One-pot three-component condensation

Finally, a one-pot, three-component condensation reaction in water provides an efficient procedure for the synthesis of furo[2,3-r/ pyrimidine-2,4(1/7,3//)-diones 303 (Scheme 26). A, A -Dimethylbarbituric acid 301 and 4-nitrobenzaldehyde 302 are reacted with a series of isocyanides to give good yields of the 6-amino products 303 <2002TL9151, 2005SC535>. 

The use of a pyrimidine precursor continues to be the more popular approach to furo pyrimidines. The one-pot three-component condensation reactions of alkyl or aryl isocyanides with A[A -dimethylbarbituric acid in the presence of terephthaldialdehyde proceeded spontaneously at room temperature in DMF to give good yields of the corresponding l,4-bis(6-alkyl or arylamino-1,3-dimethylfurano[2,3-4]pyrimidin-2,4(l//,3//)-dione-5-yl)benzenes <2006BMCL3697>. 

A 20-membered library of 1,3,5-lriazincs was prepared in a parallel format employing a one-pot, three-component condensation of anilines, dicyandi-amide and acetone. The reaction time was reduced from 22 hours (reflux in... 

Resin-bouda-amino esters, besides being traditionally used for making peptides, have served as key intermediates for the construction of various heterocyclic scaffolds. Thus, they react smoothly with isocyanates to form ureas, which upon heating under acidic conditions cyclize to form hydantoins 53 [27]. A one-pot, three-component condensation of resin-bound a-amino esters with aldehydes and a-mercapto acids affords 4-thiazolidi-... 

Very recently, Maiti and coworkers150 developed a new methodology for the synthesis of dihydropyrimidones, 246, by a one-pot three-component condensation using a catalytic amount of LiBr, under very mild reaction conditions (Scheme 76). 

The reaction of amines with 1,2-diketo substrates led to a variety of substituted imidazole derivatives. Treatment of various substituted anilines 88 with glyoxals 89 gave the imine intermediate 90, which was then cyclized to the 1-arylimidazoles 91 with paraformaldehyde and ammonium chloride under acidic conditions <0382661>. A one-pot, three-component condensation of benzil 92, benzonitrile derivatives and primary amines on the surface of silica gel under solvent-free conditions and microwave irradiation provided tetrasubstituted imidazoles 93<03TL1709>. 

Tetrasubstituted imidazoles (xxviii) were also obtained in high yields by a one-pot, three-component condensation of benzyl, benzonitrile derivatives and 1° amines on the surface of silica gel under solvent free microwave condition [2]. 

A general method for the synthesis of these compounds by a solvent-free, catalyst-free, one-pot, three-component condensation of carbonyl compound, amine and diethyl phosphate has been demonstrated by Ranu et (Scheme 5.50). 

The easily accessible neutral ionic liquid [pmImJBr promoted a one-pot three-component condensation of an amine, carbon disulfide, and an activated alkene/dichloromethane/epoxide to produce the corresponding dithiocarbamates (Scheme 5.60) in high yields at room temperature. The reactions were very fast in ionic liquids relative to those in other reaction media. These reactions did not require any additional catalyst or solvent. The ionic liquid was recovered and recycled for subsequent reactions. 

A basic ionic liquid, [bmIm]OH, efficiently promotes a one-pot, three-component condensation of aldehydes, malononitrile and thiophenols to produce highly substituted pyridines (Scheme 5.61) in high yields at room temperature. These pyridines have much potential for therapeutic activity. This... 

In 2009, Zhang et al. have investigated the preparation of thiazolidinones via the one-pot three-component condensations of aldehydes, amines, and 2-mercaptoacetic acid in ionic liquids (Fig. 12.13) [9]. 

Shaabani et al. reported a facile method for the synthesis of imidazo[ 1,2-a]azines by a one-pot three-component condensation of an aldehyde, a 2-aminoazine, and trimethylsilylcyanide, as an isocyanide equivalent, in the presence of l-n-butyl-3-methyUmidazolium bromide ([bmim][Br]) as a promoter under classical heating conditions in high yields with rather short reaction times (Fig. 12.16) [12]. 

The ionic liquid [bmim] [OH] has also been used as an efficient catalyst for the synthesis of a variety of 4H-benzo[b]pyran derivatives by a one-pot three-component condensation of aldehydes, cyclohexa-l,3-diones, and malononitrile/ethyl cyanoacetate at room temperature (Fig. 12.28) [20]. 

A simple, efficient, and eco-friendly procedure has been developed using tetrabutylanunonium bromide ((TBAB), 10 mol%) as a novel neutral ionic liquid catalyst for the synthesis of 2,4,5-triaryl imidazoles by a one-pot three-component condensation of benzil, aryl aldehydes, and ammonium acetate in refluxing isopropanol (Fig. 12.73) [44]. 

A series of l-acylimino-3if-thiazoline derivatives 104 are prepared by a one-pot three-component condensation of arylisothiocyanates 100, primary amines 101 and a-halocarbonyl derivatives 102 presumably via intermediates 103 <05TL419>. 

Tetrasubstituted imidazoles have been prepared in high yield by one-pot three-component condensation of benzil, benzonitrile derivatives, and primary amines adsorbed on silica gel without solvent (Scheme 10.87) [169]. Under irradiation conditions yields range from 58 to 92% (8 min). 

Another group of compounds which can be synthesized by a MCR under MW conditions are pyridones. Pyridone derivatives 15 have found many applications in the preparation of azo-dyes, especially as disperse dyes for polymeric materials [42]. It is possible to prepare these compounds by one-pot three-component condensation of a jS-cyanoester, a /i-keto ester, and a primary amine (Scheme 17.11) [43]. 

A microwave dielectric heating assisted TSIL phase synthesis [45] of 1,4-dihydropyridines, 3,4-dihydropyrimidin-2(lH)-ones, pyridines and polyhydroquinolines using a TSIL as a soluble support was described. The efficiency of the ionic liquid phase organic synthesis (loLiPOS) methodology was demonstrated by using a one-pot three-component condensation. The stmcture of the intermediates... 

Mondal et al. reported the synthesis of a new robust, non-air-sensitive, metal-free triazine-functionalized mesoporous organocatalyst TFMO-1 (Figure 1.5) and successfully used this material as an excellent catalyst in the one-pot three-component condensation reactions for the syntheses of 2-amino-chromene derivatives under solvent-free conditions (Mondal et al., 2012). TFMO-1 is an easily separable heterogeneous organocatalyst devoid of metal ions and thus is highly desirable to address industrial and environmental concerns. 

Chen et al. (2007) demonstrated a very simple, efficient, and practical method for the synthesis of DHPMs and thioderivatives through a one-pot, three-component condensation of aldehydes, 1,3-dicarbonyl compounds, and urea or thiourea catalyzed by SSA under solvent-free conditions (Scheme 6.3). The main features of this method are its operational simplicity, good yields, use of cheap, commercially available chemicals, recyclability with the comparable activity of the catalyst, and that it is cost effective and environmentally benign. 

Balalaie et al. (2003) reported a one-pot, three-component condensation of benzil, benzonitrile derivatives, and primary amines on the surface of silica gel with acidic character under microwave irradiation as a new and efficient method to produce 1,2,4,5-tetrasubstituted imidazoles (Scheme 6.14). This methodology offers several advantages, such as solvent-free conditions, the use of substances without any modi-hcation or activation, high yields, shorter reaction times, and reusability of solid catalysts, and it is environmentally benign compared to the existing methodologies. 

The synthesis of 1,4-dihydropyridines (45) by four-component condensation reaction of 1,3-dicarbonyls (43), aldehydes (1), and ammonium carbonate (44) in an aqueous medium was reported at 60°C within 1.5-2.5 h (Scheme 9.11) (Tamaddon and Moradi 2012). ZnO nanoparticles can be used as a heterogeneous catalyst (Yavari and Beheshti 2011) for the one-pot three-component condensation of isatoic anhydride (46), amines (47), and aldehydes (48) to afford the corresponding 2,3-disubstituted quinazolin-4(l//)-ones (49) (Scheme 9.12). A short reaction time (3 h), solvent-free conditions, and an atom-economic nature are the significant advantages of the present method. The catalyst showed good recyclability without much loss of its catalytic activity. 

In continuation of our efforts in the development of new synthetic routes for the synthesis of heterocyclic compounds using nanocatalysts, we have recently reported a novel synthesis of 3,4,5-trisubstituted furan-2(5H)-one derivatives by the one-pot three-component condensation of aldehydes, amines, and dimethyl acetylenedicar-boxylate (DMAD) by nsing nanoparticulate ZnO as a catalyst in Et0H H20 (1 1) at 90°C (Scheme 9.30) (Tekale et al. 2013). Almost all the employed aldehydes and amines reacted smoothly to afford excellent yields of the prodncts, irrespective of the natnre of the snbstitnent present on the aldehyde or amine. The plausible mechanism for the synthesis of furan-2(5 f)-ones using nano-ZnO is depicted in Figure 9.3. The catalyst promotes the formation of enamines (99) from amines (97) and DMAD (96). ZnO polarizes the carbonyl group of aldehydes to form a polarized adduct (100) which reacts with the enamines, followed by cyclization with the elimination of methanol molecules to afford the corresponding trisubstituted furanone derivatives (98). 

Gold nanoparticles on ZnO were used as a catalyst for the rapid one-pot three-component condensation of amines (106), aldehydes (107), and phenyl acetylene (20), affording the selective synthesis of propargylamines (108) at room temperature (Scheme 9.32) (Gonzalez-Bejar et al. 2013). Propargylic alcohols constitute important building blocks for many biologically active compounds and natural products. 

N. Gommermann, P. Knochel, Chem.-Eur. J. 2006, 12, 4380-4392. Practical highly enantioselective synthesis of propargylamines through a copper-catalyzed one-pot three-component condensation reaction. 

A. Hajra, Green Chem. 2002, 4, 551-554. A simple and green procedure for the synthesis of a-aminophosphonate by a one-pot three-component condensation of carbonyl compound, amine and diethyl phosphite without solvent and catalyst, (b) S. Chandrasekhar, C. Narshmulu, S. S. Sultana,... 

The synthesis of 2,4,5-trisubstituted-lH-imidazoles via the one-pot three-component condensation of benzil/benzoin, aldehydes and ammonium acetate under solvent-free conditions has been achieved using the BAIL, (4-sulfobutyl)tris(4-sul-fophenyl) phosphonium hydrogen sulfate as a catalyst [142] (Scheme 4.13). 

An efficient one-pot three-component condensation of aldehydes, thiols, and malononitrile has been developed (Scheme 5.30) in the presence of calcium oxide NPs. Highly substituted pyridines as privileged medicinal scaffolds have been efficiently prepared via caibon-caibon and caibon-heteroatombond formation [80],... 

As mentioned previously in this book, the quest for sustainable, atom-economical, and environmentally friendly chemical processes is a big current issue. Besides one-pot, sequential reaction processes (generally catalyzed by either metals or enzymes), multicomponent reactions have become very important [51]. The Petasis reaction, alternatively called Petasis horono Mannich reaction, is a mUd multicomponent reaction, which was reported first by Petasis and Akritopoulou in 1993 [52]. This reaction allows the one-pot three-component condensation of an aryl- or alkylboronic acid, an amine, and an aldehyde (or generally a carbonylic compound) to generate substituted amines at room temperature (Scheme 6.38). 

Keywords Aldehydes, indoles, C-H activated acids (4-hydroxycoumarin, 4-hydroxy-6-methyl-2//-pyran-2-one, dimedone, AAA -dimethylbarbituric acid, Meldrum s acid), L-proline, solvent-free, room temperature, grinding, one-pot three-component condensation, gewt-(P-dicarbonyl)arylmethanes... 

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