有生物活性的哒嗪酮-氨基甲酸酯类衍生物的合成

氨基甲酸酯衍生物;有生物活性的哒嗪酮-氨基甲酸酯类衍生物的合成     

Synthesis of Pyridazinones through the Copper(I)‐Catalyzed Multicomponent Reaction of Aldehydes,Hydrazines, and Alkynylesters

The copper‐catalyzed multicomponent cyclization reaction, which combined aldehydes, hydrazines, and alkynylesters, was applied in the synthesis of pyridazinones. The reaction was regioselective and gave only six‐membered pyridazinones in the complete absence of five‐membered pyrazoles or a regioisomeric mixture. During this investigation, the use of 2‐halobenzaldehyde as the starting material, under identical reaction conditions, gave 6‐(2‐ethoxyphenyl)pyridazinones after sequential Michael addition/1,2‐addition/Ullmann cross‐coupling reactions.     

Synthesis of Novel Heterocyclic Compounds with Expected Antibacterial Activities from 4‐(4‐Bromophenyl)‐4‐oxobut‐2‐enoic Acid

This research describes the utility of 4‐(4‐bromophenyl)‐4‐oxobut‐2‐enoic acid as a key starting material for preparation of a novel series of aroylacrylic acids, pyridazinones, and furanones derivatives. These heterocyclic compounds were synthesized by reaction of 4‐(4‐bromophenyl)‐4‐oxobut‐2‐enoic acid with benzimidazole, ethyl glycinate hydrochloride, anthranilic acid and o‐phenylenediamine under Aza–Michael addition conditions. Every Aza–Michael adduct was allowed to react with haydrazine hydrate and acetic anhydride to form pyridazinones and furanones derivatives, respectively. In further step, some pyridazinones were allowed to react with ethyl acetoacetate, acetyl acetone, acetyl chloride, and aromatic aldehydes to form novel heterocylces. Finally, studying antibacterial activities of these compounds was performed.     

A novel synthesis of 2-arylaminothiazolo[4,5-d]pyridazinones

The reaction of 5(4)-amino-4(5)-chloropyridazin-3(2H)-ones 1 (9 ) with methyl dithiocarbamates 2 gave 2-arylaminothiazolo[4,5-d]pyridazinones 3 (10 ). Treatment of 5(4)-alkylamino-4(5)-chloropyridazin-3(2H)-ones 5 (12 ) with 2 afforded the corresponding 2-aryliminothiazolo[4,5-d]pyridazinones 6 (13 ). Cyclization of 1a with phenylisothiocyanate produced 2-amino- and 2-iminothiazolo[4,5-d]pyridazinones 3a and 16 .     

4(And 5)-cyclopropylamino-5(and 4)halo-3(2H)pyridazinones. Formation and characterization of isomers

The reactions of 4,5-dihalo-3(2H)pyridazinones with ammonia and amines gave mixtures of 5-amino-4-halo- and 4-amino-5-halo-3(2H)pyridazinones separated by chromatography. Structures were elucidated by means of retention values (R_f) and confirmed by independent synthesis.     

General synthesis of: 5-substituted-3-acyl-4-carbethoxypyrazoles 3,6-subslituted-5-carbethoxy-4(h)pyridazinones and 3,7-substitutedpyrazoio[3,4-d] pyridazine-4(5h)ones via reactions between 2-hydroxy,methoxy, and acetoxy-3(2h)furanones and hydrazine

Synthesis of substituted 3-acyl-4-carbethoxypyrazoles, 5-earbethoxy-4(1H)pyridazinones and pyrazolo[3,4-d]pyridazine-4(5H)ones is described. They involve the reaction of the 2,5-substituted-4-earbelhoxy-2-hydroxy, methoxy and acetoxy-3(2H)furanones with hydrazine hydrate. The reaction was found to be dependent on the hydroxy, methoxy or acetoxy substituents of these furanones and proceeds with ring opening followed by cy clisation. Pyrazoles were formed with hydroxy or methoxy substituents while pyridazinones are afforded with acetoxy group. The pyrazoles so formed were readily converted to pyrazolo[3,4-d] pyridazinones by condensation with excess hydrazine.     

Rational Design,Green Synthesis,and Initial Evaluation of a Series of Full‐Color Tunable Fluorescent Dyes Enabled by the Copper‐Catalyzed N‐Arylation of 6‐Phenyl Pyridazinones and Their Application in Cell Imaging

There is widespread interest in the application, optimization, and evolution of the transition‐metal‐catalyzed arylation of N‐heteroarenes to discover full‐color tunable fluorescent core frameworks. Inspired by the versatile roles of pyridazinone in organic synthesis and medicinal chemistry, herein, we report a simple and efficient copper‐catalyzed cross‐coupling reaction for the N‐functionalization of pyridazinones in neat water. To achieve the efficient conversion of pyridazinones and organic halides in aqueous phase, a series of copper‐salen complexes composed of different Schiff base ligands were investigated by rational design. A final choice of fine‐tuned hydrophilicity balanced with lipophilicity among the candidates was confirmed, which affords excellent activity towards the reaction of a wide range of pyridazinones and organic halides. More importantly, the products as N‐substituted pyridazinones were synthesized rationally by this methodology as full‐color tunable fluorescent agents (426–612 nm). The N2 position of pyridazinones was modified by different aryl group such as benzothiazole, N,N‐dimethylaniline, 3‐quinoline, 4‐isoquinoline and 2‐thiophene, resulting in a series of full‐color tunable fluorescent reagents. Meanwhile, the effects of electron‐donating and electron‐withdrawing groups of the 6‐substituted phenyl ring have also been investigated to optimize the fluorescent properties. These fluorescent core frameworks were studied in several cell lines as fluorescent dyes. Different colors from blue to red were observed by using fluorescence microscopy and confocal microscopy.     

Facile and convenient strategy towards synthesis of 4-substituted 2-aminothiazolo[4,5-d]pyridazinones

Convenient synthesis of 4-substituted 2-aminothiazolo[4,5-d]pyridazinones has been achieved in 12 steps with overall yield of 19% by employing Grignard reaction as the key step. The route utilizes well established thiazole ring formation followed by Grignard reaction to introduce substitution at 4-position effectively. In addition to the use of inexpensive chemicals, the present route first time gave access to the 4-substituted 2-aminothiazolo [4,5-d]pyridazinones with free amino group at C-2 position.     

Triton B–Mediated Mild,Convenient, and Efficient Method for the Selective Alkylation of Cyclic Secondary Amines and Thiols

Alkylation of cyclic secondary amines, thiols, and pyridazinones has been demonstrated with alkyl halides using Triton B as base and reaction medium.     

The reaction of pyridazinones with nucleophiles. An unusual reaction with cyanide

Studies on the synthesis of pyridazinone analogues of pyridone cardiotonics are reported. The synthetic scheme involves the reaction of pyridazinones and chloropyridazinones with nucleophiles. Addition occurred twice with cyanide as the nucleophile, thus providing a novel dicyanopyridazinone.     

Facile Synthesis of 3(2H)‐Pyridazinones and 2(3H)‐Furanones of Anticipated Biological Activities

3‐Aroyl‐2‐arylpropionic acids 2a‐e were utilized to synthesize 3(2H)‐pyridazinones 3a‐e and 2(3H)‐furanones 6 through reaction with hydrazine hydrate and freshly distilled acetic anhydride, respectively, in the hope of obtaining new 3(2H)‐pyridazinones with no ulcerogenic side effect or with negligible general side effects as those currently used NSAID_S as well as biologically active 2(3H)‐furanones.     

Reactions of 3-carboxyacryloylhydrazines III. Correlation of acid dehydration products with NMR spectra

The dehydration of 3-carboxyacryloylhydrazines in acid media has been shown to give either aminomaleimides or pyridazinones. Criteria, using nmr techniques, are presented for correlating the nmr spectra with product formation.     

Pyridazines. VI. Some 6-substituted 3(2H)pyridazinones

A series of 6-substituted 3(2H)pyridazinones was prepared. The 6-substituent was either aromatic of heter-aromatic in structure. A few basically-substituted representatives were also made.     

An efficient chemo- and regioselective three component synthesis of pyridazinones and phthalazinones using activated KSF

<正>The first three-component and regioselective synthesis of pyridazinones and phthalazinones from arenes,anhydrides and ArNHNH_2 in the presence of efficient recyclable heterogeneous catalyst,montmorillonite-KSF,in high yield and short reaction time is reported.     

Synthesis of [1,4]benzodioxino[2,3‐c and 2,3‐d]pyridazinones

Reaction of chloropyridazin‐3‐one 1, 5 and 10 with catechol in the presence of potassium carbonate gave the corresponding [1,4]benzodioxino[2,3‐e and/or 2,3‐d]pyridazinones 2, 7, 8 and 11 .     

An efficient one‐pot synthesis of pyridazinones and phthalazinones using HY‐zeolite

The first one‐pot synthesis of pyridazinones and phthalazinones from arenes, cyclic anhydrides, and ArNHNH₂ in the presence of efficient recyclable heterogeneous catalyst, HY‐zeolite, in high yield and short reaction time is reported. J. Heterocyclic Chem., (2011).     

Concise routes to pyrazolo[1,5-a]pyridin-3-yl pyridazin-3-ones

Cycloaddition of pyridine N-imine with 6-alkyl-4-oxohex-5-ynoates followed by condensation with hydrazine provides concise access to pharmacologically active 6-(pyrazolo[1,5-a]pyridin-3-yl)pyridazinones. For the first time alkynyl heterocycles are also shown to be effective dipolarophiles for pyridine N-imine, and analogous compounds can be accessed directly in modest yields through the reaction of 6-(alkyn-1-yl)pyridazin-3-one derivatives.     

A new route to 5,6-diarylpyridazin-3-ones by metalation and cross-coupling of pyridazines

Starting from 3,6-dichloropyridazine, a new route is described to antihypertensive 5,6-diarylpyridazin-3-ones. This pathway comprises the regioselective metalation followed by a substitution of the trimethylsilyl moeity. The introduction of iodine by another metalation allowed the cross coupling of arylboronic acids. The 6-methoxy group was then cleaved to afford the pyridazinones.     

Confirmation and prevention of halogen exchange: practical and highly efficient one-pot synthesis of dibromo- and dichloropyridazinones

Commercially available anilines were converted by a two step, one-pot process to the corresponding pyridazinones in good to excellent yields. During the process research, a significant halogen exchange was confirmed and prevented which allowed the process to be scaled to multikilogram quantities.     

Heterocyclic compounds from 3-(4-phenyl) benzoyl propionic acid

3-(4-Phenyl) benzoyl propionic acid was used as the starting material for the synthesisof furanones (2), pyrrolinones (5), pyridazinones (7), benzoxazinones (8) and quinazolinones (9-11). The behaviour of the derivatives of furanones and benzoxazinones toward different nucleophiles is reported.