Aromatization, of 1,4-dihydropyridines

Yadav JS, Reddy BVS, Basak AK, Baishya G, Narsaiah AV (2006) lodoxybenzoic acid (IBX) an efficient and novel oxidizing agent for the aromatization of 1,4-dihydropyridines. Synthesis 451 54... 

Xia JJ, Wang GW (2005) One-pot synthesis and aromatization of 1,4-dihydropyridines in refluxing water. Synthesis 2379-2383... 

Nitration and oxidation. Clay-supported Cu(N03)2, unlike clayfen (12,231), > shelf-stable for months. Like clayfen, it is a convenient source of N02+ and can leave thioacetals or selenoacetals to the carbonyl compound at 25° in high yield. It effects aromatization of 1,4-dihydropyridines in 80-92% yield. In the presence i acetic anhydride, it can effect nitration even of halobenzenes at 25° with marked, - jra-preference, which can be enhanced by use of lower temperatures. 

Zolfigol, M. A., Kiany-Borazjani, M., Sadeghi, M. M., Mohammadpoor-Baltork, I., Memarian, H. R. Aromatization of 1,4-dihydropyridines under mild and heterogeneous conditions. Synth. Commun. 2000, 30, 3919-3923. 

Phenyl-l,2,4-tiiazole-3,5-dione 180 was found to be a novel and reusable reagent for the aromatization of 1,4-dihydropyridines under mild eonditions <05TL5581>. 1-Benzylsulfanyl-... 

M. A. Zolfigol, A. G. Choghamarani, M. Shahamirian, M. Safaiee, 1. Mohammadpoor-Baltork, S. Mallakpour, M. Abdollahi-Alibeik, Tetrahedron Lett. 2005, 46, 5581-5584. 4-Phenyl-l,2,4-triazole-3,5-dione as a novel and reusable reagent for the aromatization of 1,4-dihydropyridines under mild conditions. 

M. Montazerozohori, B. Karami, M. Nasr-Esfahani, S. A. Musavi, Heterocycl. Commun. 2007, 13, 289-294. Silver salts/iodine monochloride as a new oxidation system for the oxidative aromatization of 1,4-dihydropyridines. 

M. Filipan-Litvic, M. Litvic, I. Cepanec, V. Vinkovic, Arkivoc 2008, (xi), 96-103. Antimony(V) chloride-promoted room temperature aromatization of 1,4-dihydropyridines in non-acidic solvent. 

Das Sharma S, Hazarika P, Konwar D (2008) A simple, green and one-pot four-component synthesis of 1,4-dihydropyridines and their aromatization. Catal Commun 9 709-714... 

Marubayashi et al. <1997J(P2)1309> have also shown that solid-state dimerization is possible and propose that there is a buffer zone in the crystal structure of 1,4-dihydropyridines that governs the solid-state photodimerization process. This is exemplified by the fact that dimethyl l,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicar-boxylate 83 cannot undergo solid-state photodimerization (Equation 21), whereas the structurally related (4/ 3, l / 3 )-methyl-l-phenyl-2-piperidinoethyl-l,4-dihydro-2,6-dimethyl-4-(2-thienyl)pyridine-3,5-dicarboxylate 84 affords a single product 5 (Scheme 2). Interestingly, when the photodimerization conditions are applied to the corresponding solution-phase reaction, the sole product is that of aromatization giving product 85. 

A large number of 1,4-dihydropyridines were prepared from 3,5-diformyl-4-ethynyl-4//-pyran (85d). Thus compounds 568a,b and 569a-c were isolated after the reaction of 85d with primary amines,62,442 ammonium acetate,440 urea, and thiourea.440 As shown in Scheme 34, some aromatic amines react with both 3,5-aldehydic groups to afford 1,4-dihydropyridine Schifif bases 570.62,442... 

Tetrahydroquinolones can be transformed also by (diacetoxyiodo)benzene 3 to the aromatic arylquinolines, a structure found in various alkaloids [101]. Depending on the reagent, it is possible to oxidize flavanones 50 either into flavones 51 or into rearranged isoflavones 52 [102, 103]. (Diacetoxyiodo)-benzene 3 or the polymer-supported reagent 18 were also efficient reagents for the oxidation of 1,4-dihydropyridines 53 to the corresponding pyridine derivatives 54, Scheme 23 [104]. 

The Hantzsch synthesis of dihydropyridines represents a classical example of MCR, generating an array of diversely substituted heterocycles in a one-pot reaction procedure. Given that the reaction requires elevated temperatures and extended reaction times to proceed, acceleration of the process by microwave irradiation could be envisioned. Indeed, dielectric heating of aldehyde (aliphatic or aromatic) and 5 equivalents of /i-keloesler in aqueous 25% NH4OH (used both as reagent and solvent) at 140-150 °C for merely 10-15 min furnished 4-aryl-l,4-dihydropyridines in 51-92% yield after purification on a silica gel column [100]. The Hantzsch synthesis under reflux conditions ( 100 °C) featured a remarkably longer time (12 hours) and lower yields (15- 72%). To demonstrate the suitability of the procedure for the needs of combinatorial chemistry, a 24-membered library of 1,4-dihydropyridines (DHP) was prepared (Scheme 36). 

B. Zeynizadeh, K. A. Dilmaghani, M. Mirzaei, Asian J. Chem. 2009, 21, 2969-2972. Mild and efficient method for aromatization of Hantzsch esters of 1,4-dihydropyridines with HIOj. 

A one-pot Hantzsch reaction in aqueous medium without any solvent or catalyst is known for the synthesis of 1,4-dihydropyridines. Tamaddon and coworkers have reported the synthesis of 1,4-dihydropyridines 107 by the reaction of aldehydes 51 and methyl/ethyl acetoacetates 106 in aqueous ammonium carbonate at 55-60 °C (Scheme 35) [88]. Recently, a similar study has also been carried out by Yang and coworkers to obtain dihydro-pyridines [89]. Another example of dihydro pyridine ring formation in water employs methyl/ethyl acetoacetates and aromatic aldehydes with 6-amino-l,3-dimethyluracil in the presence of thiourea dioxide as the catalyst [90]. The utilization of water as a solvent and indium(III) chloride as a promoter for the formation of dihydropyridine ring is reported by Khurana and coworkers in the reaction of with 6-amino-l,3-dimethyluracil, aldehydes, and 1,3-diketones [91]. 

Analogous to DPNH (144-146), 1,4-dihydropyridines (147) act as reducing agents. For instance, the conversion of aromatic nitro compounds to amines (148) and reduction of enones to ketones (749) has been achieved. 

Formation of the ammonium salt of the bistetronate 118 followed by heating results in cyclization to the 1,4-dihydropyridine, which can be aromatized to give 119 by treatment with nitric/sulfuric acids (Equation 27)... 

Heravi MM, Behbahani FK, Oskooie HA, Shoar RH (2005) Catalytic aromatization of Hantzsch 1,4-dihydropyridines by ferric perchlorate in acetic acid. Tetrahedron Lett 46 2775-2777... 

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