A simple and effective synthesis of benzolactones and benzolactams by noncatalytic benzylic oxidation of cyclic benzylic ethers and N-protected cyclic benzylic amines with sodium chlorite as an oxidant

Article abstract of DOI:10.1055/s-0032-1316747

Sodium chlorite (NaClO was shown to be capable of oxidizing cyclic benzylic ethers and N-protected cyclic benzylic amines in a heterogeneous solvent system of 1,1,1-trichloroethane and water at 55-65°C to give synthetically useful benzolactones and benzolactams, respectively, in high-to-excellent yields. Georg Thieme Verlag Stuttgart ? New York.

Full text of DOI:10.1055/s-0032-1316747

PAPER
▌2903
paper
A Simple and Effective Synthesis of Benzolactones and Benzolactams by
Noncatalytic Benzylic Oxidation of Cyclic Benzylic Ethers and N-Protected
Cyclic Benzylic Amines with Sodium Chlorite as an Oxidant
Noncatalytic Benzylic Oxidations with Sodium Chlorite
Ai-Ru Song,a,b Jun Yu,a Chi Zhang*a
a
State Key Laboratory of Elemento-Organic Chemistry, The Research Institute of Elemento-Organic Chemistry, Nankai University,
Tianjin 300071, P. R. of China
Fax 86(22)23503627; E-mail: zhangchi@nankai.edu.cn
b
Tianjin Key Laboratory of Water Resources and Environment, Tianjin Normal University, Tianjin 300387, P. R. of China
Received: 04.05.2012; Accepted after revision: 20.06.2012
tries.11 In the field of synthetic organic chemistry, sodium
Abstract: Sodium chlorite (NaClO2) was shown to be capable of
chlorite has found a number of applications that have been
oxidizing cyclic benzylic ethers and N-protected cyclic benzylic
well documented in a recent review.12 Sodium chlorite fa-
amines in a heterogeneous solvent system of 1,1,1-trichloroethane
cilitates both catalytic and noncatalytic epoxidation reac-
tions of olefins.13 It also efficiently oxidizes iodoarene to
iodoarene dichlorides and 2-iodobenzoic acids to 1-chlo-
ro-1,2-benziodoxol-3(1H)-ones.14 Moreover, Salvador
and co-workers have shown that sodium chlorite, in com-
bination with tert-butyl hydroperoxide under stoichiomet-
ric conditions or with N-hydroxyphthalimide under
catalytic conditions, can be used to effect allylic and ben-
zylic oxidation reactions.15 Tomioka and co-workers re-
ported the oxidation of imines by using sodium chlorite
under buffered conditions to give the corresponding am-
ides.16 Here, as part of our ongoing program on the explo-
ration of new reactions of sodium chlorite, we describe a
simple and effective method for the synthesis of benzolac-
tones and benzolactams by benzylic oxidation of cyclic
benzylic ethers or N-protected cyclic benzylic amines, re-
spectively, using sodium chlorite as an oxidant in the ab-
sence of a catalyst.
and water at 55–65 °C to give synthetically useful benzolactones
and benzolactams, respectively, in high-to-excellent yields.
Key words: lactones, lactams, amines, ethers, oxidations, hetero-
cycles
Benzolactone and benzolactam units are common struc-
tural motifs in a large number of natural products, many
of which exhibit a broad spectrum of biological activi-
ties.1 Benzolactones and benzolactams can also serve as
key intermediates in the synthesis of various natural prod-
ucts.1b,2 As a result, a number of methods have been devel-
oped for the synthesis of benzolactones and benzolactams.
Examples include the transition-metal-catalyzed carbon-
ylation of aromatic compounds with tethered oxygen and
nitrogen nucleophiles,3 cobalt- or iridium-catalyzed re-
gioselective [2+2+2] cycloadditions of alkynyl alcohols
or alkynyl amines with two molecules of propiolates,4 pal-
ladium-catalyzed sequential alkylation/lactonization reac-
tions of benzoic acids with alkyl halides,5 sp3 C–H bond
activation of ortho-alkyl aromatic carboxylic acid deriva-
tives to produce benzolactones,6 oxidation of 1,2-ben-
zenedimethanol to give a phthalide,7 and Bischler–
Napieralski cyclization of phenethylcarbamates to give
3,4-dihydroisoquinolinones.8 Alternatively, the direct ox-
idation of readily available cyclic benzylic ethers and N-
protected cyclic benzylic amines constitutes another effi-
cient synthetic path to benzolactones and benzolactams.9
In the past two decades, some oxidation systems have
been developed for such transformations, but most of
these require toxic metal-based oxidizing agents, in par-
ticular, those based on chromium or cobalt.10 It is there-
fore desirable to explore new oxidation system for these
transformations.
We began by examining the reaction of isochroman (1a;
3,4-dihydro-1H-isochromene) under the same conditions
that we previously used in the epoxidation of olefins.13a
Isochroman (1a) was treated with 3.0 equivalents of sodi-
um chlorite in a 4:1 v/v mixture of acetonitrile and water
at 55–65 °C. The oxidative product isochroman-1-one
(2a; 3,4-dihydro-1H-isochromen-1-one) was formed in
35% yield with 75% conversion of 1a after five hours. By
chance, we found that the use of 4:1 v/v mixture of
1,1,2,2-tetrachloroethane and water as the solvent system
gave a much better yield (70%) of 2a with 80% conver-
sion of 1a after eight hours. We then conducted a screen-
ing study of organic solvents under the same reaction
conditions (Table 1). A mixture of 1,1,1-trichloroethane
and water gave the highest yield of 2a after eight hours
(entry 2). Other chlorinated hydrocarbons (chloroform,
1,2-dichloroethane, dichloromethane, and carbon tetra-
chloride) were also tested (entries 3–6), but none of these
gave a better result than 1,1,1-trichloroethane. The use of
ethyl acetate or tetrahydrofuran gave only a low conver-
sion of 1a (entries 7 and 8). We therefore examined the ef-
fect of the volume ratio of 1,1,1-trichloroethane and water
(entries 9–10), and we found that a 4:1 v/v mixture of
1,1,1-trichloroethane was, indeed, optimal. When the re-
Sodium chlorite (NaClO2) is a cheap and green oxidizing
reagent that is widely used in water treatment and as a
bleaching agent in the paper, pulp, and textiles indus-
SYNTHESIS 2012, 44, 2903–2909
Advanced online publication: 30.07.2012
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0
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7
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1
1
4
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DOI: 10.1055/s-0032-1316747; Art ID: SS-2012-F0416-OP
© Georg Thieme Verlag Stuttgart · New York

2904
A.-R. Song et al.
PAPER
action was carried out in water alone, 2a was obtained in underwent regiospecific oxidation to give the lactam 2g in
36% yield (entry 11).
84% yield within 2.5 hours (entry 7). N-Protected cyclic
benzylic amines bearing electron-donating or electron-
withdrawing substituents on the phenyl ring were also ef-
ficiently transformed into the corresponding benzolac-
tams 2h–l in high yields (entries 8–12). In the case of tert-
butyl phenanthridine-5(6H)-carboxylate (1m), the desired
oxidative product 2m was obtained in 84% yield after six
hours (entry 13). Furthermore, the reaction was success-
fully extended to the benzo-fused five-membered-ring
substrate 2-tosylisoindoline (1n) (entry 14).
Table 1 Screening Study of Organic Solvents and the Effect of the
Volume Ratio of the Organic Solvent and Water
O
NaClO2 (3.0 equiv)
O
O
organic solvent/H2O
55–65 °C, 8 h
1a (1 mmol)
2a
Entry
Solvent systema
(volume ratio v/v)
Conv.
(%)
Yieldb
(%)
A gram-scale oxidation of N-tert-butoxycarbonyl-1,2,3,4-
tetrahydroisoquinoline (1d) (25 mmol, 5.8 g) performed
under standard conditions gave 2d in 95% yield after three
hours.
1
2
Cl2CHCHCl2/H2O (4:1)
Cl3CMe/H2O (4:1)
CHCl3/H2O (4:1)
DCE/H2O (4:1)
CH2Cl2/H2O (4:1)
CCl4/H2O (4:1)
EtOAc/H2O (4:1)
THF/ H2O (4:1)
Cl3CMe/H2O (9:1)
Cl3CMe/H2O (1:1)
H2O
80
85
67
20
6
70
75
55
10
trace
4
To obtain some clues regarding the reaction pathway, we
performed a radical-inhibition experiment by the addition
of 2,2,6,6-tetramethylpiperidin-1-yloxy (TEMPO) (0.25
equiv) in the oxidation of 1d; this decreased the yield of
2d to 50%, compared with 94% obtained under the stan-
dard conditions (Table 2, entry 4). This result suggests
that the reaction involves free-radical species. We have
previously demonstrated that yellow ClO2, a quite stable
free radical, is produced on heating sodium chlorite at
aqueous acetonitrile at 55–65 °C.13a Because the present
reactions were performed with sodium chlorite as an oxi-
dant in an aqueous biphasic solvent mixture at 55–65 °C,
we thought it likely that ClO2 is formed in this case also.
To confirm this, we conducted a UV–visible spectrometry
experiment. When a mixture of sodium chlorite (3 mmol)
in 1,1,1-trichloroethane (8 mL) and water (2 mL) was
heated for one hour at 55–65 °C, the UV spectrum of the
resulting yellow organic phase showed the characteristic
absorption of ClO2 (λmax = 359 nm).17
3
4
5
6
25
25
25
91
74
65
7
10
c
8
–
9
70
63
36
10
11
a Total volume 10 mL.
b Isolated yield.
c Not detected.
On the basis of the above results, we propose the reaction
mechanism that is shown in Scheme 1. First, the benzylic
hydrogen is abstracted by ClO2 to form a benzylic carbon-
centered radical A, which is stabilized by the α-oxygen
atom.18 A second ClO2 radical then couples with radical A
to give the intermediate B, which eliminates a molecule of
hypochlorous acid (HClO) to give the final product 2a, in
a similar manner to that proposed by Tomioka.16
Next, we examined a range of cyclic benzylic ethers and
N-protected cyclic benzylic amines under our optimized
reaction conditions (Table 2). Like isochroman, two other
cyclic benzylic ethers, 6,7-dimethoxyisochroman (1b)
and 1,3-dihydro-2-benzofuran (1c; phthalan), were
smoothly converted into the corresponding benzolactones
2b and 2c, respectively, in high yields (entries 2 and 3). In
the case of N-protected cyclic benzylic amines, N-tert-bu-
toxycarbonyl-1,2,3,4-tetrahydroisoquinoline (1d) was
readily oxidized to the benzolactam 2d in excellent yield
(94%) within 2.5 hours (entry 4). When the amount of so-
dium chlorite was reduced to two equivalents, the oxida-
tion of 1d gave 2d in only 72% yield, which confirmed the
need to use three equivalents of sodium chlorite to pro-
duce a high yield. Two other N-protecting groups, tosyl
and acetyl, were well tolerated under the reaction condi-
tions (entries 5–6).In the case of N-benzyl-1,2,3,4-tetra-
hydroisoquinoline (1g), the cyclic benzylic C–H bond
In conclusion, we have developed a simple and effective
protocol for the synthesis of benzolactones and benzolac-
tams by benzylic oxidations of cyclic benzylic ethers and
N-protected cyclic benzylic amines by using sodium chlo-
rite as an oxidant in the absence of a catalyst. Because of
its simplicity, efficiency, and cost-effectiveness, coupled
with the ready availability of sodium chlorite, the protocol
could provide an attractive method for synthesizing ben-
zolactones and benzolactams.
Synthesis 2012, 44, 2903–2909
© Georg Thieme Verlag Stuttgart · New York

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Noncatalytic Benzylic Oxidations with Sodium Chlorite
2905
Table 2 Oxidation of Cyclic Benzyl Ethers and N-Protected Cyclic Benzyl Amines with Sodium Chlorite
Entry Substratea
Product
Time (h)
Conv. (%)
85
Yieldb (%)
O
O
O
1
8
75
1a
2a
O
MeO
O
MeO
O
2
5
100
100
86
75
MeO
MeO
1b
2b
O
O
3
O
2.5
1c
2c
2d
2e
2f
O
O
O
O
Boc
N
N
Boc
N
4
2.5
100
92
94
90
1d
Ts
Ts
O
N
N
N
5
18
1e
O
N
N
6
2.5
2.5
2
90
100
100
80
84
86
1f
Bn
Bn
O
7
1g
2g
MeO
Boc
N
N
MeO
Boc
N
N
8
MeO
MeO
1h
2h
O
MeO
Bn
MeO
Bn
9
2
8
100
100
80
81
MeO
MeO
1i
2i
O
O2N
Boc
N
O2N
Boc
N
10
1j
2j
© Georg Thieme Verlag Stuttgart · New York
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A.-R. Song et al.
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Table 2 Oxidation of Cyclic Benzyl Ethers and N-Protected Cyclic Benzyl Amines with Sodium Chlorite (continued)
Entry Substratea
Product
Time (h)
Conv. (%)
85
Yieldb (%)
O
O
O
O2N
O2N
N
N
11
8
72
66
1k
2k
O
O
O
Cl
Cl
N
N
12
7
6
80
97
1l
2l
O
Boc
N
Boc
N
13
84
65
1m
2m
2n
O
N
Ts
N
Ts
14
24
87
1n
a Reactions were conducted with 1 mmol of substrate.
b Isolated yield.
H
•
• ClO2
• ClO2
O
O
H
– HClO2
A
1a
O
OClO
O
O
– HClO
2a
B
Scheme 1 Plausible reaction mechanism
400 MHz by using a Bruker Avance 300 or 400 spectrometer with
CDCl3 as the solvent; 13C NMR spectra were similarly recorded at
75 or 100 MHz. IR spectra were recorded on a Bruker FT-IR
EQUINOX 55 spectrometer in KBr pellets. Elementary analysis
was carried out with an Elemental Vario EL analyzer. High-resolu-
tion mass spectra were recorded on a Varian 7.0T FTMS mass spec-
trometer. PE, where used, had a boiling range of 60–90 °C.
Figure 1 (A) UV spectrum of ClO2 in the organic phase from a re-
action mixture of NaClO2 (3 mmol) and acetic anhydride (3 mmol) in
4:1 v/v 1,1,1-trichloroethane/water (10 mL) at room temperature.17
(B) UV spectrum of the organic phase in our system. Sodium chlorite
(3 mmol) in 4:1 v/v 1,1,1-trichloroethane/water (10 mL) was heated
at 55–60 °C for one hour. The organic phase from the mixture was
separated and subjected to UV measurement. (C) UV spectrum of
1,1,1-trichloroethane.
CAUTION: NaClO2 can explode on impact. Intimate mixtures
with organic matter may be very sensitive to heat, impact, or fric-
tion.
Oxidation of Cyclic Benzylic Ethers or N-Protected Cyclic Ben-
zylic Amines; Typical Procedure
NaClO2 (338 mg, 3 mmol) was added to a stirred mixture of the ap-
propriate cyclic benzylic ether or N-protected cyclic benzylic amine
(1 mmol) in 4:1 v/v MeCCl3–H2O (10 mL) at r.t. The reaction flask
was then placed in an oil bath at 55–65 °C. After the time indicated
in Table 2, the mixture was cooled to r.t. and the reaction was
NaClO2 (80% pure) was purchased from Sigma–Aldrich and used
without further purification. The known products were identified by
comparison of their 1H NMR and 13C NMR spectra with those re-
1
ported in the literature. H NMR spectra were recorded at 300 or
Synthesis 2012, 44, 2903–2909
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Noncatalytic Benzylic Oxidations with Sodium Chlorite
2907
quenched with sat. aq Na2S2O3 (10 mL). The mixture was diluted
with CH2Cl2 (30 mL) and the aqueous phase was separated and ex-
tracted with CH2Cl2 (2 × 30 mL). The organic layers were com-
bined, washed successively with H2O and brine, dried (Na2SO4),
and concentrated in vacuo to give a crude product that was purified
by flash column chromatography.
2-Benzyl-3,4-dihydro-1(2H)-isoquinolinone (2g)8a
Colorless oil; yield: 200 mg (84%).
1H NMR (300 MHz, CDCl3): δ = 8.15 (d, J = 7.5 Hz, 1 H), 7.26–
7.44 (m, 7 H), 7.15 (d, J = 7.5 Hz, 1 H), 4.80 (s, 2 H), 3.48 (t, J =
6.6 Hz, 2 H), 2.93 (t, J = 6.6 Hz, 2 H).
13C NMR (75 MHz, CDCl3): δ = 164.24, 137.84, 137.20, 131.41,
129.12, 128.35, 128.11, 127.75, 127.15, 126.73, 126.67, 50.17,
45.10, 27.76.
tert-Butyl 1-Oxo-3,4-dihydroisoquinoline-2(1H)-carboxylate
(2d); Gram-Scale Preparation
NaClO2 (75 mmol, 8.5 g) was added to a stirred mixture of 1d (25
mmol, 5.8 g) in 4:1 v/v MeCCl3–H2O (250 mL) at r.t. The flask was
then placed in an oil bath at 55–65 °C and the mixture was vigor-
ously stirred for 3 h. The mixture was then cooled to r.t. and the re-
action was quenched by cautious addition of sat. aq Na2S2O3 (200
mL). The aqueous phase was separated and extracted with CH2Cl2
(2 × 100 mL). The organic layers were combined, washed succes-
sively with H2O and brine, dried (Na2SO4), concentrated in vacuo,
and purified by flash column chromatography; yield: 5.8 g (95%).
tert-Butyl 6,7-Dimethoxy-1-oxo-3,4-dihydroisoquinoline-2(1H)-
carboxylate (2h)20
White solid; yield: 265 mg (86%); mp 124–127 °C.
1H NMR (400 MHz, CDCl3): δ = 7.65 (s, 1 H), 6.64 (s, 1 H), 3.98
(t, J = 6.4 Hz, 2 H), 3.94 (s, 3 H), 3.91 (s, 3 H), 2.94 (t, J = 6.2 Hz,
2 H), 1.59 (s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 163.59, 153.17, 152.68, 147.92,
133.69, 121.40, 110.97, 108.89, 82.71, 55.81, 44.46, 27.89, 27.77.
3,4-Dihydro-1H-isochromen-1-one (2a)10b
2-Benzyl-6,7-dimethoxy-3,4-dihydroisoquinolin-1(2H)-one
(2i)21
Colorless oil; yield: 111 mg (75%).
1H NMR (400 MHz, CDCl3): δ = 8.10 (d, J =7.6 Hz, 1 H), 7.55 (t,
J = 7.4 Hz, 1 H), 7.40 (t, J = 7.6 Hz, 1 H), 7.27 (d, J = 7.6 Hz, 1 H),
4.55 (t, J = 6.0 Hz, 2 H), 3.07 (t, J = 6.0 Hz, 2 H).
White solid; yield: 238 mg (80%); mp 97–99 °C.
1H NMR (400 MHz, CDCl3): δ = 7.67 (s, 1 H), 7.33–7.34 (m, 5 H),
6.63 (s, 1 H), 4.79 (s, 2 H), 3.95 (s, 3 H), 3.92 (s, 3 H), 3.48 (t, J =
6.8 Hz, 2 H), 2.88 (t, J = 6.6 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 164.78, 139.36, 133.38, 129.90,
127.30, 127.03, 124.95, 67.05, 27.46.
13C NMR (100 MHz, CDCl3): δ = 164.48, 151.62, 147.74, 137.39,
131.55, 128.45, 127.83, 127.22, 121.63, 110.48, 109.07, 55.89,
55.84, 50.28, 45.46, 27.49.
6,7-Dimethoxy-3,4-dihydro-1H-isochromen-1-one (2b)19
White solid; yield: 179 mg (86%); mp 138–140 °C.
1H NMR (300 MHz, CDCl3): δ = 7.56 (s, 1 H), 6.69 (s, 1 H), 4.52
(t, J = 6.0 Hz, 2 H), 3.95 (s, 3 H), 3.93 (s, 3 H), 2.99 (t, J = 6.0 Hz,
2 H).
tert-Butyl 7-Nitro-1-oxo-3,4-dihydroisoquinoline-2(1H)-car-
boxylate (2j)
White solid; yield: 237 mg (81%); mp 159–161 °C.
13C NMR (75 MHz, CDCl3): δ = 164.87, 153.44, 148.25, 133.83,
117.13, 111.60, 109.02, 67.12, 55.91, 55.87, 27.19.
IR (KBr): 3112, 3085, 3068, 2984, 2937, 1964, 1726, 1691, 1614,
1526, 1481, 1433, 1372, 1343, 1306, 1230, 1155, 1223, 922, 851,
750 cm–1.
1H NMR (300 MHz, CDCl3): δ = 9.01 (d, J = 2.4 Hz, 1 H), 8.32 (dd,
J = 2.4, 8.4 Hz, 1 H), 7.43 (d, J = 8.4 Hz, 1 H), 4.05 (t, J = 6.3 Hz,
2 H), 3.13 (t, J = 6.3 Hz, 2 H), 1.60 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 161.70, 152.45, 147.55, 146.00,
130.80, 128.62, 126.96, 124.79, 83.93, 43.70, 28.37, 27.99.
HRMS (ESI): m/z [M + H]+ calcd for C14H17N2O5: 293.1132; found:
2-Benzofuran-1(3H)-one (2c)3b
White solid; yield: 101 mg (75%); mp 72–74 °C.
1H NMR (400 MHz, CDCl3): δ = 7.93 (d, J = 7.6 Hz, 1 H), 7.70 (t,
J = 7.6 Hz, 1 H), 7.50–7.57 (m, 2 H), 5.34 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 171.00, 146.43, 133.90, 128.88,
125.52, 122.04, 69.56.
293.1135.
tert-Butyl 1-Oxo-3,4-dihydroisoquinoline-2(1H)-carboxylate
(2d)10a
2-Acetyl-7-nitro-3,4-dihydroisoquinolin-1(2H)-one (2k)
White solid; yield: 169 mg (72%); mp 159–161 °C.
White solid; yield: 232 mg (94%); mp 71–74 °C.
1H NMR (300 MHz, CDCl3): δ = 8.16 (d, J = 7.5 Hz, 1 H), 7.44–
7.49 (m, 1 H), 7.35 (d, J = 7.4 Hz, 1 H), 7.20 (d, J = 7.5 Hz, 1 H),
4.00 (t, J = 6.3 Hz, 2 H), 3.00 (t, J = 6.1 Hz, 2 H), 1.59 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 163.28, 152.50, 139.08, 132.33,
128.94, 128.82, 126.74, 126.63, 82.44, 43.97, 27.77, 27.59.
IR (KBr): 3433, 3371, 2967, 1984, 1849, 1695, 1614, 1519, 1473,
1432, 1371, 1343, 1321, 1308, 1270, 1225, 1168, 1103, 1056, 1007,
935, 860, 834, 787, 773, 697, 654, 610, 537 cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.98 (d, J = 2.4 Hz, 1 H), 8.36 (dd,
J = 2.4, 8.4 Hz, 1 H), 7.49 (d, J = 8.4 Hz, 1 H), 4.17 (t, J = 6.6 Hz,
2 H), 3.13 (t, J = 6.4 Hz, 2 H), 2.70 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 173.22, 163.62, 147.62, 146.63,
130.52, 128.79, 127.45, 124.81, 41.04, 28.21, 27.54.
HRMS (ESI): m/z [M + H]+ calcd for C11H11N2O4: 235.0713; found:
235.0716.
2-Tosyl-3,4-dihydroisoquinolin-1(2H)-one (2e)3b
White solid; yield: 272 mg (90%); mp 135–137 °C.
1H NMR (300 MHz, CDCl3): δ = 7.97–8.01 (m, 3 H), 7.47 (t, J = 7.5
Hz 1 H), 7.27–7.34 (m, 3 H), 7.22 (d, J = 7.5 Hz, 1 H), 4.23 (t, J =
6.3 Hz, 2 H), 3.13 (t, J = 6.2 Hz, 2 H), 2.42 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 163.33, 144.63, 139.21, 136.16,
133.40, 129.32, 129.04, 128.47, 128.13, 127.62, 127.31, 44.67,
28.84, 21.52.
2-Acetyl-7-chloro-3,4-dihydroisoquinolin-1(2H)-one (2l)
White solid; yield: 148 mg (66%); mp 96–97 °C.
IR (KBr): 3431, 3205, 3079, 3033, 3006, 2936, 2938, 2905, 1694,
1601, 1573, 1483, 1419, 1364, 1313, 1290, 1269, 1219, 1193, 1166,
1054, 1002, 896, 826, 774, 703, 657, 635, 610 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.05 (s, 1 H), 7.40 (d, J = 8.0 Hz,
1 H), 7.14 (d, J = 8.0 Hz, 1 H), 4.03 (t, J = 6.4 Hz, 2 H), 2.89 (t, J =
6.4 Hz, 2 H), 2.59 (s, 3 H).
2-Acetyl-3,4-dihydroisoquinolin-1(2H)-one (2f)18g
White solid; yield: 151 mg (80%); mp 102–104 °C.
1H NMR (300 MHz, CDCl3): δ = 8.14 (d, J = 7.8 Hz, 1 H), 7.51 (t,
J = 7.5 Hz, 1 H), 7.38 (t, J = 7.5 Hz, 1 H), 7.26 (d, J = 7.5 Hz, 1 H),
4.11 (t, J = 6.3 Hz, 2 H), 2.99 (t, J = 6.2 Hz, 2 H), 2.66 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 173.57, 165.62, 140.17, 133.27,
129.42, 128.95, 127.26, 41.63, 28.04, 27.50.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2903–2909

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A.-R. Song et al.
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13C NMR (100 MHz, CDCl3): δ = 173.54, 164.5, 138.45, 133.48,
J. Am. Chem. Soc. 2004, 126, 14342. (e) Wu, X.;
133.29, 130.51, 129.32, 128.82, 41.54, 27.61, 27.56.
HRMS (ESI): m/z [M + H]+ calcd for C11H11ClNO2: 224.0473;
found: 224.0475.
Mahalingam, A. K.; Alterman, M. Tetrahedron Lett. 2004,
45, 4635. (f) Morimoto, T.; Fujioka, M.; Fuji, K.; Tsutsumi,
K.; Kakiuchi, K. Chem. Lett. 2003, 32, 154. (g) Kayaki, Y.;
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43, 1684.
tert-Butyl 6-Oxophenanthridine-5(6H)-carboxylate (2m)
White solid; yield: 248 mg (84%); mp 174–177 °C.
IR (KBr): 2978, 1755, 1659, 1609, 1489, 1437, 1372, 1329, 1253,
1151, 847, 743, 719, 629 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.50 (d, J = 8.0 Hz, 1 H), 8.26–
8.29 (m, 2 H), 7.81 (t, J = 7.6 Hz, 1 H), 7.61 (t, J = 7.6 Hz, 1 H),
7.51 (t, J = 7.6 Hz, 1 H), 7.35 (t, J = 7.6 Hz, 1 H), 7.16 (d, J = 8.4
Hz, 1 H), 1.73 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 159.69, 151.10, 134.19, 133.75,
133.12, 129.47, 128.26, 128.18, 128.02, 124.77, 123.24, 121.81,
118.18, 114.29, 86.37, 27.48.
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Maheswari, C. U.; Ghantasala, S.; Jyothi, C.; Reddy, K. R.
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7365.
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Chemistry; Kent, J. A., Ed.; Van Nostrand Reinhold: New
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Cunningham, G. L. Ind. Eng. Chem. 1940, 32, 899.
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216, 449.
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Anal. Calcd for C18H17NO3: C, 73.20; H, 5.80; N, 4.74. Found: C,
73.19; H, 5.82; N, 4.73.
2-Tosylisoindolin-1-one (2n)3b
White solid; yield: 187 mg (65%); mp 176–177 °C.
1H NMR (300 MHz, CDCl3): δ = 7.95 (d, J = 8.4 Hz, 2 H), 7.73 (d,
J = 8.1 Hz, 1 H), 7.56 (t, J = 7.2 Hz, 1 H), 7.37–7.41 (m, 2 H), 7.26
(d, J = 8.4 Hz, 2 H), 4.84 (s, 2 H), 2.34 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 166.09, 145.22, 140.95, 135.28,
133.84, 130.14, 129.73, 128.79, 128.12, 125.01, 123.30, 49.82,
21.65.
Acknowledgment
This work was financially supported by The National Natural Sci-
ence Foundation of China (Nos. 21172110 and 21121002), Program
for New Century Excellent Talents in University (NCET-07-0461),
and the Tianjin Natural Science Foundation (09JCYBJC05900).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
nnfomartit
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