N-Allylation of amines with allyl acetates using chitosan-immobilized palladium

Article abstract of DOI:10.1039/c3ra47899h

A simple procedure for N-allylation of amines with allyl acetates has been developed using a biodegradable and easily recyclable heterogeneous chitosan-supported palladium catalyst. The general methodology, applicable to a wide range of substrates, has sustainable features that include a ligand-free reaction with simple workup, recycling and reusability of the catalyst.

Full text of DOI:10.1039/c3ra47899h

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N-Allylation of amines with allyl acetates using
chitosan-immobilized palladium
Cite this: DOI: 10.1039/x0xx00000x
R. B. Nasir Baig, Buchi R. Vaddula, Michael A. Gonzalez, Rajender S.
Varma*
Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
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A simple procedure for N-Allylation of amines with allyl acetates Results and Discussion
has been developed using a biodegradable and easily recyclable
In view of our earlier success in the development of heterogeneous
heterogeneous chitosan-supported palladium catalyst. The
general methodology, applicable to wide range of substrates, has
sustainable features that include a ligand-free reaction with
simple workup, recycling and reusability of the catalyst.
supported catalysis using palladium,12 we decided to explore the
application of allyl acetates using the benign support, chitosan. The
objective is to develop a general and ligandꢀfree protocol for the Nꢀ
allylation reactions by using a chitosanꢀPd catalyst. The first step in
the accomplishment of this goal was the synthesis of catalyst by
immobilization palladium Pd(0) over chitosan which was
accomplished by reducing PdCl2 in an aqueous suspension of
chitosan at pH 9 (adjusted using 25% ammonia, basic media) by
using sodium borohydride at room temperature to afford the
chitosanꢀPd catalyst (Scheme 1).
Introduction
NꢀAllylamines are important structural motifs in organic chemistry
and are found in a wide range of biologically active natural
products.1 They are important intermediates in natural product
synthesis and have been successfully used for the total synthesis of
many alkaloids such as rosephilin, strychnine, (+)ꢀγꢀlycorane, and
other natural products.2 The efficient synthesis of Nꢀallylamines via
Nꢀallylation of amines is an important organic transformation
because of their importance in natural products and amino acid
synthesis.3 Palladium catalyzed TsujiꢀTrost type Nꢀallylation of
allylic compounds namely allylic alcohols, allylic halides, allylic
carbonates and allylic acetates, is considered as one of the most
important method for the synthesis of Nꢀallylamines.4 The Nꢀ
allylation reaction proceeds via the intermediate formation of η3ꢀ
allylꢀPd complex with allylic precursors such as allyl acetates
followed by coupling with amines to give Nꢀallylamines.5
OH
OH
O
O
O
HO
O
OH
O
OH
HO
O
NH2
O
HO
O
PdCl2/NaBH4
H2N
OH
O
O
HO
Pd
Water, NH3
over night
NH2
NH2
HO
O
O
O
O
O
HO
HO
NH2
NH2
Scheme 1. Synthesis of ChitosanꢀPd (ChPd) catalyst
Nonꢀrenewable petrochemical feedstocks are considered the major
source of polymer supports.6 Due to environmental consciousness,
there is
a growing thrust for alternative, ecofriendly, and
biodegradable polymer support to be used for recyclable
heterogeneous catalysis.7 The studies on the application of bioꢀ
derived polymers as heterogeneous supports in catalysis proved that
these compounds can serve as efficient and cheap alternatives.7
Naturally abundant chitosan may prove to be an ideal support in the
development of recyclable catalysts. As chitosanꢀsupported catalysts
have been used for many reactions.8 In continuation of our effort
toward the development of sustainable methods for organic
synthesis,10ꢀ11 herein, we report a simple and efficient method for the
Nꢀallylation of amines with allyl acetates using chitosanꢀpalladium
catalyst.
Figure 1a. SEM image of ChPd
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DOI: 10.1039/C3RA47899H
formation occurred in the absence of catalyst (Table 1, entry 8). The
same reaction, when carried out separately in the presence of
chitosan failed as well, but the chitosanꢀPd catalyst gave good
product yields thus confirming the essential role of palladium as the
catalyst. Using these optimized conditions, the reaction was studied
for its substrate scope with different amines and allylic acetates
(Table 2).
The variation in the structure of allyl acetates has not showed any
peculiar effect on yield and product outcome of the reaction (Table
2, Entry 1ꢀ9). Interestingly, a branched cinnamyl acetate, 1ꢀ
phenylallyl acetate (Table 2, Entry 10) also provided linear trans
product (Table 2, entry 10), which confirms the intermediacy of η3ꢀ
allylꢀPd complex in the reaction. The effect of various nitrogen
nucleophiles in progress of the reaction was examined. The reaction
of cinnamyl acetate with morpholine, piperidine, benzylamine, (S)ꢀ
methylbenzylamine, 2ꢀmethylpiperidine, and N-methyl piperazine
resulted in very good yields (84ꢀ92%) of corresponding allyl amines
(Table 2, entries 1ꢀ10), which indicates that the progress of the
reaction is not much influenced by the structural variation of amines.
Figure 1b. XRD pattern of ChPd
Table 2 ChPd catalyzed Nꢀallylation of allyl acetates a
The chitosan supported Pd material was separated using a centrifuge
and dried under vacuum at 50 C for 12 hours. The catalyst was
Product
Entry Amine
Substrate
Yield
o
O
1
N
N
OAc
characterized by SEM (Figure 1a) and Xꢀray diffraction XRD
(Figure 1b); the signals pertaining to Pd metal were not detected in
XRD, possibly due to its low percentage. However, the presence of
Pdꢀmetal has been confirmed by inductively coupled plasmaꢀatomic
emission spectroscopy (ICPꢀAES) analysis and the weight
percentage of Pd was found to be 5.19%.
88%
O
O
N
H
O
OAc
OAc
2
84%
89%
N
H
O
N
N
3
O
O
N
H
O
MeO
MeO
The ChitosanꢀPd catalyst was examined in the Nꢀallylation of amines
with allylic acetates in the presence of K2CO3 as base. In our first
attempt, a mixture of morpholine, cinnamyl acetate, K2CO3, and the
Pd catalyst in water was heated at 100 oC for 8 h. The desired
product was not detected; instead cinnamyl acetate was hydrolyzed
to cinnamyl alcohol. In order to optimize the reaction conditions, a
series of experiments were performed (Table 1).
OAc
OAc
4
92%
91%
89%
N
H
5
N
N
H
NH2
N
OAc
OAc
6
7
H
N
H
NH2
87%
91%
Table 1. Reaction optimization
O
ChPd
H
N
N
OAc
N
N
OAc
Solvent, K2CO3
O
8
N
H
N
Cl
N
Cl
Temp (oC)
Entry
Solvent
H2O
Time
Yield
OAc
OAc
9
87%
85%
N
H
1
2
100
66
8 h
0%
8%
10
N
N
H
THF
24 h
a) Reaction conditions: 1 mmol of allyl acetate,1.2 mmol of amine, 2 mmol of K2CO3,
30 mg of ChPd catalyst, 4 mL of DMF, 120 oC, over night
3
4
Dioxane
Toluene
101
110
24 h
24 h
18%
21%
In order to establish the recyclability of the catalyst, the catalyst was
separated by filtration or centrifugation and washed with water and
acetone followed by drying in vacuum at 50 oC. The recovered
catalyst was used at least five times without loosing it activity (ESI,
Table1). Metal leaching was studied by ICPꢀAES analysis of the
catalyst before and after the reaction cycles. The Pd weight
percentage was found to be 5.19% before the reaction and 5.11%
after the reaction. The TEM image of the recycle catalyst taken after
the reaction did not show significant change in the morphology of
the catalyst (ESI, Fig. 1), which indicates the retention of the
catalytic activity after recycling. No significant Pd metal was
detected in the reaction solvent after completion of the reaction. This
5
6
DMA
DMA
100
130
12 h
12 h
67%
84%
7
8
DMF
120
120
12 h
12 h
88%
0%
DMF (without catalyst)
Among the different conditions explored to optimize the reaction,
heating at 120 °C in DMF for 12 h provided the best results (Table 1,
entry 6). The active role of palladium in the catalytic cycle of the
reaction was established by control experiments; no product
2 | J. Name., 2012, 00, 1-3
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Conclusion
A simple and sustainable procedure for the Nꢀallylation of amines
has been developed using
a biodegradable and recyclable
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heterogeneous chitosanꢀsupported Pd catalyst. This unprecedented
general methodology deploys chitosan directly (unmodified) and is
applicable to aliphatic, benzylamines, substituted and unsubstituted
allyl acetates. Sustainable features of this protocol include a ligandꢀ
free reaction with simple workup, and recycling and reusability of
the catalyst.
Experimental Procedure
A mixture of allyl acetate (1.0 mmol), amine (1.2 mmol), chitosanꢀ
Pd (30 mg), and potassium carbonate (2.0 mmol) in anhydrous DMF
(4 mL) was heated at 120 °C under N2 atmosphere for 12ꢀ15 h. Upon
completion of the reaction, as indicated by TLC, the reaction mixture
was diluted with water and centrifuged/filtered to separate the
catalyst. The decanted liquid was extracted with ethyl acetate (3x10
mL); the organic layer was dried over anhydrous sodium sulfate and
evaporated under reduced pressure to afford the crude product. The
crude product was purified by passing through a short silica gel
column (ethyl acetate/hexane) and identification of the pure products
by spectroscopic means; 1H and 13C NMR spectra of the
representative compounds are provided in the supporting
information.
Acknowledgements
R.B.N.B. and B.R.V. were supported by the Postgraduate Research
Program at the National Risk Management Research Laboratory
administered by the Oak Ridge Institute for Science and Education
through an interagency agreement between the U.S. Department of
Energy and the U.S. Environmental Protection Agency. We thank
Dr. M. Nadagouda for recording XRD data and valuable
suggestions.
Notes and References
Sustainable Technology Division, National Risk Management
Research Laboratory, U. S. Environmental Protection Agency,26
West Martin Luther King Drive, MS 443, Cincinnati, Ohio 45268,
USA. Eꢀmail:Varma.Rajender@epa.gov, Fax: +1 513ꢀ569ꢀ7677;
Tel: +1 513ꢀ487ꢀ2701
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Varma, Green Chem. 2012,14, 67ꢀ71; c) V. Polshettiwar, B.
Baruwati and Rajender S. Varma Chem. Commun. 2008, 6318ꢀ
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