An Easy Synthesis of Enaminones in Water as Solvent

Abstract

Enaminones were prepared from b-ketoesters or 1,3-diketones and primary amines in water as solvent Enaminones and related compounds possessing the structural unit N-C=C-Z (Z = COR, CO 2 R, CN, etc.) are versatile synthetic intermediates that combine the ambident nucleophilicity of enamines with the ambident eletrophilicity of enones. 1 Some procedures reported for the synthesis of b-enaminocarbonyl derivatives include the reaction of amines and 1,3-diketones supported over clay K 10 /ultra-sound 2 or silica under microwave irradiation, 3 reaction of b-amino ketones in the presence of triethylamine promoted by Pd(II), 4 and reactions of a-metalated imines with esters. 5 However, the generally employed method for the preparation entails the reaction between ammonia or a primary or secondary amine with 1,3-dicarbonyl compound in benzene solution with azeotropic removal of the water formed. [6][7][8][9][10] We report here, a simple procedure for the synthesis of benamino esters and enaminoketones (1) starting from bketoesters or 1,3-diketones and primary amines in water as solvent (Scheme 1). The main advantages of this methodology are: (a) the reaction is simple to perform; (b) the reaction occurs at room temperature; (c) the yields are good to high, (d) acid catalysis is not necessary, (e) the reaction works for a variety of primary amines; and (f) purification of the enaminones is not necessary. With secondary amines or simple carbonyl compounds, no reaction was observed. The reaction worked very well to soluble amines, but with less soluble amines the yield was moderated and it was necessary to use high excess of amine (3 equivalents). When b-ketoester and 1,3-diketones reacted with ethylene-diamine, diaminones were observed as products (1h and 1m). Scheme 1Since there are two carbonyl groups in the starting material and 2 equivalents of amine were added, there should be several products in this reaction, i.e., the amine may react with one or both of carbonyl groups. Thus, there should be three products from b-ketoester and two from 1,3-diketone, however, only enaminones were observed as products. This probably occurs because the acetyl portion of the starting dicarbonyl compounds is more reactive than the ester or aromatic conjugated carbonyl. When the enaminone is formed, it is stabilized by resonance, blocking the formation of other products. The conjugation effect also justifies the formation of only one product from acetylacetone.The probable explanation for the formation of enaminones in water is their tautomeric forms (A and B) associated with the hydrogen bond. 11,12 Enaminones of all types exist predominantly in the carbonyl form and are stabilized by the contribution of the zwitterionic form (C), 13 which can be solvated by water preventing hydrolysis of the formed enaminone. This explanation can be supported by the fact that no reaction was observed using secondary amines or simple carbonyl compounds (Scheme 2). Scheme 2In summary, we have provided a remarkably viable alternative route for the synthesi...

A General and Efficient Method for the Preparation of β‐Enamino Ketones and Esters Catalyzed by Indium Tribromide

“…[18] A variety of catalysts such as HCl, [19] H 2 SO 4 , [20] p-TSA, [21] HOAc, [22] trimethylsilyl trifluoromethanesulfonate (TMSTf), [23] montmorillonite K10 under microwave irradiation [24] or ultrasound, [25] I 2 , [19b] BF 3 · OEt 2 , [26] Al 2 O 3 , [27] silica gel, [28] Zn(ClO 4 ) 2 · 6 H 2 O, [29] CeCl 3 · 7 H 2 O, [30] NaAuCl 4 , [31] and natural clays [32] have been employed to effect this transformation. Recently, this condensation reaction has also been performed in water [33,34] or in ionic liquid medium. [30,35] Although these methods are suitable for certain synthetic conditions, sometimes, however, many of these procedures are associated with one or more disadvantages such as long reaction time, low yield, use of volatile organic solvents, requirement of excess of reagents or catalysts, special apparatus and harsh reaction conditions.…”

Recent development in preparation reactivity and biological activity of enaminoketones and enaminothiones and their utilization to prepare heterocyclic compounds

“…Enaminones of all types exist predominantly in the carbonyl form A and are stabilized by the contribution of the zwitterionic form (C - Figure 3) which can be solvated by water preventing hydrolysis of the formed enaminone. When the enaminone is formed, it is stabilized by resonance, blocking the formation of other products [26].The conjugate addition of benzyl carbamate 14 to α,β-unsaturated ketones 15 catalysed by Cu (II) -Cu(OTf) 2 complexes, leads to β-aminoketones 16 bearing a benzyloxy carbonyl moiety (Figure 10), which can easily undergo further conversions using well-established protective group chemistry [27].Synthesis of Enaminones Through Ring-opening of Isoxazoles.Isoxazoles are generally considered as useful synthons in organic synthesis, and 5-alkyl or 5-aryl isoxazole in the presence of iron dichloride, as catalyst, undergo reductive cleavage to enaminoketones [21,28]. Reduction of isoxazoles gave enaminoketones as the only products.…”

Cobalt(II) chloride-mediated synthesis of beta-enamino compounds under solvent-free conditions

“…This condensation reaction has also been performed in water. 37 However, there are always some drawbacks with these procedures such as long reaction time, 26,33 high temperature, 15 use of costly catalysts, 23,24,35 high catalyst loading, 22,31 use of an additional ultrasound 19 or microwave oven 30 etc. So, the development of new reagents with great efficiency, convenient procedure, and delivery of better yields is of great interest.…”