 90% (2.30 g, 9.0 mmol); white
crystal; mp 70.5−71 °C (hexane−EtOAc) (lit.43 mp 72−74 °C); H
1
NMR (500 MHz, CDCl3) δ 7.58 (1H, d, J = 5.6 Hz), 7.67−7.76 (3H,
m), 8.12 (1H, d, J = 8.7 Hz), 8.26 (1H, d, J = 5.6 Hz); 13C NMR (125
MHz, CDCl3) δ 121.3, 127.3, 127.5, 129.0, 131.1, 132.0, 132.9, 136.2,
143.1; IR (KBr) 1612, 1578, 1541 cm−1; EIMS m/z (rel int) 128
(100), 255 (64, M+). Anal. Calcd for C9H6IN: C, 42.38; H, 2.37; N,
5.49. Found: C, 42.65; H, 2.37; N, 5.34.
1-Iodo-5-methoxyisoquinoline (10B): yield 88% (2.51 g, 8.8
mmol); white needle; mp 115.5−116 °C (hexane−EtOAc); 1H
NMR (500 MHz, CDCl3) δ 4.02 (3H, s), 7.05 (1H, d, J = 8.2 Hz),
7.57 (1H, t, J = 8.2 Hz), 7.68 (1H, d, J = 8.2 Hz), 7.98 (1H, d, J = 5.6
Hz), 8.24 (1H, d, J = 5.6 Hz); 13C NMR (125 MHz, CDCl3) δ 55.9,
108.2, 110.0, 115.7, 124.5, 126.6, 128.7, 132.6, 142.6, 154.5; IR (KBr)
1578, 1483 cm−1; EIMS m/z (rel int) 285 (100, M+). Anal. Calcd for
C10H8INO: C, 42.13; H, 2.83; N, 4.91. Found: C, 41.77; H, 3.05; N,
4.53.
(2-Bromo-4,5-methylenedioxyphenyl)isoquinolin-1-ylacetonitrile
(12c): yield 76% (1.95 g, 5.3 mmol); white granule; mp168−169 °C
1
(hexane−EtOAc); H NMR (500 MHz, CDCl3) δ 5.89 (1H, s), 5.95
(1H, s), 6.43 (1H, s), 6.81 (1H, s), 7.06 (1H, s), 7.60 (1H, t, J = 8.2
Hz), 7.68−7.71 (2H, m), 7.87 (1H, d, J = 8.2 Hz), 7.93 (1H, d, J = 8.2
Hz), 8.62 (1H, d, J = 5.7 Hz); 13C NMR (125 MHz, CDCl3) δ 42.2,
102.2, 109.8, 112.8, 114.2, 117.9, 121.6, 123.8, 125.6, 127.3, 127.8,
128.4, 130.5, 136.8, 142.0, 148.1, 148.8, 153.3; IR (KBr) 2251 cm−1;
ESIMS m/z (rel int) 367 (100, [M + 1]+), 369 (98, [M + 3]+) ;
HRESIMS m/z calcd for C18H12BrN2O2 367.0077, found 367.0079
[M + 1]+.
1-Iodo-5,6-dimethoxyisoquinoline (10C): yield 87% (2.74 g, 8.7
1
mmol); white needle; mp 91−91.5 °C (hexane−EtOAc); H NMR
(2-Bromo-5-trifluoromethylphenyl)isoquinolin-1-ylacetonitrile
(500 MHz, CDCl3) δ 3.98 (3H, s), 4.04 (3H, s), 7.42 (1H, d, J = 9.3
Hz), 7.82 (1H, d, J = 5.8 Hz), 7.88 (1H, d, J = 9.3 Hz), 8.15 (1H, d, J
= 5.8 Hz); 13C NMR (125 MHz, CDCl3) δ 56.5, 61.3, 115.0, 116.3,
126.9, 127.4, 129.8, 131.9, 141.3, 142.6, 151.9; IR (KBr) 1614, 1580,
1551, 1476 cm−1; EIMS m/z (rel int) 315 (100, M+). Anal. Calcd for
C11H10INO2: C, 41.93; H, 3.20; N, 4.45. Found: C, 42.05; H, 3.60; N,
4.36.
(12d): yield 89% (2.44 g, 6.2 mmol); pale yellow needle; mp 147−148
1
°C (hexane−EtOAc); H NMR (500 MHz, CDCl3) δ 6.54 (1H, s),
7.48 (1H, dd, J = 8.3, 1.9 Hz), 7.67 (1H, t, J = 8.3 Hz), 7.71−7.81 (4H,
m), 7.92 (1H, d, J = 8.3 Hz), 8.03 (1H, d, J = 8.3 Hz), 8.58 (1H, d, J =
5.7 Hz); 13C NMR (125 MHz, CDCl3) δ 41.7, 117.3, 121.9, 123.2 (q, J
= 271 Hz), 123.4, 125.7, 126.9 (q, J = 4 Hz), 127.4, 127.5 (q, J = 4
Hz), 128.0, 128.6, 130.7, 130.8 (q, J = 33 Hz), 133.8, 135.4, 136.8,
142.1, 152.0; IR (KBr) 2245 cm−1; ESIMS m/z (rel int) 391 (100, [M
+ 1]+), 393 (97, [M + 3]+). Anal. Calcd for C18H10BrF3N2: C, 55.27;
H, 2.58; N, 7.16. Found: C, 55.21; H, 2.66; N, 7.19.
1-Iodo-7-methoxyisoquinoline (10D): yield 84% (2.39 g, 8.4
1
mmol); white needle; mp 86.5−87 °C (hexane−EtOAc); H NMR
(500 MHz, CDCl3) δ 4.00 (3H, s), 7.35−7.37 (2H, m), 7.51 (1H, d, J
= 5.4 Hz), 7.65 (1H, d, J = 8.8 Hz), 8.16 (1H, d, J = 5.4 Hz); 13C
NMR (125 MHz, CDCl3) δ 55.6, 110.5, 121.1, 124.1, 125.8, 128.9,
131.7, 133.3, 141.3, 159.8; IR (KBr) 1622, 1580, 1547, 1499 cm−1;
EIMS m/z (rel int) 158 (100), 285 (31, M+); HREIMS m/z calcd for
C10H8INO 284.9651, found 284.9641 [M]+.
(2-Bromophenyl)(5-methoxyisoquinolin-1-yl)acetonitrile (12e):
yield 76% (1.88 g, 5.3 mmol); white granule; mp 146−147 °C
1
(hexane−EtOAc); H NMR (500 MHz, CDCl3) δ 4.00 (3H, s), 6.46
(1H, s), 6.99 (1H, t, J = 7.8 Hz), 7.19 (1H, t, J = 7.8 Hz), 7.25 (1H, t, J
= 7.8 Hz), 7.37 (1H, d, J = 7.8 Hz), 7.49−7.50 (2H, m), 7.63 (1H, d, J
= 7.8 Hz), 8.09 (1H, d, J = 5.8 Hz), 8.59 (1H, d, J = 5.8 Hz); 13C
NMR (125 MHz, CDCl3) δ 42.5, 55.7, 107.7, 115.4, 115.9, 117.8,
123.6, 126.5, 128.2, 128.5, 129.5, 130.2, 130.4, 133.2, 134.4, 141.6,
152.4, 155.2; IR (KBr) 2245 cm−1; ESIMS m/z (rel int) 353 (100, [M
+ 1]+), 355 (93, [M + 3]+). Anal. Calcd for C18H13BrN2O: C, 61.21;
H, 3.71; N, 7.93. Found: C, 61.40; H, 3.98; N, 8.04.
1-Iodo-6,7-(methylenedioxy)isoquinoline (10E): yield 75% (2.24 g,
7.5 mmol); white needle; mp 181−182 °C (hexane−EtOAc); 1H
NMR (500 MHz, CDCl3) δ 6.14 (2H, s), 6.99 (1H, s), 7.41 (1H, d, J
= 5.5 Hz), 7.46 (1H, s), 8.10 (1H, d, J = 5.5 Hz); 13C NMR (125
MHz, CDCl3) δ 102.1, 102.8, 109.1, 120.8, 124.7, 129.6, 134.5, 142.1,
149.7, 151.4; IR (KBr) 1576, 1458, 1404 cm−1; EIMS m/z (rel int)
172 (100), 299 (80, M+). Anal. Calcd for C10H6INO2: C, 40.16; H,
2.02; N, 4.68. Found: C, 40.28; H, 2.14; N, 4.62.
(2-Bromo-4,5-dimethoxyphenyl)(5-methoxyisoquinolin-1-yl)-
acetonitrile (12f): yield 85% (2.46 g, 6.0 mmol); white needle; mp
General Procedure for the Preparation of (2-Bromophenyl)-
isoquinolin-1-yl-acetonitrile 12. Sodium amide (43.8 mmol) was
added to a mixture of the 1-iodoisoquinolines 10 (7.0 mmol) and (2-
bromophenyl)acetonitriles 11 (8.8 mmol) in tetrahydrofuran (100
mL) while being stirred and cooled in an ice bath. The reaction
mixture was then refluxed overnight under N2. After cooling, the
resulting solution was quenched with water (50 mL) and extracted
with EtOAc (3 × 100 mL). The combined extracts were washed with
water, dried with anhydrous MgSO4, filtered, and evaporated under
reduced pressure. The residue was purified by column chromatog-
raphy over silica gel eluting with hexane−EtOAc (5:1) to give the pure
(2-bromophenyl)isoquinolin-1-yl-acetonitriles 12. The full spectral
data of 12a−t are described as follows.
1
144−145 °C (hexane−EtOAc); H NMR (500 MHz, CDCl3) δ 3.67
(3H, s), 3.85 (3H, s), 4.01 (3H, s), 6.40 (1H, s), 6.88 (1H, s), 7.00
(1H, d, J = 7.4 Hz), 7.06 (1H, s), 7.49−7.55 (2H, m), 8.09 (1H, d, J =
5.8 Hz), 8.62 (1H, d, J = 5.8 Hz); 13C NMR (125 MHz, CDCl3) δ
42.1, 55.7, 56.0, 56.2, 107.7, 112.4, 113.6, 115.4, 115.5, 115.9, 118.2,
126.2, 126.4, 128.5, 129.5, 141.5, 149.1, 149.9, 152.9, 155.2; IR (KBr)
2245 cm−1; ESIMS m/z (rel int) 413 (100, [M + 1]+), 415 (92, [M +
3]+). Anal. Calcd for C20H17BrN2O3: C, 58.13; H, 4.15; N, 6.78.
Found: C, 58.12; H, 4.16; N, 6.90.
(2-Bromo-4,5-methylenedioxyphenyl)(5-methoxyisoquinolin-1-
yl)acetonitrile (12g): yield 95% (2.64 g, 6.7 mmol); white crystal; mp
1
170−171 °C (hexane−EtOAc); H NMR (500 MHz, CDCl3) δ 4.01
(3H, s), 5.90 (1H, d, J = 1.3 Hz), 5.95 (1H, d, J = 1.3 Hz), 6.39 (1H,
s), 6.80 (1H, s), 7.00 (1H, d, J = 6.7 Hz), 7.06 (1H, s), 7.46−7.52 (2H,
m), 8.09 (1H, d, J = 5.8 Hz), 8.61 (1H, d, J = 5.8 Hz); 13C NMR (125
MHz, CDCl3) δ 42.5, 55.8, 102.2, 107.7, 109.8, 112.8, 114.3, 115.4,
(2-Bromophenyl)isoquinolin-1-ylacetonitrile (12a): Yield 97%
(2.19 g, 6.8 mmol); white needle; mp 160−161 °C (hexane−
EtOAc) (lit.44 mp 152.5 °C); H NMR (500 MHz, CDCl3) δ 6.52
1
(1H, s), 7.21 (1H, td, J = 7.8, 1.7 Hz), 7.27 (1H, td, J = 7.8, 1.7 Hz),
4978
dx.doi.org/10.1021/jo400645g | J. Org. Chem. 2013, 78, 4974−4984

The Journal of Organic Chemistry
Article
116.0, 117.9, 126.4, 127.5, 128.5, 129.6, 141.6, 148.1, 148.8, 152.6,
155.3; IR (KBr) 2249 cm−1; ESIMS m/z (rel int) 397 (100, [M + 1]+),
399 (94, [M + 3]+). Anal. Calcd for C19H13BrN2O3: C, 57.45; H, 3.30;
N, 7.05. Found: C, 57.71; H, 3.33; N, 7.03.
134.5, 140.3, 151.6, 159.0; IR (KBr) 2249 cm−1; ESIMS m/z (rel int)
353 (100, [M + 1]+), 355 (97, [M + 3]+). Anal. Calcd for
C18H13BrN2O: C, 61.21; H, 3.71; N, 7.93. Found: C, 61.25; H,
4.03; N, 8.06.
(2-Bromo-5-trifluoromethylphenyl)(5-methoxyisoquinolin-1-yl)-
(2-Bromo-4,5-dimethoxyphenyl)(7-methoxyisoquinolin-1-yl)-
acetonitrile (12h): yield 75% (2.21 g, 5.3 mmol); white needle; mp
acetonitrile (12n): yield 100% (2.89 g, 7.0 mmol); white granule; mp
1
1
145−146 °C (hexane−EtOAc); H NMR (500 MHz, CDCl3) δ 4.01
148−149 °C (hexane−EtOAc); H NMR (500 MHz, CDCl3) δ 3.67
(3H, s), 6.48 (1H, s), 7.02 (1H, dd, J = 6.6, 1.8 Hz), 7.46 (1H, dd, J =
8.4, 1.6 Hz), 7.52−7.56 (2H, m), 7.75−7.77 (2H, m), 8.11 (1H, d, J =
5.8 Hz), 8.56 (1H, d, J = 5.8 Hz); 13C NMR (125 MHz, CDCl3) δ
42.0, 55.8, 107.9, 115.0, 116.3, 117.3, 123.3 (q, J = 271 Hz), 126.5,
126.9 (q, J = 3 Hz), 127.4, 127.5 (q, J = 3 Hz), 128.8, 129.7, 130.8 (q, J
= 33 Hz), 133.8, 135.5, 141.7, 151.4, 155.4; IR (KBr) 2247 cm−1;
ESIMS m/z (rel int) 421 (100, [M + 1]+), 423 (93, [M + 3]+). Anal.
Calcd for C19H12BrF3N2O: C, 54.18; H, 2.87; N, 6.65. Found: C,
54.36; H, 2.92; N, 6.78.
(3H, s), 3.86 (3H, s), 3.91 (3H, s), 6.39 (1H, s), 6.90 (1H, s), 7.06
(1H, s), 7.18 (1H, s), 7.33 (1H, d, J = 9.0 Hz), 7.62 (1H, d, J = 5.6
Hz), 7.76 (1H, d, J = 9.0 Hz), 8.54 (1H, d, J = 5.6 Hz); 13C NMR (125
MHz, CDCl3) δ 42.1, 55.7, 55.9, 56.1, 101.5, 112.1, 113.4, 115.1,
118.1, 121.2, 123.7, 126.1, 126.7, 129.2, 132.3, 140.1, 149.3, 150.0,
151.9, 159.0; IR (KBr) 2245 cm−1; ESIMS m/z (rel int) 413 (100, [M
+ 1]+), 415 (97, [M + 3]+). Anal. Calcd for C20H17BrN2O3: C, 58.13;
H, 4.15; N, 6.78. Found: C, 58.08; H, 4.19; N, 6.69.
(2-Bromo-4,5-methylenedioxyphenyl)(7-methoxyisoquinolin-1-
yl)acetonitrile (12o): yield 84% (2.33 g, 5.9 mmol); white crystal; mp
(2-Bromophenyl)(5,6-dimethoxyisoquinolin-1-yl)acetonitrile
1
(12i): yield 91% (2.44 g, 6.4 mmol); white granule; mp 196−197 °C
205−207 °C (hexane−EtOAc); H NMR (500 MHz, CDCl3) δ 3.89
1
(hexane−EtOAc); H NMR (500 MHz, CDCl3) δ 3.99 (3H, s), 4.00
(3H, s), 5.90 (1H, d, J = 1.1 Hz), 5.96 (1H, d, J = 1.1 Hz), 6.38 (1H,
s), 6.83 (1H, s), 7.07 (1H, s), 7.10 (1H, d, J = 2.2 Hz), 7.32 (1H, dd, J
= 9.0, 2.2 Hz), 7.62 (1H, d, J = 5.6 Hz), 7.76 (1H, d, J = 9.0 Hz), 8.53
(1H, d, J = 5.6 Hz); 13C NMR (125 MHz, CDCl3) δ 42.5, 55.8, 101.5,
102.3, 109.7, 112.5, 114.1, 117.9, 121.3, 123.8, 126.7, 127.5, 129.3,
132.4, 140.3, 148.3, 149.0, 151.8, 159.1; IR (KBr) 2249 cm−1; ESIMS
m/z (rel int) 397 (100, [M + 1]+), 399 (90, [M + 3]+). Anal. Calcd for
C19H13BrN2O3: C, 57.45; H, 3.30; N, 7.05. Found: C, 57.66; H, 3.58;
N, 7.02.
(3H, s), 6.44 (1H, s), 7.19 (1H, td, J = 7.9, 1.6 Hz), 7.26 (1H, td, J =
7.9, 1.1 Hz), 7.36 (1H, d, J = 9.3 Hz), 7.40 (1H, dd, J = 7.9, 1.6 Hz),
7.64 (1H, dd, J = 7.9, 1.1 Hz), 7.73 (1H, d, J = 9.3 Hz), 7.94 (1H, d, J
= 6.0 Hz), 8.52 (1H, d, J = 6.0 Hz); 13C NMR (125 MHz, CDCl3) δ
42.4, 56.5, 61.3, 115.3, 116.3, 117.8, 120.7, 121.5, 123.5, 128.3, 130.2,
130.5, 133.0, 133.2, 134.4, 141.9, 142.2, 151.4, 152.9; IR (KBr) 2245
cm−1; ESIMS m/z (rel int) 383 (100, [M + 1]+), 385 (97, [M + 3]+).
Anal. Calcd for C19H15BrN2O2: C, 59.55; H, 3.95; N, 7.31. Found: C,
59.60; H, 3.90; N, 7.39.
(2-Bromo-5-trifluoromethylphenyl)(7-methoxyisoquinolin-1-yl)-
acetonitrile (12p): yield 80% (2.36 g, 5.6 mmol); white needle; mp
(2-Bromo-4,5-dimethoxyphenyl)(5,6-dimethoxyisoquinolin-1-yl)-
1
acetonitrile (12j): yield 100% (3.10 g, 7.0 mmol); white needle; mp
164−165 °C (hexane−EtOAc); H NMR (500 MHz, CDCl3) δ 3.92
1
122−123 °C (hexane−EtOAc); H NMR (500 MHz, CDCl3) δ 3.69
(3H, s), 6.46 (1H, s), 7.16 (1H, s), 7.37 (1H, d, J = 9.0 Hz), 7.47 (1H,
d, J = 8.4 Hz), 7.64 (1H, d, J = 5.5 Hz), 7.78−7.80 (2H, m), 7.82 (1H,
s), 8.50 (1H, d, J = 5.5 Hz); 13C NMR (125 MHz, CDCl3) δ 42.0,
55.7, 101.2, 117.3, 121.6, 123.2 (q, J = 271 Hz), 123.8, 126.9, 127.0 (q,
J = 3 Hz), 127.4, 127.6 (q, J = 4 Hz), 129.6, 131.1 (q, J = 33 Hz),
132.5, 133.8, 135.6, 140.5, 150.5, 159.3; IR (KBr) 2249 cm−1; ESIMS
m/z (rel int) 421 (100, [M + 1]+), 423 (93, [M + 3]+). Anal. Calcd for
C19H12BrF3N2O: C, 54.18; H, 2.87; N, 6.65. Found: C, 54.17; H, 3.16;
N, 6.85.
(3H, s), 3.85 (3H, s), 3.99 (3H, s), 4.01 (3H, s), 6.38 (1H, s), 6.91
(1H, s), 7.06 (1H, s), 7.37 (1H, d, J = 9.3 Hz), 7.79 (1H, d, J = 9.3
Hz), 7.95 (1H, d, J = 5.9 Hz), 8.54 (1H, d, J = 5.9 Hz); 13C NMR (125
MHz, CDCl3) δ 42.0, 56.0, 56.2, 56.4, 61.3, 112.3, 113.4, 115.3 (2 ×
C), 116.3, 118.2, 120.8, 121.4, 126.2, 132.9, 141.8, 142.1, 149.1, 149.9,
151.4, 153.3; IR (KBr) 2245 cm−1; ESIMS m/z (rel int) 443 (100, [M
+ 1]+), 445 (100, [M + 3]+). Anal. Calcd for C21H19BrN2O4: C, 56.90;
H, 4.32; N, 6.32. Found: C, 56.70; H, 3.98; N, 6.02.
(2-Bromo-4,5-methylenedioxyphenyl)(5,6-dimethoxyisoquinolin-
(2-Bromophenyl)(6,7-methylenedioxyisoquinolin-1-yl)acetonitrile
1-yl)acetonitrile (12k): yield 97% (2.90 g, 6.8 mmol); white granule;
(12q): yield 92% (2.36 g, 6.4 mmol); white granule; mp 229−230 °C
1
1
mp 147−148 °C (hexane−EtOAc); H NMR (500 MHz, CDCl3) δ
(hexane−EtOAc); H NMR (500 MHz, CDCl3) δ 6.07 (1H, s), 6.11
3.99 (3H, s), 4.00 (3H, s), 5.90 (1H, s), 5.95 (1H, s), 6.37 (1H, s),
6.82 (1H, s), 7.06 (1H, s), 7.36 (1H, d, J = 9.3 Hz), 7.70 (1H, d, J =
9.3 Hz), 7.94 (1H, d, J = 5.9 Hz), 8.53 (1H, d, J = 5.9 Hz); 13C NMR
(125 MHz, CDCl3) δ 42.3, 56.4, 61.2, 102.2, 109.7, 112.7, 114.1,
115.3, 116.3, 117.9, 120.7, 121.3, 127.4, 132.9, 141.8, 142.1, 148.1,
148.8, 151.4, 153.0; IR (KBr) 2239 cm−1; ESIMS m/z (rel int) 427
(100, [M + 1]+), 429 (96, [M + 3]+). Anal. Calcd for C20H15BrN2O4:
C, 56.22; H, 3.54; N, 6.56. Found: C, 56.47; H, 3.50; N, 6.55.
(2-Bromo-5-trifluoromethylphenyl)(5,6-dimethoxyisoquinolin-1-
yl)acetonitrile (12l): yield 93% (2.94 g, 6.5 mmol); pale yellow needle;
(1H, s), 6.28 (1H, s), 7.10 (1H, s), 7.18 (1H, s), 7.20 (1H, t, J = 7.9
Hz), 7.25−7.28 (1H, m), 7.40 (1H, d, J = 7.9 Hz), 7.51 (1H, d, J = 5.6
Hz), 7.64 (1H, d, J = 7.9 Hz), 8.45 (1H, d, J = 5.6 Hz); 13C NMR (125
MHz, CDCl3) δ 42.5, 99.9, 101.9, 103.5, 117.8, 121.0, 123.1, 123.6,
128.3, 130.2, 130.5, 133.2, 134.3, 135.5, 141.4, 149.3, 150.9, 151.1; IR
(KBr) 2241 cm−1; ESIMS m/z (rel int) 367 (100, [M + 1]+), 369 (95,
[M + 3]+). Anal. Calcd for C18H11BrN2O2: C, 58.88; H, 3.02; N, 7.63.
Found: C, 58.60; H, 3.14; N, 7.42.
(2-Bromo-4,5-dimethoxyphenyl)(6,7-methylenedioxyisoquinolin-
1-yl)acetonitrile (12r): yield 87% (2.60 g, 6.1 mmol); white needle;
1
1
mp 161−162 °C (hexane−EtOAc); H NMR (500 MHz, CDCl3) δ
mp 192−193 °C (hexane−EtOAc); H NMR (500 MHz, CDCl3) δ
4.01 (3H, s), 4.03 (3H, s), 6.46 (1H, s), 7.42 (1H, d, J = 9.3 Hz), 7.47
(1H, d, J = 8.4 Hz), 7.76−7.81 (3H, m), 7.97 (1H, d, J = 5.9 Hz), 8.47
(1H, d, J = 5.9 Hz); 13C NMR (125 MHz, CDCl3) δ 41.8, 56.5, 61.3,
115.6, 116.6, 117.3, 120.2, 121.6, 123.2 (q, J = 271 Hz), 126.9 (q, J = 3
Hz), 127.4, 127.6 (q, J = 4 Hz), 130.9 (q, J = 33 Hz), 133.1, 133.8,
135.4, 142.0, 142.3, 151.5, 151.8; IR (KBr) 2245 cm−1; ESIMS m/z
(rel int) 451 (100, [M + 1]+), 453 (96, [M + 3]+). Anal. Calcd for
C20H14BrF3N2O2: C, 53.23; H, 3.13; N, 6.21. Found: C, 52.90; H,
2.99; N, 6.20.
3.68 (3H, s), 3.86 (3H, s), 6.07 (1H, s), 6.11 (1H, s), 6.21 (1H, s),
6.88 (1H, s), 7.06 (1H, s), 7.09 (1H, s), 7.21 (1H, s), 7.50 (1H, d, J =
5.6 Hz), 8.47 (1H, d, J = 5.6 Hz); 13C NMR (125 MHz, CDCl3) δ
42.1, 56.0, 56.2, 100.0, 101.9, 103.4, 112.3, 113.6, 115.4, 118.2, 121.0,
122.9, 126.1, 135.5, 141.3, 149.1, 149.3, 150.0, 150.9, 151.5; IR (KBr)
2245 cm−1; ESIMS m/z (rel int) 427 (100, [M + 1]+), 429 (94, [M +
3]+). Anal. Calcd for C20H15BrN2O4: C, 56.22; H, 3.54; N, 6.56.
Found: C, 56.43; H, 3.66; N, 6.31.
(2-Bromo-4,5-methylenedioxyphenyl)(6,7-methylenedioxyisoqui-
(2-Bromophenyl)(7-methoxyisoquinolin-1-yl)acetonitrile (12m):
nolin-1-yl)acetonitrile (12s): yield 97% (2.79 g, 6.8 mmol); white
1
yield 74% (1.83 g, 5.2 mmol); white granule; mp 156−157 °C
granule; mp 233−235 °C (hexane−EtOAc); H NMR (500 MHz,
1
(hexane−EtOAc); H NMR (500 MHz, CDCl3) δ 3.87 (3H, s), 6.45
CDCl3) δ 5.91 (1H, d, J = 1.2 Hz), 5.96 (1H, d, J = 1.2 Hz), 6.08 (1H,
d, J = 0.7 Hz), 6.11 (1H, d, J = 0.7 Hz), 6.20 (1H, s), 6.80 (1H, s),
7.06 (1H, s), 7.10 (1H, s), 7.14 (1H, s), 7.51 (1H, d, J = 5.6 Hz), 8.46
(1H, d, J = 5.6 Hz); 13C NMR (125 MHz, CDCl3) δ 42.5, 99.9, 101.9,
102.2, 103.5, 109.7, 112.8, 114.2, 117.9, 121.1, 122.9, 127.3, 135.5,
141.4, 148.1, 148.9, 149.3, 150.9, 151.3; IR (KBr) 2245 cm−1; ESIMS
(1H, s), 7.10 (1H, s), 7.19 (1H, t, J = 7.9 Hz), 7.24 (1H, t, J = 7.9 Hz),
7.32 (1H, d, J = 9.0 Hz), 7.41 (1H, d, J = 7.9 Hz), 7.61 (1H, d, J = 5.6
Hz), 7.65 (1H, d, J = 7.9 Hz), 7.75 (1H, d, J = 9.0 Hz), 8.52 (1H, d, J
= 5.6 Hz); 13C NMR (125 MHz, CDCl3) δ 42.5, 55.7, 101.6, 117.9,
121.3, 123.5, 123.7, 126.8, 128.6, 129.3, 130.3, 130.5, 132.4, 133.1,
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m/z (rel int) 411 (100, [M + 1]+), 413 (93, [M + 3]+); HRESIMS m/
z calcd for C19H12BrN2O4 410.9975, found 410.9977 [M + 1]+.
(2-Bromo-5-trifluoromethylphenyl)(6,7-methylenedioxyisoquino-
lin-1-yl)acetonitrile (12t): yield 91% (2.77 g, 6.4 mmol); white
3]+); HREIMS m/z calcd for C17H10BrF3NO 379.9892, found
379.9883 [M + 1]+.
(2-Bromophenyl)(5-methoxyisoquinolin-1-yl)methanone (13e):
yield 94% (643 mg, 1.88 mmol); pale yellow granule; mp 141−142
1
1
granule; mp 226−228 °C (hexane−EtOAc); H NMR (500 MHz,
°C (hexane−EtOAc); H NMR (500 MHz, CDCl3) δ 4.04 (3H, s),
CDCl3) δ 6.10 (1H, s), 6.13 (1H, s), 6.29 (1H, s), 7.13 (1H, s), 7.22
(1H, s), 7.47 (1H, dd, J = 8.4, 1.5 Hz), 7.52 (1H, d, J = 5.6 Hz), 7.76−
7.78 (2H, m), 8.41 (1H, d, J = 5.6 Hz); 13C NMR (125 MHz, CDCl3)
δ 42.0, 99.5, 102.1, 103.7, 117.3, 121.4, 123.1, 123.3 (q, J = 271 Hz),
126.9 (q, J = 4 Hz), 127.4, 127.5 (q, J = 4 Hz), 130.9 (q, J = 33 Hz),
133.8, 135.5, 135.6, 141.6, 149.6, 150.0, 151.1; IR (KBr) 2243 cm−1;
ESIMS m/z (rel int) 435 (100, [M + 1]+), 437 (96, [M + 3]+). Anal.
Calcd for C19H10BrF3N2O2: C, 52.44; H, 2.32; N, 6.44. Found: C,
52.23; H, 2.27; N, 6.66.
7.06 (1H, d, J = 8.0 Hz), 7.36 (1H, td, J = 8.0, 1.7 Hz), 7.45 (1H, td, J
= 8.0, 1.0 Hz), 7.58 (1H, dd, J = 8.0, 1.0 Hz), 7.63 (1H, t, J = 8.0 Hz),
7.65 (1H, dd, J = 8.0, 1.7 Hz), 8.22 (1H, d, J = 5.7 Hz), 8.33 (1H, d, J
= 8.0 Hz), 8.52 (1H, d, J = 5.7 Hz); 13C NMR (125 MHz, CDCl3) δ
55.6, 107.6, 117.9, 118.4, 120.5, 127.2, 127.4, 129.1, 129.7, 130.9,
131.9, 133.0, 140.8, 141.3, 153.2, 154.5, 196.6; IR (KBr) 1682 cm−1;
ESIMS m/z (rel int) 342 (100, [M + 1]+), 344 (90, [M + 3]+). Anal.
Calcd for C17H12BrNO2: C, 59.67; H, 3.53; N, 4.09. Found: C, 59.35;
H, 3.28; N, 3.75.
(2-Bromo-4,5-dimethoxyphenyl)(5-methoxyisoquinolin-1-yl)-
methanone (13f): yield 84% (675 mg, 1.68 mmol); pale yellow
crystal; mp 153−154 °C (hexane−EtOAc); 1H NMR (500 MHz,
CDCl3) δ 3.92 (6H, s), 4.04 (3H, s), 7.01 (1H, s), 7.05 (1H, d, J = 8.2
Hz), 7.33 (1H, s), 7.59 (1H, t, J = 8.2 Hz), 8.09 (1H, d, J = 8.2 Hz),
8.20 (1H, d, J = 5.7 Hz), 8.53 (1H, d, J = 5.7 Hz); 13C NMR (125
MHz, CDCl3) δ 55.7, 56.1, 56.3, 107.7, 113.6, 114.1, 116.0, 117.8,
118.0, 127.4, 128.8, 129.7, 132.5, 141.0, 148.4, 152.2, 154.6, 154.8,
195.6; IR (KBr) 1678 cm−1; ESIMS m/z (rel int) 424 (100, [M + 1]+),
426 (99, [M + 3]+); HRESIMS m/z calcd for C19H16BrNO4Na
424.0160, found 424.0163 [M + Na]+.
(2-Bromo-4,5-methylenedioxyphenyl)(5-methoxyisoquinolin-1-
yl)methanone (13g): yield 67% (517 mg, 1.34 mmol); pale yellow
crystal, mp 153−154 °C (hexane−EtOAc). 1H NMR (500 MHz,
CDCl3) δ 4.03 (3H, s), 6.05 (2H, s), 7.01 (1H, s), 7.04 (1H, d, J = 8.4
Hz), 7.17 (1H, s), 7.59 (1H, t, J = 8.4 Hz), 8.15 (1H, d, J = 8.4 Hz),
8.20 (1H, d, J = 5.7 Hz), 8.52 (1H, d, J = 5.7 Hz); 13C NMR (125
MHz, CDCl3) δ 55.7, 102.4, 107.7, 111.3, 113.5, 113.9, 118.0, 118.1,
127.5, 128.9, 129.8, 134.1, 141.0, 147.5, 150.9, 154.3, 154.6, 195.4; IR
(KBr) 1668 cm−1; ESIMS m/z (rel int) 386 (100, [M + 1]+), 388 (97,
[M + 3]+). Anal. Calcd for C18H12BrNO4: C, 55.98; H, 3.13; N, 3.63.
Found: C, 56.28; H, 3.52; N, 3.76.
(2-Bromo-5-trifluoromethylphenyl)(5-methoxyisoquinolin-1-yl)-
methanone (13h): yield 55% (410 mg, 1.10 mmol); pale yellow
crystal; mp 137−138 °C (hexane−EtOAc); 1H NMR (500 MHz,
CDCl3) δ 4.05 (3H, s), 7.08 (1H, d, J = 8.3 Hz), 7.59 (1H, dd, J = 8.3,
1.7 Hz), 7.76 (1H, t, J = 8.3 Hz), 7.71 (1H, d, J = 8.3 Hz), 7.87 (1H, d,
J = 1.7 Hz), 8.27 (1H, d, J = 5.6 Hz), 8.44 (1H, d, J = 8.3 Hz), 8.52
(1H, d, J = 5.6 Hz); 13C NMR (125 MHz, CDCl3) δ 55.8, 107.8,
117.8, 119.2, 123.7 (q, J = 271 Hz), 124.3, 127.5 (q, J = 4 Hz), 127.6,
128.1 (q, J = 3 Hz), 129.7, 129.9 (q, J = 33 Hz), 130.0, 133.7, 141.0,
142.6, 151.8, 154.7, 195.6; IR (KBr) 1682 cm−1; ESIMS m/z (rel int)
410 (100, [M + 1]+), 412 (96, [M + 3]+). Anal. Calcd for
C18H11BrF3NO2: C, 52.71; H, 2.70; N, 3.41. Found: C, 52.70; H,
2.90; N, 3.40.
General Procedure for the Preparation of (2-Bromophenyl)-
isoquinolin-1-ylmethanone 13. A solution of nitriles 12 (2.00
mmol) in tetrahydrofuran (30 mL) was added to sodium hydride
(60% dispersion in oil, 120 mg, 3.00 mmol), which had been washed
with hexane, and the mixture was stirred at room temperature for 1 h.
Then, a slow stream of oxygen gas was passed through the mixture for
3 h. The resulting solution was quenched with water (30 mL) and
extracted with EtOAc (3 × 60 mL). The combined extracts were
washed with water, dried with anhydrous MgSO4, filtered, and
evaporated under reduced pressure. The residue was purified by
column chromatography over silica gel eluting with hexane−EtOAc
(5:1) to give the pure (2-bromophenyl)isoquinolin-1-ylmethanones
13. The full spectral data of 13a−t are described as follows.
(2-Bromophenyl)isoquinolin-1-ylmethanone (13a): yield 95%
(593 mg, 1.90 mmol); pale yellow crystal; mp 103−104 °C
1
(hexane−EtOAc); H NMR (500 MHz, CDCl3) δ 7.37 (1H, t, J =
7.8 Hz), 7.46 (1H, t, J = 7.8 Hz), 7.59 (1H, d, J = 7.8 Hz), 7.66 (1H, d,
J = 7.8 Hz), 7.72−7.78 (2H, m), 7.81 (1H, d, J = 5.5 Hz), 7.91 (1H, d,
J = 8.2 Hz), 8.53 (1H, d, J = 5.5 Hz), 8.79 (1H, d, J = 8.2 Hz); 13C
NMR (125 MHz, CDCl3) δ 120.6, 124.0, 126.5, 126.8, 127.1, 127.3,
129.0, 130.6, 131.0, 132.1, 133.2, 137.0, 141.3, 141.4, 154.0, 196.7; IR
(KBr) 1667 cm−1; ESIMS m/z (rel int) 312 (100, [M + 1]+), 314 (94,
[M + 3]+); HRESIMS m/z calcd for C16H11BrNO 312.00185, found
312.00183 [M + 1]+.
(2-Bromo-4,5-dimethoxyphenyl)isoquinolin-1-ylmethanone
(13b): yield 96% (714 mg, 1.92 mmol); pale yellow crystal; mp 109.5−
1
110 °C (hexane−EtOAc); H NMR (500 MHz, CDCl3) δ 3.92 (3H,
s), 3.93 (3H, s), 7.02 (1H, s), 7.34 (1H, s), 7.71 (1H, t, J = 8.2 Hz),
7.76 (1H, t, J = 8.2 Hz), 7.80 (1H, d, J = 5.6 Hz), 7.91 (1H, d, J = 8.2
Hz), 8.54 (1H, d, J = 5.6 Hz), 8.55 (1H, d, J = 8.2 Hz); 13C NMR (125
MHz, CDCl3) δ 56.1, 56.3, 113.6, 114.0, 115.9, 123.4, 126.4, 126.7,
127.0, 128.7, 130.5, 132.4, 136.8, 141.3, 148.4, 152.2, 155.4, 195.5; IR
(KBr) 1680 cm−1; ESIMS m/z (rel int) 372 (100, [M + 1]+), 374 (95,
[M + 3]+); HRESIMS m/z calcd for C18H15BrNO3 372.0230, found
372.0240 [M + 1]+.
(2-Bromophenyl)(5,6-dimethoxyisoquinolin-1-yl)methanone
(2-Bromo-4,5-methylenedioxyphenyl)isoquinolin-1-ylmethanone
(13c): yield 81% (577 mg, 1.62 mmol); white granule; mp 131−132
°C (hexane−EtOAc) (lit.45 mp 150 °C); 1H NMR (500 MHz,
CDCl3) δ 6.02 (2H, s), 7.00 (1H, s), 7.17 (1H, s), 7.68 (1H, t, J = 8.1
Hz), 7.72 (1H, t, J = 8.1 Hz), 7.60 (1H, d, J = 5.6 Hz), 7.88 (1H, d, J =
8.1 Hz), 8.51 (1H, d, J = 5.6 Hz), 8.61 (1H, d, J = 8.1 Hz); 13C NMR
(125 MHz, CDCl3) δ 102.4, 111.1, 113.4, 113.8, 123.5, 126.3, 126.6,
127.0, 128.7, 130.5, 133.9, 136.8, 141.2, 147.4, 150.8, 154.8, 195.2; IR
(KBr) 1665 cm−1; ESIMS m/z (rel int) 356 (100, [M + 1]+), 358 (92,
[M + 3]+). Anal. Calcd for C17H10BrNO3: C, 57.33; H, 2.83; N, 3.93.
Found: C, 57.03; H, 2.90; N, 3.61.
(13i): yield 89% (662 mg, 1.78 mmol); pale yellow crystal; mp 125−
1
126 °C (hexane−EtOAc); H NMR (500 MHz, CDCl3) δ 4.03 (3H,
s), 4.07 (3H, s), 7.37 (1H, td, J = 7.9, 1.6 Hz), 7.46 (1H, td, J = 7.9, 1.0
Hz), 7.51 (1H, d, J = 9.4 Hz), 7.59 (1H, dd, J = 7.9, 1.0 Hz), 7.64 (1H,
dd, J = 7.9, 1.6 Hz), 8.08 (1H, d, J = 5.9 Hz), 8.46 (1H, d, J = 5.9 Hz),
8.58 (1H, d, J = 9.4 Hz); 13C NMR (125 MHz, CDCl3) δ 56.5, 61.3,
117.2, 117.7, 120.6, 122.5, 123.5, 127.3, 131.0, 132.0, 133.1, 133.2,
141.2, 141.3, 141.4, 151.3, 153.6, 196.9; IR (KBr) 1682 cm−1; ESIMS
m/z (rel int) 372 (100, [M + 1]+), 374 (100, [M + 3]+). Anal. Calcd
for C18H14BrNO3: C, 58.08; H, 3.79; N, 3.76. Found: C, 58.20; H,
4.06; N, 3.77.
(2-Bromo-5-trifluoromethylphenyl)isoquinolin-1-ylmethanone
(13d): yield 59% (448 mg, 1.18 mmol); white needle; mp 125−126 °C
(hexane−EtOAc); 1H NMR (500 MHz, CDCl3) δ 7.61 (1H, d, J = 8.3
Hz), 7.73 (1H, d, J = 8.3 Hz), 7.77−7.91 (2H, m), 7.85−7.87 (2H, m),
7.94−7.95 (1H, m), 8.53 (1H, d, J = 5.5 Hz), 8.90−8.92 (1H, m); 13C
NMR (125 MHz, CDCl3) δ 123.6 (q, J = 271 Hz), 124.3, 124.7, 126.3,
126.8, 127.2, 127.5 (q, J = 3 Hz), 128.1 (q, J = 3 Hz), 129.5, 130.0 (q, J
= 33 Hz), 130.7, 133.7, 137.0, 141.3, 142.4, 152.4, 195.5; IR (KBr)
1682 cm−1; ESIMS m/z (rel int) 380 (100, [M + 1]+), 382 (99, [M +
(2-Bromo-4,5-dimethoxyphenyl)(5,6-dimethoxyisoquinolin-1-yl)-
methanone (13j): yield 91% (786 mg, 1.82 mmol); pale yellow
1
granule; mp 161−162 °C (hexane−EtOAc); H NMR (500 MHz,
CDCl3) δ 3.92 (3H, s), 3.93 (3H, s), 4.03 (3H, s), 4.06 (3H, s) 7.02
(1H, s), 7.32 (1H, s), 7.48 (1H, d, J = 9.4 Hz), 8.06 (1H, d, J = 5.8
Hz), 8.35 (1H, d, J = 9.4 Hz), 8.47 (1H, d, J = 5.8 Hz); 13C NMR (125
MHz, CDCl3) δ 56.1, 56.3, 56.5, 61.3, 113.5, 114.0, 116.0, 116.9,
117.1, 122.4, 123.4, 132.4, 133.1, 141.4, 141.5, 148.4, 151.4, 152.2,
155.0, 195.7; IR (KBr) 1667 cm−1; ESIMS m/z (rel int) 432 (100, [M
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+ 1]+), 434 (95, [M + 3]+); HRESIMS m/z calcd for C20H19BrNO5
432.0441, found 432.0442 [M + 1]+.
C18H11BrF3NO2: C, 52.71; H, 2.70; N, 3.41. Found: C, 52.92; H,
2.79; N, 3.67.
(2-Bromophenyl)(6,7-methylenedioxyisoquinolin-1-yl)-
methanone (13q): yield 92% (655 mg, 1.84 mmol); pale yellow
crystal; mp 182−183 °C (hexane−EtOAc) (lit.46 mp 173−175 °C);
1H NMR (500 MHz, CDCl3) δ 6.14 (2H, s), 7.14 (1H, s), 7.35 (1H,
td, J = 7.7, 1.7 Hz), 7.44 (1H, t, J = 7.7 Hz), 7.58 (1H, d, J = 7.7 Hz),
7.60 (1H, dd, J = 7.7, 1.7 Hz), 7.62 (1H, d, J = 5.4 Hz), 8.21 (1H, s),
8.37 (1H, d, J = 5.4 Hz); 13C NMR (125 MHz, CDCl3) δ 101.9, 102.5,
102.7, 120.4, 123.5, 124.7, 127.2, 130.6, 131.7, 133.0, 135.9, 140.7,
141.7, 150.3, 150.9, 151.5, 197.3; IR (KBr) 1680 cm−1; ESIMS m/z
(rel int) 356 (100, [M + 1]+), 358 (96, [M + 3]+). Anal. Calcd for
C17H10BrNO3: C, 57.33; H, 2.83; N, 3.93. Found: C, 57.55; H, 3.09;
N, 3.67.
(2-Bromo-4,5-methylenedioxyphenyl)(5,6-dimethoxyisoquinolin-
1-yl)methanone (13k): yield 94% (782 mg, 1.88 mmol); pale yellow
1
granule; mp 190−191 °C (hexane−EtOAc); H NMR (500 MHz,
CDCl3) δ 4.02 (3H, s), 4.05 (3H, s), 6.05 (2H, s), 7.02 (1H, s), 7.16
(1H, s), 7.47 (1H, d, J = 9.4 Hz), 8.06 (1H, d, J = 5.8 Hz), 8.41 (1H, d,
J = 9.4 Hz), 8.46 (1H, d, J = 5.8 Hz); 13C NMR (125 MHz, CDCl3) δ
56.5, 61.3, 102.4, 111.2, 113.4, 113.8, 117.0, 117.3, 122.4, 123.4, 133.1,
134.0, 141.3, 141.4, 147.4, 150.8, 151.3, 154.5, 195.5; IR (KBr) 1682
cm−1; ESIMS m/z (rel int) 416 (100, [M + 1]+), 418 (100, [M + 3]+);
HRESIMS m/z calcd for C19H15BrNO5 416.0128, found 416.0130 [M
+ 1]+.
(2-Bromo-5-trifluoromethylphenyl)(5,6-dimethoxyisoquinolin-1-
yl)methanone (13l): yield 65% (572 mg, 1.30 mmol); pale yellow
crystal; mp 163−164 °C (hexane−EtOAc); 1H NMR (500 MHz,
CDCl3) δ 4.03 (3H, s), 4.08 (3H, s), 7.54 (1H, d, J = 9.4 Hz), 7.60
(1H, dd, J = 8.4, 1.8 Hz), 7.72 (1H, d, J = 8.4 Hz), 7.86 (1H, d, J = 1.8
Hz), 8.12 (1H, d, J = 5.8 Hz), 8.46 (1H, d, J = 5.8 Hz), 8.70 (1H, d, J
= 9.4 Hz); 13C NMR (125 MHz, CDCl3) δ 56.5, 61.3, 117.6, 118.4,
122.5, 123.3, 123.5 (q, J = 271 Hz), 124.3, 127.4 (q, J = 4 Hz), 128.1
(q, J = 3 Hz), 129.9 (q, J = 33 Hz), 133.3, 133.6, 141.3, 141.5, 142.4,
151.4, 152.1, 195.7; IR (KBr) 1690 cm−1; ESIMS m/z (rel int) 440
(100, [M + 1]+), 442 (98, [M + 3]+); HRESIMS m/z calcd for
C19H14BrF3NO3 440.0104, found 440.0098 [M + 1]+.
(2-Bromo-4,5-dimethoxyphenyl)(6,7-methylenedioxyisoquinolin-
1-yl)methanone (13r): yield 79% (657 mg, 1.58 mmol); white
1
granule; mp 169−170 °C (hexane−EtOAc); H NMR (500 MHz,
CDCl3) δ 3.92 (6H, s), 6.14 (2H, s), 7.01 (1H, s), 7.14 (1H, s), 7.28
(1H, s), 7.61 (1H, d, J = 5.5 Hz), 7.94 (1H, s), 8.38 (1H, d, J = 5.5
Hz); 13C NMR (125 MHz, CDCl3) δ 56.1, 56.3, 101.8, 102.4, 102.7,
113.2, 113.9, 115.9, 123.0, 124.5, 132.8, 135.7, 140.7, 148.4, 149.9,
151.0, 151.9, 153.0, 196.1; IR (KBr) 1674 cm−1; ESIMS m/z (rel int)
416 (100, [M + 1]+), 418 (93, [M + 3]+); HRESIMS m/z calcd for
C19H15BrNO5 416.0128, found 416.0124 [M + 1]+.
(2-Bromo-4,5-methylenedioxyphenyl)(6,7-methylenedioxyisoqui-
nolin-1-yl)methanone (13s): yield 94% (752 mg, 1.88 mmol); pale
(2-Bromophenyl)(7-methoxyisoquinolin-1-yl)methanone (13m):
yield 88% (602 mg, 1.76 mmol); pale yellow granule; mp 104−105
1
yellow needle; mp 220−222 °C (hexane−EtOAc); H NMR (500
MHz, CDCl3) δ 6.05 (2H, s), 6.13 (2H, s), 7.01 (1H, s), 7.12 (1H, s),
7.13 (1H, s), 7.61 (1H, d, J = 5.5 Hz), 8.02 (1H, s), 8.37 (1H, d, J =
5.5 Hz); 13C NMR (125 MHz, CDCl3) δ 101.9, 102.4, 102.5, 102.7,
111.0, 113.3, 113.5, 123.2, 124.6, 134.4, 135.8, 140.7, 147.4, 150.1,
150.6, 151.0, 152.4, 195.9; IR (KBr) 1667 cm−1; ESIMS m/z (rel int)
400 (100, [M + 1]+), 402 (94, [M + 3]+). Anal. Calcd for
C18H10BrNO5: C, 54.02; H, 2.52; N, 3.50. Found: C, 53.90; H,
2.70; N, 3.41.
1
°C (hexane−EtOAc); H NMR (500 MHz, CDCl3) δ 4.00 (3H, s),
7.36 (1H, t, J = 7.9 Hz), 7.42 (1H, d, J = 9.0 Hz), 7.45 (1H, t, J = 7.9
Hz), 7.59−7.61 (2H, m), 7.75 (1H, d, J = 5.4 Hz), 7.81 (1H, d, J = 9.0
Hz), 8.26 (1H, s), 8.44 (1H, d, J = 5.4 Hz); 13C NMR (125 MHz,
CDCl3) δ 55.6, 103.5, 120.5, 124.1, 124.2, 127.2, 128.5, 128.6, 130.6,
131.7, 132.9, 133.1, 139.7, 141.8, 151.3, 160.1, 197.4; IR (KBr) 1668
cm−1; ESIMS m/z (rel int) 342 (100, [M + 1]+), 344 (97, [M + 3]+).
Anal. Calcd for C17H12BrNO2: C, 59.67; H, 3.53; N, 4.09. Found: C,
59.66; H, 3.85; N, 3.85.
(2-Bromo-5-trifluoromethylphenyl)(6,7-methylenedioxyisoquino-
lin-1-yl)methanone (13t): yield 53% (449 mg, 1.06 mmol); pale
1
(2-Bromo-4,5-dimethoxyphenyl)(7-methoxyisoquinolin-1-yl)-
yellow granule; mp 175−176 °C (hexane−EtOAc); H NMR (500
methanone (13n): yield 96% (772 mg, 1.92 mmol); white granule;
MHz, CDCl3) δ 6.16 (2H, s), 7.15 (1H, s), 7.58 (1H, dd, J = 8.4, 2.1
Hz), 7.65 (1H, d, J = 5.4 Hz), 7.71 (1H, d, J = 8.4 Hz), 7.82 (1H, d, J
= 2.1 Hz), 8.33 (1H, s), 8.36 (1H, d, J = 5.4 Hz); 13C NMR (125
MHz, CDCl3) δ 102.0, 102.3, 102.8, 123.6, 124.1, 124.2, 124.9, 127.1
(q, J = 4 Hz), 127.9 (q, J = 3 Hz), 129.9 (q, J = 33 Hz), 133.5, 136.1,
140.7, 142.9, 150.0, 150.7, 151.1, 196.0; IR (KBr) 1682 cm−1; ESIMS
m/z (rel int) 424 (89, [M + 1]+), 426 (89, [M + 3]+). Anal. Calcd for
C18H9BrF3NO3: C, 50.97; H, 2.14; N, 3.30. Found: C, 51.17; H, 2.07;
N, 3.22.
1
mp 158−159 °C (hexane−EtOAc). H NMR (500 MHz, CDCl3) δ
3.92 (3H, s), 3.93 (3H, s), 3.97 (3H, s), 7.03 (1H, s), 7.28 (1H, s),
7.41 (1H, d, J = 9.0 Hz), 7.73 (1H, d, J = 5.3 Hz), 7.81 (1H, d, J = 9.0
Hz), 7.99 (1H, s), 8.45 (1H, d, J = 5.3 Hz); 13C NMR (125 MHz,
CDCl3) δ 55.5, 56.1, 56.3, 103.5, 113.3, 113.8, 115.9, 123.5, 124.1,
128.3, 128.5, 132.8, 132.9, 139.6, 148.3, 151.9, 152.8, 159.7, 196.2; IR
(KBr) 1667 cm−1; ESIMS m/z (rel int) 402 (100, [M + 1]+), 404 (95,
[M + 3]+); HRESIMS m/z calcd for C19H17BrNO4 402.03355, found
402.03348 [M + 1]+.
General Procedure for the Reductive Photocyclization of 1-
(2-Bromobenzoyl)isoquinolines 13. NaBH4 (0.750 mmol) was
carefully added to a stirred solution of the bromo ketones 13 (0.500
mmol) in hot methanol (200 mL). After cooling, the resulting solution
was irradiated in a quartz reactor equipped with a medium pressure
mercury lamp (450 W) at room temperature. The reactions were
monitored using TLC. Water (5 mL) was added until TLC showed
the reaction to be complete. The solution was then evaporated, and
the residue was dissolved in CHCl3 (400 mL). The solution was
washed with water (3 × 50 mL). The organic phase was dried with
anhydrous MgSO4, filtered, and evaporated under reduced pressure.
The residue was purified by column chromatography over silica gel
and eluted with CHCl3−MeOH (20:1) to yield the pure dibenzo-
[de,g]quinolin-7-ones 8. The full spectral data of dibenzo[de,g]-
quinolin-7-ones 8a−t are described as follows.
(2-Bromo-4,5-methylenedioxyphenyl)(7-methoxyisoquinolin-1-
yl)methanone (13o): yield 88% (679 mg, 1.76 mmol); pale yellow
crystal; mp146−147 °C (hexane−EtOAc); 1H NMR (500 MHz,
CDCl3) δ 3.97 (3H, s), 6.05 (2H, s), 7.03 (1H, s), 7.12 (1H, s), 7.40
(1H, d, J = 9.0, 2.4 Hz), 7.73 (1H, d, J = 5.4 Hz), 7.80 (1H, d, J = 9.0
Hz), 8.07 (1H, d, J = 2.4 Hz), 8.44 (1H, d, J = 5.4 Hz); 13C NMR (125
MHz, CDCl3) δ 55.6, 102.4, 103.5, 111.0, 113.4, 113.6, 123.7, 124.1,
128.4, 128.6, 132.8, 134.5, 139.6, 147.4, 150.6, 152.2, 159.9, 196.0; IR
(KBr) 1668 cm−1; ESIMS m/z (rel int) 386 (100, [M + 1]+), 388 (95,
[M + 3]+). Anal. Calcd for C18H12BrNO4: C, 55.98; H, 3.13; N, 3.63.
Found: C, 56.07; H, 3.22; N, 3.44.
(2-Bromo-5-trifluoromethylphenyl)(7-methoxyisoquinolin-1-yl)-
methanone (13p): yield 74% (607 mg, 1.48 mmol); pale yellow
1
granule; mp 121−122 °C (hexane−EtOAc); H NMR (500 MHz,
CDCl3) δ 4.02 (3H, s), 7.44 (1H, dd, J = 9.1, 2.0 Hz), 7.59 (1H, dd, J
= 8.4, 2.0 Hz), 7.73 (1H, d, J = 8.4 Hz), 7.78 (1H, d, J = 5.3 Hz), 7.81
(1H, d, J = 2.0 Hz), 7.83 (1H, d, J = 9.1 Hz), 8.39 (1H, d, J = 2.0 Hz),
8.44 (1H, d, J = 5.3 Hz); 13C NMR (125 MHz, CDCl3) δ 55.6, 103.4,
123.6 (q, J = 271 Hz), 124.2, 124.3, 124.8, 127.1 (q, J = 4 Hz), 127.8
(q, J = 3 Hz), 128.7, 128.8, 129.8 (q, J = 33 Hz), 133.0, 133.6, 139.7,
143.0, 149.7, 160.6, 196.2; IR (KBr) 1680 cm−1; ESIMS m/z (rel int)
410 (100, [M + 1]+), 412 (93, [M + 3]+). Anal. Calcd for
Dibenzo[de,g]quinolin-7-one (8a): yield 55% (63.5 mg, 0.275
mmol); yellow solid; mp 222−224 °C (lit.47 mp 222−222.5 °C); H
1
NMR (600 MHz, CDCl3) δ 7.60 (1H, t, J = 7.8 Hz), 7.78 (1H, td, J =
7.8, 1.2 Hz), 7.87 (1H, t, J = 7.8 Hz), 7.98−8.00 (2H, m), 8.30 (1H, d,
J = 7.8 Hz), 8.45 (1H, d, J = 7.8 Hz), 8.56 (1H, dd, J = 7.8, 1.2 Hz),
9.06 (1H, d, J = 5.4 Hz); 13C NMR (150 MHz, CDCl3) δ 123.1, 124.5,
124.6, 125.1, 128.6, 128.7, 129.1, 129.2, 131.0, 131.6, 134.1, 134.9,
136.9, 145.5, 146.7, 182.7; IR (KBr) 1665 cm−1; EIMS m/z (rel int)
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231 (100, M+); HREIMS m/z calcd for C16H9NO 231.0684, found
231.0686 [M]+.
2,3-Dimethoxydibenzo[de,g]quinolin-7-one (8i): yield 61% (88.8
mg, 0.305 mmol); orange solid; mp 179−180 °C (lit.47 mp 190−191
1
°C); H NMR (500 MHz, CDCl3) δ 4.12 (3H, s), 4.18(3H, s), 7.55
9,10-Dimethoxydibenzo[de,g]quinolin-7-one (8b): yield 77%
(112.0 mg, 0.385 mmol); orange granule; mp 257−259 °C (lit.47
(1H, t, J = 7.9 Hz), 7.74 (1H, t, J = 7.9 Hz), 8.14−8.17 (2H, m), 8.22
(1H, d, J = 5.6 Hz), 8.51 (1H, d, J = 7.9 Hz), 8.97 (1H, d, J = 5.6 Hz);
13C NMR (125 MHz, CDCl3) δ 57.1, 61.7, 113.9, 119.1, 120.8, 122.6,
125.3, 128.7, 129.0, 131.3, 133.2, 133.8, 134.5, 143.5, 145.2, 146.3,
151.2, 182.8; IR (KBr) 1667 cm−1; EIMS m/z (rel int) 291 (100, M+);
HREIMS m/z calcd for C18H13NO3 291.0895, found 291.0888 [M]+.
2,3,9,10-Tetramethoxydibenzo[de,g]quinolin-7-one (8j): yield
1
mp 255−256 °C); H NMR (500 MHz, CDCl3) δ 4.06 (3H, s), 4.12
(3H, s), 7.56 (1H, s), 7.77 (1H, t, J = 7.8 Hz), 7.87−7.92 (3H, m),
8.22 (1H, d, J = 7.8 Hz), 9.02 (1H, d, J = 5.3 Hz); 13C NMR (125
MHz, CDCl3) δ 56.2, 56.3, 104.4, 109.6, 123.8, 123.9, 124.6, 125.8,
127.8, 128.5, 129.6, 130.7, 136.5, 145.1, 146.7, 150.1, 154.0, 181.3; IR
(KBr) 1651 cm−1; EIMS m/z (rel int) 291 (100, M+); HREIMS m/z
calcd for C18H13NO3 291.0895, found 291.0905 [M]+.
1
70% (122.9 mg, 0.350 mmol); dark red solid; mp 208−210 °C; H
NMR (500 MHz, CDCl3) δ 4.06 (3H, s), 4.09 (3H, s), 4.12 (3H, s),
4.17 (3H, s), 7.40 (1H, s), 7.87 (1H, s), 7.88 (1H, s), 8.17 (1H, d, J =
5.6 Hz), 8.94 (1H, d, J = 5.6 Hz); 13C NMR (125 MHz, CDCl3) δ
56.2, 56.3, 57.4, 61.7, 104.1, 109.8, 113.8, 118.8, 120.3, 125.4, 125.7,
129.4, 133.1, 143.3, 145.0, 146.4, 149.9, 151.1, 154.1, 181.7; IR (KBr)
1643 cm−1; EIMS m/z (rel int) 351 (100, M+); HREIMS m/z calcd
for C20H17NO5 351.1107, found 351.1103 [M]+.
9,10-(Methylenedioxy)dibenzo[de,g]quinolin-7-one (8c): yield
1
69% (94.9 mg, 0.345 mmol); orange granule; mp 300 °C dec; H
NMR (600 MHz, CDCl3) δ 6.15 (2H, s), 7.62 (1H, s), 7.81 (1H, t, J =
7.2 Hz), 7.91−7.95 (3H, m), 8.21 (1H, d, J = 7.2 Hz), 9.03 (1H, d, J =
5.4 Hz); 13C NMR (150 MHz, CDCl3) δ 102.3, 102.4, 107.7, 123.9,
124.3, 124.8, 127.8, 128.2, 128.7, 130.9, 132.0, 136.7, 145.5, 146.7,
149.1, 153.2, 181.2; IR (KBr) 1659 cm−1; EIMS m/z (rel int) 275
(100, M+); HREIMS m/z calcd for C17H9NO3 275.0582, found
275.0586 [M]+.
2,3-Dimethoxy-9,10-(methylenedioxy)dibenzo[de,g]quinolin-7-
one (8k): yield 78% (130.7 mg, 0.390 mmol); dark red solid; mp 264−
1
266 °C; H NMR (500 MHz, CDCl3) δ 4.09 (3H, s), 4.13 (3H, s),
9-Trifluoromethyldibenzo[de,g]quinolin-7-one (8d): yield 33%
(49.3 mg, 0.165 mmol); pale yellow solid; mp 238−243 °C
6.08 (2H, s), 7.22 (1H, s), 7.65 (1H, s), 7.68 (1H, s), 8.10 (1H, d, J =
5.4 Hz), 8.88 (1H, d, J = 5.4 Hz); 13C NMR (125 MHz, CDCl3) δ
56.9, 61.6, 101.7, 102.2, 107.1, 113.6, 118.7, 119.7, 124.9, 127.1, 131.4,
132.8, 143.0, 144.9, 146.0, 148.4, 151.0, 152.8, 181.1; IR (KBr) 1649
cm−1; EIMS m/z (rel int) 335 (100, M+); HREIMS m/z calcd for
C19H13NO5 335.0794, found 335.0786 [M]+.
1
(sublimation); H NMR (500 MHz, CDCl3) δ 7.85 (1H, t, J = 8.0
Hz), 7.89 (1H, d, J = 8.0 Hz), 7.95 (1H, d, J = 5.3 Hz), 7.99 (1H, d, J
= 8.0 Hz), 8.27 (1H, d, J = 8.0 Hz), 8.38 (1H, d, J = 8.0 Hz), 8.69 (1H,
s), 9.03 (1H, d, J = 5.3 Hz); 13C NMR (125 MHz, CDCl3) δ 123.5 (q,
J = 271 Hz), 123.8, 124.5, 125.3, 125.7, 126.0 (q, J = 4 Hz), 126.9,
129.8, 129.9 (q, J = 3 Hz), 130.9, 131.0 (q, J = 33 Hz), 131.4, 136.7,
137.4, 145.7, 146.0, 181.2; IR (KBr) 1672 cm−1; EIMS m/z (rel int)
299 (100, M+); HREIMS m/z calcd for C17H8F3NO 299.0558, found
299.0560 [M]+.
9-Trifluoromethyl-2,3-dimethoxydibenzo[de,g]quinolin-7-one
(8l): yield 80% (143.6 mg, 0.400 mmol); orange solid; mp 221−223
1
°C; H NMR (500 MHz, CDCl3) δ 4.15 (3H, s), 4.19 (3H, s), 7.88
(1H, d, J = 8.4 Hz), 8.07 (1H, s), 8.16 (1H, d, J = 8.4 Hz), 8.20 (1H, d,
J = 5.5 Hz), 8.69 (1H, s), 8.94 (1H, d, J = 5.5 Hz); 13C NMR (125
MHz, CDCl3) δ 57.2, 61.7, 115.2, 119.5, 120.9, 123.3, 123.4, 123.6 (q,
J = 271 Hz), 126.2 (q, J = 4 Hz), 129.9 (q, J = 3 Hz), 130.6 (q, J = 33
Hz), 131.2, 133.1, 137.3, 144.6, 145.4, 145.7, 150.9, 181.6; IR (KBr)
1667 cm−1; EIMS m/z (rel int) 359 (100, M+); HREIMS m/z calcd
for C19H12F3NO3 359.0769, found 359.0760 [M]+.
3-Methoxydibenzo[de,g]quinolin-7-one (8e): yield 86% (112.2
1
mg, 0.430 mmol); orange needle; mp 201−203 °C; H NMR (500
MHz, CDCl3) δ 4.06 (3H, s), 6.97 (1H, d, J = 8.0 Hz), 7.47 (1H, t, J =
8.0 Hz), 7.66 (1H, t, J = 8.0 Hz), 8.03 (1H, d, J = 8.0 Hz), 8.15 (1H, d,
J = 8.0 Hz), 8.23 (1H, d, J = 5.1 Hz), 8.46 (1H, d, J = 8.0 Hz), 8.99
(1H, d, J = 5.1 Hz); 13C NMR (125 MHz, CDCl3) δ 56.0, 107.7,
119.7, 120.5, 122.3, 125.0, 125.7, 127.8, 128.8, 129.9, 130.7, 133.8,
135.2, 145.0, 146.2, 156.5, 182.7; IR (KBr) 1657 cm−1; EIMS m/z (rel
int) 261 (100, M+); HREIMS m/z calcd for C17H11NO2 261.0790,
found 261.0798 [M]+.
1-Methoxydibenzo[de,g]quinolin-7-one (8m): yield 63% (82.2 mg,
1
0.315 mmol); orange solid; mp 179−180 °C; H NMR (500 MHz,
CDCl3) δ 4.20 (3H, s), 7.52 (1H, t, J = 8.0 Hz), 7.62 (1H, d, J = 9.2
Hz), 7.71 (1H, t, J = 8.0 Hz), 7.86 (1H, d, J = 5.2 Hz), 7.93 (1H, d, J =
9.2 Hz), 8.60 (1H, d, J = 8.0 Hz), 8.94 (1H, d, J = 5.2 Hz), 9.08 (1H,
d, J = 8.0 Hz); 13C NMR (125 MHz, CDCl3) δ 56.5, 112.9, 119.5,
124.7, 126.1, 127.7, 128.7, 128.9, 130.5, 131.6, 132.3, 133.8, 134.8,
143.3, 145.5, 158.6, 182.4; IR (KBr) 1645 cm−1; EIMS m/z (rel int)
261 (100, M+); HREIMS m/z calcd for C17H11NO2 261.0790, found
261.0792 [M]+.
3,9,10-Trimethoxydibenzo[de,g]quinolin-7-one (8f): yield 95%
1
(152.0 mg, 0.475 mmol); orange solid; mp 268−270 °C; H NMR
(500 MHz, CDCl3) δ 4.02 (3H, s), 4.03 (3H, s), 4.04 (3H, s), 6.78
(1H, d, J = 7.9 Hz), 7.14 (1H, s), 7.71 (1H, s), 7.76 (1H, d, J = 7.9
Hz), 8.14 (1H, d, J = 5.4 Hz), 8.94 (1H, d, J = 5.4 Hz); 13C NMR (125
MHz, CDCl3) δ 55.9, 56.1, 56.2, 103.5, 107.4, 109.2, 119.2, 120.3,
124.2, 124.8, 124.9, 129.6, 130.1, 144.6, 146.1, 149.2, 154.0, 155.9,
181.3; IR (KBr) 1645 cm−1; EIMS m/z (rel int) 321 (100, M+);
HREIMS m/z calcd for C19H15NO4 321.1001, found 321.1008 [M]+.
3-Methoxy-9,10-(methylenedioxy)dibenzo[de,g]quinolin-7-one
(8g): yield 80% (122.0 mg, 0.400 mmol); dark red solid; mp 260−273
1,9,10-Trimethoxydibenzo[de,g]quinolin-7-one (8n): yield 95%
1
(152.5 mg, 0.475 mmol); orange solid; mp 250−252 °C; H NMR
(500 MHz, CDCl3) δ 4.06 (3H, s), 4.08 (3H, s), 4.22 (3H, s), 7.62
(1H, d, J = 9.2 Hz), 7.86 (1H, d, J = 5.2 Hz), 7.91 (1H, d, J = 9.2 Hz),
8.04 (1H, s), 8.67 (1H, s), 8.95 (1H, d, J = 5.2 Hz); 13C NMR (125
MHz, CDCl3) δ 55.8, 56.2, 56.8, 109.8, 110.9, 113.5, 119.6, 124.4,
125.7, 126.5, 129.9, 130.0, 132.4, 143.4, 145.9, 148.8, 153.4, 157.8,
181.1; IR (KBr) 1634 cm−1; EIMS m/z (rel int) 321 (100, M+);
HREIMS m/z calcd for C19H15NO4 321.1001, found 321.1004 [M]+.
1-Methoxy-9,10-(methylenedioxy)dibenzo[de,g]quinolin-7-one
(8o): yield 81% (123.5 mg, 0.405 mmol); dark red solid; mp 275−277
1
°C (sublimation); H NMR (600 MHz, CDCl3) δ 4.08 (3H, s), 6.10
(2H, s), 7.04 (1H, d, J = 8.4 Hz), 7.51 (1H, s), 7.89 (1H, s), 8.11 (1H,
d, J = 8.4 Hz), 8.31 (1H, d, J = 5.4 Hz), 9.02 (1H, d, J = 5.4 Hz); 13C
NMR (150 MHz, CDCl3) δ 56.0, 101.6, 102.1, 107.4, 107.6, 119.5,
120.7, 124.4, 125.5, 126.8, 129.9, 132.6, 145.2, 146.2, 148.2, 153.2,
156.4, 181.3; IR (KBr) 1647 cm−1; EIMS m/z (rel int) 305 (100, M+);
HREIMS m/z calcd for C18H11NO4 305.0688, found 305.0684 [M]+.
9-Trifluoromethyl-3-methoxydibenzo[de,g]quinolin-7-one (8h):
yield 99% (162.9 mg, 0.495 mmol); yellow solid; mp 220 °C
(sublimation); 1H NMR (500 MHz, CDCl3) δ 4.13 (3H, s), 7.09 (1H,
d, J = 8.3 Hz), 7.88 (1H, d, J = 8.3 Hz), 8.18 (1H, d, J = 8.3 Hz), 8.30
(1H, d, J = 8.3 Hz), 8.33 (1H, d, J = 5.4 Hz), 8.74 (1H, s), 9.06 (1H, d,
J = 5.4 Hz); 13C NMR (125 MHz, CDCl3) δ 56.2, 107.7, 119.0, 120.1,
123.1, 123.7 (q, J = 271 Hz), 125.2, 126.1 (q, J = 4 Hz), 127.2, 129.8,
129.9 (q, J = 34 Hz), 130.1, 130.6, 138.0, 145.5, 145.7, 157.6, 181.7; IR
(KBr) 1663 cm−1; EIMS m/z (rel int) 329 (100, M+); HREIMS m/z
calcd for C18H10F3NO2 329.0664, found 329.0672 [M]+.
1
°C; H NMR (500 MHz, CDCl3) δ 4.19 (3H, s), 6.12 (2H, s), 7.60
(1H, d, J = 9.1 Hz), 7.83 (1H, d, J = 4.6 Hz), 7.89 (1H, d, J = 9.1 Hz),
8.00 (1H, s), 8.55 (1H, s), 8.92 (1H, d, J = 4.6 Hz); 13C NMR (125
MHz, CDCl3) δ 56.6, 102.0, 107.6, 108.4, 113.3, 119.6, 124.5, 125.5,
128.2, 130.3, 131.7, 132.3, 143.5, 145.6, 147.6, 152.7, 158.2, 180.9; IR
(KBr) 1643 cm−1; EIMS m/z (rel int) 305 (100, M+); HREIMS m/z
calcd for C18H11NO4 305.0688, found 305.0682 [M]+.
9-Trifluoromethyl-1-methoxydibenzo[de,g]quinolin-7-one (8p):
yield 80% (131.6 mg, 0.400 mmol); yellow solid; mp 232−234 °C;
1H NMR (500 MHz, CDCl3) δ 4.24 (3H, s), 7.62 (1H, d, J = 9.3 Hz),
7.80 (1H, d, J = 8.8 Hz), 7.83 (1H, d, J = 5.1 Hz), 7.95 (1H, d, J = 9.3
Hz), 8.77 (1H, s), 8.92 (1H, d, J = 5.1 Hz), 9.05 (1H, d, J = 8.8 Hz);
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13C NMR (125 MHz, CDCl3) δ 56.6, 111.4, 119.4, 123.8 (q, J = 271
Hz), 125.1, 125.6 (q, J = 4 Hz), 126.3, 129.4 (q, J = 33 Hz), 129.5,
129.6 (q, J = 3 Hz), 131.5, 131.9, 132.2, 137.4, 143.8, 144.9, 159.5,
181.3; IR (KBr) 1659 cm−1; EIMS m/z (rel int) 324 (100, M+);
HREIMS m/z calcd for C18H10F3NO2 329.0664, found 329.0672
[M]+.
A. G.; Machado, G. M. C.; Leon, L. L. P. J. Nat. Prod. 2006, 69, 292−
294.
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A.; Clark, A. M. J. Nat. Prod. 2002, 65, 856−859.
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1,2-(Methylenedioxy)dibenzo[de,g]quinolin-7-one (8q): yield 45%
(61.9 mg, 0.225 mmol); yellow solid; mp 279−281 °C (lit.48 mp 280−
1
282 °C); H NMR (500 MHz, CDCl3) δ 6.34 (2H, s), 7.14 (1H, s),
7.54 (1H, t, J = 7.2 Hz), 7.70 (1H, t, J = 7.2 Hz), 7.73 (1H, d, J = 5.4
Hz), 8.55 (1H, d, J = 7.2 Hz), 8.59 (1H, d, J = 7.2 Hz), 8.85 (1H, d, J
= 5.4 Hz); 13C NMR (125 MHz, CDCl3) δ 102.4, 103.2, 108.1, 123.2,
124.2, 127.3, 128.6, 128.8, 131.3, 132.8, 133.9, 135.7, 144.9, 145.4,
147.9, 151.7, 182.4; IR (KBr) 1651 cm−1; EIMS m/z (rel int) 275
(100, M+); HREIMS m/z calcd for C17H9NO3 275.0582, found
275.0579 [M]+.
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S.; Wang, Z. T.; Fujiwara, T. Chem. Pharm. Bull. 2002, 50, 1195−1200.
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2001, 67, 593−598.
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62, 133−136.
Dicentrinone (8r): yield 81% (135.7 mg, 0.405 mmol); yellow solid;
mp 300 °C dec (lit.49 mp 300 °C dec); 1H NMR (500 MHz, CDCl3) δ
3.95 (3H, s), 4.06 (3H, s), 6.34 (2H, s), 7.06 (1H, s), 7.70 (1H, d, J =
5.2 Hz), 7.86 (1H, s), 7.92 (1H, s), 8.86 (1H, d, J = 5.2 Hz); 13C NMR
(125 MHz, CDCl3) δ 56.1, 56.2, 102.4, 102.7, 108.2, 108.8, 109.5,
122.6, 124.0, 125.9, 127.7, 135.5, 144.7, 145.4, 147.0, 149.5, 151.5,
153.8, 181.2; IR (KBr) 1643 cm−1; EIMS m/z (rel int) 335 (100, M+);
HREIMS m/z calcd for C19H13NO5 335.0794, found 335.0790 [M]+.
Cassameridine (8s): yield 53% (84.5 mg, 0.265 mmol); brown
solid; mp 320 °C dec (lit.50 mp 300 °C); 1H NMR (500 MHz, CDCl3
+ CF3CO2D + D2O) δ 6.22 (2H, s), 6.60 (2H, s), 7.41 (1H, s), 7.77
(1H, s), 8.06 (1H, s), 8.30 (1H, d, J = 5.8 Hz), 8.94 (1H, d, J = 5.8
Hz); 13C NMR (125 MHz, CDCl3 + CF3CO2D) δ 103.4, 103.5, 105.0,
107.5, 107.6, 108.6, 121.6, 124.7, 126.6, 130.1, 134.1, 135.1, 142.9,
150.0, 151.6, 155.9, 158.3, 174.4; IR (KBr) 1682 cm−1; EIMS m/z (rel
int) 319 (100, M+); HREIMS m/z calcd for C18H9NO5 319.0481,
found 319.0488 [M]+.
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9-Trifluoromethyl-1,2-(methylenedioxy)dibenzo[de,g]quinolin-7-
one (8t): yield 72% (123.5 mg, 0.360 mmol); yellow solid; mp 350 °C
1
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dec; H NMR (600 MHz, CDCl3) δ 6.44 (2H, s), 7.25 (1H, s), 7.81
(1H, d, J = 5.4 Hz), 7.93 (1H, d, J = 8.4 Hz), 8.75 (1H, d, J = 8.4 Hz),
8.92 (1H, d, J = 5.4 Hz); 13C NMR (150 MHz, CDCl3) δ 102.9, 104.3,
106.7, 123.3, 123.6 (q, J = 270 Hz), 124.7, 125.9, 128.0, 129.9, 130.3
(q, J = 33 Hz), 131.2, 135.6, 135.7, 144.8, 145.3, 149.0, 151.8, 181.4;
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z calcd for C18H8F3NO3 343.0456, found 343.0459 [M]+.
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New York, 1973; Vol. 14, pp 225−264.
ASSOCIATED CONTENT
■
S
* Supporting Information
1
Copies of the H and 13C NMR spectra of compounds 8, 10,
(24) Shamma, M.; Moniot, J. M. Isoquinoline Alkaloid Research 1972−
1977; Plenum Press: New York, 1978.
12, and 13. This material is available free of charge via the
Internet at http://pubs.acs.org.
(25) Grundon, M. F.; Shamma, M. In The Alkaloids; Grundon, M. F.,
Eds.; London, 1981; Vol. 10, pp 126−134.
(26) Liu, Y. C.; Chen, Z. F.; Peng, Y.; Liang, H. Linchan Huaxue Yu
Gongye 2011, 31, 109−116.
AUTHOR INFORMATION
Corresponding Author
*E-mail: thchuang@mail.cmu.edu.tw.
Notes
■
(27) Shamma, M.; Guinaudeau, H. Tetrahedron 1984, 40, 4795−
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Lett. 2007, 48, 8166−8169.
The authors declare no competing financial interest.
(29) Taylor, W. I. Tetrahedron 1961, 14, 42−45.
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(30) Castedo, L.; Saa, J. M.; Suau, R.; Villaverde, C. Heterocycles
ACKNOWLEDGMENTS
1980, 14, 1131−1134.
■
(31) Orito, K.; Uchiito, S.; Satoh, Y.; Tatsuzawa, T.; Harada, R.;
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Financial support from the National Science Council of the
Republic of China (NSC 101-2113-M-039-004-MY2) and
China Medical University (CMU101-S-08) is gratefully
acknowledged.
(32) Gerecke, M.; Brossi, A. Helv. Chim. Acta 1979, 62, 1549−1558.
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1985, 26, 4559−4560.
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