Silica supported Fe(HSO4)3 as an efficient, heterogeneous and recyclable catalyst for synthesis of β-enaminones and β-enamino esters

Article abstract of DOI:10.1016/j.molcata.2012.07.021

A series of β-substituted enaminones were prepared through the one-pot reaction of β-dicarbonyl compounds with various amines in the presence of silica ferric hydrogensulfate under solvent free conditions at room temperature. The reactions proceed smoothl

Full text of DOI:10.1016/j.molcata.2012.07.021

Journal of Molecular Catalysis A: Chemical 363–364 (2012) 430–436
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Silica supported Fe(HSO4)3 as an efficient, heterogeneous and recyclable catalyst
for synthesis of ␤-enaminones and ␤-enamino esters
Hossein Eshghi∗, Seyed Mohammad Seyedi, Elham Safaei, Mohammad Vakili, Abolghasem Farhadipour,
Mohtaram Bayat-Mokhtari
Department of Chemistry, School of Sciences, Ferdowsi University of Mashhad, Mashhad 91775-1436, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 3 May 2012
Received in revised form 15 July 2012
Accepted 18 July 2012
Available online 10 August 2012
A series of ␤-substituted enaminones were prepared through the one-pot reaction of ␤-dicarbonyl com-
pounds with various amines in the presence of silica ferric hydrogensulfate under solvent free conditions
at room temperature. The reactions proceed smoothly in excellent yield, high chemoselectivity and with
an easy work-up. Catalytic amount of Fe(HSO4)3·SiO2 catalyzed one-pot reaction of linear and cyclic ␤-
diketones and ␤-keto esters with aromatic and aliphatic amines. The B3LYP/6-31G** full optimizations
were carried out for enol-enamine tautomers of enaminones.
This paper is dedicated to Professor Sayyed
Faramarz Tayyari on the occasion of his
65th birthday and his ongoing 35 years
research in the field of ␤-dicarbonyl
hydrogen bonding.
© 2012 Elsevier B.V. All rights reserved.
Keywords:
Amine
␤-Dicarbonyl compounds
␤-Enaminones
Silica ferric hydrogensulfate
1. Introduction
metal triflates and tedious workup [10], requirement of drastic
conditions and use of harmful reagents [11], use of homogenous
The enaminones and enamino esters are very stable struc-
tural motifs which are prepared by inexpensive raw materials.
Hence they are considered as excellent starting materials in
organic synthesis. Enaminones and enamino esters are used as
versatile building blocks for synthesis of important heterocyclic
compounds, nitrogen containing compounds, naturally occurring
alkaloids, pharmaceutical drugs with antiepileptic, anticonvulsant
and antitumor properties [1–8]. They even served as synthons for
␥-aminoalcohol, ␤-aminoacids which are a class of very stable com-
pounds useful in asymmetric catalysis as a chelating agent [9].
Condensation reactions of carbonyl compounds with amines in
the presence of various acid catalysts like Yb(OTf)3 [10], Zn(O4Cl)2
[11,12], InBr3 [13], CoCl2 [14], and LiHSO4·SiO2 [15] are well
reported for the synthesis of ␤-enaminones and enamino esters.
Additionally, non-conventional techniques such as microwave and
ultrasound are also reported [16–18]. However, these methods are
associated with certain drawbacks like use of moisture sensitive
and non recyclable catalyst [12–14]. Hence there is sufficient scope
for the development of heterogeneous, reusable catalytic system,
which could catalyze the synthesis of enaminones and enamino
esters at milder operating conditions.
In this paper, we report a fast, clean and highly efficient
method for the synthesis of ␤-enaminones and ␤-enamino esters
via condensation of ␤-dicarbonyl compounds with amines using
Fe(HSO4)3·SiO2 as a non-toxic, readily producible, heterogeneous
and reusable catalytic system (Scheme 1).
2. Experimental
2.1. General
Chemicals were either prepared in our laboratories or purchased
from Merck, Fluka and Aldrich Chemical Companies. All yields refer
to the isolated products. Melting points were recorded on an Elec-
tro thermal type 9100 melting point apparatus. IR spectra were
recorded on a Thermo Nicolet AVATAR-370-FTIR spectrophotome-
ter. The 1H and 13C NMR spectra were recorded on a Bruker AC 100
and Bruker DRX-400 Avance spectrometers at 400 and 100.65 MHz,
∗
Corresponding author. Tel.: +98 5118795457; fax: +98 5118795457.
E-mail address: heshghi@um.ac.ir (H. Eshghi).
1381-1169/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molcata.2012.07.021

H. Eshghi et al. / Journal of Molecular Catalysis A: Chemical 363–364 (2012) 430–436
431
Ar
O
HN
O
O
Fe(HSO4)3.SiO2
R1
R2
+
ArNH2
R1
R2
Solvent-free. r.t
3
1
2
R1, R2 = alkyl, aryl, cycloalkyl, alkoxy
Scheme 1. Synthesis of ␤-enaminones and ␤-enamino esters in the presence of Fe(HSO4)3·SiO2.
Methyl (Z)-3-aniline-2-butenoate (3e): yield 90%; m.p = 48–49 ◦C,
lit. [13] m.p 46–47 ◦C; 1H NMR (CDCl3, 100 MHz) ı: 10.3 (b, 1H),
Table 1
Conditions optimization of the reaction between aniline and acetylacetone.
7.0–7.3 (m, 5H), 4.7 (s, 1H), 3.67 (s, 3H), 2.0 (s, 3H(. IR (KBr, cm−1
)
Entry
Solvent
CH3OH
Catalyst
Mol (%)
Condition
Yield (%)
ꢀ: 3248, 1651, 1606, 1590, 1262, 786.
1
2
Fe(HSO4)3
Fe(HSO4)3
10
10
10
25
50
25
25
25
25
25
Reflux, 1 h
r.t, 1 h
50
50
80
89
89
89
87
85
85
84
Methyl(Z)-3-(4-methoxy aniline)-2-butenoate (3f): yield 93%;
m.p = 65–67 ◦C, lit. [13] oil; 1H NMR (CDCl3, 100 MHz) ı:10.2 (b,
1H), 7.0 (AB-q, 4H), 4.8 (s, 1H), 3.75 (s, 3H), 3.06 (s, 3H), 2.0 (s, 3H).
IR (KBr, cm−1) ꢀ: 3264, 1651, 1613, 1513, 1246, 788.
Methyl (Z)-3-(4-toluidino)-2-butenoate (3g): yield 91%;
m.p = 58–60 ◦C, lit. [13] m.p 57–58 ◦C; 1H NMR (CDCl3, 100 MHz)
ı: 10.3 (b, 1H), 7.1 (AB-q, 4H), 4.3 (s, 1H), 3.65 (s, 3H), 2.4 (s,
3H), 1.95 (s, 3H). IR (KBr, cm−1) ꢀ: 3264, 1651, 1598, 1275,
1163.
Methyl (Z)-3-(4-choloroaniline)-2-butenoate (3h): yield 85%;
m.p = 61–62 ◦C, lit. [13] m.p 60–61 ◦C; 1H NMR(CDCl3, 100 MHz) ı:
10.4 (b, 1H), 7.2 (AB-q, 4H), 6.6 (b, 1H), 4.85 (s, 1H), 3.7 (s, 3H), 2.1
(s, 3H). IR (KBr, cm−1) ꢀ: 3374, 1652, 7618, 1271, 1167.
CH3OH
3
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
Fe(HSO4)3/SiO2
Fe(HSO4)3/SiO2
Fe(HSO4)3/SiO2
Fe(HSO4)3/SiO2
Fe(HSO4)3/SiO2
Fe(HSO4)3/SiO2
Fe(HSO4)3/SiO2
Fe(HSO4)3/SiO2
r.t, 20 min
r.t, 7 min
r.t, 7 min
r.t, 7 min
r.t, 7 min
r.t, 7 min
r.t, 7 min
r.t, 7 min
4a
5
6b
7c
8d
9e
10f
a
Optimum conditions.
b–f
Reusability of the catalyst in the new runs.
respectively. Chemical shifts are reported in ppm downfield from
TMS as internal standard; coupling constants J are given in Hertz.
Elemental analyses were obtained on a Thermo Finnigan Flash EA
micro-analyzer. Silica supported ferric hydrogensulfate prepared
as we previously reported [19].
(Z)-3-Anilino-1-phenyl-2-buten-1-one
(3i):
yield
93%;
m.p = 108–110 ◦C, lit. [15] m.p 109–111 ◦C; 1H NMR (CDCl3,
100 MHz) ı: 13.1 (b, 1H), 8.0 (m, 2H), 7.1–7.5 (m, 8H), 5.95 (s, 1H),
2.3 (s, 3H). IR (KBr, cm−1) ꢀ: 3435, 1621, 1589, 1547, 1325, 752.
(Z)-3-(4-Methoxyaniline)-1-phenyl-2-buten-1-one (3j): yield
95%; m.p = 103–105 ◦C; 1H NMR (CDCl3, 400 MHz) ı: 13.99 (b, OH,
0.083H), 12.96 (b, NH, 0.917H), 7.95 (d, 2H, J = 6.4 Hz), 7.47 (m, 3H),
7.14 (d, 2H, J = 7.6 Hz), 6.93 (d, 2H, J = 8.0 Hz), 5.90 (s, 1H), 3.85 (s,
3H), 2.10 (s, 3H). 13C NMR (CDCl3, 100 MHz) ı: 188.4, 163.2, 157.9,
140.2, 131.5, 130.8, 128.3, 127.1, 126.6, 93.6, 55.5, 20.3. IR (KBr,
cm−1) ꢀ: 3051, 3010, 2949, 2830, 1623, 1607, 1587, 1508, 1330,
768.
2.2. General procedure for the synthesis of compounds 3a–3t
A mixture of the ␤-dicarbonyl compound (2 mmol), the amine
(2 mmol) and Fe(HSO4)3·SiO2 [0.22 g containing 0.25 mmol of
Fe(HSO4)3] was stirred in solvent free condition at room temper-
ature for the appropriate time (Table 1). After completion of the
reaction as indicated by TLC, the mixture was diluted by ethyl
acetate (20 ml). The insoluble catalyst was separated by filtration
and rinsed with ethyl acetate, dried and re-used. The solvent of
the filtrate was evaporated and the crude product was purified by
recrystallization from EtOH/H2O (1/1).
(Z)-1-Phenyl-3-(4-toluidino)-2-buten-1-one (3k): yield 91%;
m.p = 90–92 ◦C; 1H NMR (CDCl3, 400 MHz) ı: 13.96 (b, OH, 0.246H),
12.95 (b, NH, 0.754H), 7.96 (m, 2H), 7.47 (m, 3H), 7.20 (m, 2H),
7.11 (m, 2H), 5.91 (s, 1H), 2.34 (s, 3H), 2.15(s, 3H). 13C NMR (CDCl3,
100 MHz) ı: 188.5, 162.6, 140.1, 136.0, 135.7, 130.8, 129.8, 128.3,
127.1, 124.9, 93.9, 21.0, 20.4. IR (KBr, cm−1) ꢀ: 3047, 2912, 1993,
1899, 1821, 1622, 1572, 754, 506.
(Z)-3-(4-Choloroanilino)-1-phenyl-2-buten-1-one (3l): yield 81%;
m.p = 126–128 ◦C; 1H NMR (CDCl3, 400 MHz) ı: 14.05 (b, OH,
0.242H), 13.10 (b, NH, 0.758H), 7.94 (d, 2H, J = 6.8 Hz), 7.47 (m, 3H),
7.37 (d, 2H, J = 7.2 Hz), 7.14 (d, 2H, J = 7.6 Hz), 5.95 (s, 1H), 2.17 (s,
3H). 13C NMR (CDCl3, 100 MHz) ı: 189.0, 161.8, 139.8, 137.3, 131.3,
131.1, 129.4, 128.4, 127.1, 125.9, 94.7, 20.5. IR (KBr, cm−1) ꢀ: 3411,
3080, 3051, 1623, 1588, 1549, 1326, 766.
Spectral data of the prepared compounds:
(Z)-4-Anilino-3-penten-2-one (3a): yield 89%; m.p = 45–47 ◦C, lit.
[15] m.p 47–49 ◦C; 1H NMR (CDCl3, 100 MHz) ı: 12.5 (b, 1H), 6.9–7.3
(m, 5H), 5.15 (s, 1H), 2.1 (s, 3H), 1.95 (s, 3H). IR (KBr, cm−1) ꢀ: 3435,
3051, 2994, 2924, 1614, 1596, 1282, 764, 696.
(Z)-4-(4-Methoxyanilino)-3-penten-2-one (3b): yield 91%;
m.p = 45–47 ◦C, lit. [13] m.p 41–43 ◦C; 1H NMR (CDCl3, 100 MHz)
ı: 12.3 (b, 1H), 6.9 (AB-q, 4H), 5.1 (s, 1H), 3.7 (s, 3H), 2.07 (s, 3H),
1.88 (s, 3H). IR (KBr, cm−1) ꢀ: 3447, 3358, 3219, 2990, 2916, 1617,
1567, 1494, 1277, 1091.
3-Anilino-5,5-dimethyl-2-cyclohexen-1-one (3m): yield 86%;
m.p = 184–185 ◦C, lit. [15] m.p 184–186 ◦C; 1H NMR (CDCl3,
100 MHz) ı: 7.1–7.4 (m, 5H), 6.4 (b, 1H), 5.6 (s, 1H), 2.25 (m, 4H),
2.25 (m, 4H), 1.1(s, 6H). IR (KBr, cm−1) ꢀ: 3231, 1597, 1573, 1244,
705.
(Z)-4-(4-Toluidino)-3-penten-2-one
(3c):
yield
90%;
m.p = 63–65 ◦C, lit. [15] m.p 66–68 ◦C; 1H NMR (CDCl3, 100 MHz) ı:
12.4 (b, 1H), 7.1 (m, 4H), 5.15 (s, 1H), 2.4 (s, 3H) 2.1 (s, 3H), 1.9 (s,
3H). IR (KBr, cm−1) ꢀ: 3440, 3031, 2994, 2921, 2855, 1610, 1567,
1276, 808.
3-(4-Methoxy aniline)-5,5-dimethyl-2-cyclohexen-1-one (3n):
yield 91%; m.p = 193–195 ◦C, lit. [15] m.p 192–194 ◦C; 1H NMR
(CDCl3, 100 MHz) ı: 7.1 (b, 1H), 6.9 (AB-q, 4H), 5.3 (s, 1H), 3.75 (s,
3H), 2.25 (AB-q, 4H), 1.05 (s, 6H). IR (KBr, cm−1) ꢀ: 3206, 1607,
1568, 1536, 1509, 1243.
(Z)-4-(4-Choloroanilino)-3-penten-2-one (3d): yield 85%;
m.p = 59–60 ◦C, lit. [13] m.p 61–62 ◦C; 1H NMR (CDCl3, 100 MHz)
ı: 12.45 (b, 1H), 7.2 (m, 4H), 5.25 (s, 1H), 2.15 (s, 3H), 2.0 (s, 3H).
IR (KBr, cm−1) ꢀ: 3448, 3354, 3219, 3060, 2990, 2921, 1617, 1567,
1494, 1276.

432
H. Eshghi et al. / Journal of Molecular Catalysis A: Chemical 363–364 (2012) 430–436
Table 2
Enamination of ␤-dicarbonyl compounds in the presence of Fe(HSO4)3·SiO2.
Entry
Dicarbonyl compound
Amine
Product
Time (min)
Yield (%)a
3a
O
HN
O
O
O
O
O
O
O
O
O
O
O
O
NH2
1
7
89
OMe
OMe
Me
3b
O
HN
HN
NH2
Me
2
3
4
5
6
12
12
16
40
40
91
90
85
–
3c
O
NH2
Cl
Cl
3d
O
HN
NH2
NO2
NH2
NO2
No reaction
No reaction
Cl
NH2
–
F
Br
Br
O
O
O
O
NH2
7
8
No reaction
40
12
–
3e
O
HN
NH2
OMe
OMe
OMe
OMe
MeO
90
OMe
OMe
Me
3f
O
O
O
O
O
O
O
O
O
HN
NH2
Me
MeO
9
10
11
16
16
16
93
91
85
3g
HN
HN
NH2
Cl
MeO
Cl
3h
NH2
MeO

H. Eshghi et al. / Journal of Molecular Catalysis A: Chemical 363–364 (2012) 430–436
433
Table 2 (Continued)
Entry
Dicarbonyl compound
Amine
Product
Time (min)
Yield (%)a
3i
O
HN
O
O
O
O
O
O
O
O
NH2
Ph
Ph
Ph
Ph
12
13
14
12
93
95
91
OMe
OMe
Me
3j
O
HN
HN
HN
NH2
Me
Ph
16
16
3k
O
NH2
Cl
Ph
Cl
3l
O
NH2
Ph
O
Ph
3m
15
16
25
25
81
86
O
O
N
H
NH2
OMe
3n
O
O
MeO
O
O
O
N
H
NH2
Me
17
18
20
20
91
90
3o
Me
O
O
N
NH2
Cl
H
3p
O
Cl
O
N
NH2
H
19
20
30
15
60
90
3q
O
O
O
O
O
O
O
N
NH2
H
OMe
3r
O
MeO
N
NH2
Me
H
21
22
10
13
92
91
3s
O
Me
N
NH2
H

434
H. Eshghi et al. / Journal of Molecular Catalysis A: Chemical 363–364 (2012) 430–436
Table 2 (Continued)
Entry
Dicarbonyl compound
Amine
Product
3t
Time (min)
Yield (%)a
Cl
O
Cl
O
O
N
H
NH2
H
23
20
87
a
Isolated yields.
R3
R3-NH2
R3
H
H
R3
H
N
O
N
O
N
R1
R2
R1
R2
R1
R2
R1
R2
OH
O
O
O
OH
[Fe]
[Fe]
[Fe]
[Fe]
-H2O
IV
III
II
SiO2
SiO2
I
SiO2
SiO2
[Fe] = Fe(HSO4)3
Scheme 2. Suggested mechanism for the synthesis of ␤-enaminones and ␤-enamino esters.
5,5-Dimethyl-3-(4-toluidino)-2-cyclohexen-1-one (3o): yield
90%; m.p = 199–201 ◦C, lit. [21] m.p 203–204 ◦C; 1H NMR (CDCl3,
100 MHz) ı: 7.5 (AB-q, 4H), 6.95 (b, 1H), 5.5 (s, 1H), 2.3 (AB-q, 4H),
1.1 (s, 6H). IR (KBr, cm−1) ꢀ: 3244, 1608, 1575, 1282, 1147,812.
After the above optimization, we chose a variety of structurally
different amines including aliphatic and aromatic amines were con-
densed with various 1,3-diketones like methyl acetoacetate, acetyl
acetone and 1,3-cyclohexanedione using Fe(HSO4)3·SiO2 as a het-
erogeneous catalyst at room temperature (Scheme 1). The results
are shown in Table 2. All the isolated products were well charac-
terized by their IR, 1H NMR spectral analysis.
It was also found that amines containing electron donating
groups gave better yield and showed good reactivity in compar-
ison to amines having electron withdrawing groups, owing to the
availability of the lone pair on nitrogen. However, electron with-
drawing substituents were failed in this reaction. The condensation
of aliphatic amines as well as diamines with ␤-dicarbonyl com-
pounds was also efficiently performed and after further studies on
ligand abilities and biological activities will be published.
Reusability of the catalyst is the most significant advantage of
our method. For the reaction of aniline with acetylacetone no signif-
icant loss of the product yield was observed when Fe(HSO4)3·SiO2
was reused after five times of recycling (Table 1, entries 6–10).
It is clear from our results that the Fe(HSO4)3·SiO2 catalyzed
condensation reaction of 1,3-dicarbonyls with the amines provides
a remarkably rapid and viable alternative route for the synthesis of
␤-enaminones. This paper reports for the first time a regio- and
chemoselective enamination of ␤-dicarbonyl compounds under
mainly solvent free conditions using silica ferric hydrogensulphate
at room temperature in excellent yields and purity.
Suggested mechanism for this reaction was shown in Scheme 2.
According to, electron releasing substituted anilines which have
nucleophilic identity carry on the first step of reaction and then
by stabilizing the cationic intermediate III forwarded intermedi-
ate II to products and catalyst was regenerated. Electron releasing
groups such as 4-methyl or 4-methoxy aniline reacted with all ␤-
dicarbonyl compounds in high yields but 4-chloroaniline reacted
in relatively longer reaction times and lower yields. Strong elec-
tron withdrawing groups such as nitro group (Table 2, entries 5–7)
failed in this reaction because of low nucleophilic identity.
Fig. 1 shows two possible enol forms of compound 3a. As it is
cleared, one form is in enolic state (3aenol) and another is in enamine
3-(4-Choloroaniline)-5,5-dimethyl-2-cyclohexen-1-one
(3p):
yield 60%; m.p = 208–209 ◦C, lit. [21] m.p 208–210 ◦C; 1H NMR
(CDCl3, 100 MHz) ı: 6.9–7.3 (m, 5H), 5.4 (s, 4H), 2.25 (AB-q, 4H),
1.1 (s, 3H), 1.05 (s, 3H). IR (KBr, cm−1) ꢀ: 3244, 1611, 1574, 1284,
1149.
3-Anilino-2-cyclohexen-1-one (3q): yield 90%; m.p = 179–180 ◦C,
lit. [17] m.p 178–180 ◦C; 1H NMR (CDCl3, 100 MHz) ı: 6.6–7.4 (m,
6H), 5.5 (s, 1H), 2.2–2.5 (m, 4H), 1.9 (m, 2H). IR (KBr, cm−1) ꢀ: 3264,
1604, 1593, 1571, 1527, 1244.
3-(4-Methoxy aniline)-2-cyclohexen-1-one (3r): yield 92%;
m.p = 163–164 ◦C, lit. [22] m.p 164–166 ◦C; 1H NMR (CDCl3,
100 MHz) ı: 6.95 (AB-q, 4H), 6.2 (b, 1H), 5.35 (S, 7H), 3.75 (S, 3H),
2.2–2.5 (m, 4H), 2.0 (m,2H). IR (KBr, cm−1) ꢀ: 3220, 1571, 1535,
1510, 1240, 1185.
3-(4-Toluidino)-2-cyclohexen-1-one
(3s):
yield
91%;
m.p = 150–152 ◦C; 1H NMR (CDCl3, 100 MHz) ı: 7.1 (AB-q, 4H), 6.8
(b, 1H), 5.5 (s, 1H), 2.2–2.5 (m, 4H), 2.3 (s, 3H), 2.0 (m, 2H). IR (KBr,
cm−1) ꢀ: 3214, 1572, 1535, 1512, 1243, 1184.
3-(4-Choloroaniline)-2-cyclohexen-1-one (3t): yield 87%;
m.p = 191–192 ◦C, lit. [21] m.p 190–191.5 ◦C; 1H NMR (CDCl3,
100 MHz) ı: 7.4 (b, 1H), 7.1 (AB-q, 4H), 5.45 (s, 1H), 2.2–2.5 (m,
4H), 1.95 (m, 2H). IR (KBr, cm−1) ꢀ: 3250, 1602, 1569, 1520,
1245.
3. Results and discussion
Initially condensation of aniline and acetylacetone was selected
as a model reaction, and the influence of various reaction param-
eters like catalyst, temperature and time was examined (Table 1).
Fe(HSO4)3·SiO2 proved to be the most efficient because the reac-
tion could be carried out in excellent yield and short reaction time.
The best reaction conditions require the presence of a small amount
of Fe(HSO4)3·SiO2 (25 mol%) under solvent-free condition at room
temperature.

H. Eshghi et al. / Journal of Molecular Catalysis A: Chemical 363–364 (2012) 430–436
435
Table 3
Calculated energies (Hartrees), the energy differences between 3aenamine and 3aenol kcal/mol, and some selected parameters of the enamine and enol tautomers of 3a in gas
phase and in some solvents.a
Solution/parameters 3aenamine
3aenol
ꢁEb
N
H (Å) H· · ·O (Å)
N· · ·O (Å) NHO (◦)
E
N· · ·H (Å)
O
H (Å) N· · ·O (Å) NHO (◦)
E
Gas
CHCl3
CH3CN
Ethanol
Cyclohexane
Water
1.033
1.032
1.031
1.031
1.032
1.031
1.749
1.741
1.769
1.768
1.755
1.769
2.637
2.646
2.651
2.651
2.642
2.652
141.6
141.3
141.1
141.1
141.4
141.1
−557.0012778
−557.0064494
−557.0085458
−557.0083881
−557.0040765
−557.008747
1.604
1.558
1.582
1.583
1.596
1.583
1.024
1.028
1.029
1.023
1.026
1.029
2.542
2.534
2.531
2.531
2.538
2.531
149.9
150.5
150.8
150.8
150.2
150.8
−556.9936801
−556.9974235
−556.9990001
−556.9988801
−556.9956836
−556.9991539
4.8(4.5)
5.7(4.9)
6.0(5.2)
6.0(5.2)
5.3(4.5)
6.0(5.2)
a
All calculated at B3LYP/6-31G**.
ꢁE, energy difference between 3aenamine and 3aenol in kcal/mol, the corrected value for the ZPE is given in parenthesis.
b
Table 4
Comparison of enamination of acetylacetone with aniline by Fe(HSO4)3·SiO2 with literature reported methods.
Entry
Catalyst mole (%)
Solvent
Temperature (◦C)
Reaction time
Isolated yield (%)
Ref.
1
2
3
4
5
Yb(OTf)3, 5
[Hbim]BF4
LiHSO4·SiO2, 20
P2O5·SiO2, 11.5
Fe(HSO4)3·SiO2, 12.5
–
r.t
28
80
r.t
r.t
12 h
99
91
91
85
89
[10]
[20]
[15]
[23]
[Hbim]BF4
25 min
10 min
10 min
7 min
–
–
–
Present work
(3j–3l) 400 MHz 1H NMR spectra in CDCl3 and observed NH group
at 13 ppm (enaminones as major tautomers of 3j–3l, 75.4–91.7%)
and OH group at 14 ppm (enols as minor tautomers of 3j–3l,
8.3–24.6%). Hydroxyl group is acidic than amine group and so, H· · ·N
hydrogen bonding of OH group with imine (14 ppm) is stronger
than H· · ·O hydrogen bonding of NH group with carbonyl group
(13 ppm), respectively. However, experimental data showed enam-
ino ketones and enamino esters exist usually as enamine form. The
parent keto forms were not observed.
Table 4 shows efficiency of our catalyst compared to other cat-
alysts reported in the literature. The results of enamination of
acetylacetone with aniline by Fe(HSO4)3·SiO2 was compared with
some reported methods. The results revealed that the reaction
times and catalyst loading in our method were significantly lower
than reported methods.
4. Conclusion
In conclusion, we have developed an efficient protocol for syn-
thesis of ␤-enaminones and ␤-enamino esters using silica ferric
hydrogensulfate as a heterogeneous, recyclable and stable catalyst.
The reaction was optimized with respect to various parameters and
could be employed for the condensation of different dicarbonyl
compounds and amines. The advantages offered by this protocol
include high yields of desired products, under ambient conditions
with diverse substrate compatibility making it an important sup-
plement to the existing methods.
Fig. 1. Optimized structures of two possible enol forms of compound 3a: (3aenol
right and (3aenamine) left.
)
state (3aenamine). The B3LYP/6-31G** full optimizations were car-
ried out for each forms of 3a. Table 3 reports the optimized energies
and some selected parameters of these tautomers in gas phase and
in some solvents. However, this calculation suggests that enamine
form (3aenamine) is stable tautomer in gas and solution phases. In
gas phase the energy differences is 4.8 kcal/mol, whereas in solu-
tion increased to 5.3–6.0 kcal/mol due to more stabilized 3aenamine
with higher dipole moment in solvents.
Acknowledgements
We are grateful to Ferdowsi University of Mashhad Research
Council for their financial support of this work (GN: 3/18349).
In the 1H NMR (100 MHz, CDCl3) spectra of compounds 3m–3t
which exist in its enaminones form show a broad singlet in
6.2–7.4 region for NH group. However, this group can not form
an intramolecular hydrogen bonding. This signal was shifted
to 10.2–10.4 ppm for enamino esters 3e–3h which includes an
intramolecular hydrogen bonding of NH group with ester carbonyl
group. Compounds 3a–3d show a broad singlet in 12.2–12.5 ppm
for NH group hydrogen bonded with ketone carbonyl group. In
compounds 3i–3l, this signal was shifted to 13–13.1 ppm which
for accurate assignment to NH or OH group we prepared their
Appendix A. Supplementary data
Supplementary data associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/j.molcata.
2012.07.021.
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