Diene synthesis with 2-pyrones and 2-pyridones XIV. 1,4-Cycloadducts of 1-alkyl-2-pyridones with N-phenylmaleinimide and maleinimide

1-Alkyl-2-pyridones react with N-phenylmaleinimide and maleinimide stereoselectively via the scheme of the diene synthesis to give imides of 8-alkyl-8-azabicyclo[2.2.2]-4-octen-7-one-1,2-dioic acid. 3-Unsubstituted 2-pyridones form adducts with an endo configuration, whereas 1,3-dimethyl-2-pyridone gives an exo adduct under the same conditions. The endo- and exo-bridge adducts readily undergo retrograde diene disintegration on heating.     

Liquid-phase synthesis of 2,3-dihydro-4-pyridones: one-pot three-component aza Diels-Alder reaction of Danishefsky's diene with aldehydes and PEG-supported amine

An efficient liquid-phase synthesis technique for the construction of 2,3-dihydro-4-pyridones on soluble polymer support has been developed, which utilized one-pot reaction of Danishefsky's diene with aldehydes and polymer-supported amine.     

Alkaline salt-catalyzed aza Diels-Alder reactions of Danishefsky's diene with imines in water under neutral conditions

Two- or three-component aza Diels-Alder reactions of Danishefsky's diene with imines or aldehydes and amines in water took place smoothly under neutral conditions in the presence of a catalytic amount of an alkaline salt such as sodium triflate to afford dihydro-4-pyridones in high yields.     

Diene synthesis with 5-chloro-1-alkyl-2-pyridones

For the first time, we describe the diene synthesis of 5-chloro-1-alkyl-2-pyridones with N-phenylmaleic imide and have shown that the reaction proceeds nonstereoselectively with formation of a mixture of [4+2]cycloadducts with anendo andexo configuration. We have obtained 1,4-cycloadducts with 4-phenyl-1,2,4-triazoline-3,5-dione.M. V. Lomonosov Moscow State University, Moscow 119899. Translated from Khimiya Geterotsklicheskikh Soedinenii, No. 5, pp. 687–691, May, 1997.     

Diels-Alder reactions of nitro-2(1H)-pyridones with 2,3-dimethyl-1,3-butadiene

Diels-Alder (DA) reactions of 3- or 5-nitro-2(1H)-pyridones and nitro-2(1H)-pyridones containing a methoxycarbonyl group with 2,3-dimethyl-1,3-butadiene were examined. The DA reactions of 3-nitro-2(1H)-pyridones in this paper represent, to the best of our knowledge, the first report of DA reactions of 3-substituted 2(1H)-pyridones and consequent production of isoquinolones. Performing the same reactions with 5-nitro-2(1H)-pyridones yielded quinolones. DA reactions of 2(1H)-pyridones with nitro and methoxycarbonyl groups produced isoquinolones, quinolones and phenanthridones (the double DA adducts), aromatized or hydrogenated. The substituent effect was evaluated by calculating the activation energy, using the ab initio MO method.     

Solid-phase synthesis of pyridones and pyridopyrazines as peptidomimetic scaffolds

[formula: see text] We report the syntheses of peptidomimetic opioids containing the core structure N-alkyl-2-alkyl-2,3-dihydro-4-pyridone. By employing imines bound on a solid support and the Danishefsky diene, this [4 + 2] cyclocondensation reaction facilitates the synthesis of novel complex heterocycles. The central reaction is carried out under mild conditions and employs readily available building blocks. In this study we demonstrate the suitability of N-alkyl-2-alkyl-2,3-dihydro-4-pyridones as a central scaffold for peptidomimetics and establish the scope of this [4 + 2] cyclocondensation reaction with imino acids on a solid phase. We also combine the synthesis of diketopiperazines with the [4 + 2] cyclocondensation reaction to form a 9,9a-dihydro-2H-pyrido-[1,2a]- pyrazine-3,8(1,4-dialkyl)dione, a bicyclic molecule containing a pyridopyrazine core structure.     

2-pyridones from cyanoacetamides and enecarbonyl compounds: application to the synthesis of nothapodytine B

The condensation of an enone or enal with cyanoacetamide derivatives and t-BuOK furnishes either 3-cyano-2-pyridones or 3-unsubstituted-2-pyridones, depending on whether the reaction is carried out in the presence or in the absence of O(2). In the first case, in situ oxidation of Michael-type intermediates takes place; in the second case, the products result from "decyanidative aromatization" of such intermediates. A one-step synthesis of 3-alkyl-2-pyridones has been devised on the basis of decyanative union of an enone/enal and a 2-alkylcyanoacetamide. The new reaction forms the centerpiece of an unusually concise synthesis of nothapodytine B (mappicine ketone).     

Recent advances in synthesis of 2-pyridones: a key heterocycle is revisited

Owing to the versatile applications in different areas including biology, natural compounds, dyes, and fluorescent materials, the synthesis of 2-pyridone compounds is an important research field and has attracted a great deal of attention. In this review, 2-pyridones new synthetic methods are classified to tree classes including reactions based on pyridine rings, cyclization, and cycloaddition reactions.     

Cycloaddition reactions of 4-sulfur-substituted dihydro-2-pyridones and 2-pyridones with conjugated dienes

Cycloaddition reactions of sulfoxide- and sulfone-substituted dihydro-2-pyridones and 2-pyridones with electron-rich dienes gave new bicyclic and tricyclic products in good to fair yields. The reactivity, regioselectivity, and stereoselectivity of these reactions were compared with semi-empirical theoretical calculations. Evidence is provided for rather unusual two parallel reaction pathways for the cross-Diels-Alder reaction of a sulfone-substituted 2-pyridone with cyclopentadiene.     

Regiocontrolled preparation of 3-acyl-6-aryl-2-pyridones via condensation of 3-aryl-3-chloropropeniminium salts with β-keto-amides

Α series of substituted 3-acyl-6-aryl-2-pyridones have been prepared in one-step reactions via condensation of 3-aryl-3-chloropropeniminium salts with β-keto-amides. This efficient synthesis has the advantages of high yields and simple reaction procedures.     

Diels-Alder reactions of 3-and 5-methyl-1-vinylpyrazoles with cyclohexa-1,3-diene and hydrogenation of the reaction products

The behavior of isomeric vinylpyrazoles in the Diels-Alder reactions with cyclohexa-1,3-diene was studied to show that the spatial location of the vinyl group on the N² atom does not affect the diene synthesis.     

Specific Features of the Reaction of 2-Nitro- and 2-Bromo-2-Nitroethenylphosphonates with Furan

Investigation of the reactions of phosphorylated 2-nitro- and 2-bromo-2-nitroethenes with furan showed that bis(2-chloroethyl) 2-nitroethenylphosphonate reacts with this heterocycle according to the pathway of diene condensation, while in the case of 2-bromo-2-nitroethenylphosphonate by two pathways, the complete diene synthesis accompanied by aromatization, and the electrophilic substitution at C²-atom of the furan with the subsequent partial dehydrohalogenation.     

Scalable synthesis of functionalised 2-pyridones via [4+2] cycloaddition reactions of 2-pyrazinones and alkynylboronates

The multigram synthesis of N-protected 2-pyridone boronic acid derivatives via a [4+2] cycloaddition of alkynylboronates with 2-pyrazinones is presented. The reactions are highly chemoselective, and generally highly regioselective although trimethylsilyl-substituted alkynylboronates have proven to be an exception. Nonetheless, in this latter case, separation of regioisomers was successfully accomplished via high performance counter-current chromatography allowing isolation of analytically pure 2-pyridones. Further derivatisations of trimethylsilyl-substituted 2-pyridone boronates were performed providing access to a selection of functionalised scaffolds.     

Heterocycles. Part V. Reaction of α,β-unsaturated carbonyl compounds with arylacetamides. A synthesis of 2-pyridone derivatives

The reaction of 1,3-diaryl-2-propene-1-ones I with arylacetamides II, in the presence of sodium ethoxide under reflux, for two hours, gave the corresponding 3,4,6-triaryl-3,4-dihydro-2(1H)-pyridones IV. However, when the reaction of these ketones was carried out in the presence of sodium hydride, they gave the corresponding 3,4,6-triaryl-2(1H)-pyridones VI or a mixture of IV and VI. When 1,3-diaryl-2-propyne-1-ones V were reacted with arylacetamides, in the presence of sodium hydride, they yielded the corresponding 2-pyridones VI. Treatment of compounds IV with selenium produced the corresponding 2-pyridones VI. Acetylation of the latter compounds gave the corresponding 2-acetyl derivatives VIII. The structure of all products was confirmed by chemical and spectroscopic evidence, and the mechanism of the reactions was discussed.     

Synthesis of Some Halogen- and Nitro-substituted Nicotinic Acids and Their Fragmentation Under Electron Impact

Features of electrophilic and nucleophilic substitution under chlorination and nitration reactions conditions have been investigated for 6-hydroxy- and 6-methyl-substituted derivatives of 3-cyano-4-methyl-2(1H)-pyridones. The polychloro- and nitro-substituted 3-cyano-4-methylpyridines obtained were used as synthons in the synthesis of some polyhalo- and nitro-substituted nicotinic acids and their amides. The fragmentation pathways of the synthesized compounds under electron impact have been studied.     

Synthesis and evaluation of dihydroimidazolo and dihydrooxazolo ring-fused 2-pyridones—targeting pilus biogenesis in uropathogenic bacteria

Dihydrothiazolo ring-fused 2-pyridones have previously been shown to inhibit pilus assembly in uropathogenic Escherichia coli. Methods have now been developed to synthesize both dihydroimidazolo and dihydrooxazolo ring-fused 2-pyridones. To obtain the nitrogen analogs, Cbz-protected imidazolines were reacted with an acyl-Meldrum's acid derivative under acidic conditions. To prepare the oxygen analogs, a one-pot procedure was developed that allowed synthesis of dihydrooxazolo ring-fused 2-pyridones starting from acylated serine derivatives. After hydrolysis to their corresponding carboxylic acids and lithium carboxylates, biological evaluation revealed that the sulfur could be replaced by an oxygen atom and still maintains the ability to inhibit pilus assembly in uropathogenic E. coli. However, introducing a secondary amine instead of oxygen resulted in a substantial decrease in biological activity.     

Regioselective synthesis of two types of highly substituted 2-pyridones through similar multicomponent reactions

The refluxing of a mixture of ethylcyanoacetate, aromatic aldehydes, and primary monoamines in ethanol produces highly substituted 2-amino-6-pyridones such as 2-amino-1-(alkyl)-5-cyano-6-oxo-4-(aryl)-1,6-dihydropyridine-3-ethylcarboxylates in one-pot. On the other hand the refluxing of a mixture of ethylcyanoacetate, aromatic aldehydes, and primary diamines (1,2-ethylenediamine/1,3-propylenediamine) in ethanol furnishes symmetrical zwitterionic 2-pyridones such as 1-(2-amino-ethyl/3-amino-propyl)-6-hydroxy-2-oxo-4-(aryl)-1,2-dihydropyridine-3,5-dicarbonitriles. The result shows that primary diamines and monoamines react differently in the reactions, which provides new mechanistic insight into the regioselective synthesis of these biologically important compounds.     

Diels–Alder Additions to 2,2’-Biaceanthrylene

A series of Diels–Alder reactions between the diene 2,2’-biaceanthrylene and several dienophiles is presented. The diene is a cyclopenta-fused polycyclic aromatic hydrocarbon with anthracene units linked by two cyclopentene rings. Depending on the dienophile, the major product was the result of a single addition (dimethyl acetylenedicarboxylate) or double addition (quinone, benzyne) to the diene. Single crystal X-ray analysis of the quinone-derivative shows a propeller-like structure composed of mixed enantiomers. The synthesis and photophysical properties of these compounds are presented.     

Synthesis and reactivity of a stable precursor of 2-cyano-1,3-butadiene

A new, productive synthesis of 3-cyano-2,5-dihydrothiophene-1,1-dioxide (3) is described. This substituted sulfolene serves as a stable precursor of 2-cyano-1,3-butadiene and can be used in the Diels-Alder reactions without isolation of the unstable diene.The Diels-Alder reactions of 2-cyano-1,3-butadiene appear to proceed in high yield only with electron-deficient dienophiles, but ¹³C NMR shows that in some cases the products are a mixture of regioisomeric cycloadducts.     

Microwave-promoted synthesis of amino-substituted 2-pyridone derivatives via palladium-catalyzed amination reaction

A rapid and efficient synthesis of amino-substituted 2-pyridones was demonstrated by palladium-catalyzed amination reaction under microwave irradiation. This high-speed synthesis provided a number of amino-substituted 2-pyridones from the corresponding bromo-2-benzyloxypyridines via palladium-catalyzed amination followed by hydrogenolysis of benzyl ether.