Vicinal diamination of 1,4-dihydropyridines (original) (raw)
HETEROCYCLES, 2002
Dedicated to Emeritus Professor Miha Tišler, University of Ljubljana, on the occasion of his 75 th birthday Abstract -4-{3-Dimethylamino-1-[2-(dimethylamino)vinyl]prop-2-enylidene}-2phenyl-1,3-oxazol-5(4H)-one (3) and 5-{3-dimethylamino-1-[2-(dimethylamino)vinyl]prop-2-enylidene}-3-methyl-2-thioxo-1,3-thiazolidin-4-one (15) were prepared from 4-(1-methylethylidene)-2-phenyl-1,3-oxazol-5(4H)-one (2) and 5-(1-methylethylidene)-2-thioxo-1,3-thiazolidin-4-one (11), respectively. Treatment of compounds ( ) and ( ) with primary amines afforded 1,4-dihydropyridine derivatives ( ) and ( ) in 19-94% yields. Reactions of oxazolones (5) with hydrazine hydrate gave the corresponding imidazolones (6), while upon base-or acid-catalysed methanolysis of 5 methyl (benzoylamino)(1-substituted pyridin-4(1H)-ylidene)acetates (7) were obtained. Catalytic hydrogenation of 7a furnished α-(piperidin-4-yl)glycine derivative (8) and/or α-(pyridin-2-yl)glycine derivative (9). The interest in dihydropyridines is due to the unique ability of these compounds to act as NAD(P)H analogues of 1,4-dihydronicotinamide. 1 They are most extensively studied as calcium antagonists, 2 however, they also exhibit hepatoprotective, 3 antitumor, 4 antidiabetic, 5 bronchodilating, 6 and other pharma-cological activities 7-9 (Figure ). Figure 1. Examples of Pharmacologically Important 1,4-Dihydropyridine Derivatives. H N Me Me NO 2 MeOOC COOMe Nifedipine (calcium channel blocker) H N Me Me O Cl Cl Clopidol (antiparasitic) N O COOH N Ciprofloxacin (antibiotic) HN F There are several methods for the preparation of 1,4-dihydropyridine derivatives described in the literature. The most widely used method is Hantzsch-type cyclocondensation reaction 11,12 (Scheme 1). Hantzch Three-Component Synthesis of 1,4-Dihydropyridines.
Dihydropyrimidines are an important class of heterocyclic compounds reported in 1893 for the first time by P.Biginelli and possess wide spectrum of biological properties.Several catalysts have been used for the preparation of dihydropyrimidines but the procedures associated with them are difficult.So this requires a new procedure using a catalyst which is readily available and with easy procedure.The present work overcomes the difficulty by carrying out the synthesis of novel Dihydropyrimidine derivatives using aromatic aldehydes, methylacetoacetate ,thiourea and phosphorous pentoxide. All the synthesized compounds were characterized by IR and 1 H NMR Spectroscopy. The compounds were evaluated for their antibacterial, antifungal and antioxidant activities. IVa and IVd compound show good antimicrobial activities. The compound IVb and IVd have significant antioxidant properties.
2016
1,4-Dihydropyridines (1,4-DHPs) are recognized as one of the most versatile pharmacophores present as central core in many pharmaceuticals. Low yield and harsh reaction conditions prompted the researchers for the development of new environmental-friendly methods for the synthesis of 1,4-DHPs. This review explored the development of various green chemistry approaches using new catalysts developed for constructing novel 1,4-dihydropyridine and its derivatives. The present review also encompasses the synthesis of some novel 1, 4-DHPs derivatives with novel pharmacological actions. We have restricted our review of synthesis and pharmacological actions of 1,4-DHPs from 2006 onwards.
Helvetica Chimica Acta, 2011
Dedicated to Prof. Hooshang Pirelahi on the occasion of his 70th birthday The four-component reaction of dimethyl acetylenedicarboxylate (¼ dimethyl but-2-ynedioate; DMAD), aromatic aldehydes, and malononitrile (¼ propanedinitrile) leads to polyfunctionalized 1,4dihydropyridine derivatives. The reaction proceeds at room temperature and in the presence of a catalytic amount (20%) of (NH 4) 2 HPO 4 as a base in aqueous media.
Organic letters, 2016
Regio- and stereoselective addition of alkyl Grignard reagents to pyridine-N-oxides gave C2-alkylated N-hydroxy-1,2,5,6-tetrahydropyridines and trans-2,3-disubstituted N-hydroxy-1,2,5,6-tetrahydropyridines in good to excellent yields. These intermediates were aromatized or alternatively reduced in one-pot methodologies for efficient syntheses of alkylpyridines or piperidines, respectively. These reactions have a broad substrate scope and short reaction times.
Organocatalyzed regioselective and enantioselective synthesis of 1,4- and 1,2-dihydropyridines
Synthetic Communications, 2020
Herein, we introduce one of the first examples of asymmetric organocatalyzed synthesis of 1,2-dihydropyridines, affording enantioselective access to and partially solving regioselectivity challenges in the synthesis of dihydropyridines. We demonstrate that through modification of organocatalysts both 1,2-and 1,4-dihydropyridines (1,2and 1,4-DHPs) can be obtained with high regioselectivity (ratio of 1,2-DHP/1,4-DHP from 95/5 to 0/100) and enantioselectivity (33% ee for 1,2-DHPs and up to 98% ee for 1,4-DHPs) in good yields (up to 87%).
Monatshefte Fur Chemie - MONATSH CHEM, 2010
Benzothieno[2,3-c]pyridinium and benzothieno[2,3-c]quinolinium salts were synthesized either by quaternization of benzothieno[2,3-c]pyridines, or recyclization of benzothieno[2,3-c]pyrylium salts with primary amines. One-pot synthesis of benzothieno[3,2-g]indolizinium salts from 1-(3-chloropropyl)-benzothieno[2,3-c]pyrylium included consequent recyclization of the pyrylium core by ammonia into a pyridine intermediate and its further intramolecular quaternization reaction. Depending on the structure of benzothieno-annelated pyridinium salts, their reaction with sodium borohydride in methanol results in reduction of the pyridine core into tetrahydropyridine or dihydropyridine derivatives. Whereas reduction of benzothieno[2,3-c]pyridinium and benzothieno[3,2-g]indolizinium salts readily yields benzothieno-annelated tetrahydropyridines as a complex mixture of stereoisomers, reduction of benzothieno[2,3-c]quinolinium salts results in dihydropyridine derivatives. The structure of the latt...
Scope and Limitations of an Efficient Four-Component Reaction for Dihydropyridin-2-ones
The Journal of Organic Chemistry, 2010
A broad range of isonitrile-functionalized 3,4-dihydropyridin-2-ones could be prepared using a fourcomponent reaction between phosphonates, nitriles, aldehydes, and isocyanoacetates. The reaction involves initial formation of a 1-azadiene intermediate which is trapped in situ by an isocyanoacetate to give the desired heterocyclic scaffold through cyclocondensation. The full scope and limitations of this four-component reaction are described. Variation of the nitrile and aldehyde inputs proved to be extensively possible, but variation of the phosphonate input remains limited. Regarding the isocyanoacetate, R-aryl isocyanoacetates give moderate to high yields and result in a complete diastereoselectivity for the 3,4-cis isomer. R-Alkyl isocyanoacetates gave the corresponding dihydropyridin-2-ones in moderate yields, most of them as mixtures of diastereomers. Elevated temperatures during cyclocondensation generally increased the yield and resulted in a change of the diastereomeric ratio in favor of the cis-diastereomer. In addition to isocyanoacetates, a limited number of other R-acidic esters resulted in the formation of dihydropyridin-2-ones, albeit in much lower yield. Computational studies show that the observed difference in yield cannot be simply correlated to specific physical properties (including acidity) of the different R-acidic esters.
Synthesis and Stereochemistry of 3Hydroxy1,2,3,6-tetrahydropyridines
Russian Journal of Organic Chemistry, 2005
A series of 1-benzyl-3-hydroxy-1,2,3,6-tetrahydropyridines, multipurpose synthons for fine organic synthesis and potential antiviral compounds, was prepared by the rearrangement of a number of 1-benzyl-3,4- epoxypiperidines under treatment with lithium amides. 3,4-Epoxypiperidines were obtained by oxidation of 1,2,5,6- tetrahydropyridines trifluoroacetates with a trifluoroperacetic acid. Convenient synthetic routes were found and developed. A conformation analysis of the series of stable 3,4-epoxypiperidines and 3-hydroxy-1,2,3,6- tetrahydropyridines was carried out.