Rhodium(III)-Catalyzed ortho -C-H Alkylation of 2-Arylbenzothiazoles and 2-Arylthiazoles with Potassium Alkyltrifluoroborates

Article abstract of DOI:10.1055/s-0036-1588936

A general and efficient Rh(III)-catalyzed ortho-C-H alkylation of 2-arylbenzothizazoles and 2-arylthiazoles with potassium alkyltrifluoroborates has been developed. The present method leads to the construction of a library of alkylated 2-arylbenzothiazole

Full text of DOI:10.1055/s-0036-1588936

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2017, 49, A–J
paper
A
Y. Ping et al.
Paper
Synthesis
Rhodium(III)-Catalyzed ortho-C–H Alkylation of 2-Arylbenzothi-
azoles and 2-Arylthiazoles with Potassium Alkyltrifluoroborates
Yuanyuan Ping
Zhaobin Chen
Qiuping Ding*
Yiyuan Peng
R1
[RhCp*Cl2]2 (4 mol%)
AgSbF6 (16 mol%)
R1
R2
R2
N
S
N
S
+
RBF3K
Ag2O (1.0 equiv)
CH2Cl2, 85 °C
(3.0 equiv)
R
34 examples
up to 99% yield
R = Me, nBu, Bn, cPr
Key Laboratory of Small Functional Organic Molecule, Ministry
of Education and Jiangxi’s Key Laboratory of Green Chemistry,
Jiangxi Normal University, Nanchang, Jiangxi 330022,
P. R. of China
dingqiuping@jxnu.edu.cn
Received: 03.11.2016
Accepted after revision: 16.12.2016
Published online: 14.02.2017
boroxine and alkylboronic acids.18a Recently, Rodríguez and
co-workers developed the Mn(III)-mediated direct alkyla-
tion of polyaromatic hydrocarbons and benzene with alkyl-
boronic acids.18b Zhang18c and Gevorgyan,18d respectively,
reported the amino acid-promoted and Pd(II)-catalyzed
pyridyldiisopropylsilyl-directed C–H alkylation using alkyl-
boronic acids as alkyl reagents. In addition, Molander and
co-workers reported manganese(III) acetate catalyzed di-
rect alkylation of heteroaryls using potassium alkyl- and
alkoxymethyltrifluoroborates.18e In 2013, Sanford described
Pd(II) and MnF3 co-promoted direct alkylation of arylpyri-
dines and anilides in the presence of potassium organotri-
fluoroborates. Yu disclosed the monoprotected amino acid-
accelerated and Pd(II)-catalyzed alkylation of phenylacetic
and benzoic acids using potassium alkyltrifluoroborated
and alkylboronic acids as coupling partners.18f In 2015, Li
also reported the Rh(III)-catalyzed C–H alkylation of arenes
using alkyltrifluoroborates.18g Recently, Liu also reported
the Rh(III)-catalyzed site-selective C–H alkylation of pyri-
dones using organoboron reagents.18h
DOI: 10.1055/s-0036-1588936; Art ID: ss-2016-h0772-op
Abstract A general and efficient Rh(III)-catalyzed ortho-C–H alkylation
of 2-arylbenzothizazoles and 2-arylthiazoles with potassium alkyltri-
fluoroborates has been developed. The present method leads to the
construction of a library of alkylated 2-arylbenzothiazoles and 2-arylthi-
azoles with yields up to 99%.
Key words alkylation, alkyltrifluoroborates, 2-arylbenzothiazoles, 2-
arylthiazoles, transition metal
Alkyl, especially methyl is one of the most common
building blocks in small organic molecules, which is a key
structural feature of many biologically active molecules.1
The introduction of such a simple unit usually can dramati-
cally improve the biological and physical properties of
pharmaceuticals, pesticides, and organic functional materi-
als. It is well known that many marketed drugs contain at
least one methyl group bound to the core skeleton.2
Over the past decade, complementary to traditional
Friedel–Crafts alkylation synthesis strategies, transition-
metal-catalyzed alkylation reactions have been quickly ad-
vanced due to the atom economical and environmental be-
nign properties.3 Transition-metal-catalyzed directing
group assisted alkylation has been extensively reported us-
ing various alkylating reagents, such as alkyl halides,4 al-
kylzinc halides,5 alcohols,6 alkanes,7 alkenes,8 allyl ace-
tates,9 amides,10 amino acids,11 ethers,12 epoxides,13 nitroal-
kanes,14 organotin reagents,15 peroxides,16 α-diazoesters,17
and organboron reagents.18
Among these alkyl coupling partners, organboron re-
agents are particularly attractive due to their commercial
availability and synthetic accessibility, low cost, and low
toxicity. In 2006, Yu developed pyridine-directed Pd(II)-cat-
alyzed alkylation of sp2 and sp3 C–H bonds with methyl-
2-Arylbenzothiazoles are versatile structural motifs in
organic medicinal and material chemistry due to their re-
markable pharmacological activities19 and fluorescent
properties.20 Recently, transition-metal-catalyzed C–H
bond functionalization of 2-arylbenzothiazoles with vari-
ous coupling partners has been reported by us21 and other
groups.17b,22 A series of arylated,21a acetoxylated,21b haloge-
nated,21c,d aminated,21e acylated,21f,g,22b,c trifluoromethylthi-
olated,21h cyanated,21i alkylenated,22a alkylated (using α-di-
azo esters as alkylating reagents),17b hydroxylated,22d,e and
nitrated22f 2-arylbenzothiazole derivatives have been pre-
pared. Based on these precedents, we present herein anoth-
er Rh(III)-catalyzed ortho-alkylation of 2-arylbenzothi-
azoles and 2-arylthiazoles by using alkyltrifluoroborates as
the alkyl group source.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

B
Y. Ping et al.
Paper
Synthesis
Recent investigations of C–H alkylation of arenes pro-
moted us to use Rh(III)/Ag catalytic system for our designed
reaction.18g,h Initially, we chose 2-(o-tolyl)benzothiazole
(1a) and potassium methyltrifluoroborate (MeBF3K, 2a) as
model substrates to optimize the coupling reaction condi-
tions, using AgF and Ag2O as oxidant, respectively (Table 1,
entries 1 and 2). To our delight, Ag2O was found to promote
the reaction more efficiently than with AgF in ClCH2CH2Cl
(DCE). Screening of other solvents revealed that CH2Cl2 was
the optimal one in this transformation (entries 2–7). Then,
a range of other silver oxidants were screened for this cou-
pling reaction in dichloromethane. Ag2CO3 and AgOAc were
effective to accelerate this reaction with relatively less
yields 75% (entries 9 and 10), whereas AgNO3 and AgBF4
were totally ineffective (entries 11 and 12). Fortunately, we
were pleased to find that the efficiency was almost main-
tained even when 1.0 equivalent of oxidant (Ag2O) was used
(entry 14, 84%). In addition, the use of Ag2O was very im-
portant, and no reaction took place in the absence of oxi-
dant. Further investigation indicated that lowering the re-
action temperature (85 °C) did not affect the reactivity (en-
try 17, 84%), while a decrease in the amount of MeBF3K (2.0
equiv) reduced the yield of the desired product 3a to 71%
(entry 19).
The substrate scope of this benzothiazole-assisted or-
tho-C–H methylation with MeBF3K (2a) was next investi-
gated under the optimal conditions using [RhCp*Cl2]2 (4
mol%), AgSbF6 (16 mol%), and Ag2O (1.0 equiv). As shown in
Scheme 1, moderate to excellent methylation yields were
obtained. The reaction of ortho-substituted 2-arylbenzothi-
azoles 1b,c (R2 = OMe, F) was found to be excellent for this
transformation to provide the desired products 3b,c in al-
most quantitative yields. The reaction was also compatible
with 2-(benzothiazol-2-yl)phenol (1d; R2 = OH) to give the
corresponding methylated product 3d in moderate yield
(50%). Substrates bearing electron-donating or -withdraw-
ing group (R1 = Me, F, and Cl) on the phenyl ring of benzo-
thiazole afforded smoothly the desired products 3e–h,j–m
in excellent yields (88–99%), apart from 6-fluoro-2-(2-
methoxyphenyl)benzothiazole (1i), which delivered the de-
sired product 3i only in 60% yield under optimal reaction
conditions. It should be noted that the reaction of meta-
methyl-substituted substrate 1n preferentially occurred at
the less hindered position to give the monomethylated 2-
arylbenzothiazole 3n in good yield (88%). Subsequently, the
methylation reaction of symmetrical substrates 1o–r (R2 =
4-N,N-dimethyl, 4-NH2, 4-Me, H) was examined under the
standard reaction conditions, which delivered mono- and
dialkylated products 3o–q, 1a, and 3a in relatively low
yields and regioselectivity.
Table 1 Optimization of Reaction Conditionsa
Me
N
[RhCp*Cl2]2
(4 mol%)
AgSbF6
(16 mol%)
S
Me
1a
N
S
+
oxidant
(x equiv)
solvent
MeBF3K
Me
2a
3a
100 °C, 24 h
Entry
Oxidant (x equiv)
Solvent
Yield (%)b
1
2
AgF (2.8)
DCE
21
Ag2O (2.8)
Ag2O (2.8)
Ag2O (2.8)
Ag2O (2.8)
Ag2O (2.8)
Ag2O (2.8)
AgF (2.8)
DCE
54
3
1,4-dioxane
toluene
MeCN
DMF
46
4
67
5
25
6
42
7
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
88
8
42
9
Ag2CO3 (2.8)
AgOAc (2.8)
AgNO3 (2.8)
AgBF4 (2.8)
Ag2O (2.0)
Ag2O (1.0)
Ag2O (0.5)
–
75
10
11
12
13
14
15
16
17c
18d
19e
75
trace
trace
85
84
30
trace
84
Ag2O (1.0)
Ag2O (1.0)
Ag2O (1.0)
79
71
a Reaction conditions: 2-(o-tolyl)benzothiazole (1a; 0.2 mmol), MeBF3K (2a;
0.6 mmol, 3.0 equiv), [RhCp*Cl2]2 (4.0 mol%), AgSbF6 (16 mol%), oxidant (x
equiv) in a solvent (2.0 mL) at 100 °C for 24 h.
b Isolated yield.
c Reaction was performed at 85 °C.
d Reaction was performed at 70 °C.
e Reaction was performed using MeBF3K (2a; 0.4 mmol, 2.0 equiv).
yield. In addition, 2-(2-methoxyphenyl)thiazole (4b) also
underwent the ortho-C–H methylation reaction efficiently
to afford the desired product 5b in 87% yield. Interestingly,
the meta-methyl-substituted 2-(m-tolyl)thiazole (4d) gave
the product 5d selectively at the less sterically hindered po-
sition in good yield (71%).
However, 2-(3-fluorophenyl)thiazole (4e) with a less
hindered fluorine atom at the meta-position of 2-phenyl
ring gave a mixture of dimethylated product 2-(3-fluoro-
2,6-dimethylphenyl)thiazole 5e(di) in 33% isolated yield
and the monomethylated product 2-(5-fluoro-2-methyl-
phenyl)thiazole 5e(mono) in 33% NMR yield (See Support-
ing Information). In the case of 2-(naphthalen-2-yl)thiazole
(4f), mono- and dimethylated products were formed in
Furthermore, the methylation of 2-arylthiazoles 4 with
MeBF3K (2a) under the same conditions (Scheme 2) was
studied. Fortunately, 2-(o-tolyl)thiazole (4a) was trans-
formed perfectly to give the desired product 5a in 99%
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

C
Y. Ping et al.
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Synthesis
R2
R2
[RhCp*Cl2]2 (4 mol%)
AgSbF6 (16 mol%)
N
S
N
S
1
R1
R1
+
MeBF3K
(3.0 equiv)
2a
Ag2O (1.0 equiv)
CH2Cl2, 85 °C
Me
3
Me
N
MeO
F
N
N
S
S
S
Me
Me
Me
3b, 99%
3a, 84%
3c, 99%
HO
N
Me
Me
Me
N
S
N
S
S
Me
Cl
Me
Me
3d, 50%
3e, 98%
3f, 98%
Me
MeO
MeO
N
S
N
S
N
S
F
Me
Me
F
Me
Me
F
Me
3i, 60%
3g, 99%
3h, 95%
F
F
N
S
N
S
N
S
F
Cl
Me
Me
Me
3k, 98%
3j, 95%
3l, 95%
MeO
Me
Me
Me
N
N
S
N
N
S
S
Cl
Me
Me
Me
3m, 88%
3o, 30%
3n, 88%
Me
Me
N
S
N
N
S
NH2
S
Cl
Me
83%
mono(1a)/di(3a) = 4:5
Me
3p, 21%
Me
3q, 35%
Scheme 1 Rh(III)-catalyzed methylation of 2-arylbenzothiazoles 1 with various substituents
moderate yields with monomethylated at the less hindered
position as the major product. Symmetrical substrates like
the para-methyl-substituted or unsubstituted 2-phenylthi-
azoles 4g and 4h also reacted with 2a smoothly under the
present conditions and led to mixtures of mono- and di-
methylated products 5g/5g′ and 5h/5h′ in good yields with
moderate selectivity.
Furthermore, the generality of this selective alkylation
of 2-(2-methoxyphenyl)benzothiazole (1b) and 2-(2-meth-
oxyphenyl)thiazole (4b) was explored with different boron
reagent 2 as the alkylating reagent under optimal reaction
conditions (Scheme 3). The results revealed that the cou-
pling partners in this catalytic system are not limited only
to methyl boron reagent MeBF3K (2a). Long-chain aliphatic
boron reagent 2b efficiently reacted to provide the corre-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

D
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Synthesis
R1
R1
[RhCp*Cl2]2 (4 mol%)
AgSbF6 (16 mol%)
N
S
N
S
+
MeBF3K
(3.0 equiv)
2a
Ag2O (1.0 equiv)
CH2Cl2, 85 °C
Me
4
5
Me
Me
F
MeO
Me
N
S
N
N
S
N
S
S
Me
Me
Me
5a, 99%
5b, 87%
5c, 47%
5d, 71%
(Me)H
N
(Me)H
(Me)H
F
Me
N
N
Me
N
S
S
S
Me
S
Me
H(Me)
Me
5e, 77%
mono/di = 4:3
5f, 64%
mono/di = 3:1
5g, 90%
mono/di = 1:2
5h, 60%
mono/di = 1:3
Scheme 2 Rh(III)-catalyzed methylation of 2-arylthiazoles 4
sponding products 3r and 5i in 99% and 63% isolated yield,
respectively. Boron reagents containing a benzyl 2c or cy-
clopropyl group 2d also gave the corresponding benzylation
product 3s and 5j and the cycloalkylation product 3t in
moderate to good yields.
Based on recent Rh-catalyzed direct ortho-C–H bond
functionalization of arenes,18g,h a plausible mechanism for
the present Rh(III)-catalyzed direct alkylation is shown in
Scheme 4. Initially, an active cationic RhCp*(SbF6)2 species
may generate from the precursor [RhCp*Cl2]2 promoted by
the addition of AgSbF6. Then, the active Rh(III) species facil-
itates the formation of a five-membered rhodacycle species
I via C–H bond activation. Subsequently, the intermediate II
is formed through transmetalation between the rhodacycle
species I and boron reagent 2. Finally, C–C reductive elimi-
nation of intermediate II will afford the desired alkylated
product 3 or 5 along with Rh(I) species, which undergoes
reoxidation by oxidant Ag2O to regenerate the active cation-
ic Rh(III) species for the following catalytic cycle.
In summary, we have successfully developed the rhodi-
um-catalyzed direct ortho-C–H bond alkylation of 2-aryl-
benzothiazoles and 2-arylthiazoles by using alkyltrifluo-
MeO
MeO
[RhCp*Cl2]2 (4 mol%)
N
S
AgSbF6 (16 mol%)
N
S
RBF3K
+
Ag2O (1.0 equiv)
CH2Cl2, 85 °C
(3.0 equiv)
R
1b/4b
2
3/5
MeO
MeO
MeO
N
MeO
N
S
N
S
N
S
S
Me
nBu
Bn
3b, 99%
3r, 99%
3s, 52%
3t, 42%
MeO
MeO
MeO
MeO
N
N
N
N
S
S
S
S
Me
nBu
Bn
5j, 76%
5b, 87%
5i, 63%
5k, trace
Scheme 3 Scope of alkyl trifluoroborates 2
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

E
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Synthesis
[RhCp*Cl2]2
R2
AgSbF6
S
N
AgCl
RhCp*(SbF6)2
1 or 4
Ag + H2O
Ag2O
C–H activation
Oxidation
HSbF6
R2
[RhCp*]
S
N
III
Rh
SbF6
Cp*
Reductive
elimination
I
S
N
R2
R1
S
RBF3K
R2
2
N
RhIII
Transmetalation
R1
3 or 5
Cp*
II
Scheme 4 Proposed catalytic pathway
roborates as the alkyl group source. The results show that
methyl, long-chain aliphatic group, and benzyl as well as
cycloalkyl boron reagents are all compatible with the pres-
ent alkylation protocol. No β-H elimination was observed in
the present catalytic system. The reaction was found to be
highly efficient providing a library of alkylated 2-arylben-
zothiazoles and 2-arylthiazoles, which are widely present
in many pharmaceuticals and biologically active natural
products.
completion of the reaction (monitored by TLC), the solvent was con-
centrated in vacuo, and the residue was purified by flash column
chromatography on silica gel with PE/EtOAc (30:1–20:1) as the eluent
to give the desired product 3.
2-(2,6-Dimethylphenyl)benzo[d]thiazole (3a)23a
White solid; yield: 40.0 mg (84%); mp 108.8–110.9 °C; Rf = 0.5
(PE/EtOAc, 20:1).
1H NMR (400 MHz, CDCl3): δ = 8.12 (d, J = 8.0 Hz, 1 H), 7.95 (d, J = 7.8
Hz, 1 H), 7.53 (t, J = 7.4 Hz, 1 H), 7.44 (t, J = 7.6 Hz, 1 H), 7.26 (d, J = 8.2
Hz, 1 H), 7.14 (d, J = 7.6 Hz, 2 H), 2.21 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 167.5, 153.4, 137.3, 136.3, 133.5,
129.5, 127.6, 126.0, 125.1, 123.4, 121.5, 20.1.
Unless otherwise stated, all commercial reagents were used as re-
ceived. All solvents were dried and distilled according to standard
procedures. Flash column chromatography was performed using sili-
ca gel (60 Å pore size, 32–63 μm, standard grade). Analytical TLC was
performed using glass plates pre-coated with 0.25 mm 230–400
mesh silica gel impregnated with a fluorescent indicator (254 nm).
TLC plates were visualized by exposure to ultraviolet light. Organic
solutions were concentrated on rotary evaporator at 25–35 °C/~20
Torr. NMR spectra are recorded in parts per million from internal TMS
on the δ scale. 1H and 13C NMR spectra were recorded in CDCl3 on a
Bruker DRX-400 spectrometer operating at 400 MHz and 100 MHz,
respectively. All chemical shift values are quoted in ppm and coupling
constants in Hz. High-resolution mass spectrometry (HRMS) was car-
ried out on a micrOTOF II Instrument.
2-(2-Methoxy-6-methylphenyl)benzo[d]thiazole (3b)
Pale yellow liquid; yield: 50.0 mg (99%); Rf = 0.4 (PE/EtOAc, 20:1).
1H NMR (400 MHz, CDCl3): δ = 8.04 (d, J = 8.2 Hz, 1 H), 7.86 (d, J = 8.0
Hz, 1 H), 7.43 (t, J = 7.6 Hz, 1 H), 7.34 (t, J = 7.6 Hz, 1 H), 7.26 (t, J = 8.0
Hz, 1 H), 6.85 (d, J = 7.6 Hz, 1 H), 6.77 (d, J = 8.4 Hz, 1 H), 3.69 (s, 3 H),
2.20 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 164.7, 157.8, 153.2, 139.5, 136.5,
130.9, 130.6, 125.7, 124.9, 123.4, 122.7, 121.4, 108.5, 55.8, 20.1.
HRMS (ESI): m/z [M + H]+ calcd for C15H14NOS+: 256.0796; found:
256.0791.
2-(2-Fluoro-6-methylphenyl)benzo[d]thiazole (3c)21c
Rhodium(III)-Catalyzed ortho-C–H Alkylation of 2-Arylbenzothi-
azoles and 2-Arylthiazoles with Potassium Alkyltrifluoroborates;
General Procedure
White solid; yield: 48.0 mg (99%); mp 37.6–43.8 °C; Rf = 0.5 (PE/EtOAc,
20:1).
1H NMR (400 MHz, CDCl3): δ = 8.05 (d, J = 8.2 Hz, 1 H), 7.86 (d, J = 8.0
Hz, 1 H), 7.44 (t, J = 7.6 Hz, 1 H), 7.35 (t, J = 7.6 Hz, 1 H), 7.28–7.23 (m,
1 H), 7.03 (d, J = 7.6 Hz, 1 H), 6.95 (t, J = 9.0 Hz, 1 H), 2.32 (s, 3 H).
A suspension of the respective 2-arylbenzodthiazole 1 (0.2 mmol), al-
kylboron reagent 2 (0.6 mmol, 3.0 equiv), [RhCp*Cl2]2 (4.9 mg, 4
mol%), AgSbF6 (10.9 mg, 16 mol%), and Ag2O (46.3 mg, 1.0 equiv) in
CH2Cl2 (2.0 mL) was stirred at 100 °C under air for 24 h. After the
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Y. Ping et al.
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Synthesis
13C NMR (100 MHz, CDCl3): δ = 161.2, 160.6 (d, 1JC,F = 248 Hz), 153.2,
13C NMR (100 MHz, CDCl3): δ = 163.6, 157.9, 151.4, 139.5, 136.7,
135.0, 130.5, 127.2, 123.0, 122.8, 122.7, 121.1, 108.6, 55.8, 21.5, 20.1.
HRMS (ESI): m/z [M + H]+ calcd for C16H16NOS+: 270.0953; found:
270.0947.
4
3
3
140.3 (d, JC,F = 2 Hz), 136.2, 131.0 (d, JC,F = 10 Hz), 126.2 (d, JC,F = 3
Hz), 126.1, 125.4, 123.6, 121.8 (d, 2JC,F = 14 Hz), 121.4, 113.2 (d, 2JC,F
=
22 Hz), 20.3.
2-(Benzo[d]thiazol-2-yl)-3-methylphenol (3d)
6-Fluoro-2-(2-methoxy-6-methylphenyl)benzo[d]thiazole (3i)
Pale yellow liquid; yield: 33.0 mg (60%); Rf = 0.4 (PE/EtOAc, 20:1).
1H NMR (400 MHz, CDCl3): δ = 8.04 (dd, J = 8.8, 4.8 Hz, 1 H), 7.60 (dd,
J = 8.2, 2.4 Hz, 1 H), 7.34 (t, J = 8.0 Hz, 1 H), 7.23 (dt, J = 2.4, 8.8 Hz, 1
H), 6.93 (d, J = 7.6 Hz, 1 H), 6.85 (d, J = 8.4 Hz, 1 H), 3.78 (s, 3 H), 2.28
(s, 3 H).
White solid; yield: 24.0 mg (50%); mp 85.3–86.9 °C; Rf = 0.4 (PE/EtOAc,
30:1).
1H NMR (400 MHz, CDCl3): δ = 13.91 (s, 1 H), 8.04 (d, J = 8.2 Hz, 1 H),
7.94 (d, J = 8.0 Hz, 1 H), 7.54 (t, J = 7.6 Hz, 1 H), 7.43 (t, J = 7.6 Hz, 1 H),
7.26 (t, J = 7.8 Hz, 1 H), 7.02 (d, J = 8.2 Hz, 1 H), 6.82 (d, J = 7.4 Hz, 1 H),
2.79 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 167.7, 159.8, 149.3, 137.5, 133.0,
131.7, 126.8, 125.4, 122.6, 121.9, 120.9, 116.7, 116.3, 23.8.
HRMS (ESI): m/z [M + H]+ calcd for C14H12NOS+: 242.0640; found:
4
1
13C NMR (100 MHz, CDCl3): δ = 164.4 (d, JC,F = 3 Hz), 160.4 (d, JC,F
=
4
3
244 Hz), 157.9, 149.9 (d, JC,F = 1 Hz), 139.6, 137.5 (d, JC,F = 11 Hz),
130.8, 124.3 (d, 3JC,F = 9 Hz), 122.9, 122.5, 114.3 (d, 2JC,F = 25 Hz), 108.6,
107.4 (d, 2JC,F = 26 Hz), 55.9, 20.3.
242.0634.
HRMS (ESI): m/z [M + H]+ calcd for C15H13FNOS+: 274.0702; found:
274.0696.
2-(2,6-Dimethylphenyl)-6-methylbenzo[d]thiazole (3e)
6-Fluoro-2-(2-fluoro-6-methylphenyl)benzo[d]thiazole (3j)21c
Faint yellow solid; yield: 49.0 mg (98%); mp 80.9–82.3 °C; Rf = 0.5
(PE/EtOAc, 20:1).
White solid; yield: 50.0 mg (95%); mp 62.0–64.3 °C; Rf = 0.4 (PE/EtOAc,
30:1).
1H NMR (400 MHz, CDCl3): δ = 7.98 (dd, J = 9.2, 5.2 Hz, 1 H), 7.54 (dd,
J = 8.0, 2.4 Hz, 1 H), 7.30–7.24 (m, 1 H), 7.18 (dt, J = 2.8, 8.8 Hz, 1 H),
7.04 (d, J = 7.6 Hz, 1 H), 6.96 (t, J = 9.0 Hz, 1 H), 2.33 (s, 3 H).
1H NMR (400 MHz, CDCl3): δ = 7.91 (d, J = 8.4 Hz, 1 H), 7.64 (s, 1 H),
7.25 (d, J = 8.4 Hz, 1 H), 7.17 (t, J = 7.6 Hz, 1 H), 7.04 (d, J = 7.6 Hz, 2 H),
2.43 (s, 3 H), 2.11 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 166.3, 151.6, 137.4, 136.5, 135.2,
133.7, 129.4, 127.5, 122.9, 121.2, 21.5, 20.1.
HRMS (ESI): m/z [M + H]+ calcd for C16H16NS+: 254.0998; found:
254.0992.
13C NMR (100 MHz, CDCl3): δ = 160.9 (d, 4JC,F = 3.4 Hz), 160.7 (d, 1JC,F
=
1
4
245 Hz), 160.6 (d, JC,F = 248 Hz), 160.9 (d, JC,F = 3.4 Hz), 149.8 (d,
4JC,F = 1.4 Hz), 140.3 (d, 4JC,F = 1.2 Hz), 137.2 (d, 3JC,F = 11.2 Hz), 131.2 (d,
3JC,F = 9.2 Hz), 126.3 (d, 4JC,F = 3.2 Hz), 124.5 (d, 3JC,F = 9.4 Hz), 121.4 (d,
2JC,F = 13.9 Hz), 114.8 (d, 2JC,F = 24.7 Hz), 113.2 (d, 2JC,F = 22 Hz), 107.5
(d, 2JC,F = 26.5 Hz), 20.3 (d, 4JC,F = 2.5 Hz).
6-Chloro-2-(2,6-dimethylphenyl)benzo[d]thiazole (3f)
Pale yellow liquid; yield: 53.0 mg (98%); Rf = 0.5 (PE/EtOAc, 20:1).
1H NMR (400 MHz, CDCl3): δ = 7.93 (d, J = 8.8 Hz, 1 H), 7.83 (d, J = 2.0
Hz, 1 H), 7.40 (dd, J = 8.8, 2.0 Hz, 1 H), 7.19 (t, J = 7.6 Hz, 1 H), 7.05 (d,
J = 7.6 Hz, 2 H), 2.11 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 167.9, 152.0, 137.5, 137.3, 133.1,
131.2, 129.7, 127.7, 126.8, 124.2, 121.1, 20.1.
2-(2-Fluoro-6-methylphenyl)-6-methylbenzo[d]thiazole (3k)
White solid; yield: 50.0 mg (98%); mp 72.3–74.5 °C; Rf = 0.4 (PE/EtOAc,
30:1).
1H NMR (400 MHz, CDCl3): δ = 8.00 (d, J = 8.4 Hz, 1 H), 7.73 (s, 1 H),
7.35–7.30 (m, 2 H), 7.10 (d, J = 7.6 Hz, 1 H), 7.02 (t, J = 9.0 Hz, 1 H),
2.51 (s, 3 H), 2.39 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 160.6 (d, 1JC,F = 248 Hz), 160.1, 151.4,
140.3 (d, 4JC,F = 1 Hz), 136.4 (d, 4JC,F = 1 Hz), 135.6, 130.9 (d, 3JC,F = 9 Hz),
127.7, 126.2 (d, 3JC,F = 3 Hz), 123.0, 121.9 (d, 2JC,F = 14 Hz), 121.1, 113.1
(d, 2JC,F = 22 Hz), 21.5, 20.2.
HRMS (ESI): m/z [M + H]+ calcd for C15H13ClNS+: 274.0457; found:
274.0456.
2-(2,6-Dimethylphenyl)-6-fluorobenzo[d]thiazole (3g)
White solid; yield: 51.0 mg (99%); mp 54.3–55.5 °C; Rf = 0.5 (PE/EtOAc,
20:1).
1H NMR (400 MHz, CDCl3): δ = 7.96 (dd, J = 8.8, 4.8 Hz, 1 H), 7.53 (dd,
J = 8.0, 2.4 Hz, 1 H), 7.23–7.13 (m, 2 H), 7.05 (d, J = 7.6 Hz, 2 H), 2.12 (s,
6 H).
HRMS (ESI): m/z [M + H]+ calcd for C15H13FNS+: 258.0753; found:
258.0753.
6-Chloro-2-(2-fluoro-6-methylphenyl)benzo[d]thiazole (3l)21c
4
1
13C NMR (100 MHz, CDCl3): δ = 167.1 (d, JC,F = 3 Hz), 160.5 (d, JC,F
=
White solid; yield: 53.0 mg (95%); mp 101.2–102.9 °C; Rf = 0.5
(PE/EtOAc, 30:1).
4
3
244 Hz), 150.1 (d, JC,F = 1 Hz), 137.4 (d, JC,F = 11 Hz), 137.3, 133.2,
3
2
129.7, 127.7, 124.4 (d, JC,F = 10 Hz), 114.6 (d, JC,F = 25 Hz), 107.7 (d,
1H NMR (400 MHz, CDCl3): δ = 8.03 (d, J = 8.8 Hz, 1 H), 7.92 (d, J = 2.0
Hz, 1 H), 7.48 (dd, J = 8.8, 2.0 Hz, 1 H), 7.38–7.33 (m, 1 H), 7.13 (d, J =
8.0 Hz, 1 H), 7.04 (t, J = 9.0 Hz, 1 H), 2.41 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 161.7, 160.6 (d, 1JC,F = 249 Hz), 151.7,
140.3 (d, 4JC,F = 1 Hz), 137.4 (d, 4JC,F = 1 Hz), 131.4, 131.2 (d, 3JC,F = 9 Hz),
126.9, 126.4 (d, 3JC,F = 3 Hz), 124.3, 121.3 (d, 2JC,F = 14 Hz), 121.0, 113.3
(d, 2JC,F = 22 Hz), 20.4.
2JC,F = 27 Hz), 20.1.
HRMS (ESI): m/z [M + H]+ calcd for C15H13FNS+: 258.0753; found:
258.0756.
2-(2-Methoxy-6-methylphenyl)-6-methylbenzo[d]thiazole (3h)
White solid; yield: 51.0 mg (95%); mp 74.3–76.5 °C; Rf = 0.3 (PE/EtOAc,
20:1).
1H NMR (400 MHz, CDCl3): δ = 7.98 (d, J = 8.4 Hz, 1 H), 7.70 (s, 1 H),
7.31 (t, J = 8.2 Hz, 1 H), 7.30 (d, J = 8.0 Hz, 1 H), 6.91 (d, J = 7.6 Hz, 1 H),
6.83 (d, J = 8.0 Hz, 1 H), 3.75 (s, 3 H), 2.50 (s, 3 H), 2.26 (s, 3 H).
6-Chloro-2-(2-methoxy-6-methylphenyl)benzo[d]thiazole (3m)
White liquid; yield: 51.0 mg (88%); Rf = 0.3 (PE/EtOAc, 30:1).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

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Synthesis
1H NMR (400 MHz, CDCl3): δ = 8.00 (d, J = 8.8 Hz, 1 H), 7.89 (d, J = 2.0
Hz, 1 H), 7.44 (dd, J = 8.8, 2.0 Hz, 1 H), 7.33 (t, J = 8.0 Hz, 1 H), 6.92 (d,
J = 7.6 Hz, 1 H), 6.84 (d, J = 8.4 Hz, 1 H), 3.78 (s, 3 H), 2.29 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 164.6, 157.9, 153.3, 144.3, 136.6,
130.6, 125.6, 124.9, 123.4, 122.5, 121.8, 121.3, 108.4, 55.8, 33.3, 33.0,
22.4, 13.8.
13C NMR (100 MHz, CDCl3): δ = 165.2, 157.9, 151.8, 139.5, 137.7,
HRMS (ESI): m/z [M + H]+ calcd for C18H20NOS+: 298.1266; found:
130.9, 130.8, 126.5, 124.1, 122.9, 122.3, 120.9, 108.6, 55.8, 20.3.
298.1260.
HRMS (ESI): m/z [M + H]+ calcd for C15H13ClNOS+: 290.0406; found:
290.0407.
2-(2-Benzyl-6-methoxyphenyl)benzo[d]thiazole (3s)
Faint yellow solid; yield: 31.0 mg (47%); mp 76.3–78.4 °C; Rf = 0.2
(PE/EtOAc, 30:1).
2-(2,5-Dimethylphenyl)benzo[d]thiazole (3n)23b
White liquid; yield: 42.0 mg (88%); Rf = 0.4 (PE/EtOAc, 30:1).
1H NMR (400 MHz, CDCl3): δ = 8.03 (d, J = 8.0 Hz, 1 H), 7.80 (d, J = 8.0
Hz, 1 H), 7.40 (t, J = 7.6 Hz, 1 H), 7.31 (t, J = 7.6 Hz, 1 H), 7.26 (t, J = 8.0
Hz, 1 H), 7.10–7.02 (m, 3 H), 6.93 (d, J = 6.4 Hz, 2 H), 6.78 (t, J = 6.8 Hz,
2 H), 3.92 (s, 2 H), 3.68 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 164.4, 158.0, 153.2, 142.6, 140.4,
136.7, 130.8, 129.0, 128.4, 128.3, 128.2, 125.9, 125.7, 124.9, 123.4,
122.8, 122.6, 121.3, 109.0, 55.9, 39.0.
1H NMR (400 MHz, CDCl3): δ = 8.09 (d, J = 8.0 Hz, 1 H), 7.91 (d, J = 7.6
Hz, 1 H), 7.58 (s, 1 H), 7.49 (t, J = 7.8 Hz, 1 H), 7.39 (t, J = 7.6 Hz, 1 H),
7.25–7.17 (m, 2 H), 2.61 (s, 3 H), 2.38 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 168.1, 153.8, 138.8, 135.6, 134.1,
132.9, 131.5, 131.0, 130.8, 126.1, 125.0, 123.3, 121.3, 20.8.
HRMS (ESI): m/z [M + H]+ calcd for C21H18NOS+: 332.1102; found:
332.1104.
4-(Benzo[d]thiazol-2-yl)-N,N,3-trimethylaniline (3o)
Yellow granular solid; yield: 16.0 mg (30%); mp 93.4–96.5 °C; Rf = 0.4
(PE/EtOAc, 30:1).
2-(2-Cyclopropyl-6-methoxyphenyl)benzo[d]thiazole (3t)
1H NMR (400 MHz, CDCl3): δ = 8.01 (d, J = 8.0 Hz, 1 H), 7.86 (d, J = 8.0
Hz, 1 H), 7.75 (d, J = 8.2 Hz, 1 H), 7.44 (t, J = 7.6 Hz, 1 H), 7.32 (t, J = 7.6
Hz, 1 H), 6.63 (d, J = 2.8 Hz, 1 H), 6.61 (s, 1 H), 3.03 (s, 6 H), 2.72 (s, 3
H).
13C NMR (100 MHz, CDCl3): δ = 168.8, 154.1, 151.3, 138.5, 135.1,
132.0, 125.8, 124.2, 122.6, 121.1, 121.0, 114.4, 109.6, 40.1, 22.5.
Faint yellow solid; yield: 20.0 mg (36%); mp 63.3–65.8 °C; Rf = 0.2
(PE/EtOAc, 30:1).
1H NMR (400 MHz, CDCl3): δ = 8.05 (d, J = 8.4 Hz, 1 H), 7.85 (d, J = 8.0
Hz, 1 H), 7.42 (t, J = 7.8 Hz, 1 H), 7.33 (t, J = 7.6 Hz, 1 H), 7.25 (t, J = 8.2
Hz, 1 H), 7.19–7.17 (m, 1 H), 7.12–7.09 (m, 1 H), 6.73 (d, J = 8.4 Hz, 1
H), 6.52 (d, J = 7.6 Hz, 1 H), 3.67 (s, 3 H), 1.79–1.72 (m, 1 H), 0.73–0.66
(m, 2 H), 0.62–0.58 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 164.9, 157.7, 153.4, 145.0, 136.7,
130.9, 128.36 (d, J = 12.2 Hz), 125.9, 125.6, 124.9, 123.4, 121.4, 116.4,
108.2, 55.9, 37.9, 13.2, 9.3.
HRMS (ESI): m/z [M + H]+ calcd for C16H17N2S+: 269.1102; found:
269.1107.
4-(Benzo[d]thiazol-2-yl)-3-methylaniline (3p)
Yellow solid; yield: 10.0 mg (21%); mp 92.1–94.3 °C; Rf = 0.2 (PE/EtOAc,
30:1).
1H NMR (400 MHz, CDCl3): δ = 8.03 (d, J = 8.4 Hz, 1 H), 7.87 (d, J = 8.0
Hz, 1 H), 7.64 (d, J = 8.0 Hz, 1 H), 7.46 (t, J = 7.6 Hz, 1 H), 7.34 (t, J = 7.6
Hz, 1 H), 6.61 (s, 1 H), 6.58 (d, J = 2.0 Hz, 1 H), 3.91 (s, 2 H), 2.64 (s, 3
H).
13C NMR (100 MHz, CDCl3): δ = 168.5, 154.0, 148.1, 139.0, 132.3,
125.9, 124.5, 123.5, 122.9, 121.1, 117.4, 112.5, 83.2, 21.8.
HRMS (ESI): m/z [M + H]+ calcd for C14H13N2S+: 241.0795; found:
241.0794.
HRMS (ESI): m/z [M + H]+ calcd for C17H16NOS+: 282.0947; found:
282.0955.
2-(2,6-Dimethylphenyl)thiazole (5a)
Pale yellow liquid; yield: 37.0 mg (99%); Rf = 0.4 (PE/EtOAc, 20:1).
1H NMR (400 MHz, CDCl3): δ = 7.93 (d, J = 3.6 Hz, 1 H), 7.46 (d, J = 3.4
Hz, 1 H), 7.23 (t, J = 7.8 Hz, 1 H), 7.10 (d, J = 7.6 Hz, 2 H), 2.13 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 166.5, 142.8, 137.7, 133.4, 129.1,
127.4, 120.1, 20.1.
HRMS (ESI): m/z [M + H]+ calcd for C11H12NS+: 190.0690; found:
190.0685.
6-Chloro-2-mesitylbenzo[d]thiazole (3q)
White liquid; yield: 20.0 mg (35%); Rf = 0.5 (PE/EtOAc, 30:1).
2-(2-Methoxy-6-methylphenyl)thiazole (5b)
1H NMR (400 MHz, CDCl3): δ = 7.93 (d, J = 8.4 Hz, 1 H), 7.83 (d, J = 2.0
Hz, 1 H), 7.40 (dd, J = 8.8, 2.0 Hz, 1 H), 6.88 (s, 2 H), 2.26 (s, 3 H), 2.09
(s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 168.3, 152.1, 139.7, 137.6, 137.1,
131.1, 130.3, 128.5, 126.7, 124.1, 121.1, 21.2, 20.0.
Pale yellow liquid; yield: 36 mg (87%); Rf = 0.3 (PE/EtOAc, 20:1).
1H NMR (400 MHz, CDCl3): δ = 7.92 (d, J = 3.6 Hz, 1 H), 7.46 (d, J = 3.6
Hz, 1 H), 7.28 (t, J = 8.0 Hz, 1 H), 6.90 (d, J = 7.6 Hz, 1 H), 6.82 (d, J = 8.4
Hz, 1 H), 3.76 (s, 3 H), 2.24 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 163.5, 157.8, 142.3, 139.6, 130.1,
122.8, 122.5, 120.2, 108.4, 55.7, 20.4.
HRMS (ESI): m/z [M + H]+ calcd for C16H15ClNS+: 288.0612; found:
288.0608.
HRMS (ESI): m/z [M + H]+ calcd for C11H12NOS+: 206.0640; found:
206.0634.
2-(2-Butyl-6-methoxyphenyl)benzo[d]thiazole (3r)
White liquid; yield: 59.0 mg (99%); Rf = 0.3 (PE/EtOAc, 30:1).
2-(2-Fluoro-6-methylphenyl)thiazole (5c)
1H NMR (400 MHz, CDCl3): δ = 8.02 (d, J = 7.6 Hz, 1 H), 7.83 (d, J = 8.0
Hz, 1 H), 7.41 (t, J = 7.8 Hz, 1 H), 7.33–7.25 (m, 2 H), 6.86 (d, J = 7.6 Hz,
1 H), 6.74 (d, J = 8.0 Hz, 1 H), 3.66 (s, 3 H), 2.49 (t, J = 8.0 Hz, 2 H),
1.47–1.39 (m, 2 H), 1.16–1.11 (m, 2 H), 0.69 (t, J = 7.2 Hz, 3 H).
Transparent liquid; yield: 18.0 mg (47%); Rf = 0.3 (PE/EtOAc, 20:1).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

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1H NMR (400 MHz, CDCl3): δ = 7.98 (d, J = 3.2 Hz, 1 H), 7.53 (d, J = 3.6
Hz, 1 H), 7.34–7.27 (m, 1 H), 7.10 (d, J = 7.6 Hz, 1 H), 7.02 (t, J = 9.0 Hz,
1 H), 2.37 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 160.5 (d, 1JC,F = 247 Hz), 160.4, 142.8,
140.3 (d, 4JC,F = 1 Hz), 130.4 (d, 3JC,F = 9 Hz), 126.3 (d, 3JC,F = 3 Hz), 121.5
(d, 2JC,F = 14 Hz), 120.6 (d, 4JC,F = 2 Hz), 113.1 (d, 2JC,F = 22 Hz), 20.5.
13C NMR (100 MHz, CDCl3): δ = 167.3, 142.9, 134.6, 134.5, 133.8,
131.7, 131.0, 127.8, 126.5, 126.3, 125.6, 124.5, 120.4, 20.9, 16.4.
HRMS (ESI): m/z [M + H]+ calcd for C15H14NS+: 240.0847; found:
240.0842.
2-(2,4-Dimethylphenyl)thiazole [5g(mono)]
HRMS (ESI): m/z [M + H]+ calcd for C10H9FNS+: 194.0440; found:
Transparent liquid; yield: 12.0 mg (30%); Rf = 0.5 (PE/EtOAc, 10:1).
194.0434.
1H NMR (400 MHz, CDCl3): δ = 7.89 (d, J = 3.6 Hz, 1 H), 7.62 (d, J = 7.6
Hz, 1 H), 7.37 (d, J = 3.2 Hz, 1 H), 7.12 (s, 1 H), 7.09 (d, J = 7.6 Hz, 1 H),
2.56 (s, 3 H), 2.37 (s, 3 H).
2-(2,5-Dimethylphenyl)thiazole (5d)23c
White liquid; yield: 27.0 mg (71%); Rf = 0.6 (PE/EtOAc, 20:1).
1H NMR (400 MHz, CDCl3): δ = 7.90 (d, J = 3.2 Hz, 1 H), 7.55 (s, 1 H),
7.37 (d, J = 3.2 Hz, 1 H), 7.19–7.12 (m, 2 H), 2.54 (s, 3 H), 2.36 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 168.1, 142.9, 139.4, 136.3, 132.2,
130.2, 130.1, 126.8, 119.0, 21.3, 21.2.
HRMS (ESI): m/z [M + H]+ calcd for C11H12NS+: 190.0681; found:
190.0685.
13C NMR (100 MHz, CDCl3): δ = 168.0, 142.8, 135.5, 133.3, 132.7,
131.3, 130.5, 130.1, 119.2, 20.9, 20.8.
2-Mesitylthiazole [5g(di)]23c
2-(3-Fluorophenyl)thiazole (4e)/2-(5-Fluoro-2-methylphenyl)thi-
azole [5e(mono); 4e/5e(mono): 1:1]
White solid; yield: 24.0 mg (60%); mp 51.2–53.3 °C; Rf = 0.3 (PE/EtOAc,
10:1).
Pale yellow liquid; 43 mg; Rf = 0.5 (PE/EtOAc, 20:1).
1H NMR (400 MHz, CDCl3): δ = 7.92 (d, J = 3.4 Hz, 1 H), 7.45 (d, J = 3.4
Hz, 1 H), 6.93 (s, 2 H), 2.32 (s, 3 H), 2.10 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 166.8, 142.8, 139.0, 137.6, 130.5,
128.3, 120.1, 21.1, 20.1.
1H NMR (400 MHz, CDCl3): δ = 7.93 (d, J = 3.6 Hz, 1 H), 7.88 (d, J = 3.2
Hz, 1 H), 7.74–7.69 (m, 2 H), 7.47–7.36 (m, 4 H), 7.27–7.21 (m, 1 H),
7.15–7.09 (m, 2 H), 2.48 (d, J = 2.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 166.8 (d, 4JC,F = 3 Hz), 166.6 (d, 4JC,F = 3
1
1
2-(o-Tolyl)thiazole [5h(mono)]23d
Hz), 163.0 (d, JC,F = 245 Hz), 161.6 (d, JC,F = 243 Hz), 143.9, 143.2,
135.5 (d, 3JC,F = 8 Hz), 135.0 (d, 3JC,F = 5 Hz), 130.5 (d, 3JC,F = 8 Hz), 126.8
(d, 3JC,F = 9 Hz), 125.7 (d, 4JC,F = 2 Hz), 124.1 (d, 2JC,F = 18 Hz), 122.3 (d,
4JC,F = 3 Hz), 119.9, 119.5, 116.8 (d, 2JC,F = 21 Hz), 116.0 (d, 2JC,F = 24 Hz),
113.4 (d, 2JC,F = 23 Hz), 12.0 (d, 4JC,F = 6 Hz).
Transparent liquid; yield: 5.0 mg (15%); Rf = 0.5 (PE/EtOAc, 20:1).
1H NMR (400 MHz, CDCl3): δ = 7.93 (d, J = 3.2 Hz, 1 H), 7.72 (d, J = 7.6
Hz, 1 H), 7.41 (d, J = 3.6 Hz, 1 H), 7.34–7.28 (m, 3 H), 2.59 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 168.0, 143.0, 136.6, 133.0, 131.5,
130.1, 129.4, 126.1, 119.4, 21.4.
2-(3-Fluoro-2,6-dimethylphenyl)thiazole [5e(di)]
Pale yellow liquid; yield: 14.0 mg (34%); Rf = 0.4 (PE/EtOAc, 20:1).
1H NMR (400 MHz, CDCl3): δ = 7.96 (d, J = 3.6 Hz, 1 H), 7.51 (d, J = 3.2
Hz, 1 H), 7.09–7.00 (m, 2 H), 2.09 (s, 3 H), 2.04 (d, J = 2.4 Hz, 3 H).
2-(2,6-Dimethylphenyl)thiazole [5h(di)]
Transparent liquid; yield: 17.0 mg (45%); Rf = 0.3 (PE/EtOAc, 20:1).
1H NMR (400 MHz, CDCl3): δ = 7.94 (d, J = 3.6 Hz, 1 H), 7.48 (d, J = 3.6
Hz, 1 H), 7.24 (t, J = 7.2 Hz, 1 H), 7.11 (d, J = 7.6 Hz, 2 H), 2.14 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 166.6, 142.9, 137.7, 133.4, 129.2,
127.5, 120.2, 20.2.
4
1
13C NMR (100 MHz, CDCl3): δ = 165.3 (d, JC,F = 3 Hz), 159.4 (d, JC,F
=
3
4
241 Hz), 143.0, 134.9 (d, JC,F = 5 Hz), 133.2 (d, JC,F = 3 Hz), 128.2 (d,
3JC,F = 9 Hz), 125.0 (d, 2JC,F = 17 Hz), 120.5, 115.8 (d, 2JC,F = 23 Hz), 19.7,
12.1.
HRMS (ESI): m/z [M + H]+ calcd for C11H11FNS+: 208.0596; found:
HRMS (ESI): m/z [M + H]+ calcd for C11H12NS+: 190.0690; found:
208.0601.
190.0685.
2-(3-Methylnaphthalen-2-yl)thiazole [5f(mono)]
2-(2-Butyl-6-methoxyphenyl)thiazole (5i)
White solid; yield: 20.0 mg (45%); mp 57.8–61.2 °C; Rf = 0.4 (PE/EtOAc,
Transparent liquid; yield: 31.0 mg (63%); Rf = 0.4 (PE/EtOAc, 20:1).
20:1).
1H NMR (400 MHz, CDCl3): δ = 7.92 (d, J = 3.2 Hz, 1 H), 7.47 (d, J = 3.2
Hz, 1 H), 7.32 (t, J = 8.0 Hz, 1 H), 6.92 (d, J = 7.6 Hz, 1 H), 6.81 (d, J = 8.4
Hz, 1 H), 3.75 (s, 3 H), 2.51 (t, J = 8.0 Hz, 2 H), 1.48–1.39 (m, 2 H),
1.28–1.19 (m, 2 H), 0.80 (t, J = 7.2 Hz, 3 H).
1H NMR (400 MHz, CDCl3): δ = 8.19 (s, 1 H), 7.96 (d, J = 3.6 Hz, 1 H),
7.85 (d, J = 8.0 Hz, 1 H), 7.78 (d, J = 8.0 Hz, 1 H), 7.74 (s, 1 H), 7.52–7.43
(m, 2 H), 7.42 (d, J = 3.2 Hz, 1 H), 2.72 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 167.8, 143.2, 133.7, 133.6, 131.8,
13C NMR (100 MHz, CDCl3): δ = 163.5, 157.9, 144.6, 142.3, 130.2,
131.6, 129.8, 129.4, 128.0, 127.0, 126.9, 125.8, 119.5, 21.7.
122.3, 121.9, 120.2, 108.4, 55.8, 33.3, 33.0, 22.5, 13.8.
HRMS (ESI): m/z [M + H]+ calcd for C14H12NS+: 226.0690; found:
HRMS (ESI): m/z [M + H]+ calcd for C14H18NOS+: 248.1104; found:
226.0685.
248.1116.
2-(1,3-Dimethylnaphthalen-2-yl)thiazole [5f(di)]
2-(2-Benzyl-6-methoxyphenyl)thiazole (5j)
Faint yellow solid; yield: 9.0 mg (18%); mp 90.3–92.9 °C; Rf = 0.2
Pale yellow liquid; yield: 43.0 mg (76%); Rf = 0.3 (PE/EtOAc, 20:1).
(PE/EtOAc, 20:1).
1H NMR (400 MHz, CDCl3): δ = 7.90 (d, J = 3.2 Hz, 1 H), 7.41 (d, J = 3.2
Hz, 1 H), 7.30 (t, J = 8.0 Hz, 1 H), 7.17–7.11 (m, 3 H), 6.98 (d, J = 6.8 Hz,
2 H), 6.84 (d, J = 8.0 Hz, 2 H), 3.96 (s, 2 H), 3.75 (s, 3 H).
1H NMR (400 MHz, CDCl3): δ = 8.04–8.01 (m, 1 H), 7.98 (d, J = 3.4 Hz, 1
H), 7.81–7.79 (m, 1 H), 7.60 (s, 1 H), 7.54–7.48 (m, 3 H), 2.47 (s, 3 H),
2.24 (s, 3 H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–J

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Synthesis
13C NMR (100 MHz, CDCl3): δ = 163.2, 157.9, 142.7, 142.2, 140.6,
130.4, 128.9, 128.1, 125.8, 122.7, 122.6, 120.5, 109.0, 55.8, 39.0.
HRMS (ESI): m/z [M + H]+ calcd for C17H16NOS+: 282.0947; found:
282.0946.
(6) Some recent reports: (a) Lee, D. H.; Kwon, K. H.; Yi, C. S. J. Am.
Chem. Soc. 2012, 134, 7325. (b) Han, S. H.; Choi, M.; Jeong, T.;
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Acknowledgment
Financial Support from National Natural Science Foundation of China
(21262016, 21662017) and Natural Science Foundation of Jiangxi
Province of China (20133ACB20008) is gratefully acknowledged.
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Hiyama, T. Angew. Chem. Int. Ed. 2012, 51, 5679. (b) Wang, Z.;
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Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0036-1588936.
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