An efficient chemo-And stereoselective synthesis of enaminones and enaminoesters using (Bromodimethyl)sulfonium bromide under solvent-free conditions

Article abstract of DOI:10.1002/hc.20477

(Bromodimethyl)sulfonium bromide has efficiently been employed for chemo- and stereoselective conversions of β-dicarbonyl compounds into β-enaminones and β-enaminoesters by a treatment with amines at room temperature under solvent-free conditions.

Full text of DOI:10.1002/hc.20477

Heteroatom Chemistry
Volume 19, Number 6, 2008
An Efficient Chemo- and Stereoselective
Synthesis of Enaminones and Enaminoesters
Using (Bromodimethyl)sulfonium Bromide
Under Solvent-Free Conditions
Biswanath Das, Boddu Shashi Kanth, Anjoy Majhi,
and Kongara Ravinder Reddy
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 23 November 2007; revised 4 April 2008
SiO2/HClO4 [10], Al2O3 [11], montmorillonite K-10
ABSTRACT: (Bromodimethyl)sulfonium bromide
[12], Bi(TFA)3 [13], Bi(TFA)3-TBAB [14], NaAuClO4
has efficiently been employed for chemo- and stereose-
[15], Zn(ClO4)2·6H2O [16], CeCl3·7H2O [17], InBr3
lective conversions of β-dicarbonyl compounds into β-
[18], and CAN [19] have been developed. However,
enaminones and β-enaminoesters by a treatment with
many of these methods have many disadvantages
amines at room temperature under solvent-free condi-
such as high temperatures, long reaction times, low
ꢀ
C
tions.
2008 Wiley Periodicals, Inc. Heteroatom Chem
yields, strongly acidic conditions, and use of costly
reagents and hazardous solvents. Thus, an improved
method for the preparation of β-enaminones and
β-enaminoesters is essential.
19:630–633, 2008; Published online in Wiley InterScience
(www.interscience.wiley.com). DOI 10.1002/hc.20477
INTRODUCTION
RESULTS AND DISCUSSION
β-Enaminones and β-enaminoesters are valuable in-
termediates for the synthesis of different bioactive
molecules [1] including antibacterial, antitumor,
and anticonvulsant agents [2]. They are also used for
the preparation of amino acids [3], aminols [4,5],
peptides [6], and alkaloids [7]. β-Enaminones can
be prepared by condensation of β-dicarbonyl com-
pounds with amines under reflux in an aromatic sol-
vent with azeotropic removal of water [8]. Recently,
some other methods applying SiO2/microwaves [9],
As a part of our work [20] on the development
of useful synthetic methodologies, we have discov-
ered that β-enaminones and β-enaminoesters can
efficiently be synthesized from β-dicarbonyl com-
pounds by treatment with amines in the presence
of (bromodimethyl)sulfonium bromide (Scheme 1).
R2
Me2S+BrBr-
Solvent-free
NH
87
O
O
O
R2 NH2
+
R1
R1
r.t., 10 25 min
-
This article is Part 156 in the series “Studies on novel synthetic
methodologies.”
Correspondence to: Biswanath Das; e-mail: biswanathdas@
yahoo.com.
-
94%
1
2
3
Contract grant sponsor: UGC, New Delhi, India.
Contract grant sponsor: CSIR, New Delhi, India.
2008 Wiley Periodicals, Inc.
c
ꢀ
SCHEME 1
630

Chemo- and Stereoselective Synthesis of Enaminones and Enaminoesters Using (Bromodimethyl)sulfonium Bromide 631
A series of β-enaminones and β-enaminoesters
were prepared from different β-dicarbonyls (β-
diketones and β-ketoesters) and amines (aromatic
and aliphatic) under solvent-free conditions. The
products were formed in excellent yields within a
short period of time (10–25 min). Considering yields
and reaction times (bromodimethyl)sulfonium bro-
mide was found to be more efficient than several
other reagents that are previously used.
spectra that showed the appearance of the proton of
the NH group in the range of δ 8.5–12.5.
(Bromodimethyl)sulfonium bromide [21] works
under mild reaction conditions. Previously, it was
utilized to carry out some synthetic transformations
but its catalytic activity was not fully explored. In the
present case, it has been efficiently employed for the
preparation of enamine derivatives.
In conclusion, we have described a simple
and efficient method for the synthesis of β-
enaminones and β-enaminoesters by the treatment
of β-dicarbonyl compounds with amines, using (bro-
modimethyl)sulfonium bromide as a catalyst. The
mildness of the conversion, solvent-free conditions,
short reaction times, and high yields are the notable
In the present method, an amine attacks only
a ketone carbonyl of a diketone or a ketoester.
Thus, the other carbonyl group will always be free.
The products (Table 1) were found to possess (Z)-
selectivity secured by an intramolecular hydrogen
1
bonding. This was evidenced from their H NMR
TABLE 1 Synthesis of β-Enaminones and β-Enamino Esters Using (Bromodimethyl)Sulfonium Bromide Under Solvent-Free
Conditionsa
Entry
a
R1
R2
Time (min)
20
Product
Isolated Yield (%)
93
O
C
CH3
NH
C
CH
Me
Ph
CH3
O
C
CH3
C
CH
NH
b
c
Me
Me
p-Me-Ph
Ph-CH2
18
23
91
93
CH3
O
CH3
C
CH
C
CH2
NH
CH3
NH
(CH2)2
O
CH3
C
C
CH
N
H
d
e
f
Me
Me
Me
Me
OEt
24
17
18
20
15
91
89
93
92
N
CH3
H
O
CH3
C
CH3
CH
C
NH
(CH3)2CH
O
C
CH
C
CH3
CH2
NH
(CH3)2CH-CH2
CH3-(CH2)7
Ph
CH3
O
CH3
CH3
NH
C
CH
C
(CH2)7
g
h
CH3
O
C
OEt
C
CH
NH
94
CH3
(Continued)
Heteroatom Chemistry DOI 10.1002/hc

632 Das et al.
TABLE 1 Continued
Entry
R1
R2
Time (min)
15
Product
Isolated Yield (%)
93
O
C
OEt
C
NH
CH
CH
i
OEt
o-Me-Ph
CH3
O
Cl
C
NH
NH
NH
C
OEt
j
OEt
OEt
OEt
p-Cl-Ph
20
17
15
91
90
87
CH3
O
OEt
OEt
C
CH
C
HO
k
l
p-OH-Ph
Ph-(CH2)2
CH3
O
C
C
CH
(CH2)2
CH3
(CH2)2
NH
O
C
OEt
C
CH
N
H
m
n
OEt
OEt
OEt
20
16
15
93
89
88
N
H
CH3
O
C
OEt
NH
C
CH
(CH3)2CH
CH3
O
NH
C
CH
C
OEt
(CH2)7
CH3
o
CH3-(CH2)7
CH3
aThe structures of the products were determined from spectral (1H NMR and MS) data.
The spectral (1H NMR and MS) data of some
representative products are given below:
advantages of the present method. An important util-
ity of (bromodimethyl)sulfonium bromide is also
disclosed.
1
3b: H NMR (200 MHz, CDCl3): δ 12.20 (1H, br
s), 7.11 (2H, d, J = 7.8 Hz), 6.97 (2H, d, J = 7.8 Hz),
5.12 (1H, s), 2.35 (3H, s), 2.09 (3H, s), 1.94 (3H, s);
EIMS: m/z 189 [M+.].
EXPERIMENTAL
1
3d: H NMR (200 MHz, CDCl3): δ 10.87 (1H, br
General Experimental Procedure
s), 9.19 (1H, s), 7.92 (1H, dd, J = 8.0, 1.5 Hz), 7.28
(1H, dd, J = 8.0, 1.5 Hz), 7.18–6.98 (3H, m), 4.85 (1H,
s), 3.50–3.22 (2H, m), 3.03–2.96 (2H, m), 1.96 (3H,
s), 1.83 (3H, s); FABMS: m/z 265 [M + Na]+.
To a mixture of a dicarbonyl compound (1 mmol)
and an amine (1.2 mmol), (bromodimethyl)
sulfonium bromide (10 mol%) was added. The mix-
ture was stirred at room temperature, and the re-
action was monitored by TLC. After completion of
the reaction, the mixture was diluted with water
(10 mL) and extracted with EtOAc (3 × 10 mL). The
extract was concentrated, and the gummy residue
was subjected to column chromatography [silica gel:
hexane-EtOAc (4:1)] to obtain pure β-enaminone or
β-enaminoester.
1
3e: H NMR (200 MHz, CDCl3): δ 10.80 (1H, br
s), 4.87 (1H, s), 3.72 (1H, m), 1.96 (3H, s), 1.94 (3H,
s), 1.26 (6H, d, J = 7.0 Hz); EIMS: m/z 141 [M+.].
1
3i: H NMR (200 MHz, CDCl3): δ 10.29 (1H, br
s), 7.08 (2H, d, J = 8.0 Hz), 6.95 (2H, d, J = 8.0 Hz),
4.60 (1H, s), 4.11 (2H, q, J = 7.0 Hz), 2.35 (3H, s),
1.96 (3H, s), 1.24 (3H, t, J = 7.0 Hz); FABMS: m/z
242 [M + Na]+.
Heteroatom Chemistry DOI 10.1002/hc

Chemo- and Stereoselective Synthesis of Enaminones and Enaminoesters Using (Bromodimethyl)sulfonium Bromide 633
1
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1
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Heteroatom Chemistry DOI 10.1002/hc