Efficient synthesis of benzene-fused 6/7-membered amides: Via Xphos Pd G2 catalyzed intramolecular C-N bond formation

Article abstract of DOI:10.1039/c7ra09160e

An efficient approach for benzene-fused 6/7-membered amides via intramolecular amidation of aryl chlorides catalyzed by a Buchwald-Hartwig second generation Pd catalyst (Xphos Pd G2) has been successfully developed. This catalyst system allows the primary amides which have only modest nucleophilicity to be coupled successfully even with electron rich aryl chlorides in short reaction time. The intramolecular amidation reaction also has good chemoselectivity and excellent functional group compatibility.

Full text of DOI:10.1039/c7ra09160e

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Efficient synthesis of benzene-fused 6/7-
membered amides via Xphos Pd G2 catalyzed
intramolecular C–N bond formation†
Cite this: RSC Adv., 2017, 7, 51972
ab Ke Li,b Rongliang Zhai,ab Ting Liang,ab Xiaodie Guia and Rongli Zhangb
*
Zhou Xu,
An efficient approach for benzene-fused 6/7-membered amides via intramolecular amidation of aryl
chlorides catalyzed by a Buchwald–Hartwig second generation Pd catalyst (Xphos Pd G2) has been
successfully developed. This catalyst system allows the primary amides which have only modest
nucleophilicity to be coupled successfully even with electron rich aryl chlorides in short reaction time.
The intramolecular amidation reaction also has good chemoselectivity and excellent functional group
compatibility.
Received 18th August 2017
Accepted 30th October 2017
DOI: 10.1039/c7ra09160e
rsc.li/rsc-advances
Introduction
Benzene-fused amides are important organic compounds
commonly encountered in biologically relevant natural or
synthetic pharmaceutical compounds.1–3 Some methods were
developed towards the synthesis of these scaffolds which are
mainly benzene-fused 6-membered amides known as 2H-1,4-
benzoxazin-3-(4H)-one derivatives.4–6 However, the substituent
diversity in the products is limited and more importantly, it is
difficult to synthesize benzene-fused seven-membered amides.
Organic halides are some of the most common industrially
used compounds and widely used as starting materials for many
chemical transformations. The efficient cleavage of C–X (X ¼
halogen atom) bonds has been actively studied by organic
chemists. Among them, palladium catalysts developed by Buch-
wald and Hartwig proved to be the most useful ones for the C–N
bond formation.7,8 The amination of aryl halogens by transition
metal catalyzed coupling methodology has been the subject of
signicant interest during past few decades, but the amidation
reaction has not yet fully studied. Electron-decient amides have
been difficult coupling partners due to their modest nucleophi-
licity and intolerance of strong base. Although, amidation of aryl
bromides and iodides have become the well-established
processes in the reaction,9–12 however, largely absent from the
literature on Pd-catalyzed amidation reactions is the description
of an efficient method for coupling aryl chlorides.
Scheme 1 Benzene-fused amides: prior arts and design.
construct the valuable molecular structure of benzene-fused
amides. Laha et al. reported the synthesis of dibenzoazepi-
nones via the intramolecular amination of aryl bromide (not aryl
chlorides) in 18 h with yield of 68–94%.13 While, Lautens et al.
reported the synthesis of 3,4-dihydroquinolinones via the reac-
tion between arylboronic acid and acrylamide (Scheme 1).14
As part of our continuing efforts for accessing biologically
hetero compounds by metal-catalyzed reactions,15 herein, we
report a facile, efficient, convenient and generally applicable
method for the intramolecular amidation of organic halides to
synthesize oxo-containing 6/7 membered benzene-fused amides
with excellent yield using commerical available XPhos Pd G2 as
the catalyst.
To the best of our knowledge, there are limited literature
reports the intramolecular amidation of aryl chlorides which can
aDepartment of Chemistry, Xuzhou Medical University, Xuzhou 221004, China. E-mail:
xuzhou@xzhmu.edu.cn
bJiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou
Results and discussion
At the outset of our investigation, we employed 1a as the
substrate for the preparation of the desired benzene-fused 7-
membered amide 2a. Aer considerable amount of efforts on
Medical University, Xuzhou 221004, China
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c7ra09160e
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Table 2 Formation of benzene-fused 7-membered amide: reaction
condition discovery and optimization, we were able to obtain 2a
with 97% isolated yield in 5 h.
scopes.a,b
The reaction conditions, as shown in the equation in Table 1,
including the use of Xphos Pd G2 as the most effective catalyst,
1,4-dioxane as the optimal solvent, and Cs2CO3 as the base.
Indeed, other catalysts, such as Ph3PPdCl, JohnPhos Pd G2,
Xphos PdCl2 all fared much worse than Xphos Pd G2 in terms of
reaction rate and efficiency (entries 1–3 vs. 5). We also per-
formed the reaction with catalysts Xphos Pd G1, Xphos Pd G3
and Xphos Pd G4. All of them gave almost the same result with
Xphos Pd G2 (entries 4–7). However, Xphos Pd G2 is the
cheapest one. Thus, we chose it as catalyst for further investi-
gation. The combination of Pd(OAc)2 and ligand Xphos cannot
proceed the transformation either (entry 8). The reaction can be
faster and more efficiency when Cs2CO3 was used as the base
instead of K2CO3 (entry 5 vs. entry 9). The best solvent for the
reaction is 1,4-dioxane. Toluene is equal efficiency, but DMSO
or DMF doesn't work for the reaction (entries 10, 12 and 13).
The substrate 1a can also convert smoothly to product 2a at
80 ꢀC, but requires longer reaction time (entry 14). Lowering the
reaction temperature to 50 ꢀC, the reaction could hardly happen
and only trace product observed even prolonging the reaction
time to 36 h (entry 15). Substrate concentration has limited
effect on the reaction. When the concentration of the substrate
a
The reactions were carried in Schlenk ask under Ar. 1b–1j (0.5 mmol),
Xphos Pd G2 (5 mol%), 1,4-dioxane (2 ml), Cs2CO3 (1.5 equiv.), 110 ꢀC.
Isolated yield.
b
Table 1 Optimization for the reaction conditiona
was 0.25 M, it gave the best result with 99% yield. Increasing or
decreasing the concentration of 1a, both gave slightly lower
yield (entries 16 and 17). Higher the catalyst loading can faster
the reaction with same yield (entry 18). Lowering the catalyst
loading to 2.5% makes the reaction much difficult to proceed
(entry 19). Small amount of water could hinder the reaction and
slow down the reaction rate and yield (entry 20).
With the optimal conditions (Table 1, entry 9) in hand, we
then set out to explore the substrate scope of the reaction for
constructing benzene-fused 7-membered amides. As shown in
Table 2, even electron-rich aryl chlorides can furnish the
transformation in short time. A methyl (entry 1), a uoro (entry
2), a triuoromethyl (entries 3 and 4) or methoxyls (entry 5)
substitution at the benzene ring were readily allowed and these
reactions proceeded smoothly to afford the corresponding
benzene-fused amides in good to excellent yields. In the case of
Entry
Catalyst
Base
Solvent
Time
Yieldb
1
2
3
4
5
6
7
8
PPh3PdCl
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
DMSO
H2O
MePh
DMF
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
24 h
24 h
24 h
5 h
5 h
5 h
5 h
24 h
2 h
24 h
24 h
8 h
24 h
8 h
36 h
4 h
4 h
2.5 h
12 h
24 h
NR
Johnphos Pd
Xphos PdCl2
Xphos Pd G1
Xphos Pd G2
Xphos Pd G3
Xphos Pd G4
Pd(OAc)2/Xphos
XPhos Pd G2
XPhos Pd G2
XPhos Pd G2
XPhos Pd G2
XPhos Pd G2
XPhos Pd G2
XPhos Pd G2
XPhos Pd G2
XPhos Pd G2
XPhos Pd G2
XPhos Pd G2
XPhos Pd G2
18%
84%
95%
97%
94%
97%
NR
99%
Trace
14%
96%
NR
98%
Trace
97%
96%
97%
Trace
84%
9
10
11
12
13
14c
15d
16e
17f
18g
19h
20i
a
The reactions were carried in Schlenk asks. 1a (0.5 mmol), Pd*
b
(5 mol%), solvent (2 ml), base (1.5 equiv.), 110 ꢀC. Isolated yield.
c
d
The reaction temperature is 80 ꢀC. The reaction temperature is
50 ꢀC. e Substrate concentration is 0.25 M. Substrate concentration is
f
g
h
0.5 M. The catalyst loading is 7.5 mol%. The catalyst loading is
2.5 mol%. i H2O (5 ml) was added.
Scheme 2 (a) Chemoselectivity of the reaction. (b) Unsuccessful
example.
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With the success in the formations of benzene-fused seven
membered rings, we subsequently turned to explore the 6-
membered ring formation. As expected, the benzene-fused 6-
membered rings are much easier formed than the seven
membered ones both in efficiency and yields. We found a broad
range of 6-membered ring amides possessing various func-
tional groups could be achieved with high yields in short reac-
tion times (Table 3).
Scheme 3 (R)-2g was formed without detectable ee erosion.
However, it needs to point out that the substrate used for the
formation of 2n is aryl bromide (entry 4). The intramolecular
amidation reaction could not proceed when the corresponding
aryl chloride was used. Electron-rich aryl chlorides can also
couple with amides successfully in short time affording the
products in excellent yields (entries 5–7). For the sterically
hindered aryl chloride, the amidation reaction was successfully
proceeded affording 2r in 96% yield (entry 8). Even for 2-(2-
aminophenoxy)acetamide which has a very strong electron
donating amino-group which deactivated the C–Cl bond could
also undergo the intramolecular amidation and gives product
2s in 85% yield (entry 9).
2-(1-phenylethoxy)acetamide as the substrate, 2g could be ob-
tained with 89% yield in 5.5 h, which the reaction time was
longer than that of 2a.
The chemoselectivity of the system was also briey explored.
When there are more than one chloro-groups on the ring, the
reaction can hardly proceed. For example, as shown in
Scheme 2, when 1h0 was used as the substrate, only trace of 2h
was observed by NMR. Fortunately, when 1h was used instead of
1h0, 2h could be achieved successfully with 83% yield (entry 7)
which indicated that the reaction had good chemoselectivity.
Unfortunately, when we explored this chemistry with thio-
phene substrate, no expected product was observed (Scheme
2b). For other heteroaromatic amides 1i-1j, the amidation
reaction could proceed smoothly. When (1-(pyridin-3-yl)ethoxy)
acetamide 1i was used, 2i could be obtained with 89% yield in
4.5 h (entry 8). Oxazepino[5,6-b]quinolin-2(3H)-one 2j was also
obtained with good yield (entry 9).
Conclusions
In conclusion, an efficient protocol for C–N cross-coupling
reactions has been described. This catalyst system allows the
primary amides which have only modest nucleophilicity could
couple successfully even with electron rich aryl chlorides which
can afford valuable benzene-fused 6/7-membered amides with
high yield in short reaction time. The catalyst system also has
good chemoselectivity and excellent functional group compat-
ibility which supplies an important alternative way to the
synthesis of benzene-fused 6/7-membered amides.
When Table 2, entry 6 was performed using the (R)-substrate
(83% ee) under the optimal conditions, (R)-2g was formed
without detectable ee erosion (Scheme 3).
Table 3 Formation of benzene-fused 6-membered amide: reaction
scopes.a,b
Experimental section
General experimental methods
Commercially available reagents were used without further
purication. The solvents used for experiment research were all
through pretreatment on condition of anaerobic and without
water. Reactions were monitored by thin layer chromatography
(TLC) using silicycle precoated silica gel plates. Flash column
chromatography was performed over silicycle silica gel (300–400
1
mesh). H NMR and 13C NMR spectra were recorded on JMTC-
400/54/SS 400 MHz spectrometers using residue solvent peaks
1
as internal standards (CHCl3, H: 7.26 ppm; 13C: 77.00 ppm).
Infrared spectra were recorded with a PerkinElmer Spectrum
Two FT-IR spectrometer and are reported in reciprocal centi-
meter (cmꢁ1). Mass spectra were recorded with MicroTof-II
using electron spray ionization (MeOH or CH3CN as solvent)
or Waters GCT Premier time-of-ight mass spectrometer with
a eld ionization (FI) ion source.
General procedure for the synthesis of benzene-fused 6/7-
membered amides
a
The reactions were carried in Schlenk ask under Ar. Substrate 1k–1s
2-((2-chlorobenzyl)oxy)acetyl chloride 1 (0.25 mmol), Cs2CO3
(122.65 mg, 0.375 mmol) and Pd Xphos G2 (9.8 mg, 0.0125
(0.5 mmol), Xphos Pd G2 (5 mol%), 1,4-dioxane (2 ml), Cs2CO3 (1.5
equiv.), 110 ꢀC. b Isolated yield.
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mmol) were added into Schlenk tube. The mixture was stirred
under argon and dry 1,4-dioxane (1 ml) was added and heated to
110 C. The reaction was monitored by TLC. Aer the reaction
nished, the product was isolated with column
chromatography.
8,9-Dimethoxy-3,5-dihydrobenzo[e][1,4]oxazepin-2(H)-one 2f
90% yield, m.p. 148–149 ꢀC; 1H NMR (400 MHz, CDCl3): d ppm
3.87 (s, 3H), 3.88 (s, 3H), 4.61 (s, 2H), 4.67 (s, 2H), 6.58 (d, J ¼
8.8 Hz, 1H), 6.78 (d, J ¼ 8.8 Hz, 1H), 8.30 (s, 1H); 13C NMR (100
MHz, CDCl3): d ppm 55.9, 60.8, 72.9, 74.1, 106.6, 121.8, 122.8,
129.5, 136.8, 152.3, 172.4; IR: v (cmꢁ1): 3195.3, 1661.6, 1391.6,
1112.3. HRMS calcd for C11H13NO4 (M + Na)+ 246.0742, found
246.0736.
ꢀ
3,5-Dihydrobenzo[e][1,4]oxazepin-2(H)-one 2a
99% yield, m.p. 156–157 ꢀC; 1H NMR (400 MHz, CDCl3): d ppm
4.58 (s, 2H), 4.75 (s, 2H), 6.87 (d, J ¼ 8.0 Hz, 1H), 7.06 (t, J ¼
7.6 Hz, 1H), 7.14 (d, J ¼ 7.2 Hz, 1H), 7.26–7.27 (m, 1H), 7.72 (s,
1H); 13C NMR (100 MHz, CDCl3): d ppm 72.8, 73.5, 119.2, 123.7,
128.6, 128.7, 129.2, 135.7, 173.2; IR v (cmꢁ1): 3357.3, 3171.4,
1635.8, 1431.5, 1377.8; HRMS calcd for C9H9NO2 (M ꢁ H)+
162.0555, found 162.0559.
5-Methyl-3,5-dihydrobenzo[e][1,4]oxazepin-2(H)-one 2g
89% yield, m.p. 120–121 ꢀC; 1H NMR (400 MHz, CDCl3): d ppm
1.64 (d, J ¼ 6.4 Hz, 3H), 4.54 (d, J ¼ 2.4 Hz, 2H), 4.78 (q, J ¼
6.4 Hz, 1H), 6.99 (dd, J1 ¼ 8.4H, J2 ¼ 0.4 Hz, 1H), 7.01 (td, J1 ¼
7.6 Hz, J2 ¼ 0.4 Hz, 1H), 7.23–7.29 (m, 2H), 8.68 (s, 1H); 13C NMR
(100 MHz, CDCl3): d ppm 19.0, 71.1, 75.2, 120.0, 123.9, 125.9,
128.8, 132.7, 136.0, 173.7; IR v (cmꢁ1): 3196.7, 3065.5, 2997.0,
2903.1, 1656.9; HRMS calcd for C10H11NO2 (M ꢁ H)+ 176.0721,
found 176.0725. For corresponding chiral R-2g: ꢁ78ꢀ (c 0.10,
acetone), 83% ee (determined by a chiral AD-H column, iPrOH/
hexane ¼ 10/90, tmajor ¼ 14.26 min, tminor ¼ 15.40 min).
8-Methyl-3,5-dihydrobenzo[e][1,4]oxazepin-2(H)-one 2b
96% yield, m.p. 154–155 ꢀC; 1H NMR (400 MHz, CDCl3): d ppm
2.33 (s, 3H), 4.57 (s, 2H), 4.70 (s, 2H), 6.79 (s, 1H), 6.87 (d, J ¼
7.6 Hz, 1H), 7.02 (d, J ¼ 7.6 Hz, 1H), 8.75 (s, 1H); 13C NMR (100
MHz, CDCl3): d ppm 21.0, 72.5, 73.3, 119.9, 124.5, 125.9, 128.4,
135.7, 139.3, 173.5; IR v (cmꢁ1): 3377.0, 3184.2, 2962.5, 1656.5,
1259.5; HRMS calcd for C10H11NO2 (M + Na)+ 200.0687, found
200.0673.
6-Chloro-3,5-dihydrobenzo[e][1,4]oxazepin-2(H)-one 2h
83% yield, m.p. 172–173 ꢀC; 1H NMR (400 MHz, CDCl3): d ppm
4.52 (s, 2H), 4.99 (s, 2H), 6.78 (d, J ¼ 7.6 Hz, 1H), 7.11–7.19 (m,
2H), 7.70 (s, 1H); 13C NMR (100 MHz, CDCl3): d ppm 69.8, 73.1,
118.2, 124.9, 126.6, 129.2, 133.7, 137.5, 173.0; IR v (cmꢁ1):
3246.6, 2918.9, 1671.0, 1480.4, 1258.1; HRMS calcd for
C9H8ClNO2 (M + Na)+ 220.0141, found 220.0143.
8-Fluoro-3,5-dihydrobenzo[e][1,4]oxazepin-2(H)-one 2c
94% yield, m.p. 166–167 ꢀC; 1H NMR (400 MHz, d6-DMSO):
d ppm 4.43 (s, 2H), 4.65 (s, 2H), 6.79 (dt, J1 ¼ 8.0 Hz, J2 ¼ 2.4 Hz,
1H), 6.92 (dd, J1 ¼ 10.4 Hz, J2 ¼ 2.4 Hz, 1H), 7.17 (d, J ¼ 8.4 Hz,
1H), 10.30 (s, 1H); 13C NMR (100 MHz, d6-DMSO): d ppm 71.7,
73.8, 106.2 (d, J ¼ 25.8 Hz), 109.4 (d, J ¼ 21.1 Hz), 126.0 (d, J ¼
2.8 Hz), 130.6 (d, J ¼ 9.6 Hz), 139.1 (d, J ¼ 10.5 Hz), 162.3 (d, J ¼
41.4 Hz), 173.4; 19F NMR: ꢁ113.9; IR v (cmꢁ1): 3194.0, 3066.2,
1661.0, 1603.5, 1372.5; HRMS calcd for C9H8FNO2 (M + Na)+
204.0437, found 204.0430.
5-Methyl-3,5-dihydropyrido[2,3-e][1,4]oxazepin-2(H)-one 2i
89% yield, m.p. 106–106.5 ꢀC; 1H NMR (400 MHz, CDCl3): d ppm
1.64 (d, J ¼ 6.4 Hz, 3H), 4.64 (d, J ¼ 6.0 Hz, 2H), 4.73 (q, J ¼
6.4 Hz, 1H), 7.04 (dd, J1 ¼ 7.6 Hz, J2 ¼ 4.8 Hz, 1H), 7.53 (d, J ¼
7.8 Hz, 1H), 8.40 (d, J ¼ 4.8 Hz, 1H), 9.38 (s, 1H); 13C NMR (100
MHz, CDCl3): d ppm 18.9, 72.2, 75.0, 118.7, 127.4, 134.7, 147.6,
149.1, 173.0; IR v (cmꢁ1): 3180.4, 1662.7, 1634.3, 1401.8, 1315.7;
HRMS calcd for C9H10N2O2 (M + Na)+ 201.0640, found 201.0623.
7-(Triuoromethyl)-3,5-dihydrobenzo[e][1,4]oxazepin-2(1H)-
one 2d
90% yield, 1H NMR (400 MHz, CDCl3): d ppm 4.62 (s, 2H), 4.78
(s, 2H), 7.24–7.31 (m, 3H), 8.91 (s, 1H); 13C NMR (100 MHz,
CDCl3): d ppm 70.1, 70.2, 123.9 (q, J ¼ 3.9 Hz), 124.5 (q, J ¼ 267.2
Hz), 126.2 (q, J ¼ 3.9 Hz), 129.3, 131.8 (q, J ¼ 32.6 Hz), 133.5,
138.6, 171.6; 19F NMR: d ppm 78.8; IR v (cmꢁ1): 2979.8, 1663.7,
1334.6, 1121.5; HRMS calcd for C10H8F3NO2 (M ꢁ H) 230.0427,
found 230.0425.
8-Methyl-3,5-dihydro-[1,4]oxazepino[5,6-b]quinolin-2(H)-one 2j
85% yield, m.p. 134–135 ꢀC; 1H NMR (400 MHz, CDCl3): d ppm
2.51 (s, 3H), 4.69 (s, 2H), 4.85 (s, 2H), 7.51 (d, J ¼ 7.6 Hz, 2H),
7.77 (d, J ¼ 8.4 Hz, 1H), 7.80 (s, 1H), 8.47 (s, 1H); 13C NMR (100
MHz, CDCl3): d ppm 21.5, 72.2, 74.3, 123.3, 125.0, 126.1, 127.2,
132.8, 135.7, 145.0, 147.6, 172.3; IR v (cmꢁ1): 2919.9, 1658.6,
1447.8, 1084.8, 656.7; HRMS calcd for C13H12N2O2 (M ꢁ H)+
227.0821, found 227.0848.
8-(Triuoromethyl)-3,5-dihydrobenzo[e][1,4]oxazepin-2(H)-
one 2e
92% yield, m.p. 128–129 ꢀC; 1H NMR (400 MHz, CDCl3): d ppm
4.56 (s, 2H), 4.77 (s, 2H), 7.09 (d, J ¼ 8.4 Hz, 1H), 7.37 (s, 1H),
7.53 (d, J ¼ 8.4 Hz, 1H), 9.44 (s, 1H); 13C NMR (100 MHz, CDCl3):
d ppm 72.9, 74.0, 119.6, 123.9 (q, J ¼ 270.2 Hz), 125.7 (q, J ¼ 32.6
2H-Benzo[b][1,4]oxazin-3(4H)-one 2k6a,16,17
Hz), 125.7 (q, J ¼ 3.9 Hz), 126.4 (q, J ¼ 3.9 Hz), 129.2, 138.9, Known compound, 99% yield; 1H NMR (400 MHz, CDCl3):
174.5; 19F NMR: d ppm 62.1; IR v (cmꢁ1): 2919.9, 1658.6, 1447.8, d ppm 4.63 (s, 2H), 6.82–6.98 (m, 4H), 8.07 (s, 1H); 13C NMR (100
1084.8, 656.7; HRMS calcd for C10H8F3NO2 (M ꢁ H)+ 230.0427, MHz, CDCl3): d ppm 67.2, 116.0, 116.8, 122.7, 124.3, 126.0,
found 230.0429.
143.6, 165.9.
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2-Methyl-2H-benzo[b][1,4]oxazin-3(4H)-one 2l17
8-Amino-2H-benzo[b][1,4]oxazin-3(4H)-one 2s20
Known compound, 97% yield; 1H NMR (400 MHz, CDCl3): Known compound, 85% yield; 1H NMR (400 MHz, CDCl3):
d ppm 1.59 (d, J ¼ 6.8 Hz, 3H), 4.67 (q, J ¼ 6.8 Hz, 1H), 6.88–6.89 d ppm 4.73 (s, 2H), 6.73 (dd, J1 ¼ 8.0 Hz, J2 ¼ 1.2 Hz, 1H), 6.90 (t,
(m, 1H), 6.96–6.97 (m, 3H), 9.68 (s, 1H); 13C NMR (100 MHz, J ¼ 8.0 Hz, 1H), 7.06 (dd, J1 ¼ 8.0 Hz, J2 ¼ 1.2 Hz, 1H), 8.61 (s,
CDCl3): d ppm 16.2, 73.2, 115.9, 117.0, 122.6, 124.1, 126.4, 143.1, 1H); 13C NMR (100 MHz, CDCl3): d ppm 67.4, 114.3, 122.2,
168.9.
122.9, 125.1, 127.1, 139.8, 165.4.
2H-Benzo[b][1,4]thiazin-3(4H)-one 2m18,19
Conflicts of interest
Known compound, 99% yield; 1H NMR (400 MHz, CDCl3):
d ppm 3.44 (s, 2H), 6.90 (d, J ¼ 8.0 Hz, 1H), 7.01 (dt, J1 ¼ 8.0 Hz,
J2 ¼ 1.2 Hz, 1H), 7.17 (dt, J1 ¼ 7.6 Hz, J2 ¼ 1.2 Hz, 1H), 7.31 (d, J
¼ 7.8 Hz, 1H), 9.11 (s, 1H); 13C NMR (100 MHz, CDCl3): d ppm
29.9, 117.4, 119.9, 123.9, 127.2, 127.8, 136.3, 166.4;
There are no conicts to declare.
Acknowledgements
The authors thank the Natural Science Foundation of the
Jiangsu Higher Education (Grant No. 15KJB150029), the Project
of Science and Technology of Xuzhou Government (No.
KC16SG250) and the Natural Science Foundation of Jiangsu
Province (Grants No. BK 20171175). The work is also sponsored
by Qing Lan Project of Jiangsu Province and Zhen Xing Project
of XZMC.
2-Methyl-2H-benzo[b][1,4]thiazin-3(4H)-one 2n18,19
Known compound, 98% yield; 1H NMR (400 MHz, CDCl3):
d ppm 1.50 (d, J ¼ 7.2 Hz, 3H), 3.56 (q, J ¼ 7.2 Hz, 1H), 6.89 (d, J
¼ 8.4 Hz, 1H), 7.02 (t, J ¼ 6.8 Hz, 1H), 7.18 (t, J ¼ 8.0 Hz, 1H),
7.30–7.31 (m, 1H), 8.86 (s, 1H); 13C NMR (100 MHz, CDCl3):
d ppm 15.4, 37.0, 116.9, 119.4, 123.8, 127.1, 128.1, 136.0, 168.9.
Notes and references
7-Methyl-2H-benzo[b][1,4]oxazin-3(4H)-one 2o18
1 (a) H. Otsuka, Y. Hirani, T. Nagao and K. Yamasaki, J. Nat.
Prod., 1988, 51, 74; (b) A. S. Bourlot, I. Sanchez, G. Dureng,
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(c) D. A. Dudley, A. M. Bunker, L. Chi, W. L. Cody,
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R. Fringuelli, D. Pietrella, F. Schiaffella, A. Guarraci,
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2002, 10, 1681.
Known compound, 95% yield; 1H NMR (400 MHz, CDCl3):
d ppm 2.28 (s, 3H), 4.60 (s, 2H), 6.67 (s, 1H), 6.78 (d, J ¼ 8.0 Hz,
1H), 6.87 (d, J ¼ 8.4 Hz, 1H), 9.41 (s, 1H); 13C NMR (100 MHz,
CDCl3): d ppm 20.7, 67.2, 116.5, 116.7, 120.3, 124.7, 125.8, 132.5,
166.6.
6-Methyl-2H-benzo[b][1,4]oxazin-3(4H)-one 2p18,19
Known compound, 95% yield; 1H NMR (400 MHz, CDCl3):
d ppm 2.28 (s, 3H), 4.60 (s, 2H), 6.67 (s, 1H), 6.78 (dd, J1 ¼ 8.4 Hz,
J2 ¼ 1.2 Hz, 1H), 6.86 (d, J ¼ 7.6 Hz, 1H), 9.36 (s, 1H); 13C NMR
(100 MHz, CDCl3): d ppm 20.6, 67.2, 116.4, 116.5, 124.7, 125.7,
132.5, 141.4, 166.7.
2 T. B. Lanni Jr, K. L. Greene, C. N. Kolz, K. S. Para, M. Visnick,
J. L. Mobley, D. T. Dudley, T. J. Baginski and M. B. Liimatta,
Bioorg. Med. Chem. Lett., 2007, 17, 756.
3 C. Su, C. Tseng, C. Ramesh, H. Liu, C. Huang and C. Yao, Eur.
J. Med. Chem., 2017, 132, 90.
4 H. Chan, Synthesis, 1984, 10, 851.
6-Methoxy-2H-benzo[b][1,4]oxazin-3(4H)-one 2q18,19
Known compound, 96% yield; 1H NMR (400 MHz, CDCl3):
d ppm 3.76 (s, 3H), 4.57 (s, 2H), 6.40 (d, J ¼ 2.4 Hz, 1H), 6.50 (dd,
J1 ¼ 8.6 Hz, J2 ¼ 3.2 Hz, 1H), 6.85 (d, J ¼ 8.8 Hz, 1H), 8.93 (s, 1H);
13C NMR (100 MHz, CDCl3): d ppm 55.8, 67.4, 102.1, 108.8,
117.2, 126.8, 137.6, 155.3, 166.6.
5 (a) T. Miki, M. Kori, H. Mabuchi, H. Banno, R. Tozawa,
M. Nakamura, S. Itokawa, Y. Sugiyama and H. Yukimasa,
Bioorg. Med. Chem., 2002, 10, 401; (b) E. Feng, H. Huang,
Y. Zhou, D. Ye, H. Jiang and H. J. Liu, J. Org. Chem., 2009,
74, 2846; (c) A. Shari, M. Barazandeh, A. Saeed and
M. Mirzaei, Tetrahedron Lett., 2010, 51, 1852; (d) D. Chen,
Z. Wang and W. Bao, J. Org. Chem., 2010, 75, 5768.
6 (a) D. Chen, G. Shen and W. Bao, Org. Biomol. Chem., 2009, 7,
4067; (b) A. Shari, M. Ansari, H. Darabi and M. Abaee,
Tetrahedron Lett., 2016, 57, 529.
7 (a) J. F. Hartwig, Acc. Chem. Res., 1998, 31, 852; (b)
J. F. Hartwig, Acc. Chem. Res., 2008, 41, 1534.
8 (a) J. P. Wolfe, S. Wagaw, J. F. Marcoux and S. L. Buchwald,
Acc. Chem. Res., 1998, 31, 805; (b) A. R. Muci and
S. L. Buchwald, Top. Curr. Chem., 2002, 219, 131.
1H-Naphtho[2,1-b][1,4]oxazin-2(3H)-one 2r
96% yield, m.p. 207–208 ꢀC; 1H NMR (400 MHz, CDCl3): d ppm
4.76 (s, 2H), 7.22 (d, J ¼ 8.2 Hz, 1H), 7.43 (td, J1 ¼ 7.8 Hz, J2 ¼
0.8 Hz, 1H), 7.54 (d, J ¼ 9.2 Hz, 1H), 7.58 (td, J1 ¼ 7.8 Hz, J2 ¼
1.2 Hz, 1H), 7.83 (d, J ¼ 8.4 Hz, 1H), 7.94 (d, J ¼ 8.0 Hz, 1H), 9.66
(s, 1H); 13C NMR (100 MHz, CDCl3): d ppm 67.5, 117.4, 118.7,
119.0, 123.0, 124.3, 124.7, 127.0, 128.7, 130.0, 140.6, 166.0; IR v
(cmꢁ1): 3189.9, 2961.3, 2877.5, 1681.8, 1458.9; HRMS calcd for
C
12H9NO2 (M + Na)+ 222.0531, found 222.0527.
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