Dual C-H activations of electron-deficient heteroarenes: Palladium-catalyzed oxidative cross coupling of thiazoles with azine N-oxides

Article abstract of DOI:10.1016/j.tet.2012.10.048

The palladium-catalyzed, copper-promoted cross-dehydrogenative-coupling (CDC) of electron-deficient thiazoles with azine N-oxides through dual C-H activations was developed. It was found that copper(II) pivalate was an efficient dual-function reagent for the oxidative cross-coupling reactions, playing the roles of both an oxidant and a C-H bond activation promoter. This methodology provides a simple way to construct 2-thiazolyl pyridine moiety.

Full text of DOI:10.1016/j.tet.2012.10.048

Accepted Manuscript
Dual C-H activations of electron-deficient heteroarenes: palladium-catalyzed oxidative
cross coupling of thiazoles with azine N-oxides
Xiao-Pu Fu, Qing-Qing Xuan, Li Liu, Dong Wang, Yong-Jun Chen, Chao-Jun Li
PII:
S0040-4020(12)01608-0
10.1016/j.tet.2012.10.048
TET 23651
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 6 September 2012
Revised Date: 11 October 2012
Accepted Date: 16 October 2012
Please cite this article as: Fu X-P, Xuan Q-Q, Liu L, Wang D, Chen Y-J, Li C-J, Dual C-H activations of
electron-deficient heteroarenes: palladium-catalyzed oxidative cross coupling of thiazoles with azine N-
oxides, Tetrahedron (2012), doi: 10.1016/j.tet.2012.10.048.
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Dual C-H activations of electron-deficient
heteroarenes: palladium catalyzed oxidative
cross coupling of thiazoles and azine N-
oxides
Leave this area blank for abstract info.
Xiao-Pu Fu, Qing-Qing Xuan, Li Liu*, Dong Wang, Yong-Jun Chen, Chao-Jun Li*
10 mol% Pd(OAc)2
Y
Y
S
S
N
Cu(OPiv)2, CuBr
H
R1
H
R1
R2
Cs2CO3
R2
N
N
O
N
O
Dioxane/DMSO, 110oC
23 examples, up to 82% yield

ACCEPTED MANUSCRIPT
1
Tetrahedron
journal homepage: www.elsevier.com
Dual C-H activations of electron-deficient heteroarenes: palladium-catalyzed
oxidative cross coupling of thiazoles with azine N-oxides
Xiao-Pu Fu,a Qing-Qing Xuan,a Li Liu,a* Dong Wang,a Yong-Jun Chena and Chao-Jun Lib*
a Beijing National Laboratory for Molecular Science (BNLMS), CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese
Academy of Sciences, Beijing 100190, China.
b Department of Chemistry, McGill University, Montreal, Quebec, H3A 2K6 Canada.
ARTICLE INFO
ABSTRACT
article history:
Received
Received in revised form
Accepted
The palladium-catalyzed, copper-promoted cross-dehydrogenative-coupling (CDC) of
electron-deficient thiazoles with azine N-oxides through dual C-H activations was
developed. It was found that copper(II) pivalate was an efficient dual-function reagent
for the oxidative cross-coupling reactions, playing the roles of both an oxidant and a
C-H bond activation promoter. This methodology provides a simple way to construct
2-thiazolyl pyridine moiety.
Available online
Keywords:
Double C-H activations
Cross-dehydrogenative coupling
Thiazoles
2009 Elsevier Ltd. All rights reserved.
Azine N-oxides
Copper(II) pivalate
Electro-deficient heteroarenes
1. Introduction
homocoupling of electron-poor heterocycles and polyfluorinated
arenes have been reported,14 the cross-coupling between electron-
The biaryls and their biheteroaryl analogs are ubiquitous
structural cores of natural products, pharmaceuticals, biological
and functional materials. Among these molecules, 2-thiazolyl
deficient (hetero)arenes were still rare. Ofial has reported the
Pd(II)-catalyzed cross-coupling of benzazoles with azoles.15
Later on, You and co-workers developed the oxidative cross-
coupling between two structurally similar azoles.16 Very recently,
Cu(OAc)2-mediated dehydrogenative cross-coupling between
two heteroarenes has been realized.17 However, the dual
oxidative C-H/C-H cross-coupling of electron-deficient
pyridine moiety are frequently found in various bioactive
compounds (Figure 1)1,
A widely employed protocol to
2
construct the C–C bond of bi(hetero)aryls is transition-metal-
catalyzed cross-coupling reactions of (hetero)aryl halide with
(hetero)arylmetallics.3 However, many arylmetallics, especially
HO
metallated electron-deficient heteroarenes, are not easily
H
O
available or sluggish to undergo coupling reactions.4,
For
5
O
S
S
O
NH
S
NH
N
NH
O
instance, the formation of 2-azolyl pyridine via Pd(0)-catalyzed
cross-coupling reaction between 2-haloheteroarenes and
organometallics inevitably encounter these difficulties (Scheme 1,
Eqs. 1 and 2).6 Recently, Pd(0)-catalyzed direct arylation
reactions, in which one coupling partner is an unactivated arene,
have emerged as potentially more efficient synthetic approach
than the conventional strategy (Scheme 1, Eq. 3).7, 8 Obviously,
an even more attractive alternative is the direct (hetero)arylation
through dual C–H activations of two unactivated (hetero)arenes
(i.e., the cross-dehydrogenative coupling, CDC).9, 10
N
S
O
N
N
S
HN
O
N
O
N
S
O
N
NH
O
N
NH
O
O
S
N
H
HN
N
HN
HO
O
S
OH
O
TMC435350
HCV NS3/4A protease inhibitor
Micrococcin P1
N
O
Cl
O
O
N
N
MeS
H
N
OMe
N
N
N
N
HO
N
S
S
O
Me
Although an array of oxidative C-H/C-H cross-coupling
processes have been well developed, the suitable substrates are
still restricted to electron-rich and directing-group-containing
(hetero)arenes in order to achieve high reactivity and
regioselectivity.11, 12 Few reaction systems have been employed
for the catalytic arylation of electron-deficient arenes with
electron-neutral arenes.13 Despite several protocols for the
Iodopyridone
Tuberculostatic
activity
Figure 1. Natural and bioactive compounds containing 2-
azolyl pyridine scaffold

ACCEPTED MANUSCRIPT
2
Tetrahedron
heteroarenes still remain challenging due to their competitive
Table 1. Optimization of Conditionsa
10 mol%Pd(OAc)2
homocoupling. Based on our ongoing interest in exploring C-C
bond formations via CDC reactions,18,19 herein, we would like to
report the palladium-catalyzed oxidative cross-coupling of
thiazoles with azine N-oxides though dual C-H bond activations
for the synthesis of 2-thiazolyl pyridine compounds (Scheme 1,
eq. 4).
S
N
S
oxidant, base, additive
Solvent(5%DMSO)
N2, 12 h, 110oC
H
H
N
O
N
N
O
3a
1a
2a
Entry
Oxidant
Ag2CO3
Base
-
Additives
Yieldb(%)
26
1
2
-
Reported works
AgOAc
-
-
20
R2
Y
3
Cu(OAc)2
-
-
35
R1
X
M
(1)
4
Cu(OAc)2·H2O
Cu(OAc)2
-
-
20
N
N
N
5
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
-
44
R2
Y
N
Pd(0)
Y
N
R2
6
Cu(OPiv)2
Cu(tAmylCO2)2
Cu(EtCO2)2
Cu(iPrCO2)2
Cu(1-AdCO2)2
Cu(OPiv)2
Cu(OPiv)2
Cu(OPiv)2
-
56
R1
M
R1
X
(2)
(3)
7
-
49
N
M=Si, Sn, Zn, B X=Cl, Br, I
8
-
41
Y=N, O, S
R2
Y
9
-
40
R1
X
H
N
N
10
11
12c
13d
-
29
X=Cl, Br, I
Single C-H
activation
CuBr
CuBr
CuBr
67
66
This work
60
R2
R2
S
S
R1
aReaction conditions: Pd(OAc)2 (0.05 mmol, 10 mol%),
oxidant (1.5mmol, 3.0 equiv.), Cs2CO3 (0.5 mmol, 1.0 equiv),
pyridine N-oxide (2.0 mmol, 4.0 equiv), dioxane/DMSO (19:1,
4.0 mL, 1.3 M) and benzothiazole (0.5 mmol, 1.0 equiv), N2, 110
ꢀ, 12h.
Pd(II)
(4)
R1
H
N
O
H
N
N
O
Oxidant
N
[H]
Dual C-H activation
R2
S
R1
N
N
b1HNMR yields with 1,3,5-trimethoxybenzene as an internal
standard.
Scheme 1. Access to 2-azolyl pyridines through metal-
catalyzed cross-coupling reactions
cDioxane/DMSO(19:1, 5 mL, 1.0 M).
dDioxane/DMSO(19:1, 2.5 mL, 2.0M).
2. Results and discussion
2.1. Optimization of Conditions
with electron-donating groups afforded the corresponding
products in better yields than those with electron-withdrawing
groups. A range of functional groups, including fluoro, chloro,
bromo and ester, were tolerated under the optimized reaction
conditions, providing opportunity for further functionalization.
Initially, the reaction of benzothiazole 1a with N-oxide
pyridine 2a using Pd(OAc)2 as a catalyst (10 mol%) was carried
out in dioxane. 20 When a silver(I) salt, frequently employed as an
oxidant in the C-H activation reactions,11a-e, 13a-c was used in the
coupling reaction of 1a with 2a, the desired product 3a was
obtained in <26% yield (Table 1, entries 1 and 2). Cu(OAc)2 was
found to be more effective in this reaction, producing 3a in 35%
yield (entry 3). You and co-workers recently reported Pd(II)-
catalyzed oxidative cross-coupling between azoles and electron-
Next, the scope of azine N-oxide substrates was briefly
surveyed. Various electron-withdrawing or electron-donating
substituents did not affect the reaction significantly. For 3-
picoline-N-oxide (2b), cross coupling reaction occurred
preferentially at the ortho position that is more sterically
accessible and gave 3k in 51% yield (3k/3k’=4:1, entry 11).
When 2-picoline-N-oxide (2d, entry 13) was used, only 22%
yield of coupling-product was isolated (3m) which could be
caused by the formation of an unreactive palladacycle
intermediate. Noteworthy that the chloro, nitro, ester, alkoxy,
trifluoromethyl and acetyl groups were all compatible with the
reaction conditions well. In addition, quinoline N-oxide (2m) and
pyrazine N-oxide (2l) were also efficient substrates and afforded
moderate yields (entries 22, 23). Unfortunately, benzoxazole and
benzimiazole could not react with pyridine N-oxide under the
optimized conditions. The structure of 3c was unambiguously
confirmed by X-ray crystallographic analysis (Figure 2).
rich heteroarenes in the presence of the Cu(OAc)2·H2O.11f,
m
However, the use of Cu(OAc)2·H2O as an oxidant in the reaction
of 1a with 2a gave an inferior yield (20%, entry 4). On the other
hand, alkali carbonates play an important role in the coupling
reaction. After screening of various bases, the yield increased to
44% in the presence of Cs2CO3 (entries 5 vs 3). Subsequently, we
investigated various copper(II) carboxylates (Table 1, entries 6-
10). It was found that Cu(OPiv)2 was the oxidant of choice and
the desired product 3a was obtained in 56% yield (entry 6).
When CuBr was used as an additive, the yield of 3a was
increased to 67%. It is noteworthy that a high concentration gave
inferior results (entry 13). The combinative system provided the
best results for dual C-H activations of electron-deficient
(hetero)arenes, suppressing the homo-coupling side reaction
efficiently and favoring the CDC reactions.
2.2. Substrates Scope
With the optimal reaction conditions in hand, the scope of
substrates was investigated and various 2-thiazolyl pyridine N-
oxides were obtained in moderate to good yields (40-82 %, Table
2). To our delight, not only benzothiazoles (1a-g) but also
thiazoles derivatives (1h-j) smoothly underwent the cross-
dehydrogenative-couplings (CDC). In general, benzothiazoles
Figure 2. The X-ray crystal structure of 3c (Thermal ellipsoids
are drawn at the 50% probability level).

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3
Table 2. Substrate scope of the CDC reaction between thiazoles and azine N-oxides
Pd(OAc)2 (10 mol%), CuBr (0.1eq)
Y
S
N
Y
S
N
Cu(OPiv)2 (3.0 eq.), Cs2CO3 (1.0 eq.)
R1
R1
H
H
R2
R2
Dioxane/DMSO, 0.13 M
110oC, N2
N
O
N
O
3
1
2
Azine
N-oxide
Yieldb
(%)
Azine
N-oxide
Yieldb
(%)
Entry
Entry
Thiazole
Product
Thiazole
Product
S
S
N
S
3l
1
2
3
3a
67
12
1a
61
2c
N
N
O
N
O
2a
N
N
N
N
O
1a
O
S
S
N
S
3m
2d
2a
1a
3b
70
72
13
22
82
N
N
N
O
N
O
O
OBn
1b
OBn
MeO
S
N
MeO
S
N
S
N
3n
3c
14c,d
2a
2a
2a
2a
2a
2a
2a
1a
1a
1a
1a
1a
1j
2e
N
N
O
N
O
1c
O
OMe
OMe
Cl
S
Cl
S
N
S
4
5
6
7
3d
59
67
58
47
15c,d
3o
65
65
64
51
2f
N
N
O
N
N
N
1d
O
O
Cl
Cl
S
N
S
N
S
3p
3e
16
2g
N
N
N
N
O
O
Cl 1e
Cl
O
CO2Et
CO2Et
F
S
F
S
N
S
3f
17
2h
3q
N
N
O
N
N
N
O
Ac
1f
O
O
Br
S
Br
S
S
3g
18
2i
N
3r
3s
N
O
N
N
O
N
N
1g
O
O
S
S
N
EtO2C
8c,d
1h
3h
54
57
19c,d
62
51
S
2i
N
N
N
O
N
O
NO2
NO2
S
S
N
S
9c,d
3i
20
1a
2j
3t
N
N
AcO
N
N
O
N
O
AcO
1i
O
CF3
CF3
EtO2C
S
EtO2C
S
N
S
10c,d
2a
64
21
1a
2k
2l
66
3j
3u
N
N
O
N
O
N
N
O
1j
N
S
N
N
S
N
3v
3k
51
13
22d,e
1a
1a
40
53
N
O
N
O
N
O
1a
11
N
O
2b
S
S
23c,d
3w
3k'
N
O
N
N
N
N
2m
O
O
aReaction conditions: Pd(OAc)2 (0.05 mmol, 10 mol%), Cu(OPiv)2 (1.5mmol, 3.0 eq.), Cs2CO3 (0.5 mmol, 1.0 eq.), azine N-oxide
(2.0 mmol, 4.0 eq.), CuBr (0.05 mmol, 10 mol%), dioxane/DMSO (19:1, 4.0 mL, 1.3 M) and thiazoles (0.5 mmol, 1.0 eq.), N2, 110ꢀ,
12h.
bIsolated yield.
cHeated at 120 ꢀ.
dCuCl was used as an additive instead of CuBr.
eHeated at 130 ꢀ.

ACCEPTED MANUSCRIPT
4
Tetrahedron
The resultant coupling products can be deoxygenated to give
Kinetic isotope effect experiments were performed and a
kinetic isotope effect (KIE) of kH/kD = 3.0 was observed, thus
indicating that the cleavage of the C-H bond of pyridine N-oxide
is involved in the product determining step (Scheme 3).
2-thiazollypyridine 4 in high yield by reacting with PCl3 (Scheme
2).
S
N
PCl3
S
N
DCM, reflux, 5 h
N
10 mol%Pd(OAc)2
N
S
N
O
3.0 eq. Cu(OPiv)2
1.0 eq. Cs2CO3
3a
4,
86%
N
N
O
Scheme 2. Deoxygenation of 2-thiazolyl pyridine N-oxides
O
S
N
4.0 eq.
10 mol% CuBr
H
S
N
D5
D4
Solvent(5%DMSO)
0.13M
2.3. Mechanistic Studies
N2, 110 oC 12 h
1.0 eq
N
O
N
To gain insight into the reaction mechanism, we investigated
the effect of additives on the coupling reaction. Cu(I) was shown
to be an efficient C-H bond activator in direct arylation of N-
heteroarenes. 11m,f,16,21 However, it was unexpected to find that the
addition of CuBr to the system of Pd(OAc)2/Cu(OAc)2 reduced
the yield of 3a to 33% while an increased amount of
bisbenzothiazole byproduct was produced (Table 3, entry 1 vs 2).
This observation might be attributed to the copper(I)-facilitated
C-H metalation of thiazole and subsequent dimerization. We
speculated that if the C-H bond of pyridine N-oxide could be
activated further to match the reactivity of thiazolylmetal species,
the dimerization of benzothiazole would be inhibited to some
extent.
It was reported that carboxylate anion is often involved in C-
H bond cleavage and can enhance the efficiency of C-C bond
formation in metal-catalyzed direct arylation.11b,j,22 However, the
addition of either a catalytic or stoichiometric amount of cesium
pivalate showed no effect (entries 3, 4). This effect is probably
due to the fact that the excess acetate saturated the catalyst and
thus prevented pivalate ion from binding to the metal center. A
higher amount of cesium pivalate was even detrimental to the
reaction (entry 5). We envisioned that Cu(OPiv)2 might be a
suitable reagent playing the roles of both an oxidant as well as a
C-H bond activation promoter. When Cu(OPiv)2 was chosen as a
dual-function reagent, the desired product 3a was obtained in
67% yield while the yield of homocoupling byproduct 5
decreased to 11% (entry 6).
O
kH/kD 3.0
4.0 eq.
Scheme 3. Kinetic isotope effect experiments
Although the mechanism remains to be elucidated, a plausible
reaction pathway to rationalize this transformation is illustrated
in Scheme 4 on the basis of the experimental observations. The
catalytic cycle may involve the following five steps: 1) formation
of benzothiazolyl copper(I) 6 through C-H metalation of
benzothiazole; 2) transmetalation with Pd(II) to form aryl-Pd(II)
intermediate 7; 3) coordination with pyridine N-oxide and C-H
metalation through a concerted metalation-deprotonation (CMD)
process using pivalate ion as proton shuttle; 4) reductive
elimination to afford the coupling product 3aꢁ 5) oxidation of
Pd(0) to Pd(II) by Cu(II).
Cu(II)
Cu(I)
S
Pd(0)
N
N
Pd(II)
S
N
O
3a
Cu(I)
6
H
O
N
O
d
P
O
N
Cu(I)
PdX
S
N
S
S
7
H
1a
8
N
Table 3. Effect of additives on the oxidative cross-coupling
reactiona
S
N
Cs2CO3
Piv
S
2
N
O
5
2a
10 mol%Pd(OAc)2
Cu(II), Cs2CO3
N
3a
N
O
S
N
Scheme 4. Proposed reaction pathways for oxidative cross
coupling between benzothiazole and pyridine N-oxide
H
H
dioxane(5%DMSO)
N2, 12 h, 110oC
S
N
S
N
O
1a
2a
N
3. Conclusion
5
Yieldb(%)
5
Entry
Oxidant
Cu(OAc)2
Cu(OAc)2
Additives
Yield b(%) 3a
In summary, we have developed a palladium-catalyzed
copper-promoted cross-dehydrogenative coupling (CDC)
between electron-deficient thiazoles and azine N-oxides in
moderate to good yields. Copper(II) pivalate was an efficient
dual-function reagent for the oxidative C-H/C-H cross-coupling
reactions, playing the roles of both an oxidant as well as a C-H
bond activation promoter. This methodology provides an
efficient way to construct 2-thiazolyl pyridine moiety, which is
abundant in bioactive compounds.
1
2
-
44
33
24
30
CuBr (0.1 eq.)
CsOPiv/CuBr
(0.3 eq. / 0.1 eq.)
CsOPiv/CuBr
(1.0 eq. / 0.1 eq.)
CsOPiv/CuBr
3
4
Cu(OAc)2
Cu(OAc)2
45
43
26
22
5
6
Cu(OAc)2
Cu(OPiv)2
23
67
35
11
(3.0 eq. / 0.1 eq.)
CuBr (0.1 eq.)
aReaction conditions: Pd(OAc)2 (0.05 mmol, 10 mol%),
oxidant (1.5mmol, 3.0 equiv), Cs2CO3 (0.5 mmol, 1.0 equiv),
pyridine N-oxide (2.0 mmol, 4.0 equiv), dioxane/DMSO (19:1,
4.0 mL, 1.3 M) and benzothiazole (0.5 mmol, 1.0 equiv), N2, 110
ꢀ, 12h.
4. Experimental
4.1. General
1
All the H and 13C NMR were recorded on a Bruker-AV 300
spectrometer and chemical shifts reported in CDCl3 or DMSO-d6
with tetramethylsilane as an internal standard. IR spectra were
recorded on a Bruker tensor 27 infrared spectrometer. Melting
points were measured on a Beijing-Tiker X-4 apparatus without
correction. HRMS spectra were recorded on a GCT-Mass
b1HNMR yields with 1,3,5-trimethoxybenzene as an internal
standard.

ACCEPTED MANUSCRIPT
5
Micromass spectrometer. Unless otherwise noted all reagents and
used without further purification. Dioxane was distilled over Na
substrates were purchased from commercial sources and were
and benzophenone, and stored under N2 in dark. Copper bromide
was purified by washing with glacial acetic acid, absolute
ethanol and ether sequentially, dried under high vacuum and then
stored under N2. All reagents were weighed and handled in air at
room temperature. Column chromatography was performed
using silica gel (200-300 mesh). TLC was performed on glass-
backed silica plates.
organic phase was dried over Na2SO4, concentrated under
vacuum, and purified by column chromatography on silica gel
(eluent: DCM/acetone=20:1) to provide the desired product 3a as
a pale yellow solid (75 mg, 67% yield).
4.4.2. 2-(benzo[d]thiazol-2-yl)pyridine 1-oxide(3a)
Pale yellow solid (76 mg, 67% yield), m.p.= 159-162ꢀ; IR
1
(KBr, cm-1) 1437, 1321, 985, 761; H NMR (CDCl3, 300 MHz)
4.2. Experimental Procedure for the Synthesis of Copper(II)
Carboxylates
7.37-7.42 (m, 1H), 7.46-7.51 (m, 2H), 7.55-7.60 (m, 1H), 8.05(d,
1H, J =6.5Hz), 8.14 (d, 1H, J = 8.1Hz), 8.41 (d, 1H, J = 6.5 Hz),
8.79 (dd, 1H, J = 8.1Hz, 2.1Hz); 13C NMR (CDCl3, 75MHz)
121.9, 123.3, 125.6, 125.9, 126.6, 136.6, 1 39.5, 142.4, 151.8,
156.3; ESI-HRMS (m/z): [M+H]+ calcd. for C12H9N2OS,
229.04301, found 229.04300
Copper(II) carboxylates were synthesized according to the
literature procedure with small modifications.23 Cu(OH)2 (0.48
mol, 50 g, 94% purity, 1.0 equiv) were added to the solution of
pivalic acid (1.0 mol, 103.3 g, 2.1 equiv) in ethanol (500 mL)
and refluxed for 16 h. The undissolved solid was filtered off and
the filtrate was concentrated under reduced pressure to 200 mL.
Copper(II) pivalate was recrystallized from EtOH, washed with
EtOH, ether, and dried under high vacuum to give 108 g of a
bluish-green solid (84% yield). Other copper(II) carboxylates
were prepared according to above procedure with slightly
modifications: after filtering off the undissolved solid in hot
reaction mixture, water was added to the cooled filtrate and the
resulting precipitate was collected by filtration.
4.4.3. 2-(6-methylbenzo[d] thiazol-2-yl)pyridine 1-
oxide(3b)
Pale yellow solid (85 mg, 70% yield)., m.p.= 177-179ꢀ; IR
1
(KBr, cm-1) 1427, 984, 806, 764; H NMR (CDCl3, 300 MHz)
2.54( s, 3H), 7.33-7.40 (m,2H), 7.43-7.49 (m, 1H), 7.82 (s, 1H),
8.01(d, 1H, J =8.4Hz), 8.39 (d, 1H, J = 6.5Hz), 8.75 (dd, 1H, J
= 8.2 Hz, 2.0Hz); 13C NMR (CDCl3, 75MHz) 21.8, 121.4, 122.8,
125.3, 125.5, 125.9, 128.5, 136.3, 137.0, 139.5, 142.6, 150.2,
155.4; ESI-HRMS (m/z): [M+H]+ calcd. for C12H11N2OS,
243.05866, found 243.05873.
4.3. Experimental Procedure for the Synthesis of
Thiazoles
4.4.4. 2-(6-methoxybenzo[d] thiazol-2-yl)pyridine
1-oxide (3c)
Thiazoles (1b-f, j) were prepared from 2-aminothiazoles
according to the reported procedure with slight modifications.24
Yellow solid (93 mg, 72% yield). m.p.= 196-198ꢀ; IR (KBr,
1
cm-1) 1600, 1492, 1431, 1230, 1020, 773; H NMR (CDCl3, 300
To
a
mechanically-stirred
solution
of
2-amino-6-
MHz) 3.93( s, 3H), 7.17 (dd, 1H, J = 9.0 Hz, 2.5 Hz), 7.32-7.37
(m, 1H), 7.44-7.48 (m, 2H), 8.00 (d, 1H, J = 9.0Hz), 8.38(d, 1H,
J =6.6 Hz), 8.71 (dd, 1H, J = 8.2Hz, 1.9Hz); 13C NMR (CDCl3,
75MHz) 55.9, 102.9, 117.4, 124.1, 125.1, 125.3, 126.1, 138.5,
139.5, 142.7, 146.8, 154.0, 158.5; ESI-HRMS (m/z): [M+H]+
calcd. for C13H11N2O2S, 259.05357, found 259.05392.
chlorobenzothiazole (4g, 21.7 mmol, 1.0 equiv) in 84% aq.
phosphoric acid (80 mL) was added a solution of sodium nitrite
(9.0 g, 13 mmol, 6.0 equiv) in water (28 mL) dropwise below the
surface at -10ꢀ. After stirring at -10ꢀ for another 2 h, a 50% aq.
solution of hypophosphorous acid (60 mL) was added dropwise
to the resulting thick syrup mixture at -5ꢀ. The reaction mixture
was warmed to room temperature, stirred overnight and then
diluted with water (300 mL). Na2CO3 was added portionwise to
adjust to pH=8 and extracted with DCM. The organic phase was
dried over Na2SO4, concentrated under vacuum, and purified
over column chromatography (petroleum ether/EtOAc=100:1) to
give 6-chlorobenzothiazole as white solid (2.2 g, 59% yield).
4.4.5. 2-(6-chlorobenzo[d]thiazol-2-yl)pyridine 1-
oxide(3d)
Yellow solid (78 mg, 59% yield). m.p.= 214-216ꢀ; IR (KBr,
1
cm-1) 1428, 1315, 1252, 764; H NMR (CDCl3, 300 MHz) 7.38-
7.44 (m, 1H), 7.47-7.54 (m, 2H), 8.01(d, 1H, J = 2.0Hz), 8.04 (d,
1H, J = 8.8Hz), 8.41(d, 1H, J=6.4Hz), 8.75 (dd, 1H, J = 8.4 Hz,
2.1Hz); 13C NMR (CDCl3, 75MHz) 121.5, 124.3, 125.7, 125.9,
126.2, 127.6, 132.0, 137.9, 139.5, 142.3, 150.5, 157.0; ESI-
HRMS (m/z): [M+H]+ calcd. for C12H8ClN2OS, 263.00404,
found 263.00412.
4.4. Palladium Catalyzed Oxidative Cross Coupling of
Thiazoles and Azine N-oxides
4.4.1. General Procedure
A flame-dried 25-mL Schlenk flask equipped with a magnetic
stir bar was charged with Pd(OAc)2 (11.2 mg, 0.05 mmol, 10
mol%), copper(II) pivalate (400 mg, 1.5 mmol, 3.0 equiv),
Cs2CO3 (163 mg, 0.5 mmol, 1.0 equiv), pyridine N-oxide (190
mg, 2.0 mmol, 4.0 equiv) and CuBr(7 mg, 0.05 mmol, 10 mol%).
The flask was fitted with a rubber septum, evacuated and refilled
with argon (repeating 3 times). Dioxane/DMSO (19:1, 4.0 mL)
and benzothiazole (67.3 mg, 0.5 mmol, 1.0 equiv) were added
via syringes under an atmosphere of N2. The septum was then
replaced by a teflon-coated screw cap under N2. The reaction
mixture was stirred at room temperature for 15 min and then in a
preheated oil bath (at 110 ꢀ) for 12 h, cooled down to room
temperature, diluted with DCM (15 mL) and filtered through a
celite pad. The filtrate was then washed twice with 10-20 mL of
DCM. The combined organic extracts were washed with 5 mL of
saturated NH4Cl aq. solution (containing 1% v/v ammonium
hydroxide) to remove the residual copper(II). The blue aqueous
phase was extracted with DCM (15 mL x 3). The combined
4.4.6. 2-(4-chlorobenzo[d] thiazol-2-yl)pyridine 1-
oxide (3e)
Pale yellow solid (88 mg, 67% yield); m.p.= 196-198ꢀ; IR
1
(KBr, cm-1) 1451, 1428, 989, 765, 741; H NMR (CDCl3, 300
MHz) 7.37-7.44 (m,2H), 7.47-7.53 (m, 1H), 7.59 (dd, 1H, J =
7.7 Hz, 0.9Hz), 7.93(dd, 1H, J =8.0Hz, 0.9Hz), 8.41 (d, 1H, J =
6.3Hz), 8.89 (dd, 1H, J = 8.1 Hz, 2.1Hz); 13C NMR (CDCl3,
75MHz)120.6, 126.0, 126.1, 126.2, 126.5, 126.8, 128.4, 138.2,
139.4, 142.3, 149.0, 157.2; ESI-HRMS (m/z): [M+H]+ calcd. for
C12H8ClN2OS, 263.00404, found 263.00424.
4.4.7. 2-(6-fluorobenzo[d] thiazol-2-yl)pyridine 1-
oxide (3f)
Yellow solid (78 mg, 59% yield). m.p.= 231-233ꢀ; IR (KBr,
1
cm-1) 1492, 1430, 1250, 1192, 846, 777; H NMR (CDCl3, 300
MHz) 7.27-7.33 (m, 1H), 7.37-7.42 (m, 1H), 7.46-7.51 (m, 1H),
7.69 (dd, 1H, J = 8.1 Hz, 2.5Hz), 8.07(dd, 1H, J =9.0Hz, 4.7Hz),
8.40 (d, 1H, J = 6.3Hz), 8.74 (dd, 1H, J = 8.1 Hz, 2.0Hz); 13C

ACCEPTED MANUSCRIPT
6
Tetrahedron
NMR (CDCl3, 75MHz) 107.6(d, J = 26.0Hz), 115.9(d, J =
135.8, 137.3, 139.1, 141.5, 151.7, 157.6; ESI-HRMS (m/z):
25.2Hz), 124.6(d, J = 9.4Hz), 125.5, 125.7, 126.2, 137.9(d, J =
10.6Hz), 139.5, 142.3, 148.7, 156.3(d, J = 3.4Hz), 159.4, 162.7;
ESI-HRMS (m/z): [M+H]+ calcd. for C12H8FN2OS, 247.03359,
found 247.03362.
[M+H]+ calcd. for C12H11N2OS, 243.05866, found 243.05886
4.4.13. 2-(benzo[d]thiazol-2-yl)-4-methylpyridine
1-oxide (3l)
Pale yellow solid (74 mg, 61% yield). m.p.= 171-173ꢀ; IR
(KBr, cm-1) 3053, 1452, 1421, 1252, 1208, 757; 1H NMR
(CDCl3, 300 MHz) 2.49 ( s, 3H), 7.17 (dd, 1H, J = 6.6 Hz, 2.4
Hz), 7.45-7.50 (m, 1H), 7.53-7.59 (m, 1H), 8.04 (d, 1H, J =
7.9Hz), 8.12(d, 1H, J =8.1Hz), 8.58 (d, 1H, J = 2.0Hz); 13C
NMR (CDCl3, 75MHz) 20.6, 121.9, 123.2, 125.5, 125.9, 126.6,
126.7, 136.8, 137.7, 138.8, 141.4, 151.8, 156.7; ESI-HRMS
(m/z): [M+H]+ calcd. for C13H11N2OS, 243.05866, found
243.05883.
4.4.8. 2-(6-bromobenzo[d]thiazol-2-yl)pyridine 1-
oxide (3g)
White solid (72 mg, 47% yield). m.p.= 221-223ꢀ; IR (KBr,
1
cm-1) 1489, 1462, 1427, 1314, 812, 763; H NMR (CDCl3, 300
MHz) 7.39-7.44 (m, 1H), 7.47-7.52 (m, 1H), 7.66 (dd, 1H, J =
8.8 Hz, 1.9 Hz ), 7.98 (d, 1H, J = 8.7 Hz), 8.18(d, 1H, J =
1.7Hz), 8.41 (d, 1H, J = 6.5 Hz), 8.76 (dd, 1H, J =8.1 Hz, 2.0
Hz); 13C NMR (CDCl3, 75MHz) 119.8, 124.5, 124.6, 125.7,
125.9, 126.2, 130.3, 138.4, 139.5, 142.2, 150.8, 157.0; ESI-
HRMS (m/z): [M+H]+ calcd. for C12H8BrN2OS, 306.95352,
found 306.95370.
4.4.14. 2-(benzo[d]thiazol-2-yl)-6-methylpyridine
1-oxide (3m)
White solid (27 mg, 22% yield), m.p.= 144-147ꢀ; IR (KBr,
1
cm-1) 1469, 1445, 1388, 763, 735; H NMR (CDCl3, 300 MHz)
4.4.9. 2-(4,5-dimethylthiazol-2-yl)pyridine 1-oxide
(3h)
2.66( s, 3H), 7.35-7.37 (m, 2H), 7.44-7.49 (m, 1H), 7.53-7.58 (m,
1H), 8.04(d, 1H, J =7.9Hz), 8.12 (d, 1H, J = 8.2Hz), 8.66-8.70
(m, 1H); 13C NMR (CDCl3, 75MHz) 18.1, 121.9. 123.3, 123.4,
125.5, 125.8, 126.1, 126.5, 136.7, 142.3, 149.2, 152.0, 157.2;
ESI-HRMS (m/z): [M+H]+ calcd. for C12H11N2OS, 243.05866,
found 243.05869
Pale yellow solid (56 mg, 54% yield), m.p.= 47-149ꢀ; IR
1
(KBr, cm-1) 1492, 1433, 1239, 841, 787; H NMR (CDCl3, 300
MHz) 2.45 (s, 6H), 7.21-7.27 (m, 1H), 7.35-7.40 (m, 1H), 8.32
(d, 1H, J =6.4 Hz), 8.52 (d, 1H, J =8.2 Hz); 13C NMR (CDCl3,
75MHz) 11.3, 15.1, 123.7, 125.9, 131.5, 139.2, 142.5, 149.6,
150.2; ESI-HRMS (m/z): [M+H]+ calcd. for C10H11N2OS,
207.05866, found 207.05858
4.4.15. 2-(benzo[d]thiazol-2-yl)-4-(benzyloxy)
pyridine 1-oxide (3n)
4.4.10. 2-(4-(2-acetoxyethyl)-5-methylthiazol-2-
yl)pyridine 1-oxide(3i)
Brown solid (137 mg, 82% yield), m.p.= 186-188ꢀ; IR (KBr,
1
cm-1) 1621, 1485, 1448, 1187, 990, 749; H NMR (CDCl3, 300
Pale yellow solid solid (79 mg, 57% yield), m.p.= 98-100ꢀ;
MHz) 5.28( s, 2H), 6.99-7.03 (m, 1H), 7.39-7.51 (m, 6H), 7.55-
7.60 (m, 1H), 8.05(d, 1H, J =7.9Hz), 8.14 (d, 1H, J = 8.1Hz),
8.28 (d, 1H, J = 7.3 Hz), 8.38 (d, 1H, J = 3.4Hz); 13C NMR
(CDCl3, 75MHz) 71.4, 114.9, 122.0, 123.4, 126.0, 126.6, 127.9,
128.9, 129.0, 135.0, 137.1, 140.4, 142.8, 151.8, 156.6, 156.7;
ESI-HRMS (m/z): [M+H]+ calcd. for C19H15N2OS, 335.08487,
found 335.08504
1
IR (KBr, cm-1) 1727, 1438, 1237, 1043, 772; H NMR (CDCl3,
300 MHz) 2.07 (s, 3H), 2.49 (s, 3H), 3.17 (t, 2H, J =6.6 Hz),
4.30 (t, 2H, J =6.6 Hz), 7.26-7.29 (m, 1H), 7.37-7.42 (m, 1H),
8.33(d, 1H, J =6.5Hz), 8.54 (dd, 1H, J = 8.2 Hz, 1.9 Hz); 13C
NMR (CDCl3, 75MHz) 15.3, 21.0, 26.0, 64.0, 123.8, 124.0,
125.9, 131.7, 139.1, 142.2, 150.3, 151.5, 170.9, 219.2; ESI-
HRMS (m/z): [M+H]+ calcd. for C13H15N2O3S, 279.07979, found
279.07995
4.4.16. 2-(benzo[d]thiazol-2-yl)-4-methoxypyridine
1-oxide(3o)
4.4.11. 2-(5-(ethoxycarbonyl)-4-methylthiazol-2-
yl)pyridine 1-oxide (3j)
Pale yellow solid (84 mg, 65% yield), m.p.= 173-175 ꢀ; IR
1
(KBr, cm-1) 1621, 1473, 1423, 1325, 1198, 1012, 784, 769; H
Pale yellow solid (84 mg, 64% yield), m.p.=132-134 ꢀ; IR
NMR (CDCl3, 300 MHz) 4.03 (s, 3H), 6.95-6.97 (m, 1H), 7.55-
7.60 (m, 1H), 8.05(d, 1H, J =7.9 Hz), 8.13 (d, 1H, J =8.2 Hz),
8.27-8.29 (m, 2H); 13C NMR (CDCl3, 75MHz) 56.5, 107.6.
114.3, 121.9, 123.2, 125.9, 126.5, 137.0, 140.2, 142.8, 151.7,
156.5, 157.6; ESI-HRMS (m/z): [M+H]+ calcd. for C13H11N2O2S,
259.05357, found 259.05365.
1
(KBr, cm-1) 1712, 1432, 1261, 1101, 768; H NMR (CDCl3, 300
MHz) 1.40 (t, 3H, J =7.1 Hz), 2.83 (s, 3H), 4.38 (t, 2H, J =7.1
Hz), 7.33-7.39 (m, 1H), 7.42-7.47 (m, 1H), 8.39(d, 1H, J
=6.3Hz), 8.63 (dd, 1H, J = 8.2 Hz, 2.1 Hz); 13C NMR (CDCl3,
75MHz) 14.4, 17.7, 61.3, 124.6, 124.8, 125.2, 125.9, 139.3,
141.9, 156.2, 159.8, 163.1; ESI-HRMS (m/z): [M+H]+ calcd. for
C12H13N2O3S, 265.06414, found 265.06427
4.4.17. 2-(benzo[d]thiazol-2-yl)-4-chloropyridine
1-oxide(3p)
4.4.12. 2-(benzo[d]thiazol-2-yl)-5-methylpyridine
1-oxide (3k) and 2-(benzo[d]thiazol-2-yl)-3-
methylpyridine 1-oxide(3k’)
White solid (85 mg, 65% yield), m.p.= 178-180ꢀ; IR (KBr,
1
cm-1) 1475, 1417, 1268, 759, 716; H NMR (CDCl3, 300 MHz)
7.35 (dd, 1H, J =3Hz, 7.0 Hz), 7.48-7.53 (m, 1H), 7.56-7.62 (m,
2H), 8.05(d, 1H, J =7.5Hz), 8.15 (d, 1H, J = 8.0Hz), 8.32 (d, 1H,
J =7.0 Hz), 8.79 (d, 1H, J = 3.0Hz); 13C NMR (CDCl3, 75MHz)
122.0, 123.6, 125.3, 125.8, 126.4, 126.9, 132.5, 136.8, 140.3,
143.1, 151.9, 155.3; ESI-HRMS (m/z): [M+H]+ calcd. for
C12H8ClN2OS, 263.00404, found 263.00410
3k was isolated as white solid (66 mg, 51% yield) and 3k’ as
pale solid (16 mg, 13% yield) respectively. 3k: m.p.= 167-169ꢀ;
1
IR (KBr, cm-1) 1425, 1398, 1299, 1273, 820, 753, 724; H NMR
(CDCl3, 300 MHz) 2.42( s, 3H), 7.30 (d, 1H, J =8.4Hz), 7.44-
7.49 (m, 1H), 7.53-7.59 (m, 1H), 8.03(d, 1H, J =8.0Hz), 8.12 (d,
1H, J = 8.1Hz), 8.26 (s, 1H), 8.65 (d, 1H, J = 8.4Hz); 13C NMR
(CDCl3, 75MHz)18.4, 121.8, 123.1, 124.9, 125.7, 126.5, 127.6,
136.5, 136.9, 139.0, 140.0, 151.8, 156.7; ESI-HRMS (m/z):
[M+H]+ calcd. for C12H11N2OS, 243.05866, found 243.05880.
3k’: m.p.= 119-122ꢀ; IR (KBr, cm-1) 1436, 1322, 1281, 1199,
4.4.18. 2-(benzo[d]thiazol-2-yl)-4-(ethoxycarbonyl)
pyridine 1-oxide(3q)
White solid (96 mg, 64% yield), m.p.= 185-187ꢀ; IR (KBr,
1
cm-1) 1719, 1425, 165, 1238, 1112, 759; H NMR (CDCl3, 300
1
MHz) 1.48 (t, 3H, J = 7.1 Hz), 4.49 (q, 2H, J =7.1 Hz), 7.48-
7.54 (m, 1H), 7.57-7.62 (m, 1H), 7.97(dd, 1H, J =6.8 Hz, 2.5Hz),
8.05 (d, 1H, J =7.6 Hz), 8.18 (d, 1H, J =8.1 Hz), 8.42 (d, 1H, J
= 6.8 Hz), 9.35 (d, 1H, J =2.5 Hz); 13C NMR (CDCl3, 75MHz)
959, 795, 758, 729; H NMR (CDCl3, 300 MHz) 3.02( s, 3H),
7.23-7.35 (m, 2H), 7.46-7.57 (m, 2H), 8.04(d, 1H, J =7.8Hz),
8.14 (d, 1H, J = 8.0Hz), 8.34 (d, 1H, J = 6.2Hz); 13C NMR
(CDCl3, 75MHz) 23.7, 121.5, 123.7, 124.1, 126.1, 126.2, 129.8,

ACCEPTED MANUSCRIPT
7
14.4, 62.4, 122.0, 123.6, 125.2, 126.2, 126.3, 126.8, 127.6, 136.5,
157.2; ESI-HRMS (m/z): [M+H]+ calcd. for C16H11N2OS,
279.05866, found 279.05872.
139.9, 142.6, 152.0, 155.7, 163.5; ESI-HRMS (m/z): [M+H]+
calcd. for C15H13N2O3S, 301.06414, found 301.06417
4.4.19. 4-acetyl-2-(benzo[d] thiazol-2-yl)pyridine
1-oxide(3r)
Acknowledgements
Pale yellow solid (69 mg, 51% yield), m.p.= 203-205 ꢀ; IR
(KBr, cm-1) 1687, 1607, 1422, 1268, 1225, 765; 1H NMR
(CDCl3, 300 MHz) 2.77 (s, 3H), 7.49-7.54 (m, 1H), 7.58-7.63 (m,
1H), 7.93(dd, 1H, J =6.8 Hz, 2.5Hz), 8.06 (d, 1H, J =8.0 Hz),
8.18 (d, 1H, J =8.0 Hz), 8.43 (d, 1H, J = 6.8 Hz), 9.26 (d, 1H, J
=2.5 Hz); 13C NMR (CDCl3, 75MHz) 26.7, 122.0, 123.4, 123.5,
125.3, 126.4, 126.9, 132.9, 136.5, 140.2, 142.5, 151.9, 155.7,
194.1; ESI-HRMS (m/z): [M+H]+ calcd. for C14H11N2O2S,
271.05357, found 271.05370.
We are grateful to the National Natural Foundation of China,
Ministry of Science and Technology (No. 2011CB808600) and
the Chinese Academy of Sciences for the financial support.
Supplementary data
Experimental details, screening of other reaction parameters
1
and H and 13C NMR spectra are available free of charge via the
Internet.
4.4.20. 4-acetyl-2-(5-(ethoxycarbonyl)-4-
methylthiazol-2-yl)pyridine 1-oxide(3s)
Pale yellow solid (95 mg, 62% yield), m.p.=184-186 ꢀ; IR
1
(KBr, cm-1) 1701, 1677, 1281, 1236, 1102; H NMR (CDCl3,
References and notes
300 MHz) 1.41 (t, 3H, J =7.1 Hz), 2.74 (s, 3H), 2.85 (s, 3H),
4.39 (t, 2H, J =7.1 Hz), 7.89 (dd, 1H, J =6.9 Hz, 2.6 Hz), 8.41(d,
1H, J =6.9Hz), 9.09 (d, 1H, J =2.6 Hz); 13C NMR (CDCl3,
75MHz) 14.5, 17.7, 26.6, 61.4, 123.1, 124.4, 124.9, 132.9, 139.9,
141.8, 155.5, 160.1, 162.9, 194.1; ESI-HRMS (m/z): [M+H]+
calcd. for C12H15N2O4S, 307.07470, found 307.07527
1.
2.
For reviews on biology and synthesis of micrococcin P1, see:
Ciufolini, M. A.; Lefranc, D. Nat. Prod. Rep. 2010, 27, 330 and
references therein.
(a) Raboisson, P.; de Kock, H.; Rosenquist, A.; Nilsson, M.;
Salvador-Oden, L.; Lin, T. I.; Roue, N.; Ivanov, V.; Wahling, H.;
Wickstrom, K.; Hamelink, E.; Edlund, M.; Vrang, L.; Vendeville,
̈
̈
S.; Van de Vreken, W.; McGowan, D.; Tahri, A.; Hu, L.; Boutton,
C.; Lenz, O.; Delouvroy, F.; Pille, G.; Surleraux, D.; Wigerinck,
P.; Samuelsson, B.; Simmen, K. Bioorg. Med. Chem. Lett. 2008,
4.4.21. 2-(benzo[d]thiazol-2-yl)-4-nitropyridine 1-
oxide(3t)
18, 4853; (b) Clarke, M. O.; Byun, D.; Chen, X.; Doerffler, E.;
Leavitt, S. A.; Sheng, X. C.; Yang, C. Y.; Kim, C. U. Bioorg.
Yellow solid (70 mg, 51% yield). m.p.= 231-233ꢀ; IR (KBr,
1
cm-1) 1516, 1340, 1283, 1089, 764; H NMR (CDCl3, 300 MHz)
Med. Chem. Lett
ss-Fink, G.; Casini, A.; Edafe, F.; Dyson, P. J. J. Organomet.
Chem. 2010 695, 1119; (d) Rzuczek, S. G.; Pilch, D. S.; Liu, A.;
Liu, L.; LaVoie, E. J.; Rice, J. E. J. Med. Chem. 2010 53, 3632;
. 2012, 22, 1095; (c) Gras, M.; Therrien, B.; Sü
7.52-7.57 (m, 1H), 7.60-7.65 (m, 1H), 8.07(d, 1H, J =8.0 Hz),
8.15-8.22 (m, 2H), 8.47 (d, 1H, J =7.2 Hz), 9.59 (d, 1H, J =2.9
Hz); 13C NMR ((DMSO-D6, 75MHz) ; 119.4, 120.2, 122.5,
123.2, 126.6, 127.2, 135.5, 141.4, 141.8, 142.9, 151.1, 154.8;
ESI-HRMS (m/z): [M+H]+ calcd. for C12H8N3O3S, 274.02809,
found 274.02827.
,
,
(e) Maloney, K. N.; MacMillan, J. B.; Kauffman, C. A.; Jensen, P.
R.; DiPasquale, A. G.; Rheingold, A. L.; Fenical, W. Org. Lett.,
2009
Janowiec, M.; Zwolska, Z.; Augustynowicz-Kopec, E.
Phosphorus Sulfur Silicon Relat. Elem. 2005 180, 2543.
, 11, 5422; (f) Foks, H.; Pancechowska-Ksepko, D,;
,
4.4.22. 2-(benzo[d]thiazol-2-yl)-4-(trifluoromethyl)
pyridine 1-oxide(3u)
3.
For reviews on transition-metal-catalyzed cross-coupling
reactions for aryl-aryl bond formation, see: (a) Hassan, J.;
Sévignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Chem. Rev.
White solid (97 mg, 66% yield). m.p.= 171-173ꢀ; IR (KBr,
1
cm-1) 1328, 1251, 1180, 1116, 764; H NMR (CDCl3, 300 MHz)
2002
,
102, 1359; (b) Magano, J.; Dunetz, J. R. Chem. Rev. 2011
,
111, 2177; (c) Corbet, J. -P.; Mignani, G. Chem. Rev. 2006
,
106
,
7.50-7.64 (m, 3H), 8.06(d, 1H, J = 7.6 Hz), 8.18(d, 1H, J
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Yellow solid (46 mg, 40% yield), m.p.= 191-193ꢀ; IR (KBr,
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