Phenacyl Bromides Revisited: Facile Synthesis of Some New Pyrazoles,Pyridazines, and Their Fused Derivatives

Phenacylmalononitriles 8a , 8b react with hydrazines under dry conditions to afford the pyrazole derivatives 9a , 9b , 9c , 9d and in refluxing dioxane to afford the pyrazolo[3,4‐c]pyridazine derivatives 11a , 11b , 11c , 11d and the pyridazine‐6‐imine derivatives 12a , 12b , 12c , 12d . Compounds 12a , 12b were transformed into their oxo analogs 13a , 13b upon reflux in ethanolic HCl, whereas 12c , 12d were transformed into the furan derivatives 14a , 14b under the same reaction conditions (reflux in ethanolic HCl). Compounds 8a , 8b could be transformed directly into the benzoyl‐pyrazole derivatives 16a , 16b , 16c , 16d upon coupling with diazotized aromatic amines in pyridine. The structures of the new compounds were substantiated by elemental analyses and spectral data as well as x‐ray crystallographic analysis. Plausible mechanisms for the unexpected transformations are suggested.     

2,6-吡啶二甲酰双吡唑衍生物的合成

合成了4个吡唑及其衍生物,其结构经元素分析,IR,1^HNMR和^13CNMR等表征。     

Regioselective Synthesis of Polyaza Pyrimidines and Polyaza Pyrazoles under One‐Pot Multicomponent Reaction Conditions

Convenient methods of synthesis of novel polyaza pyrimidines and polyaza pyrazoles have been described in this paper. The synthetic method is based on one‐pot, three‐component cyclocondensation of α‐oxoketene dithioacetals, 2,6‐diaminopyridine, and guanidine/hydrazine. Polyaza S,N‐acetals have been generated in situ by treating α‐oxoketene dithioacetals with 2,6‐diaminopyridine in the presence of n‐butyl lithium, which were subsequently treated with guanidine nitrate and hydrazine hydrate to afford polyaza pyrimidines and polyaza pyrazoles, respectively.     

阴离子型β-环糊精衍生物的合成

以β-环糊精与对甲苯磺酰氯反应制得6-对甲苯磺酰基-β-环糊精酯(1); 1分别与牛磺酸和L-天冬氨酸反应合成了两个阴离子型β-环糊精衍生物单-6-牛磺酸-β-环糊精(2)和单-6-L-天冬氨酸-β-环糊精(3),总收率分别为56.1%和48.7%,其中化合物2未见文献报道,其结构经¹H NMR, ¹³C NMR和MS（ESI）表征。并对后处理过程进行了优化。     

Synthesis of Chitosan-La2O3 Nanocomposite and Its Utility as a Powerful Catalyst in the Synthesis of Pyridines and Pyrazoles

Recently, the development of nanocatalysts based on naturally occurring polysaccharides has received a lot of attention. Chitosan (CS), as a biodegradable and biocompatible polysaccharide, is considered to be an excellent template for the design of a hybrid biopolymer-based metal oxide nanocomposite. In this case, lanthanum oxide nanoparticles doped with chitosan at different weight percentages (5, 10, 15, and 20 wt% CS/La₂O₃) were prepared via a simple solution casting method. The prepared CS/La₂O₃ nanocomposite solutions were cast in a Petri dish in order to produce the developed catalyst, which was shaped as a thin film. The structural features of the hybrid nanocomposite film were studied by FTIR, SEM, and XRD analytical tools. FTIR spectra confirmed the presence of the major characteristic peaks of chitosan, which were modified by interaction with La₂O₃ nanoparticles. Additionally, SEM graphs showed dramatic morphological changes on the surface of chitosan, which is attributed to surface adsorption with La₂O₃ molecules. The prepared CS/La₂O₃ nanocomposite film (15% by weight) was investigated as an effective, recyclable, and heterogeneous base catalyst in the synthesis of pyridines and pyrazoles. The nanocomposite used was sufficiently stable and was collected and reused more than three times without loss of catalytic activity.     

Synthesis and Anticancer Activity of Some New Fused Pyrazoles and Their Glycoside Derivatives

4‐(4‐Chlorobenzylidene)‐2,5‐diphenyl‐2,3‐dihydro‐3H‐pyrazol‐3‐one 3a and 4‐(3,4‐dimethoxybenzylidene)‐5‐phenyl‐2,3‐dihydro‐3H‐pyrazol‐3‐one 3b were prepared and were reacted with phenylhydrazine, thiosemicarbazide, hydroxylamine hydrochloride, ethyl acetoacetate, diethylmalonate, malononitrile, ethyl cyanoacetate, and thiourea yielding fused pyrazole derivatives. Some of the new compounds were reacted with cyclic and acyclic sugars to produce new S‐, O‐, and N‐glycoside derivatives. The antitumor activity against the human breast cancer cells (MCF‐7) was assessed. Four of the new compounds showed IC₅₀ values less than those of the positive control, indicating that these four compounds are better anticancer agents than doxorubicin.     

Synthesis of Pyrimidines,Thienopyrimidines, and Pyrazolopyrimidines

5-Ethoxycarbonyl-4-methyl-2-phenylpyrimidin-6(1H)-thione ( 3 ), which was prepared from the reaction of ethyl g -aminocrotonate 1 with benzoyl isothiocyanate ( 2 ) in refluxing acetone, was reacted with a series of halopgenated reagents to give S-alkyl derivatives 4a-g . Upon treatment of compounds 4a-c with sodium ethoxide were cyclized into thienopyrimidine 10a-c . Pyrimidinethione 3 was reacted with hydrazine hydrate to give hydroxypyrazolopyrimidine derivative 6 . The later compound was obtained by heating compound 4a with hydrazine hydrate under neat conditions, but when the reaction was carried using hydrazine hydrate in ethanol, the corresponding carbohydrazide 5 was produced.     

Synthesis of Glycoside Derivatives Employing the Ferrier Rearrangement 1

Abstract

Various glycals underwent smooth Lewis acid-catalysed allylic rearrangement reactions with O-nucleophiles to yield 2,3-unsaturated glycoside derivatives. In the hexose series predominantly α-D-, and in the pentose series β-D-anomers resulted. Among others Ω-cyano- as well as Ω-benzyloxycarbonylamino functionalised alcohols could be used successfully. With diols the corresponding 1,1′-bridged disaccharides could be obtained.

     

Synthesis of Pyrimidines,Thienopyrimidines and Pyrazolopyrimidine

5‐Ethoxycarbonyl‐4‐methyl‐2‐phenylpyrimidin‐6(1H)‐thione ( 3 ), which was prepared from the reaction of ethyl β‐aminocrotonate 1 with benzoyl isothiocyanate ( 2 ) in refluxing acetone, was reacted with halo compounds to give S‐alkyl derivatives 4a‐h . Treatment of compounds 4a‐c with sod. ethoxide cyclized into thienopyrimidine 10a‐c . Hydrazinolysis of compound 3 gave hydroxypyrazolopyrimidine derivative 6 . Also the latter compound was obtained upon heating compound 4a with hydrazine hydrate under neat conditions, but when compound 4a refluxed with hydrazine hydrate in ethanol the corresponding carbohydrazide 5 was produced.     

Nitriles in Organic Synthesis: Synthesis of Pyrido[2,1-b]benzothiazole Derivatives and Polyfunctionally-substituted Pyridines

A variety of pyrido[2,1-b]benzothiazole derivatives could be prepared by reaction of 2-cyanomethylbenzothiazole, formaldehyde, and various active methylene reagents. Also some polyfunctionally-substituted pyridines were prepared by reaction of 2-cyanomethylbenzothiazole, formaldehyde, and an -functionally substituted acrylonitrile.     

One-Pot and Two-Chamber Methodologies for Using Acetylene Surrogates in the Synthesis of Pyridazines and Their D-Labeled Derivatives

Acetylene surrogates are efficient tools in modern organic chemistry with largely unexplored potential in the construction of heterocyclic cores. Two novel synthetic paths to 3,6-disubstituted pyridazines were proposed using readily available acetylene surrogates through flexible C₂ unit installation procedures in a common reaction space mode (one-pot) and distributed reaction space mode (two-chamber): (1) an interaction of 1,2,4,5-tetrazine and its acceptor-functionalized derivatives with a CaC₂−H₂O mixture performed in a two-chamber reactor led to the corresponding pyridazines in quantitative yields; (2) [4+2] cycloaddition of 1,2,4,5-tetrazines to benzyl vinyl ether can be considered a universal synthetic path to a wide range of pyridazines. Replacing water with D₂O and vinyl ether with its trideuterated analog in the developed procedures, a range of 4,5-dideuteropyridazines of 95–99% deuteration degree was synthesized for the first time. Quantum chemical modeling allowed to quantify the substituent effect in both synthetic pathways.     

Synthesis of Steroidal Pyrimidines

Selected aryl aldehydes were treated with 17-oxo-5-androsten-3β-yl acetate (I) to give the corresponding 16-arylidene 17-oxo-5-androsten-3β-yl acetates(IIa-e). Condensation of these chalcones with urea revealed the formation of the corresponding substituted pyrimidin-2′-ones (IIIa-e) respectively.     

Cascade Multicomponent Synthesis of Indoles,Pyrazoles, and Pyridazinones by Functionalization of Alkenes

The development of multicomponent reactions for indole synthesis is demanding and has hardly been explored. The present study describes the development of a novel multicomponent, cascade approach for indole synthesis. Various substituted indole derivatives were obtained from simple reagents, such as unfunctionalized alkenes, diazonium salts, and sodium triflinate, by using an established straightforward and regioselective method. The method is based on the radical trifluoromethylation of alkenes as an entry into Fischer indole synthesis. Besides indole synthesis, the application of the multicomponent cascade reaction to the synthesis of pyrazoles and pyridazinones is described.     

3,6-双取代哒嗪的合成和介晶性

哒嗪衍生物;3;6-双取代哒嗪的合成和介晶性     

Kost-Sagitullin Rearrangement and Other Isomerization Recyclizations of Pyrimidines. (Review)

Data on the isomerization recyclizations of pyrimidines, particularly the Kost-Sagitullin and other transformations accompanied by substitution of an endocyclic atom in pyrimidine by an extracyclic nitrogen or carbon atom (N-N, N-C, or C-C recyclizations), are summarized and analyzed. Data from research on the Kost-Sagitullin and certain other isomerization transformations of pyrimidines at the Institute of Organic Chemistry, National Academy of Sciences of the Republic of Armenia, in recent years are presented. In memory of Aleksei Nikolaevich Kost — a distinguished scientist, a warmhearted person, and a teacher. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1445–1480, October, 2005.     

芳氧基哒嗪衍生物的合成及除草活性

以3,6－二氯哒嗪为原料,合成了6类芒氧基哒嗪类衍生物,研究了它们的合成方法,并测定了所得产物的除草活性。所有化合物均经^1H NMR和元素分析确证,部分化合物经IR和MS确证,生测结果表明,部分化合具有一定的除草活性。