Catalyst-free thiolation of indoles with sulfonyl hydrazides for the synthesis of 3-sulfenylindoles in water

Article abstract of DOI:10.1039/c6gc00313c

A catalyst-free thiolation of indoles with sulfonyl hydrazides was efficiently developed in water under mild conditions without any ligand or additive. The reaction provided a variety of 3-sulfenylindoles with good to excellent yields and the only by-products were nitrogen and water.

Full text of DOI:10.1039/c6gc00313c

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Catalyst-free thiolation of indoles with sulfonyl hydrazides for the
synthesis of 3-sulfenylindoles in water
Yu Yang, Sheng Zhang, Lin Tang, Yanbin Hu, Zhenggen Zha and Zhiyong Wang*a
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
A catalystꢀfree thiolation of indoles with sulfonyl hydrazides was efficiently developed in water under
mild conditions without any ligand or additive. The reaction provided a variety of 3ꢀsulfenylindoles with
good to excellent yields and the byꢀproducts were only nitrogen and water.
Indroduction
10 The formation of CꢀS bonds represents a key step in the chemical
synthesis because of their prevalence in many biologically active
compounds and organic materials.1 In the past decade, for
constructing CꢀS bonds, the metalꢀcatalyzed direct CꢀH
activation, in which involved the use of the complexes and salts
15 of palladium,2 copper,3 rhodium,4 ruthenium,5 and iron,6 has
become one of the traditional dominant methods (Figure 1a).
However, with the desire of chemists to minimize synthetic steps
and the amount of toxic waste in the construction of CꢀS bond,
and, moreover, to find milder and more selective transformations,
20 the concepts of green chemistry7 have witnessed explosive
developments in the past few years due to their advantages. As a
consequence of the often green chemical character, usually these
green
and
sustainable procedures
involved
various
heterocatalysis,8 metalꢀfree catalysis9 or catalystꢀfree synthesis.10
3ꢀsulfenylindoles as one of the most common motifs based on
the formation of CꢀS bonds, represent pharmaceutically and
biologically important structures with their broad spectrum of
biological and pharmaceutical activities, including antiꢀHIV
activity, inhibitory activity against tubulin polymerization, antiꢀ
25
30 cancer activity, antiꢀobesity activity and so on.11 With continued
interest in the concepts of green chemistry, much effort has been
devoted to the development of simple and general synthetic
methods to access this structural moiety. Also, some significant
improvements have been made in recent years. Of the many
35 methods developed, the employment of iodine,12 base, or
nanoparticles for the tansformations to circumvent the need of the
aforementioned transitionꢀmetal complexes and salts has
remained one of the most widely adopted approaches (Figure 1b).
For instance, in 2013, Tian et al. developed an iodineꢀcatalyzed
40 regioselective sulfenylation of indoles with sulfonyl hydrazides
(Figure 1c).13 Subsequently, baseꢀpromoted sulfenylation
reactions to synthesize 3ꢀsulfenylated indoles have been recently
developed by Zhang14 and Wen,15 in which few examples of
indoles were described with disulfides and thiols as the thiol
45 source respectively.
Figure 1. a) The metalꢀcatalyzed direct CꢀH activation to contrast CꢀS
bonds; b) iodineꢀcatalyzed or baseꢀpromoted 3ꢀsulfenylation of indoles; c)
50 iodineꢀcatalyzed sulfenylation of indoles with sulfonyl hydrazides; d)
heterogeneously catalyzed direct CꢀH thiolation of heteroarenes; e)
catalystꢀfree thiolation of indoles in water.
And very recently, a general methodology for the direct thiolation
of electronꢀrich heteroarenes was developed by Glorius and coꢀ
55 workers, in which Pd/Al2O3, a recoverable and commercially
available heterogeneous catalyst, and CuCl2 were employed
(Figure 1d).16 However, the catalyst, additive and toxic organic
solvent were employed in these reactions, which leaded to the
concerns on the environmental amity. Particularly, for the request
60 of environmental benignity and economical cost, the new
methodology under catalystꢀfree conditions in water still remains
an ongoing challenge for organic chemists.17
As a continuation of our interest in inꢀwater and onꢀwater
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DOI: 10.1039/C6GC00313C
green chemical methodologies in organic synthesis,10a,18 and,
moreover, in view of the importance of 3ꢀsulfenylindoles and 30 Rising the temperature had no effect on the yield while lowering
Screening of the temperature indicated 140 °C to be optimal.
related scaffolds, we report herein on a simple water promoted
thiolation of indoles with sulfonyl hydrazides (Figure 1e). In
combination with recent reports on the direct CꢀH thiolation to
construct 3ꢀsulfenylindoles, this methodology can be carried out
the reaction temperature decreased the yields largely (Table 1,
entries 5ꢀ7). When the water was replaced with organic solvents,
the yeilds of the products decreased a lot, affording few or trace
amount of the desired products (Table 1, entries 8ꢀ15). This
5
in water without any catalyst, ligand or additive, affording a 35 implied that the water promoted this thiolation. When the reaction
much more environmentally benign and economical way.
was subjected to air atmosphere instead of nitrogen, a relatively
lower yield was obtained (Table 1, entry 16). After screening, 1a
with 2a in the presence of nitrogen at 140 °C using water as the
solvent was optimized as the optimal reaction conditions.
Results and discussion
10 At the outset of this investigation, indoles (1a) and 4ꢀ
methylbenzenesulfonhydrazide (2a) were used as the substrates,
while Pd/DNA was dispersed in water18 as a catalyst to optimize
the reaction conditions. The reaction afforded the 3ꢀsulfenylated
product 3aa in only 25% yield, with a recovery of the starting
15 materials (Table 1, entry 1). Similarly, Au/DNA catalyst gave a
poor result with a yield of 23%. In order to increase the
temperature, the template of the nanoꢀcatalyst was changed into
titanium dioxide and carbon respectively, affording the
corresponding product with 67% and 68% yield respectively
20 (Table 1, entry 3 and 4). As different nanoꢀmetals has little effect
on the yields (Table 1, entries 1ꢀ4), we then carried out the
reaction in the absence of catalyst. Surprisingly the reaction could
give the product 3aa with a yield of 68% in net water (Table 1,
entry 5).
40
With the optimal conditions in hand, the scope of this
transformation was subsequently investigated. The examples of
the reactions between indoles and sulfonyl hydrazides were
presented in Scheme 1. The optimized reaction conditions were
found to be applicable to a series of substituted aryl sulfonyl
45 hydrazides (2a-s) and indoles (1a-l), affording the corresponding
products with moderate to excellent yields in most cases. The
effect of substituents on the aryl ring of the sulfonylhydrazides
was examined. It was found that
a
variety of aryl
sulfonylhydrazides could be converted to the desired products
50 (3aa−3am) in good to excellent yields regardless of electronꢀ
t
donating groups (R = Me, Pr, Bu, OMe, OCF3) or electronꢀ
withdrawing groups (R = F, Cl, Br, CN, CF3, NO2) on the phenyl
ring. In general, the substrates with electronꢀdonating groups on
the phenyl ring gave slightly higher yields (3aa–3af) than that of
55 electronꢀwithdrawing groups (3ag–3am). Nevertheless, the steric
hindrance had great influence on the reaction. For instance,
orthoꢀnitro benzeneꢀsulfonylhydrazides afforded a trace amount
25 Table 1 Optimization of the reaction conditionsa
of
the
desired
product
3an.
Disubstituted
benzenesulfonylhydrazides can also be employed as the reaction
60 substrates, furnishing the thiolation product 3ao and 3ap with
good yields. It is notable that different positions of the
substituents on the naphthalene significantly affected the reaction
activity. For instance, 3aq was obtained with a yield of in 99%
while 3ar was generated with a yield of 67% . When the aryl ring
65 of the sulfonylhydrazide was replaced by the thiophene ring, the
correponding thiolation product was hardly obtained.
Next, the scope of the indoles was examined. As shown in
Scheme 3, the indoles with various functional groups can be
transformed into the desired products (3bb-3lb) smoothly. Either
70 the electronic effect or the steric effect had little influence on the
reaction except for the strong electronꢀwithdrawing nitroꢀgroup
(3ib) and big block ester group (3kb). For example, different
substituents on 1ꢀ, 2ꢀ, 4ꢀ, 5ꢀ, and 6ꢀpositon of the indole ring
could give the desired product with good yields (3bbꢀ3gb) in
75 spite of the substitution at different position. As for the substrate
1i, bearing nitro group on the indole ring, the thiolation was
sluggish to afford the thiolation product 3ib with a low yield of
35%. Pleasingly,
a Nꢀheteroarylꢀbearing indole could be
performed well in the reaction, giving the corresponding product
80 with a yield of 65% (Scheme 1, 3kb). Encouraged by this green
synthesis, simple manipulation and a broad scope of the reaction
substrates of this developed methodology, we then proceeded to
conduct scaleꢀup experiments to examine the synthetic utility.
a Reaction conditions: 1a (0. 1 mmol), 2a (0.25 mmol), catalyst (2 mol %),
solvent (1 mL), under N2, 24 h. b Isolated yields based on 1a, c under air.
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Scheme 2. The scaleꢀup reaction: 1a (7.5 mmol) and 2a (18.75 mmol) in
20 mL of H2O, 140 °C, under N2, 24 h. Product 3aa was isolated in 78%
yeild.
When 7.5 mmol of indole 1a was reacted with 18.75 mol of 4ꢀ
methylphenylꢀsulfonhydrazide 2a, the corresponding product 3aa
can be obtained with a satisfactory yield of 78%, demonstrating a
great potential in parmaceutical synthesis (Scheme 2). The
method could be used to prepare precursors of some important
bioactive molecules.
5
Scheme 4. The proposed mechanism for the reaction.
10 Studies on the reaction mechanism
Conclusions
To get an insight into the mechanism of the thiolation process,
several controlled experiments were conducted. First, the
beheviour of the sulfonyl hydrazides under the standard
conditions was conducted. When the 4ꢀmethylbenzene
15 sulfonhydrazide (2a) alone was employed, the reaction afforded
1,2-dipꢀtolyldisulfane (4) in 25% yield and 4ꢀmethylbenzeneꢀ
sulfonothioic acid Sꢀ(4ꢀmethylphenyl) ester (5) in 57% yield
(Scheme 3b). Subsequently, using 4 as the reagent under the
standard conditions had no reaction while employing 5 could
20 afford 3aa in 88% yield (Scheme 3b and 3c), suggesting that 4ꢀ
methylbenzeneꢀsulfonothioic acid Sꢀ(4ꢀmethylphenyl) ester (5)
might be an intermediate in this reaction. It is noteworthy that the
reaction mixture was weak acidic at the end of the reaction,
which indicate that a small amount of acid is produced.
40 A waterꢀpromoted thiolation of indoles with sulfonyl hydrazides
was developed, affording 3ꢀsulfenylindoles with good to
excellent yields. This thiolation can be carried out under
environmentally benign conditions without any catalyst, additive,
ligand or organic solvent. Also, the byꢀproducts were nitrogen
45 and water, no any pollution on the environment. Besides, the
reaction has a broad scope of the reaction substrates, a variety of
functional groups can tolerate the reaction conditions well.
Ongoing research including further mechanistic details,
expanding the substrate scope and applications in organic
50 synthesis are currently underway.
Experimental
A mixture of arylsulfonyl hydrazides (0.25 mmol) and indoles
(0.1 mmol) in water (1 mL) was put into a schlenk at 140 °C
under magnetic stirring for 24 h under nitrogen. After the reaction
55 was finished, the mixture was extracted with EtOAc (3 × 5 mL)
and then the combined organic extracts were washed with brine
(15 mL), dried over sodium sulfate, and filtered. The solvent was
removed under reduced pressure and the residue was purified by
flash column chromatography (hexane/ethyl acetate = 6:1) to give
60 compound 3.
Acknowledgements
25
We are grateful to the National Nature Science Foundation of
China (21272222, 91213303, 21172205, J1030412).
Scheme 3. Mechanistic investigations of the thiolation process.
On the basis of the aforementioned investigations and previous
reports,3,13,19 a possible reaction pathway was proposed and
depicted in scheme 4. Initially, sulfonylhydrazides transform into
30 minor product 4 and major intermediate 5 which can dissociate
into 6 in the presence of water. Subsequently, the FriedelꢀCrafts
process happens between 6 and indoles, affording intermediate 7
and 8. The intermediate 7 resonates with sulfurꢀcentered anion 9,
which can form sulfinic acids 10 in the presence of water. At the
35 same time, the intermediate 8 quickly tansforms into product 3aa
with the release of hydrogen ion.
Notes and references
65 a Hefei National Laboratory for Physical Sciences at Microscale, CAS
Key Laboratory of Soft Matter Chemistry and Department of Chemistry &
Collaborative Innovation Center of Suzhou Nano Science and
Technology, University of Science and Technology of China, Hefei,
230026, P. R. China. Fax: (+86) 551-360-3185; E-mail:
70 zwang3@ustc.edu.cn
† Electronic Supplementary Information (ESI) available: Experimental
Details, characterization of catalysts and characterization of products. See
DOI: 10.1039/b000000x/
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1. (a) Y T. Kondo, T.Mitsudo, Chem. Rev., 2000, 100, 3205; (b) C.
Shen, P. Zhang, Q. Sun, S. Bai, T. S. Andy Hor, X. Liu, Chem. Soc.
Rev., 2015, 44, 291; (c) L.ꢀH. Zou, J. Reball, J. Mottweiler and C.
Bolm, Chem. Commun., 2012, 48, 11307; (d) S. R. Neufeldt and M.
S. Sanford, Acc. Chem. Res., 2012, 45,936; (e) C. Zhang, C. Tang
and N. Jiao, Chem. Soc. Rev., 2012, 41, 3464.
2. (a) Z. Duan, S. Ranjit, P. Zhang and X. Liu, Chem. Eur. J., 2009, 15,
3666; (b) K. Inamoto, Y. Arai, K. Hiroya and T. Doi, Chem.
Commun., 2008, 5529; (c) M . A. FernándezꢀRodríguez, Q. Shen and
J. F. Hartwig, Chem. Eur. J., 2006, 12, 7782; (d) M. A. Fernándezꢀ
Rodríguez, Q. L. Shen and J. F. Hartwig, J. Am. Chem. Soc., 2006,
128, 2180; (e) K. Inamoto, C. Hasegawa, K. Hiroya and T. Doi, Org.
Zhou, PCT Int. Appl, WO 0130343, 2001; (f) V. S. N. Ramakrishna,
V. S. Shirsath, R. S. Kambhampati, S. Vishwakarma, N. V.
Kandikere, S. Kota and V. Jasti, PCT Int. Appl, WO 2007020653,
2007; (g) M. Nuth, H. Guan, N. Zhukovskaya, Y. L. Saw and R. P.
Ricciardi, J. Med. Chem., 2013, 56, 3235.
75
5
10
15
20
25
30
35
40
45
50
55
60
65
70
12. (a) J. B. Azeredo, M. Godoi, G. M. Martins, C. C. Silveira and A. L.
Braga, J. Org. Chem., 2014, 79, 4125; (b) C.ꢀR. Liu and L.ꢀH. Ding,
Org. Biomol. Chem., 2015,13, 2251; (c) W. Ge and Y. Wei, Green
Chem., 2012, 14, 2066.
13. F.ꢀL. Yang and S.ꢀK. Tian, Angew. Chem. Int . Ed., 2013, 52, 4929.
14. P. Sang, Z. Chen, J. Zou and Y. Zhang, Green Chem., 2013, 15, 2096.
15. Y. Liu, Y. Zhang, C. Hu, J.ꢀP. Wan and C. Wen, RSC Adv.,2014, 4,
35528.
80
Lett.,2008, 10, 5147; (f) X. Zhao, E. Dimitrijević and V. M. Dong, J.
Am. Chem. Soc., 2009, 131, 3466; (g) M. Iwasaki, M. Iyanaga, Y. 85 16. S. VásquezꢀCéspedes, A. Ferry, L. Candish and F. Glorius,
Tsuchiya, Y. Nishimura, W.ꢀJ. Li, Z.ꢀP. Li and Y. Nishihara, Chem.
Eur. J. , 2014, 20, 2459.
Angew.Chem. Int. Ed., 2015, 54, 5772.
17. (a) C.ꢀJ. Li and L. Chen, Chem. Soc. Rev., 2006, 35, 68; (b) G. V.
Oshovsky, D. N. Reinhoudt, and W. Verboom, Angew. Chem . Int.
Ed., 2007, 46, 2366; (c) A. Chanda and V. V. Fokin, Chem. Rev.,
2009, 109, 725; (d) M. B. Gawande, V. D. B. Bonifácio, R. Luque, P.
S. Brancoa and R. S. Varma, Chem. Soc. Rev., 2013, 42, 5522; (e) W.
Liu, L. Li and C.ꢀJ. Li, Nat. Commun., 2015, 6, 6526.
3. (a) X.ꢀW. Li, Y.ꢀL. Xu, W.ꢀQ. Wu, C. Jiang, C.ꢀR. Qi, and H. Jiang,
Chem. Eur. J., 2014, 20, 7911; (b) J. Cheng, C. Yi, T.ꢀJ. Liu and C.
Lee, Chem. Commun., 2012, 48, 8440; (c) L. D. Tran, I. Popov and
O. Daugulis, J. Am. Chem. Soc., 2012, 134, 18237; (d) Z. Wu, H.
Song, X. Cui, C. Pi, W. Du and Y. Wu, Org. Lett., 2013, 15, 1270;
(e) A. Zhou, X. Liu, K. Yang, S. Zhao and Y. Liang, Org. Biomol.
Chem., 2011, 9, 5456; (f) S. Zhang, P. Qian, M. Zhang, M. Hu and J.
90
18. (a) Y. Wang, D.ꢀP. Zhu, L. Tang, S.ꢀJ. Wang, Z. Wang, Angew.
Chem. Int. Ed., 2011, 50, 8917.
Cheng, J. Org. Chem., 2010, 75, 6732; (g) X. Chen, X.ꢀS. Hao, C. E. 95 19. X. Zhao, L. P. Zhang, T. Li, G. Liu, H. Wang and K. Lu, Chem.
Goodhue and J.ꢀQ. Yu, J. Am. Chem. Soc., 2006, 128, 6790.
4. (a) M. Arisawa, K. Fujimoto, S. Morinaka and M. Yamaguchi, J. Am.
Chem. Soc., 2005, 127, 12226; (b) Y.ꢀX. Yang, W. Hou, L.ꢀH. Qin,
J.ꢀJ. Du, H.ꢀJ. Feng, B. Zhou and Y.ꢀC. Li, Chem. Eur. J., 2014, 20,
416; (c) M. Arisawa, F. Toriyama and M. Yamaguchi, Tetrahedron
Lett., 2011, 52, 2344.
5. (a) M. Chen, Z.ꢀT. Huang and Q.ꢀY. Zheng, Chem. Commun., 2012,
48, 11686; (b) O. Saidi, J. Marae, A. E. W. Ledger, P. Liu, M. F.
Mahon, G. KociokꢀKo¨hn, M. K. Whittlesey and C. G. Frost, J.
Am.Chem. Soc., 2011, 133, 19298; (c) Y. Cheng, J. Yang, Y. Qu and
P. Li, Org. Lett., 2012, 14, 98.
6. (a) H. Wang, L. Wang, J. Shang, X. Li, H. Wang, J. Gui and A. Lei,
Chem. Commun., 2012, 48, 76.
7. (a) C.ꢀJ. Li, B. M. Trost, Proc. Natl. Acad. Sci., 2008, 105, 13197; (b)
M.ꢀO. Simon and C.ꢀJ. Li, Chem. Soc. Rev., 2012, 41, 1415; (c) P.
Anastas, N. Eghbali, Chem. Soc. Rev., 2010, 39, 301; (d) T. P. Loh
and G.ꢀL. Chua, Chem. Commun., 2006, 2739.
Commun., 2014, 50, 13121.
8. (a) A. R. Rosario, K. K. Casola, C. E. S. Oliveira and G. Zeni, Adv.
Synth. Catal., 2013, 355, 2960.
9. (a) C. Sun, H. Li, D. Yu, M. Yu, X. Zhou, X. Lu, K. Huang,S. Zheng,
B. Li and Z. Shi, Nat. Chem., 2010, 2, 1044; (b) Q.ꢀQ. Lu, J. Zhang,
F.ꢀL. Wei, Y. Qi, H.ꢀM. Wang, Z.ꢀL. Liu and A. Lei, Angew. Chem.
Int. Ed., 2013, 52, 7156; (c) Q.ꢀQ Lu, J. Zhang, G.ꢀL. Zhao, Y. Qi,
H.ꢀM. Wang, and A. Lei, J. Am. Chem. Soc., 2013, 135, 11481; (d)
R. Tang, Y. Xie, Y. Xie, J. Xiang and J. Li, Chem. Commun., 2011,
47, 12867; (e) S.ꢀR. Guo, Y.ꢀQ. Yuan and J.ꢀN. Xiang, Org. Lett.,
2014, 15, 4654; (f) W. Ge and Y. Wei, Green Chem., 2012, 14, 2066;
(g) Y.ꢀP. Zhu, M. Lian, F.ꢀC. Jia, M.ꢀC. Liu, J.ꢀJ. Yuan, Q.ꢀH. Gao
and A.ꢀX. Wu, Chem. Commun., 2012, 48, 9086; (h) C. Chen, L.ꢀL.
Chu and F. Qing, J. Am. Chem. Soc., 2012, 134,12454; (i) L. Zou, J.
Reball, J. Mottweiler and C. Bolm, Chem. Commun., 2012, 48, 11307;
(j) P. Sang, Z.ꢀK. Chen, J.ꢀW. Zou and Y.ꢀH. Zhang, Green Chem.,
2013, 15, 2096; (k) Q. Wu, D.ꢀB. Zhao, X.ꢀR. Qin, J.ꢀB. Lan and J.ꢀS.
You, Chem. Commun., 2011, 47, 9188.
10. (a) Y. Yang, L. Tang, S. Zhang, X. Guo, Z. Zha, and Z. Wang, Green
Chem., 2014, 16, 4106; (b) T. Miao, P.ꢀH. Li, Y.ꢀC. Zhang, and L.
Wang, Org. Lett., 2015, 17, 832.
11. (a) R. Silvestri, G. De Martino, G. La Regina, M. Artico, S. Massa, L.
Vargiu, M. Mura, A. G. Loi, T. Marceddu, P. La Colla, J. Med.
Chem., 2003, 46, 2482; (b) R. Ragno, A. Coluccia, G. La Regina, G.
De Martino, F. Piscitelli, A. Lavecchia, E. Novellino, A. Bergamini,
C. Ciaprini, A. Sinistro, G. Maga, E. Crespan, M. Artico and R.
Silvestri, J. Med. Chem., 2006, 49, 3172; (c) Y. Maeda, M. Koyabu,
T. Nishimura and S. Uemura, J. Org. Chem., 2004, 69, 7688; (d) G.
La Regina, M. C. Edler, A. Brancale and R. Silvestri, J. Med. Chem.,
2007, 50, 2865; (e) J. P. Berger, T. W. Doebber, M. Leibowitz, D. E.
Moller, R. T. Mosley, R. L. Tolman, J. Ventre, B. B. Zhang and G.
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A water promoted thiolation of indoles with sulfonyl hydrazides developed under mild conditions in
water