Selective C-H chalcogenation of thiazoles: Via thiazol-2-yl-phosphonium salts

Article abstract of DOI:10.1039/d0ob00684j

Thiazoles and benzothiazoles undergo regioselective C2-H chalcogenation via the sequence of thiazole C2-functionalization with phosphines to produce phosphonium salts which in turn react with S- and Se-centered nucleophiles to give products of C2-H chalco

Full text of DOI:10.1039/d0ob00684j

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Oligonucleotide modifi cations enhance probe stability for
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DOI: 10.1039/D0OB00684J
ARTICLE
Selective C-H Sulfenylation of Thiazoles via Thiazol-2-yl-
phosphonium Salts
Received 00th January 20xx,
Accepted 00th January 20xx
a
a
a
a
You Zi, Konrad Wagner, Fritz Schömberg and Ivan Vilotijevic*
DOI: 10.1039/x0xx00000x
In memory of Prof. Dr. Ernst Anders, professor of organic chemistry at Friedrich Schiller University Jena from 1993 to 2007.
Thiazoles and benzothiazoles undergo regioselective C2-H chalcogenation via the sequence of thiazole C2-functionalization
with phosphines to produce phosphonium salts which in turn react with S- and Se-centered nucleophiles to give products
of C2-H chalcogenation and allow for recovery of the starting phosphine. The atom economical sequence proceeds under
mild conditions and features broad scope for both the nucleophiles (electron-rich, electron-poor, sterically hindered thiols)
and the various substituted benzothiazoles. The access to the substituted medicinally relevant C2-thio benzothiazoles also
enables stereoselectivity improvements in the modified Julia olefinations.
Introduction
Thiazoles and benzothiazoles are important constituents of
1
electronic materials, common intermediates in organic
2
3
synthesis, and a regular occurrence in natural products and
4
biologically active molecules. They are the most common
aromatic 5-membered N-heterocycles among FDA approved
5
pharmaceuticals. Vast majority of these bioactive molecules
feature a heteroatom substituent at C2 which highlights the
need for methods to introduce such substituents and makes
these methods valuable tools in medicinal chemistry.
2
-thio-substituted (benzo)thiazoles, such as the wideband
microbicide TCMTB (
),6 cathepsin-D inhibitor ( ),7 heat shock
protein 90 inhibitor (
)8 and PPAR receptor activator ( ),9
have attracted attention for their biological activities (Scheme
a). Other 2-thio-substituted (benzo)thiazoles are common
A
B
C
D
1
intermediates in organic synthesis where they are used to
construct double bonds via Julia olefination10 or as substrates
for transition metal-catalysed coupling reactions.11 While other
strategies to prepare 2-thio-substituted thiazoles exist,12 C2-H
thiolation (and chalcogenation) is of particular interest as a
method for their direct functionalization. Despite the
apparent demand, the methods for C2-H thiolation of thiazoles
have thus far been limited to transition metal mediated
processes that (i) typically proceed under harsh conditions at
temperatures between 120 and 140 °C with long reactions
times,13-14 (ii) use stoichiometric amounts of transition metal
salts and/or (iii) require the use of strong oxidants (Scheme
Scheme 1 (a) Examples of biologically active C2-thio benzothiazole derivatives; (b)
previous work for C2 thiolation of (benzo)thiazoles and (c) our approach.
settings common in medicinal chemistry. A recent report of
photochemically promoted Cu-catalyzed chalcogenation of
thiazoles which proceeds at room temperature and improves
the functional group tolerance is an important improvement in
this field but it requires a specific photochemical setup and is
1
b).14 These features greatly limit the reaction scope and
prevent general application of such methods in more complex
limited to synthesis of diaryl sulphides (Scheme 1b).15
general method for C2-H thiolation of thiazoles that proceeds
A
a. Institute of Organic Chemistry and Macromolecular Chemistry, Friedrich Schiller
University Jena, Humboldtstr. 10, 07743 Jena, Germany.
Email: ivan.vilotijevic@uni-jena.de
†
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
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under mild conditions with broad substrates scope, uses
readily available starting materials and avoids the use of
transition metals would provide a simple way to create the C2-
S bond of interest and generate libraries of medicinally
relevant C2-thio substituted thiazoles.
View Article Online
DOI: 10.1039/D0OB00684J
Early work of Anders demonstrated the ease of synthesis of
heteroaryl phosphonium salts by activating the corresponding
heterocycle with triflic anhydride and exposing the resulting
intermediate to a phosphine nucleophile.16 In our work on
phosphine promoted reactions of Michael acceptors that
proceed via vinylphosphonium intermediates,17 we found out
that such intermediates readily undergo reactions with
heteroatom-centered nucleophiles which suggested that a
two-step sequence where regioselective formation of the
phosphonium salt and a subsequent reaction with suitable
nucleophile would constitute an efficient and selective C2-H
functionalization of (benzo)thiazoles.18 Recent work on the
related reactions with pyridinylphosphonium salts also
supported the feasibility of this approach.19 Here we show that
such thiazol-2-yl-phosphonium salts undergo highly efficient
chalcogenation with a broad range of thiols, thiophenols and a
Se-centered nucleophile and produce a variety of C2-
chalcogen substituted thiazoles in excellent yields (Scheme 1c).
Results and discussion
In our initial study, benzothiazole was selected as the model
system and converted to the corresponding benzo[d]thiazol-2-
yltriphenylphosphonium triflate salt (1a) which was then used
in reactions with 1-octanethiol. The reactions required
nucleophile activation by a base. Sodium hydride proved to be
a suitable and atom economical solution for this. With slight
excess of the thiol, the reaction between 1-octanethiol and the
benzo[d]thiazol-2-yltriphenylphosphonium triflate yielded the
product 3a in excellent yield. The reactions proceeded with
high rates at room temperature in THF. The main side product
was the triphenylphosphine which could be recovered at the
end of the reaction making the entire process atom
economical. The ease of preparation of benzo[d]thiazol-2-
yltriphenylphosphonium triflate and its favourable solubility
profile enabled the two-step sequence to be carried out in one
pot with removal of excess ammonium salt by precipitation of
Scheme 2 Thiolation of benzothiazole with different thiols. Conditions: phosphonium
salt (0.2 mmol), pronucleophile (0.3 mmol), NaH (0.3 mmol), THF (2 mL, 0.1 M), at 0 °C
to room temperature. [a] Conditions: phosphonium salt (0.2 mmol), pronucleophile
the phosphonium salt and decanting between the steps. (0.15 mmol), NaHMDS (0.3 mmol), THF (2 mL, 0.1 M), at -78 °C to room temperature. [b]
Conditions: phosphonium salt (0.2 mmol), pronucleophile (0.1 mmol), NaH (0.2 mmol),
THF (2 mL, 0.1 M), at 0 °C to room temperature.
Although typical reactions used 1.5 equivalents of the thiol and
sodium hydride, lower quantities (1.1 equiv.) were often
sufficient to achieve good yields for the desired products.
S-centered nucleophile with products 3c and 3l derived from t-
With fast turnaround in the optimization studies, the
BuSH and 2,6-dimethylphoenylthiol produced in 99% and 93%
attention was focused on exploration of the reaction scope.
yields respectively. The double thioetherification to produce
Primary, secondary, tertiary alkyl and benzylic thiols all
3
u
proceeded with satisfactory yield as did the reactions with
thiols with extended conjugation and those containing other
heterocycles like pyridine (3s 3t).
produced the desired thioethers in nearly quantitative yields
3a 3h, Scheme 2). Thiophenols also gave the desired products
in high yields (3i 3u) with electron rich and electron poor
thiophenols showing comparable efficacy (3j 3r). The reactions
appeared to be tolerant of steric crowding in the vicinity of the
(
-
-
-
To test the selectivity for S- and O-centered nucleophiles,
-mercaptopropan-1-ol and 6-mercaptohexan-1-ol were
-
3
2
| J. Name., 2012, 00, 1-3
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O rP gl ea na is ce &d Bo i on mo to al e dc juu l sa tr mC haer mg i ins ts ry
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tested under optimized conditions. 6-mercaptohexan-1-ol
ARTICLE
The scope for the benzothiazol-2-yl-phosphonium triflates
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provided the desired product 3v in 70% yield, while 3- has been explored by employing various
D
s
O
u
I:
b
1
s
0
t
.
i
1
t
0
u
3
t
9
e
/D
d
0
s
O
a
B
lt
0
s
06th84
at
J
1
6
mercaptopropan-1-ol produced 3x in 45% yield alongside the were available via the method outlined by Anders. Salts
product of double functionalization of the mercaptoalcohol derived from substituted benzothiazoles carrying both
with two benzothiazoles in small quantities. Product 3w could electron-donating and electron-withdrawing substituents in
positions 5, 6 and 7 have been examined. 1-octanethiol was
used as a model nucleophile in these reactions to determine
that they all proceed with nearly quantitative yields regardless
of the electronic properties of the salt (Scheme 4). Ethers (3ad
be isolated in 33% yield when 2 equiv. of phosphonium salt 1a
were used in combination with 2 equiv. of sodium hydride.
and 3ae), aryl halides (3af-3ai), nitriles (3aj and 3ak), nitro
compounds (3al) were well tolerated in these reactions. In
addition to salts derived from benzothiazoles, that derived
from simple thiazole was also a competent substrate in this
reaction (3ab). Finally, a few diverse combinations of
phosphonium salts and the thiols showed the generality of the
Scheme 3 Synthesis of the diarylselenide 3v via reaction of phosphonium salt and Se-
centered nucleophile. Conditions: phosphonium salt (0.2 mmol), PhSeSePh (0.3 mmol),
NaH (0.6 mmol), THF (2 mL, 0.1 M), at 0 °C to room temperature.
process (3am-3ar).
A series of control experiments was carried out to show
that the formation of the phosphonium salt is indeed
necessary for successful C-H functionalization. The direct use
To test the feasibility of the same approach in construction
of C-Se bonds, benzo[d]thiazol-2-yltriphenylphosphonium
triflate was subjected to reaction with Se-centered nucleophile of S-nucleophiles in combination with N-triflyl salts of
generated by reduction of diphenyl diselenide with sodium benzothiazole, similar to the previously reported methods for
20
hydride to produce the 2-(phenylselanyl)thiazole 3y in yield of C4-functionalization of pyridines, failed to produce any of the
7% (Scheme 3). Dimethyl diselenide gave the corresponding C2-sulfenylation products.
7
Having access to a variety of electronically different C2-thio
substituted benzothiazoles, piqued our curiosity about the
possibility of exploiting electronic effects of these substituents
to address selectivity issues in modified Julia olefination
reactions that otherwise proceed with lower selectivity. We
hypothesized that electronic effects of the substituents may
change the selectivity of the reactions by changing the nature
of transition states in the selectivity determining addition of
the sulfone stabilized anion to the aldehyde or by changing the
kinetics of individual elementary steps during the olefination
reactions that may ultimately enable different equilibria to be
established.10 With this in mind, for our model study we
methylselenide 3aa in 67% yield. Dibenzyl diselenide failed to
produce any of the desired product likely due to the high
reactivity of the resulting 2-(benzylselanyl)benzo[d]thiazole.
selected the typical modified Julia olefination substrate (3a
)
and the two substituted starting materials, one featuring an
electron donating (3ad) and the other featuring electron
withdrawing group (3aj) (Scheme 5). The three sulfones were
easily accessed from the corresponding sulfides by mCPBA
oxidation. Applying the typical conditions for modified Julia
Scheme 4 Reaction scope for substituted thiazoles. Conditions: phosphonium salt (0.2
mmol), pronucleophile (0.3 mmol), NaH (0.3 mmol), THF (2 mL, 0.1 M), at 0 °C to room
temperature.
Scheme 5 Modified Julia olefination using differently substituted sulfones.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
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olefination with 4a resulted in a 3.2:1 mixture of Z-5 and E-5 1H), 4.14 (t, J = 6.7 Hz, 2H), 3.62 (t, J = 7.0 Hz, 2H), 2.93 (t, J =
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favouring the Z product. Under the same conditions, both 4ad 6.9 Hz, 2H), 1.69 – 1.57 (m, 2H), 1.48 – 1
D
.3
) δ 171.64, 166.05, 153.14,
.6:1, respectively) while maintaining similar efficacy. Future 135.28, 126.03, 124.28, 121.53, 120.99, 64.81, 34.42, 30.59,
O
1
I:
(
1
m
0.
,
10
2
3
H
9
)
/
,
D
0
0
.
O
9
B
4
0
(
0
t
6
,
8
J
4
=
J
13
and 4aj gave the products
5
with higher selectivity (6.7:1 and 7.4 Hz, 3H). C NMR (75 MHz, CDCl
3
5
studies will be directed towards understanding and further 28.21, 19.12, 13.70. HRMS: [EI]: m/z calculated for C14
H
17NO
2
S
2
+
[
1
2
M] 295.0701, found 295.0701. IR (ATR): 2958, 1732, 1462,
establishing the substituent effect in these reactions.
-1
427, 1350, 1176, 999, 756 cm .
2
4
-(benzylthio)benzo[d]thiazole (3e)
1
Yield: 96%. H-NMR (300 MHz, CDCl
3
) δ 7.94 (dd, J = 8.2, 1.1 Hz,
Conclusions
1
7
1
1
2
H), 7.76 (dd, J = 8.0, 1.2 Hz, 1H), 7.53 – 7.41 (m, 3H), 7.40 –
In conclusion, the regioselective C2-H functionalization of
thiazoles with phosphines followed by the highly efficient base
promoted reaction with S-centered nucleophiles is an effective
way to produce C2-thio thiazole derivatives. The reactions
proceed under mild conditions, use simple starting materials
and feature broad scope that includes both alkyl thiols and
thiophenols. Electronic and steric factor do not significantly
change the high efficacy of reactions of phosphonium salts
with S- and Se-nucleophiles. The substituted C2-thio
benzothiazoles can be of use in organic synthesis to improve
the selectivity of the modified Julia olefination reactions.
Applications of this methodology to rapidly generate targeted
libraries of compounds for medicinal chemistry are envisioned.
1
3
3
.27 (m, 4H), 4.63 (s, 2H). C-NMR (75 MHz, CDCl ) δ 166.43,
53.17, 136.18, 135.34, 129.16, 128.73, 127.78, 126.08, 124.30,
21.57, 121.03, 37.72.
2
5
-((4-fluorobenzyl)thio)benzo[d]thiazole (3f)
1
Yield: 99%. H NMR (300 MHz, CDCl
3
) δ 7.98 – 7.86 (m, 1H),
7
7
1
3
1
2
.81 – 7.74 (m, 1H), 7.49 – 7.39 (m, 3H), 7.36 – 7.28 (m, 1H),
13
3
.10 – 6.95 (m, 2H), 4.59 (s, 2H). C NMR (75 MHz, CDCl ) δ
66.02, 162.27 (d, J = 246.6 Hz), 153.07, 135.34, 132.13 (d, J =
.3 Hz), 130.82 (d, J = 8.2 Hz), 128.52 (d, J = 12.2 Hz), 126.12,
24.39, 121.31 (d, J = 39.0 Hz), 115.60 (d, J = 21.6 Hz), 36.86.
2
6
-((4-methoxybenzyl)thio)benzo[d]thiazole (3g)
1
Yield: 99%. H NMR (300 MHz, CDCl
7
6
CDCl
1
3
) δ 7.97 – 7.89 (m, 1H),
.79 – 7.73 (m, 1H), 7.48 – 7.37 (m, 3H), 7.35 – 7.27 (m, 1H),
13
.91 – 6.85 (m, 2H), 4.58 (s, 2H), 3.80 (s, 3H). C NMR (75 MHz,
) δ 166.61, 159.19, 153.18, 135.30, 130.37, 127.99,
3
Experimental
26.06, 124.26, 121.53, 121.02, 114.12, 55.28, 37.34.
General procedure for the thiolation of thiazole derivatives
NaH (0.3 mmol) was added to the pronucleophile (0.3 mmol)
in dry THF (0.1 M) under inert atmosphere at 0 °C. After
stirring for half an hour at room temperature, the
27
2
-((1-phenylethyl)thio)benzo[d]thiazole (3h)
1
Yield: 99%. H-NMR (300 MHz, CDCl
7
1
3
) δ 7.97 – 7.89 (m, 1H),
.79 – 7.71 (m, 1H), 7.54 – 7.48 (m, 2H), 7.43 (ddd, J = 8.3, 7.3,
.3 Hz, 1H), 7.39 – 7.27 (m, 4H), 5.18 (q, J = 7.0 Hz, 1H), 1.87 (d,
18
phosphonium salt (0.2 mmol) was added subsequently at 0
C followed by three quick vacuum/nitrogen refills. The
13
J = 7.0 Hz, 3H). C-NMR (75 MHz, CDCl
3
) δ 165.87, 153.20,
°
1
1
2
41.80, 135.43, 128.69, 127.78, 127.41, 126.01, 124.33, 121.71,
reaction mixture was warmed up to room temperature and
quenched by addition of a small amount of water when it
completed. The crude product was purified by column
chromatography using ethyl acetate in petroleum ether.
20.97, 47.58, 22.67.
23
-(phenylthio)benzo[d]thiazole (3i)
1
Yield: 82%. H-NMR (300 MHz, CDCl
3
) δ 7.90 (dt, J = 8.2, 0.9 Hz,
1
7
1
1
2
H), 7.81 – 7.71 (m, 2H), 7.66 (dt, J = 7.8, 1.0 Hz, 1H), 7.57 –
2
1
2
-(octylthio)benzo[d]thiazole (3a)
.45 (m, 3H), 7.42 (ddd, J = 8.3, 7.3, 1.3 Hz, 1H), 7.33 – 7.23 (m,
1
Yield: 97%. H-NMR (300 MHz, CDCl
3
) δ 7.99 – 7.82 (m, 1H),
13
H). C-NMR (75 MHz, CDCl
3
) δ 169.72, 153.93, 135.54,
7
=
1
.82 – 7.70 (m, 1H), 7.42 (td, J = 8.2, 7.8, 1.2 Hz, 1H), 7.29 (td, J
35.39, 130.50, 129.94, 126.17, 124.33, 121.96, 120.80.
7.9, 1.1 Hz, 1H), 3.35 (t, J = 7.4 Hz, 2H), 1.83 (p, J = 7.3 Hz, 2H),
.56 – 1.42 (m, 2H), 1.42 – 1.19 (m, 8H), 0.99 – 0.79 (m, 3H).
23
-(p-tolylthio)benzo[d]thiazole (3j)
1
Yield: 99%. H-NMR (300 MHz, CDCl
3
) δ 7.88 (dt, J = 8.2, 0.8 Hz,
1
3
3
C-NMR (75 MHz, CDCl ) δ 167.41, 153.37, 135.15, 125.97,
1
7
2
H), 7.67 – 7.61 (m, 3H), 7.41 (ddd, J = 8.3, 7.3, 1.3 Hz, 1H),
1
2
2
24.07, 121.44, 120.89, 33.64, 31.80, 29.20, 29.15, 29.07,
8.79, 22.66, 14.12.
.33 – 7.28 (m, 2H), 7.28 – 7.20 (m, 1H), 2.45 (s, 3H).
28
-(m-tolylthio)benzo[d]thiazole (3k)
22
-(isopropylthio)benzo[d]thiazole (3b)
1
Yield: 94%. H-NMR (300 MHz, CDCl
3
) δ 7.89 (dt, J = 8.2, 0.9 Hz,
1
Yield: 92%. H-NMR (300 MHz, CDCl
3
) δ 7.90 (d, J = 8.1 Hz, 1H),
1
7
1
1
1
2
H), 7.66 (dt, J = 7.9, 0.9 Hz, 1H), 7.60 – 7.53 (m, 2H), 7.45 –
7
.82 – 7.71 (m, 1H), 7.43 (ddd, J = 8.2, 7.3, 1.3 Hz, 1H), 7.30
.35 (m, 2H), 7.35 – 7.31 (m, 1H), 7.27 (ddd, J = 8.3, 7.3, 1.2 Hz,
(
ddd, J = 8.4, 7.3, 1.2 Hz, 1H), 4.10 (hept, J = 6.8 Hz, 1H), 1.53 (s,
13
H), 2.42 (s, 3H). C-NMR (75 MHz, CDCl
3
) δ 170.10, 153.94,
13
3
1
2
H), 1.51 (s, 3H). C-NMR (75 MHz, CDCl
3
) δ 166.45, 153.42,
39.99, 135.88, 135.53, 132.39, 131.32, 129.74, 129.56, 126.13,
24.27, 121.91, 120.77, 21.31.
35.29, 125.97, 124.22, 121.61, 120.91, 39.47, 23.31.
2
3
-(tert-butylthio)benzo[d]thiazole (3c)
29
-((2,6-dimethylphenyl)thio)benzo[d]thiazole (3l)
1
Yield: 99%. H NMR (300 MHz, CDCl
3
) δ 8.00 (ddd, J = 8.1, 1.3,
1
Yield: 93%. H-NMR (300 MHz, CDCl
3
) δ 7.88 (dt, J = 8.2, 0.8 Hz,
0
1
.6 Hz, 1H), 7.81 (ddd, J = 7.9, 1.4, 0.6 Hz, 1H), 7.50 – 7.41 (m,
H), 7.40 – 7.36 (m, 1H), 1.62 (s, 9H).
1
3
2
H), 7.67 – 7.57 (m, 1H), 7.44 – 7.33 (m, 2H), 7.30 – 7.21 (m,
H), 2.56 (s, 6H).
butyl 3-(benzo[d]thiazol-2-ylthio)propanoate (3d)
30
-((4-methoxyphenyl)thio)benzo[d]thiazole (3m)
1
Yield: 21%. H NMR (300 MHz, Chloroform-d) δ 7.92 – 7.84 (m,
1
Yield: 83%. H-NMR (300 MHz, CDCl
3
) δ 7.87 (ddd, J = 8.2, 1.2,
1
H), 7.78 – 7.74 (m, 1H), 7.46 – 7.39 (m, 1H), 7.34 – 7.28 (m,
0
.6 Hz, 1H), 7.71 – 7.61 (m, 3H), 7.40 (ddd, J = 8.3, 7.3, 1.3 Hz,
4
| J. Name., 2012, 00, 1-3
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ARTICLE
1
3
1
5
2
H), 7.25 (ddd, J = 8.0, 7.3, 1.2 Hz, 1H), 7.05 – 6.97 (m, 2H), 135.61, 135.52, 133.77, 133.74, 131.22, 129.77, 128.18, 127.91,
.88 (s, 3H). C-NMR (75 MHz, CDCl ) δ 171.93, 161.70, 154.18, 127.79, 127.04, 127.02, 126.20, 124.36, 121.99, 120.83.
3
37.60, 135.40, 126.09, 124.06, 121.75, 120.75, 120.17, 115.51, bis(4-(benzo[d]thiazol-2-ylthio)phenyl)sulfane (3u)
View Article Online
DOI: 10.1039/D0OB00684J
13
1
5.48.
Yield: 66%. H-NMR (300 MHz, CDCl
3
) δ 7.91 (dt, J = 8.2, 0.8 Hz,
3
1
-((4-fluorophenyl)thio)benzo[d]thiazole (3n)
2H), 7.74 – 7.66 (m, 6H), 7.49 – 7.40 (m, 6H), 7.31 (ddd, J = 8.3,
) δ7.89 (ddd, J = 8.1, 1.2, 7.3, 1.2 Hz, 2H). C-NMR (75 MHz, CDCl
1
13
Yield: 77%. H-NMR (300 MHz, CDCl
3
3
) δ 168.25, 153.77,
0
1
1
1
.6 Hz, 1H), 7.80 – 7.63 (m, 3H), 7.42 (ddd, J = 8.3, 7.3, 1.3 Hz, 137.93, 135.66, 135.59, 131.97, 129.29, 126.32, 124.62,
13
3 16 2 5
) δ 169.54, 122.12, 120.89. HRMS: [EI]: m/z calculated for C26H N S
[M]+
H), 7.35 – 7.09 (m, 3H). C-NMR (75 MHz, CDCl
64.20 (d, J = 252.2 Hz,), 153.92, 137.79 (d, J = 8.8 Hz), 135.44, 515.9917, found 515.9913. IR (ATR): 3063, 2924, 1570, 1454,
-
1
26.26, 125.09 (d, J = 3.6 Hz), 124.41, 121.97, 120.82, 117.25 1423, 1385, 1092, 1076, 1007, 818, 748, 721 cm .
(
2
d, J = 22.2 Hz).
6-(benzo[d]thiazol-2-ylthio)hexan-1-ol (3v)
1
-((2-fluorophenyl)thio)benzo[d]thiazole (3o)
Yield: 70%. H-NMR (300 MHz, CDCl
3
) δ 7.80 (d, J = 7.8 Hz, 1H),
1
Yield: 81%. H-NMR (300 MHz, CDCl
3
) δ 7.90 (dt, J = 8.1, 0.8 Hz, 7.68 (dd, J = 7.9, 0.6 Hz, 1H), 7.38 – 7.29 (m, 1H), 7.25 – 7.18
1
H), 7.75 (td, J = 7.7, 7.2, 1.9 Hz, 1H), 7.71 – 7.65 (m, 1H), 7.60 (m, 1H), 3.58 (t, J = 6.4 Hz, 2H), 3.28 (t, J = 6.0 Hz, 2H), 1.84 –
13
–
7.50 (m, 1H), 7.42 (ddd, J = 8.4, 7.3, 1.3 Hz, 1H), 7.32 – 7.22 1.70 (m, 2H), 1.54 – 1.35 (m, 6H). C-NMR (75 MHz, CDCl
3
) δ
(
m, 3H). 13C-NMR (75 MHz, CDCl
3
) δ 167.40, 162.69 (d, J = 167.36, 153.24, 135.09, 126.04, 124.16, 121.42, 120.93, 62.79,
2
1
1
51.4 Hz), 153.80, 137.39, 135.62, 133.16 (d, J = 8.2 Hz), 33.49, 32.52, 29.14, 28.48, 25.22. HRMS: [EI]: m/z calculated
+
26.23, 125.33 (d, J = 4.1 Hz), 124.51, 122.10, 120.84, 117.25, for C13
H
17NOS
2
[M] 267.0752, found 267.0748. IR (ATR): 3282,
16.85 (d, J = 22.7 Hz). 19F NMR (377 MHz, CDCl
-1
3
) δ -104.89. 2927, 1647, 1539, 1458, 1307, 995, 756 cm .
+
HRMS: [EI]: m/z calculated for C13
H
8
FNS
2
[M] 261.0082, found 2-((3-(benzo[d]thiazol-2-yloxy)propyl)thio)benzo[d]thiazole
2
cm .
2
61.0082. IR (ATR): 3066, 1454, 1423, 1219, 1002, 817, 721 (3w)
-1
1
3
Yield: 33%. H-NMR (300 MHz, CDCl ) δ 7.76 (d, J = 7.7 Hz, 1H),
7.67 (d, J = 7.3 Hz, 1H), 7.62 – 7.53 (m, 2H), 7.36 – 7.25 (m, 2H),
) δ 7.93 – 7.86 (dt, J = 8.2, 7.24 – 7.13 (m, 2H), 4.67 (t, J = 6.0 Hz, 2H), 3.48 (t, J = 7.0 Hz,
-((4-bromophenyl)thio)benzo[d]thiazole (3p)31
1
Yield: 91%. H-NMR (300 MHz, CDCl
0
J = 8.3, 7.3, 1.3 Hz, 1H), 7.30 (ddd, J = 8.3, 7.3, 1.2 Hz, 1H). C- 166.20, 153.20, 149.26, 135.24, 131.88, 126.02, 126.01, 124.27,
3
13
.9 Hz, 1H), 7.73 – 7.65 (m, 1H), 7.61 – 7.55 (m, 4H), 7.43 (ddd, 2H), 2.42 – 2.29 (m, 2H). C-NMR (75 MHz, CDCl
3
) δ 172.63,
13
NMR (75 MHz, CDCl
3
) δ 168.07, 153.78, 136.56, 135.57, 133.13, 123.55, 121.53, 121.27, 120.96, 120.83, 69.94, 29.85, 28.76.
+
1
29.05, 126.31, 125.18, 124.59, 122.11, 120.88.
HRMS: [EI]: m/z calculated for
C
10
H
12NOS
2
[M-
28
+
2
-((3-(trifluoromethyl)phenyl)thio)benzo[d]thiazole (3q)
benzothiazole+H] 226.0355, found 226.0360. IR (ATR): 2924,
1
) δ 8.05 – 7.99 (m, 1H), 1716, 1624, 1535, 1427, 1249, 1219, 995, 756 cm-1.
Yield: 91%. H-NMR (300 MHz, CDCl
3
7
7
1
1
1
.97 – 7.89 (m, 2H), 7.79 – 7.69 (m, 2H), 7.61 (t, J = 7.8 Hz, 1H), 3-(benzo[d]thiazol-2-ylthio)propan-1-ol (3x)
1
.45 (ddd, J = 8.3, 7.2, 1.3 Hz, 1H), 7.33 (ddd, J = 8.3, 7.3, 1.2 Hz, Yield: 45%. H-NMR (300 MHz, CDCl
3
) δ 7.75 (d, J = 8.1 Hz, 1H),
) δ 166.70, 153.66, 137.92, 7.65 (d, J = 7.9 Hz, 1H), 7.38 – 7.29 (m, 1H), 7.25 – 7.18 (m, 1H),
35.66, 132.26 (d, J = 32.9 Hz), 131.59, 131.34 (q, J = 3.7 Hz), 3.68 (t, J = 5.9 Hz, 2H), 3.46 (t, J = 5.9 Hz, 2H), 1.95 (td, J = 11.1,
13
H). C-NMR (75 MHz, CDCl
3
1
3
3
30.29, 126.88 (q, J = 3.7 Hz), 126.41, 124.83, 123.40 (d, J =294 5.9 Hz, 2H). C-NMR (75 MHz, CDCl ) δ 168.91, 152.41, 135.02,
Hz), 122.29, 120.95.
126.24, 124.49, 121.06, 121.02, 59.02, 33.11, 29.83. HRMS: [EI]:
-((4-(trifluoromethyl)phenyl)thio)benzo[d]thiazole (3r)31
m/z calculated for C10
H
11NOS
[M] 225.0282, found 225.0278.
+
2
2
1
Yield: 86%. H-NMR (300 MHz, CDCl
3
) δ 7.94 (dt, J = 8.2, 0.8 Hz, IR (ATR): 3294, 2927, 1535, 1458, 1423, 1238, 1049, 995, 756
-1
1
7
H), 7.87 – 7.79 (m, 2H), 7.77 – 7.66 (m, 3H), 7.46 (ddd, J = 8.3, cm .
.3, 1.3 Hz, 1H), 7.34 (ddd, J = 8.2, 7.3, 1.2 Hz, 1H). C-NMR 2-(phenylselanyl)benzo[d]thiazole (3y)
13
23
1
(
75 MHz, CDCl
3
) δ 165.77, 153.57, 135.83, 135.28, 134.12, Yield: 77%. H-NMR (300 MHz, CDCl
3
) δ 7.94 (dt, J = 8.2, 0.9 Hz,
1
1
2
31.76 (q, J = 32 Hz), 126.57 (q, J = 3.7 Hz), 126.44, 124.99, 1H), 7.89 – 7.80 (m, 2H), 7.72 – 7.67 (m, 1H), 7.55 – 7.38 (m,
23.66 (q, J = 266 Hz), 122.41, 120.99.
4H), 7.32 – 7.24 (m, 1H).
32
[33]
-(pyridin-2-ylthio)benzo[d]thiazole (3s)
2-(methylselanyl)benzo[d]thiazole (3aa)
1
1
Yield: 65%. H-NMR (300 MHz, CDCl
3
) δ 8.61 (ddd, J = 4.9, 1.9, Yield: 67%. H-NMR (300 MHz, CDCl
3
) δ 7.89 – 7.81 (m, 1H),
0
7
.9 Hz, 1H), 8.00 (ddd, J = 8.1, 1.3, 0.7 Hz, 1H), 7.82 (ddd, J = 7.72 (dd, J = 8.0, 0.6 Hz, 1H), 7.39 – 7.29 (m, 1H), 7.27 – 7.19
.9, 1.4, 0.6 Hz, 1H), 7.68 (ddd, J = 8.0, 7.4, 1.9 Hz, 1H), 7.55 (dt, (m, 1H), 2.62 (s, 3H). C-NMR (75 MHz, CDCl ) δ 160.08,
3
13
J = 8.0, 1.0 Hz, 1H), 7.47 (ddd, J = 8.2, 7.2, 1.4 Hz, 1H), 7.37 153.98, 136.26, 126.04, 124.20, 121.55, 120.93, 8.06.
ddd, J = 8.4, 7.2, 1.3 Hz, 1H), 7.24 (ddd, J = 7.4, 4.9, 1.2 Hz, 1H). 2-(octylthio)thiazole (3ab)
(
1
3
1
C-NMR (75 MHz, CDCl
3 3
) δ 162.51, 154.74, 152.72, 149.95, Yield: 93%. H-NMR (300 MHz, CDCl ) δ 7.66 (d, J = 3.4 Hz, 1H),
1
2
37.42, 136.26, 126.23, 125.10, 125.07, 122.57, 122.48, 121.01. 7.20 (d, J = 3.4 Hz, 1H), 3.28 – 3.12 (m, 2H), 1.76 (p, J = 7.6, 7.2
21
-(naphthalen-2-ylthio)benzo[d]thiazole (3t)
Hz, 2H), 1.55 – 1.37 (m, 2H), 1.37 – 1.20 (m, 8H), 0.97 – 0.80 (m,
1
13
Yield: 90%. H-NMR (300 MHz, CDCl
3
) δ 8.30 (d, J = 1.7 Hz, 1H), 3H). C-NMR (75 MHz, CDCl
3
) δ 166.32, 143.60, 119.45, 35.51,
7
.98 – 7.85 (m, 4H), 7.74 (dd, J = 8.6, 1.8 Hz, 1H), 7.67 – 7.55 32.68, 30.12, 30.03, 29.96, 29.66, 23.54, 15.00. HRMS [EI]: m/z
+
(
m, 3H), 7.42 (ddd, J = 8.3, 7.2, 1.3 Hz, 1H), 7.27 (ddd, J = 8.1, calculated for C11
H
19NS
2
[M] 229.0959, found 229.0959. IR
13
-1
7
.3, 1.2 Hz, 1H). C-NMR (75 MHz, CDCl
3
) δ 169.65, 153.94, (ATR): 2924, 2854, 1739, 1384, 1018, 864, 705 cm
-methyl-2-(octylthio)benzo[d]thiazole (3ac)
6
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O rP gl ea na is ce &d Bo i on mo to al e dc juu l sa tr mC haer mg i ins ts ry
Page 6 of 8
ARTICLE
Journal Name
1
Yield: 99%. H-NMR (300 MHz, CDCl
.58 – 7.53 (m, 1H), 7.22 (dd, J = 8.2, 1.7 Hz, 1H), 3.33 (t, J = 6.0 [EI]: m/z calculated for C15
Hz, 2H), 2.46 (s, 3H), 1.88 – 1.76 (m, 2H), 1.54 – 1.43 (m, 2H), 357.0227. IR (ATR): 2920, 2851, 1740, 1408, 1231, 1204, 1146,
3
View Article Online
) δ 7.75 (d, J = 8.3 Hz, 1H), 33.63, 31.78, 29.13, 29.13, 29.04, 28.77, 22.65, 14.10. HRMS:
DOI: 10.1039/D0OB00684J
+
7
2
H20BrNS [M] 357.0221, found
13
-1
1
.37 – 1.25 (m, 8H), 0.89 (t, J = 6.0 Hz, 3H). C-NMR (75 MHz, 1011, 891, 868 cm .
CDCl
3
) δ 166.04, 151.48, 135.31, 134.13, 127.41, 120.95, 7-bromo-2-(octylthio)benzo[d]thiazole (3ai)
1
1
1
20.76, 33.69, 31.79, 29.22, 29.13, 29.06, 28.78, 22.65, 21.40, Yield: 99%. H-NMR (300 MHz, CDCl
4.10. HRMS: [EI]: m/z calculated for C16
3
) δ 7.71 (dd, J = 8.1, 1.0 Hz,
[M] 293.1272, 1H), 7.33 (dd, J = 7.8, 1.0 Hz, 1H), 7.23 – 7.17 (m, 1H), 3.26 (t, J
+
H
23NS
2
found 293.1265. IR (ATR): 2924, 2855, 1601, 1447, 1258, 1204, = 7.4 Hz, 2H), 1.75 (p, J = 7.3 Hz, 2H), 1.47 – 1.35 (m, 2H), 1.30
-1
13
1
114, 1065, 995, 818 cm .
3
– 1.15 (m, 8H), 0.84 – 0.78 (m, 3H). C-NMR (75 MHz, CDCl ) δ
6
-ethoxy-2-(octylthio)benzo[d]thiazole (3ad)
168.02, 153.20, 137.91, 127.19, 126.79, 120.10, 113.15, 33.71,
1
Yield: 86%. H-NMR (300 MHz, CDCl
3
) δ 7.75 (d, J = 8.9 Hz, 1H), 31.78, 29.12, 29.08, 29.03, 28.75, 22.64, 14.10. HRMS: [EI]:
+
7
7
–
.22 (d, J = 2.5 Hz, 1H), 7.00 (dd, J = 8.9, 2.5 Hz, 1H), 4.07 (q, J = m/z calculated for C15
.0 Hz, 2H), 3.31 (t, J = 7.4 Hz, 2H), 1.81 (p, J = 7.3 Hz, 2H), 1.54 IR (ATR): 2924, 2855, 1740, 1450, 1377, 999, 775 cm .
1.40 (m, 5H), 1.40 – 1.18 (m, 8H), 0.89 (t, J = 6.0 Hz, 3H). 13C- 2-(octylthio)benzo[d]thiazole-6-carbonitrile (3aj)
H
20BrNS
2
[M] 357.0221, found 357.0224.
-1
1
NMR (75 MHz, CDCl
3
) δ 156.28, 147.84, 136.47, 121.90, 115.16, Yield: 98%. H-NMR (300 MHz, CDCl
3
) δ 8.05 (d, J = 1.6 Hz, 1H),
1
1
3
1
5
04.79, 64.09, 33.83, 31.79, 29.27, 29.13, 29.05, 28.77, 22.65, 7.88 (d, J = 8.4 Hz, 1H), 7.65 (dd, J = 8.4, 1.6 Hz, 1H), 3.37 (t, J =
4.84, 14.10. HRMS: [EI]: m/z calculated for C17
[M]+ 7.3 Hz, 2H), 1.83 (p, J = 7.3 Hz, 2H), 1.56 – 1.41 (m, 2H), 1.41 –
23.1378, found 323.1370. IR (ATR): 2924, 2855, 1601, 1447, 1.17 (m, 8H), 0.96 – 0.82 (m, 3H). C-NMR (75 MHz, CDCl
H
25NOS
2
13
3
) δ
-
1
258, 1204, 1115, 1065, 1038, 995, 937, 818 cm .
172.94, 155.70, 135.66, 129.51, 125.34, 121.82, 118.81, 107.27,
33.73, 31.76, 29.10, 29.10, 29.01, 28.74, 22.63, 14.10. HRMS:
-methoxy-2-(octylthio)benzo[d]thiazole (3ae)
1
[M]+ 304.1068, found
Yield: 95%. H-NMR (300 MHz, CDCl
3
) δ 7.60 (d, J = 8.8 Hz, 1H), [EI]: m/z calculated for C16
H
20
N
S
2 2
7
3
.40 (d, J = 2.5 Hz, 1H), 6.94 (dd, J = 8.8, 2.5 Hz, 1H), 3.88 (s, 304.1068. IR (ATR): 2920, 2843, 2222, 1427, 1400, 1308, 1246,
-
1
H), 3.33 (t, J = 6.0 Hz, 2H), 1.82 (p, J = 7.2 Hz, 2H), 1.54 – 1.42 1192, 1003, 826 cm .
13
(
(
m, 2H), 1.36 – 1.24 (m, 8H), 0.89 (t, J = 6.0 Hz, 3H). C-NMR 2-(octylthio)benzo[d]thiazole-5-carbonitrile (3ak)
75 MHz, CDCl
1
3
) δ 168.60, 158.88, 154.57, 126.75, 121.07, Yield: 99%. H-NMR (300 MHz, CDCl
3
) δ 8.12 (d, J = 1.5 Hz, 1H),
1
2
3
1
6
13.78, 104.47, 55.60, 33.69, 31.79, 29.15, 29.14, 29.06, 28.78, 7.84 (d, J = 8.3 Hz, 1H), 7.52 (dd, J = 8.2, 1.6 Hz, 1H), 3.37 (t, J =
2.65, 14.11. HRMS: [EI]: m/z calculated for C16
[M]+ 7.3 Hz, 2H), 1.83 (p, J = 7.3 Hz, 2H), 1.56 – 1.41 (m, 2H), 1.36 –
09.1221, found 309.1216. IR (ATR): 2928, 2855, 1744, 1597, 1.23 (m, 8H), 0.92 – 0.86 (m, 3H). C-NMR (75 MHz, CDCl
H
23NOS
2
13
3
) δ
-1
466, 1416, 1319, 1026, 810 cm .
170.83, 153.00, 140.20, 126.56, 125.07, 121.86, 118.85, 109.65,
33.66, 31.77, 29.12, 29.06, 29.02, 28.75, 22.64, 14.11. HRMS:
-fluoro-2-(octylthio)benzo[d]thiazole (3af)
1
[M]+ 304.1068, found
Yield: 94%. H-NMR (300 MHz, CDCl
3
) δ 7.71 (dd, J = 8.9, 4.8 Hz, [EI]: m/z calculated for C16
H
20
N
S
2 2
1
3
2
H), 7.35 (dd, J = 8.1, 2.6 Hz, 1H), 7.05 (td, J = 8.9, 2.6 Hz, 1H), 304.1061. IR (ATR): 2924, 2855, 1744, 1431, 1412, 1018, 826
-1
.24 (t, J = 7.4 Hz, 2H), 1.73 (p, J = 7.3 Hz, 2H), 1.46 – 1.33 (m, cm .
H), 1.32 – 1.16 (m, 8H), 0.80 (t, J = 6.0 Hz, 3H). 13C-NMR (75 6-nitro-2-(octylthio)benzo[d]thiazole (3al)
1
MHz, CDCl
3
) δ 166.84 (d, J = 3.0 Hz), 159.75 (d, J = 244.6 Hz), Yield: 86%. H-NMR (300 MHz, CDCl
3
) δ 8.66 (d, J = 2.3 Hz, 1H),
1
50.01 (d, J = 1.8 Hz), 136.09 (d, J = 11.1 Hz), 122.12 (d, J = 9.2 8.29 (dd, J = 9.0, 2.3 Hz, 1H), 7.89 (d, J = 9.0 Hz, 1H), 3.40 (t, J =
Hz), 114.26 (d, J = 24.5 Hz), 107.37 (d, J = 26.9 Hz), 33.70, 31.78, 7.4 Hz, 2H), 1.85 (p, J = 7.4 Hz, 2H), 1.55 – 1.43 (m, 2H), 1.40 –
19
13
2
3
9.18, 29.12, 29.04, 28.76, 22.64, 14.10. F NMR (377 MHz, 1.25 (m, 8H), 0.89 (t, J = 6.0 Hz, 3H). C-NMR (75 MHz, CDCl )
CDCl
3
) δ -117.55. HRMS: [EI]: m/z calculated for C15
H
20FNS
2
δ 174.64, 157.10, 143.96, 135.48, 121.84, 121.12, 117.30,
+
[
M] 297.1021, found 297.1020. IR (ATR): 2924, 2855, 1601, 33.79, 31.76, 29.10, 29.01, 28.99, 28.75, 22.63, 14.09. HRMS:
-
1
+
1
6
566, 1447, 1308, 1254, 1192, 995, 907, 810 cm .
-chloro-2-(octylthio)benzo[d]thiazole (3ag)
[EI]: m/z calculated for C15
20 2 2 2
H N O S [M] 324.0966, found
324.0966. IR (ATR): 2924, 2851, 1512,1327, 1265, 1118, 1049,
1
) δ 7.76 (d, J = 8.7 Hz, 1H), 1003, 829 cm-1.
Yield: 99%. H-NMR (300 MHz, CDCl
3
3
4
7
7
–
.73 (d, J = 2.1 Hz, 1H), 7.37 (dd, J = 8.7, 2.1 Hz, 1H), 3.34 (t, J = 6-ethoxy-2-(propylthio)benzo[d]thiazole (3am)
.3 Hz, 2H), 1.83 (p, J = 7.3 Hz, 2H), 1.48 (p, J = 6.8 Hz, 2H), 1.37 Yield: 80%. H-NMR (300 MHz, CDCl
1.25 (m, 8H), 0.89 (t, J = 6.0 Hz, 3H). 13C-NMR (75 MHz, CDCl
1
3
) δ 7.75 (d, J = 8.9 Hz, 1H),
3
) 7.22 (d, J = 2.5 Hz, 1H), 7.00 (dd, J = 8.9, 2.5 Hz, 1H), 4.06 (q, J =
δ 168.10, 151.93, 136.31, 129.89, 126.67, 122.02, 120.54, 7.0 Hz, 2H), 3.29 (t, J = 7.2 Hz, 2H), 1.85 (h, J = 7.3 Hz, 2H), 1.44
1
3
3
[
3
1
5
3.68, 31.77, 29.13, 29.12, 29.03, 28.75, 22.64, 14.10. HRMS: (t, J = 7.0 Hz, 3H), 1.08 (t, J = 7.4 Hz, 3H). C-NMR (75 MHz,
EI]: m/z calculated for C15 ) δ 163.91, 156.29, 147.83, 136.47, 121.90, 115.17,
[M]+ 313.0726, found CDCl
13.0726. IR (ATR): 2920, 2855, 2191, 1431, 1300, 1261, 1196, 104.78, 64.09, 35.72, 22.76, 14.84, 13.38.
H
20ClNS
2
3
-
1
103, 999, 814 cm .
5-methoxy-2-((4-methoxybenzyl)thio)benzo[d]thiazole
2
6
-bromo-2-(octylthio)benzo[d]thiazole (3ah)
(3an)
1
1
Yield: 99%. H-NMR (300 MHz, CDCl
3
) δ 7.93 (d, J = 1.9 Hz, 1H), Yield: 83%. H-NMR (300 MHz, CDCl
3
) δ 7.59 (d, J = 8.8 Hz, 1H),
7
7
1
.51 (d, J = 8.5 Hz, 1H), 7.31 (dd, J = 8.5, 1.9 Hz, 1H), 3.26 (t, J = 7.43 (d, J = 2.5 Hz, 1H), 7.41 – 7.34 (m, 2H), 6.96 (dd, J = 8.8,
.4 Hz, 2H), 1.74 (p, J = 7.3 Hz, 2H), 1.48 – 1.34 (m, 2H), 1.27 – 2.5 Hz, 1H), 6.91 – 6.83 (m, 2H), 4.55 (s, 2H), 3.89 (s, 3H), 3.80
13
13
.16 (m, 8H), 0.81 (t, J = 6.0 Hz, 3H). C-NMR (75 MHz, CDCl
3
)
3
(s, 3H). C-NMR (75 MHz, CDCl ) δ 167.72, 159.18, 158.94,
δ 169.49, 154.48, 133.95, 127.03, 124.31, 121.84, 119.61,
6
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
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Page 7 of 8
O rP gl ea na is ce &d Bo i on mo to al e dc juu l sa tr mC haer mg i ins ts ry
Journal Name
ARTICLE
2
005, 289; (f) A. R. de Lera, B. Vaz, R. Alvarez anVdiewJ.AArti.clSeoOuntlione,
Synlett, 2005, 294.
D. Davyt and G. Serra, Mar. Drugs, 2010,
1
5
2
54.40, 130.33, 127.94, 126.92, 121.18, 114.11, 113.96, 104.57,
5.62, 55.28, 37.42.
DOI: 10.1039/D0OB00684J
3
4
8, 2755.
35
-(benzylthio)-6-chlorobenzo[d]thiazole (3ao)
(a) R. Van Ginckel, H. Bruwiere, P. Moelans, B. Janssen, W.
Floren, B. Van der Leede, J. Van Dun, G. Sanz, M. Venet, and
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Yield: 99%. H-NMR (300 MHz, CDCl
3
) δ 7.81 (d, J = 8.7 Hz, 1H),
7
4
5
.72 (d, J = 2.1 Hz, 1H), 7.51 – 7.44 (m, 2H), 7.41 – 7.30 (m, 4H),
.61 (s, 2H).
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1
Yield: 99%. H-NMR (300 MHz, CDCl
3
) δ 7.95 (d, J = 1.9 Hz, 1H),
7
4
1
1
C
1
2
.50 (d, J = 8.5 Hz, 1H), 7.34 – 7.24 (m, 3H), 6.82 – 6.73 (m, 2H),
(
1
3
3
.46 (s, 2H), 3.71 (s, 3H). C-NMR (75 MHz, CDCl ) δ 168.63,
(
59.23, 154.27, 134.10, 130.37, 127.80, 127.20, 124.39, 121.94,
19.68, 114.13, 55.29, 37.30. HRMS: [EI]: m/z calculated for
(
+
15
H
12BrNOS
2
[M] 515.9917, found 364.9544. IR (ATR): 2916,
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-
1
608, 1508, 1419, 1246, 1172, 1014, 829, 794 cm .
-(p-tolylthio)benzo[d]thiazole-6-carbonitrile (3aq)
1
Yield: 99%. H-NMR (300 MHz, CDCl
7
3
) δ 7.95 – 7.92 (m, 1H),
.89 (dd, J = 8.5, 0.6 Hz, 1H), 7.69 – 7.59 (m, 3H), 7.39 – 7.31
1
3
(
m, 2H), 2.47 (s, 3H). C-NMR (75 MHz, CDCl
3
) δ 177.96,
57.47, 142.93, 136.68, 132.03, 130.50, 126.12, 126.03, 123.19,
19.69, 108.25, 22.43. HRMS: [EI]: m/z calculated for
1
1
C
2
2
+
5
E. Vitaku, D. T. Smith and J. T. Njardarson, J. Med. Chem.,
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15 10 2 2
H N S [M] 282.0285, found 282.0285. IR (ATR): 3089,
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-1
6
7
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-((4-methoxybenzyl)thio)benzo[d]thiazole-5-carbonitrile
(3ar)
1
Yield: 99%. H-NMR (300 MHz, CDCl
7
7
3
) δ 8.08 (d, J = 1.5 Hz, 1H),
.76 (d, J = 8.2 Hz, 1H), 7.45 (dd, J = 8.3, 1.6 Hz, 1H), 7.35 –
1999, 9, 2531.
8
L. Zhang, J. Fan, K. Vu, K. Hong, J. Y. Le Brazidec, J. Shi, M.
Biamonte, D. J. Busch, R. E. Lough, R. Grecko, Y. Ran, J. L.
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.24 (m, 2H), 6.84 – 6.75 (m, 2H), 4.51 (s, 2H), 3.72 (s, 3H). C-
) δ 169.98, 159.33, 152.82, 140.32, 130.40,
27.47, 126.71, 125.19, 121.96, 118.81, 114.18, 109.75, 55.30,
7.33. HRMS: [EI]: m/z calculated for C16 OS
[M]+
12.0391, found 312.0391. IR (ATR): 2920, 2229, 1739, 1508,
NMR (75 MHz, CDCl
3
1
3
3
1
H
12
N
2
2
9
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435, 1249, 1172, 1006, 813 cm .
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Conflicts of interest
There are no conflicts to declare.
K. Ando, T. Kobayashi and N. Uchida, Org. Lett., 2015, 17
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Acknowledgements
This work was supported by the Carl-Zeiss Foundation
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Pospíšil, J. Org. Chem., 2012, 77, 6358; (j) D. Gueyrard, R.
Haddoub, A. Salem, N. S. Bacar and P. G.
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(
endowed professorship to I.V.) and Friedrich Schiller
University Jena. We thank Dr. Peter Bellstedt, and Dr. Nico
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Dr. Wenxue Huang for synthesis of starting materials.
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