Peroxide-mediated oxidative coupling of primary alcohols and disulfides: Synthesis of 2-substituted benzothiazoles

Article abstract of DOI:10.1016/j.tetlet.2019.05.021

A peroxide-mediated protocol for the synthesis of 2-substituted benzothiazoles was developed, starting from bis(o-aminophenyl) disulfides and primary alcohols. Eleven differently 2-substituted benzothiazoles were prepared in moderate to excellent yields using di-tert-butyl peroxide (DTBP) as an oxidant.

Full text of DOI:10.1016/j.tetlet.2019.05.021

Accepted Manuscript
Peroxide-mediated oxidative coupling of primary alcohols and disulfides: syn-
thesis of 2-substituted benzothiazoles
Nathalia B. Padilha, Filipe Penteado, Maria C. Salomão, Eric F. Lopes, Luana
Bettanin, Daniela Hartwig, Raquel G. Jacob, Eder J. Lenardão
PII:
S0040-4039(19)30459-9
https://doi.org/10.1016/j.tetlet.2019.05.021
TETL 50793
DOI:
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
8 March 2019
8 May 2019
10 May 2019
Please cite this article as: Padilha, N.B., Penteado, F., Salomão, M.C., Lopes, E.F., Bettanin, L., Hartwig, D., Jacob,
R.G., Lenardão, E.J., Peroxide-mediated oxidative coupling of primary alcohols and disulfides: synthesis of 2-
substituted benzothiazoles, Tetrahedron Letters (2019), doi: https://doi.org/10.1016/j.tetlet.2019.05.021
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Peroxide-mediated oxidative coupling of primary alcohols and
disulfides: synthesis of 2-substituted benzothiazoles
a
a
a
a
Nathalia B. Padilha, Filipe Penteado, Maria C. Salomão, Eric F. Lopes, Luana
a
a
a
a,
Bettanin, Daniela Hartwig, Raquel G. Jacob and Eder J. Lenardão *
aLaboratório de Síntese Orgânica Limpa - LASOL - CCQFA - Universidade Federal de Pelotas -
UFPel - P.O. Box 354 - 96010-900, Pelotas, RS, Brazil.
*
e-mail: lenardao@ufpel.edu.br; phone/FAX: +55 53 3275 7533.
ABSTRACT
A peroxide-mediated protocol for the synthesis of 2-substituted benzothiazoles was
developed, starting from bis(o-aminophenyl) disulfides and primary alcohols. Eleven
differently 2-substituted benzothiazoles were prepared in moderate to excellent yields
using di-tert-butylperoxide (DTBP) as an oxidant.
Keywords: benzothiazoles; C-S bond formation; oxidative coupling; disulfides
INTRODUCTION
Nitrogen-containing heterocycles are one of the most important classes of naturally
occurring compounds, with a crucial role in many biological processes. They represent the
active pharmaceutical ingredient of countless drugs, are present in high-performance
1
materials and are used as dyes. Among this impressive class of compounds, 2-
substituted benzothiazoles have attracted significant attention, since this subclass is
present in the core motif of various bioactive compounds, playing a crucial role in drug
2
discovery. In this context, the most famous 2-substituted benzothiazole derivative is
®
Riluzole (1), a worldwide marketed drug, used for the treatment of amyotrophic lateral
3
sclerosis (ALS), a motor neuron disease. In addition to the importance of these
compounds as therapeutics, they also have attracted attention due to their photophysical
4
properties. For instance, thioflavin T (2) has been extensively used for the detection of
deposited amyloid fibrils in humans, which are related to the development of several
5
diseases, including Alzheimer’s (AD) and Parkinson’s diseases (PD). In this context,
Pittsburgh Compound B (3), a radiative analogue of thioflavin T, was clinically approved for
AD diagnosis, through amyloid-imaging positron emission tomography (PET) (Scheme 1).6
1

Cl
Me
N
S
N
Me
N
Me HO
N
S
11CH3
NH2
NH
F3C
O
Me
S
Riluzole
Thioflavin T
Pittsburgh Compound B
2
3
1
Scheme 1. Representative important 2-substituted benzothiazoles.
As a consequence of the notable biological properties of 2-substituted
benzothiazoles, the development of efficient synthetic methodologies to access these
7
compounds selectively is highly desirable. The most widespread strategy to construct 2-
substituted benzothiazoles is via the condensation reaction between 2-aminobenzenethiol
8
or 2-aminoaryldisulfides and carbonyl partners, including aldehydes and organic acid
derivatives, such as, carboxylic acids, amides,10 acyl chlorides11 and α-keto acids.12
Additionally, C-H activation strategies using 2H-benzothiazoles as starting materials, have
been investigated.13 In this context, alcohols have been explored as substrates in
dehydrogenative annulation reactions with 2-aminobenzenethiol via transition metal-
catalyzed,14 strong base-catalyzed15 and electrochemical-assisted16 synthetic strategies.
These protocols however, present some drawbacks, including long reaction times and
complex reaction apparatus. Thus, the development of methods using simple, ease to
handle and widely available substrates for the synthesis of 2-substituted benzothiazoles is
desirable. Herein, we describe a simple and efficient peroxide-mediated dehydrogenative
annulation of alcohols and 2-aminoaryldisulfides to access 2-alkyl and 2-aryl benzothiazole
derivatives.
9
RESULTS AND DISCUSSION
Initially, bis(o-aminophenyl) disulfide 4a (prepared via the mild DMSO-promoted
oxidation of 2-aminobenzenethiol)17 and ethanol 5a were examined as model substrates
using di-tert-butyl peroxide (DTBP; 2 equiv.) as the oxidant, aiming to prepare 2-
methylbenzo[d]thiazole 6a (Table 1). The first reactions were performed at 120 ºC in a
sealed tube, and after stirring for 3 h and 6 h, the desired product 6a was formed in 17%
and 25% yield, respectively (Table 1, entries 1-2). In order to investigate the influence of
the temperature in this transformation, the reaction was carried out at 150 ºC, and a
remarkable improvement was observed, giving product 6a in 61% yield after 6 h (Table 1,
2

entry 3). Additionally, by increasing the amount of the oxidant to 3 and 4 equiv., a
proportional increase in the yield was observed, giving product 6a in 83% and 97% yield,
respectively (Table 1, entries 4-5). Next, we evaluated the efficiency of different oxidants,
including tert-butyl hydroperoxide (TBHP in H O and in decane) and H O . However, none
2
2
2
of them were effective in the reaction, giving product 6a in low yield (TBHP) or even failing
completely (H O ) (Table 1, entries 6-8). Finally, the amount of EtOH was reduced to 0.5
2
2
mL and 0.25 mL, giving product 6a in 43% and 31% yield, respectively (Table 1, entries 9-
0).
1
Table 1. Reaction optimization for the synthesis of 6a.a
NH2
N
S
oxidant
temperature
time
+
EtOH
Me
S)2
5a
6a
4
a, 0.25 mmol
"sealed tube"
Entry 5a (mL)
Oxidant (equiv)
DTBP (2)
Temperature (ºC) Time (h) Yield 6a (%)b
1
2
3
4
5
6
7
8
9
1
1
120
120
150
150
150
150
150
150
150
150
3
6
6
6
6
6
6
6
6
6
17
25
61
83
97
13
28
NR
43
31
DTBP (2)
1
DTBP (2)
1
DTBP (3)
1
DTBP (4)
1
TBHP 70% in H
TBHP in decane (4)
(4)
2
O (4)
1
1
2 2
H O
0.5
0.25
DTBP (4)
DTBP (4)
10
a
In a reaction vial were added 4a (0.25 mmol), EtOH 5a and the oxidant. The reaction
vial was sealed, and the mixture stirred for the stated temperature and time. b Reaction
yields were obtained after preparative thin-layer chromatography.
With the optimized reaction conditions in hand (Table 1, entry 5),18 the scope and
limitations for the reaction of bis(o-aminophenyl) disulfide 4a with several primary alcohols
1
1
5
was performed (Table 2). n-Butanol 5b (R = C H ) and isoamyl alcohol 5c (R = C H )
3 7 5 11
were suitable substrates, giving the respective products 6b and 6c in 55% and 40% yield,
respectively. These are interesting results, because the synthesis of 2-alkyl-substituted
benzothiazoles is not trivial, with a reduced number of methods compared to their 2-aryl
3

7
analogues. Benzyl alcohol 6d and its derivatives were also tolerated in the reaction,
affording the respective 2-arylbenzothiazoles in modest to good yields. Thus, product 6d
1
1
(
R = C H ) was obtained in 77% yield, while the para-substituted 6e (R = 4-ClC H ) and
6
5
6
4
1
6
f (R = 4-NO C H ) were isolated in 49% and 35% yield respectively, after 6 h. A longer
2 6 4
reaction time of 10 h was necessary when sterically hindered ortho-substituted benzylic
1
alcohol 5g (R = 2-MeOC H ) was used, giving the expected product 6g in 25% yield.
6
4
Additionally, 2-pyridylbenzothiazole 6h was formed in 88% yield, while 2-
furfurylbenzothiazole 6i was obtained in 40% yield. The bulky 2,6-di-tert-butyl-4-
(hydroxymethyl)phenol 5j reacted smoothly with 4a to give the expected product 6j in 48%
yield (Table 2). The presence of an electron-withdrawing group (Cl) in the para-position of
bis(o-aminophenyl) disulfide (4b) did not influence the reactivity with ethanol 5a, affording
the respective benzothiazole 6k in 93% yield.
Table 2. Study of the reaction scope for the synthesis of products 6.a
R
NH2
R
N
S
DTBP (4 equiv)
50 ºC, 6 h
R1
OH
a-j
R1
+
1
S)2
"
sealed tube"
5
6a-k
4
a-b
N
N
S
N
N
S
Me
Ph
S
S
6a, 97%
6b, 55%
6c, 40%
6d, 77%
MeO
N
S
N
S
N
S
N
S
N
Cl
NO2
25%b
6e, 49%
6f, 35%
6g
6h, 88%
,
N
S
O
Cl
N
S
N
OH
Me
S
6i, 40%
6k, 93%
6j, 48%
a
In a reaction vial were added the substrate 4 (0.25 mmol), the alcohol source 5 (1 mL) and DTBP (4
equiv). Then, the reaction vial was sealed, and the solution stirred for 6 h at 150 ºC. Reaction yields
b
were obtained after preparative thin-layer chromatography. Reaction was carried out for 10 h.
4

Thus, in order to gain mechanistic insights into this protocol, several control
experiments were performed (Scheme 2). Initially, the reaction between 4a and 5a was
carried out in the presence of TEMPO and hydroquinone as radical scavengers. In both
cases the formation of compound 6a was not observed, meaning that radical species are
involved in key reaction steps (Scheme 2, #1 and #2). When MeOH 5j was used as the
alcohol source instead of ethanol, the respective benzothiazole was not detected, and the
starting disulfide 4a was recovered (Scheme 2, #3). The same result was obtained when i-
PrOH 5k (a secondary alcohol) was employed in the reaction with 4a (Scheme 2, #4).
Finally, benzaldehyde 7a was employed instead of EtOH 5a under the standard reaction
o
conditions, and after 6 h at 150 C, bis(o-aminophenyl) disulfide 4a was completely
consumed to give the expected product 6c in 39% yield, together the dihydro-derivative 8d
(18%) and the imine derivative 9d (43% yield) (Scheme 2, #5).
Control Experiments
DTBP (4 equiv)
NH2
N
S
TEMPO (4 equiv)
50 ºC, 6 h
sealed tube"
#
1
+
EtOH
Me
1
S)2
5a
"
6a
4a
not observed
DTBP (4 equiv)
hydroquinone(4 equiv)
a
+
5a
6a
#
2
3
4
150 ºC, 6 h
not observed
"
sealed tube"
DTBP (4 equiv)
50 ºC, 6 h
sealed tube"
4a + MeOH
No Reaction
#
1
5
j
"
DTBP (4 equiv)
4
a + i-PrOH
#
4
5
No Reaction
150 ºC, 6 h
2k
"
sealed tube"
H
N
O
N
Ph
N
S
Ph
H
DTBP (4 equiv)
4a
+
Ph +
+
#
Ph
H
150 ºC, 6 h
S
S)2
7a
"
sealed tube"
6d, 39%
8d, 18%
9d, 43%
Scheme 2. Control experiments under the optimized reaction conditions.
Taken together, these results suggest that a radical process is involved and that the
stability of the radical species is important; presumably the reaction did not work with
MeOH because it would generate an unstable methyl radical. Additionally, the use of
5

primary alcohols is mandatory to provide two hydrogen atoms for the required radical
oxidation steps. It was also confirmed that the reaction proceeds via the oxidation of the
alcohol substrate to an aldehyde; however, utilization of the alcohol is mandatory to afford
the product in acceptable yields (Scheme 2).
19
Thus, based on the control experiments and previous reports, a plausible reaction
mechanism was proposed. Initially, DTBP is decomposed under heating to the radical
t

BuO , which promotes a radical oxidation of the primary alcohol 5 to the radical species I.
Subsequently, the S-S bond of substrate 4a undergoes radical substitution by radical
intermediate I, giving the thioether intermediate II. Hence, oxidation of intermediate II
affords the radical intermediate III, which in the presence of the tert-butoxyl radical
undergoes a hydrogen atom transfer (HAT) reaction to give intermediate IV. After the
intramolecular annulation of ketone IV, the respective dihydrobenzothiazole 8 is formed.
Finally, a dehydration reaction converts intermediate 8 into the desired product 6 (Scheme
3).
t
t
BuO O Bu
NH2

S
S
tBuO
tBuOH
H N 4a
2
NH2
S
H
R1 OH
R1
OH
I
5
II
HO
R1
tBuO
tBuOH
NH2
S
t
t
NH2
BuOH BuO
H
N
R1
-
H O
2
6
S
S
OH
HAT
8
IV O
R1
III HO
R1
Scheme 3. Plausible reaction mechanism for the synthesis of benzothiazole 6.
CONCLUSION
In summary, we have described a new and general protocol to prepare 2-substituted
benzothiazoles in moderate to excellent yields. The good tolerance to access 2-alkyl-
substituted benzothiazoles, which are in general difficult to prepare, and the use of readily
available primary alcohols as starting material are notable features of the method. In
6

addition, this protocol avoids the use of unpleasant smelling thiols, which are commonly
used as substrates in the synthesis of 2-substituted benzothiazoles.
ACNOWLEDGEMENTS
This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de
Nível Superior - Brasil (CAPES) - Finance Code 001. FAPERGS CNPq and FINEP are
acknowledged for financial support.
REFERENCES
1
. (a) Quin, L. D.; Tyrell, J. A. Fundamentals of Heterocyclic Chemistry, Wiley-VCH,
Weinheim, 2010. (b) Alvarez-Builla, J.; Vaquero, J. J.; Barluenga, J. Modern
Heterocyclic Chemistry, Wiley-VCH, Weinheim, 2010. (c) Katritzky, A. R.; Rees, C. W.
(eds.) Comprehensive Heterocyclic Chemistry, Pergamon Press, Oxford, 1984. (d)
Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V. (eds.) Comprehensive Heterocyclic
Chemistry II, Pergamon Press, Oxford, 1996. (e) Gomtsyan, A. Chem. Heterocycl.
Comp. 2012, 48, 7-10. (f) Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem. Rev. 2003,
103, 893-930. (f) Achelle, S.; Baudequin, C.; Plé, N. Dyes Pigm. 2013, 98, 575-600. (g)
Lipunova, G. N.; Nosova, E. V.; Charushin, V. N.; Chupakhin, O. N. Curr. Org. Synth.
2
018, 15, 793-814. (h) Achelle, S.; Rodríguez-López, J.; Guen, F. R. ChemistrySelect
018, 3, 1852-1886. (i) Raoui, M.; Massue, J.; Azarias, C.; Jacquemin, D.; Ulrich, G.
2
Chem. Commun. 2016, 52, 9216-9219.
2
. (a) Hutchinson, I.; Chua, M.-S.; Browne, H. L.; Trapano, V.; Bradshaw, T. D.; Wastwell,
A. D. Stevens, M. F. G. J. Med. Chem. 2001, 44, 1446-1455. (b) Cressier, D.; Prouillac,
C.; Hernandez, P.; Amourette, C.; Diserbo, M.; Lion, C.; Rima, G. Bioorg. Med. Chem.
2009, 17, 5275-5284. (c) Singh, M.; Singh, S. K.; Gangwar, M.; Nath, G.; Singh, S. K.
RSC Adv. 2014, 4, 19013-19023. (d) Aiello, S.; Wells, G.; Stone, E. L.; Kadri, H.; Bazzi,
R.; Bell, D. R.; Stevens, M. F. G.; Matthews, C. S.; Bradshaw, T. D.; Westwell, A. D. J.
Med. Chem. 2008, 51, 5135-5139. (e) Mortimer, C. G.; Wells, G.; Crochard, J.-P.;
Stone, E. L.; Bradshaw, T. D.; Stevens, M. F. G.; Westwell, A. D. J. Med. Chem. 2006,
49, 179-185. (f) Easmon, J.; Pürstinger, G.; Thies, K.-S.; Heinisch, G.; Hofmann, J. J.
Med. Chem. 2006, 49, 6343-6350. (g) Massari, S.; Daelemans, D.; Barreca, M. L.;
Knezevich, A.; Sabatini, S.; Cecchetti, V.; Marcello, A.; Pannecouque, C.; Tabarrini, O.
7

J. Med. Chem. 2010, 53, 641-648. (h) Bradshaw, T. D.; Westwell, A. D. Curr. Med.
Chem. 2004, 11, 1009-1021.
3. (a) Harriet, M. B.; Bret, F.; Paul, B. Drugs 1996, 52, 549-563. (b) Doble, A. Neurology
1
996, 47, 233-241.
. (a) So, Y.-H.; Zaleski, J. M.; Murlick, C.; Ellaboudy, A. Macromolecules 1996, 29, 2783-
795. (b) Roh, S.-G.; Kim, Y.-H.; Seo, K. D.; Lee, D. H.; Kim, H. K.; Park, Y.-I.; Park, J.-
4
2
W.; Lee, J.-H. Adv. Funct. Mater. 2009, 19, 1663-1671. (c) Anthony, K.; Brown, R. G.;
Hepworth, J. D.; Hodgson, K. W.; May, B.; West, M. A. J. Chem. Soc., Perkin Trans. 2
1984, 0, 2111-2117. (d) Padalkar, V. S.; Tathe, A.; Gupta, V. D.; Patil, V. S.;
Phatangare, K.; Sekar, N. J. Fluoresc. 2012, 22, 311-322. (e) Xu, L.; Wang, Q.; Zhang,
Y. Dyes Pigments 2017, 136, 732-743. (f) Lu, Y.-J.; Yan, S.-C.; Chan, F.-Y.; Zou, L.;
Chung, W.-H.; Wong, W.-L.; Qiu, B.; Sun, N.; Chan, P.-H.; Huang, Z.-S.; Gu, L.-Q.;
Wong, K.-Y. Chem. Commun. 2011, 47, 4971-4973.
5. (a) Kelly, J. W. Structure 1997, 5, 595-600. (b) Hashimoto, M.; Masliah, E. Brain Pathol.
1999, 9, 707-720. (c) Koo, E. H.; Lansbury, P. T., Jr.; Kelly, J. W. Proc. Natl. Acad. Sci.
U.S.A. 1999, 96, 9989-9990. (d) Uversky, V. N.; Talapatra, A.; Gillespie, J. R.; Fink, A.
L. Med. Sci. Monitor 1999, 5, 1001-1012. (e) Uversky, V. N.; Talapatra, A.; Gillespie, J.
R.; Fink, A. L. Med. Sci. Monitor 1999, 5, 1238-1254. (f) Naiki, H.; Higuchi, K.;
Hosokawa, M.; Takeda, T. Anal. Biochem. 1989, 177, 244-249. (g) Naiki, H.; Higuchi,
K.; Matsushima, K.; Shimada, A.; Chen, W. H.; Hosokawa, M.; Takeda, T. Lab. InVest.
1
990, 62, 768–773. (h) LeVine, H., III Protein Sci. 1993, 2, 404-410. (i) LeVine, H., III
Amyloid: Int. J. Exp. Clin. Invest. 1995, 2, 1-6. (j) LeVine, H., III Arch. Biochem. Biophys.
997, 342, 306–316. (k) LeVine, H., III Methods Enzymol. 1999, 309, 274-284. (l)
1
Allsop, D.; Swanson, L.; Moore, S.; Davies, Y.; York, A.; El-Agnaf, O. M.; Soutar, I.
Biochem. Biophys. Res. Commun. 2001, 285, 58-63. (m) Yoshiike, Y.; Chui, D. H.;
Akagi, T.; Tanaka, N.; Takashima, A. J. Biol. Chem. 2003, 278, 23648-23655.
6
. (a) Klunk, W. E.; Engler, H.; Nordberg, A.; Wang, Y.; Blomqvist, G.; Holt, D. P.;
Bergström, M.; Savitcheva, I.; Huang, G. F.; Estrada, S.; Ausén, B.; Debnath, M. L.;
Barletta, J.; Price, J. C.; Sandell, J.; Lopresti, B. J.; Wall, A.; Koivisto, P.; Antoni, G.;
Mathis, C. A.; Långström, B. Ann. Neurol. 2004, 55, 306-319. (b) Prince, J. C.; Klunk,
W. E.; Lopresti, B. J.; Lu, X.; Hoge, J. A.; Ziolko, S. K.; Holt, D. P.; Meltzer, C. C.;
DeKosky, S. T.; Mathis, C. A. J. Cereb. Blood Flow Metab. 2005, 25, 1528-1547. (c)
Lopresti, B. J.; Klunk, W. E.; Mathis, C. A.; Hoge, J. A.; Ziolko, S. K.; Lu, X.; Meltzer, C.
C.; Schimmel, K.; Tsopelas, N. D.; DeKosky, S. T.; Price, J. C. J. Nucl. Med. 2005, 46,
8

1959-1972. (d) Klunk, W. E.; Lopresti, B. J.; Ikonomovic, M. D.; Lefterov, I. M.;
Koldamova, R. P.; Abrahamson, E. E.; Debnath, M. L.; Holt, D. P.; Huang, G.-F.; Shao,
L.; DeKosky, S. T.; Price, J. C.; Mathis, C. A. J. Neurosci. 2005, 25, 10598-10606. (e)
Murray, M. E.; Lowe, V. J.; Graff-Radford, N. R.; Liesinger, A. M.; Cannon, A.;
Przybelski, S. C.; Rawal, B.; Parisi, J. E.; Petersen, R. C.; Kantarci, K.; Ross, O. A.;
Duara, R.; Knopman, D. S.; Jack, C. R.; Dickson, D. W. Brain 2015, 138, 1370-1381. (f)
Butters, M. A.; Klunk, W. E.; Mathis, C. A.; Price, J. C.; Ziolko, S. K.; Hoge, J. A.;
Tsopelas, N. D.; Lopresti, B. J.; Reynolds, C. F.; DeKosky, S. T.; Meltzer, C. C.
Alzheimer Dis. Assoc. Disord. 2008, 22, 261-268.
7. Prajapati, N. P.; Vekariya, R. H.; Borad, M. A.; Patel, H. D. RSC Adv. 2014, 4, 60176-
6
0208.
. (a) Parikh, N.; Kumar, D.; Roy, S. R.; Chakraborti, A. K. Chem. Commun. 2011, 47,
797-1799. (b) Riadi, Y.; Mamouni, R.; Azzalou, R.; Haddad, M. E.; Routier, S.;
8
1
Guillaumet, G.; Lazar, S. Tetrahedron Lett. 2011, 52, 3492-3495. (c) Bahrami, K.;
Khodaei, M. M.; Naali, F. J. Org. Chem. 2008, 73, 6835-6837. (d) Itoh, T.; Nagata, K.;
Ishikawa, H.; Ohsawa, A. Heterocycles 2004, 63, 2769-2783. (e) Maphupha, M.; Juma,
W. P.; de Koning, C. B.; Brady, D. RSC Adv. 2018, 8, 39496-39510. (f) Ye, L.-M.; Chen,
J.; Mao, P.; Mao, Z.-F.; Zhang, X.-J.; Yan, M. Tetrahedron Lett. 2017, 58, 874-876. (g)
Wang, Z.; Tang, R.; Li, J. Chin. J. Chem. 2011, 29, 314-320. (h) Yang, X.; Xu, Y.; Chen,
J.; Ding, J.; Wu, H.; Su, W. J. Chem. Res. 2009, 11, 682-685. (i) Yang, D.; Zhu, X.; Wei,
W.; Sun, N.; Yuan, L.; Jiang, M.; You, J.; Wang, H. RSC Adv. 2014, 4, 17832-17839.
. (a) Hein, D. W.; Alheim, R. J.; Leavitt, J. J. J. Am. Chem. Soc. 1957, 79, 427-429. (b)
Sharghi, H.; Asemani, O. Synth. Commun. 2009, 39, 860-867. (c) T. G. Deligeorgiev,
Dyes Pigm. 1990, 12, 243–248; (d) Rudrawar, S.; Kondaskar, A.; Chakraborti, A. K.
Synthesis 2005, 15, 2521-2526. (e) Seijas, J. A.; Vázquez-Tato, M. P.; Carballido-
Reboredo, M. R.; Crecente-Campo, J. Synlett 2007, 2, 313-317.
9
1
1
1
0. Tang, R.-Y.; Xie, Y.-X.; Xie, Y.-L.; Xiang, J.-N.; Li, J.-H. Chem. Commun. 2011, 47,
12867-12869.
1. Nadaf, R. N.; Siddiqui, S. A.; Thomas, D.; Lahoti, R. J.; Srinivasan, K. V. J. Mol. Catal.
A 2004, 214, 155-160.
2. (a) Penteado, F.; Viera, M. M.; Perin, G.; Alves, D.; Jacob, R. G.; Santi, C.; Lenardão,
E. J. Green Chem. 2016, 18, 6675-6680. (b) Lima, D. B.; Penteado, F.; Vieira, M. M.;
Alves, D.; Perin, G.; Santi, C.; Lenardão, E. J. Eur. J. Org. Chem. 2017, 3830-3836.
9

1
3. (a) Kondo, Y.; Komine, T.; Sakamoto, T. Org. Lett. 2000, 2, 3111-3113. (b) Gallagher,
W. P.; Maleczka, R. E. J. Org. Chem. 2003, 68, 6775-6779. (c) Sezen, B.; Sames, D.
Org. Lett. 2003, 5, 3607-3610. (d) Chiong, H.; Daugulis, O. Org. Lett. 2007, 9, 1449-
1
451. (e) Turner, G.; Morris, J.; Greaney, M. Angew. Chem. Int. Ed. 2007, 46, 7996-
000. (f) Do, H.; Daugulis, O. J. Am. Chem. Soc. 2007, 129, 12404-12405. (g) Huang,
8
J.; Chan, J.; Chen, Y.; Borths, C. J.; Kyle, K. D.; Larsen, R. D.; Faul, M. M. J. Am.
Chem. Soc. 2010, 132, 3674-3675. (h) Hachiya, H.; Hirano, K.; Satoh, T.; Miura, M.
Angew. Chem. Int. Ed. 2010, 49, 2202-2205. (i) Zhang, F. Z.; Greaney, M. F. Angew.
Chem. Int. Ed. 2010, 49, 2768-2771. (j) Yang, Z.; Chen, X.; Wang, S.; Liu, J.; Xie, K.;
Wang, A.; Tan, Z. J. Org. Chem. 2012, 77, 7086-7091. (k) Wang, J.; Zhang, X.-Z.;
Chen, S.-Y.; Yu, X.-Q. Tetrahedron 2014, 70, 245-250.
14. (a) Bala, M.; Verma, P. K.; Sharma, U.; Kumar, N.; Singh, B. Green Chem. 2013, 15,
1687-1693. (b) Wang, D.; Albero, J.; García, H.; Li, Z. J. Catal. 2017, 349, 156-162.
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1
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5. Shi, X.; Guo, J.; Liu, J.; Ye, M.; Xu, Q. Chem. Eur. J. 2015, 21, 9988-9993.
6. Lai, Y.-L.; Ye, J.-S.; Huang, J.-M. Chem. Eur. J. 2016, 22, 5425-5429.
7. (a) Fristad, W. E.; Peterson, J. R. Synth. Commun. 1985, 15, 1-5. (b) Rivero, M. R.;
Alonso, I.; Carretero, J. C. Chem. Eur. J. 2004, 10, 5443-5459.
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8. General procedure for the preparation of the 2-substituted benzothiazoles 6a-k:
In a 5 mL glass ampoule were added the disulfide 4a or 4b (0.25 mmol), the primary
alcohol 5a-j (1.0 mL for liquids and 1.0 mmol for solids) and DTBP (4 equiv). Then, the
ampoule was sealed, and the system was heated (150 ºC) for 6 h under magnetic
stirring. Upon reaction completion, the unreacted volatile alcohol derivatives were
removed by vacuum and the desired product was isolated by preparative thin-layer
chromatography using a mixture of hexanes and AcOEt. Spectroscopic data for all of
the prepared compounds are available in the Supporting Information.
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9. (a) Zhang, S.-Y.; Zhang, F.-M.; Tu, Y.-Q. Chem. Soc. Rev. 2011, 40, 1937-1949. (b)
Campos, K. R. Chem. Soc. Rev. 2007, 36, 1069-1084. (c) Pan, S.; Liu, J.; Li, H.;
Wang, Z.; Guo, X.; Lo, Z. Org. Lett. 2010, 12, 1932-1935. (d) Guo, S.-R.; Yuan, Y.-Q.;
Xiang, J.-N. Org. Lett. 2013, 15, 4654-4657.
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