Synthesis of 2-thio-substituted benzothiazoles via a domino condensation/S -arylation/heterocyclization process

Article abstract of DOI:10.1021/jo200535e

Condensation of carbon disulfide with thiols in the presence of K ₂CO₃ generates carbonotrithioate salts in situ, which undergo coupling with 2-iodoanilines and subsequent intramolecular condensation and elimination under assistance of CuBr to afford 2-thio-substituted benzothiazoles. Both aliphatic and aromatic thiols are compatible with this process, delivering the corresponding heterocycles with good diversity.

Full text of DOI:10.1021/jo200535e

NOTE
pubs.acs.org/joc
Synthesis of 2-Thio-Substituted Benzothiazoles via a Domino
Condensation/S-Arylation/Heterocyclization Process
Liu Shi,† Xiangqian Liu,† Hui Zhang,† Yongwen Jiang,‡ and Dawei Ma*,‡
†Department of Chemistry, Shanghai University, Shanghai 200444, China
‡State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
S Supporting Information
b
ABSTRACT: Condensation of carbon disulfide with thiols in the
presence of K2CO3 generates carbonotrithioate salts in situ, which
undergo coupling with 2-iodoanilines and subsequent intramolecular
condensation and elimination under assistance of CuBr to afford 2-thio-
substituted benzothiazoles. Both aliphatic and aromatic thiols are compatible with this process, delivering the corresponding
heterocycles with good diversity.
n recent years, an increasing number of 2-thio-substituted
benzothiazoles have been designed and synthesized for biolo-
I
gical evaluation. The discovered biological activities of these
heterocycles include overcoming multidrug resistance in cancer
chemotherapy displayed by compound 1 (Figure 1);1a inhibiting
the enzyme activity of 5-lipoxygenase (5-LO) and cathepsin-D
performed by benzothiazoles 2,1b 5,1d and 6,1f respectively;
antagonizing the activity of CCR3 receptors shown by com-
pound 3;1c as well as antituberculotic activity exhibited by
compound 4.1e
For assembly of 2-thio-substituted benzothiazoles, 2-mercap-
tobenzothiazoles have been frequently used as the key inter-
mediates. They could react with alkyl halides under basic
conditions2 and alcohols under Mitsunobu conditions3 to afford
2-alkylthiobenzothiazoles or be coupled with aryl halides and aryl
boronic acids under the catalysis of copper and iron to furnish
2-arylthiobenzothiazoles.4,5 This classical approach requires the
prepreparation of 2-mercaptobenzothiazoles via condensation of
carbon disulfide with 2-aminothiophenols.6 Since substituted
2-aminothiophenols are not conveniently available, it is highly
desired to explore alternative methods. Recently, Patel and co-
workers reported a direct access to 2-arylthiobenzothiazoles by
copper-catalyzed intramolecular CꢀS bond formation of ditho-
carbamate salts (generated from 2-haloanilines and carbon
disulfide) and subsequent coupling with aryl halides.7 The same
group also discovered that 2-thio-substituted benzothiazoles
could be elaborated from 2-haloaryl isothiocyanates and thiols
via a cascade condensation/coupling process.8
Figure 1. Structures of bioactive 2-thio-substituted benzothiazoles.
benzothiazoles 13 if nucleophiles were replaced with thiols. Thus,
we undertook an investigation to explore this possibility, and the
results are disclosed here.
Using the reaction of 2-iodoaniline 15a with carbon disulfide
and benzyl mercaptane as a model, we examined the suitable
conditions, and the results are summarized in Table 1. Under our
previous optimized conditions (1.0 equiv CuCl2 2H2O, 110 °C
3
In a recent communication, our group described that
2-N-substituted benzothiazoles 12 could be prepared via a cop-
per-catalyzed three-component reaction (2-haloanilines, carbon
disulfide, and amines as depicted in Scheme 1).9 The transforma-
tion was believed to go through a domino condensation/S-aryla-
tion/heterocyclization process (Nu = NRR0). We speculated that a
similar transformation would occur to provide 2-thio-substituted
in DMF),9 the reaction took place to give the desired product 13a
in 27% yield, together with side product 14a with 32% yield
(entry 1). An improved result was observed by changing copper
Received: March 15, 2011
Published: April 15, 2011
r
2011 American Chemical Society
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|

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NOTE
Scheme 1. Possible Reaction Course for Three-Component
Syntheses of 2-N-Substituted Benzothiazoles 12 and 2-Thio-
Substituted Benzothiazoles 13
Table 1. Screening of Reaction Conditions for Reaction of
2-Iodoaniline, CS2, and Benzyl Mercaptanea
entry
Cu source
solvent
yield of 13a (%)b
1
CuCl2 2H2O (1 equiv)
DMF
27c
56
3
2
CuCl (2 equiv)
CuBr (2 equiv)
CuBr (3 equiv)
CuBr (3 equiv)
CuBr (3 equiv)
CuBr (3 equiv)
CuBr (3 equiv)
CuBr (3 equiv)
CuBr (3 equiv)
CuBr (3 equiv)
DMF
3
DMF
59
4
DMF
70
5
DMF
85
6
DMF
78d
79e
57
7
DMF
8
DMSO
toluene
1,4-dioxane
DMF
9
35
10
11
28
74f
salt to more reactive CuCl and CuBr and increasing their amount
to 2 equiv (entries 2 and 3). Further increasing the amount of
CuBr to 3 equiv gave a better yield (entry 3). Since the first step
of the three-component synthesis is the condensation of thiol
with carbon disulfide, we envisioned that changing the operation
procedure might be helpful to inhibit the formation of side
products. Accordingly, we first reacted BnSH with carbon
disulfide at room temperature for 1 h and then added CuBr
and 2-iodoaniline before heating. This manipulation was proven
useful, providing 13a with 85% yield (entry 5).
Further studies revealed that changing base to K3PO4 and
Cs2CO3 was possible (entries 6 and 7), although the yields were
slightly decreased. However, changing solvent to DMSO, to-
luene, and 1,4-dioxane all gave considerably low yields (entries
8ꢀ10), indicating that using DMF as the reaction media is
essential for this transformation. Additionally, it was found that
at 90 °C the reaction still worked to give 13a with 74% yield
(entry 11).
Having the optimized reaction conditions in hand, we explored
the scope and limitation of the three-component reaction. We first
examined the reaction with a series of substituted 2-iodoaniline. It
was found that both electron-deficient and electron-rich aryl iodides
were applicable for this transformation, affording the corresponding
substituted 2-benzylthiobenzothiazols 13bꢀ13i with 58ꢀ83%
yields (Table 2, entries 1ꢀ8). For S-nucleophiles, 4-chlorobenzyl
mercaptane provided 13j in 74% yield (entry 9); simple aliphatic
thiols including primary, secondary, and tertiary thiols also proceeded
well to deliver benzothiazoles 13kꢀ13o with satisfactory yields
(entries 10ꢀ14); functionalized aliphatic thiols such as N-Boc-
protected 2-aminoethanethiol, ethyl 3-mercaptopropanoate, and
2-furanylmethanethiol also worked to afford the corresponding
products 13pꢀ13s (entries 15ꢀ18). In case of ethyl 3-mercapto-
propanoate, a relatively low yield was observed (entry 17), pre-
sumably because of poor stability of the product 13r. Additionally,
thiophenols were found compatible with this process, although the
yields were moderate (entries 19ꢀ22). Furthermore, benzothiazolo-
[4,5-b]pyrindine 13x was obtained from 3-iodo-2-amino-pyridine
with 56% yield (entry 23). Noteworthy is that a wide range of
functional groups such as nitro, ester, nitrile, ketone, methoxy, and
carbamate were tolerated under the present reaction conditions,
which would allow preparing more complex 2-thio-substituted
a Reaction conditions. A (for entries 1ꢀ4): 2-iodoaniline (1.0 mmol),
CS2 (1.2 mmol), BnSH (1.5 mmol), copper salt (1ꢀ3 mmol), K2CO3
(3.0 mmol), DMF, 110 °C, 12 h. B (for entries 5ꢀ11): CS2 (1.2 mmol),
BnSH (1.2 mmol), K2CO3 (3.0 mmol), DMF, rt, 1 h; then 2-iodoaniline
(1.0 mmol), CuBr (3 mmol), 110 °C, 12 h. b Isolated yield. c Compound
14a was isolated in 32% yield. d K3PO4 was used as the base. e Cs2CO3
was used as the base. f The reaction was carried out at 90 °C.
benzothiazoles by further operations. Indeed, benzothiazoles 13o
and 13p could be used for the synthesis of antituberculotic agent 41e
and 5-lipoxylgenase inhibitor 5,1d respectively.
In conclusion, we have developed a facile and diverse method
for assembling 2-thio-substituted benzothiazoles by using conve-
niently available reagents. This study also demonstrated that the
carbonotrithioate salts that generated from thiols and carbon
disulfide are suitable coupling partner for copper-catalyzed
arylation.10 Our discovery may prompt further explorations to
discover new coupling partners for cross-coupling reactions.
’ EXPERIMENTAL SECTION
Typical Procedure for Reaction of 2-Iodoanilines with Car-
bon Disulfide and Aliphatic Thiols. A mixture of K2CO3 (3.0 mmol),
thiol (1.2 mmol), and CS2 (1.2 mmol) in DMF (2.0 mL) was stirred at rt
for 1 h before CuBr (3.0 mmol) and 2-iodoaniline (1.0 mmol) were added.
The resultant mixture was heated at 110 °C for 6 h. The cooled solution was
partitioned between ethyl acetate and water. The organic layer was washed
with water and brine and dried over Na2SO4. After removal of solvent in
vacuo, the residue was chromatographed to give the corresponding
benzothiazole.
Typical Procedure for Reaction of 2-Iodoanilines with
Carbon Disulfide and Thiolphenols. An oven-dried Schlenk tube
was charged with K2CO3 (1.5 mmol), CuBr (1.75 mmol), evacuated,
and backfilled with argon. After DMF (1.0 mL), thiophenol (1.0 mmol),
and CS2 (0.75 mmol) were injected, the reaction mixture was stirred at rt
for 1 h before 2-iodoaniline (0.5 mmol) in DMF (1.0 mL) was added.
The resultant mixture was heated at 110 °C for 6 h. The cooled solution
was partitioned between ethyl acetate and water. Ethyl acetate extract
workup followed by chromatography afforded the product.
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NOTE
Table 2. Formation of 2-Thio-Substituted Benzothiazoles from 2-Iodoanilines, CS2, and Thiolsa
a Reaction conditions: CS2 (1.2 mmol), thiol (1.2 mmol), K2CO3 (3.0 mmol), DMF, rt, 1 h; then 2-iodoaniline (1.0 mmol), CuBr (3 mmol), 110 °C, 6 h.
b Isolated yield. c The reaction was carried out at 90 °C.
1
2-(Benzylthio)benzo[d]thiazole (13a). H NMR (300 MHz,
CDCl3) δ 7.90 (d, J = 8.1 Hz, 1H), 7.74 (d, J = 7.5 Hz, 1H), 7.55ꢀ7.20
(m, 7H), 4.60 (s, 2H); ESI-MS m/z 258.1 (M þ H)þ.
Hz, J = 1.8 Hz, 1H), 7.90 (d, J = 8.4 Hz, 1H), 7.46 (d, J = 6.9 Hz, 2H),
7.39ꢀ7.25 (m, 3H), 4.63 (s, 2H), 3.94 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 170.7, 166.6, 156.0, 135.8, 135.3, 129.2 (2C), 128.8 (2C), 127.9,
127.5, 126.0, 123.1, 121.1, 52.3, 37.7; ESI-MS m/z 316.1 (M þ H)þ;
HRMS (EI) calcd for C16H13NO2S2 (Mþ) 315.0388, found 315.0385.
2-(Benzylthio)benzo[d]thiazole-6-carbonitrile (13e). 1H NMR
(400 MHz, CDCl3) δ 8.05 (s, 1H), 7.92 (d, J = 8.4 Hz, 1H), 7.67 (d, J = 8.8
2-(Benzylthio)-6-(trifluoromethyl)benzo[d]thiazole (13b).
1H NMR (300 MHz, CDCl3) δ 8.03 (s, 1H), 7.96 (d, J = 8.4 Hz, 1H),
7.66 (d, J = 8.4 Hz, 1H), 7.46 (d, J = 7.5 Hz, 2H), 7.38ꢀ7.22 (m, 3H),
4.63 (s, 2H); ESI-MS m/z 326.1 (M þ H)þ.
Hz, 1H), 7.46 (d, J = 6.8 Hz, 2H), 7.38ꢀ7.25 (m, 3H), 4.64 (s, 2H); 13
C
2-(Benzylthio)-6-nitrobenzo[d]thiazole (13c). 1H NMR (300
MHz, CDCl3) δ 8.66 (s, 1H), 8.31 (d, J = 9.0 Hz, 1H), 7.93 (d, J = 9.3
Hz, 1H), 7.47 (d, J = 6.9 Hz, 2H), 7.40ꢀ7.25 (m, 3H), 4.65 (s, 2H); ESI-
MS m/z 303.0 (M þ H)þ.
NMR (100 MHz, CDCl3) δ 171.9, 155.5, 135.8, 135.6, 129.6, 129.2 (2C),
128.9 (2C), 128.1, 125.5, 122.0, 118.8, 107.5, 37.8; ESI-MS m/z283.0 (M þ
H)þ; HRMS (EI) calcd for C15H10N2S2 (Mþ) 282.0285, found 282.0279.
2-(Benzylthio)-6-methoxybenzo[d]thiazole (13f). 1H NMR
(300 MHz, CDCl3) δ 7.78 (d, J = 8.7 Hz, 1H), 7.43 (d, J = 6.6 Hz, 2H),
Methyl 2-(Benzylthio)benzo[d]thiazole-6-carboxylate (13d).
1H NMR (300 MHz, CDCl3) δ 8.46 (d, J = 0.9 Hz, 1H), 8.10 (dd, J = 8.7
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NOTE
7.38ꢀ7.23 (m, 3H), 7.21 (d, J = 2.4 Hz, 1H), 7.02 (dd, J = 9.0 Hz, J = 2.7
Hz, 1H), 4.56 (s, 2H), 3.84 (s, 3H); ESI-MS m/z 288.1 (M þ H)þ.
2-(Benzylthio)-5-(trifluoromethyl)benzo[d]thiazole (13g).
1H NMR (300 MHz, CDCl3) δ 8.15 (s, 1H), 7.84 (d, J = 8.7 Hz, 1H),
7.53 (d, J = 8.1 Hz, 1H), 7.46 (d, J = 6.9 Hz, 2H), 7.38ꢀ7.22 (m, 3H), 4.63
(s, 2H); 13C NMR (100 MHz, CDCl3) δ 169.1, 152.8, 139.1, 136.0, 129.2
(2C), 128.8 (2C), 128.8 (q, J = 32.8 Hz, 1C), 127.9, 124.3 (q, J = 271.3
Hz, 1C), 121.5, 120.7 (q, J = 3.6 Hz, 1C), 118.6 (q, J = 3.6 Hz, 1C), 37.7;
ESI-MS m/z 326.1 (M þ H)þ; HRMS (EI) calcd for C15H10F3NS2
(Mþ) 325.0207, found 325.0211.
353.2 (M þ H)þ; HRMS (EI) calcd for C16H20N2O3S2 (Mþ) 352.0915,
found 352.0928.
1
Methyl 3-(Benzo[d]thiazol-2-ylthio)propanoate (13r). H
NMR (300 MHz, CDCl3) δ 7.86 (d, J = 8.1 Hz, 1H), 7.75 (d, J = 8.1 Hz,
1H), 7.42 (dd, J = 7.2 Hz, J = 7.8 Hz, 1H), 7.30 (dd, J = 7.8 Hz, J = 7.2 Hz,
1H), 3.73 (s, 3H), 3.61 (t, J = 6.9 Hz, 2H), 2.94 (t, J = 6.9 Hz, 2H); 13C
NMR (100 MHz, CDCl3) δ 172.0, 165.9, 153.2, 135.3, 126.1, 124.3,
121.6, 121.0, 51.9, 34.2, 28.2; ESI-MS m/z 254.3 (M þ H)þ; HRMS
(EI) calcd for C11H11NO2S2 (Mþ) 253.0231, found 253.0234.
2-((Furan-2-ylmethyl)thio)benzo[d]thiazole (13s). 1H NMR
(400 MHz, CDCl3) δ 7.90 (d, J = 8.0 Hz, 1H), 7.76 (d, J = 8.0 Hz, 1H),
7.43 (t, J = 7.6 Hz, 1H), 7.37 (s, 1H), 7.30 (t, J = 7.6 Hz, 1H), 6.35 (d, J =
2.8 Hz, 1H), 6.31 (s, 1H), 4.64 (s, 2H); 13C NMR (100 MHz, CDCl3) δ
165.6, 153.2, 149.6, 142.6, 135.5, 126.1, 124.4, 121.7, 121.1, 110.8, 109.1,
30.1; ESI-MS m/z 248.0 (M þ H)þ; HRMS (EI) calcd for C12H9NOS2
(Mþ) 247.0126, found 247.0129.
2-(Benzylthio)-5-methoxybenzo[d]thiazole (13h). 1H NMR
(300 MHz, CDCl3) δ 7.58 (d, J = 8.7 Hz, 1H), 7.46 (d, J = 6.3 Hz, 2H),
7.43 (d, J = 2.7 Hz, 1H), 7.38ꢀ7.25 (m, 3H), 6.95 (dd, J = 8.7 Hz, J = 2.7
Hz, 1H), 4.59 (s, 2H), 3.88 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
167.6, 159.1, 154.5, 136.3, 129.2 (2C), 128.8 (2C), 127.9, 127.1, 121.3,
114.0, 104.8, 55.6, 37.8; ESI-MS m/z 288.1 (M þ H)þ; HRMS (EI)
calcd for C15H13NOS2 (Mþ) 287.0439, found 287.0440.
1
2-(Phenylthio)benzo[d]thiazole (13t). H NMR (300 MHz,
CDCl3) δ 7.88 (d, J = 8.4 Hz, 1H), 7.78ꢀ7.70 (m, 2H), 7.65 (d, J = 7.8
Hz, 1H), 7.56ꢀ7.44 (m, 3H), 7.41 (td, J = 7.8 Hz, J = 1.2 Hz, 1H), 7.27
(t, J = 7.2 Hz, 1H); ESI-MS m/z 244.1 (M þ H)þ.
1
2-(Benzylthio)-5,6-dimethylbenzo[d]thiazole (13i). H NMR
(300 MHz, CDCl3) δ 7.68 (s, 1H), 7.49 (s, 1H), 7.44 (d, J = 6.9 Hz, 2H),
7.35ꢀ7.22 (m, 3H), 4.57 (s, 2H), 2.37 (s, 3H), 2.34 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 164.9, 152.1, 136.5, 135.2, 133.7, 132.8, 129.2 (2C),
128.8 (2C), 127.8, 122.0, 121.1, 37.9, 20.2, 20.1; ESI-MS m/z 286.1 (M þ
H)þ; HRMS (EI) calcd for C16H15NS2 (Mþ) 285.0646, found 285.0643.
2-((4-Chlorobenzyl)thio)benzo[d]thiazole(13j).1HNMR(300
MHz, CDCl3) δ 7.89 (d, J = 8.1 Hz, 1H), 7.75 (d, J = 8.4 Hz, 1H),
7.47ꢀ7.35 (m, 3H), 7.34ꢀ7.24 (m, 3H), 4.56 (s, 2H); 13C NMR (100
MHz, CDCl3) δ 165.8, 153.1, 135.4, 135.0, 133.6, 130.5 (2C), 128.9 (2C),
126.2, 124.5, 121.6, 121.1, 36.9; ESI-MS m/z 292.0 (M þ H)þ; HRMS
(EI) calcd for C14H10ClNS2 (Mþ) 290.9943, found 290.9944.
2-((4-Methoxyphenyl)thio)benzo[d]thiazole (13u). 1H NMR
(300 MHz, CDCl3) δ 7.86 (d, J = 8.1 Hz, 1H), 7.70ꢀ7.60 (m, 3H), 7.39
(td, J = 7.5 Hz, J = 1.2 Hz, 1H), 7.25 (td, J = 7.2 Hz, J = 1.2 Hz, 1H),
7.04ꢀ6.97 (m, 2H), 3.88 (s, 3H); ESI-MS m/z 274.4 (M þ H)þ.
6-Fluoro-2-((4-methoxyphenyl)thio)benzo[d]thiazole (13v).
1H NMR (300 MHz, CDCl3) δ 7.82ꢀ7.75 (m, 1H), 7.66 (d, J = 8.7 Hz,
2H), 7.32 (dd, J = 7.8 Hz, J = 2.7 Hz, 1H), 7.12 (td, J = 8.7 Hz, J = 2.7 Hz,
1H), 7.01 (d, J = 8.7 Hz, 2H), 3.88 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ 171.3 (d, J = 2.9 Hz, 1C), 161.8, 159.8 (d, J = 243.5 Hz, 1C), 150.8 (d, J =
1.4 Hz, 1C), 137.6 (2C), 136.4 (d, J = 10.9 Hz, 1C), 122.6 (d, J = 9.5 Hz,
1C), 119.9, 115.6 (2C), 114.4 (d, J = 24.1 Hz, 1C), 107.2 (d, J = 26.2 Hz,
1C), 55.5; ESI-MS m/z 292.0 (M þ H)þ; HRMS (EI) calcd for
C14H10FNOS2 (Mþ) 291.0188, found 291.0191.
1
2-(Propylthio)benzo[d]thiazole (13k). H NMR (400 MHz,
CDCl3) δ 7.86 (d, J = 8.4 Hz, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.40 (t, J =
7.6 Hz, 1H), 7.28 (t, J = 7.6 Hz, 1H), 3.33 (t, J = 7.6 Hz, 2H), 1.90ꢀ1.80
(m, 2H), 1.09 (t, J = 7.2 Hz, 3H); ESI-MS m/z 210.0 (M þ H)þ.
2-((4-Methoxyphenyl)thio)-5,6-dimethylbenzo[d]thiazole
(13w). 1H NMR (300 MHz, CDCl3) δ 7.65 (d, J = 9.0 Hz, 2H), 7.62 (s,
1H), 7.37 (s, 1H), 6.99 (d, J = 9.0 Hz, 2H), 3.87 (s, 3H), 2.34 (s, 3H),
2.30 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.0, 161.6, 152.9, 137.5
(2C), 135.2, 133.5, 132.9, 122.1, 120.8, 120.6, 115.4 (2C), 55.5, 20.1,
20.0; ESI-MS m/z 302.0 (M þ H)þ; HRMS (EI) calcd for C16H15NOS2
(Mþ) 301.0595, found 301.0599.
1
2-(i-Propylthio)benzo[d]thiazole (13l). H NMR (400 MHz,
CDCl3) δ 7.88 (d, J = 8.0 Hz, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.41 (t, J =
7.6 Hz, 1H), 7.29 (t, J = 7.6 Hz, 1H), 4.14ꢀ4.02 (m, 1H), 1.50 (d, J = 7.2
Hz, 6H); ESI-MS m/z 210.0 (M þ H)þ.
1
2-(tert-Butylthio)benzo[d]thiazole (13m). H NMR (400 MHz,
CDCl3) δ7.98 (d, J= 8.4 Hz, 1H), 7.79 (d, J=7.6Hz,1H),7.44(t,J=7.2Hz,
1H), 7.34 (t, J = 7.2 Hz, 1H), 1.60 (s, 9H); ESI-MS m/z 224.1 (M þ H)þ.
1
2-(Benzylthio)thiazolo[4,5-b]pyridine (13x). H NMR (300
1
2-(Cyclopentylthio)benzo[d]thiazole (13n). H NMR (300
MHz, CDCl3) δ 8.62 (dd, J = 4.8 Hz, J = 1.2 Hz, 1H), 8.08 (dd, J = 7.8
Hz, J = 1.8 Hz, 1H), 7.48 (d, J = 7.5 Hz, 2H), 7.38ꢀ7.25 (m, 3H),
7.24ꢀ7.18 (m, 1H), 4.72 (s, 2H); 13C NMR (100 MHz, CDCl3) δ
171.5, 163.7, 147.6, 135.9, 129.8, 129.3 (2C), 128.9, 128.8 (2C), 127.9,
119.0, 37.5; ESI-MS m/z 259.3 (M þ H)þ; HRMS (EI) calcd for
C13H10N2S2 (Mþ) 258.0285, found 258.0284.
MHz, CDCl3) δ 7.88 (d, J = 8.1 Hz, 1H), 7.76 (d, J = 8.1 Hz, 1H),
7.45ꢀ7.36 (m, 1H), 7.33ꢀ7.24 (m, 1H), 4.18ꢀ4.06 (m, 1H),
2.40ꢀ2.20 (m, 2H), 1.90ꢀ1.65 (m, 6H); ESI-MS m/z 235.9 (M þ H)þ.
2-(Cyclopentylthio)-6-nitrobenzo[d]thiazole (13o). 1H NMR
(300 MHz, CDCl3) δ 8.68 (d, J = 2.1 Hz, 1H), 8.30 (dd, J = 9.0 Hz, J =
2.1 Hz, 1H), 7.90 (d, J = 8.7 Hz, 1H), 4.24ꢀ4.12 (m, 1H), 2.45ꢀ2.26 (m,
2H), 1.92ꢀ1.65 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 174.8, 157.2,
143.9, 135.5, 121.8, 121.2, 117.3, 46.9, 33.7 (2C), 24.9 (2C); ESI-MS m/z
281.0 (M þ H)þ; HRMS (EI) calcd for C12H12N2O2S2 (Mþ) 280.0340,
found 280.0335.
tert-Butyl (2-(Benzo[d]thiazol-2-ylthio)ethyl)carbamate
(13p). 1H NMR (400 MHz, CDCl3) δ 7.86 (d, J = 8.0 Hz, 1H), 7.75
(d, J = 8.0 Hz, 1H), 7.42 (t, J = 7.6 Hz, 1H), 7.30 (t, J = 7.6 Hz, 1H), 5.30
(s, 1H), 3.63ꢀ3.53 (m, 2H), 3.52ꢀ3.44 (m, 2H), 1.43 (s, 9H); ESI-MS
m/z 311.0 (M þ H)þ; HRMS (EI) calcd for C14H18N2O2S2 (Mþ)
310.0810, found 310.0812.
’ ASSOCIATED CONTENT
1
Supporting Information. Copies of H NMR and 13C
S
b
NMR spectra for all heterocycle products. This material is available
free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: madw@mail.sioc.ac.cn.
tert-Butyl (2-((6-Acetylbenzo[d]thiazol-2-yl)thio)ethyl)
carbamate (13q). H NMR (300 MHz, CDCl3) δ 8.38 (d, J = 1.2
Hz, 1H), 8.02 (dd, J = 8.4 Hz, J = 1.8 Hz, 1H), 7.87 (d, J = 8.7 Hz, 1H),
5.23 (s, 1H), 3.65ꢀ3.56 (m, 2H), 3.56ꢀ3.47 (m, 2H), 2.67 (s, 3H), 1.43
(s, 9H); 13C NMR (100 MHz, CDCl3) δ 196.9, 171.1, 155.9, 155.8, 135.6,
133.1, 126.5, 121.8, 121.1, 79.2, 39.9, 33.6, 28.4 (3C), 26.7; ESI-MS m/z
1
’ ACKNOWLEDGMENT
The authors are grateful to the Chinese Academy of Sciences,
National Natural Science Foundation of China (grant 20621062
and 20872156) for their financial support.
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The Journal of Organic Chemistry
NOTE
’ REFERENCES
(1) (a) Zhang, J.-T.; Qi, J.; Feng, H.; Dong, Z. WO2010048603,
2010. (b) Choudhary, A. N.; Kumar, A.; Jural, V. Mini-Rev. Med. Chem.
2010, 10, 705. (c) Naya, A.; Kobayashi, K.; Ishikawa, M.; Ohwaki, K.;
Saeki, T.; Noguchi, K.; Ohtake, N. Bioorg. Med. Chem. Lett. 2001,
11, 1219. (d) Greco, M. N.; Hageman, W. E.; Powell, E. T.; Tighe,
J. J.; Persico, F. J. J. Med. Chem. 1992, 35, 3180. (e) Waisser, K.; Sidoova,
E.; Odlerova, Z.; Goeckeritz, W.; Drsata, J. Pharmazie 1987, 42, 536. (f)
Dumas, J.; Brittelli, D.; Chen, J.; Dixon, B.; Hatoum-Mokdad, H.; Konig,
G.; Sibley, R.; Witowsky, J.; Wong, S. Bioorg. Med. Chem. Lett. 1999,
9, 2531. (g) Koꢀcí, J.; Klimeꢀsovꢁa, V.; Waisser, K.; Kaustovꢁa, J.; Dahsec, H.;
M€ollmann, U. Bioorg. Med. Chem. Lett. 2002, 12, 3275. (h) Franchini, C.;
Muraglia, M.; Corbo, F.; Florio, M. A.; Di Mola, A.; Rosato, A.; Matucci,
R.; Nesi, M.; van Bambeke, F.; Vitali, C. Arch. Pharm. Chem. Life Sci.
2009, 342, 605. (i) Zhang, L.; Fan, J.; Vu, K.; Hong, K.; Le Brazidec, J.-Y.;
Shi, J.; Biamonte, M.; Busch, D. J.; Lough, R. E.; Grecko, R.; Ran, Y.;
Sensintaffar, J. L.; Kamal, A.; Lundgren, K.; Burrows, F. J.; Mansfield, R.;
Timony, G. A.; Ulm, E. H.; Kasibhatla, S. R.; Boehm, M. F. J. Med. Chem.
2006, 40, 5352.
(2) (a) Prabakaran, K.; Khan, F. N. Phosphorus, Sulfur Silicon Relat.
Elem. 2010, 185, 825. (b) Kumar, R. V.; Kumar, K. V. S. R. S.; Gopal,
K. R. J. Heterocycl. Chem. 2005, 42, 153. (c) Ghosh, A. K.; Zajc, B. J. Org.
Chem. 2009, 74, 8531.
(3) (a) Kuroda, K.; Maruyama, Y.; Hayashi, Y.; Mukaiyama, T. Bull.
Chem. Soc. Jpn. 2009, 82, 381. (b) Kuroda, K.; Hayashi, Y.; Mukaiyama,
T. Chem. Lett. 2008, 37, 592. (c) Kawano, Y.; Kanebo, N.; Mukaiyama,
T. Chem. Lett. 2005, 34, 1612. (d) McCrea-Hendrick, M.; Nichols, C. J.
Synth. Commun. 2009, 39, 3611.
(4) (a) Feng, Y.-S.; Li, Y.-Y.; Tang, L.; Wu, W.; Xu, H.-J. Tetrahedron
Lett. 2010, 51, 2489. (b) Larsson, P.; Correa, A.; Carril, M.; Norrby, P.;
Bolm, C. Angew. Chem., Int. Ed. 2009, 48, 5691. (c) Correa, A.; Carril,
M.; Bolm, C. Angew. Chem., Int. Ed. 2008, 47, 2880. (d) Wu, W.-Y.;
Wang, J.-C.; Tsai, F.-Y. Green Chem. 2009, 11, 326.
(5) Savarin, C.; Srogl, J.; Liebeskind, L. S. Org. Lett. 2002, 4, 4309.
(6) (a) Ballabeni, M.; Ballini, R.; Bigi, F.; Maggi, R.; Parrini, M.;
Predieri, G.; Sartori, G. J. Org. Chem. 1999, 64, 1029. (b) Harizi, A.;
Romdhane, A.; Mighri, Z. Tetrahedron Lett. 2000, 41, 5833.
(7) Murru, S.; Ghosh, H.; Sahoo, S. K.; Patel, B. Org. Lett. 2009, 11,
4254.
(8) Murru, S.; Mondal, P.; Yella, R.; Patel, B. Eur. J. Org. Chem.
2009, 5406.
(9) Ma, D.; Lu, X.; Shi, L.; Zhang, H.; Jiang, Y.; Liu, X. Angew. Chem.,
Int. Ed. 2011, 50, 1118.
(10) For selected examples of copper-catalyzed S-arylation, see: (a)
Bates, C. G.; Gujadhur, R. K.; Venkataraman, D. Org. Lett. 2002, 4, 2803.
(b) Kwong, F. Y.; Buchwald, S. L. Org. Lett. 2002, 4, 3517. (c) Lv, X.;
Bao, W. J. Org. Chem. 2007, 72, 3863. (d) Gonzalez-Arellano, C.; Luque,
R.; Macquarrie, D. J. Chem. Commun. 2009, 1410. (e) Jammi, S.;
Sakthivel, S.; Rout, L.; Mukherjee, T.; Mandal, S.; Mitra, R.; Saha, P.;
Punniyamurthy, T. J. Org. Chem. 2009, 74, 1971. (f) Gan, J.; Ma, D. Org.
Lett. 2009, 11, 2788. (g) Jiang, Y.; Xie, S.; Qin, Y.; Zhang, X.; Ma, D. Org.
Lett. 2009, 11, 5250. (h) Ma, D.; Xie, S.; Xue, P.; Zhang, X.; Dong, J.;
Jiang, Y. Angew. Chem., Int. Ed. 2009, 48, 4222.
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