Heterogeneous intermolecular hydroamination of terminal alkynes with aromatic amines

Article abstract of DOI:10.1016/j.tetlet.2005.11.001

Heterogeneous intermolecular hydroamination of alkynes with aromatic amines using inexpensive transition metal-exchanged clay catalysts was investigated. Reaction of terminal alkynes with aromatic amines gave higher yields of imines.

Full text of DOI:10.1016/j.tetlet.2005.11.001

Tetrahedron
Letters
Tetrahedron Letters 47 (2006) 141–143
Heterogeneous intermolecular hydroamination of terminal
alkynes with aromatic amines
Ganapati V. Shanbhag, Suresh M. Kumbar, Trissa Joseph and Shivappa B. Halligudi*
Inorganic Chemistry and Catalysis Division, National Chemical Laboratory, Pune 411008, India
Received 16 August 2005; revised 23 October 2005; accepted 1 November 2005
Available online 17 November 2005
Abstract—Heterogeneous intermolecular hydroamination of alkynes with aromatic amines using inexpensive transition metal-
exchanged clay catalysts was investigated. Reaction of terminal alkynes with aromatic amines gave higher yields of imines.
Ó 2005 Elsevier Ltd. All rights reserved.
The direct addition of N–H bonds of ammonia or
amines to alkenes and alkynes (hydroamination reac-
tion) offers a very attractive straightforward approach
for the synthesis of substituted amines and their deriva-
tives without any by-product formation.1 One such class
of compounds is aromatic imines, which are used in the
preparation of nitrogen-containing compounds such as
secondary,2a,b and tertiary amines,2c nitrogen hetero-
cycles,2d,e carboxylic amides,2f,g b-enamino esters2h and
amino alcohols.2i The classical method for imine synthe-
sis is amination of aldehydes or ketones, but direct
hydroamination of alkynes is 100% atom efficient and
can be used in domino reactions, where water as a side
product must be avoided.
salts.3 Later, alkali metals,4a metallocenes of Zr4b and
complexes of lanthanides and actinides,5 have been de-
signed to promote these reactions. In recent studies
moisture- and air-sensitive titanium complexes,6 and
more expensive metal complexes of Ru,7 Rh,8 Ir,8c Pd9
and Au10 have been the most widely used catalysts for
hydroamination of alkynes.
However, homogeneous methods suffer from tedious
work-ups and low recyclability of the catalyst. There
are a few reports available on the use of heterogeneous
catalysts for hydroamination of alkynes. Muller and
¨
co-workers have developed metal-exchanged zeolites
for alkyne hydroamination, which favoured Markovni-
kov addition products (Scheme 1).11 Also, Pd complexes
immobilized on a silica support were reported for intra-
molecular cyclization of amino-alkynes.12
Initially the catalytic intermolecular hydroamination of
alkynes was carried out in the presence of Hg and Tl
R'
R'
H
H
H
N
H
Catalyst
N
H
R
+
R
H
N
R'
+
H
R
R'
R'
N
N
+
R
H
Me
R
Markovnikov
anti-Markovnikov
Scheme 1. Possible imine products from hydroamination of terminal alkynes.
Keywords: Hydroamination; Clay; Copper; Alkyne; Amine; Heterogeneous.
*
Corresponding author. Tel.: +91 20 25893300; fax: +91 20 5893761; e-mail: sb.halligudi@ncl.res.in
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.11.001

142
G. V. Shanbhag et al. / Tetrahedron Letters 47 (2006) 141–143
Montmorillonite K-10 (hereafter K-10) is an acid-acti-
vated clay with an octahedral layer of alumina sand-
wiched between two tetrahedral silica layers.13 The
interlamellar space contains layer charge compensat-
ing cations like K+, Na+ and Ca+, which can be
exchanged easily with transition metal cations by a
normal ion exchange method. In our earlier studies,
we reported metal-exchanged clay for intermolecular
hydroamination of phenylacetylene with aniline.14
Therein, the effect of different substituents on aromatic
amines and the efficiency of the catalyst for the hydro-
amination of different alkynes are discussed.
alkynes with aniline (Table 2). Aromatic alkynes were
more reactive than aliphatic alkynes17 while terminal
alkynes gave the highest yields. Internal alkynes (entries
4 and 6) did not undergo the reaction probably due to
the steric hindrance by the bulky groups attached to
the triple bond. The activated alkynes with electron-
donating substituents, CH3– and CH3O– gave better
yields (entries 7 and 8) whereas the alkyne with the elec-
tron-withdrawing NO2 substituent was least reactive
(entry 9).
The nature of the substituents on the anilines had a sig-
nificant effect on the hydroamination reaction (Table 3).
The aniline derivatives with electron-donating groups at
the ortho and para positions reacted smoothly with 1a
(>90% yield) to give the corresponding imines. Interest-
ingly, sterically demanding amines like 2,4,6-trimethyl-
aniline and 2-isopropylaniline (entries 5 and 6), gave
higher imine yields indicating that bulkier groups
All catalysts were prepared by ion exchange of K-10
with aqueous metal acetate solutions under identical
conditions.15 Reactions were conducted in a round bot-
tom flask with toluene as the solvent unless otherwise
stated.16 Among the different M2+ exchanged K-10
clays, Cu2+ gave the highest yields for the hydroamina-
tion of 1a with p-toluidine (Table 1) and hence was used
as the catalyst in further studies. The higher activity of
Cu2+ and Zn2+ in hydroamination is due to their mod-
erately hard Lewis acidity.11c The reaction proceeded
with high regeoselectivity, only the Markovnikov addi-
tion product being observed in all cases.
Table 3. Hydroamination of phenylacetylene with aromatic aminesa
R
N
Cu-K-10
RNH2
Ph
H
+
toluene, 110 ˚C
Ph
Markovnikov
To gain a greater insight into the scope and limitations
of our method we examined the reactions of different
Entry
1
R
Time (h)
Yield (%)
C6H5
10
20
10
20
20
20
20
20b
20
20
20
20
20
48
48
20
93
99
84
99
98
99
95
91
99
99
95
32
68
NR
NR
88
Table 1. Intermolecular hydroamination of phenylacetylene with
p-toluidinea
2
2-CH3C6H4
3
4
5
4-CH3C6H4
2,4-(CH3)2C6H3
2,4,6-(CH3)3C6H2
p-Tol
N
Catalyst
p-CH3C6H4NH2
Ph
H
+
toluene, 110 ˚C
Ph
1a
Entry
Markovnikov product
6
7
8
9
10
11c
12c
13
2-i-PrC6H4
4-i-PrC6H4
4-CH3OC6H4
2-ClC6H4
Catalyst
Yield (%)
1
2
3
4
5
6
7b
Cu-K-10
Zn-K-10
Pd-K-10
Co-K-10
Ni-K-10
Mn-K-10
H+-K-10
64
52
8
5
3
4-BrC6H4
4-O2NC6H4
4-HOCC6H4
1-Naphthyl
3
2
a Conditions: Amine/alkyne 2:1, 4 ml toluene, 110 °C, 10 wt % catalyst,
NR = no reaction. Yields were determined by GC analysis and are
referred to the alkyne. Reaction conditions are not optimized. 100%
selectivity for the Markovnikov product was observed in each case.
b Isolated yield.
a Conditions: Amine/alkyne 2:1, 4 ml toluene, 110 °C, 10 wt % catalyst,
4 h. All yields were determined by GC analysis and are referred to the
alkyne. 100% selectivity for the Markovnikov product was observed
in each case.
c Solvent was 1,4-dioxane, reaction at 100 °C.
b Unexchanged clay.
Table 2. Hydroamination of alkynes with anilinea
Entry
Alkynes
Temp (°C)
Time (h)
Yield (%)
1
1-Hexyne
1-Hexyne
1-Heptyne
3-Hexyne
Phenylacetylene
Diphenylacetylene
4-Ethynyltoluene
4-Ethynylanisole
1-Ethynyl-2-nitrobenzene
80
110
110
110
110
110
110
110
110
20
20
20
48
10
48
10
10
20
5
45
55
NR
93
NR
87
84
2b
3b
4b
5
6
7
8
9
32
a Conditions: Amine/alkyne 2:1, 4 ml toluene, 10 wt % catalyst. Yields were determined by GC analysis and are referred to the alkyne. Reaction
conditions are not optimized, NR = no reaction, 100% selectivity for the Markovnikov product was observed in each case.
b Reaction was carried out in a Parr autoclave under N2.

G. V. Shanbhag et al. / Tetrahedron Letters 47 (2006) 141–143
143
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Tokunaga, M.; Eckert, M.; Wakatsuki, Y. Angew. Chem.,
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around the NH2– group do not affect the reactivity of
the amine. The amines with electron-withdrawing sub-
stituents, Cl– and Br– were less reactive (entries 9 and
10), whereas amines with stronger electron-withdrawing
substituents, NO2 and CHO, did not undergo the hydro-
amination reaction at all (entries 11 and 12). This reac-
tion also took place smoothly with 1-naphthylamine
(entry 13).
In conclusion, we have demonstrated that an environ-
mentally friendly, inexpensive and reusable transition
metal ion exchanged montmorillonite K-10 can be used
efficiently for intermolecular hydroamination of termi-
nal alkynes with aromatic amines.
10. Mizushima, E.; Hayashi, T.; Tanaka, M. Org. Lett. 2003,
5, 3349–3352.
Acknowledgements
11. (a) Penzien, J.; Muller, T. E.; Lercher, J. A. Chem.
¨
Commun. 2000, 1753–1754; (b) Penzien, J.; Muller, T. E.;
¨
Lercher, J. A. Micropor. Mesopor. Mater. 2001, 48, 285–
291; (c) Penzien, J.; Haeßner, C.; Jentys, A.; Ko¨hler, K.;
G.V.S. acknowledges C.S.I.R. New Delhi, for the award
of a Senior Research Fellowship. T.J. thanks DST, New
Delhi, for a Young Scientist Fellowship.
Muller, T. E.; Lercher, J. A. J. Catal. 2004, 221, 302–312;
¨
(d) Penzien, J.; Abraham, A.; Bokhoven, J. A.; Jentys, A.;
Muller, T. E.; Sievers, C.; Lercher, J. A. J. Phys. Chem. B
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15. Typical procedure for catalyst preparation: Montmoril-
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solution of Cu(CH3CO2)2 (0.05 mol dmÀ3) at 80 °C for
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16. Typical procedure for the M2+-K-10 catalyzed hydro-
amination reaction: Synthesis of N-(1-phenylethylidene)-
2,4,6-trimethylaniline (entry 5, Table 3): phenylacetylene
(5.37 mmol, 0.55 g) and 2,4,6-trimethylaniline (10.73
mmol, 1.45 g) were added to a stirred mixture of Cu-K-
10 (0.2 g) in toluene (4 mL). The reaction mixture was
stirred at 110 °C for 20 h under a N2 atmosphere in an oil
bath. The mixture was then cooled and filtered to remove
the catalyst and the solvent was removed by distillation.
The mixture was dried in vacuo and purified by column
chromatography on neutral alumina as the stationary
phase (petroleum ether/ethyl acetate, 200/1). Yield: 91%,
light brown oil: 1H NMR (CDCl3, 200 MHz): d = 7.86–
8.01 (m, 2H), 7.31–7.48 (m, 3H), 6.80 (s, 2H), 2.21 (s, 3H),
1.99 (s, 3H), 1.92 (s, 6H). 13C NMR (CDCl3): d = 165.57
(C), 146.50 (C), 139.33 (C), 131.96 (C), 130.43 (CH),
128.56 (CH), 128.43 (CH), 127.12 (CH), 125.63 (C), 20.81
(CH3), 17.96 (CH3), 17.48 (CH3). FT IR (neat, cmÀ1):
3025, 2940, 1638, 1207, 1025, 856, 762, 629. GCMS m/z
(relative intensity): 237 (64) [M+], 222 (100), 207 (47), 103
(52), 91 (55), 77 (40).
17. The reactions involving aliphatic alkynes were carried out
in a Parr autoclave under N2.