Synthesis of pyrazoles via CuI-mediated electrophilic cyclizations of α,β-alkynic hydrazones

Synthesis of pyrazoles via electrophilic cyclization of α,β-alkynic hydrazones by copper(I) iodide is described. When treated with copper(I) iodide in the presence of triethylamine in refluxing acetonitrile, α,β-alkynic hydrazones, prepared readily from hydrazines and propargyl aldehydes and ketones, undergo electrophilic cyclization to afford pyrazole derivatives in good to excellent yields. The reaction appears to be general for a variety of α,β-alkynic hydrazones and tolerates the presence of aliphatic, aromatic, and ferrocenyl moieties with electron-withdrawing and electron-donating substituents.     

A novel synthesis of 1,2,4-oxadiazoles and isoxazoles

A novel synthesis of 1,2,4-oxadiazoles and isoxazoles is described by utilizing the reactions between amidoximes and α,β-alkynic aldehydes and/or ketones. Conjugate addition products, obtained from amidoximes and α,β-alkynic aldehydes and/or ketones, afford 1,2,4-oxadiazoles and isoxazoles when treated with bases and acids, respectively. 1,2,4-Oxadiazoles can also be synthesized directly from amidoximes and α,β-alkynic aldehydes in a one-pot manner under basic conditions. The reactions are general for a variety of starting compounds and tolerate the presence of aryl, heteroaryl and alkyl groups.     

One-pot synthesis of iodine-substituted 1,4-oxazepines

A facile one-pot method for the synthesis of iodine-substituted 1,4-oxazepines is reported. When reacted with ZnCl₂ and I₂ in DCM at 40?°C, N-propargylic β-enaminones, prepared by the conjugate addition of propargylamine to α,β-alkynic ketones, underwent 7-exo-dig cyclization by zinc chloride and concomitant reaction with molecular iodine to afford 2-(iodomethylene)-2,3-dihydro-1,4-oxazepines in good to high yields. This cyclization was found to occur with broad scope of substrates and high tolerance of functional groups. The resulting iodine-containing 1,4-oxazepines can be further elaborated to more complex structures by subsequent cross-coupling reactions, which may provide a platform for biological studies.     

One-stage procedure of synthesis of highly reactive α-chloro-β-ketoacetals. 4-chloropyrazoles from α-chloro-β-ketodimethoxyacetals

Conditions were developed where the reaction of alkyl 1,2-dichlorovinyl ketones with alcohols and 1,2-dihydroxybenzenes led to the formation of the corresponding open-chain and cyclic α-chloro-β-ketoacetals. The reaction of α-chloro-β-alkylketodimethoxyacetals with alkyl-, benzyl-, and arylhydrazines resulted in 1,3-substituted 4-chloropyrazoles in 70–90% yields demonstrating that primarily formed 2,2-dimethoxy-1-chloroethyl alkyl ketones hydrazones underwent heterocyclization.     

[4 + 2]-Cycloadditionen von α,β-ungesättigten Hydrazonen. Teil 1. Pyridin-2,3-dicarboximide aus 1-(Dimethylamino)-1,4-dihydropyridin-Derivaten

[4 + 2] Cycloadditions of α,β-Unsaturated Hydrazones to Pyridine-2,3-dicarboximides via 1-(Dimethylamino)-1,4-dihydropyridine Derivatives The [4 + 2] Cycloaddition of α,β-unsaturated hydrazones of type 1 (1-aza-1,3-butadienes) with 2-halogenomaleimides 4 affords 1,4-dihydropyridines 6 which, after treatment with an acid, yield highly substituted pyridine-2,3-dicarboximide derivatives 7 (Scheme 1).     

[4+2]-Cycloadditionen von α,β-ungesättigten Hydrazonen. Teil 2. Pyridin-2,3-dicarboximide aus 1,4-Dihydropyridin-Derivaten

[4+2] Cycloaddition of α,β-Unsaturated Hydrazones to Pyridine-2,3-dicarboximides via 1,4-Dihydropyridine Derivatives The [4 + 2] cycloaddition of α,β-unsaturated hydrazones of type 1 (1-aza-1,2-butadienes) with maleimides (e.g. 2b ) affords the tetrahydropyridines of type 8. Elimination of dimethylamine to 9 is easily achieved by treatment of 8 with silica gel at elevated temperature. Oxidation of the dihydropyridines 9 leads to highly substituted pyridine-2,3-dicarboxylic-acid dervatives 4 .     

Enantioselective conjugate addition of donor-acceptor hydrazones to α,β-unsaturated aldehydes through formal diaza-ene reaction: access to 1,4-dicarbonyl compounds

Donor-acceptor monosubstituted hydrazones participate as suitable reagents able to undergo an enantioselective formal diaza-ene reaction with α,β-unsaturated aldehydes under chiral secondary amine catalysis. This constitutes a new approach for the enantioselective conjugate addition of hydrazones to enals under metal-free conditions and leads to the formation of γ-hydrazono carboxylic acids after oxidation/[1,3]-H shift. The methodology is also useful for the synthesis of enantioenriched β-substituted α-keto-1,5-diesters by using the hydrazone moiety as a masked carbonyl group.     

Iodine catalyzed conjugate addition of mercaptans to α,β-unsaturated carboxylic acids under solvent-free condition

We have described herein molecular iodine catalyzed Michael addition of thiol to α,β-unsaturated carboxylic acids. This environmentally benign catalytic system (iodine) used under mild and solvent-free conditions to achieve the corresponding adducts in excellent yield.     

Studies on the oxidation of hydrazones with iodine and with phenylselenenyl bromide in the presence of strong organic bases; an improved procedure for the synthesis of vinyl iodides and phenyl-vinyl selenides

The oxidation of hydrazones by iodine in the presence of strong organic bases (guanidines) has been studied. Improved yields of vinyl iodides can be obtained by inverse addition using dry solvents and with a final heating period where appropriate. The reaction has been extended to various dihydrazones with interesting results.In complementary studies hydrazones have been oxidized by phenylselenenyl bromide in the presence of strong organic bases to give the corresponding phenyl vinyl selenides in good yield.     

α,β-Epoxyketon → Alkinon-Fragmentierung II: Pyrolytischer Zerfall der Hydrazone aus α,β-Epoxyketonen und N-Amino-aziridinen. Über synthetische Methoden, 4. Mitteilung

Numerous examples illustrate the course of the thermolysis of hydrazones derived from α,β-epoxyketones and 2-phenyl- or trans-2,3-diphenyl-1-amino-aziridines. This process constitutes a preparatively useful method for the fragmentation of α,β-epoxyketones to acetylenic carbonyl compounds including acetylenic aldehydes. Monohydrazones from phenylglyoxal and substituted N-amino-aziridines decompose smoothly and stereospecifically to the corresponding olefins and diazoacetophenone; such a process might also be useful for the preparation of other α-diazocarbonyl compounds.     

Iodine/MeOH as a novel and versatile reagent system for the synthesis of α-ketothiocyanates

Ketones possessing α-hydrogens undergo smooth thiocyanation with ammonium thiocyanate in the presence of molecular iodine in refluxing methanol to produce the corresponding α-ketothiocyanates in excellent yields with high selectivity. The use of iodine makes this procedure simple, convenient and cost effective.     

2-[1-(1,2,4-三唑)甲基]-3-乙酰基-2,5-二取代芳基-1,3,4-噁二唑啉类化合物的合成

在冰醋酸存在下, 4-取代苯乙酮和溴素容易进行溴代反应, 得到α-溴-4-取代苯乙酮; 将其和1,2,4-三唑在丙酮中反应, 得到α-(1,2,4-三唑-1-基)-4-取代苯乙酮2; 在冰醋酸催化下, 2和4-取代苯甲酰肼1进行缩合, 得到相应酰腙衍生物3; 化合物3在乙酸酐的作用下环化生成一系列2-[1-(1,2,4-三唑)甲基]-3-乙酰基-2,5-二取代芳基-1,3,4-噁二唑啉4. 化合物4的结构经IR, 1H NMR, MS, 元素分析和单晶衍射确证.     

An iodine-mediated green synthesis of 1,3,4-oxadiazoles under solvent-free conditions using grinding technique

Abstract

An eco-friendly efficient synthesis of symmetrical and unsymmetrical 2,5-disubstituted 1,3,4-oxadiazoles is described through the reaction of aromatic hydrazides with aryl aldehydes obtained by grinding them in the presence of catalytic amounts of molecular iodine in a mortar in a single step. The present method avoids the isolation of N-acyl hydrazones prior to their oxidative cyclization and avoids the use of organic solvents at any stage of the reaction.     

Reactions of ketone dilithio α,β-dianions with imines and hydrazones: an anionic access to γ-amino ketones

The reactions of ketone dilithio α,β-dianions with imines and hydrazones were investigated. The nucleophilic addition reaction to C-N double bonds took place selectively at the β-position of dianions to form lithium Z-enolates containing a lithium amide portion, which is then transformed into γ-amino ketones and related compounds by the subsequent reaction with electrophiles.     

Halogenation of vinyl ketoximes. Synthesis of isoxazoles and preparation and silver ion-promoted reactions of 4-halo-2-isoxazolines

Reaction of several α,β-unsaturated ketoximes with N-bromosuccinimide (NBS) gave isoxazoles, but yields were lower and the reaction less general than a similar transformation using iodine under basic conditions. With β,β-disubstituted oximes, 4-halo-5,5-disubstituted-2-isoxazolines were obtained using NBS, iodine, or N-chlorosuccinimide. Treatment of the 4-bromoisoxazo-lines with silver acetate or silver nitrate caused either elimination with rearrangement to give isoxazoles or substitution at C-4, depending upon the nature of the substituents at C-5.     

Iodine-catalyzed 1,4-addition of 2-(trimethylsilyloxy)furan to α,β-unsaturated ketones: a facile synthesis of γ-butenolides

The α,β-unsaturated compounds undergo smooth conjugate addition with 2-(trimethylsilyloxy)furan (TMSF) in the presence of 10 mol % of iodine under mild and neutral conditions to afford the corresponding γ-substituted butenolides in high yields and with good diastereoselectivity. The use of iodine makes this procedure simple, convenient and cost effective.     

Synthesis of 3-substituted 5-arylisoxazoles from α,β-unsaturated oximes

The synthesis of 3-substituted 5-arylisoxazoles from oximes of α,β-unsaturated ketones is studied. The formation of the isoxazole derivatives takes place by cyclization of oximes in the presence of iodine and potassium iodide. The presence of isoxazoline is detected. On the basis of the results a plausible mechanism is suggested.     

A Short Synthesis of Fusaric Acid and Analogues

Fusaric acid (5-n-butyl-pyridine-2-carboxylic acid) and other substituted picolinic acid derivatives are synthesized in two steps from readily available α,β-unsaturated hydrazones and 2-chloroacrylonitrile in high yield.     

Halodephosphorylation of α,β-unsaturated phosphonic acid monoesters

Reaction of α,β-ethylenic and acetylenic phosphonic acid monoesters with (biscollidine)iodine(I) or (biscollidine)bromine(I) hexafluorophosphate led to α,β-unsaturated halides by, without precedent, dephosphorylation reactions.     

2-(N-Hydroxylamino) sulfone synthesis by indium-iodine-triggered aza-Michael type addition of nitroarenes to vinyl sulfones

One-pot reduction-triggered 1,4-addition reaction of various nitroarenes to the α,β-unsaturated sulfones was investigated. In the presence of indium/iodine in MeOH at room temperature, nitroarenes reduced in situ reacted with vinyl sulfones and produced β-(N-hydroxylamino) sulfones in good yields.