Hantzsch condensation

The modified Hantzsch condensation of nitroacetone, 2,l,3-benzoxadiazol-4-carboxaldehyde 253, and ( S,ZR)-Z-(3,5-dinitrophenylcarbonylamino)-2-methoxycarbonyl-l-methylethyl 3-aminocrotonate afforded a mixture of the two diastereomers that differ in configuration (S or R) at the C-4 position of the 1,4-DHP ring (DHP - dehydropeptidase) (Equation 49) <2004JME254>. 

Sapkal SB, SheUce KE, Shingate BB, Shingare MS (2009) Nickel nanoparticle-catalyzed facile and efficient one-pot synthesis of polyhydroquinoline derivatives via Hantzsch condensation under solvent-lfee conditions. Tetrahedron Lett 50 1754-1756... 

A novel solid-phase synthesis of pyrrolo[3,4- ]pyridines using a sequence of Knoevenagel and Hantzsch condensation reactions has been reported <199981951 >. The reactions lead to a variety of highly substituted pyrrolo[3,4- ]pyridines, 70. 

Solid-phase syntheses have become increasingly popular during the period of this review, with examples including the synthesis of 5,6,7,8-tetrahydro[l,6]naphthyridines from Meldrum s acids derived from /3-amino alcohols via Hantzsch condensation and cyclization with cyclative cleavage from the resin (using 70% trifluoroacetic acid (TFA)/dichloromethane (DCM) followed by 5% triethylamine/DCM) <1999S1951> and also of isoquinolinones and 5-oxo-5,6-dihydro-[l,6]naphthyridines <1995JOC5748>. 

Solid-phase synthesis of pyrido[2,3 pytirtiidines 514 was achieved by Hantzsch condensation of Wang resin-supported Knoevenagel derivative 513 with 6-aminouracil derivatives 512 as an a-oxo enamine component in the presence of ceric ammonium nitrate (CAN) in DMA followed by hydrolysis with TFA in CH2GI2. Compound 513 was prepared by treatment of a hydroxylated polymer, such as Wang or Sasrin resin, with diketene, followed by condensation with benzaldehyde (Equation 41) <1996TL4643>. 

Nearly a century later with the recognition that DHPMs possessed similar pharmacological profiles to the Nifedipine class [9a] of DHP calcium channel modulators 2 (formed via the Hantzsch condensation 1882, Scheme 11.2 [9b]), the Biginelli reaction witnessed a dramatic upsurge in popularity [10],... 

The product of Step 2 was also used in the Hantzsch condensation to prepare phthaloyl amlodipine, a precursor for amlodipine besylate (3). 

A new series of polyhydroquinolines 64 has been prepared by Shingare and co-workers [111] using nanosized Ni as a heterogeneous catalyst in a one-pot synthesis via Hantzsch condensation by reacting an aldehyde, dimedone, ethyl aceto-acetate and ammonium acetate in a domestic microwave oven. Ni (80 0.5 nm), having a higher surface to volume ratio, has given the best results in terms of short reaction times and excellent product yields. This method has demonstrated that Ni, in the form of nanoparticles, is a potential alternative catalyst for the Hantzsch... 

Thiazole esters 252a-c were prepared by Hantzsch condensation with a thioamide in good yield except in the case of 252c, bearing a methyl ester (Scheme 101) <2006JA2995>. 

A library of 500 bipyridines was synthesized using a solid state combinatorial approach using five beta-ketoesters, 10 aldehydes, and 10 enamines through sequential Knoevenagel/Hantzsch condensation reactions.56... 

A semiautomated fluorometric procedure for quantitating triglycerides was presented by Kessler and Lederer in 1965 (K6). This is based on the Hantzsch condensation reaction between an amine, j8-diketone, and an aldehyde (Bl, Nl). Isopropanolic extracts of serum are prepared manually, and at this point can also be used for the determination of cholesterol and phospholipids. Triglycerides can be determined after treatment with Zeolite, as employed by Van Handel and Zilversmit... 

Heterocycle formation (Hantzsch condensation, Pictet-Spengler, Fischer synthesis of indoles, Pd-heteroannulation)... 

The reagents stayed in the aqueous phase. The product precipitated as formed. The hydrotropic solution showed no problems after being recycled four times. This method has also been used in the Hantzsch condensation (8.39) where, again, the product was recovered by filtration. 

As an example, we present a solution-phase multigeneration strategy towards highly substituted thiazoles based on the Hantzsch condensation of thioureas 33 with 2-bromomethyl ketones 34 to give 2-aminothiazoles 35 in high yields, as shown in Scheme 3.4.4, using liquid-liquid phase extraction (LPE) and liquid-solid phase extraction (SPE). 

Panek and co-workersdescribed syntheses of suitably bis-functionalized tris-oxazoles as intermediates leading to kabiramide C, halichondramide, and ulapualide A based on sequential application of a modified Hantzsch condensation methodology (Scheme 1.395). For example, condensation of cinnamide with ethyl... 

Amidation of the ester and protection of the alcohol gave 1553, which was elaborated to the tris-oxazole 1554 via a third modified Hantzsch condensation-cyclodehydration sequence followed by DIBAL-H reduction of the ester. 

It is also interesting to note that Van Bergen and Kellogg have used the Hantzsch condensation to construct the pyridine ring in situ <76CC964>. Construction of the pyridine unit from the / -keto ester places the pyridine nitrogen exocyclic (12), unlike (9)-(ll) in which the pyridine N is endocyclic. 

The Hantzsch strategy has been applied in the synthesis of the dopamine Da-agonist pramipexole, a molecule comprising a fused bicyclic tetrahydrobenzothiazole substructure. The synthesis starts with a-bromination of protected 4-aminocyclohexanone followed by the Hantzsch condensation with thiourea. Deprotection and then chiral resolution yield the -enantiomer. Reductive amination leads to pramipexole, which is isolated as the dihydrochloride. ... 

Maheswara et al. (2006) have developed a simple HC104-Si02-catalysed one-pot synthesis of 1,4-DHPs by Hantzsch condensation of aliphatic and heterocyclic... 

Polyhydroquinoline derivatives have been prepared efficiently in a one-pot synthesis via Hantzsch condensation using nano-sized Nickel (Ni) as a heterogeneous catalyst under microwave irradiation by Shingare et al. [87] (Scheme 5.36). 

Keywords Aldehydes, dimedone, active methylene compounds, ammonium acetate, solvent-free, catalyst-free, room temperature, grinding, one-pot multicomponent synthesis, Hantzsch condensation, polyhydroquinolines... 

Adibi, H., Samimi, H. A., and Beygzadeh, M. (2007). Iron(Itl) trifluoroacetate and trifluoromethane-sulfonate Recyclable Lewis acid catalysts for one-pot synthesis of 3,4-dihydropyrimidinones or their sulfur analogues and 1,4-dihydropyridines via solvent-free BigineUi and Hantzsch condensation protocols. Catal. Common., 8, 2119-2124. 

A. Debache, L. Chouguiat, R. Boulcina, B. Carboni, A one-pot multi-component synthesis of dihydropyrimidinone/ thione and dihydropyri-dine derivatives via Biginelli and Hantzsch condensations using f-BuOK as a catalyst under solvent-free conditions, Open Org. Chem. J. 6 (2012) 12-20. 

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