Organocatalytic syntheses of benzoxazoles and benzothiazoles using aryl iodide and oxone via C-H functionalization and C-O/S bond formation

Article abstract of DOI:10.1021/jo501216h

An organocatalytic protocol for the syntheses of 2-substituted benzoxazoles and benzothiazoles is described from alkyl-/arylanilides and alkyl-/arylthioanilides using 1-iodo-4-nitrobenzene as catalyst and oxone as an inexpensive and environmentally safe terminal oxidant at room temperature in air via oxidative C-H functionalization and C-O/S bond formation. The procedure is simple and general and provides an effective route for the construction of functionalized 2-alkyl-/arylbenzoxazoles and 2-alkyl-/arylbenzothiazoles with moderate to high yields. The synthetic and mechanistic aspects have been described.

Full text of DOI:10.1021/jo501216h

Article
pubs.acs.org/joc
Organocatalytic Syntheses of Benzoxazoles and Benzothiazoles
using Aryl Iodide and Oxone via C−H Functionalization and C−O/S
Bond Formation
Santhosh Kumar Alla, Pradeep Sadhu, and Tharmalingam Punniyamurthy*
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
S
* Supporting Information
ABSTRACT: An organocatalytic protocol for the syntheses of
2-substituted benzoxazoles and benzothiazoles is described
from alkyl-/arylanilides and alkyl-/arylthioanilides using 1-
iodo-4-nitrobenzene as catalyst and oxone as an inexpensive
and environmentally safe terminal oxidant at room temper-
ature in air via oxidative C−H functionalization and C−O/S
bond formation. The procedure is simple and general and provides an effective route for the construction of functionalized 2-
alkyl-/arylbenzoxazoles and 2-alkyl-/arylbenzothiazoles with moderate to high yields. The synthetic and mechanistic aspects have
been described.
The classical methods utilized for the synthesis of
benzoxazoles and benzothiazoles involve the condensation of
2-aminophenol and 2-aminothiophenol with either aldehyde or
carboxylic acid followed by oxidative cyclization.7,8 However,
these approaches often suffer due to limited substrate scope and
sometimes with the harsh reaction conditions such as
requirement of elevated temperature (∼210 °C).9 To overcome
these drawbacks, considerable effort has been recently devoted
to develop new approaches for the construction of C−O/S
bonds via cross-coupling and C−H functionalization processes.
For examples, copper-,10 cobalt-,11 and iron-catalyzed12 C−O/S
cross-coupling of 2-haloanilides/2-halothioanilides and copper-
catalyzed13 inter-/intramolecular domino C−N/O cross-
coupling of 1,2-dihalobenzene with benzamides has been
successfully utilized for the construction of benzoxazoles and
benzothiazoles, while C−H functionalization followed by C−
O/S bond formation has been explored for the synthesis of
benzoxazoles and benzothiazoles using palladium-,14 ruthe-
nium-,15 iron-,16 and copper-based17 catalytic systems as well as
a stoichiometric amount of phenyliodinebis(trifluoroacetate)
(PIFA).18
INTRODUCTION
■
The construction of benzoxazole and benzothiazole structural
motifs has been a topic of immense interest in recent years due
to their presence in a number of natural products and
biologically active compounds. For examples, the benzoxazole
scaffold is found in naturally occurring cytotoxic compounds,
such as UK-1,1 salvianen,2 AJI9561,3 and antimycrobacterial
pseudopteroxazole.4 Some of the recent medicinal chemistry
applications of benzoxazoles and benzothiazoles include the
HIV-1 reverse transcriptase inhibitors,5a melatonin receptor
agonists,5b antitumor agents,5c 5HT3 receptor agonists,5d
selective peroxisome proliferator-activated receptor γ antagonist
JTP-426467,5e estrogen receptor-β agonist ERB-041,5f and
orexin receptor antagonist5g (Figure 1). Furthermore, benzox-
azoles are used as herbicides, such as Fenoxaprop, and as
fluorescent probes such as bis-benzoxazolyl ethylenes and
arenes.6 The development of general and effective methods for
the synthesis of functionalized benzoxazoles and benzothiazoles
is thus important in organic synthesis.
In recent years, hypervalent iodine catalyzed oxidative
transformations have emerged as powerful strategies for
carbon−carbon and carbon−heteroatom bond formation due
to their unique features as mild, safe, and environmentally
benign characterstics.19−23 These processes are generally found
to be effective in fluoro alcohols, as they have a high ionizing
ability and low nucleophilicity and stabilize the cationic
intermediates generated during the reactions.20c−k Herein, we
wish to report an efficient organocatalytic protocol for the
synthesis of substituted benzoxazoles and benzothiazoles from
aryl-/alkylanilides and aryl-/alkylthioanilides using 1-iodo-4-
Figure 1. Examples of some biologically active substituted
benzoxazoles and benzothiazoles.
Received: May 30, 2014
© XXXX American Chemical Society
A
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a
Table 1. Optimization of the Reaction Conditions
b
entry
ArI (20 mol %)
oxidant (1.5 equiv)
additive (3.0 equiv)
solvent
conversion (%)
yield (%)
1
PhI
oxone
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
CH2Cl2
THF
5
3
2
PhI
oxone
TfOH
BF3·Et2O
TMSOTf
PTSA·H2O
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
TfOH
37
24
25
n.d.
4
31
19
16
n.d.
2
3
PhI
oxone
4
PhI
oxone
5
PhI
oxone
6
PhI
NaBO3·4H2O
30% H2O2
Na2S2O8
mCPBA
oxone
7
PhI
2
2
8
PhI
10
23
93
17
5
7
9
PhI
21
88
10
3
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
4-NO2C6H4I
4-MeC6H4I
4-OMeC6H4I
2-IC6H4COOH
4-NO2C6H4I
4-NO2C6H4I
4-NO2C6H4I
4-NO2C6H4I
4-NO2C6H4I
4-NO2C6H4I
4-NO2C6H4I
4-NO2C6H4I
4-NO2C6H4I
4-NO2C6H4I
4-NO2C6H4I
oxone
oxone
oxone
31
5
24
3
oxone
oxone
n.d.
n.d.
63
35
70
72
12
7
n.d.
n.d.
oxone
toluene
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
c
oxone
56
d
oxone
28
e
oxone
61
f
oxone
64
NaBO3·4H2O
30% H2O2
Na2S2O8
mCPBA
oxone
7
4
12
43
n.d.
9
9
38
n.d.
5
4-NO2C6H4I
oxone
a
Reaction conditions: 1a (0.25 mmol), ArI (20 mol %), oxidant (0.37 mmol), additive (0.75 mmol), solvent (1.5 mL), room temperature, 12 h. n.d.
b
c
d
e
1
= not detected. Determined by 400 MHz H NMR spectroscopy. Oxone (0.25 mmol) was used. TfOH (0.25 mmol) was used. TfOH (0.5
mmol) was used. 4-NO2C6H4I (10 mol %) was used.
f
nitrobenzene as catalyst and oxone (2KHSO5·KHSO4·K2SO4)
as the terminal oxidant in hexafluoro-2-propanol (HFIP) at
room temperature. The protocol affords a potential route for
the access of the target products with wide substrate scope.
In contrast, iodobenzene with electron donating substituents
(4-methyl and 4-methoxy) gave inferior results, whereas 2-
iodobenzoic acid yielded 2a in 31% conversion (entries 11−
13). Solvent screening experiments showed that the choice of
solvent was crucial and the best results were obtained using
HFIP, while CH2Cl2, toluene, and THF were not effective,
affording 2a in <5% conversion (entries 14−16). Lowering the
amount of either aryl iodide (10 mol %) or oxidant (1 equiv) or
additive (2 equiv) led to the product formation in <72%
conversion (entries 17−20). Furthermore, the screening of the
oxidants NaBO3·4H2O, mCPBA, Na2S2O8, and 30% H2O2 with
1-iodo-4-nitrobenzene led to inferior results (entries 21−24).
Control experiments confirmed that, in the absence of aryl
iodide, no reaction was observed and the starting material was
recovered intact (entry 25). In addition, the reaction using 1-
iodo-4-nitrobenzene without TfOH as an additive yielded 2a in
9% conversion (entry 26).
To explore the scope and functional group compatibility of
this protocol, a series of alkyl-/arylanilides were subjected to
the optimized reaction conditions (Table 2). First, the reactivity
of unsubstituted arylanilide and the substrates equipped with
electron-withdrawing and -donating groups in the anilide aryl
ring was tested. The reaction of N-phenylbenzamide 1b
afforded benzoxazole 2b in 12% yield. A similar result was
observed with the substrate 1c, having a 2-methoxy substituent.
RESULTS AND DISCUSSION
■
First, the optimization of the reaction conditions was studied
using N-p-tolylbenzamide (1a) as a model substrate in the
presence of different aryl iodides, terminal oxidants, additives,
and solvents at room temperature (Table 1). To our delight,
the reaction occurred to give the target benzoxazole 2a in 12 h
with 5% conversion when the substrate 1a, iodobenzene (0.2
equiv), and oxone (1.5 equiv) were stirred in HFIP
(hexafluoro-2-propanol) at room temperature (entry 1). The
use of TfOH (3.0 equiv, trifluoromethanesulfonic acid) as an
additive led to increase the product 2a formation to 37%,
whereas BF3·OEt2 and TMSOTf gave the target molecule with
24 and 25% conversions, respectively (entries 2−4). In
contrast, PTSA·H2O (p-toluenesulfonic acid) showed no effect
and the starting material was recovered intact (entry 5). In a set
of oxidants screened, oxone afforded superior results in
comparison to those of NaBO3·4H2O, mCPBA, Na2S2O8, and
30% H2O2 (entries 6−9). Subsequent catalyst screening
revealed that iodobenzene with a 4-nitro substituent exhibited
greater reactivity, leading to 2a in 93% conversion (entry 10).
B
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the amide aryl ring were studied. In general, these substrates
smoothly underwent reaction with good yields. For examples,
the reactions of the substrates 1r−w with 2-methyl, 3-methyl,
4-chloro, 4-methoxy, 4-methyl, and 4-nitro substituents gave
the corresponding 2-arylbenzoxazoles 2r−w in 81−91% yields.
Similarly, the substrates 1x,y bearing R = 1-naphthyl and 2-furyl
substituents underwent reaction to give the benzoxazoles 2x,y
in 70 and 90% yields, respectively. Then, the utility of the
procedure for the synthesis of 2-alkylbenzoxazoles was
explored. Interestingly, the reactions took place to furnish the
desired 2-alkylbenzoxazoles with moderate to good yields. For
examples, the substrates 1z,aa with R = ethyl and isopropyl
substituents underwent cyclization to give the benzoxazoles
2z,aa in 63 and 80% yields, respectively, whereas the reaction of
the substrate 1ab with R = tert-butyl afforded 2-tert-
butylbenzoxazole 2ab in 45% yield.
The scope and utility of the protocol was further explored for
the reaction of variously substituted analogous alkyl-/
arylthioanilides (Table 3). The reactions readily occurred to
give the desired 2-alkyl-/2-arylbenzothiazoles with enhanced
yields. For examples, N-phenylthiobenzamide 3a underwent
reaction to afford 2-phenylbenzothiazole 4a in 84% yield, while
the substrate 3b having a 2-methyl substituent afforded 4b in
41% yield. The reaction of the substrate 3c having a 3-methoxy
group afforded a 1:32 mixture of 7-methoxy-2-phenylbenzo-
thiazole 4ca and 5-methoxy-2-phenylbenzothiazole 4cb in 89%
yield. A similar result was obtained with the substrate 3d having
a 3-methyl substituent, providing a 1:3.3 mixture of 7-methyl-2-
phenylbenzothiazole (4da) and 5-methyl-2-phenylbenzothia-
zole (4db) in 79% yield. In contrast, the substrates 3e,m with 3-
nitro and 4-nitro substituents showed no reaction and the
starting materials were recovered intact. However, the reaction
of the substrates 3f,i−l,o,q having 4-bromo, 4-chloro, 4-fluoro,
4-methoxy, 4-methyl, 2,4-dimethyl, and 3,5-dichloro substitu-
ents readily occurred to give the corresponding benzothiazoles
4f,i−l,o,q in 61−89% yields, whereas the substrates 3g,h,n
having 4-cyano, 4-ester, and 4-trifluoromethyl substituents
exhibited moderate reactivity, giving the target products in 38−
44% yields. In addition, the substrate 3p bearing 3,4-dimethyl
substituents underwent reaction to give a 1:2.4 mixture of 6,7-
dimethyl-2-phenylbenzothiazole 4pa and 5,6-dimethyl-2-phe-
nylbenzothiazole 4pb in 75% yield. On the other hand, the
substrates 3r−w containing 2-methyl, 3-methyl, 4-fluoro, 4-
methoxy, 4-methyl, and 4-nitro substituents on the thioamide
aryl ring smoothly underwent reaction to give the correspond-
ing 2-arylbenzothiazoles 4r−w in 86−95% yields. Likewise, the
cyclization of the substrates 3x−z having 1-naphthyl and 2-furyl
substituents could be carried out to afford the corresponding
benzothiazoles 4x−z in 75−88% yields. Furthermore, this
protocol was compatible for the synthesis of 2-alkylbenzothia-
zoles. For examples, the substrates 3aa,ab, with R = ethyl and
isopropyl substituents, readily cyclized to provide the desired 2-
alkylbenzothiazoles 4aa,ab in 63 and 88% yields, respectively,
whereas 3ac having R = tert-butyl underwent reaction to give
the target benzothiazole 4ac in 81% yield.
Table 2. 1-Iodo-4-nitrobenzene-Catalyzed Synthesis of
Benzoxazoles with Oxone
a
time
(h)
product (yield
entry
Ar
R
(%))
1
C6H5
1b
1c
1d
1e
1f
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
48
48
48
48
1
2b (12)
2c (15)
2d (n.d.)
2e (n.d.)
2f (n.d.)
2g (88)
2h (91)
2i (19)
2
2-OMeC6H4
3-OMeC6H4
3-NO2C6H4
4-OAcC6H4
4-BrC6H4
3
4
5
6
1g
1h
1i
12
3
7
4-ClC6H4
8
4-CNC6H4
4-CO2EtC6H4
4-FC6H4
48
48
5
9
1j
2j (14)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
1k
2k (77)
2l (n.d.)
2m (82)
2n (n.d.)
2o (25)
2p (70)
2qa,qb (75)
2r (91)
2s (84)
2t (89)
4-COMeC6H4 1l
48
12
12
48
12
12
12
12
12
12
12
24
12
8
4-MeOC6H4
4-NO2C6H4
4-CF3C6H4
2,4-Me2C6H3
3,4-Me2C6H3
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
1m
1n
1o
1p
1q
1r
b
2-MeC6H4
3-MeC6H4
4-ClC6H4
4-OMeC6H4
4-MeC6H4
4-NO2C6H4
1-naphthyl
2-furyl
1s
1t
1u
1v
1w
1x
1y
1z
1aa
2u (81)
2v (82)
2w (81)
2x (70)
2y (90)
2z (63)
2aa (80)
2ab (45)
Et
iPr
12
20
24
1ab tBu
a
Reaction conditions: 1a−ab (0.36 mmol), 1-iodo-4-nitrobenzene (20
mol %), oxone (0.54 mmol), TfOH (1.08 mmol), HFIP (2.5 mL),
room temperature. Contained 6,7-dimethyl- (2qa) and 5,6-dimethyl-
b
2-phenylbenzoxazoles (2qb) (1:2.2).
The substrate 1d with a 3-methoxy group underwent
decomposition, while 1e substituted with a 3-nitro group failed
to react and the starting material was recovered intact.
However, the reactions of the substrates 1g,h,k,m with 4-
bromo, 4-chloro, 4-fluoro and 4-methoxy substituents readily
occurred to furnish the corresponding substituted benzoxazoles
2g,h,k,m in 77−91% yields, whereas 1i,j,o having electron-
withdrawing 4-cyano, 4-ester, and 4-trifluoromethyl groups
were less reactive, giving the benzoxazoles 2i,j,o in 14−25%
yields. Furthermore, the substrate 1f with a 4-acetoxy group
underwent hydrolysis, while 1l,n having 4-keto and 4-ntiro
substituents showed no reaction and the starting materials were
recovered. These results indicate the involvement of an
electrophilic aromatic substitution process in the cyclization
reaction. Furthermore, the reaction of the substrate 1p with 2,4-
dimethyl substituents provided the benzoxazole 2p in 70%
yield, whereas 1q having 3,4-dimethyl substituents afforded a
1:2.2 mixture of 6,7-dimethyl-2-phenylbenzoxazole 2qa and
5,6-dimethyl-2-phenylbenzoxazole 2qb in 75% yield. These
results suggest that the regioselectivity of the cyclization
depends on the arene substituents. Next, the reactions of the
substrates having electron-donating and -withdrawing groups in
Finally, the scaleup of the protocol was studied with 1a as a
representative example (Scheme 1). As expected, the reaction
readily occurred to furnish the desired 2-arylbenzoxazole 2a in
82% yield.
To investigate the reaction kinetics, an intermolecular
competitive reaction between equimolar amounts of 1a-d2
and 1a was conducted under the typical reaction conditions.
At 23% conversion, the reaction revealed the intermolecular
C
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Table 3. 1-Iodo-4-nitrobenzene-Catalyzed Synthesis of
Benzothiazoles with Oxone
Scheme 2. Intermolecular Kinetic Isotope Experiment
a
time
(h)
product (yield
(%))
entry
Ar
R
1
C6H5
3a
3b
3c
3d
3e
3f
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
12
12
6
4a (84)
2
2-MeC6H4
3-MeOC6H4
3-MeC6H4
3-NO2C6H4
4-BrC6H4
4b (41)
b
c
3
4ca,cb (89)
4
12
48
12
48
48
5
4da,db (79)
4e (n.d.)
4f (89)
5
Scheme 3. Radical Scavenger Experiment with N-tert-Butyl-
α-phenylnitrone
6
7
4-CNC6H4
3g
4g (41)
4h (38)
4i (88)
8
4-CO2EtC6H4 3h
9
4-ClC6H4
4-FC6H4
3i
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
3j
12
12
12
12
48
12
12
12
12
12
8
4j (83)
4-MeOC6H4
4-MeC6H4
4-NO2C6H4
4-CF3C6H4
2,4-Me2C6H3
3,4-Me2C6H3
3,5-Cl2C6H3
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
1-naphthyl
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
3k
3l
4k (87)
4l (89)
3m
3n
3o
3p
3q
3r
4m (n.d.)
4n (44)
4o (61)
4pa,pb (75)
4q (72)
4r (95)
catalyze the oxidative cyclization of the substrates C to give the
intermediate D, which could be stabilized by HFIP.20h,j
Intramolecular cyclization of D can give the cationic
intermediate E, accompanied by the liberation of iodobenzene
A, which could be reoxidized to B. The intermediate E can
furnish the target products 2 and 4 by aromatization (Scheme
4).
d
2-MeC6H4
3-MeC6H4
4-FC6H4
4-OMeC6H4
4-MeC6H4
4-NO2C6H4
Ph
3s
4s (93)
4t (90)
3t
3u
3v
3w
3x
3y
3z
3aa
12
12
24
10
8
4u (93)
4v (89)
4w (86)
4x (88)
4y (81)
4z (75)
4aa (63)
4ab (88)
4ac (81)
CONCLUSIONS
■
In summary, we have developed a simple and general
organocatalytic protocol for the synthesis of 2-arylbenzoxazoles
and 2-arylbenzothiazoles using 1-iodo-4-nitrobenzene as
catalyst in the presence of oxone as terminal oxidant at room
temperature. This protocol can readily be extended to the
construction of 2-alkylbenzoxazoles and 2-alkylbenzothiazoles.
2-furyl
1-naphthyl
15
12
12
12
Et
3ab iPr
3ac
tBu
a
Reaction conditions: 3a−ab (0.36 mmol), 1-iodo-4-nitrobenzene (20
EXPERIMENTAL SECTION
■
mol %), oxone (0.54 mmol), TfOH (1.08 mmol), HFIP (2.5 mL),
room temperature. Contained 7-methoxy- (4ca) and 5-methoxy-2-
phenylbenzothiazoles (4cb) (1:32). Contained 7-methyl- (4da) and
5-methyl-2-phenylbenzothiazoles (4db) (1:3.3). Contained 6,7-
dimethyl- (4pa) and 5,6-dimethyl-2-phenylbenzothiazoles (4pb)
(1:2.4).
General Information. All chemicals and solvents were purchased
from commercial suppliers and were used as received. Substituted
anilides were prepared from anilines and acid chlorides.24
Thiobenzanilides were prepared by thionation of the corresponding
anilides with Lawesson‘s reagent.14 Purification of the reaction
products was carried out by column chromatography using silica gel
(230−400 mesh). analytical TLC was performed on silica gel G/GF
254 plates. NMR spectra were recorded on 400 and 600 MHz NMR
spectrometers using CDCl3 as solvent and Me4Si as internal standard,
and the broad-band decoupling of carbon data was proton-decoupled
13C{1H}. Chemical shifts (δ) are reported in ppm, and spin−spin
b
c
d
Scheme 1. Gram-Scale Synthesis
coupling constants (J) are given in Hz. Melting points were
determined using a melting point apparatus and are uncorrected.
FT-IR spectra were recorded using an IR spectrometer. Elemental
analyses were recorded using a CHNS analyzer. High-resolution mass
spectra (HRMS) were recorded on a ESI-MS TOF instrument.
General Procedure for 1-Iodo-4-nitrobenzene-Catalyzed
Synthesis of Substituted Benzoxazoles/Benzothiazoles 2a−
ab and 4a−ac. Oxone (1.5 equiv) was added to a stirred solution of
anilide/thioanilide (0.36 mmol, 1.0 equiv), 4-nitroiodobenzene (20
mol %), and triflic acid (3.0 equiv) in HFIP (2.5 mL) at room
temperature in air. The mixture was stirred, and the progress of the
reaction was monitored by TLC using ethyl acetate and hexane as
eluent. The reaction mixture was then treated with saturated Na2S2O3
(1 mL) and NaHCO3 (1 mL) solutions. The resultant mixture was
extracted using ethyl acetate (3 × 10 mL) and washed with brine (2 ×
5 mL) and water (1 × 5 mL). Drying (Na2SO4) and evaporation of the
kinetic isotopic effect PH/PD = 1.0, which suggests that the C−
H bond breaking step was not involved in the rate-determining
step (Scheme 2).22 Then, the application of a radical scavenger
for IIII species, N-tert-butyl-α-phenylnitrone,20c was studied.
However, the radical scavenger did not affect the reaction, and
the target 2-arylbenzoxazole 2a was obtained in 88% yield
(Scheme 3). This result reveals that the radical was not
involved in the cyclization process. Thus, the reaction of aryl
iodide A with TfOH and oxone can generate an active
hypervalent iodine(III) species, PhI(OTf)2 (B),23 that can
D
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The Journal of Organic Chemistry
Article
Scheme 4. Proposed Catalytic Cycle
solvent gave a residue that was purified by silica gel column
chromatography using hexane and ethyl acetate as eluent to afford
analytically pure substituted benzoxazoles and benzothiazoles.
6-Methyl-2-phenylbenzo[d]oxazole (2a): analytical TLC on silica
gel, 1/9 ethyl acetate/hexane Rf = 0.54; white solid; 66 mg, 88% yield;
2-Phenylbenzo[d]oxazole-6-carbonitrile (2i): analytical TLC on
silica gel, 1/9 ethyl acetate/hexane Rf = 0.58; white solid; 15.0 mg,
19% yield; mp 198−199 °C; H NMR (400 MHz, CDCl3) δ 8.27−
1
8.24 (m, 2H), 7.90 (d, J = 0.8 Hz, 1H), 7.84 (d, J = 8.8 Hz, 1H), 7.65
(dd, J = 8.0 Hz, 1.2 Hz, 1H), 7.61−7.52 (m, 3H); 13C{1H} NMR (150
MHz, CDCl3) δ 166.3, 150.3, 146.2, 132.9, 129.4, 129.1, 128.4, 126.3,
121.2, 119.0, 115.1, 108.4; FT-IR (KBr) 2924, 1700, 1630, 1601, 1552,
1517, 1482, 1456, 1409, 1351, 1327, 1292, 1225, 1111, 1047 cm−1.
Anal. Calcd for C14H8N2O: C, 76.35; H, 3.66; N, 12.72. Found: C,
76.30; H, 3.65; N, 12.76. HRMS (ESI) m/z: [M + H]+ calcd for
C14H8N2OH 221.0709, found 221.0711.
mp 91−92 °C (lit.10a mp 93 °C); H NMR (400 MHz, CDCl3) δ
1
8.23−8.21 (m, 2H), 7.63 (d, J = 8.4 Hz, 1H), 7.51−7.50 (m, 3H), 7.37
(s, 1H), 7.16 (d, J = 8.4 Hz, 1H), 2.49 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 162.3, 150.8, 139.8, 135.2, 131.0, 128.6, 127.25, 127.2,
125.6, 119.1, 110.5, 21.5; FT-IR (KBr) 3054, 2919, 1647, 1615, 1554,
1482, 1448, 1337, 1247, 1173, 1126, 1052, 1021 cm−1. Anal. Calcd for
C14H11NO: C, 80.36; H, 5.30; N, 6.69. Found: C, 80.29; H, 5.32; N,
6.73. HRMS (ESI) m/z: [M + H]+ calcd for C14H11NOH 210.0913,
found 210.0922.
Ethyl 2-phenylbenzo[d]oxazole-6-carboxylate (2j): analytical TLC
on silica gel, 1/9 ethyl acetate/hexane Rf = 0.46; white solid; 13 mg,
1
14% yield; mp 76−77 °C; H NMR (600 MHz, CDCl3) δ 8.29−8.28
2-Phenylbenzo[d]oxazole (2b): analytical TLC on silica gel, 1/9
ethyl acetate/hexane Rf = 0.62; white solid; 8.0 mg, 12% yield; mp
(m, 3H), 8.11 (dd, J = 7.8 Hz, 1.2 Hz, 1H), 7.80 (d, J = 8.4 Hz, 1H),
7.60−7.54 (m, 3H), 4.45 (q, J = 7.2 Hz, 2H), 1.45 (t, J = 7.2 Hz, 3H);
13C{1H} NMR (150 MHz, CDCl3) δ 166.4, 165.8, 150.7, 146.2, 132.4,
129.3, 128.2, 127.8, 126.9, 126.6, 119.7, 112.5, 61.5, 14.6; FT-IR (KBr)
2980, 1713, 1614, 1582, 1476, 1447, 1431, 1365, 1346, 1318, 1292,
1262, 1226, 1187, 1051, 1020 cm−1. Anal. Calcd for C16H13NO3: C,
71.90; H, 4.90; N, 5.24. Found: C, 71.85; H, 4.91; N, 5.30. HRMS
(ESI) m/z: [M + H]+ calcd for C16H13NO3H 268.0968, found
268.0961.
102−103 °C (lit.17 mp 102 °C); H NMR (400 MHz, CDCl3) δ
1
8.26−8.24 (m, 2H), 7.78−7.75 (m, 1H), 7.59−7.56 (m, 1H), 7.53−
7.51 (m, 3H), 7.35−7.33 (m, 2H); 13C{1H} NMR (100 MHz, CDCl3)
δ 163.1, 150.9, 142.2, 131.6, 129.0, 127.7, 127.3, 125.2, 124.7, 120.1,
110.7; FT-IR (KBr) 3063, 2920, 1722, 1615, 1550, 1448, 1345, 1284,
1239, 1194, 1145, 1104, 1055, 1022, 1002 cm−1. Anal. Calcd for
C13H9NO: C, 79.98; H, 4.65; N, 7.17. Found: C, 79.92; H, 4.66; N,
7.21. HRMS (ESI) m/z: [M + H]+ calcd for C13H9NOH 196.0757,
found 196.0759.
6-Fluoro-2-phenylbenzo[d]oxazole (2k): analytical TLC on silica
gel, 1/9 ethyl acetate/hexane Rf = 0.62; white solid; 59 mg, 77% yield;
mp 106−107 °C (lit.10a mp 109 °C); 1H NMR (400 MHz, CDCl3) δ
8.21−8.18 (m, 2H), 7.69 (dd, J = 8.4 Hz, 4.8 Hz, 1H), 7.52−7.50 (m,
3H), 7.30 (dd, J = 7.6 Hz, 2.0 Hz, 1H), 7.11−7.06 (m, 1H); 13C{1H}
NMR (100 MHz, CDCl3) δ 163.9, 162.1 (d, J = 242.5 Hz), 151.0 (d, J
= 15.3 Hz), 138.6 (d, J = 1.6 Hz), 131.8, 129.1, 127.7, 127.1, 120.5 (d,
J = 10.7 Hz), 112.8 (d, J = 24.4 Hz), 99.0 (d, J = 28.2 Hz); FT-IR
(KBr) 3055, 2920, 1624, 1556, 1490, 1451, 1345, 1289, 1256, 1210,
1129, 1103, 1049, 1021 cm−1. Anal. Calcd for C13H8FNO: C, 73.23;
H, 3.78; N, 6.57. Found: C, 73.18; H, 3.77; N, 6.61. HRMS (ESI) m/
z: [M + H]+ calcd for C13H8FNOH 214.0663, found 214.0661.
6-Methoxy-2-phenylbenzo[d]oxazole (2m): analytical TLC on
silica gel, 1/9 ethyl acetate/hexane Rf = 0.54; white solid; 66 mg, 82%
yield; mp 78−79 °C (lit.25e mp 75 °C); 1H NMR (400 MHz, CDCl3)
δ 8.19−8.17 (m, 2H), 7.63 (d, J = 9.2 Hz, 1H), 7.50−7.48 (m, 3H),
7.10 (d, J = 2.0 Hz, 1H), 6.95 (dd, J = 9.2 Hz, 2.4 Hz, 1H), 3.86 (s,
3H); 13C{1H} NMR (100 MHz, CDCl3) δ 162.4, 158.5, 151.9, 136.1,
131.3, 129.1, 127.6, 127.4, 120.2, 113.0, 95.7, 56.2; FT-IR (KBr) 3064,
2930, 1619, 1555, 1487, 1449, 1346, 1321, 1290, 1219, 1144, 1110,
1052, 1023 cm−1. Anal. Calcd for C14H11NO2: C, 74.65; H, 4.92; N,
6.22. Found: C, 74.60; H, 4.93; N, 6.28. HRMS (ESI) m/z: [M + H]+
calcd for C14H11NO2H 226.0863, found 226.0862.
4-Methoxy-2-phenylbenzo[d]oxazole (2c): analytical TLC on silica
gel, 1/9 ethyl acetate/hexane Rf = 0.46; white solid; 12 mg, 15% yield;
mp 65−66 °C (lit.17 mp 67 °C); H NMR (400 MHz, CDCl3) δ
1
8.31−8.29 (m, 2H), 7.52−7.50 (m, 3H), 7.31−7.26 (m, 1H), 7.22 (d, J
= 8.0 Hz, 1H), 6.83 (d, J = 8.0 Hz, 1H), 4.07 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3) δ 162.1, 152.4, 151.8, 132.0, 131.5, 129.0, 127.8,
127.4, 125.9, 106.2, 103.6, 56.4; FT-IR (KBr) 3066, 2960, 1625, 1510,
1486, 1445, 1428, 1355, 1322, 1269, 1240, 1097, 1056, 1019 cm−1.
Anal. Calcd for C14H11NO2: C, 74.65; H, 4.92; N, 6.22. Found: C,
74.71; H, 4.90; N, 6.17. HRMS (ESI) m/z: [M + H]+ calcd for
C14H11NO2H 226.0863, found 226.0859.
6-Bromo-2-phenylbenzo[d]oxazole (2g): analytical TLC on silica
gel, 1/9 ethyl acetate/hexane Rf = 0.60; white solid; 87 mg, 88% yield;
mp 96−97 °C (lit.17 mp 95 °C); H NMR (400 MHz, CDCl3) δ
1
8.23−8.20 (m, 2H), 7.74 (d, J = 1.6 Hz, 1H), 7.63 (d, J = 8.8 Hz, 1H),
7.55−7.50 (m, 3H), 7.48 (dd, J = 8.4 Hz, 2.0 Hz, 1H); 13C{1H} NMR
(100 MHz, CDCl3) δ 163.8, 151.5, 141.6, 132.1, 129.2, 128.3, 127.9,
126.9, 121.2, 118.2, 114.4; FT-IR (KBr) 2960, 1638, 1557, 1506, 1449,
1422, 1328, 1257, 1041 cm−1. Anal. Calcd for C13H8BrNO: C, 56.96;
H, 2.94; N, 5.11. Found: C, 57.04; H, 2.92; N, 5.07. HRMS (ESI) m/
z: [M + H]+ calcd for C13H8BrNOH 273.9862, found 273.9860.
6-Chloro-2-phenylbenzo[d]oxazole (2h): analytical TLC on silica
gel, 1/9 ethyl acetate/hexane Rf = 0.63; white solid; 75 mg, 91% yield;
mp 104−105 °C (lit.10a mp 107 °C); 1H NMR (400 MHz, CDCl3) δ
8.22−8.20 (m, 2H), 7.67 (d, J = 8.4 Hz, 1H), 7.58 (d, J = 1.6 Hz, 1H),
7.54−7.51 (m, 3H), 7.33 (dd, J = 8.8 Hz, 2.0 Hz, 1H); 13C{1H} NMR
(100 MHz, CDCl3) δ 163.9, 151.1, 141.1, 132.0, 130.9, 129.2, 127.9,
126.9, 125.5, 120.7, 111.4; FT-IR (KBr) 3059, 2926, 1618, 1552, 1488,
1450, 1331, 1263, 1051, 1022 cm−1. Anal. Calcd for C13H8ClNO: C,
67.99; H, 3.51; N, 6.10. Found: C, 68.09; H, 3.49; N, 6.04. HRMS
(ESI) m/z: [M + H]+ calcd for C13H8ClNOH 230.0367, found
230.0367.
2-Phenyl-6-(trifluoromethyl)benzo[d]oxazole (2o): analytical TLC
on silica gel, 1/9 ethyl acetate/hexane Rf = 0.52; white solid; 24 mg,
1
25% yield; mp 100−101 °C; H NMR (400 MHz, CDCl3) δ 8.27−
8.25 (m, 2H), 7.86 (d, J = 9.2 Hz, 2H), 7.63 (d, J = 8.0 Hz, 1H), 7.58−
7.52 (m, 3H); 13C{1H} NMR (150 MHz, CDCl3) δ 165.6, 150.4,
145.1, 132.5, 129.3, 128.2, 127.5, 126.7, 123.5, 122.1, 120.6, 108.7 (q, J
= 4.5 Hz); FT-IR (KBr) 2962, 1615, 1555, 1491, 1454, 1338, 1290,
1166, 1154, 1126, 1110, 1048 cm−1. Anal. Calcd for C14H8F3NO: C,
63.88; H, 3.06; N, 5.32. Found: C, 63.94; H, 3.04; N, 5.27. HRMS
(ESI) m/z: [M + H]+ calcd for C14H8F3NOH 264.0631, found
264.0625.
E
dx.doi.org/10.1021/jo501216h | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
4,6-Dimethyl-2-phenylbenzo[d]oxazole (2p): analytical TLC on
silica gel, 1/9 ethyl acetate/hexane Rf = 0.75; white solid; 56 mg, 70%
yield; mp 128−129 °C; 1H NMR (400 MHz, CDCl3) δ 8.24−8.21 (m,
2H), 7.50−7.48 (m, 3H), 7.19 (s, 1H), 6.96 (s, 1H), 2.61 (s, 3H), 2.44
(s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 162.0, 151.1, 139.5,
135.3, 131.2, 130.0, 129.0, 127.8, 127.6, 126.6, 108.2, 22.0, 16.7; FT-IR
(KBr) 3059, 2922, 1614, 1554, 1489, 1447, 1337, 1291, 1264, 1224,
1069, 1049, 1019 cm−1. Anal. Calcd for C15H13NO: C, 80.69; H, 5.87;
N, 6.27. Found: C, 80.61; H, 5.89; N, 6.31. HRMS (ESI) m/z: [M +
H]+ calcd for C15H13NOH 224.1070, found 224.1071.
8.10 (d, J = 8.0 Hz, 2H), 7.64 (d, J = 8.4 Hz, 1H), 7.56 (d, J = 2.0 Hz,
1H), 7.32−7.29 (m, 3H), 2.42 (s, 3H); 13C{1H} NMR (75 MHz,
CDCl3) δ 163.9, 150.8, 142.4, 140.9, 130.3, 129.7, 127.6, 125.1, 123.8,
120.2, 111.1, 21.6; FT-IR (KBr) 2920, 2853, 1616, 1554, 1500, 1440,
1426, 1408, 1329, 1257, 1234, 1170, 1119, 1050, 1013 cm−1. Anal.
Calcd for C14H10ClNO: C, 69.00; H, 4.14; N, 5.75. Found: C, 68.95;
H, 4.13; N, 5.80. HRMS (ESI) m/z: [M + H]+ calcd for
C14H10ClNOH 244.0524, found 244.0524.
6-Chloro-2-(4-nitrophenyl)benzo[d]oxazole (2w): analytical TLC
on silica gel, 1/9 ethyl acetate/hexane Rf = 0.72; white solid; 80 mg,
1
6,7-Dimethyl-2-phenylbenzo[d]oxazole (2qa) and 5,6-Dimethyl-
2-phenylbenzo[d]oxazole (2qb): analytical TLC on silica gel, 1/9
ethyl acetate/hexane Rf = 0.63; white solid; 60 mg, 75% yield; mp
81% yield; mp 182−183 °C; H NMR (400 MHz, CDCl3) δ 8.41−
8.36 (m, 4H), 7.73 (d, J = 8.4 Hz, 1H), 7.64 (d, J = 2.0 Hz, 1H), 7.40
(dd, J = 8.0 Hz, 2.0 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ
161.5, 151.4, 150.0, 140.9, 132.5, 132.3, 128.7, 126.2, 124.4, 121.4,
111.8; FT-IR (KBr) 3087, 1947, 1603, 1595, 1554, 1518, 1460, 1409,
1349, 1327, 1312, 1263, 1109, 1048, 1011 cm−1. Anal. Calcd for
C13H7ClN2O3: C, 56.85; H, 2.57; N, 10.20. Found: C, 56.81; H, 2.56;
N, 10.24. HRMS (ESI) m/z: [M + H]+ calcd for C13H7ClN2O3H
275.0218, found 275.0216.
1
141−142 °C; H NMR (400 MHz, CDCl3) δ 8.25−8.20 (m, 4H),
7.51−7.46 (m, 8H), 7.34 (s, 1H), 7.14 (d, J = 7.6 Hz, 1H), 2.48 (s,
3H), 2.39 (s, 3H), 2.37 (s, 3H), 2.35 (s, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 162.6, 162.5, 149.6, 140.5, 139.8, 134.6, 134.0, 133.5,
131.4, 131.3, 129.1, 128.4, 128.0, 127.73, 127.7, 127.62, 127.6, 126.5,
120.2, 119.6, 116.6, 111.1, 20.8, 20.5, 19.5, 12.5; FT-IR (KBr) 3057,
2922, 1613, 1552, 1488, 1464, 1446, 1334, 1262, 1152, 1049, 1020,
999 cm−1. Anal. Calcd for C15H13NO: C, 80.69; H, 5.87; N, 6.27.
Found: C, 80.64; H, 5.86; N, 6.30. HRMS (ESI) m/z: [M + H]+ calcd
for C15H13NOH 224.1070, found 224.1072.
6-Chloro-2-(naphthalen-1-yl)benzo[d]oxazole (2x): analytical
TLC on silica gel, 1/9 ethyl acetate/hexane Rf = 0.72; yellow solid;
1
70 mg, 70% yield; mp 101−102 °C; H NMR (400 MHz, CDCl3) δ
9.44 (d, J = 8.8 Hz, 1H), 8.41 (dd, J = 7.6 Hz, 0.8 Hz, 1H), 8.04 (d, J =
8.4 Hz, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.77 (d, J = 8.0 Hz, 1H), 7.72−
7.68 (m, 1H), 7.64 (d, J = 1.6 Hz, 1H), 7.61−7.56 (m, 2H), 7.37 (dd, J
= 8.4 Hz, 2.0 Hz, 1H); 13C{1H} NMR (150 MHz, CDCl3) δ 163.6,
150.5, 141.3, 134.2, 132.9, 131.1, 130.8, 129.6, 128.9, 128.3, 126.8,
126.4, 125.4, 125.1, 123.3, 120.9, 111.4; FT-IR (KBr) 3045, 2926,
1895, 1609, 1589, 1541, 1508, 1459, 1427, 1395, 1323, 1263, 1250,
1131, 1108, 1073, 1054, 966 cm−1. Anal. Calcd for C17H10ClNO: C,
72.99; H, 3.60; N, 5.01. Found: C, 72.93; H, 3.62; N, 5.06. HRMS
(ESI) m/z: [M + H]+ calcd for C17H10ClNOH 280.0524, found
280.0523.
6-Chloro-2-(o-tolyl)benzo[d]oxazole (2r): analytical TLC on silica
gel, 1/9 ethyl acetate/hexane Rf = 0.70; white solid; 80 mg, 91% yield;
mp 89−90 °C (lit.25g mp 85 °C); 1H NMR (400 MHz, CDCl3) δ 8.14
(d, J = 7.2 Hz, 1H), 7.69 (d, J = 8.4 Hz, 1H), 7.59 (d, J = 1.6 Hz, 1H),
7.41−7.39 (m, 1H), 7.35−7.31 (m, 3H), 2.78 (s, 3H); 13C{1H} NMR
(150 MHz, CDCl3) δ 164.2, 150.7, 141.2, 139.2, 132.1, 131.4, 130.8,
130.1, 126.3, 126.0, 125.3, 120.8, 111.3, 22.4; FT-IR (KBr) 2957, 2923,
1614, 1547, 1461, 1325, 1255, 1235, 1165, 1059, 1023 cm−1. Anal.
Calcd for C14H10ClNO: C, 69.00; H, 4.14; N, 5.75. Found: C, 69.06;
H, 4.12; N, 5.68. HRMS (ESI) m/z: [M + H]+ calcd for
C14H10ClNOH 244.0524, found 244.0524.
6-Chloro-2-(furan-2-yl)benzo[d]oxazole (2y): analytical TLC on
6-Chloro-2-(m-tolyl)benzo[d]oxazole (2s): analytical TLC on silica
gel, 1/9 ethyl acetate/hexane Rf = 0.68; white solid; 74 mg, 84% yield;
mp 98−99 °C (lit.25g mp 99 °C); 1H NMR (400 MHz, CDCl3) δ 8.04
(s, 1H), 8.01 (d, J = 7.2 Hz, 1H), 7.65 (d, J = 8.4 Hz, 1H), 7.56 (d, J =
1.6 Hz, 1H), 7.41−7.35 (m, 2H), 7.32 (dd, J = 8.4 Hz, 1.6 Hz, 1H),
2.44 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 164.1, 151.0, 141.1,
139.0, 132.8, 130.7, 129.0, 128.4, 126.7, 125.4, 125.0, 120.5, 111.4,
21.5; FT-IR (KBr) 3059, 2922, 1618, 1553, 1485, 1428, 1327, 1264,
1242, 1072 cm−1. Anal. Calcd for C14H10ClNO: C, 69.00; H, 4.14; N,
5.75. Found: C, 68.95; H, 4.13; N, 5.79. HRMS (ESI) m/z: [M + H]+
calcd for C14H10ClNOH 244.0524, found 244.0526.
6-Chloro-2-(4-chlorophenyl)benzo[d]oxazole (2t): analytical TLC
on silica gel, 1/9 ethyl acetate/hexane Rf = 0.70; white solid; 84 mg,
89% yield; mp 148−149 °C (lit.25g mp 148 °C); 1H NMR (400 MHz,
CDCl3) δ 8.15−8.12 (m, 2H), 7.66 (d, J = 8.8 Hz, 1H), 7.57 (d, J = 2.0
Hz, 1H), 7.50−7.47 (m, 2H), 7.34 (dd, J = 8.4 Hz, 1.6 Hz, 1H);
13C{1H} NMR (100 MHz, CDCl3) δ 162.9, 151.1, 141.0, 138.3, 131.1,
129.5, 129.1, 125.7, 125.4, 120.7, 111.5; FT-IR (KBr) 3064, 2923,
1616, 1594, 1551, 1482, 1460, 1403, 1328, 1282, 1260, 1230, 1109,
1090, 1047, 1010 cm−1. Anal. Calcd for C13H7Cl2NO: C, 59.12; H,
2.67; N, 5.30. Found: C, 59.03; H, 2.70; N, 5.33. HRMS (ESI) m/z:
[M + H]+ calcd for C13H7Cl2NOH 263.9977, found 263.9977.
6-Chloro-2-(4-methoxyphenyl)benzo[d]oxazole (2u): analytical
TLC on silica gel, 1/9 ethyl acetate/hexane Rf = 0.52; white solid;
76 mg, 81% yield; mp 147−148 °C (lit.25i mp 140 °C); 1H NMR (400
MHz, CDCl3) δ 8.15 (d, J = 7.6 Hz, 2H), 7.62 (d, J = 8.0 Hz, 1H),
7.54 (s, 1H), 7.30 (d, J = 8.8 Hz, 1H), 7.02 (d, J = 8.0 Hz, 2H), 3.88
(s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 164.1, 162.8, 151.1,
141.3, 130.3, 129.7, 125.3, 120.3, 119.4, 114.7, 111.3, 55.7; FT-IR
(KBr) 3073, 2924, 1621, 1602, 1505, 1454, 1440, 1333, 1263, 1257,
1177, 1055, 1024 cm−1. Anal. Calcd for C14H10ClNO2: C, 64.75; H,
3.88; N, 5.39. Found: C, 64.82; H, 3.87; N, 5.32. HRMS (ESI) m/z:
[M + H]+ calcd for C14H10ClNO2H 260.0473, found 260.0473.
6-Chloro-2-p-tolylbenzo[d]oxazole (2v): analytical TLC on silica
gel, 1/9 ethyl acetate/hexane Rf = 0.70; white solid; 72 mg, 82% yield;
mp 129−130 °C (lit.25g mp 126 °C); 1H NMR (400 MHz, CDCl3) δ
silica gel, 1/9 ethyl acetate/hexane Rf = 0.40; pale yellow solid; 71 mg,
90% yield; mp 78−79 °C; H NMR (400 MHz, CDCl3) δ 7.66−7.62
1
(m, 2H), 7.55 (d, J = 2.0 Hz, 1H), 7.33 (dd, J = 8.4 Hz, 2.0 Hz, 1H),
7.27 (d, J = 3.2 Hz, 1H), 6.62−6.60 (m, 1H); 13C{1H} NMR (100
MHz, CDCl3) δ 155.9, 150.4, 146.2, 142.2, 140.6, 131.0, 125.7. 120.7,
114.9, 112.5, 111.3; FT-IR (KBr) 3062, 3039, 1635, 1606, 1538, 1455,
1427, 1326, 1290, 1264, 1232, 1160, 1089, 1057, 1011 cm−1. Anal.
Calcd for C11H6ClNO2: C, 60.16; H, 2.75; N, 6.38. Found: C, 60.24;
H, 2.73; N, 6.33. HRMS (ESI) m/z: [M + H]+ calcd for
C11H6ClNO2H 220.0160, found 220.0163.
6-Chloro-2-ethylbenzo[d]oxazole (2z): analytical TLC on silica gel,
1/9 ethyl acetate/hexane Rf = 0.50; colorless liquid; 41 mg, 63% yield;
1H NMR (400 MHz, CDCl3) δ 7.56 (d, J = 8.4 Hz, 1H), 7.47 (d, J =
2.0 Hz, 1H), 7.27 (dd, J = 8.4 Hz, 2.0 Hz, 1H), 2.96 (q, J = 8.0 Hz,
2H), 1.44 (t, J = 8.0 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ
169.1, 151.2, 140.4, 130.3, 124.9, 120.2, 111.2, 22.3, 11.0; FT-IR (KBr)
3104, 2920, 1618, 1576, 1466, 1451, 1358, 1267, 1225, 1152, 1075,
1055 cm−1. Anal. Calcd for C9H8ClNO: C, 59.52; H, 4.44; N, 7.71.
Found: C, 59.45; H, 4.46; N, 7.74. HRMS (ESI) m/z: [M + H]+ calcd
for C9H8ClNOH 182.0367, found 182.0365.
6-Chloro-2-isopropylbenzo[d]oxazole (2aa): analytical TLC on
silica gel, 1/9 ethyl acetate/hexane Rf = 0.52; colorless liquid; 56 mg,
1
80% yield; H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 8.8 Hz, 1H),
7.47 (d, J = 2.0 Hz, 1H), 7.26−7.24 (m, 1H), 3.24−3.17 (m, 1H), 1.44
(d, J = 7.2 Hz, 6H); 13C{1H}NMR (100 MHz, CDCl3) δ 172.2, 151.2,
140.3, 130.3, 124.9, 120.3, 111.2, 29.1, 20.4; FT-IR (KBr) 3098, 2988,
1614, 1570, 1465, 1446, 1367, 1266, 1232, 1138, 1083, 1054 cm−1.
Anal. Calcd for C10H10ClNO: C, 61.39; H, 5.15; N, 7.16. Found: C,
61.46; H, 5.14; N, 7.12. HRMS (ESI) m/z: [M + H]+ calcd for
C10H10ClNOH 196.0524, found 196.0525.
2-(tert-Butyl)-6-chlorobenzo[d]oxazole (2ab):25j analytical TLC
on silica gel, 1/9 ethyl acetate/hexane Rf = 0.68; colorless liquid; 34
1
mg, 45% yield; H NMR (400 MHz, CDCl3) δ 7.60 (d, J = 8.4 Hz,
1H), 7.50 (d, J = 2.0 Hz, 1H), 7.29 (dd, J = 8.4 Hz, 2.0 Hz, 1H), 1.49
(s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 174.4, 151.2, 140.2,
130.2, 124.8, 120.4, 111.2, 34.4, 28.6; FT-IR (KBr) 2977, 2870, 1614,
F
dx.doi.org/10.1021/jo501216h | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
1569, 1458, 1428, 1364, 1326, 1259, 1232, 1129, 1109, 1053 cm−1.
Anal. Calcd for C11H12ClNO: C, 63.01; H, 5.77; N, 6.68. Found: C,
63.07; H, 5.78; N, 6.63. HRMS (ESI) m/z: [M + H]+ calcd for
C11H12ClNOH 210.0680, found 210.0686.
HRMS (ESI) m/z: [M + H]+ calcd for C14H8N2SH 237.0481, found
237.0482.
Ethyl 2-phenylbenzo[d]thiazole-6-carboxylate (4h): analytical
TLC on silica gel, 1/9 ethyl acetate/hexane Rf = 0.56; white solid;
39 mg, 38% yield; mp 192−193 °C (lit.14a mp 196 °C); 1H NMR (400
MHz, CDCl3) δ 8.61 (d, J = 0.8 Hz, 1H), 8.17 (dd, J = 8.8 Hz, 1.6 Hz,
1H), 8.10−8.06 (m, 3H), 7.51−7.48 (m, 3H), 4.44 (q, J = 7.2 Hz,
2H), 1.44 (t, J = 7.2 Hz, 3H);; 13C{1H} NMR (150 MHz, CDCl3) δ
171.5, 166.3, 157.1, 135.1, 133.4, 131.7, 129.3, 127.9, 127.7, 127.4,
123.9, 123.0, 61.4, 14.5; FT-IR (KBr) 2975, 1708, 1684, 1628, 1506,
1477, 1441, 1408, 1390, 1325, 1273, 1226, 1133, 1056, 1030 cm−1.
Anal. Calcd for C16H13NO2S: C, 67.82; H, 4.62; N, 4.94; S, 11.32.
Found: C, 67.72; H, 4.64; N, 4.98; S, 11.38. HRMS (ESI) m/z: [M +
H]+ calcd for C16H13NO2SH 284.0740, found 284.0749.
2-Phenylbenzo[d]thiazole (4a): analytical TLC on silica gel, 1/9
ethyl acetate/hexane Rf = 0.62; white solid; 64 mg, 84% yield; mp
101−102 °C (lit.10e mp 99 °C); 1H NMR (400 MHz, CDCl3) δ 8.09−
8.05 (m, 3H), 7.90 (d, J = 7.6 Hz, 1H), 7.50−7.46 (m, 4H), 7.39−7.35
(m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 168.2, 154.3, 135.2,
133.8, 131.1, 129.2, 127.7, 126.5, 125.3, 123.4, 121.8; FT-IR (KBr)
3034, 1634, 1510, 1479, 1454, 1445, 1434, 1314, 1225, 1159, 1071,
1028 cm−1. Anal. Calcd for C13H9NS: C, 73.90; H, 4.29; N, 6.63; S,
15.18. Found: C, 73.99; H, 4.27; N, 6.59; S, 15.15. HRMS (ESI) m/z:
[M + H]+ calcd for C13H9NSH 212.0528, found 212.0528.
4-Methyl-2-phenylbenzo[d]thiazole (4b):16 analytical TLC on
silica gel, 1/9 ethyl acetate/hexane Rf = 0.80; white solid; 33 mg,
6-Chloro-2-phenylbenzo[d]thiazole (4i): analytical TLC on silica
gel, 1/9 ethyl acetate/hexane Rf = 0.64; white solid; 78 mg, 88% yield;
mp 156−157 °C (lit.15 mp 160 °C); H NMR (400 MHz, CDCl3) δ
1
1
41% yield; mp 41−42 °C; H NMR (400 MHz, CDCl3) δ 8.11−8.09
8.06−8.04 (m, 2H), 7.97 (d, J = 8.4 Hz, 1H), 7.87 (d, J = 2.0 Hz, 1H),
7.50−7.48 (m, 3H), 7.45 (dd, J = 8.4 Hz, 1.6 Hz, 1H); 13C{1H} NMR
(150 MHz, CDCl3) δ 168.7, 152.9, 136.4, 133.4, 131.4, 131.3, 129.3,
127.7, 127.3, 124.1, 121.4; FT-IR (KBr) 3076, 2923, 1587, 1545, 1479,
1438, 1306, 1246, 1224, 1104, 1072, 1053 cm−1. Anal. Calcd for
C13H8ClNS: C, 63.54; H, 3.28; N, 5.70; S, 13.05. Found: C, 63.48; H,
3.26; N, 5.73; S, 13.09. HRMS (ESI) m/z: [M + H]+ calcd for
C13H8ClNSH 246.0139, found 246.0142.
(m, 2H), 7.73−7.71 (m, 1H), 7.49−7.47 (m, 3H), 7.27−7.26 (m, 2H),
2.80 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 166.8, 153.7, 135.2,
134.2, 133.6, 130.9, 129.2, 127.7, 127.0, 125.3, 119.2, 18.6; FT-IR
(KBr) 3061, 2920, 1577, 1478, 1445, 1314, 1223, 1179, 1072, 970
cm−1. Anal. Calcd for C14H11NS: C, 74.63; H, 4.92; N, 6.22; S, 14.23.
Found: C, 74.70; H, 4.90; N, 6.20; S, 14.20. HRMS (ESI) m/z: [M +
H]+ calcd for C14H11NSH 226.0685, found 226.0682.
7-Methoxy-2-phenylbenzo[d]thiazole (4ca) and 5-Methoxy-2-
phenylbenzo[d]thiazole (4cb). Characterization Data for 4cb:
analytical TLC on silica gel, 1/9 ethyl acetate/hexane Rf = 0.54;
6-Fluoro-2-phenylbenzo[d]thiazole (4j): analytical TLC on silica
gel, 1/9 ethyl acetate/hexane Rf = 0.62; white solid; 68 mg, 83% yield;
white solid; 77 mg, 89% yield; mp 71−72 °C (lit.14a mp 75 °C); H
mp 133−134 °C (lit.15 mp 137 °C); H NMR (400 MHz, CDCl3) δ
1
1
NMR (400 MHz, CDCl3) δ 8.05−8.04 (m, 2H), 7.73 (d, J = 8.8 Hz,
1H), 7.55 (s, 1H), 7.46 (s, 3H), 7.03 (d, J = 8.4 Hz, 1H); 13C{1H}
NMR (100 MHz, CDCl3) δ 169.5, 159.3, 155.6, 133.9, 131.0, 129.2,
127.6, 127.1, 122.0, 115.7, 105.7, 55.8; FT-IR (KBr) 2936, 1601, 1558,
1465, 1430, 1329, 1279, 1248, 1160, 1139, 1076, 1025, 969 cm−1.
Anal. Calcd for C14H11NOS: C, 69.68; H, 4.59; N, 5.80; S, 13.29.
Found: C, 69.75; H, 4.60; N, 5.78; S, 13.25. HRMS (ESI) m/z: [M +
H]+ calcd for C14H11NOSH 242.0634, found 242.0634.
8.05−8.02 (m, 2H), 8.01 (dd, J = 9.2 Hz, 4,8 Hz, 1H), 7.57 (dd, J = 7.6
Hz, 2.4 Hz, 1H), 7.49−7.47 (m, 3H), 7.23 (td, J = 8.8 Hz, 2.8 Hz,
1H); 13C{1H} NMR (100 MHz, CDCl3) δ 167.9 (d, J = 3.0 Hz), 161.8
(d, J = 244.8 Hz), 150.9 (d, J = 1.5 Hz), 136.2 (d, J = 11.4 Hz), 133.4,
131.2, 129.2, 127.6 (d, J = 4.6 Hz), 124.3 (d, J = 9.1 Hz), 115.2 (d, J =
25.2 Hz), 108.1 (d, J = 26.6 Hz); FT-IR (KBr) 3078, 2921, 1896,
1608, 1562, 1513, 1482, 1454, 1443, 1316, 1307, 1276, 1260, 1249,
1118, 1072, 1050, 1029 cm−1. Anal. Calcd for C13H8FNS: C, 68.10; H,
3.52; N, 6.11; S, 13.99. Found: C, 68.15; H, 3.51; N, 6.14; S, 13.94.
HRMS (ESI) m/z: [M + H]+ calcd for C13H8FNSH 230.0434, found
230.0438.
7-Methyl-2-phenylbenzo[d]thiazole (4da)25f and 5-methyl-2-
phenylbenzo[d]thiazole (4db):18a analytical TLC on silica gel, 1/9
ethyl acetate/hexane Rf = 0.72; white solid; 64 mg, 79% yield; mp
1
129−130 °C; H NMR (400 MHz, CDCl3) δ 8.11−8.05 (m, 3H),
6-Methoxy-2-phenylbenzo[d]thiazole (4k): analytical TLC on
7.92 (d, J = 8.4 Hz, 1H), 7.87 (s, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.50−
7.45 (m, 7H), 7.42 (t, J = 7.6 Hz, 1H), 7.21−7.16 (m, 2H), 2.59 (s,
3H), 2.50 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3) δ 168.3, 167.7,
154.7, 154.2, 136.6, 135.8, 134.0, 132.2, 131.9, 131.1, 131.0, 129.2,
129.15, 127.71, 127.7, 127.0, 126.7, 126.3, 125.6, 123.4, 121.3, 120.9,
21.7, 21.6; FT-IR (KBr) 3066, 2921, 1601, 1502, 1476, 1441, 1313,
1276, 1230, 1152, 1071, 967 cm−1. Anal. Calcd for C14H11NS: C,
74.63; H, 4.92; N, 6.22; S, 14.23. Found: C, 74.57; H, 4.91; N, 6.26; S,
14.26. HRMS (ESI) m/z: [M + H]+ calcd for C14H11NSH 226.0685,
found 226.0686.
silica gel, 1/9 ethyl acetate/hexane Rf = 0.50; white solid; 76 mg,
87% yield; mp 114−115 °C (lit.15 mp 116 °C); H NMR (400 MHz,
1
CDCl3) δ 8.04−8.01 (m, 2H), 7.95 (d, J = 8.8 Hz, 1H), 7.47−7.44 (m,
3H), 7.34 (d, J = 2.8 Hz, 1H), 7.09 (dd, J = 9.2 Hz, 2.8 Hz, 1H), 3.88
(s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 165.7, 157.9, 148.9,
136.6, 133.9, 130.7, 129.1, 127.4, 123.9, 115.8, 104.3, 55.9; FT-IR
(KBr) 3072, 2970, 1602, 1558, 1511, 1483, 1464, 1280, 1266, 1225,
1118, 1097, 1059, 999 cm−1. Anal. Calcd for C14H11NOS: C, 69.68; H,
4.59; N, 5.80; S, 13.29. Found: C, 69.61; H, 4.60; N, 5.84; S, 13.33.
HRMS (ESI) m/z: [M + H]+ calcd for C14H11NOSH 242.0634, found
242.0632.
6-Bromo-2-phenylbenzo[d]thiazole (4f): analytical TLC on silica
gel, 1/9 ethyl acetate/hexane Rf = 0.66; white solid; 93 mg, 89% yield;
mp 146−147 °C (lit.14b mp 150 °C); 1H NMR (400 MHz, CDCl3) δ
8.06−8.04 (m, 2H), 8.02 (d, J = 2.0 Hz, 1H), 7.91 (d, J = 8.4 Hz, 1H),
7.58 (dd, J = 8.8 Hz, 2.0 Hz, 1H), 7.49−7.47 (m, 3H); 13C{1H} NMR
(100 MHz, CDCl3) δ 168.7, 153.2, 136.8, 133.3, 131.4, 130.0, 129.3,
127.7, 124.5, 124.3, 118.9; FT-IR (KBr) 3074, 1637, 1509, 1478, 1445,
1395, 1304, 1276, 1248, 1225, 1091, 1072 cm−1. Anal. Calcd for
C13H8BrNS: C, 53.81; H, 2.78; N, 4.83; S, 11.05. Found: C, 53.72; H,
2.80; N, 4.85; S, 11.11. HRMS (ESI) m/z: [M + H]+ calcd for
C13H8BrNSH 289.9634, found 289.9634.
6-Methyl-2-phenylbenzo[d]thiazole (4l): analytical TLC on silica
gel, 1/9 ethyl acetate/hexane Rf = 0.62; white solid; 72 mg, 89% yield;
mp 124−125 °C (lit.15 mp 126 °C); H NMR (400 MHz, CDCl3) δ
1
8.07−8.05 (m, 2H), 7.95 (d, J = 8.8 Hz, 1H), 7.68 (s, 1H), 7.49−7.46
(m, 3H), 7.30−7.28 (m, 1H), 2.48 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 167.2, 152.5, 135.5, 135.4, 133.9, 130.9, 129.2, 128.1, 127.6,
122.9, 121.5, 21.7; FT-IR (KBr) 3053, 2914, 1603, 1552, 1480, 1309,
1256, 1227, 1125, 1075, 1062, 971 cm−1. Anal. Calcd for C14H11NS: C,
74.63; H, 4.92; N, 6.22; S, 14.23. Found: C, 74.73; H, 4.90; N, 6.17; S,
14.20. HRMS (ESI) m/z: [M + H]+ calcd for C14H11NSH 226.0685,
found 226.0683.
2-Phenylbenzo[d]thiazole-6-carbonitrile (4g): analytical TLC on
silica gel, 1/9 ethyl acetate/hexane Rf = 0.64; white solid; 35 mg, 41%
2-Phenyl-6-(trifluoromethyl)benzo[d]thiazole (4n): analytical TLC
on silica gel, 1/9 ethyl acetate/hexane Rf = 0.52; white solid; 44 mg,
44% yield; mp 157−158 °C (lit.10e mp 152 °C); 1H NMR (400 MHz,
CDCl3) δ 8.18 (s, 1H), 8.14−8.08 (m, 3H), 7.72 (d, J = 8.4 Hz, 1H),
7.52−7.50 (m, 3H); 13C{1H} NMR (150 MHz, CDCl3) δ 171.4,
156.3, 135.3, 133.3, 131.9, 129.4 (2C), 128.0, 123.7, 123.6, 123.5,
119.6 (q, J = 4.5 Hz); FT-IR (KBr) 3036, 1512, 1482, 1461, 1415,
1320, 1252, 1225, 1167, 1109, 1086, 970 cm−1. Anal. Calcd for
yield; mp 193−194 °C (lit.14a,b mp 195 °C); H NMR (400 MHz,
1
CDCl3) δ 8.22 (s, 1H), 8.11−8.08 (m, 3H), 7.73 (d, J = 8.0 Hz, 1H),
7.53−7.51 (m, 3H); 13C{1H} NMR (150 MHz, CDCl3) δ 172.5,
156.7, 135.7, 133.0, 132.3, 130.0, 129.5, 128.1, 126.6, 124.1, 118.9,
108.8; FT-IR (KBr) 2954, 2229, 1632, 1506, 1475, 1441, 1405, 1311,
1260, 1061, 970 cm−1. Anal. Calcd for C14H8N2S: C, 71.16; H, 3.41;
N, 11.86; S, 13.57. Found: C, 71.24; H, 3.39; N, 11.87; S, 13.50.
G
dx.doi.org/10.1021/jo501216h | J. Org. Chem. XXXX, XXX, XXX−XXX

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C14H8F3NS: C, 60.21; H, 2.89; N, 5.02; S, 11.48. Found: C, 60.27; H,
2.90; N, 5.00; S, 11.44. HRMS (ESI) m/z: [M + H]+ calcd for
C14H8F3NSH 280.0402, found 280.0406.
C, 59.21; H, 2.68; N, 5.31; S, 12.16. Found: C, 59.12; H, 2.67; N, 5.35;
S, 12.19. HRMS (ESI) m/z: [M + H]+ calcd for C13H7ClFNSH
264.0045, found 264.0041.
4,6-Dimethyl-2-phenylbenzo[d]thiazole (4o):25h analytical TLC
on silica gel, 1/9 ethyl acetate/hexane Rf = 0.68; white solid; 53 mg,
6-Chloro-2-(4-methoxyphenyl)benzo[d]thiazole (4u): analytical
TLC on silica gel, 1/9 ethyl acetate/hexane Rf = 0.54; white solid;
92 mg, 93% yield; mp 137−138 °C (lit.25c mp 135 °C); 1H NMR (400
MHz, CDCl3) δ 7.99 (d, J = 9.2 Hz, 2H), 7.91 (d, J = 8.8 Hz, 1H),
7.83 (d, J = 2.0 Hz, 1H), 7.42 (dd, J = 9.2 Hz, 2.4 Hz, 1H), 6.99 (d, J =
8.8 Hz, 2H), 3.87 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 168.5,
162.3, 153.0, 136.2, 130.7, 129.3, 127.1, 126.2, 123.6, 121.3, 114.6,
55.7; FT-IR (KBr) 3024, 2923, 1602, 1522, 1483, 1458, 1440, 1429,
1309, 1260, 1225, 1171, 1101, 1051, 1027, 966 cm−1. Anal. Calcd for
C14H10ClNOS: C, 60.98; H, 3.66; N, 5.08; S, 11.63; Found: C, 61.07;
H, 3.65; N, 5.05; S, 11.59. HRMS (ESI) m/z: [M + H]+ calcd for
C14H10ClNOSH 276.0244, found 276.0244.
1
61% yield; mp 89−90 °C; H NMR (400 MHz, CDCl3) δ 8.09−8.07
(m, 2H), 7.50 (s, 1H), 7.47−7.44 (m, 3H), 7.09 (s, 1H), 2.75 (s, 3H),
2.44 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 165.7, 151.9, 135.4,
135.3, 134.3, 132.9, 130.7, 129.1, 128.7, 127.6, 118.9, 21.7, 18.5; FT-IR
(KBr) 3051, 2914, 1595, 1510, 1480, 1439, 1310, 1281, 1222, 1177,
1094, 1069, 1031, 973 cm−1. Anal. Calcd for C15H13NS: C, 75.28; H,
5.47; N, 5.85; S, 13.40. Found: C, 75.36; H, 5.48; N, 5.81; S, 13.35.
HRMS (ESI) m/z: [M + H]+ calcd for C15H13NSH 240.0841, found
240.0840.
6,7-Dimethyl-2-phenylbenzo[d]thiazole (4pa) and 5,6-dimethyl-
2-phenylbenzo[d]thiazole (4pb): analytical TLC on silica gel, 1/9
ethyl acetate/hexane Rf = 0.60; white solid; 65 mg, 75% yield; mp
6-Chloro-2-p-tolylbenzo[d]thiazole (4v):25k analytical TLC on
silica gel, 1/9 ethyl acetate/hexane Rf = 0.64; white solid; 83 mg,
89% yield; mp 158−159 °C; 1H NMR (400 MHz, CDCl3) δ 7.94 (d, J
= 8.0 Hz, 3H), 7.84 (d, J = 2.0 Hz, 1H), 7.43 (dd, J = 8.4 Hz, 1.6 Hz,
1H), 7.29 (d, J = 8.4 Hz, 2H), 2.41 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 168.9, 152.9, 142.0, 136.3, 131.0, 130.7, 130.0, 127.6, 127.2,
123.9, 121.3, 21.7; FT-IR (KBr) 2918, 1610, 1542, 1481, 1426, 1308,
1232, 1210, 1098, 1048, 962 cm−1. Anal. Calcd for C14H10ClNS: C,
64.73; H, 3.88; N, 5.39; S, 12.34; Found: C, 64.79; H, 3.86; N, 5.42; S,
12.29. HRMS (ESI) m/z: [M + H]+ calcd for C14H10ClNSH 260.0295,
found 260.0295.
1
113−114 °C; H NMR (400 MHz, CDCl3) δ 8.09−8.04 (m, 4H),
7.83 (s, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.63 (s, 1H), 7.49−7.45 (m,
6H), 7.29 (d, J = 8.4 Hz, 1H), 2.50 (s, 3H), 2.41 (s, 3H), 2.39 (s, 3H),
2.38 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 167.1, 166.8, 153.1,
152.5, 136.7, 135.7, 134.9, 134.03, 134.0, 133.1, 132.6, 131.1, 130.8,
130.76, 129.5, 129.1, 129.0, 127.5, 127.2, 123.5, 121.7, 120.4, 20.4,
20.3, 19.7, 19.4; FT-IR (KBr) 3056, 2974, 1507, 1476, 1448, 1309,
1275, 1228, 1023, 947 cm−1. Anal. Calcd for C15H13NS: C, 75.28; H,
5.47; N, 5.85; S, 13.40. Found: C, 75.21; H, 5.49; N, 5.88; S, 13.42.
HRMS (ESI) m/z: [M + H]+ calcd for C15H13NSH 240.0841, found
240.0841.
6-Chloro-2-(4-nitrophenyl)benzo[d]thiazole (4w): analytical TLC
on silica gel, 1/9 ethyl acetate/hexane Rf = 0.76; white solid; 90 mg,
86% yield; mp 208−209 °C (lit.10d mp 216 °C); 1H NMR (600 MHz,
DMSO-d6) δ 8.40−8.36 (m, 5H), 8.15 (d, J = 8.4 Hz, 1H), 7.65 (d, J =
7.2 Hz, 1H); 13C{1H} NMR (150 MHz, DMSO-d6) δ 166.1, 152.2,
148.9, 137.9, 136.6, 130.9, 128.5, 127.7, 124.64, 124.6, 122.4; FT-IR
(KBr) 2920, 1684, 1653, 1597, 1518, 1403, 1346,1322, 1302, 1237,
1017, 969 cm−1. Anal. Calcd for C13H7ClN2O2S: C, 53.71; H, 2.43; N,
9.64; S, 11.03. Found: C, 53.79; H, 2.42; N, 9.61; S, 10.98. HRMS
(ESI) m/z: [M + H]+ calcd for C13H7ClN2O2SH 290.999, found
290.995.
5,7-Dichloro-2-phenylbenzo[d]thiazole (4q): analytical TLC on
silica gel, 1/9 ethyl acetate/hexane Rf = 0.72; white solid; 73 mg, 72%
yield; mp 115−116 °C; 1H NMR (400 MHz, CDCl3) δ 8.07−8.05 (m,
2H), 7.93 (d, J = 1.6 Hz, 1H), 7.51−7.50 (m, 3H), 7.38 (d, J = 1.6 Hz,
1H); 13C{1H} NMR (150 MHz, CDCl3) δ 170.6, 155.1, 134.0, 133.0,
132.8, 131.9, 129.4, 127.9, 127.4, 125.3, 121.8; FT-IR (KBr) 3060,
2921, 1570, 1537, 1507, 1441, 1424, 1379, 1262, 1098, 1067, 984
cm−1. Anal. Calcd for C13H7Cl2NS: C, 55.73; H, 2.52; N, 5.00; S,
11.44. Found: C, 55.82; H, 2.51; N, 4.95; S, 11.39. HRMS (ESI) m/z:
[M + H]+ calcd for C13H7Cl2NSH 279.9749, found 279.9749.
6-Chloro-2-(o-tolyl)benzo[d]thiazole (4r): analytical TLC on silica
gel, 1/9 ethyl acetate/hexane Rf = 0.68; white solid; 89 mg, 95% yield;
2-Phenylnaphtho[1,2-d]thiazole (4x):16 analytical TLC on silica
gel, 1/9 ethyl acetate/hexane Rf = 0.70; white solid; 83 mg, 88% yield;
1
mp 97−98 °C; H NMR (400 MHz, CDCl3) δ 8.92 (d, J = 8.4 Hz,
1
mp 95−96 °C; H NMR (400 MHz, CDCl3) δ 7.99 (d, J = 8.8 Hz,
1H), 8.20−8.17 (m, 2H), 7.95−7.90 (m, 2H), 7.81 (d, J = 8.8 Hz,
1H),7.70−7.66 (m, 1H), 7.60−7.56 (m, 1H), 7.53−7.48 (m, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 167.2, 150.6, 134.2, 132.2, 131.9,
130.8, 129.2, 129.0, 128.3, 127.5, 127.1, 126.3, 126.1, 124.2, 119.2; FT-
IR (KBr) 3047, 2922, 1509, 1472, 1442, 1394, 1361, 1251, 1069, 1025,
972 cm−1. Anal. Calcd for C17H11NS: C, 78.13; H, 4.24; N, 5.36; S,
12.27. Found: C, 78.23; H, 4.23; N, 5.30; S, 12.24. HRMS (ESI) m/z:
[M + H]+ calcd for C17H11NSH 262.0685, found 262.0685.
1H), 7.89 (d, J = 2.0 Hz, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.46 (dd, J =
8.8 Hz, 2.0 Hz, 1H), 7.37−7.30 (m, 3H), 2.64 (s, 3H); 13C{1H} NMR
(100 MHz, CDCl3) δ 168.7, 152.6, 137.6, 136.9, 132.8, 131.9, 131.3,
130.7, 130.5, 127.2, 126.4, 124.3, 121.2, 21.6 ; FT-IR (KBr) 2924,
2853, 1604, 1591, 1480, 1441, 1382, 1305, 1220, 1100, 1050 cm−1.
Anal. Calcd for C14H10ClNS: C, 64.73; H, 3.88; N, 5.39; S, 12.34.
Found: C, 64.69; H, 3.90; N, 5.36; S, 12.37. HRMS (ESI) m/z: [M +
H]+ calcd for C14H10ClNSH 260.0295, found 260.0295.
6-Chloro-2-(furan-2-yl)benzo[d]thiazole (4y): analytical TLC on
silica gel, 1/9 ethyl acetate/hexane Rf = 0.48; white solid; 69 mg, 81%
6-Chloro-2-(m-tolyl)benzo[d]thiazole (4s): analytical TLC on silica
gel, 1/9 ethyl acetate/hexane Rf = 0.68; white solid; 87 mg, 93% yield;
mp 121−122 °C; 1H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 9.2 Hz,
1H), 7.88 (s, 1H), 7.85 (d, J = 2.0 Hz, 1H), 7.82 (d, J = 7.6 Hz, 1H),
7.44 (dd, J = 8.8 Hz, 2.4 Hz, 1H), 7.38 (t, J = 7.6 Hz, 1H), 7.30 (d, J =
7.2 Hz, 1H), 2.43 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3) δ 169.0,
152.9, 139.1, 136.4, 133.3, 132.2, 131.2, 129.2, 128.1, 127.2, 125.0,
124.0, 121.4, 21.5; FT-IR (KBr) 3056, 2924, 1593, 1512, 1441, 1400,
1306, 1249, 1170, 1104, 1024 cm−1. Anal. Calcd for C14H10ClNS: C,
64.73; H, 3.88; N, 5.39; S, 12.34. Found: C, 64.67; H, 3.87; N, 5.43; S,
12.38. HRMS (ESI) m/z: [M + H]+ calcd for C14H10ClNSH 260.0295,
found 260.0298.
yield; mp 115−116 °C (lit.25c mp 119 °C); H NMR (400 MHz,
1
CDCl3) δ 7.93 (d, J = 8.8 Hz, 1H), 7.84 (d, J = 2.0 Hz, 1H), 7.60 (d, J
= 1.2 Hz, 1H), 7.44 (dd, J = 8.4 Hz, 1.6 Hz, 1H), 7.18 (d, J = 3.6 Hz,
1H), 6.59−6.58 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 158.1,
152.5, 148.5, 145.2, 135.7, 131.2, 127.5, 123.9, 121.4, 112.8, 112.0; FT-
IR (KBr) 3131, 1600, 1578, 1548, 1502, 1470, 1435, 1304, 1281, 1250,
1222, 1132, 1099, 1077, 1019 cm−1. Anal. Calcd for C11H6ClNOS: C,
56.06; H, 2.57; N, 5.94; S, 13.60; Found: C, 56.00; H, 2.56; N, 5.99; S,
13.58. HRMS (ESI) m/z: [M + H]+ calcd for C11H6ClNOSH
235.9931, found 235.9931.
6-Chloro-2-(naphthalen-1-yl)benzo[d]thiazole (4z): analytical
TLC on silica gel, 1/9 ethyl acetate/hexane Rf = 0.60; yellow solid;
80 mg, 75% yield; mp 123−124 °C; H NMR (400 MHz, CDCl3) δ
8.93 (d, J = 8.8 Hz, 1H), 8.09 (d, J = 8.4 Hz, 1H), 8.00 (d, J = 8.0 Hz,
1H), 7.93−7.90 (m, 3H), 7.62−7.48 (m, 4H); 13C{1H} NMR (150
MHz, CDCl3) δ 168.4, 153.0, 136.8, 134.3, 131.62, 131.6, 130.8, 130.6,
129.7, 128.7, 128.0, 127.3, 126.8, 126.0, 125.2, 124.5, 121.2; FT-IR
(KBr) 3059, 2924, 1618, 1552, 1488, 1450, 1426, 1331, 1263, 1051,
1022 cm−1. Anal. Calcd for C17H10ClNS: C, 69.03; H, 3.41; N, 4.74; S,
6-Chloro-2-(4-fluorophenyl)benzo[d]thiazole (4t): analytical TLC
on silica gel, 1/9 ethyl acetate/hexane Rf = 0.68; white solid; 85 mg,
90% yield; mp 151−152 °C (lit.25c mp 151 °C); 1H NMR (400 MHz,
CDCl3) δ 8.05−8.02 (m, 2H), 7.94 (d, J = 9.2 Hz, 1H), 7.85 (d, J = 2.0
Hz, 1H), 7.44 (dd, J = 8.4 Hz, 1.6 Hz, 1H), 7.19−7.15 (m, 2H);
13C{1H} NMR (100 MHz, CDCl3) δ 167.3, 166.0, 163.5, 152.8, 136.4,
131.3, 129.8 (d, J = 9.2 Hz), 127.4, 124.1, 121.4, 116.5 (d, J = 22.1
Hz); FT-IR (KBr) 3034, 2914, 1598, 1548, 1521, 1484, 1441, 1408,
1305, 1231, 1155, 1096, 1052, 965 cm−1. Anal. Calcd for C13H7ClFNS:
1
H
dx.doi.org/10.1021/jo501216h | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
10.84; Found: C, 69.11; H, 3.40; N, 4.70; S, 10.79. HRMS (ESI) m/z:
[M + H]+ calcd for C17H10ClNSH 296.0295, found 296.0297.
6-Chloro-2-ethylbenzo[d]thiazole (4aa):25b analytical TLC on
silica gel, 1/9 ethyl acetate/hexane Rf = 0.58; colorless liquid; 45 mg,
(ESI) m/z: [M + H]+ calcd for C14H12D2NO 214.1201, found
214.1207.
Intermolecular Competition Reaction. Oxone (0.75 mmol) was
added to a stirred solution of N-(p-tolyl)benzamide (1a; 0.2 mmol,
42.2 mg) and N-(p-tolyl)benzamide-d2 (1a-d2; 0.3 mmol, 63.9 mg,
82.5% deuterated), 1-iodo-4-nitrobenzene (0.1 mmol, 12.45 mg), and
triflic acid (1.5 mmol, 132 μL) in HFIP (3.5 mL) at room temperature
in air. The reaction was stopped at 23% conversion (3.5 h) and the
mixture then treated with saturated Na2S2O3 (1 mL) and NaHCO3 (1
mL) solutions. The mixture was extracted with ethyl acetate (3 × 10
mL) and washed with brine (2 × 5 mL) and water (1 × 5 mL). Drying
(Na2SO4) and evaporation of the solvent gave a residue that was
purified by silica gel column chromatography using hexane and ethyl
1
63% yield; H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 8.8 Hz, 1H),
7.79 (d, J = 1.6 Hz, 1H), 7.39 (dd, J = 8.8 Hz, 2.0 Hz, 1H), 3.14 (q, J =
7.6 Hz, 2H), 1.46 (t, J = 7.6 Hz, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 174.2, 152.0, 136.5, 130.7, 126.8, 123.4, 121.3, 27.9, 13.8;
FT-IR (KBr) 2968, 1592, 1519, 1441, 1400, 1301, 1270, 1169, 1096,
1049 cm−1. Anal. Calcd for C9H8ClNS: C, 54.68; H, 4.08; N, 7.09; S,
16.22; Found: C, 54.61; H, 4.10; N, 7.14; S, 16.20. HRMS (ESI) m/z:
[M + H]+ calcd for C9H8ClNSH 198.0139, found 198.0139.
6-Chloro-2-isopropylbenzo[d]thiazole (4ab): analytical TLC on
silica gel, 1/9 ethyl acetate/hexane Rf = 0.60; yellow liquid; 67 mg,
1
acetate as eluent (19% yield): H NMR (400 MHz, CDCl3) δ 8.23−
8.21 (m, 1.88H), 7.63 (d, J = 8.0 Hz, 0.46H), 7.52−7.49 (m, 2.93H),
1
88% yield; H NMR (400 MHz, CDCl3) δ 7.86 (d, J = 8.8 Hz, 1H),
1
7.37 (s, 0.90H), 7.16−7.14 (m, 0.91H), 2.49 (s, 3H). The H NMR
7.80 (d, J = 2.0 Hz, 1H), 7.39 (dd, J = 9.2 Hz, 2.4 Hz, 1H), 3.40−3.36
(m, 1H), 1.46 (d, J = 7.2 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3)
δ 179.2, 151.9, 136.1, 130.6, 126.7, 123.5, 121.3, 34.2, 22.9; FT-IR
(KBr) 2968, 1592, 1517, 1463, 1443, 1310, 1298, 1265, 1100, 1037,
1001 cm−1. Anal. Calcd for C10H10ClNS: C, 56.73; H, 4.76; N, 6.62; S,
15.15. Found: C, 56.81; H, 4.74; N, 6.58; S, 15.11. HRMS (ESI) m/z:
[M + H]+ calcd for C10H10ClNSH 212.0295, found 212.0296.
2-(tert-Butyl)-6-chlorobenzo[d]thiazole (4ac):25c analytical TLC
on silica gel, 1/9 ethyl acetate/hexane Rf = 0.72; colorless liquid; 66
analysis showed the kinetic isotopic effect (KIE) value PH/PD = 1.0.
ASSOCIATED CONTENT
■
S
* Supporting Information
Figures giving NMR (1H and 13C) spectra of the products 2a−
ab and 4a−ac. This material is available free of charge via the
Internet at http://pubs.acs.org.
1
mg, 81% yield; H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 8.8 Hz,
AUTHOR INFORMATION
Corresponding Author
*E-mail for T.P.: tpunni@iitg.ernet.in.
■
1H), 7.80 (d, J = 2.0 Hz, 1H), 7.39 (dd, J = 8.4 Hz, 1.6 Hz, 1H), 1.49
(s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 182.6, 152.0, 136.4,
130.6, 126.7, 123.6, 121.2, 38.6, 30.9; FT-IR (KBr) 2966, 1592, 1505,
1473, 1438, 1399, 1365, 1299, 1272, 1127, 1043, 1013 cm−1. Anal.
Calcd for C11H12ClNS: C, 58.53; H, 5.36; N, 6.20; S, 14.20. Found: C,
58.60; H, 5.34; N, 6.17; S, 14.15. HRMS (ESI) m/z: [M + H]+ calcd
for C11H12ClNSH 226.0452, found 226.0447.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge Department of Science and
Technology, New Delhi, India, and the Council of Scientific
and Industrial Research, New Delhi, India, for financial support.
P.S. thanks the UGC for an SRF Fellowship. We also thank
Central Instrumental Facility, IIT Guwahati, for NMR facilities.
Scheme 5
REFERENCES
■
Preparation of p-Toluidine-d2 (Scheme 5).22a In a microwave
reaction vial equipped with a magnetic stir bar, p-toluidine (2 mmol,
214 mg), D2O (2.5 mL) and 0.2 M HCl (1 equiv) were added. The
vial was then capped, sealed, and heated in the microwave synthesis
apparatus for 0.5 h at 180 °C. The reaction mixture was transferred to
a round-bottom flask, and the solvent was removed on a rotary
evaporator to afford the DCl salt of the p-toludine. The residue was
treated with 3 M NaOH (3 mL), and the solution was extracted using
diethyl ether (10 mL), and washed with brine (3 mL). Drying
(Na2SO4) and evaporation of the solvent under reduced pressure
afforded the deuterated p-toluidine, and the deuterium incorporation
(82.5%) was determined by 1H NMR analysis of the mixture.22e
Characterization data for the deuterated product: analytical TLC on
silica gel, 1/4 ethyl acetate/hexane Rf = 0.32; pale brown solid; 185
mg, 85% yield; 1H NMR (400 MHz, CDCl3) δ 6.96 (s, 2H), 3.47 (bs,
2H), 2.23 (s, 3H).
(1) Ueki, M.; Ueno, K.; Miyadoh, S.; Abe, K.; Shibata, K.; Taniguchi,
M.; Oi, S. J. Antibiot. 1993, 46, 1089.
(2) Don, M.-J.; Shen, C.-C.; Lin, Y.-L.; Syu, W., Jr.; Ding, Y.-H.; Sun,
C.-M. J. Nat. Prod. 2005, 68, 1066.
(3) Sato, S.; Kajiura, T.; Noguchi, M.; Takehana, K.; Kobayashi, T.;
Tsuji, T. J. Antibiot. 2001, 54, 102.
(4) (a) Rodriguez, A. D.; Ramirez, C.; Rodriguez, I. I.; Gonzalez, E.
Org. Lett. 1999, 1, 527. (b) Davidson, J. P.; Corey, E. J. J. Am. Chem.
Soc. 2003, 125, 13486.
(5) (a) Saari, W. S.; Hoffman, J. M.; Wai, J. S.; Fisher, T. E.; Rooney,
C. S.; Smith, A. M.; Thomas, C. M.; Goldman, M. E.; O’Brien, J. A. J.
Med. Chem. 1991, 34, 2922. (b) Sun, L.-Q.; Chen, J.; Takaki, K.;
Johnson, G.; Iben, L.; Mahle, C. D.; Ryan, E.; Xu, C. Bioorg. Med.
Chem. Lett. 2004, 14, 1197. (c) Bradshaw, T. D.; Westwell, A. D. Curr.
Med. Chem. 2004, 11, 1241. (d) Yoshida, S.; Shiokawa, S.; Kawano, K.;
Ito, T.; Murakami, H.; Suzuki, H.; Sato, Y. J. Med. Chem. 2005, 48,
7075. (e) Nishiu, J.; Ito, M.; Ishida, Y.; Kakutani, M.; Shibata, T.;
Matsushita, M.; Shindo, M. Diabetes, Obes. Metab. 2006, 8, 508.
(f) Leventhal, L.; Brandt, M. R.; Cummons, T. A.; Piesla, M. J.;
Rogers, K. E.; Harris, H. A. Eur. J. Pharmacol. 2006, 553, 146.
(g) Bergman, J. M.; Coleman, P. J.; Cox, C.; Hartman, G. D.; Lindsley,
C.; Mercer, S. P.; Roecker, A. J.; Whitman, D. B. PCT. Int. Appl.
WO2006127550, 2006.
Preparation of N-(p-Tolyl)benzamide-d2 (1a-d2). To a stirred
solution of p-toluidine-d2 (1.5 mmol, 163 mg) in THF (3 mL) at 0 °C
was added dropwise benzoyl chloride (1.65 mmol, 192 μL). The
resulting solution was warmed to room temperature, and stirring was
continued for an additional 24 h. The solvent was evaporated on a
rotary evaporator, and the residue was treated with ethyl acetate (5
mL). The solution was successively washed with aqueous NaHCO3 (2
mL) and brine (2 mL). Drying (Na2SO4) and evaporation of the
solvent gave a residue that was recrystallized using ethanol: analytical
TLC on silica gel, 3/7 ethyl acetate/hexane, Rf = 0.25; white solid; 236
(6) Leaver, I. H.; Milligan, B. Dyes Pigm. 1984, 5, 109.
(7) For a general overview of synthetic methods of benzoxazoles, see:
Boyd, G. V. In Science of Synthesis: Houben-Weyl Methods of Molecular
Transformations; Schaumann, E., Ed.; Thieme: Stuttgart, Germany,
2001; Vol. 11, p 481.
1
mg, 74% yield; H NMR (400 MHz, CDCl3) δ 7.87 (bs, 1H), 7.85−
7.82 (m, 2H), 7.53−7.42 (m, 3H), 7.14 (s, 2H), 2.32 (s, 3H); HRMS
I
dx.doi.org/10.1021/jo501216h | J. Org. Chem. XXXX, XXX, XXX−XXX

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Article
(8) For a general overview of synthetic methods of benzothiazoles,
see: Metzger, J. In Comprehensive Heterocyclic Chemistry; Katritzky, A.
R., Rees, C. W., Eds.; Pergamon Press: Oxford, U.K., 1984; Vol. 6, p
322.
(9) Pottorf, R. S.; Chadha, N. K.; Katkevics, M.; Ozola, V.; Suna, E.;
Ghane, H.; Regberg, T.; Player, M. R. Tetrahedron Lett. 2003, 44, 175.
(10) For selected examples, see: (a) Evindar, G.; Batey, R. A. J. Org.
Chem. 2006, 71, 1802. (b) Barbero, N.; Carril, M.; SanMartin, R.;
Dominguez, E. Tetrahedron 2007, 63, 10425. (c) Saha, P.; Ali, M. A.;
Punniyamurthy, T. Org. Synth. 2011, 8, 398. (d) Weeks, A. A.; Bagley,
M. C.; Westwell, A. D. Tetrahedron 2011, 67, 7743. (e) Park, N.; Heo,
Y.; Kumar, M. R.; Kim, Y.; Song, K. H.; Lee, S. Eur. J. Org. Chem. 2012,
1984.
(25) (a) Kawashita, Y.; Nakamichi, N.; Kawabata, H.; Hayashi, M.
Org. Lett. 2003, 5, 3713. (b) Toshihiko, N.; Katsura, H.; Yumiko, N.;
Akihiko, T.; Itaru, T.; Manabu, Y.; Toshio, T.; Kazumasa, N. Eur.
Patent EP1394142, 2004. (c) Kamila, S.; Koh, B.; Biehl, E. R. J.
Heterocycl. Chem. 2006, 43, 1609. (d) Seijas, J. A.; Vaz
P.; Carballido-Reboredo, M. R.; Crecente-Campo, J.; Romar-Lop
́
quez-Tato, M.
ez, L.
́
Synlett 2007, 313. (e) Marsden, S. P.; McGonagle, A. E.; McKeever-
Abbas, B. Org. Lett. 2008, 10, 2589. (f) Pal, S.; Patra, G.; Bhunia, S.
Synth. Commun. 2009, 39, 1196. (g) Leng, Y.; Yang, F.; Zhu, W.; Wu,
Y.; Li, X. Org. Biomol. Chem. 2011, 9, 5288. (h) Deng, H.; Li, Z.; Ke,
F.; Zhou, X. Chem. Eur. J. 2012, 18, 4840. (i) Hamdy, A. M.; Eleya, N.;
Mohammed, H. H.; Patonay, T.; Spannenberg, A.; Langer, P.
Tetrahedron 2013, 69, 2081. (j) Sedelmeier, J.; Lima, F.; Litzler, A.;
Martin, B.; Venturoni, F. Org. Lett. 2013, 15, 5546. (k) Zhang, X.;
Zeng, W.; Yang, Y.; Huang, H.; Liang, Y. Org. Lett. 2014, 16, 876.
(11) Saha, P.; Ali, M. A.; Ghosh, P.; Punniyamurthy, T. Org. Biomol.
Chem. 2010, 8, 5692.
(12) Bonnamour, J.; Bolm, C. Org. Lett. 2008, 10, 2665.
(13) For examples, see: (a) Altenhoff, G.; Glorius, F. Adv. Synth.
Catal. 2004, 346, 1661. (b) Viirre, R. D.; Evinder, G.; Batey, R. A. J.
Org. Chem. 2008, 73, 3452.
(14) (a) Downer, N. K.; Jackson, Y. A. Org. Biomol. Chem. 2004, 2,
3039. (b) Inamoto, K.; Hasegawa, C.; Hiroya, K.; Doi, T. Org. Lett.
2008, 10, 5147.
(15) Cheng, Y.; Yang, J.; Qu, Y.; Li, P. Org. Lett. 2012, 14, 98.
(16) Wang, H.; Wang, L.; Shang, J.; Li, X.; Wang, H.; Gui, J.; Lei, A.
Chem. Commun. 2012, 48, 76.
(17) Ueda, S.; Nagasawa, H. Angew. Chem., Int. Ed. 2008, 47, 6411.
(18) (a) Downer-Riley, N. K.; Jackson, Y. A. Tetrahedron 2008, 64,
7741. (b) Yu, Z.; Ma, L.; Yu, W. Synlett 2012, 23, 1534.
(19) For a book and selected reviews on hypervalent iodine
chemistry, see: (a) Hypervalent Iodine Chemistry; Wirth, T., Ed.;
Springer-Verlag: Berlin, 2003. (b) Ochiai, M.; Miyamoto, K. Eur. J.
Org. Chem. 2008, 4229. (c) Dohi, T.; Kita, Y. Chem. Commun. 2009,
2073. (d) Brown, M.; Farid, U.; Wirth, T. Synlett 2013, 424. (e) Singh,
F. V.; Wirth, T. Chem. Asian J. 2014, 9, 950.
(20) For selected examples of catalytic reactions, see: (a) Dohi, T.;
Maruyama, A.; Yoshimura, M.; Morimoto, K.; Tohma, H.; Kita, Y.
Angew. Chem., Int. Ed. 2005, 44, 6193. (b) Ochiai, M.; Takeuchi, Y.;
Katayama, T.; Sueda, T.; Miyamoto, K. J. Am. Chem. Soc. 2005, 127,
12244. (c) Antonchick, A. P.; Samanta, R.; Kulikov, K.; Lategahn, J.
Angew. Chem., Int. Ed. 2011, 50, 8605. (d) He, Y.; Pu, Y.; Shao, B.;
Yan, J. J. Heterocycl. Chem. 2011, 48, 695. (e) Ito, M.; Kubo, H.; Itani,
I.; Morimoto, K.; Dohi, T.; Kita, Y. J. Am. Chem. Soc. 2013, 135, 14078.
(f) Alla, S. K.; Kumar, R. K.; Sadhu, P.; Punniyamurthy, T. Org. Lett.
2013, 15, 1334. (g) Dohi, T.; Yamaoka, N.; Kita, Y. Tetrahedron 2010,
66, 5775. (h) Itoh, N.; Sakamoto, T.; Miyazawa, E.; Kikugawa, Y. J.
Org. Chem. 2002, 67, 7424. (i) Zhu, C.; Yoshimura, A.; Wei, Y.;
Nemykin, V. N.; Zhdankin, V. V. Tetrahedron Lett. 2012, 53, 1438.
(j) Samanta, R.; Lategahn, J.; Antonchick, A. P. Chem. Commun. 2012,
48, 3194. (k) Dohi, T.; Ito, M.; Yamaoka, N.; Morimoto, K.; Fujioka,
H.; Kita, Y. Tetrahedron 2009, 65, 10797.
(21) For the application of oxone in hypervalent iodine chemistry,
see: (a) Hussain, H.; Green, I. R.; Ahmed, I. Chem. Rev. 2013, 113,
3329. (b) Thottumkara, A. P.; Bowsher, M. S.; Vinod, T. K. Org. Lett.
2005, 7, 2933. (c) Uyanik, M.; Akakura, M.; Ishihara, K. J. Am. Chem.
Soc. 2009, 131, 251. (d) Yakura, T.; Tian, Y.; Yamauchi, Y.; Omoto,
M.; Konishi, T. Chem. Pharm. Bull. 2009, 57, 252. (e) Fabry, D. C.;
Stodulski, M.; Hoerner, S.; Gulder, T. Chem. Eur. J. 2012, 18, 10834.
(f) Yoshimura, A.; Middleton, K. R.; Todora, A. D.; Kastern, B. J.;
Koski, S. R.; Maskaev, A. V.; Zhdankin, V. V. Org. Lett. 2013, 15, 4010.
(22) (a) Martins, A.; Lautens, M. Org. Lett. 2008, 10, 4351.
(b) Schroder, N.; Wencel-Delord, J.; Glorius, F. J. Am. Chem. Soc.
̈
2012, 134, 8298. (c) Simmons, E. M.; Hartwig, J. F. Angew. Chem., Int.
Ed. 2012, 51, 3066. (d) Asako, S.; Ilies, L.; Nakamura, E. J. Am. Chem.
Soc. 2013, 135, 17755. (e) Ma, S.; Villa, G.; Thuy-Boun, P. S.; Homs,
A.; Yu, J.-Q. Angew. Chem., Int. Ed. 2014, 53, 734.
(23) (a) Zagulyaeva, A. A.; Yusubov, M. S.; Zhdankin, V. V. J. Org.
Chem. 2010, 75, 2119. (b) Ishiwata, Y.; Togo, H. Tetrahedron 2009,
65, 10720.
(24) Ueda, S.; Nagasawa, H. J. Org. Chem. 2009, 74, 4272.
J
dx.doi.org/10.1021/jo501216h | J. Org. Chem. XXXX, XXX, XXX−XXX