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

Abstract

Uma variedade de β-enaminonas e β-enamino ésteres foi sintetizada pela reação de compostos 1,3-dicarbonílicos com aminas na presença de quantidade catalítica de cloreto de cobalto(II), à temperatura ambiente na ausência de solventes. O procedimento experimental é simples e os produtos são isolados em altos rendimentos.A variety of β-enaminones and β-enamino esters can be synthesized by the reaction of 1,3-dicarbonyl compounds with amines in the presence of a catalytic amount of cobalt(II) chloride at room temperature under solvent-free condition. The experiment procedure is simple, and the products are straightforwardly isolated in high yields.Keywords: β-enaminones, β-enamino esters, 1,3-dicarbonyl compounds, amines, cobalt(II) chloride, solvent-free conditions Introduction β-Enaminones have attracted much attention due to the fact that they are important synthons for the synthesis of many biologically active compounds such as dopamine auto-receptor agonists, 1 acetylcholinestersase inhibitors 2 and anticonvulsants. 3 They are also useful intermediates for the preparation of several aminoacids, 4 aminols, 5 peptides and alkaloids. 6 Thus it is very important to search for a convenient and efficient method for the synthesis of this type of compounds. 7 Several methods have been developed for their synthesis including the reactions of imidoyl chlorides with acetonyltributyltin in the presence of palladium catalyst, 8 the addition of amines to acylacetylenes, 9 acylation of metalated ketimines using acylbenzotriazoles as acylating agents, 10 the reactions of lithiated enamines with diethyl carbonate or benzyl chloroformate, 11 the addition of ester or amide enolates to nitriles, 12 palladium-assisted amination of α-keto olefins 9 or amination with O-methylhydroxylamines in the presence of base, 13 and the reactions of alkyl azides and β-ketoesters in a one-pot procedure using 10% Pd/C catalyst and hydrogen.14 However, the most commonly used and straightforward approach for the preparation of these compounds is the direct condensation of β-dicarbonyl compounds and amines, in which the azeotropic removal of water is usually required under reflux using a Dean Stark trap in aromatic solvent. 15 organic transformations will be quite useful. As a part of our ongoing program in developing various new synthetic transformations using cheap and eco-friendly materials as catalysts, 39 we herein wish to report our results on the synthesis of β-enaminones and β-enamino esters using a catalytic amount of CoCl 2 ·6H 2 O at room temperature under solvent-free condition (Scheme 1). Results and DiscussionOur initial studies were focused on the optimization of the reaction conditions for the synthesis of β-enamino esters. Ethyl acetoacetate was chosen as a model substrate for the optimization process. The reaction of ethyl acetoacetate with aniline in the presence of 5 mol% CoCl 2 ·6H 2 O at room temperature, without any solvent, afforded the target ethyl 3-(phenylamino)but-2-enoate (3e) in 95% yield. Lower catalyst loading ca...

B2O3/Al2O3 as a new, highly efficient and reusable heterogeneous catalyst for the selective synthesis of β-enamino ketones and esters under solvent-free conditions

“…The direct enamination of 1,3-dicarbonyl compounds with amines is one of the most straightforward methods for the synthesis of β-enamino ketones and esters in the presence of various promoting agents. [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Recent reports have described the preparation of β-enamino ketones and esters catalyzed by metal triflate. 20 Although the reported methodologies are suitable for certain synthetic conditions, some of these procedures suffered from disadvantages, such as long reaction time, low yield, use of volatile organic solvents, requirement of excess of reagents or costly catalysts, special apparatus and harsh reaction conditions.…”

A solvent-free synthesis of beta-enamino trihalomethyl ketones

“…18 Unfortunately, in general, the processes to synthesize trihalomethyl substituted β-enamino ketones suffers from limitations, such as long reaction times, multi-step reactions and tedious work-up. 19,20 Thus, because of the applicability of β-enamino trihalomethyl ketones as a promising building blocks for the synthesis heterocycles, 21,22 a simple, general and high yielding onepot approach for the synthesis of this enaminones is highly desirable. In particular, it has been shown that syntheses which are carried out in solvent-free conditions are often rapid, regio-or chemoselective, occur in high yields and have environmental and economic advantages.…”

A Novel and highly selective conversion of alcohols, thiols, and silyl ethers to azides using the 2,4,6-trichloro[1,3,5]triazine/n-Bu4NN3 system

“…[2][3][4] Aliphatic azides are usually prepared by nucleophilic substitution of the corresponding halides or sulfonates by azide ion. [5][6][7][8] Due to the advantageous and attractive strategy of the direct synthesis of azides from alcohols, some limited methods have been developed. Along this line, methods based on Mitsunobu conditions [7][8][9][10][11] are widely applied.…”

“…[5][6][7][8] Due to the advantageous and attractive strategy of the direct synthesis of azides from alcohols, some limited methods have been developed. Along this line, methods based on Mitsunobu conditions [7][8][9][10][11] are widely applied. These methods utilize reagents such as hydrazoic acid, diphenylphosphoryl azide, the bispyridine complex of zinc azide or the tetrabromocyclohexadienone/Ph 3 P system as the azide source/nucleophilic component.…”