A Pd-catalyzed optional approach for the synthesis of dibenzothiophenes

Article abstract of DOI:10.1039/c8ob00235e

A direct and practical approach for the construction of DBTs was developed via a Pd-catalyzed tandem reaction, in which commercially available o-bromo-iodobenzenes combined with benzene thiols or iodobenzenes combined with o-bromo-benzene thiols were applied. These two approaches will provide an alternative for the synthesis of DBT derivatives.

Full text of DOI:10.1039/c8ob00235e

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
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A Pd-Catalyzed Optional Approach for the Synthesis of
Dibenzothiophenes
Juan Songa,*, Hao Wua, Wei Sunb, Songjiang Wanga, Haisen Suna, Kang Xiaoa, Yan Qiana and Chao
Liub,*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
A direct and practical approach for the construction of DBTs was electron mobility, fluorescence quantum efficiency and
developed via
Pd-catalyzed tandem reaction, in which thermal stability.15-18
commercially available o-bromo-iodobenzenes combined with Due to the numerous successful applications of fused
a
benzene thiols or iodobenzenes combined with o-bromo-benzene thiophene scaffolds across a wide range of fields, a number of
thiol were applied. These two approaches will provide an methods for the efficient synthesis of DBTs have been
alternative for the synthesis of DBT derivatives.
established in recent years (Scheme 1). However, except that
few examples reported by Antonchick19 and McNab20 that
using aryl benzylsulfoxides and phenyl 2-allythiobenzoates as
substrates respectively, most of methods were based on the
annulation of biphenyl21-26 (Scheme 1, type A) or diaryl sulfides
(or sulfoxides) derivations (Scheme 1, type B).27-35 These
methods were usually limited by their reliance on necessities
of prefunctionalized materials or multistep procedures, which
were less atom-economical and less environmentally friendly.
Thus, developing novel methods based on simple and
commercially available chemicals is of great interest and “one-
pot” or tandem-type strategy is appealing.
Establishing simple and efficient experimental procedure to
access value-added structures is one of the long-lasting goals
in organic synthesis. Guided by this goal, the simple multiple
bond-forming “one-pot” or tandem-type strategy has attracted
much attention, in which multiple chemical transformations
are performed sequentially in a single reaction vessel without
intermediary purification. Herein, an efficient tandem-type
reaction for the synthesis of dibenzothiophene (DBT)
derivatives is presented in the presence of palladium catalyst.
DBT derivatives constitute a privileged class of scaffolds with
numerous application in pharmaceuticals, agrochemicals, or
building blocks for the synthesis of conducting polymers.1-5
Comparing with thiophene, DBT has enhanced intramolecular
π-conjugation which resulted in much more remarkable
properties such as more excellent charge transport properties,
better thermal stability and so on. Various functionalized DBTs
have been extensively used for liquid crystals, super-
conductings, OFETs, host materials, organic light-emitting
diodes (OLEDs) and so on.6-12 Moreover, DBT is an electron-
donating unit in organic photoconductive materials.13
However, in the presence of H2O2, DBT is converted to
dibenzothiophene-S,S-dioxide14, which is used as an electron-
withdrawing unit and has been well studied due to its high
In our design, C-S and C-C bond of the central five
membered ring of DBT are consequently constructed in one
synthetic process (Scheme 1). Diphenylsulfides intermediate
(Scheme 1, I or II) is firstly produced by C-S coupling reaction,
then followed
Scheme 1. Approaches Towards the Synthesis of DBT
(1) Previous report
X
S
S
type B
R2
type A
R1
R2
R1
X
R2
R1
Y
X=H,Br
O
X=H,NH2,SR3
Y=H,Halogen
,
SCH3
(2) This work
Path A
intermediate
S
I
HS
R1
R2
R1
+
R2
Br
Br
S
I
R2
Path B
R1
I
HS
Br
S
R1
+
R2
R1
R2
Br
II
by a intramolecular cyclization proceeding through a C-H
activation process as a result to afford the desired product. It
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is worth mentioning that there are two approaches for the solvent was studied (Table 1, entries 10-13). The use of DMF
formation of diphenylsulfides intermediate (Scheme 1, path A and DMSO afforded comparable result as DMA (Table 1,
and path B) which make the substrates employed more easily entries 12-13) in 45% and 47% yield respectively
accessible and optional. desired product was observed in toluene or dioxane (Table 1,
The reaction conditions were optimized based on the model entries 10-11). Delightedly, the yield of 3a was remarkably
transformation of o-bromoiodobenzene 1a with 4- improved to 70% when the reaction temperature was
，but no
(
)
methylbenzenethiol (2a). Experiments of ligands screening increased from 120 oC to 140 oC (Table 1, entry 14).
were firstly carried out at 120 oC, together with PdCl2 as the Furthermore, increasing the loading of CsOPiv to 5 equivalents
catalyst precursor and CsOPiv as the base in DMA for 24h. As resulted in a higher yield of 85% (Table 1, entry 15).
described in Table 1, PPh3 and PCy3 (Table 1, entries 1 and 2) Meaningfully, the decrease in the catalyst of Pd(CH3CN)2Cl2
were not the suitable ligands for this tandem coupling reaction loading from 5 mol % to 2.5 mol %, also afforded 3a in 84%
and only trace or no desired product was observed. Usually, yield (Table 1, entry 16). The optimal reaction conditions thus
the substrate of thiophenol may lead to the deactivation of far being developed employing 1.25 equiv. of o-
transition-metal catalysts. We envisioned that using bidentate Bromoiodobenzene (1a), 1 equiv. of 4-methyl-benzene-thiol
ligand to improve the coordination ability may increase the (2a), 2.5 mol% of Pd(CH3CN)2Cl2, 5 mol % DPEphos, 5.0 equiv.
effect of ligand. Fortunately, when the bidentate ligands of of CsOPiv in DMA at 140 °C for 24 h. This procedure provided
dppf
(Table
1,
entry
3)
and
bis[2- 2-methyl-dibenzothiophene (3a) in 91% of isolated yield.
diphenylphosphino]phenyl]ether (DPEphos) (Table 1, entry 4) Replacing o-bromo-iodiobenzene with o-dibromobenzene
were used, 17% and 37% of the desired product 3a was gave the product 3a in a lower isolated yield of 84% (Table 1,
obtained respectively. Then, several palladium sources were entry 17).
investigated. Pd(OAc)2 provided the comparable result as PdCl2
in 36% yield (Table 1, entries 5). The yield increased to 45% the generality of this transformation. As shown in Table 2,
with Pd(CH3CN)2Cl2 as catalyst (Table 1, entry 7). However, various substituted o-bromoiodobenzenes ( ) (Table 2, entry
The optimized reaction conditions were applied to examine
1
Pd(dba)2 gave no product (Table 1, entry 6). The choice of base 1-10) coupled with 4-methylbenzenethiol (2a) were firstly
was crucial for this transformation. Switching the base from subjected to the reaction. The catalytic system could tolerate a
CsOPiv to Cs2CO3 and t-BuOK (Table 1, entries 8-9) identified variety of functional substituents on o-bromoiodobenzenes
CsOPiv as the optimal base. Finally, the effect of
including –CH3, -F, -CF3, -Cl and –NO2, which provided further
opportunities for functionalization and thus further
derivatives. In general, o-bromoiodobenzenes bearing
electron-deficient substituents (3c
,
3d
,
3g
,
3h) worked better
3e) and no
than those with electron-rich substituents (3b
,
product was observed for 4-methoxy-2-bromoiodo-benzene
(Table 2, entry 6). It is worth noting that the differences of
substituent position also had great effect on the result of
reaction. For example, 1-bromo-2-iodo-4-methylbenzene
afforded the corresponding products (3b) in 81% yield which
was higher than that of 2-bromo-1-iodo-4-methylbenzene (3e).
Moreover, for 2-bromo-4-halo-1-iodobenzenes (table 2,
entries 9-10), two isomers were isolated as a mixture in 1:1
ratio in the reaction, which indicated that C-I bond was
competitive with C-Br for the C-S coupling. Successively, the
scope of various substituted benzenethiol (2) with o-
bromoiodobenzenes
(1a) was also examined under the
optimized conditions. From Table 2 (entries 11-20), the
electronic effects of the substituents on benzenethiol exerted
a great influence on the yield of corresponding product which
was just contrary to o-bromoiodobenzenes derivations. The
benzenethiols with electron-withdrawing groups such as -F
(
3o), -Cl (3p) gave the corresponding products in moderate
yield which were obviously lower than those of electron-
donating groups (Table 2, entries 11-14). Benzenethiols
bearing strong electron-deficient substituents such as -CF3, -
NO2 (Table 2, entries 17 and 18) were less efficient for this
reaction. 3-Methylbenzenethiol gave a mixture of 3la and 3lb
in a 5:1 ratio (Table 2, entry 12) indicating the impact of steric
hindrance on regioselectivities. Moreover, α-naphthalenethiol
2 | J. Name., 2012, 00, 1-3
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was readily converted to the corresponding products (3t) in if replacing 4-nitro-iodobenzene with 4-nitro-bromobenzene.
92% yield and β- naphthalenethiol furnished a Moreover, electronic
Pd(CH3CN)2Cl2
I
S
HS
DPEphos, CsOPiv
R1
R2
+
2.5 mol% Pd(CH3CN)2Cl2
DMA, 140 o
C
2.5 mol% Pd(CH3CN)2Cl2
5 mol% DPEphos
5 equiv. CsOPiv
2 mL DMA
R1
Br
R2
S
SH
I
S
10 mol% DPEphos
5 equiv. CsOPiv
2 mL DMA
24 h
1
2
3
+
Br
S
entry
1
product
S
yield(%)
entry
product
yield(%)
3u
140 oC, 24 h
6
140 oC, 24 h
S
91
11
12
88
3a
3k
S
S
S
90b
3la : 3lb = 5 : 1
81
90
2
3
4
5
+
3la
3lb
3b
S
S
F
13
14
15
72
Pd(CH3CN)2Cl2
DPEphos, CsOPiv
3m
S
O
3c
S
I
HS
Br
R3
+
S
DMA, 140 o
C
R3
Cl
O
89
66
68
50
24 h
4
5
3
3d
3n
S
S
product
S
yield(%)
85
entry
7
product
yield (%)
entry
1
S
3e
3o
F
60c
0
S
S
3m
O
3u
S
6
7
0
16
17
18
19
20
66
0
S
O
3f
3p
Cl
S
2
3
8
trace
70
S
H2N
3x
3k
3q
85
91
S
CF3
Cl
S
S
3g
F
3C
S
81
90
9
S
F
3o
0
3v
+
3y
8
9
NO2
S
S
3h
O2
N
S
85b
3la:3lb = 5 : 1
S
4
10
trace
Cl
3p
3r
F
S
S
3lb
3la
72b
3i : 3c = 1 : 1
S
S
S
S
40/75d
30
3c
3i
F
95b
3sa : 3sb = 1 : 1
5
6
11
12
88
84
3sa
3sb
O2N
3y
3a
Cl
S
S
S
S
74b
10
21
92
3j : 3d = 1 : 1
3j
S
Cl
3t
3w
3t
a Reaction was conducted with 2 (0.20 mmol), 1 (0.25 mmol), Pd(CH3CN)2Cl2 (0.005 mmol), DPEphos (0.010
mmol), CsOPiv (5.0 equiv.) and DMA (2 mL) at 140 oC for 24 h. Isolated yield. b A mixture of two regioisomers
obtained (the ratio of products was determined by 1H NMR).
a
5
4
Reaction was conducted with (0.20 mmol), (0.25mmol), Pd(CH3CN)2Cl2 (0.005
mmol), DPEphos (0.020 mmol), CsOPiv (5.0 equiv) and DMA (2.0 mL) at 140 oC for 24 h.
Isolated yield. b A mixture of two regioisomers (the ratio of products was determined by 1
H
NMR). c CsOPiv (6 equiv.) was loaded. d The substrate was p-nitrobromobenzene.
mixture of 3sa and 3sb in 1:1 ratio. However, unfortunately,
thiophene-2-thiol afforded trace 3r (Table 2, entry 19) in the
reaction.
effect and steric hindrance of methyl group at 2-position of
iodobenzene had a great influence on the reaction and only
trace of product was obtained (Table 3, entry 2). In the case of
1-iodonaphthalene, 30% yield of desired product 3t was
obtained (Table 3, entry 12).
There are two approaches for the formation of 2-bromo-
phenyl phenyl sulfide. In addition to the above strategy, the
alternative one is to use iodobenzene and 2-
bromobenzenethiol as the substrates. However, under the
previous optimized conditions, most substrate of 2-
A putative reaction mechanism was depicted in Scheme 3.
The C-S coupling of aryl C-I bond with benzene thiol occurred
bromobenzenethiol was converted into thianthrene
6 in the
firstly to generate intermediate
addition of C-Br bond to form intermediate
intermediate underwent cyclization through
activation process to form intermediate and then afforded
A
, followed by an oxidative
Finally,
C-H
yield of 76% (Scheme 2). Delightfully, upon further
optimization of the reaction conditions, the desired product of
3u was achieved in 85% (Table3, entry 1) yield when increasing
the amount of DPEphos ligand from 5 mol% to 10 mol%. With
the new optimized reaction conditions in hand, a variety of
substituted iodobenzenes were tested. The results were
shown in Table 3. Most of employed iodobenzene derivations
reacted smoothly with 2-bromobenzenethiol under the
standard conditions to afford the corresponding products in
moderate to excellent yields. It was worth noting that the
strong electron donating (-OCH3) (Table 3, entry 7) and
electron withdrawing (-NO2) (Table 3, entry 11) substitutions
on iodobenzene partner gave the corresponding products of
3m and 3y in low yields. No product was achieved with 4-
iodoaniline. Interestingly, the yield of 3y was increased to 75%
B.
B
a
a
C
the desired product
proposal, the
3
by reductive elimination. According this
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6. J. Gao, L. Li, Q. Meng, R. Li, H. Jiang, H. Li and W. Hu, J. Mater.
Chem., 2007, 17, 1421.
7. Y. Li, H. Wu, J. Zou, L. Ying, W. Yang and Y. Cao, Org. Electron.,
2009, 10, 901-909.
8. T. H. Huang, W. T. Whang, J. Y. Shen, Y. S. Wen, J. T. Lin, T. H.
Ke, L. Y. Chen and C. C. Wu, Adv.Funct. Mater., 2006, 16, 1449-1456.
9. Y. Wang, S. R. Parkin, J. Gierschner and M. D. Watson, Org. Lett.,
2008, 10, 3307-3310.
10. J. Guo, X.-L. Li, H. Nie, W. Luo, S. Gan, S. Hu, R. Hu, A. Qin, Z.
Zhao, S.-J. Su and B. Z. Tang, Adv. Funct. Mater., 2017, 1606458.
11. X. He, T. Shan, X. Tang, Y. Gao, J. Li, B. Yang and P. Lu, J. Mater.
Chem. C., 2016, 4, 10205-10208.
12. K. Lin, S. Ming, S. Zhen, Y. Zhao, B. Lu and J. Xu, Polym. Chem.,
2015, 6, 4575-4587.
13. J. Ye, C. J. Zheng, X. M. Ou, X. H. Zhang, M. K. Fung and C. S. Lee,
Adv. Mater., 2012, 24, 3410-3414.
formation of intermediate
A was a matter of prime
14. T. A. G. Duarte, S. M. G. Pires, I. C. M. S. Santos, M. M. Q.
Simões, M. G. P. M. S. Neves, A. M. V. Cavaleiro and J. A. S.
Cavaleiro, Catal. Sci. Technol., 2016, 6, 3271-3278.
15. J. Liu, S. Hu, W. Zhao, Q. Zou, W. Luo, W. Yang, J. Peng and Y.
Cao, Macro. Rapid. Commun., 2010, 31, 496-501.
16. G. Yzambart, A. Zieleniewska, S. Bauroth, T. Clark, M. R. Bryce
and D. M. Guldi, J. Phys. Chem. C., 2017, 121, 13557-13569.
17. R. He, S. Hu, J. Liu, L. Yu, B. Zhang, N. Li, W. Yang, H. Wu and J.
Peng, J. Mater. Chem., 2012, 22, 3440.
importance. To gain a preliminary insight into this tandem
reaction, (2-bromophenyl)(p-tolyl)sulfane (Scheme 4) was
synthesized according to the literature method,36 which was
then heated under standard conditions leading to the
formation of 3a in 94% yield (Scheme 4).
7
In conclusion, we have developed a direct and highly
efficient approach for the construction of DBTs via a Pd-
catalyzed tandem reaction, using simple and commercially
available o-bromoiodobenzenes combined with benzenethiols
or iodobenzenes combined with o-bromo-benzenethiol as
substrates. These two alternatives for the combination of
substrates will certainly make this method more flexible and
attract the attention of organic chemists interested in this
class of compounds.
18. F. B. Dias, K. T. Kamtekar, T. Cazati, G. Williams, M. R. Bryce and
A. P. Monkman, Chemphyschem, 2009, 10, 2096-2104.
19. R. Samanta and A. P. Antonchick, Angew. Chem. Int .Ed Engl.,
2011, 50, 5217-5220.
20. M. Black, J. I. Cadogan and H. McNab, Org. Biomol. Chem., 2010,
8, 2961-2967.
21. M. Kienle, A. Unsinn and P. Knochel, Angew. Chem .Int. Ed Engl.,
2010, 49, 4751-4754.
Acknowledgements
22. M. Tobisu, Y. Masuya, K. Baba and N. Chatani, Chem. Sci., 2016,
7, 2587-2591.
This work was supported by the National Natural Science
Foundation of China (21673261, 21603245, 21703265 and
21573111), Key Laboratory of Organic Synthesis of Jiangsu
Province (KJS1747), the Funding from Nanjing University of Posts
and Telecommunications (NY217072, NY215016, NY215079).
23. T. H. Jepsen, M. Larsen, M. Jørgensen, K. A. Solanko, A. D. Bond,
A. Kadziola and M. B. Nielsen, Eur. J. Org. Chem., 2011, 2011, 53-57.
24. V. B. Pandya, M. R. Jain, B. V. Chaugule, J. S. Patel, B. M. Parmar,
J. K. Joshi and P. R. Patel, Synth. Commun., 2012, 42, 497-505.
25. M. Wang, Q. Fan and X. Jiang, Org. Lett., 2016, 18, 5756-5759.
26. K. Nishino, Y. Ogiwara and N. Sakai, European Journal of Organic
Chemistry, 2017, 2017, 5892-5895.
Conflicts of interest
There are no conflicts to declare”.
27. R. Che, Z. Wu, Z. Li, H. Xiang and X. Zhou, Chem.Eur. J., 2014, 20,
7258-7261.
Notes and references
1. J. Wrobel, J. Sredy, C. Moxham, A. Dietrich, Z. Li, D. R. Sawicki, L.
Seestaller, L. Wu, A. Katz, D. Sullivan, C. Tio and Z. Y. Zhang, J. Med.
Chem., 1999, 42, 3199-3202.
28. Q. Huang, S. Fu, S. Ke, H. Xiao, X. Zhang and S. Lin, Eur. J .Org.
Chem., 2015, 2015, 6602-6605.
29. R. Sanz, Y. Fernandez, M. P. Castroviejo, A. Perez and F. J.
Fananas, J. Org. Chem., 2006, 71, 6291-6294.
2. H. Ebata, E. Miyazaki, T. Yamamoto and K. Takimiya, Org. Lett.,
2007, 9, 4499-4502.
30. H. Kaida, T. Satoh, K. Hirano and M. Miura, Chem. Lett., 2015,
44, 1125-1127.
3. K. Takimiya, S. Shinamura, I. Osaka and E. Miyazaki, Adv. Mater.,
2011, 23, 4347-4370.
31. P. Oechsle and J. Paradies, Org. Lett., 2014, 16, 4086-4089.
32. T. Mori, T. Nishimura, T. Yamamoto, I. Doi, E. Miyazaki, I. Osaka
and K. Takimiya, J Am Chem Soc, 2013, 135, 13900-13913.
33. P. Saravanan and P. Anbarasan, Org. Lett., 2014, 16, 848-851.
34. K. Saito, P. K. Chikkade, M. Kanai and Y. Kuninobu, Chem. Eur. J.,
2015, 21, 8365-8368.
4. S. Zhang, X. Qiao, Y. Chen, Y. Wang, R. M. Edkins, Z. Liu, H. Li
and Q. Fang, Org. Lett., 2014, 16, 342-345.
5. J. S. Kang, T. R. Hong, H. J. Kim, Y. H. Son, R. Lampande, B. Y.
Kang, C. Lee, J.-K. Bin, B. S. Lee, J. H. Yang, J. Kim, S. Park, M. J. Cho,
J. H. Kwon and D. H. Choi, J. Mater. Chem. C., 2016, 4, 4512-4520.
4 | J. Name., 2012, 00, 1-3
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35. T. Wesch, A. Berthelot-Bréhier, F. R. Leroux and F. Colobert,
Org. Lett., 2013, 15, 2490-2493.
36. R. K. G. Craig G. Bates, and D. Venkataraman, Org. Lett., 2002,
2002, 2803.
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A Pd‐Catalyzed Optional Approach for the Synthesis of Dibenzothiophenes