Three-component condensation reaction

Scheme 6.184 Ugi-type three-component condensation reactions.

Scheme 6.201 Three-component condensation reactions leading to 4-alkylthioimidazoles.

Scheme 2.57 Three component condensation reaction using polymer supported scavenger purification alternatively the trisamine resin could be substituted for purification in this step.

Shaabani A, Rahmati A, Rezayan AH, Darvishi M, Badri Z, Sarvari A (2007) Clean s)mthesis in water Uncatalyzed three-component condensation reaction of 3-amino-l,2,4-triazole or 2-aminobenzimidazole with aldehyde in the presence of activated CH-Acids. QSAR Comb Sci 26 973-979... 

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>. 

Varma, R.S. and Kumar, D., Microwave-accelerated three-component condensation reaction on day solvent-free synthesis ofimidazo[l,2-fl] annulated pyridines, pyrazines and pyrimidines, Tetrahedron Lett., 1999, 40, 7665-7669. 

The DHPMs should be synthesized in solution using standard Biginelli three-component condensation reaction mixtures. Although microwave-assisted Biginelli reactions have been published under solvent-free conditions,46 50 we felt that such methods would... 

Although the exact reaction mechanism for this three-component condensation reaction was not confirmed in [193, 194], the hypothesized mechanism is likely to involve the initial base-catalyzed formation of the Michael adduct, and its subsequent reaction with the aminopyrazole component to furnish the tricyclic intermediate (Scheme 3.63). Elimination of water from this intermediate leads to the formation of the classic Hantzsch-type dihydropyridine... 

In 1893 the Italian chemist Pietro Biginelli [2] reported the one-pot synthesis of 4-aryl-3, 4-dihydropyrimidin-2(lff)-ones (DHPMs 1) by a three-component condensation reaction of aromatic aldehydes, urea and ethylacetoacetate (Scheme 11.1). 

Microwave reaction conditions have been reported for the synthesis of 2-pyridones in a modern version of the traditional three-component condensation reaction (Scheme 108) <2004T8633>. A library of 18 3,5,6-trisubstituted pyridines was generated and includes aryl, alkyl, and fused derivatives. 

Three component condensation reactions (Gewald reaction) between an activated nitrile, ketone or aldehyde, and sulfur has been utilized to prepare a variety of a-aminothiophenes. Recent examples utilizing this condensation reaction include the synthesis of 4,5-dialkyl-2-... 

The preparation of highly functionalization selenophenes has been accomplished utilizing a three-component condensation reaction involving ketene dithioacetals, sodium selenide, and an activated carbonyl component (Scheme 13) <2003SL855, 2004S451, 2005PS939>. Ketene dithioacetal 122 was prepared from 2,4-pentanedione by condensation with carbon disulfide followed by methylation. Treatment of compound 122 with sodium selenide and ethyl bromoacetate gave selenophene 123 in modest yield. 

A recent paper by Kiselyov et al. (91) reported the synthesis of two small SP discrete libraries of tetrahydroquinolines LI and L2 inspired by a three-component condensation reaction in solution (92-94) as depicted in Eig. 6.8. The scope of this condensation had been expanded by other groups (95-97), and the use of polymer-supjxMted metal catalysts had also been reported (98, 99) however, an SP route with a broad tolerance for different amines, aldehydes, and olefins had still not been defined prior to this work. 

Three-component condensation reactions of cyclic 1,3-diketones, 4-nitrobenzaldehyde, and alkyl or aryl isocyanides in water afforded the corresponding tetrahydrobenzofuran derivatives (04M441). 

Alkenyl epoxides. A three-component condensation reaction involves an anion, an aldehyde, and the dienylsulfonium salt. 

Using similar chemistry, the construction of perfiuoroalkyl-substituted 1,2,4-triazoles can be readily accessed through a three-component condensation reaction of aperfiuoroalkyl ester, a hydrazine, and an amidine. For example, Shreeve and coworkers prepared a series of alkylated 3-perfiuoroalkyl, 5-dimethyl-l,2,4-triazolium salts... 

FIGURE 3.86 A three-component condensation reaction to prepare perfluoroalkylated... 

Funabike, K. Noma, N. Kuzuya, G. Matusi, M. Shibata, K. A direct and general synthesis of 5-substituted 3-trifluoromethyl-l,2,4-triazoles via the three component condensation reaction of ethyl trifluoroacetate, hydrazine and amidines. J. Chem. Res. Synop. 1999, 300-301, 1999, 1301-1308. 

The Williams group published a three-component condensation reaction starting from oxindolidene acetate 158 which reacted with the azomethine yhde 161 formed in situ from the diphenylmorpholinone 160 and the isoprenoid aldehyde 159 (Scheme 32) [138-140]. The spiro compound 162 was obtained by 1,3-dipolar cycloaddition and converted further to the pentacyclic diketopiperazine 164. 

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. 

Saleh et al. (2012) have developed a novel and efficient three-component condensation reaction of an aldehyde, amino azoles, and p-keto sulfone for the synthesis of pyrimido[l,2-a]benzimidazoles (143) and pyrazolo[3,4-b]pyridines (146) under ultrasonic irradiation via utilization of P-keto sulfone as an important synthon (Schemes 8.47 and 8.48). 

Eftekhari-Sis, B. and Vahdati-Khajeh, S. 2013. Ultrasound-assisted green synthesis of pyrroles and pyridazines in water via three-component condensation reactions of arylglyoxals. Curr. Chem. Lett. 2 85-92. 

Three-component Condensation Reactions. Cu(OTf)2 catalyzes the three-component syuithesis of 3,4-dihydropyrimidin-2(l/ -ones (eq 31) in high yields via condensation of aldehydes with keto esters and ureas. For the three-component Biginelli condensation involving benzaldehyde, urea, and ethyl acetoac-etate, the reaction proceeds with a low catalyst concentration [0.5 mol % of Cu(OTf)2] at ambient temperature, yielding 3,4-dihydropyrimidin-2(l/ -one. ... 

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. 

K. -I. Serita, S. Hiraoka, T. Yokozawa, Tetrahedron Lett. 2000, 41, 7075-7078. Lewis acid-catalyzed three-component condensation reactions of aldehydes, A-silylcarbamates, and allylsilane synthesis of A-homoallylcarbamates. 

An efficient synthesis of 2/f-indazolo[2,l-(>]phthalazine-l,6,ll(13//)-trione derivatives has been achieved in one-pot reaction at room temperature from the three-component condensation reaction of phthalhydrazide, dimedone, and aromatic aldehydes under solvent-free conditions in good to excellent yields and short reaction times using reusable silica-supported Preyssler HPAs as a heterogeneous acid catalyst has been investigated (Scheme 3.14) [55]. 

Copper oxide NPs [72] showed excellent catalytic activity through three-component condensation reaction of aldehydes, malononitrile, and 4-hydroxycoumarin for the synthesis of 3,4-dihyropyrano[c]chromenes in water as a reaction medium in excellent yields and very short reaction times (Scheme 5.25). 

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