One-pot synthesis of enaminones using gold's reagent

Article abstract of DOI:10.2174/157017810791824793

Enaminones were efficiently prepared via modification for Gupton method, which depends on carrying out the latter procedure in one step reaction, avoiding the isolation of [3-(dimethylamino)-2-azaprop-2-en-1-ylidene] dimethylammonium chloride (Gold's reag

Full text of DOI:10.2174/157017810791824793

Letters in Organic Chemistry, 2010, 7, 483-486
483
One-Pot Synthesis of Enaminones Using Gold's Reagent
,a
b
b
Tamer S. Saleh* , Mohamed A. Al-Omar and Hatem A. Abdel-Aziz
a
Green Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt
b
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451,
Saudi Arabia
Received December 16, 2009: Revised March 13, 2010: Accepted March 20, 2010
Abstract: Enaminones were efficiently prepared via modification for Gupton method, which depends on carrying out the
latter procedure in one step reaction, avoiding the isolation of [3-(dimethylamino)-2-azaprop-2-en-1-
ylidene]dimethylammonium chloride (Gold's reagent) (5) which is prepared in situ from cyanuric chloride (4) then it
reacts successfully with ketone 1a-j to produce the enaminones 3a-j in suitable yields. The modified method overcomes
the drawbacks of the known methods for preparation of enaminones.
Keywords: Enaminone, cyanuric chloride, gold's reagent, DMF-DMA, Ketone.
Enaminones have proven to be valuable synthons for a
wide variety of biologically active heterocyclic ring system
for the construction of some biologically active heterocyclic
compounds [15-19].
[
1-5]. Several methods for the preparation of enaminones
We report herein the synthesis of enaminones 3a-j as
important starting materials by using Gold's reagent 5 instead
of DMF-DMA, we modified the Gupton method to become
more simple, faster, efficient and economical method for
obtaining such class of compounds and to be a promising
excellent strategy for the synthesis of enaminones for
incoming studies (Scheme 3).
have been reported [6-10], since the preparation of
dimethylformamide-dimethylacetal (DMF-DMA) first repor-
ted by Meerwin et al. [11,12], a plethora of transformations
has appeared in the literature employing formamide acetals
and their derivatives.
A Large number of articles were reported for the
synthesis of enaminones by using the commercially available
and the most effective ꢀ-dimethylamino methylenating agent
dimethylformamide-dimethylacetal (DMF-DMA) (Scheme 1)
[
3-(dimethylamino)-2-azaprop-2-en-1-ylidene]dimethyl
ammonium chloride (Gold's reagent) (5) was prepared in situ
from cyanuric chloride (4) in the presence of 6 equivalent of
dimethylformamide under reflux in dry dioxane for 1 h
followed by addition of ketone 1a-j in sodium methoxide to
[
6-9] but it is relatively expensive, moisture and heat
sensitive reagent [13,14].
Method A
O
Me
Me
O
O
Me
Me
O
+
N
Me
Ar
Me
Ar
N
Me
1a-j
2
3a-j
(DMF-DMA)
Scheme 1.
On the other hand, although, the preparation of
enaminones has been prepared by the Gupton method using
Gold's reagent in a good yields, this method has some
limitations due to the difficulties of the isolation of Gold's
reagent 5, where it is very hygroscopic and should be
handled under a moisture-free condition (Scheme 2) [10].
Thus, this is necessary to develop a more effective synthetic
procedure for enaminone.
produce the enaminones 3a-j in excellent yields (Scheme 3).
Our modification for Gupton method depends on
carrying out the latter procedure in one step reaction
avoiding the isolation of Gold's reagent 5 prepared, in our
procedure, in situ where it is very hygroscopic and should be
handled under a moisture-free environment in addition to
reducing working up time used in the isolation of this
intermediate also, we found that yield of enamiones
produced 3 affected with molar ratio of cyanuric chloride to
the ketone used. Table 1 shows the effect of using different
molar ratio of cyanuric chloride on yield of enaminones of
ketone 1a, 1b,1i or 1j which are taken as representative
examples. The reaction time, for each compound, was
examined by TLC and it was the same in the different ratios.
As an extension of our continuous efforts directed
towards the development of convenient synthetic approaches
*
Address correspondence to this author at the Green Chemistry Department,
National Research Centre, Dokki, Cairo 12622, Egypt; Tel: +20 101978724;
Fax: +202 333 70931; E-mail: tamsaid@yahoo.com
1
570-1786/10 $55.00+.00
© 2010 Bentham Science Publishers Ltd.

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84 Letters in Organic Chemistry, 2010, Vol. 7, No. 6
Saleh et al.
Method B (Gupton method)
Step 1
Cl
Me
N
Me
N
N
N
6 DMF
Cl
N
+
3 CO2
3
Me
Me
Cl
N
Cl
5
4
(Gold's reagent)
Step 2
O
Me
N
Me
N
O
MeONa
Me
N
Cl
+
Ar
N
Me
Me
Ar
Me
Me
3
a-j
1a-j
5
Scheme 2.
Method C
Cl
N
N
6 DMF
dioxane
Cl
N
Cl
4
Me
Me
N
N
N
Cl
Me
Me
O
O
5
Me
Ar
N
Ar
Me
MeONa
Me
1a-j
3a-j
Scheme 3.
Table 1. Yields of Enaminones 3a, 3b, 3i and 3j for 0.1 mol of Ketones 1a, 1b, 1i and 1j, Respectively with Different Molar Ratios
of Cyanuric Chloride (4)
Yield%
a
1
a, 1b, 1d or 1h
Cyanuric Chloride (4)
3
a
3b
3i
3j
0
.035 mol
.05 mol
0.07 mol
83
88
74
89
85
91
75
83
0
0
.1 mol
0
0
.08 mol
.09 mol
95
98
96
89
a
The molar equivalent of DMF was used in each time ꢀ 6 ꢁ moles of cyanuric chloride (4).
From these results, it is obvious that molar ratio of ketone
NMR spectra were recorded on a Varian Mercury VX-300
NMR spectrometer. H spectra were run at 300 MHz in
deuterated dimethylsulphoxide (DMSO-d ). Chemical shifts
6
were quoted in ꢀ and were related to that of the solvents.
Mass spectra were measured on a GCMS-QP1000 EX
spectrometer at 70 e.V. Elemental analyses were carried out
at the Microanalytical center of Cairo University, their
results were found to be in good agreement (±0.2%) with the
calculated values.” 2-acetyl benzothiazole (1i) [25] 2-Acetyl
benzofuran (1h) [23] and 2-acetyl-1-methy benzimidazole
1
to cyanuric chloride 1:0.7 is the most adaptable ratio for one
step synthesis of enaminones, since comparatively higher
yields are achieved and when the molar ratio of ketone to
cyanuric chloride increased (more than 1:0.7) no noticeable
change in the yield of enaminone. Table 2 shows the yield
and time of the mentioned reaction (method C).
EXPERIMENTAL
(
1j) [26] were prepared by the reported methods. Cyanuric
Melting points were measured with a Gallenkamp
apparatus and are uncorrected. IR spectra were recorded on
Shimadzu FT-IR 8101 PC infrared spectrophotometer. The
chloride (4), acetophenone, 4-bromoacetophenone, 4-
nitroacetophenone, 2-acetyl furan, 2-acetyl thiophene, 2-

One-Pot Synthesis of Enaminones Using Gold's Reagent
Letters in Organic Chemistry, 2010, Vol. 7, No. 6
485
acetyl pyrrole and 3-acetyl pyridine were used as obtained
commercially.
with ethanol, dried and finally crystallized from the proper
solvent to afford the enaminones 3a-j.
Table 2. Yields and Time of Reaction (Method C)
All the products are known and the data are found to be
identical with those that reported in the literature (Table 1)
[27].
Ar
Yield (%) / Reaction Time (h)
In conclusion, we have uncovered a facile reaction for
the preparation of enaminones. The experimental simplicity
of the reaction is especially noteworthy.
[
20]
3
3
a
9
9
9
5 / 3
[
20]
b
Br
8 / 3
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4
86 Letters in Organic Chemistry, 2010, Vol. 7, No. 6
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.78 (1H, d, J =12.8 Hz), 7.40 (3H, m), 7.70 (1H, d, J =12.8 Hz),
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2
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max
+
0
1
(M , 62%).(3J) Yield 89%; mp 150-151 C; H NMR (300 MHz,
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