Title: Aniline ortho C-H Sulfuration/Cyclization with Elemental Sulfur for

Efficient Synthesis of 2-Substituted Benzothiazoles under Metal-

Free Conditions

Authors: Guojun Deng, Jingjing Jiang, Guozheng Li, Feng Zhang, and
Hao Xie

This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.

To be cited as: Adv. Synth. Catal. 10.1002/adsc.201701560

Link to VoR: http://dx.doi.org/10.1002/adsc.201701560

Advanced Synthesis & Catalysis 10.1002/adsc.201701560

COMMUNICATION
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))

Aniline ortho C-H Sulfuration/Cyclization with Elemental

Sulfur for Efficient Synthesis of 2-Substituted Benzothiazoles
under Metal-Free Conditions
Jingjing Jiang,a Guozheng Li,a Feng Zhang,a,b* Hao Xie, Guo-Jun Denga*
a
Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally
Friendly Chemistry and Application of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan
411105, China. E-mail: [email protected]; [email protected].

Accepted Manuscript
b
College of Science, Hunan Agricultural University, Changsha, 410128, China.

Received: ((will be filled in by the editorial staff))

Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))

Abstract. A three-component synthesis of 2- addition, it is challenging to remove the trace amount

substituted benzothiazoles from aryl amines, of transition-metals from the sulfur-containing
elemental sulfur and styrenes or aryl acetylenes in 1- heterocycle products due to the strong adsorption
methylpyrrolidin-2-one (NMP) is described. Two C-S between the metal and hetero atoms. Therefore, the
and one C-N bonds were selectively formed in one- development of efficient methods for the synthesis of
pot under metal-free conditions. sulfur-containing heterocycles from simple and
readily available substrates under metal-free
Keywords: 2-substituted benzothiazoles; aromatic conditions is highly desirable.
amines; elemental sulfur; metal-free Benzothiazole derivatives are privileged motif,
which were frequently found in pharmaceuticals and
many other biologically active products.[7] Moreover,
benzothiazole moieties were also found in many
The formation of C-S bonds is important because functional molecules such as ligands for catalytic
of their prevalence in many biologically active reactions.[8] Over the past few decades, tremendous
compounds and organic functional materials.[1] The progress has been made to synthesize 2-substituted
thiolation (or sulfuration) of arenes usually involves benzothiazoles, an important class of benzothiazole
transition-metal-catalyzed cross-coupling reactions derivatives.[9] The condensation reactions of 2-
between active substrates such as organic halides with aminothiphenols with carboxylic acids, aldehydes or
thiols or disulfides.[2] These methods have the other analogous substrates under oxidative conditions
disadvantage of employing prefunctionalized were used to be the most common method to
substrates and usually require precious metal catalysts construct various 2-substituted benzothiazoles.[10]
and ligands as well as various additives to get However, 2-aminothiophenols are less readily
reasonable reaction yield. While numerous available substrates and require multi-step to prepare
approaches to C-C or C-N bond formation through from anilines.[11] In addition, most of these
direct C-H functionalization have been developed in transformations involve the use of harsh reaction
recent years,[3] C-S bond formation via C-H conditions. Anilines are one of the most commonly
functionalization has been much less developed.[4] used synthons in organic synthesis and numerous
Pioneering work by the group of Inamoto in 2008 anilines with various functional groups are easily and
utilized palladium catalyst to synthesize heterocycles commercially available. Therefore, the heterocycle
through intramolecular C-H thiolation.[5] Since then, construction based on aniline substrates is a
various Pd, Cu, Rh, and Ru catalysts have proven to straightforward approach.[12] Recently, we[13] and
be successful at promoting this kind of transformation other[14] have reported various methods for C-S bond
especially for direct thiolation of electron-rich construction via direct C-H functionalization in the
heteroarenes.[4,6] Although effective methods have absence of transition metal catalyst. These methods
been developed for direct C-S bond formation of effectively avoid the poisoning of sulfur-containing
arene C-H bonds, most of them require the use of compounds to transition-metal catalysts. Cheap and
transition-metals and/or active thiolation reagents. In

This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis 10.1002/adsc.201701560

readily available elemental sulfur was successfully the reaction was carried out under nitrogen
used as the sulfur source.[15-16] However, the synthesis atmosphere (entry 10). Decreasing the reaction
of sulfur-containing heterocycles through direct temperature slightly decreased the reaction yield
sulfuration or thiolation of aniline C-H bond has been (entry 11). When the reaction temperature was
rarely reported.[17] As our continuing interest in increased to 150 oC, the desired product was observed
sulfur-containing heterocycle construction using in 66% yield which is lower to the reaction yield at
elemental sulfur as the sulfur source under transition- 140 oC (entry 12).
metal-free conditions,[18] we herein report a three-
component synthesis of 2-substituted benzothiazoles Table2. Substrate scope with respect to styrenesa
using readily available aromatic amines, sulfur
powder and aryl acetylenes or styrenes as the starting
materials.[19]

Table1. Optimization of reaction conditionsa

Accepted Manuscript
Table3. Substrate scope with respect to aryl acetylenesa

We initiated our study by examining the reaction of

naphthalen-2-amine (1a), styrene (2a), and sulfur
powder in 1-methylpyrrolidin-2-one (NMP) under air
(sealed tube) (Table 1). To our delight, the desired
product 3a could be obtained in 54% yield in the
absence of any other additives (entry 1). Then several
iodide-containing additives were screened for this
kind of transformation. The addition of catalytic
amount of iodine and KI both resulted in lower yield
(entries 2 and 3). The reaction yield could be
improved to 67% when 20 mol% of NH4I was added
as the additive (entry 4). Reactions in other organic
solvents such as DMF, DMA and toluene all resulted
in lower yield (entries 5-8). Interestingly, the reaction
yield could be further improved to 88% when
molecular sieves were added to the reaction mixture
(entry 9), which may be attributed to its absorbing
ability of small molecule byproducts such as water Under the optimized reaction conditions, various
and H2S. Similar reaction yield was obtained when styrenes were explored for this kind of reaction (Table

This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis 10.1002/adsc.201701560

2). In general, the reactions between naphthalen-2- We also tried buta-1,3-diyn-1-ylbenzene and isoprene
amine (1a) and the styrene derivatives bearing for this reaction. However, no desired products could
electron-donating groups such as CH3 and OCH3, be observed in both cases.
halogens such Cl and Br on the aromatic ring all gave After screened various styrenes and arylacetylenes
the desired products in good yields. When a fluoro for this three-component procedure, we investigated
substituent presented, the desired product 3d was less reactive aniline substrates. However, the desired
obtained in moderate yield. The reaction activity product 5a was obtained in much lower yield when
between styrene (2a) and (E)-(2-bromovinyl)benzene aniline was used as the substrate. We then re-
(2i) is similar, whereby both gave the same product optimized the reaction conditions and we were
3a in high yield. The position of substituents on the delighted to find that the reactions could be smoothly
phenyl ring significantly affected the reaction yields, performed by increasing the amount of NH4I to 1
and lower yields were obtained when chloro was equiv. and increasing the reaction temperature to 160
o
presented at the ortho or meta position (3g and 3h). C without the addition of 4Å MS (Table 4). Under
Styrenes with a strong electron-withdrawing the modified reaction conditions, moderate to good

Accepted Manuscript
substituent like NO2 or CF3 group were not effective yields were obtained when electron-donating
and only starting materials were observed. substituted anilines were employed (5b-5l). A mixture
of 5h and 5h’ were obtained in 75% combined yield
Table 4. Substrate scope with respect to aromatic aminesa when 3-methylaniline was used as the substrate. To
our delight, single product 5i was obtained in 82%
yield when a bulky substituent was presented at the
meta position of aniline substrate. Various di-methyl-
substituted anilines also worked well under the given
reaction conditions to provide the corresponding
products in good yields (5j-5l). The position of
substituents did not significant affect the reaction
yields.

Table 5. Substrate scope with respect to 2-

acylbenzothiazole formationa

Furthermore, we examined the reactions between

naphthalen-2-amine and various arylacetylenes (Table
3). A series of para-substituted phenylacetylenes
smoothly reacted with 1a and sulfur powder to give
the desired products in moderate to good yields (3a-
3f). High yields were obtained when 4-pentyl-2-
ethynylbenzene (4e) and 4-methoxy-2-
ethynylbenzene (4f) were used as the substrates (3k
and 3c). Functional groups such as fluoro, chloro and
bromo were well tolerated under the given reaction
conditions (3d-3f). High yield was obtained when a
chloro group was located at the ortho position of After we established the 2-alkylbenzothiazole
phenylacetylene (3g). Unfortunately, alkyl-substituted synthesis under transition-metal-free conditions, we
alkenes and alkynes, such as oct-1-ene and oct-1-yne turned our attention to 2-acylbenzothiazole formation
were not effective substrate for this kind of from styrene (2a), aniline (1b) and elemental sulfur
transformation and no desired products could be via a "one-pot, two-step" process (Table 5). After
observed while the starting materials were recovered. systematic optimization of the reaction conditions of

This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis 10.1002/adsc.201701560

the second step, we got the optimized conditions for group. These experimental results further demonstrate
2-acylbenzothiazole: styrene reacted with aniline and that the thioamide is the reaction intermediate of this
elemental sulfur at 160 oC for 44 h using NH4I as the reaction.
additive and then H2O2/DMSO were added to the
reaction and the resulted mixture was further stirred
under oxygen for 24 h. For the model reaction, 6a was
isolated in 60% yield. Various 4-substituented
anilines smoothly reacted with 2a and elemental
sulfur to give the corresponding products in good
yields (6b-6d). Poly-substituted anilines also could be
used as substrates for this kind of transformation to
give the corresponding products in good yields (6e-
6g).

Accepted Manuscript
Scheme 2. Possible reaction mechanism.

On the basis of experimental observations and

previous reports,[20] a possible reaction mechanism is
proposed (Scheme 2). The reaction of aniline (1b)
with elemental sulfur generates an intermediate A.
The addition of A with unsaturated hydrocarbons
affords intermediate B,[15a-c] which further couples
aniline to give intermediate C. Subsequently, S-S
bond cleavage of C occurs to release D and thioamide
E. Oxidative cyclization of E affords the final product
5a, which proceed probably on the assistance of
iodine salt.[21,22] In the oxidative step, we suspect the
combination of sulfur and oxygen play a role of
oxidant in current system, although sulfur could be
the sole oxidant in the absence of oxygen.[23]
In summary, we have developed a novel approach
Scheme 1. Control Experiments. for the synthesis of 2-substituted benzothiazoles from
aromatic amines, sulfur powder and aryl acetylenes or
For the mechanistic studies of this transformation, a styrenes under metal-free conditions. The C-S bond
series of control experiments were conducted. The formation was realized via direct sulfuration of
addition of a scavenger into the reaction system such aromatic amine C-H bond. Elemental sulfur was used
as butylated hydroxytoluene (BHT) did not inhibited as the sulfur source as well as efficient oxidant. The
the reaction under the standard conditions (Scheme addition of NH4I could significantly improve the
1a). This means the reaction probably proceeds reaction yield. This method affords a simple approach
through a non-radical pathway. When the reaction for 2-substituted benzothiazoles from readily
was stopped within 1 h and 5 h, the desired product available starting materials. The detailed mechanism
was observed in both cases, combined with a certain and the further synthetic applications of this reaction
amount of thioamide. Furthermore, similar results are in progress in our laboratory.
were given when phenylacetylene 4a was used
instead of styrene (Scheme 1b). Then we found that Experimental Section
N,2-diphenylethanethioamide (E) could convert into
the desired product 5a in 88% yield (Scheme 1c).
General procedure for2-substituted benzothiazoles
When 2,4,6-trimethylaniline (1m) reacted with 2a or
4a under the standard reaction conditions, a thioamide Naphthalen-2-amine (1a, 72 mg, 0.5 mmol),
intermediate E1 was obtained in 84% and 75% yield, phenylethylene (2a, 24 μL, 0.2 mmol), sulfur (25.6 mg, 0.8
respectively (Scheme 1d). This intermediate could not mmol), NH4I (6 mg, 20 mol%), 4Å MS (100 mg), N-
further convert into the final product since both ortho methyl-2-pyrrolidone (NMP, 0.6 mL) were added to a 10
positions of the amine group were occupied by methyl mL oven-dried reaction vessel. The sealed reaction vessel

This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis 10.1002/adsc.201701560

was stirred at 140 oC for 12 h. After cooling to room [6] For selected examples on metal-catalyzed C-S bond
temperature, the reaction was diluted with ethyl acetate (5 formation based on C-H functionalization, see: a) S.
mL) and washed with saturated sodium chloride solution. Vásquez-Céspdes, A. Ferry, L. Candish, F. Glorius,
The organic layer was separated and the aqueous layer was Angew. Chem. Int. Ed. 2015, 54, 5772; b) Y. F. Liao, Y.
extracted with ethyl acetate for three times. The residue Peng, H. R. Qi, H. Gong, G. J. Deng, C. J. Li, Chem.
was purified by column chromatography on silica gel Commun. 2015, 51, 1031; c) H. M. Yan, Z. L. Huang,
(petroleum ether/ethyl acetate = 40:1) to yield the desired M. Chen, C. T. Li, Y. Chen, M. Gao, A. W. Lei, Org.
product 3a as yellow solid (49 mg, 88% yield), mp 89-90 Biomol. Chem. 2017, 15, 8276; d) F. H. Xiao, S. Q.
o
C. 1H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 8.8 Hz, 1H), Chen, C. Li, H. W. Huang, G. J. Deng, Adv. Synth.
7.95 – 7.82 (m, 3H), 7.55 – 7.48 (m, 2H), 7.43 – 7.35 (m, Catal. 2016, 358, 3881; e) Y. W. Zhao, Y. J. Xie, C. G.
4H), 7.34 – 7.28 (m, 1H), 4.52 (s, 2H); 13C NMR (100 Xia, H. M. Huang, Adv. Synth. Catal. 2014, 356, 2471.
MHz, CDCl3) δ 170.3, 151.2, 137.4, 132.7, 130.8, 129.2,
[7] a) G. Fontana, Curr. Bioact. Compd. 2010, 6, 284; b) T.
128.9, 128.1, 127.4, 127.0, 126.9, 125.8, 125.0, 121.4, 77.3,
D. Bradshaw, S. Wrigley, D. F. Shi, R. J. Schultz, K. D.
77.0, 76.7, 40.6; HRMS (ESI) m/z calcd. for C18H14NS+
Paull, M. F. G. Stevens, Br. J. Cancer 1998, 77, 745; c)
[M+H]+ 276.08415, found 276.08456.

Accepted Manuscript
C. G. Mortimer, G. Wells, J. P. Crochard, E. L. Stone,
T. D. Bradshaw, M. F. G. Stevens, A. D. Westwell, J.
Acknowledgements Med. Chem. 2006, 49, 179; d) B. Tekiner-Gulbas, O.
Temiz-Arpaci, I. Yildiz, N. Altanlar, Eur. J. Med. Chem.
This work was supported by the National Natural 2007, 42, 1293; e) R. S. Keri, M. R. Patil, S. A. Patil, S.
Science Foundation of China (21572194, 21502160, Bugagumpi, Eur. J. Med. Chem. 2015, 89, 207.
21372187), the Collaborative Innovation Center of [8] a) J. P. Zhang, Y. B. Zhang, J. B. Lin, X. M. Chen,
New Chemical Technologies for Environmental Chem. Rev. 2012, 112, 1001; b) S. Rajasekhar, B. Maiti,
Benignity and Efficient Resource Utilization, the K. Chanda, Synlett 2017, 28, 521; c) V. O. Rodionov, S.
Hunan Provincial Innovative Foundation for I. Presolski, S. Gardinier, Y. H. Lim, M. G. Finn, J. Am.
Postgraduate (CX2017B293). Chem. Soc. 2007, 129, 12696.
[9] For selected recent 2-substituted benzothiazole
References synthesis, see: a) D. W. Ma, S. W. Xie, P. Xue, X. J.
Zhang, J. H. Dong, Y. W. Jiang, Angew. Chem. Int. Ed.
[1] a) M. Mellah, A. Voituriez, E. Schulz, Chem. Rev. 2007, 2009, 48, 4222; b) L. Liu, F. Zhang, H. L. Wang, N.
107, 5133; b) A. R. Murphy, J. M. J. Fréchet, Chem. Zhu, B. Liu, H. L. Hong, L. M. Han, Phosphorus,
Rev. 2007, 107, 1066; c) T. Mori, T. Nishimura, T. Sulfur and Silicon 2017, 192, 464.
Yamamoto, I. Doi, E. Miyazaki, I. Osaka, K. Takimiya, [10] For selected examples, see: a) A. R. Wade, H. R.
J. Am. Chem. Soc. 2013, 135, 13900. Pawar, M. V. Biware, R. C. Chikate, Green Chem. 2015,
[2] a) I. P. Beletskaya, V. P. Ananikov, Chem. Rev. 2011, 17, 3879; b) Y. D. Sun, H. F. Jiang, W. Q. Wu, W.
111, 1596; b) T. Kondo, T. Mitsudo, Chem. Rev. 2000, Zeng, X. Wu, Org. Lett. 2013, 15, 1598; c) T. H. Zhu, S.
100, 3205; c) P. Chauhan, S. Mahajan, D. Enders, Y. Wang, G. N. Wang, S. J. Ji, Chem. Eur. J. 2013, 19,
Chem. Rev. 2014, 114, 8807. 5850; d) J. T. Yu, J. Xu, M. Lu, Appl. Organometal.
Chem. 2013, 27, 606; e) M. J. Thompson, H. Adams, B.
[3] For recent reviews on C-H activation, see: a) D. A. Chen, J. Org. Chem. 2009, 74, 3856; f) B. Shi, A. Blake,
Colby, R. G. Bergman, J. A. Ellman, Chem. Rev. 2010, I. B. Campbell, B. D. Judkins, C. J. Moody, Chem.
110, 624; b) T. W. Lyons, M. S. Sanford, Chem. Rev. Commun. 2009, 3291; g) M. S. Mayo, X. Q. Yu, X. Y.
2010, 110, 1147; c) S. H. Cho, J. Y. Kim, J. Kwak, S. Zhou, X. J. Feng, Y. Yamamoto, M. Bao, Org. Lett.
Chang, Chem. Soc. Rev. 2011, 40, 5068; d) J. Wencel- 2014, 16, 764.
Delord, T. Dröge, F. Liu, F. Glorius, Chem. Soc. Rev.
2011, 40, 4740; e) L. Ackermann, Chem. Rev. 2011, [11] a) M. T. Bogert, L. Smidth, J. Am. Chem. Soc. 1928,
111, 1315; f) L. McMurray, F. O’Hara, M. J. Gaunt, 428; b) T. B. Shaik, S. M. Ali Hussaini, V. L. Nayak, M.
Chem. Soc. Rev. 2011, 40, 1885; g) C. S. Yeung, V. M. L. Sucharitha, M. S. Malik, A. Kamal, Bio. Med. Chem.
Dong, Chem. Rev. 2011, 111, 1215; h) Z. Shi, C. Zhang, Lett. 2017, 27, 2549; c) P. K. Sharma, A. Fogla, B. S.
C. Tang, N. Jiao, Chem. Soc. Rev. 2012, 41, 3381; i) K. Rathore, M. Kumar, Res. Chem. Intermed. 2011, 37,
M. Engle, T. S. Mei, M. Wasa, J. Q. Yu, Acc. Chem. 1103.
Res. 2012, 45, 788; j) G. Song, F. Wang, X. Li, Chem. [12] For an example on 2-aminobenzothiazole synthesis
Soc. Rev. 2012, 41, 3651; k) Y. Qin, L. H. Zhu, S. Z. from anilines excess potassium thiocyanate and sodium
Luo, Chem. Rev. 2017, 117, 9433. dichloroiodate, see: V. N. Telvekar, H. M. Bachhav, V.
[4] For a review on direct C-S bond formation: C. Shen, P. K. Bairwa, Synlett 2012, 23, 2219.
Zhang, Q. Sun, S. Bai, T. S. Andy Hor, X. Liu, Chem. [13] a) F. H. Xiao, H. Xie, S. W. Liu, G. J. Deng, Adv.
Soc. Rev. 2015, 44, 291. Synth. Catal. 2014, 356, 364; b) F. H. Xiao, H. Chen, H.
[5] K. Inamoto, Y. Arai, K. Hiroya, T. Doi, Chem. Xie, S. Q. Chen, L. Yang, G. J. Deng, Org. Lett. 2014,
Commun. 2008, 5529. 16, 50; c) F. H. Xiao, S. Q. Chen, Y. Chen, H. W.
Huang, G. J. Deng, Chem. Commun. 2015, 51, 652; d)

This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis 10.1002/adsc.201701560

F. H. Xiao, S. Q. Chen, J. X. Tian, H. W. Huang, G. J. from N-substituted arylamines and elemental sulfur. For
Deng, Y. J. Liu, Green Chem. 2016, 18, 1538. our work, the three-component reaction was realized
using anilines as the substrate and aryl acetylenes and
[14] a) F. L. Yang, S. K. Tian, Angew. Chem. Int. Ed. 2013,
styrenes were used as the alkylation reagents. c) X. M.
52, 4929; b) J. W. Yuan, X. Ma, H. Yi, C. Liu, A. W.
Zhu, Y. Z. Yang, G. H. Xiao, J. X. Song, Y. Liang, G.
Lei, Chem. Commun. 2014, 50, 14386; c) Y. M. Lin, G.
B. Deng, Chem. Commun. 2017, 53, 11917.
P. Lu, G. X. Wang, W. B. Yi, Adv. Synth. Catal. 2016,
358, 4100; d) S. K. R. Parumala, R. K. Peddinti, Green [18] a) J. J. Chen, G. Z. Li, Y. J. Xie, Y. F. Liao, F. H. Xiao,
Chem. 2015, 17, 4068; e) T. Hostier, V. Ferey, G. Ricci, G. J. Deng, Org. Lett. 2015, 17, 5870; b) H. Xie, J. H.
D. G. Pardo, J. Cossy, Chem. Commun. 2015, 51, Cai, Z. L. Wang, H. W. Huang, G. J. Deng, Org. Lett.
13898; f) T. Hostier, V. Ferey, G. Ricci, D. G. Parado, J. 2016, 18, 2196; c) P. H. Ni, B. Li, H. W. Huang, F. H.
Cossy, Org. Lett. 2015, 17, 3898; g) Y. Wang, F. Zhao, Xiao, G. J. Deng, Green Chem. 2017, 19, 5553; d) B. Li,
Y. Chi, W. X. Zhang, Z. F. Xi, J. Org. Chem. 2014, 79, P. H. Ni, H. W. Huang, F. H. Xiao, G. J. Deng, Adv.
11146; h) Y. Wang, F. Zhao, Y. Zhou, Y. Chi, Z. T. Synth. Catal. 2017, 359，4300.
Wang, W. X. Zhang, Z. F. Xi, Chem. Eur. J. 2013, 19,
[19] Reaction for 2-bnezylbenzothiazole formation using

Accepted Manuscript
10643; i) Y. Wang, W. X. Zhang, Z. T. Wang, Z. F. Xi,
simple styrenes or arylacetylenes is rare. For an
Angew. Chem. Int. Ed. 2011, 50, 8122; j) Z. T. Wang, Y.
example on 2-benzylbenzoxazole formation from
Wang, W. X. Zhang, Z. M. Hou, Z. F. Xi, J. Am. Chem.
highly functionalized 1,1-dibromoethenes or (2-
Soc. 2009, 131, 15108.
bromoethynyl)benzene, see: X. S. Fan, Y. He, X. Y.
[15] For excellent reviews on using elemental sulfur for C- Zhang, S. H. Guo, Y. Y. Wang, Tetrahedron 2011, 67,
S bond construction, see: a) T. B. Nguyen, Adv. Synth. 6369.
Catal. 2017, 359, 1066; b) T. B. Nguyen, Asian J. Org.
[20] a) Y. N. Cheng, J. Yang, Y. Qu, P. X. Li, Org. Lett.
Chem. 2017, 6, 477; c) H. Liu, X. F. Jiang, Chem. Asian
2012, 14, 98; b) X. Y. Qian, S. Q. Li, J. S. Song, H. C.
J. 2013, 8, 2546; d) I. P. Beletskaya, V. P. Ananikov,
Xu, ACS Catal. 2017, 7, 2730.
Chem. Rev. 2011, 111, 1596; e) M. Mellah, A.
Voituriez, E. Schulz, Chem. Rev. 2007, 107, 5133. [21] a) G. T. Zhang, C. Liu, H. Yi, Q. Y. Meng, C. L. Bian,
H. Chen, J. X. Jian, L. Z. Wu, A. W. Lei, J. Am. Chem.
[16] For selected examples: a) L. A. Nguyen, Q. A. Ngo, P.
Soc. 2015, 137, 9273; b) V. Reg, S. M. Soria-Castro, J.
Retailleau, T. B. Nguyen, Green Chem. 2017, 19, 4289;
E. Argüello, A. B. Peñéñorg, Tetrahedron Lett. 2009,
b) T. B. Nguyen, P. Retaillean, Org. Lett. 2017, 19,
50, 4720; c) F. M. Moghaddam, D. Zargarani, J. Sulfur
4858; c) T. B. Nguyen, P. Retaillean, Org. Lett. 2017,
Chem. 2009, 30, 507.
19, 3879; d) T. B. Nguyen, P. Retailleau, Org. Lett.
2018, 20, 186; e) T. B. Nguyen, L. Ermolenko, A. Al- [22] N. K. Downer-Riley, Y. A. Jackson, Tetrahedron 2008,
Mourabit, Org. Lett. 2013, 15, 4218; f) T. B. Nguyen, K. 64, 7741.
Pasturaud, L. Ermolenko, A. Al-Mourabit, Org. Lett.
[23] a) Y. Xie, X. Chen, Z. Wang, H. Huang, B. Yi, G.-J.
2015, 17, 2562; g) T. B. Nguyen, L. Ermolenko, P.
Deng, Green Chem. 2017, 19, 4294; b) G. Li, J. Jiang, F.
Retaillean, A. Al-Mourabit, Angew. Chem. Int. Ed.
2014, 53, 13808; h) L. K. Meng, T. Fujikawa, M. Zhang, F. Xiao, G.-J. Deng, Org. Biomol. Chem. 2017,
Kuwayama, Y. Segawa, K. Itami, J. Am. Chem. Soc. 15, 10024; c) T. B. Nguyen, P. Retailleau, Adv. Synth.
Catal. 2017, 359, 3843.
2016, 138, 10351; i) Z. Y. Gu, J. J. Guo, S. Y. Wang, S.
J. Ji, Chem. Sci. 2016, 7, 4067; j) G. T. Zhang, H. Yi, H.
Chen, C. L. Bian, C. Liu, A. W. Lei, Org. Lett. 2014, 16,
6156; k) X. Wang, D. Z. Miao, X. T. Li, R. H. Hu, Z.
Yang, R. Gu, S. Q. Han, Tetrahedron 2017, 73, 5194; l)
Z. Zhou, M. C. Liu, S. Sun, E. Yao, S. Q. Liu, Z. W.
Wu, J. T. Yu, Y. Jiang, J. Cheng, Tetrahedron Lett.
2017, 58, 2571; m) X. Zhu, Y. Yang, G. Xiao, J. Song,
Y. Liang, G. Deng, Chem. Commun. 2017, 53, 11917; n)
J.-R. Zhang, Y.-Y. Liao, J.-C. Deng, K.-Y. Feng, M.
Zhang, Y.-Y. Ning, Z.-W. Lin, R.-Y. Tang, Chem.
Commun. 2017, 53, 7784; o) J.-R. Zhang, L.-Z. Zhan, L.
Wei, Y.-Y. Ning, X.-L. Zhong, J.-X. Lai, L. Xu, R.-Y.
Tang, Adv. Synth. Cat. DOI: 10.1002/adsc.201701190;
p) J.-C. Deng, S.-B. Zhuang, Q.-Z. Liu, Z.-W. Lin, Y.-L.
Su, J.-H. Chen. R.-Y. Tang, RSC Adv. 2017, 7, 54013.
[17] For three-component heterocycle formation from
anilines elemental sulfur, see: a) X. Z. Che, J. J. Jiang,
F. H. Xiao, H. W. Huang, G. J. Deng, Org. Lett. 2017,
19, 4576; b) G. Z. Li, H. Xie, J. J. Chen, Y. J. Guo, G. J.
Deng, Green Chem. 2017, 19, 4043. During the
preparation of our manuscript, Liang and co-workers
published a two-component benzothiazole formation

This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis 10.1002/adsc.201701560

COMMUNICATION
Aniline ortho C-H Sulfuration/Cyclization with
Elemental Sulfur for Efficient Synthesis of 2-
Substituted Benzothiazoles under Metal-Free
Conditions

Adv. Synth. Catal. Year, Volume, Page – Page

Jingjing Jiang, Guozheng Li, Feng Zhang,*

Hao Xie, Guo-Jun Deng*

Accepted Manuscript

This article is protected by copyright. All rights reserved.