1-Aryltriazenes in the Suzuki, Heck, and Sonogashira Reactions in Imidazolium-ILs, with [BMIM(SO3H)][OTf] or Sc(OTf)3 as Promoter, and Pd(OAc)2 or NiCl2·glyme as Catalyst

Article abstract of DOI:10.1002/ejoc.201901070

1-Aryltriazenes, the protected and more stable form of aryl-diazonium species, can be conveniently unmasked with Br?nsted acidic-IL or Sc(OTf)₃ and coupled with a host of aryl/heteroaryl boronic acids, styrenes, and aryl/alkyl acetylenes in the Suzuki, Heck and Sonogashira reactions in one-pot and in respectable isolated yields, by using palladium or nickel catalyst in readily available imidazolium ILs as solvent, under mild conditions. The scope of these reactions are explored, and the potential for recovery/reuse of the IL solvent is also addressed.

Full text of DOI:10.1002/ejoc.201901070

A Journal of
Accepted Article
Title: 1-Aryltriazenes in the Suzuki, Heck, and Sonogashira Reactions
in Imidazolium-ILs, with [BMIM(SO3H][OTf] or Sc(OTf)3 as
Promoter, and Pd(OAc)2 or NiCl2.glyme as Catalyst
Authors: Suraj M. Sutar, Hemantkumar Savanur, Shruti Malunavar,
Pavankumar Prabhala, Rajesh Kalkhambkar, and Kenneth K.
Laali
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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: Eur. J. Org. Chem. 10.1002/ejoc.201901070
Link to VoR: http://dx.doi.org/10.1002/ejoc.201901070
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10.1002/ejoc.201901070
European Journal of Organic Chemistry
1
1-Aryltriazenes in the Suzuki, Heck, and Sonogashira Reactions in Imidazolium-ILs,
with [BMIM(SO3H][OTf] or Sc(OTf)3 as Promoter, and Pd(OAc)2 or NiCl2.glyme as
Catalyst
Suraj M. Sutar,a Hemantkumar M. Savanur,a Shruti S. Malunavar,a Pavankumar Prabhala,a
Dr. Rajesh G. Kalkhambkar,a* Prof. Kenneth K. Laalib*
aDepartment of Chemistry, Karnatak University’s Karnatak Science College, Dharwad
Karnatak 580001, India; Tel. +91 836 2215403, Fax. +91836 2744334
E-mail: rgkalkhambkar@gmail.com (R. G. Kalkhambkar)
bDepartment of Chemistry, University of North Florida, 1, UNF Drive, Jacksonville, Florida
32224, USA; Tel.: +1 904 620 1503; fax: +1 904 620 3535.
E-mail: Kenneth.Laali@UNF.edu (K.K. Laali) (senior corresponding author);
https://www.unf.edu/coas/chemistry/faculty/Kenneth_Laali.aspx
Alk/Ar
Ar
Sc(OTf)3;
IL
Sc(OTf)3; IL
[PAIM][NTf2]
CuI
NiCl2-glyme
[PAIM][NTf2]
Pd(OAc)2, CuI
Alk/Ar
N
N
NH2
N
I. HCl, NaNO2,
Ar
Ar
II. Secondary amine, KOH
[BMIM(SO3H)][OTf]
B(OH)2
or
Sc(OTf)3
Ar/Het
Ar
R
IL, Pd(OAc)2 or NiCl2
R
Ar/Het
Ar
Ar
Ar
Keywords: 1-aryltriazene; cross-coupling; Pd(OAc)2 or NiCl2.glyme; [BMIM(SO3H)][OTf]
or Sc(OTf)3; [PAIM][NTf2]
Key topic: cross-coupling
TOC text: 1-aryl-triazenes as coupling partners in the Suzuki, Heck, and Sonogashira
reactions in ionic liquids.
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10.1002/ejoc.201901070
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Abstract
1-Aryltriazenes, the protected and more stable form of aryl-diazonium species, can be
conveniently unmasked with Brønsted acidic-IL or Sc(OTf)3 and coupled with a host of
aryl/heteroaryl boronic acids, styrenes, and aryl/alkyl acetylenes in the Suzuki, Heck and
Sonogashira reactions in one-pot and in respectable isolated yields, by using palladium or
nickel catalyst in readily available imidazolium ILs as solvent, under mild conditions. The
scope of these reactions are explored, and the potential for recovery/reuse of the IL solvent is
also addressed.
Introduction
1-Aryltriazenes Ar-N=N-NR2 are accessible by reaction of secondary amines with the
+ [1]
+
in-situ generated ArN2 , or directly with diazonium salts.[2] Compared to ArN2 salts, 1-
aryltriazenes have increased stability and longer shelf life, and can be readily purified.[3]
+ [3,4]
Upon treatment with protic or Lewis acids, Ar-N=N-NR2 is transformed back to ArN2 .
These attributes imply that Ar-triazenes may be ideal electrophilic partners for cross-coupling
+
reactions as substitutes for ArN2 salts. To that end, limited number of studies focusing on the
Heck[3]and Suzuki reactions[4,5] have so far been reported employing Pd(0) catalysts along
with phosphine ligands[4] or polymer-supported NHC[5], with BF3.Et2O, TFA, or HBF4 as
typical promoters[3-5] to “unmask” the triazene. For the Suzuki reaction using BF3.Et2O, it
was suggested that formation of an aryltriazenes-BF3 complex promotes trans-metallation,
possibly in a concerted fashion.[4] The reactions were performed in a variety of solvents
(DME, DMF-H2O, dioxane, DMAC, NMP, toluene, THF, and refluxing MeOH)[3,-5], and the
yields varied significantly depending on the solvent.[4]
In continuation of our work on developing synthetic methods in ILs as catalysts and
solvents,[6] and our recent studies of metal-mediated cross-coupling reactions,[7] we report
here on the utility of 1-aryltriazenes as coupling partners in the Suzuki, Heck, and
Sonogashira reactions, by employing Brønsted acidic IL and Sc(OTf)3 as promoters, and the
piperidine-appended-IL [PAIM][NTf2] as base for the Sonogashira reaction[7e,7f], without the
need for ligand. Considering the ongoing interest in the use of Ni-based catalysts in place of
Pd, and the reports of successful application of Ni in the Suzuki reaction,[8-10] we also report
on the efficacy of NiCl2.glyme as substitute for Pd(OAc)2 in the present study.
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10.1002/ejoc.201901070
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Results and Discussion
At the onset, a small library of 1-aryltriazenes was prepared in good isolated yields by
in-situ diazotization of aniline and substituted anilines and subsequent reaction with
piperidine, pyrrolidine, and morpholine (Table 1). Focusing first on the Suzuki coupling
reaction, the Ar-triazenes were reacted with a set of aryl- and heteroaryl-boronic acids
employing [BMIM(SO3H)][OTf] or Sc(OTf)3, as Brønsted and Lewis acid promoters
respectively, to unmask the triazenes, with Pd(OAc)2 as catalyst, and employing the readily
available [BMIM][BF4] and [BMIM][PF6] as solvent, under moderate heating (Table 2,
entries 1-11). Selection of [BMIM(SO3H)][OTf] and Sc(OTf)3 as promoter was based on
their demonstrated efficacy as catalyst and promoter in a host of electrophilic and metal-
mediated reactions in ILs.[6.7] In the present study they proved almost equally effective, with
yields in 96-80% range when fresh IL was used. Lower isolated yields were observed when
recycled IL solvent was used to start a new reaction, and a further decrease occurred when
recycled IL was used to start a third reaction.
Table 3 (entries 12-17) represents a survey employing NiCl2.glyme instead of
Pd(OAC)2, showing that the isolated yields were on average 7-15% lower but still generally
acceptable.
Turing our attention to the Heck coupling, the aryl-triazenes were allowed to react
with different styrenes and aryl-ethenes, using either [BMIM(SO3H)][OTf] or Sc(OTf)3 as
promoter, and with Pd(OAc)2 as catalyst, in the same IL solvents under moderate heating,
and the corresponding Heck coupling products were isolated in 92-74% yields (Table 4,
entries 18-25). Lower isolated yields were obtained when recycled ILs were used directly to
start a new reaction. When fresh IL was used, [BMIM(SO3H)][OTf] and Sc(OTf)3 proved
equally effective, but precise side by side effectiveness could not be determined due to other
variable.
Switching to NiCl2.glyme as catalyst (Table 5, entries 26-30) the Heck coupling
products were isolated in 91-78% yields, in a similar range to Pd(OAc)2, with
[BMIM(SO3H)][OTf] and Sc(OTf)3 being equally effective as promoters.
Focusing on the Sonogashira reaction, the 1-aryl-triazenes were allowed to react with
representative aryl- and alkyl-ethynes by employing Sc(OTf)3 as promoter, Pd(OAc)2 as
catalyst, and the piperidine-appended-imidazolium IL[7e,7f] as basic-IL, along with CuI, in
same IL solvents (Table 6, entries 31-39). The corresponding alkynes were isolated in good
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10.1002/ejoc.201901070
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yields (83-84%) when fresh IL was used, while the yields dropped by approximately 10%
after each solvent recycling step.
Moving on to NiCl2.glyme as catalyst for this transformation (Table 7, entries 40-45)
we found similar isolated yields, and observed similar variations in yields when recycled ILs
were used to run a new reaction.
Returning to the recycling/reuse of the IL solvent, for each type of coupling reaction a
reference reaction was selected and repeated four consecutive times in [BMIM][PF6] and in
[BMIM][BF4] solvent. The results presented in graphical format in the SI file (charts 1-3),
indicate a fairly consistent trend, and in line with our findings from a previous study,[7f]
[BMIM][PF6] exhibited a somewhat better recovery/reuse profile as compared to
[BMIM][BF4].
Conclusion
In conclusion we have demonstrated the efficacy of 1-aryltriazene as surrogates for
aryl-diazonium salts in the Suzuki, Heck, and Sonogashira cross coupling reactions in IL
solvents, with the Brønsted-acidic IL [BMIM(SO3H][OTf] and Sc(OTf)3 serving as efficient
promoters for the unmasking of Ar-N=N-NR2, and [PAIM][NTf2] serving as basic-IL in the
Sonogashira reaction. Reactions were catalyzed with Pd(OAc)2 and with NiCl2.glyme, thus
widening the scope of this protocol.
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Table 1. Synthesis of 1-aryl-triazenes
Entry
Ar-NH2
2o amine
Product
Yield* (%)
NH2
N
N
1
88
N
HN
NH2
N
N
2
81
N
HN
NH2
N
N
3
4
6
79
79
88
N
HN
HN
HN
Cl
Cl
NH2
N
N
N
NH2
N
N
N
N
Cl
Cl
O
NH2
O
N
7
8
77
80
N
HN
O
NH2
O
N
N
N
HN
*Isolated yields of pure products
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10.1002/ejoc.201901070
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Table 2. Aryl-triazenes as coupling partners in the Suzuki reaction in IL solvents, with
Pd(OAc)2 as catalyst, and Brønsted-acidic IL or Sc(OTf)3 as promoter
Timeb Yield*
Ar/Het.Boronic
acid
Entry
Ar-Triazene
Producta
IL
(h)
(%)
O
O
N
N
1
N
N
[BMIM]BF4
6
82d,f
B(OH)2
Cl
Cl
B(OH)2
96c,g
N
[BMIM]PF6
5
N
2
S
S
N
N
[BMIM]BF4
[BMIM]PF6
6
81d,f
84c,f
B(OH)2
N
3
4
O
O
N
N
6.5
B(OH)2
N
N
O
B(OH)2
N
[BMIM]PF6
[BMIM]BF4
[BMIM]BF4
[BMIM]BF4
[BMIM]BF4
[BMIM]PF6
[BMIM]BF4
6
6
80d,g
89c,f
82d,f
73e,g
80c,g
90c,g
87c,f
N
5
6
7
Cl
Cl
O
O
N
N
B(OH)2
N
O
B(OH)2
N
N
5.5
6.5
7
N
S
O
N
N
N
B(OH)2
8
9
S
O
N
N
N
B(OH)2
Cl
Cl
O
B(OH)2
B(OH)2
N
N
5.5
6
N
10
11
N
N
N
Cl
Cl
aReaction conditions: 1-Ar-triazene (1.2 mmol), Boronic acid (1.0 mmol), Promoter (1.2 mmol),
[BMIM][X](7 mL) and Pd(OAc)2 (10 mol %); bOil bath temperature 55-60oC ;cYield employing fresh
f
IL;dYield using recycled IL (2nd cycle); eYield using recycled IL (3rd cycle); Sc(OTf)3;
g[BMIM(SO3H)]OTf; *Isolated yield of pure products.
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10.1002/ejoc.201901070
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Table 3. Aryl-triazenes as coupling partners in the Suzuki reaction in IL solvents, with
NiCl2-glyme as catalyst, and Brønsted-acidic IL or Sc(OTf)3 as promoter
Timeb Yield*
Ar/Het. Boronic
acid
Entry
12
Ar-Triazene
Producta
IL
(h)
(%)
B(OH)2
82c,g
N
N
N
[BMIM]BF4
6
N
N
B(OH)2
N
[BMIM]PF6
7
78d,g
13
Cl
Cl
O
O
N
N
[BMIM]BF4
[BMIM]BF4
[BMIM]BF4
7
79c,f
71d,f
68e,g
B(OH)2
N
N
14
15
O
B(OH)2
N
N
6.5
6.5
S
O
N
N
N
B(OH)2
16
17
B(OH)2
N
N
80c,f
N
[BMIM]PF6
7
Cl
Cl
aReaction conditions: 1-Ar-triazene (1.2 mmol), Boronic acid (1.0 mmol), Promoter (1.2 mmol),
b
o
c
[BMIM][X](7 mL) and NiCl2.glyme(10 mol %); Oil bath temperature 55-60 C; Yield employing
fresh IL; dYield using recycled IL (2nd cycle);eYield using recycled IL (3rd cycle); fSc(OTf)3;
g[Bmim(SO3H)]OTf; *Isolated yield of pure products.
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Table 4. Aryl-triazenes as coupling partners in the Heck reaction in IL solvents, with
Pd(OAc)2 as catalyst, and Brønsted-acidic IL or Sc(OTf)3 as promoter
Time Yield*
Entry
Ar-Triazene
Arylethenes
Product
IL
(h)
(%)
N
N
18
N
N
[BMIM]BF4
2
74e,g
O
O
N
N
N
19
20
[BMIM]BF4
[BMIM]PF6
2.5
2
82c,f
Cl
Cl
Cl
Cl
N
N
N
78d,g
O
N
21
N
[BMIM]BF4
2.5
65e,f
O
92c,f
86c,g
N
N
22
23
[BMIM]PF6
[BMIM]PF6
2.5
3
N
N
N
N
77d,f
74d,g
N
N
24
25
[BMIM]PF6
[BMIM]BF4
3.5
3.5
N
N
N
N
aReaction conditions: 1-Ar-triazene (1.2 mmol), arylethene (1.0 mmol), Promoter (1.2 mmol),
[BMIM][X](7 mL) and Pd(OAc)2(10 mol %); bOil bath temperature 70oC; cYield employing fresh IL;
dYield using recycled IL (2nd cycle); eYield using recycled IL (3rd cycle); fSc(OTf)3;
g[BMIM(SO3H)]OTf; *Isolated yield of pure products.
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Table 5. Aryl-triazenes as coupling partners in the Heck reaction in IL solvents, with
NiCl2-glyme as catalyst and Brønsted-acidic IL or Sc(OTf)3 as promoter
Time Yield*
Entry
Ar-Triazene
Arylethene
Product
IL
(h)
(%)
N
N
26
N
N
[BMIM]PF6
3.5
78d,f
O
N
N
27
28
[BMIM]BF4
[BMIM]PF6
4
91c,e
Cl
Cl
O
N
N
N
4.5
81d,f
O
87c,e
87c,e
N
N
29
30
[BMIM]PF6
[BMIM]BF4
3,5
4
N
N
N
N
aReaction conditions: Ar-triazene (1.2 mmol), arylethene (1.0 mmol), promoter (1.2 mmol),
[BMIM][X](7 mL) and NiCl2.glyme(10 mol %); bOil bath temperature 70 oC; cYield employing fresh
d
e
f
IL; Yield using recycled IL (2nd cycle); Sc(OTf)3; [BMIM(SO3H)]OTf; *Isolated yield of pure
products
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10.1002/ejoc.201901070
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Table 6. Aryl-triazenes as coupling partners in the Sonogashira reaction in IL solvents,
Pd(OAc)2 as catalyst, Sc(OTf)3 as promoter, and [PAIM][NTf2] as base
Ar/Alkyl
acetylene
Time Yield*
Entry
Ar-triazene
Product
IL
(h)
(%)
O
[BMIM]BF4
3
84c
N
N
N
31
N
N
[BMIM]BF4
3.5
78d
N
32
33
Cl
Cl
N
N
N
[BMIM]PF6
[BMIM]BF4
[BMIM]PF6
3
3.5
4
83c
76d
63e
O
N
N
N
34
35
N
N
N
N
N
Cl
Cl
N
[BMIM]BF4
3
66e
36
37
O
[BMIM]PF6
[BMIM]PF6
[BMIM]PF6
3.5
3
78d
71d
67e
N
N
N
N
N
N
N
N
38
39
N
3.5
Cl
Cl
aReaction conditions: Ar-triazene (1.2 mmol), alkyne (1.0 mmol), [PAIM][NTf2] (3-4 mmol);
b
Sc(OTf)3 (1.2 mmol), [BMIM][X] (7 mL), Pd(OAc)2 (10 mol%) and CuI (10 mol %); Oil bath
c
d
e
temperature 50-60oC; Yield employing fresh IL; Yield using recycled IL (2nd cycle); Yield using
recycled IL (3rd cycle);*Isolated yield of pure products.
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10.1002/ejoc.201901070
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Table 7. Aryl-triazenes as coupling partners in the Sonogashira reaction in IL solvents,
with NiCl2-glyme as catalyst, Sc(OTf)3 as promoter, and [PAIM][NTf2] as base
Ar/Alkyl
acetylene
Time Yield*
Entry
Ar-Triazene
Product
IL
(h)
(%)
N
N
N
[BMIM]BF4
4
81c
40
N
N
N
[BMIM]PF6
[BMIM]BF4
5
4
75d
80c
41
Cl
Cl
N
N
N
42
43
44
O
N
N
[BMIM]BF4
[BMIM]PF6
5.5
5.5
76d
70d
N
N
N
N
N
N
Cl
Cl
N
[BMIM]PF6
5
75d
45
aReaction conditions: Ar-triazene (1.2 mmol), alkyne (1.0 mmol), [PAIM][NTf2] (3-4 mmol);
b
Sc(OTf)3 (1.2 mmol),; [BMIM][X] (7 mL), NiCl2-glyme (10 mol%) and CuI (10 mol %); Oil bath
c
d
e
temperature 50-60oC; Yield employing fresh IL; Yield using recycled IL (2nd cycle); Yield using
recycled IL (3rd cycle);*Isolated yield of pure products
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10.1002/ejoc.201901070
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Acknowledgements
The authors thank the University Sophisticated Instrument Center, KUD for GC, and GC-
MS, 1H NMR and 13C NMR. They also thank NMR Research Center, Indian Institute of
1
Science, Bangalore for H NMR and 13C NMR. Thanks are also due to Vision group on
science and technology, Govt. of Karnataka Bangalore Project No. VGST-RGS/F/GRD-
742/2017-18 for Financial assistance. K. K. L. thanks University of North Florida for the
Outstanding Faculty Scholarship and Presidential Professorship awards, Faculty scholarship
and UNF Foundation Board grants, and the Dean’s Leadership Council award.
Supporting information
Synthetic procedures, analytical data for isolated compounds, ILrecycling feasibility studies,
and NMR spectra data
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