Microwave assisted efficient aminocarbonylation of N-tosylhydrazones with molybdenum hexacarbonyl and amines

Article abstract of DOI:10.1016/j.tetlet.2013.07.149

An efficient aminocarbonylation of N-tosylhydrazones derived from aromatic aldehydes and ketones mediated by molybdenum hexacarbonyl is reported. This method is palladium-free and provides a rapid access to the α-aryl acetamides in moderate to good yields.

Full text of DOI:10.1016/j.tetlet.2013.07.149

Tetrahedron Letters 54 (2013) 5510–5513
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Microwave assisted efficient aminocarbonylation of N-tosylhydra-
zones with molybdenum hexacarbonyl and amines
⇑
K. Penta Rao, Ashok K. Basak, Amancha Raju, Vikas S. Patil, L. Krishnakanth Reddy
Jubilant Chemsys Limited, B-34, Sector-58, Noida 201301, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient aminocarbonylation of N-tosylhydrazones derived from aromatic aldehydes and ketones
mediated by molybdenum hexacarbonyl is reported. This method is palladium-free and provides a rapid
access to the a-aryl acetamides in moderate to good yields.
Received 10 June 2013
Revised 24 July 2013
Accepted 28 July 2013
Available online 6 August 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Aminocarbonylation
Tosylhydrazones
Molybdenum hexacarbonyl
Microwave synthesis
Palladium catalyzed Mo(CO)6 mediated carbonylative reac-
tions1 have been developed for rapid small scale applications
avoiding the use of toxic CO gas in a typical laboratory procedure.
For example, Mo(CO)6 was used in the preparation of carboxylic
acids,2 esters,3 amides,2a,4 and in carbonylative-cross couplings.5
Pd-free amino-carbonylation reactions of aryl halides have also
been developed.6 It has been proposed that aryl halides undergo
oxidative addition to Mo(CO)6–amine complex.6a
Recently, a Pd-catalyzed aminocarbonylation of carbenes gener-
ated from tosylhydrazones with carbon monoxide is reported by
Wang and co-workers.7 Also, Pd-catalyzed amidation of N-tosylhy-
drazones with isocyanides8 is known. However, there is no report
on Pd-free amino carbonylation reaction of tosylhydrazones med-
iated by Mo(CO)6.
With the successful result in hand, we explored the scope of
aminocarbonylation reaction on various substrates under micro-
wave irradiation (Table 1). As shown in Table 1, a series of N-tosyl-
hydrazones derived from aryl aldehydes and benzyl amine (2)
were tested. Electron-donating groups, such as the methyl or
methoxy group, on the aryl ring of N-tosylhydrazones were well
tolerated and the corresponding products were obtained in excel-
lent yields (Table 1, entries 1–5). Treatment of N-tosylhydrazone
of pyridine-3-aldehyde under this condition produced moderate
yield (Table 1, entry 7).
To expand the scope of this methodology, we investigated the
amino-carbonylation of N-tosylhydrazone derived from acetophe-
Encouraged by these findings, we hypothesized that Mo(CO)6
mediated amino-carbonylation of tosylhydrazones might be possi-
ble without using Pd catalysts (Scheme 1).
Herein, we describe an efficient Pd-free amino-carbonylation of
N-tosylhydrazones derived from aromatic aldehyes and ketones
with amines mediated by Mo(CO)6.
R
Ar
Ar
NNHTs
Base
R
Reaction of tosylhydrazone (1)8 with benzylamine (2), Mo(CO)6,
and DBU in the presence of Et4NCl in dioxane at 140 °C for 1 h was
investigated as a model reaction. Under this reaction condition we
observed the formation of product 39a in moderate yield (62%).
With the successful result of this reaction, we studied the scope
of this reaction under microwave irradiation (BiotageÒ Initiator)
at 140 °C for 45 min and obtained better yield (79%) (Scheme 2).
R
Ar
RNH2
N2
Mo(CO)6
RNH-Mo(CO)5
Mo(CO)
RNH
4
Et4NCl
Ar
R
R
O
NHR
Ar
O
RNH-Mo(CO)3
⇑
Corresponding author.
E-mail address: lkkreddy@gmail.com (L.K. Reddy).
Scheme 1. Proposed mechanism for Mo(CO)6 mediated amino-carbonylation of
tosylhydrazones.
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.07.149

K. P. Rao et al. / Tetrahedron Letters 54 (2013) 5510–5513
5511
NNHTs
NNHTs
H
N
H
N
+
+
H2N
H2N
O
O
5
3
4
1
2
2
Scheme 3. Reagents and conditions: Mo(CO)6, Et4NCl, DBU, dioxane, 140 °C,
45 min, microwave, 73% yield.
Scheme 2. Reagents and conditions: Mo(CO)6, Et4NCl, DBU, dioxane, 140 °C, 1 h,
62% yield or microwave, 140 °C, 45 min, 79% yield.
none. The reaction led to the smooth formation of product 511 in
73% yield (Scheme 3).
(Table 2, entry 4). Treatment of N-tosylhydrazones of 3-acetylthio-
phene and 3-acetylpyridine under the reaction condition produced
good yields (Table 2, entries 6 and 7) whereas moderate yield was
obtained in the case of tosylhydrazone derived from benzophe-
none (Table 2, entry 8). Aromatic amine produced lower yield
when compared to benzylamine in the amino-carbonylation reac-
tion (Table 2, entry14).
Encouraged by this result we examined N-tosylhydrazones de-
rived from various aromatic ketones and amines (Table 2). As indi-
cated in Table 2, moderate to good yields were obtained. N-
tosylhydrazones derived from aryl ketones bearing the electron
donating group on the aromatic ring produced better results (Ta-
ble 2, entries 1 and 2). When the electron withdrawing nitrile
group was present in the aryl ring, moderate yield was obtained
In summary, an efficient amino-carbonylation of N-tosylhydra-
zones derived from aromatic aldehydes and ketones mediated by
Table 1
Aminocarbonylation of N-tosylhydrazones of aldehydes (3a–3g)
Entry
Substrate 1
Substrate 2
Product 3
Isolated yielda (%)
NNHTs
H2N
H
N
1b
82c
O
2
O
O
1a
NNHTs
3a
H2N
H
N
2d
3b
4e
77c
76c
69
O
2
1b
3b
NNHTs
H2N
H
N
O
2
Cl
Cl
1c
3c
NNHTs
H2N
H
N
O
2
1d
3d
NNHTs
H2N
H
N
5f
81c
O
O
O
2
O
O
O
1e
3e
NNHTs
H2N
H
N
6g
78c
60i
2
1f
3f
NNHTs
H2N
H
N
7h
O
2
N
N
1g
3g
a
Isolated yields obtained using 1.0 mmol of N-tosylhydrazone, 1.0 mmol of amine, 2.5 mmol of DBU, 1.0 mmol of Mo(CO)6, 1.0 mmol of Et4NCl in dioxane at 140 °C for
45 min under microwave irradiation.
b
Ref. 9b.
Ref. 9a.
Ref. 9c.
Ref. 9d.
Ref. 9e.
Ref. 9f.
Ref. 9g.
Ref. 10.
c
d
e
f
g
h
i

5512
K. P. Rao et al. / Tetrahedron Letters 54 (2013) 5510–5513
Table 2
Aminocarbonylation of N-tosylhydrazones of ketones (5a–5n)
Entry
Substrate 4
Substrate 2
Product 5
Isolated yielda (%)
NNHTs
H2N
H
N
1g
76
O
2
O
O
4a
5a
NNHTs
H2N
H
N
2
75b
O
2
O
O
O
O
5b
4b
NNHTs
H2N
H
N
3
61
60
O
2
Cl
Cl
Cl
Cl
5c
4c
NNHTs
NNHTs
H2N
H
N
4g
O
2
NC
NC
4d
5d
H2N
H
N
5h
72
68
62
O
2
5e
4e
NNHTs
H2N
H
N
6
2
S
O
5f
S
4f
NNHTs
H2N
H
N
7
O
2
N
N
5g
4g
NNHTs
H2N
H
N
2
8i
51c
4h
O
5h
NNHTs
H
N
H2N
9g
74d
73e
64
O
2a
4
5i
NNHTs
H
N
H2N
10
11
O
2b
5j
4
NNHTs
CF3
H2N
H
N
CF3
CF3
CF3
2c
O
4
5k
NNHTs
CF3
CF3
H2N
H
N
12
13
66
65
2c
O
O
O
O
4a
NNHTs
5l
H2N
H
N
2c
4e
5m

K. P. Rao et al. / Tetrahedron Letters 54 (2013) 5510–5513
5513
Table 2 (continued)
Entry
Substrate 4
NNHTs
Substrate 2
Product 5
Isolated yielda (%)
H2N
H
N
14
44f
O
2d
5n
4
a
Isolated yields obtained using 1.0 mmol of N-tosylhydrazone, 1.0 mmol of amine, 2.5 mmol of DBU, 1.0 mmol of Mo(CO)6, 1.0 mmol of Et4NCl in dioxane at 140 °C for
45 min under microwave irradiation.
b
Ref. 12.
Ref. 9a.
Ref. 13.
Ref. 14.
Ref. 15.
Ref. 9b.
Ref. 16.
Ref. 17.
c
d
e
f
g
h
i
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Utkina, L. M. Synlett 2008, 100–104.
a-arylacetamide derivatives.
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4280–4283; (b) Ren, W.; Yamane, M. J. Org. Chem. 2010, 75, 3017–3020; (c)
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Acknowledgement
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We are thankful to Jubilant Chemsys management for providing
financial support and analytical facilities for the execution of this
research work.
Supplementary data
Supplementary data (synthesized compounds) associated with
this article can be found, in the online version, at http://
dx.doi.org/10.1016/j.tetlet.2013.07.149.
13. Funasaka, S.; Mukaiyama, T. Bull. Chem. Soc. Jpn 2008, 81, 148–159.
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18. General experimental procedure: To a solution of tosylhydrazone (1) (1.0 mmol)
in 1,4-dioxane (2 mL) were added molybdenum hexacarbonyl (1.0 mmol),
Et4NCl (1.0 mmol), benzylamine (2) (1.0 mmol), and DBU (2.5 mmol) in a
10 mL capacity microwave vial and the vial was sealed and irradiated with
microwave at 140 °C for 45 min. After cooling to room temperature, the
reaction mixture was filtered through a pad of celite, washed with ethyl
acetate (10 mL). The combined filtrate was washed with water, dried over
Na2SO4, and concentrated in vacuo. The residue was purified by flash column
chromatography over 12 g SNAP cartridge by eluting with gradient of 10–20%
ethyl acetate in hexane to afford N-benzyl-2-phenylacetamide (3) in 79% yield.