Silicon Tetrachloride Catalyzed Aza-Michael Addition of Amines to Conjugated Alkenes under Solvent-Free Conditions

Abstract

The efficient and very simple conjugate addition of aromatic and aliphatic amines to a,b-unsaturated carbonyl compounds under solvent-free conditions in the presence of catalytic amount of silicon tetrachloride is reported. The reaction of aryl and alkyl amines with different Michael acceptors gave the corresponding Michael adducts with simple catalyst and good to excellent yields.The aza-Michael addition reaction is one of the most important methodologies in synthetic organic chemistry for preparation of b-aminocarbonyl compounds, which not only constitute components of biologically important natural products but also serve as key intermediates for the synthesis of b-amino alcohols, antibiotics, b-amino acids, chiral auxiliaries, and other nitrogen-containing compounds. 1,2The Mannich reaction is a classical method for the synthesis of b-amino carbonyl compounds. However, the reaction has disadvantages such as harsh reaction conditions, long reaction times, and a relatively narrow scope of substrates. 3 The aza-Michael addition of nitrogen nucleophiles including amides, carbamates, sulfonamides, and amines to electron-deficient alkenes in the presence of strong base or acid catalyst has attracted considerable attention as an alternative route for the synthesis of b-amino carbonyl compounds. 4 Since some functional groups may be susceptible to strong acid or base, a variety of catalysts 5 and promoters for aliphatic amines 6 have been introduced over the past few years.However, there are still some limitations with the existing methods; for example, the range of amine nucleophiles and Michael acceptors well suited to both catalytic and stoichiometric methodologies is generally restricted to simple aliphatic amines and Michael acceptors and there have been few reports involving simple catalysts or reagents to effect these transformations. 7 Thus, development of an efficient catalytic protocol that could overcome the above-mentioned disadvantages and facilitate the addition of both aromatic/aliphatic amines to a,bunsaturated compounds remains a challenge.As a part of our research aimed at developing green chemistry by using water as the reaction medium or by performing organic transformations under solvent-free conditions, 8 we describe herein a simple, highly efficient, and eco-friendly method for the synthesis of b-amino carbonyl compounds from aromatic and aliphatic amines and a,b-unsaturated Michael acceptors under solvent-free conditions.In order to find the best reaction conditions, we first studied the reaction of aniline and methyl acrylate with different loadings of starting materials and catalyst. It was found that the reaction of methyl acrylate (1.04 equiv) and aniline (1 equiv) in the presence of commercially available silicon tetrachloride (2 mol%) under solvent-free conditions proceeded smoothly within four hours to afford the conjugate addition product exclusively and in quantitative yield. Furthermore, in organic solvents, such as CH 2 Cl 2 , MeCN, toluene, ethanol, water, and tetrahydrofuran the M...

Benefits of a Dual Chemical and Physical Activation: Direct aza-Michael Addition of Anilines Promoted by Solvent Effect under High Pressure

“…14 It is well established that α-substituted acrylates are sluggish electrophiles in hetero-Michael reactions, 15,16 and examination of the reaction of methyl methacrylate with Nmethylaniline and aniline afforded β-aminoesters in poor to moderate yields (9% and 40%, respectively; entries 8 and 9). The scope of Michael acceptors was then extended to acrylonitriles (entries [10][11][12][13][14][15][16][17]. With simple acrylonitrile, N-substituted anilines (methyl, cyclohexyl) afforded the corresponding products in >99% yield (entries 10 and 11).…”

“…Crotonitrile also appeared to be an excellent partner since the 1,4-addition with N-methylaniline proceeded very well (81% yield, entry 12). The last reactions were performed with 2-chloroacrylonitrile (entries [13][14][15][16][17]: the reaction occurred smoothly with primary and secondary aromatic amines and the corresponding α-chloro-β-aminonitriles were obtained as sole products in medium to good yields (60-86%).…”

Synthesis of Some Aminophosphonates Bearing N‐(Fluorophenyl)‐piperazynyl Moiety and Their Activity toward Serotonin Receptors

“…Diethyl 2‐[1‐(fluorophenyl)piperazin‐4‐yl]‐ethyl phosphonates 4a,b were prepared by the aza‐Michael addition of 1‐(fluorophenyl)piperazines 1a,b to diethyl vinylphosphonate (Scheme ). Reactions were carried out in refluxing methanol for 4 h and afforded phosphonates 4a,b in 72 and 78% yield, respectively.…”

An efficient synthesis of dithiocarbamates under ultrasound irradiation in water

“…During the course of our study aimed at improving the ecocompatibility of certain organic processes, we have been particularly interested in the synthesis of dithiocarbamates in water and solvent-free conditions to develop environmentally benign reactions [32][33][34][35][36][37]. Herein, we wish to report an efficient preparation of dithiocarbamate derivatives from the one-pot reaction of amines, carbon disulfide, and unsaturated enones or alkyl halides in water under ultrasound irradiation.…”