Ruthenium chloride, a new and efficient catalyst for direct amination of arenes with azodicarboxylates

Article abstract of DOI:10.1016/j.tetlet.2012.11.075

An efficient cross coupling amination of arene with azodicarboxylate to afford hydrazides catalysed by ruthenium chloride has been demonstrated. The catalyst was found to be effective across a spectrum of arenes with a variety of functional groups. The yi

Full text of DOI:10.1016/j.tetlet.2012.11.075

Tetrahedron Letters 54 (2013) 530–532
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Tetrahedron Letters
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Ruthenium chloride, a new and efficient catalyst for direct amination
of arenes with azodicarboxylates
Suleman M. Inamdar a, Vinod K. More a, Sisir K. Mandal b,
⇑
a Aditya Birla Science & Technology Centre, Plot No. 1 & 1-A/1, MIDC Taloja, Panvel, Navi Mumbai 410 208, India
b Technology Platform Department, Asian Paints R & T Centre, Plot No. C3-B/1, TTC Industrial Area, Pawane, Thane Belapur Road, Navi Mumbai 400 705, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 6 June 2012
Revised 17 November 2012
Accepted 20 November 2012
Available online 27 November 2012
An efficient cross coupling amination of arene with azodicarboxylate to afford hydrazides catalysed by
ruthenium chloride has been demonstrated. The catalyst was found to be effective across a spectrum
of arenes with a variety of functional groups. The yields are found to be modest to low depending on
the type of substrates. The catalyst can be recycled in ligand free conditions to afford the cross coupling
reaction.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Ruthenium chloride
Amination
Arene
Azodicarboxylate
Derivatives of aromatic amines are known to be biologically
active and have found applications in antibiotics,1 analgesics2
and R-adrenergic blockers.3 Monosubstituted hydrazines are also
intermediates in the preparation of heterocyclic compounds
such as pyrazoles,4 indazoles,5 imidazolinones6 and cinnolines.7
Moreover, 2-heteroaryl hydrazines8 are interesting synthetic
targets due to their efficiency as ligands for a variety of metal
complexes.9–11 Traditionally, aryl hydrazides were prepared by
treating azodicarboxylates with either an aryl lithium or an aryl
magnesium halide.12 Diprotected aryl hydrazines are generally
prepared by electrophilic amination13 of electron-rich arenes using
dialkyl azodicarboxylates or via the reaction of tert-butyl carbazates
with boronic acids catalysed by cuprous chloride at room
temperature.14
Reactions of electron rich arenes with azodicarboxylate in
the presence of various acids and metal halides are well
known.15–18,13b,19–21 Taking a step forward, gold catalysed amina-
tion of electron rich as well as electron poor arenes with better
activities has been recently reported by Zhang and co-workers22
Gold complexes are air sensitive and expensive compared to many
other metal complexes. In this respect, there is still a need for
improved and more general catalytic processes for arene amination.
Although the reaction was efficiently promoted by the above re-
agents in the presence of catalysts, they suffer from one or more
disadvantages such as use of drastic reaction conditions, poor reac-
tivity of electron deficient arenes and in many cases, the formation
of several by-products. In addition, these catalysts are moisture
sensitive and cannot be regenerated. This makes the process less
environmentally friendly and unattractive for commercialization.
Thus, there is still a need of cheaper, recyclable and environmen-
tally friendly catalysts for the direct amination of arenes. Herein,
we report a new ruthenium (III) chloride catalysed direct amina-
tion of electron rich as well as electron deficient arenes with azo-
dicarboxylates under mild reaction conditions (scheme 1).
Catalyst recyclability, recovery and performance of RuCl3 in direct
amination of anisole with diisopropyl azodicarboxylate were
evaluated.
Initially, the amination reaction between anisole and diisopro-
pyl azodicarboxylate was selected as a model reaction to optimize
the reaction conditions using RuCl3 as the catalyst.23 A preliminary
solvent screening indicated that dichloroethane could be the most
suitable solvent for the amination reaction (Table 1) among the
solvents studied.
In order to understand the effect of catalyst loading, the cross
coupling reactions were carried out at different catalyst loading
and the data are presented in Table 1. The results show that
2 mol % of RuCl3 loading gives excellent result as compared to
O
R
O
2 mol% RuCl3
Dichloroethane
O
R
+
O
N
N
O
N
N
H
O
60 o
C
O
O
R= Me, OMe, OH, halogen, etc
⇑
Corresponding author.
E-mail address: sisir.mandal@asianpaints.com (S.K. Mandal).
Scheme 1. RuCl3 catalysed direct amination of arenes with azodicaboxylate.
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.11.075

S. M. Inamdar et al. / Tetrahedron Letters 54 (2013) 530–532
531
Table 1
Effect of solvent on amination reaction of anisole catalysed by RuCl3
Table 2
RuCl3 catalysed direct amination of arenesa
a
OMe
O
O
RuCl3
R
O
OMe
O
N N
O
R
+
O
RuCl3
O
N
N
O
Dichloroethane
N
O
+
Solvent, 60 o
C
N
H
O
O
O
O
N
O
N
O
H
O
Entry
Arenes
Product
Time (h)
Yieldb
Entry
Solvent
Catalyst loading in mol %
Yieldb (%)
OMe
OMe
1
2
3
4
5
6
7
8
Dichloroethane
Dichloroethane
Dichloroethane
Dichloroethane
Dichloromethane
Methanol
Chloroform
THF
1
2
5
10
2
2
2
2
2
2
2
54
93
91
92
46c
73
70
64
58
55
76
4
12
93
a
b
c
d
e
f
O
N
41c
O
O
N
O
O
O
O
O
H
OH
OH
OH
OH
OH
5
91
86
86
79
75
O
O
O
O
O
O
O
O
N
9
10
11
Toluene
Dioxane
CH3CN
N
H
O
O
O
O
OH
a
Reaction conditions: diisopropyl azodicaboxylate (1 mmol), anisole (1.2 mmol),
RuCl3 catalyst, solvent (5 ml), 4 h, 60 °C.
5
b
Isolated yields.
Reaction perform at room temperature.
N
N
c
H
OH
1 mol % within the experimental error. There was no improvement
in the yield when the catalyst loading was more than 2 mol %.
Electronic factors play an important role in the reaction. In or-
der to understand the electronic factors the study was extended
to alternatively substituted arenes. Table 2 presents the relevant
data. Amination of anisole, phenol and 3-methyl phenol is achieved
in excellent yields in the presence of 2 mol % RuCl3 catalyst (Table
2, entries a–c). However, the reaction of 2,3,6-trimethylphenol and
2,3-dimethylphenol (Table 2, entries d–e) amination was achieved
in good yields with long reaction time. In case of 3-amino phenol,
durene and mesitylene (Table 2, entries f–h) the yield of amination
product was moderate even after a longer reaction time and excess
amount of catalyst (5 mol %). This low yield probably is due to the
crowding on the ring. Electron deficient halo-arenes such as 2-
chlorophenol, 3-bromophenol, fluorobenzene, chlorobenzene and
1,3-difluorobenzene (Table 2, entries i–m) provided poor yields
in long reaction times with 2 mol % RuCl3 catalyst. The results
show that the arenes with electron rich substituents give better
yields compared to arenes with electron deficient substituents.
In order to understand the mechanism of the reaction, we per-
formed a series of experiments with anisole and diisopropyl azodi-
carboxylate using stoichiometric amounts of RuCl3 in deuterated
chloroform under dry conditions. In the absence of arene, the 1H
NMR shifts of azodicarboxylates remained unchanged on addition
of RuCl3. However, change in 1H chemical shift was observed from
d 5.16–5.29 ppm to d 4.85–4.98 ppm when azodicarboxylate was
added to the system in the presence of both RuCl3 and arenes. De-
tailed mechanistic study is in progress.
12
15
10
N
N
H
OH
N
N
H
OH
OH
H2N
H2N
O
O
O
N
N
O
O
H
O
O
g
12
12
73
83
O
O
N
N
N
H
h
O
N
H
O
O
OH
OH
Cl
Cl
O
i
18
12
36
58
52
43
O
N
N
O
H
O
O
Br
Br
O
j
O
O
O
N
F
The reusability of RuCl3 catalyst was studied for the direct ami-
nation reaction between anisole with diisopropyl azodicarboxylate
in dichloroethane solvent at 60 °C. The results are summarized in
Table 3. The catalyst was allowed to settle down in the reaction
mixture and subsequently recovered near quantitatively by decan-
tation and reused (Table 3, entries 2–3) with a little loss of catalytic
activity compared to the fresh catalyst. The above results indicate
that the synthesis can be carried out with a minimal loss of the cat-
alyst making the method more advantageous and economic. The
gradual loss of yield in Table 3 could be due to the loss of catalyst
during recovery process in a small scale.
N
H
O
O
O
F
k
O
O
N
N
H
O
O
Cl
Cl
l
36
39
N
N
H
In conclusion, we have developed an inexpensive and efficient
method catalysed by RuCl3 for the direct amination across a spec-
(continued on next page)

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S. M. Inamdar et al. / Tetrahedron Letters 54 (2013) 530–532
11. Rose, D. J.; Maresca, K. P.; Nicholson, T.; Davison, A.; Jones, A. G.; Babich, J.;
Table 2 (continued)
Fischman, A.; Graham, W.; DeBord, J. R. D.; Zubieta, J. Inorg. Chem. 1998, 37,
2701.
Entry
Arenes
Product
Time (h)
Yieldb
12. Demers, P.; Klaubert, D. H. Tetrahedron Lett. 1987, 28, 4933.
13. (a) Bombek, S.; Lenarsic, R.; Kocevar, M.; Saint-Jalmes, L.; Desmurs, J. R.; Polanc,
S. Chem. Commun. 2002, 1494; (b) Mitchell, H.; Leblanc, Y. J. Org. Chem. 1994,
59, 682; (c) Kinart, W. J.; Kinart, C. M. J. Organomet. Chem. 2003, 665, 233.
14. Kobalka, G. W.; Guchhait, S. K. Org. Lett. 2003, 5, 4129.
15. (a) Leblanc, Y.; Boudreault, N. J. Org. Chem. 1995, 60, 4268; (b) Zaltsgendler, I.;
Leblanc, Y.; Bernstein, M. A. Tetrahedron Lett. 1993, 34, 2441; (c) Boudreault, N.;
Leblanc, Y. Org. Synth. 1997, 74, 241; (d) Bombek, S.; Pozgan, F.; Kocevar, M.;
Polanc, S. J. J. Org. Chem. 2004, 69, 2224.
16. (a) Carlin, R. B.; Moores, M. S. J. Am. Chem. Soc. 1962, 84, 4107; (b) Schroeter, S.
H. J. Org. Chem. 1969, 34, 4012.
17. Yadav, J. S.; Reddy, B. V. S.; Veerendhar, G.; Rao, R. S.; Nagaiah, K. Chem. Lett.
2002, 318.
F
F
m
30
20
F
F
O
O
N
N
O
H
O
a
Reaction conditions: diisopropyl azodicaboxylate (1 mmol), arene (1.2 mmol),
RuCl3 (2 mol %), DCE (5 ml), 60 °C.
b
Isolated yields.
c
RuCl3Á3H2O was used as catalyst.
18. Lee, K. Y.; Im, Y. J.; Kim, T. H.; Kim, J. N. Bull. Korean Chem. Soc. 2001, 22, 127.
19. Yadav, J. S.; Reddy, B. V. S.; Kumar, G. M.; Madan, C. Synlett 2001, 1781.
20. Lenarsic, R.; Kocevar, M.; Polanc, S. J. Org. Chem. 1999, 64, 2558.
21. Zaltsgendler, I.; Leblanc, Y.; Bernstein, M. A. Tetrahedron Lett 1993, 34, 2441.
22. (a) Liuqun, G.; Neo, B. S.; Zhang, Y. Org. Lett. 1872, 2011, 13; (b) Ackermann, L.;
Althammer, A.; Norn, R. Tetrahedron 2008, 64, 6115.
Table 3
RuCl3 catalyst reusability study for the amination reactiona
23. General procedure for RuCl3 catalysed direct amination reaction of arenes
with azodicarboxylate: Azodicarboxylate (1 mmol), arene (1.2 mmol) and
RuCl3 (2 mol %) were stirred in dichloroethane solvent (5 ml) at 60 °C till the
reaction is completed (Table 2). The progress of the reaction was monitored by
TLC. After the appropriate time (Table 2), the mixture was filtered to recover
the catalyst and the filtrate was evaporated under reduced pressure to get
crude product. The crude product thus obtained was purified by column
chromatography on silica gel using hexane–ethyl acetate (90:10) as eluent to
afford the pure product. All products were characterized by 1H NMR and 13C
NMR.
OMe
OMe
O
RuCl3 2 mol%
O
N N
O
DCE, 60 o
C
+
O
O
N
N
O
O
H
O
Entry
Time (h)
Yieldb
1
2
3
4
5
5
93
90
88
Spectral data for selected compounds. Diisopropyl 1-(4-methoxyphenyl)
hydrazine-1,2-dicarboxylate (Table 2, entry a). Yield: 93%; 1H NMR (200 MHz,
CDCl3): d = 1.17–1.22 (dd, 12H), 3.73 (s, 3H), 4.85–5.0(m, 2H), 6.73 (d, 2H), 6.86
(br s, 1H), 7.21 (d, 2H), 13C NMR (200 MHz, CDCl3): d = 22.06, 55.28, 69.85,
70.52, 113.77, 125.45, 125.73, 126, 126.27, 126.51, 127.38, 135.01, 155.98,
157.99; Anal. Calcd for C15H22N2O5: C, 58.05; H, 7.15; N, 9.03. Found: C, 58.11;
H, 7.13; N, 9.14.
a
Reaction conditions: diisopropyl azodicaboxylate(1 mmol), anisole (1.2 mmol),
RuCl3 (2 mol %), DCE (5 ml), 60 °C.
b
Isolated yields.
Diisopropyl 1-(4-hydroxyphenyl)hydrazine-1,2-dicarboxylate (Table 2, entry b).
Yield: 91%; 1H NMR (200 MHz, CDCl3): d = 1.22–1.29 (dd, 12H), 4.9–5.05(m,
2H), 6.63 (d, 2H), 6.92 (br s, 1H), 7.16 (d, 2H), 13C NMR (200 MHz, CDCl3):
d = 22.06, 60.39, 115.56, 125.41, 126.22, 126.75, 127.6, 134.13, 155.18, 156.14;
Anal. Calcd for C14H20N2O5: C, 56.75; H, 6.8; N, 9.45. Found: C, 56.71; H, 6.78;
N, 9.42.
Diisopropyl 1-(4-hydroxy-2-methylphenyl)hydrazine-1,2-dicarboxylate (Table 2,
entry c). Yield: 86%; 1H NMR (200 MHz, CDCl3): d = 1.21–1.29 (dd, 12H), 2.03 (s,
3H), 4.89–5.04(m, 2H), 6.44 (d, 1H), 6.58 (d, 1H), 6.89 (br s, 1H), 7.06 (d, 1H).
13C NMR (200 MHz, CDCl3): d = 22, 60.29, 69.96, 124.27, 133.12, 136.8, 155.88,
156.35, 157.4; Anal. Calcd for C15H22N2O5: C, 58.05; H, 7.15; N, 9.03. Found: C,
58.15; H, 7.14; N, 9.12.
trum of arenes with azodicarboxylates in a modest to low yields.
The effects of solvent, catalyst loading and the substituents of are-
nes are studied. The choice of arene is paramount in the selectivity
of the reaction. The method of catalyst recovery and its re-use is
provided. The protocol used in the synthesis may have a significant
advantage over other routes for the synthesis of biologically active
heterocyclic compounds.
Diisopropyl 1-(4-hydroxy-2,3-dimethylphenyl)hydrazine-1,2-dicarboxylate (Table
2, entry e). Yield: 79%; 1H NMR (200 MHz, CDCl3): d = 1.16–1.28 (dd, 12H), 2.12
(s, 3H), 2.16 (s, 3H), 4.9–5.07(m, 2H), 6.85 (br s, 1H), 6.98 (m, 2H), 13C NMR
(200 MHz, CDCl3): d = 21.98, 32.1, 48.1, 60.41, 122.32, 127.11, 132.89, 151.71,
155.94, 156.32; Anal. Calcd for C16H24N2O5: C, 58.24; H, 7.46; N, 8.64. Found: C,
58.31; H, 7.5; N, 8.56.
Diisopropyl 1-(2,4,6-trimethylphenyl)hydrazine-1,2-dicarboxylate (Table 2, entry
h). Yield: 73%; 1H NMR (200 MHz, CDCl3): d = 1.4–1.58 (dd, 12H), 2.51 (s, 6H),
2.55 (s, 6H), 5.19–5.28 (m, 2H), 6.94 (br s, 1H), 7.13 (s, 1H), 13C NMR (200 MHz,
CDCl3): d = 18.19, 20.98, 21.92, 69.89, 129.18, 129.41, 135.91, 136.45, 137.84,
138.03, 155.49, 156.2; Anal. Calcd for C18H28N2O4: C, 64.26; H, 8.39; N, 8.33.
Found: C, 64.29; H, 8.36; N, 8.34.
Diisopropyl 1-(3-chloro-4-hydroxyphenyl)hydrazine-1,2-dicarboxylate (Table 2,
entry i). Yield: 83%; 1.13–1.28 (dd, 12H), 2.29 (s, 9H), 4.9–5.07(m, 2H), 6.71 (br
s, 1H), 6.94 (s, 2H), 13C NMR (200 MHz, CDCl3): d = 18.11, 20.91, 21.95, 70.54,
129.11, 129.33, 135.83, 136.05, 136.39, 137.77, 137.96, 155.6, 155.91; Anal.
Calcd for C17H26N2O4: C, 63.33; H, 8.13; N, 8.69. Found: C, 63.31; H, 8.17; N,
8.72.
Acknowledgment
The financial assistance from Indira Gandhi Centre for Atomic
Research (IGCAR), Kalpakkam, India is kindly acknowledged.
References and notes
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5. Boudreault, N.; Leblanc, Y. Org. Synth. 1996, 74, 241.
Diisopropyl 1-(4-fluorophenyl)hydrazine-1,2-dicarboxylate (Table 2, entry k).
Yield: 43%; 1H NMR (200 MHz, CDCl3): d = 1.56–1.66 (dd, 12H), 5.27 (m, 2H),
7.12 (d, 2H) 7.17 (br s, 1H), 7.58 (d, 2H), 13C NMR (200 MHz, CDCl3): d = 22.7,
61.02, 116.19, 124.38, 126.85, 127.38, 127.84, 128.47, 134.76, 155.81, 156.78;
Anal. Calcd for C14H19FN2O4: C, 56.37; H, 6.42; N, 9.39. Found: C, 56.36; H, 6.43;
N, 9.41.
6. Bozzini, S.; Nitti, R.; Pitacco, G.; Pizzioli, A.; Russo, C. J. Heterocycl. Chem. 1966,
33, 1217.
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