J. Chem. Sci. Vol. 124, No. 2, March 2012, pp. 495–500. ꢀc Indian Academy of Sciences.
Trifluoromethanesulfonic acid promoted Dakin–West reaction: An
efficient and convenient synthesis of β-acetamido ketones
∗
RAVINDRA M KUMBHARE and MADABHUSHI SRIDHAR
Fluoroorganics Division, Indian Institute of Chemical Technology, Hyderabad 500607, India
e-mail: rakumbhare@yahoo.com, kumbhare@iict.res.in
MS received 30 December 2010; revised 13 September 2011; accepted 22 September 2011
Abstract. Trifluoromethanesulfonic acid promoted efficient condensation of an aromatic aldehyde with an
acetophenone and acetonitrile in the presence of acetylchloride as an activator producing β-acetamido carbonyl
compounds is described.
Keywords. β-Acetamido ketones; Dakin–West reaction; multicomponent synthesis;
trifluoromethanesulfonic acid.
1
. Introduction
first observation of triflic acid promoted Dakin–West
reaction of aromatic aldehydes, or acetophenones,
with acetonitrile forming β-acetamido ketones in good
yields (60–70%). However, when acetyl chloride was
used in the reaction as an activator, we observed
formation of β-acetamido carbonyl compounds with
enhanced yield (82–95%) as shown in scheme 1. Rep-
resentative results are given in table 1.
β-Acetamido carbonyl compounds are valuable building
blocks for the preparation of 1,3-amino alcohols
or β-amino acids, as well as for the synthesis of
various bioactive molecules such as the antibiotics
nikkomycins and neopolyoxines.4 The conventional
way for the preparation of these compounds is by the
1,2
3
,5
6
Dankin–West reaction using a α-amino acid and acetic
anhydride. Later on, Iqbal et al. introduced another pro-
cedure for the formation of these compounds through
the condensation of an acetophenone, an aryl aldehyde in
acetonitrile in the presence of CoCl2 7 or montmo-
rillonite K-10 clay as a catalyst and acetyl chloride
2
. Experimental
2.1 General procedure for the preparation
of β-acetamido ketones with triflic acid
and acetyl chloride
8
as a promoter. Subsequently, this reaction was stud-
ied using acetyl chloride as a promoter in the presence
9
of several other catalysts such as Cu(OTf) /Sc(OTf) ,
2
3
To a stirred solution of 4-nitrobenzaldehyde (0.30 g,
2 mmol) and 4-nitroacetophenone (0.33 g, 2 mmol) in
acetonitrile (5 mL) was added acetyl chloride (0.23 g,
10
11
12,13
14
BiOCl, ZrOCl 8H O, heteropoly acid,
I ,
2
2.
2
16
15
17
amberlyst-15, ZnO, and CeCl
Although all these
3.
methods are useful, they suffer from limitations such
as long reaction times and the handling and disposal of
inorganic acids.
3
2
mmol) and trifluoromethanesulfonic acid (0.2 mL,
mmol). The mixture was stirred at room temperature
for 30 min. and the progress of reaction was monitored
Trifluoromethanesulfonic acid or triflic acid is a well- by TLC. After completion, the mixture was poured
known Bronsted super acid and it has been exten- into crushed ice (10 g) and extracted with ethyl acetate
sively studied as a catalyst in a wide range of organic (2 × 10 mL). The organic layer was washed succes-
transformations, which include cyclizations of unsatu- sively with water (1 × 5 mL), saturated sodium bicar-
18
19
rated alcohols, acylations of alcohols, additions of bonate solution (1 × 5 mL) and brine (1×5 mL), then
2
0
allylboranes to aldehydes, annelation of aromatic sul- dried over anhy. Na SO and concentrated under vac-
2
4
21
fonamides, stereoselective Friedel–Crafts aminoalky- uum. The crude product was purified by column chro-
lations of indoles and pyrroles etc. Here, we report matography to give β–acetamido–β-(4-nitrophenyl)-4-
22
nitropropiophenone as a pale yellow solid (0.63 g, 88%,
◦
−1
mp. 152 C). IR (KBr, cm ): 3280, 3072, 1690, 1646,
1
∗
1
For correspondence
590, 1530, 1358, 1073, 995, 816, 759. H NMR
495
Kumbhare, Ravindra M
