the drawbacks of the known methods for preparation of enaminones. Keywords: ... reagent 5, where it is very hygroscopic and should be handled ... and time of the mentioned reaction (method C). ... To a mixture of cyanuric chloride (4) (12.77 g, 0.07 mol) ... The resulting solution was refluxed ... The experimental simplicity.
483
Letters in Organic Chemistry, 2010, 7, 483-486
One-Pot Synthesis of Enaminones Using Gold's Reagent Tamer S. Saleh*,a,Mohamed A. Al-Omarband Hatem A. Abdel-Azizb GCreen Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt bDepartment of Pharmaceutical Saudi Arabia
Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, 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-lylidene]dimethylammonium chloride (Gold's reagent) (5) which is prepared in situ from cyanuric chloride (4) then it reacts successfully with ketone la-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 for the construction of some biologically active heterocyclic wide variety of biologically active heterocyclic ring system ~ compounds [15-19]. [1-5]. Several methods for the preparation of enaminones We report herein the synthesis of enaminones 3a-j as have been reported [6-10], since the preparation of important starting materials by using Gold's reagent 5 instead dimethylfonnamide-dimethylacetal (DMF-DMA) fIrst reporof DMF-DMA, we modifIed the Gupton method to become ted by Meerwin et al. [11,12], a plethora of transfonnations more simple, faster, efficient and economical method for has appeared in the literature employing fonnamide acetals obtaining such class of compounds and to be a promising and their derivatives. excellent strategy for the synthesis of enaminones for A Large number of articles were reported for the incoming studies (Scheme 3). synthesis of enaminones by using the commercially available [3-(dimethylamino)-2-azaprop-2-en-l-ylidene]dimethyl and the most effective jJ-dimethylamino methylenating agent ammonium chloride (Gold's reagent) (5) was prepared in situ dimethylfonnamide-dimethylacetal (DMF-DMA) (Scheme 1) from cyanuric chloride (4) in the presence of 6 equivalent of [6-9] but it is relatively expensive, moisture and heat dimethylfonnamide under reflux in dry dioxane for 1 h sensitive reagent [13,14]. followed by addition of ketone la-j in sodium methoxide to '
Method A 0
Me +
Ac)lMe
0
0- Me
f--
2010 Bentham
Science Publishers
Ltd.
484
Saleh et al
Letters in Organic Chemistry, 2010, Vol 7, No.6 Method
B (Gupton
method)
Step 1
CI
N~N
.
6DMF
Me 3
Me
I Me -,N~N
CI)lN~Cl
I+ CI :;/N, Me
+
3COz
5
4
(Gold's reagent)
Step 2 Me
0 + Ar)lMe
I Me-'N
0
Me :;/ N
MeONa
1+ CI :;/ N , Me
.
Ar~N~Me
5
la-j
I
3a-j
Me
Scheme2. MethodC
CI
N~N
6DMF dioxane
CI)lN~Cl
I
4
0
[
Me Me I 1+Me N :;/ N :;/ N , Me CI
0
]
5 Ar~N~Me
Ar)lMe MeONa
la-j
3a-j
I Me
Scheme 3.
Table 1.
Yields of Enaminones 3a, 3b, 3i and 3j for 0.1 mol of Ketones la, lb, Ii and lj, Respectively with Different Molar Ratios of Cyanuric Chloride (4) la, lb, ld or lh
0.1 mol
Yield% Cyanuric Chloride (4)"
3a
3b
0.035 mol
83
0.05 mol
88
95
3i
3j
74
85
75
89
91
83
98
96
89
0.07 mol 0.08 mol 0.09 mol
'The molar equivalent QfDMF was used in each time '" 6 x moles of cyanuric chloride (4).
From these results, it is obvious that molar ratio of ketone 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 Melting points were measured with a Gallenkamp apparatus and are uncorrected. IR spectra were recorded on Shimadzu FT-IR 8101 PC infrared spectrophotometer. The
NMRspectra were recorded on a Varian Mercury VX-300 NMR spectrometer. IH spectra were run at 300 MHz in deuterated dimethylsulphoxide (DMSO-d6). Chemical shifts were quoted in 0 and were related to that of the solvents. Mass spectra were measured on a GCMS-QPIOOO EX spectrometer at 10 e.V. Elemental analyses were carried out at the Microanalytical center of Cairo University, their results were found to be in good agreement (:f:O.2%)with the calculated values." 2-acetyl benzotIDazole(Ii) [25] 2-Acetyl benzofurno (Ih) [23] and 2-acetyl-l-methy benzimidazole (Ij) [26] were prepared by the reported methods. Cyanuric chloride {4}, acetophenone, 4-bromoacetophenone, 4nitroacetophenone. 2-acetyl furno, 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 [mally crystallized from the proper solvent to afford the enaminones 3a-j.
Table 2.
All the products are known and the data are found to be identical with those that reported in the literature (Table 1) . [27].
Yieldsand Timeof Reaction(Method C) Ar
Yield (%) I Reaction Time (h)
[20] 95/3
