Clay catalyzed chemoselective Michael type addition of aliphatic amines to α,β-ethylenic compounds

Article abstract of DOI:10.1016/S0040-4020(01)00911-5

Application of acidic clays as heterogeneous catalysts for the Michael type addition reaction of aliphatic amines to α,β-ethylenic compounds is presented. Aromatic amines do not participate in this transformation.

Full text of DOI:10.1016/S0040-4020(01)00911-5

TETRAHEDRON
Pergamon
Tetrahedron 57 @2001) 9045±9048
Clay catalyzed chemoselective Michael type addition of aliphatic
amines to a,b-ethylenic compounds
p
Nadim S. Shaikh, Vishnu H. Deshpande and Ashutosh V. Bedekar
p,²
National Chemical Laboratory, Division of Organic Chemistry: Technology, Pune 411008, India
Dedicated to the warm memory of Ms Sarah His of Senlis, France
Received 12 June 2001; accepted 6 September 2001
AbstractÐApplication of acidic clays as heterogeneous catalysts for the Michael type addition reaction of aliphatic amines to a,b-ethylenic
compounds is presented. Aromatic amines do not participate in this transformation. q 2001 Elsevier Science Ltd. All rights reserved.
The scope of heterogeneous catalytic organic transfor-
mations is rapidly growing due to their well-documented
advantages over homogeneous catalytic systems. Clays
have emerged as ideal acidic heterogeneous catalysts as
they are available in nature and are thus inexpensive.
Effectiveness of clays to catalyze this conversion was tested
for the reaction of morpholine and acrylonitrile. To our
satisfaction, the addition product was obtained in high
yield in a very short reaction time. Different aliphatic
amines and a,b-ethylenic compounds were studied as
substrates for this transformation which were catalyzed
1
These clays have Brùnsted as well as Lewis acidic sites
8
and thus increase their utility in both types of catalytic
applications. The positive features of clays also include
high stability, ease of handling and regeneration, lack of
corrosiveness and other environmental hazards. In recent
equally well with either kaolinitic clay or commercially
available Montmorillonite K10 and the results are
presented in Table 1.
9
2
1,3
years, we and others have developed several new appli-
cations of clays in heterogeneous catalytic reactions.
Several aromatic amines such as p-chloroaniline, p-nitro-
aniline, p-anisidine, p-toluidine, o-aminophenol and
o-aminothiophenol were subjected for this reaction with
clay as catalyst and methylacrylate or acrylonitrile as the
Michael acceptors. In most of the cases, aromatic amine
remained unchanged or in some cases, only a small amount
of product of single addition was detected. This was further
established by the following two experiments @Eq. @1)). A
diamine 1 with aromatic and aliphatic amino groups incor-
porated in the same molecule was exposed to an excess of
methylacrylate in re¯uxing dichloroethane. Careful analysis
of the single product 2 revealed the inertness of aromatic
amino group while the aliphatic one underwent the addition
reaction.
One of the simple approaches towards b-amino derivatives
such as b-aminoesters is via the Lewis acid-mediated
addition of amines to a,b-ethylenic compounds. Although,
4
5
in some cases reaction occurs with no special activation, in
others stronger reaction conditions are required.
6
A new catalytic system utilizing indium trichloride has been
recently reported by Loh and Wei for the addition of
7
amines to a,b-ethylenic compounds. This catalyst is not
selective and works equally well with aliphatic as well as
aromatic amines. This encouraged us to investigate the
reaction with clay catalysts and we wish to present our
®
ndings in this paper. To the best of our knowledge, the
1
b
report by Laszlo with transition metal doped catalysts is
the only reference available in the literature for the hetero-
geneous version of this reaction.
ꢀ
1†
Keywords: heterogeneous catalyst; Michael addition reaction; amines;
a,b-ethylenic compounds.
Corresponding authors. Tel.: 191-54-264-5742; fax: 191-20-5893614;
p
Another control experiment was performed with an equal
mixture of p-anisidine 3 and morpholine with excess of
acrylonitrile under the same catalytic conditions @Eq. @2)).
e-mail: vhdeshꢀdalton.ncl.res.in; avbedekarꢀyahoo.co.in
Present address: School of Pharmaceutical Sciences, University of
Shizuoka, Yada-52-1, Shizuoka 422 8526, Japan.
²
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020@01)00911-5

9
046
Table 1. Clay catalyzed reaction of amines with a,b-ethylenic compounds
Entry Reagents Product
N. S. Shaikh et al. / Tetrahedron 57 +2001) 9045±9048
Entry
Reagents
Product
@% yield)
a
a
@
% yield)
Ethylenic components:
All the reactions were performed in re¯uxing 1,2-dichloroethane
@
a
b
EDC) as solvent for 3 h @ent. 1±4, 6 and 7) and for 6 h @ent. 5, 8±10) with 2.0 equiv. @ent. 1±4, 7 and 8) and 3.5 equiv. ethylenic component @ent. 5, 6 and 9).
Isolated yield. All the compounds were characterized by usual spectral and analytical methods.
Without catalyst.
1
1
As expected, the former remained unaffected while the latter
furnished the addition product in high yield. These experi-
ments clearly show that the Lewis acidity of clays is suitable
only to activate aliphatic amines for the addition towards
a,b-ethylenic compounds and failed for less nucleophilic
aromatic amines. We feel that this selectivity could be
useful to discriminate the two types of amines for synthetic
applications.
g-aminobutyric acid @GABA) uptake inhibitors and
12
many new analogues are being prepared recently.
ꢀ2†
ꢀ3†
Reaction of benzylamine and acrylates was separately
investigated to establish conditions for selective preparation
of mono and bis-addition products. Reaction of methyl-
acrylate with excess of benzylamine in the presence of
clay furnished 4 as a single product due to mono addition
reaction, albeit in moderate yield @Eq. 3). The reaction of
benzylamine with excess of ethylacrylate in presence of
clay gave product 5 of bis-addition in excellent yield.
Compound 5 was subjected to Dieckmann cyclization
with sodium hydride to give ethyl-N-benzyl-4-oxo-3-piperi-
dinecarboxylate 5 in moderate yield. While compound 4 is a
direct precursor of b-aminoacids, 6 is used as starting
material for the synthesis of numerous heterocyclic
Thus, we present here, a practical and selective clay cata-
lyzed Michael type addition reaction of aliphatic amines
towards a,b-ethylenic compounds.
1.Experimental
1.1. General
Melting points were recorded on electrothermal melting
point apparatus and are uncorrected. The NMRspectra
were recorded in CDCl with TMS as an internal standard
3
1
on Bruker WM 200 NMRspectrometer @ H NMR at
200 MHz and C NMRat 50 MHz). Mass spectra
were recorded on Finnigan MAT 1020B GC±MS @EI)
1
0
13
compounds, and derivatives of nipecotic acids. Nipecotic
acid derivatives have received importance as they are

N. S. Shaikh et al. / Tetrahedron 57 +2001) 9045±9048
9047
instrument. The FT-IRspectra were recorded on an ATI-
Mattson Res. Series 1 spectrometer and Microanalyses were
performed on a Carlo±Erba instrument. Reagent grade ®ne
chemicals such as all amines, a,b-ethylenic compounds and
solvents were used without further puri®cation.
228@25), 207@20), 198@40), 171@15), 142@30), 128@100),
98@50). Microanalysis for C H NO , Calcd: C, 61.99; H,
9.22; N, 5.16; found: C, 62.11; H, 9.50; N, 5.40%.
1
4
25
4
1.1.7. Methyl-%3-diisopropylamino)-propionate %Table 1,
1
entry 10). White semisolid. H NMR d 0.86 @d, Jˆ6.4 Hz,
1
.1.1. 3-Morpholin-4-yl-propionitrile %Table 1, entry 1).
A mixture of morpholine @200 mg, 2.3 mmol), acrylonitrile
244 mg, 4.6 mmol) and kaolinetic clay @20 mg, 10%, w/w)
12H), 2.28 @t, Jˆ7.5 Hz, 2H), 2.63 @t, Jˆ5.9 Hz, 2H), 2.68
@hept, Jˆ6.6 Hz, 2H), 3.49 @s, 3H). n 2935, 2810, 1725,
2
1
@
1345, 1181, 980, 847 cm . Mass @m/z) 187@10), 172@50),
158@8), 130@12), 114@60), 98@70), 70@72), 56@100). Micro-
analysis for C H NO , Calcd: C, 64.17; H, 11.23; N, 7.48;
in dry 1,2-dichloroethane @5 mL) is re¯uxed for 3 h under
Ar. After the reaction @monitored by TLC), the catalyst was
separated and the crude product was puri®ed by column
chromatography on silica gel @,10% EtOAc in light petro-
leum ether) to get pure product as yellow oil @264 mg, 82%).
1
0
21
2
found: C, 64.30; H, 11.50; N, 7.80%.
1.1.8. Methyl-{3-[4-%4-aminophenyl)piperazine-1yl]}-
1
propionate %2): Eq.1. Red oil. H NMR d 2.53 @t,
Jˆ7.3 Hz, 2H), 2.62 @t, Jˆ5.1 Hz, 4H), 2.74 @t, 7.3, 2H),
3.04 @t, Jˆ5.1 Hz, 4H), 3.31 @brs, 2H), 3.69 @s, 3H), 6.61 @d,
Jˆ8.8 Hz, 2H), 6.77 @d, Jˆ8.8 Hz, 2H). n 3373, 3017, 2950,
Similar experimental procedure is followed for other
examples and the chemical yields of isolated products are
indicated in Table 1. Compounds from entries 1±4 were
fully characterized and their analytical data were in
2
1
2824, 1731, 1513, 1261, 1215, 666 cm . Mass @m/z)
1
3
accordance with the reported values.
263@100), 248@10), 190@25), 176@12), 147@15), 120@90),
106@20), 70@80), 56@85). Microanalysis for C H N O ,
14 21 3 2
1
.1.2. 3-[4-%2-Cyanoethyl)-piperazine-1-yl]-propionitrile
Table 1, entry 5). White solid. @mp 62±638C). H NMR
Calcd: C, 63.88; H, 7.98; N, 15.96; found: C, 64.00; H,
7.91; N, 15.85%.
1
%
d 2.45±2.55 @m, 12H), 2.69 @m, 4H) n 3373, 2937, 2816,
2
1
C H N , Calcd: C, 62.50; H, 8.30; N, 29.16; found: C,
2
241 cm . Mass @m/z) 192@25), 152@100), 138@10),
1
1.1.9. Methly-%3-benzylamino)-propionate %4): Eq. 3.
1
09@80), 97@30), 83@40), 70@75), 56@60). Microanalysis for
Pale yellow oil. H NMR d 2.64 @t, Jˆ6.3 Hz, 2H), 2.95
@t, Jˆ6.8 Hz, 2H), 3.40 @brs, 1H), 3.7 @s, 3H), 3.88 @s, 2H),
1
0
16
4
6
2.27; H, 8.59; N, 29.43%.
7.2±7.4 @m, 5H). n 3217, 2921, 2861, 1742, 1550, 1417,
1
2
325, 1260, 1207, 649 cm . Mass @m/z) 193@7), 175@12),
1
1.1.3. 3-[%2-Cyanoethyl)-%3-hydroxypropyl)-amino]-pro-
pionitrile %Table 1, entry 6). Yellow oil. H NMR d 1.68
160@5), 120@10), 91@100), 77@5), 65@20), 56@5). Micro-
analysis for C H NO , Calcd: C, 68.39; H, 7.77; N, 7.25;
found: C, 68.45; H, 7.95; N, 7.43%.
1
1
1
15
2
@
2
3
m, 2H), 2.49 @t, Jˆ7.1 Hz, 4H), 2.66 @t, Jˆ7.3 Hz, 2H),
2
260, 2928, 2853, 2249, 1638, 1400, 1051 cm . Mass
.84 @t, Jˆ7.3 Hz, 4H), 3.73 @t, Jˆ6.9 Hz, 2H). n 3425,
1
1.1.10. Ethyl-{3-[benzyl-%2-ethoxycarbonyl-ethyl)-amino]-
propionate %5): Eq.3. Colorless oil. H NMR d 1.20 @t,
1
@
m/z) 181@10), 141@30), 136@50), 117@60), 97@100), 90@25),
3@30), 71@15), 54@40). Microanalysis for C H N O, Calcd:
C, 59.66; H, 8.28; N, 23.20; found: C, 59.50; H, 8.50; N,
8
Jˆ7.3 Hz, 6H), 2.47 @t, Jˆ7.3 Hz, 4H), 2.82 @t, Jˆ7.3 Hz,
4H), 3.60 @2H, s), 4.13 @quart, Jˆ7.3 Hz, 4H), 7.1±7.4 @m,
5H). n 3020, 2922, 2860, 1738, 1510, 1403, 1308, 1243,
9
15
3
2
3.40%.
2
1
1
207, 1107, 752 cm . Mass @m/z) 307@8), 278@7), 230@5),
1
7
.1.4. Ethyl%3-diethylamino)-propionate %Table 1, entry
1
220@100), 206@30), 190@5), 170@6), 146@7), 132@7), 118@10),
105@6), 91@75), 77@4), 65@5). Microanalysis for C H NO ,
Calcd: C, 66.45; H, 8.14; N, 4.56; found: C, 66.20; H, 8.41;
N, 4.66%.
). White semisolid. H NMR d 0.99 @t, Jˆ7.3 Hz, 6H), 1.21
1
7
25
4
@
t, Jˆ7.8 Hz, 3H), 2.37± 2.53 @m, 6H), 2.76 @t, Jˆ7.3 Hz,
2
425, 1265, 1110 cm . Mass @m/z) 173@8), 158@16),
2
1
1
H), 4.06 @q, Jˆ7.5 Hz, 2H). n 3405, 2912, 2833, 1732,
1
44@10), 106@10), 86@100), 72@20), 57@50). Microanalysis
1.1.11. Ethyl-%1-benzyl-4-oxo-3-piperidine)carboxylate13
%6). A solution of diester 5 @1 g; 3.26 mmol) in of anhydrous
benzene @7 mL) was slowly added, under nitrogen atmos-
phere, to a suspension of oil free sodium hydride @0.194 g;
8.14 mmol) in anhydrous benzene @9 mL). Few drops of
absolute ethanol were added to initiate the reaction, which
was then re¯uxed for 3.5 h. At the completion of reaction
@TLC), glacial acetic acid @1 mL) was added followed by
water @3 mL) at room temperature. Reaction mixture was
stirred for 30 min. The organic layer separated, dried and
concentrated in vacuum to get 0.507 g @60%) of red oil as a
pure compound.
for C H NO , Calcd: C, 62.43; H, 10.98; N, 8.09; found:
9
C, 62.10; H, 11.00; N, 8.11%.
19
2
1.1.5. 3-[%2-Hydroxy-1%R)-methyl-2%S)-phenyl-ethyl)-
methylamino]-propionitrile %Table 1, entry 8). Colorless
1
thick oil. H NMR d 0.95 @d, Jˆ6.8 Hz, 3H), 2.33 @s, 3H),
2
4
2
1
.42 @t, Jˆ6.8 Hz, 2H), 2.71±2.90 @m, 4H), 4.81 @d, Jˆ
.4 Hz, 1H), 7.20±7.40 @m, 5H). n 3401, 2963, 2920,
802, 2238, 1374, 1038, 696 cm . Mass @m/z) 218@8).
48@2), 117@10), 111@100), 105@10), 77@15), 68@25). Micro-
2
1
analysis for C H N O, Calcd: C, 71.56; H, 8.26; N, 12.84;
1
3
18
2
found: C, 71.48; H, 7.90; N, 12.92%.
1
H NMR d 1.29 @t, Jˆ7.3 Hz, 3H), 2.41 @t, Jˆ7.3 Hz, 2H),
1
.1.6. Methyl-3-[cyclohexyl-%2-methoxycarbonyl-ethyl)-
2.62 @t, Jˆ7.3 Hz, 2H), 2.81 @t, Jˆ7.3 Hz, 1H), 3.10 @d, Jˆ
7.3 Hz, 2H), 3.66 @s, 2H), 4.20 @quartet, Jˆ7.2 Hz, 2H). n
1
amino]-propionate %Table 1, entry 9). Yellow oil. H
NMR d 1.10±1.30 @m, 2H), 1.60±1.90 @m, 8H), 2.40±
2
1
2914, 1730, 1694, 1637, 1520, 1326, 1217, 1113, 740 cm .
Mass @m/z) 261@20), 232@10), 214@60), 188@50), 170@10),
146@5), 132@5), 124@35), 96@7), 91@100), 77@5), 65@7).
2
1
.60 @m, 5H), 2.90 @t, Jˆ6.8 Hz, 4H), 3.68 @s, 6H). n
2
1
745, 1150, 880 cm . Mass @m/z) 271@5), 250@10),

9048
N. S. Shaikh et al. / Tetrahedron 57 +2001) 9045±9048
Microanalysis for C H NO , Calcd: C, 68.96; H, 7.28; N,
1
Utimoto, K. Chem. Lett. 1994, 827. @d) Jenner, G. Tetrahedron
Lett. 1995, 36, 233.
5
19
3
5
.36; found: C, 69.11; H, 7.34; N, 5.56%.
7
. Loh, T.-P.; Wei, L.-L. Synlett 1998, 975.
. Sabu, K. R.; Sukumar, R.; Lalithambika, M. Bull. Chem. Soc.
Jpn 1993, 66, 3535.
8
Acknowledgements
9
. Purchased from Aldrich Chemical Co.
We wish to thank CSIR, New Delhi for the award of Pool
Of®cership to A. V. B. and Senior Research Fellowship to
N. S. S.
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