Synthesis and biological properties of 4‐substituted quinolin‐2(1H)‐one analogues

A variety of 4‐substituted quinolin‐2(1H)‐ones were prepared and evaluated for N‐methyl‐D‐aspar‐tate (NMDA) receptor binding site activity and their abilities to inhibit neurotoxicity. The 4‐(2‐car‐bethoxyethanamino)‐7‐chloro‐3‐nitroquinolin‐2(1H)‐one ( 9b ) exhibited favorable NMDA receptor binding site activity and 7‐chloro‐4‐(benzylamino)‐3‐nitroquinolin‐2(1H)‐one ( 9c ) showed the most potent neurotoxicity among them. The synthetic strategies involve the use of well known keto ester condensation and reductive ring cyclization of intermediates ( 2a‐d ) to afford 4‐substituted quinolin‐2(1H)‐ones.     

Substituted quinolinones. Part 13 a convenient route to heterocyclization reactions with 3‐substituted 4‐hydroxyquinolin‐2(1H)‐one

The reactivity of 3‐[(dimethylamino)prop‐2‐enoyl]‐4‐hydroxyl‐1‐methylquinolin‐2(1H)‐one ( 2 ) towards different nucleophilic and electrophilic reagents was investigated. The convenient synthesis of several 3‐heterocyclyl‐quinolinones such as 3‐pyridazinyl‐ 10, 11 , 3‐pyranyl 19a,b and 3‐pyrazolylquinolinones 20a,b, 22, 26a,b, 27a,b, 31 and 33 has been described starting from the 3‐acetylquinolinone 1 and enaminone 2 . In addition, certain heterocyclo[c]quinolinones such as pyrimido‐ 12, 14 pyrano‐ 3, 17a,b and pyrazolopyranoquinolinone 29 were obtained in good yields.     

Reactions of 4‐Hydroxyquinolin‐2(1H)‐ones with Acenaphthoquinone: Synthesis of New 1,2‐Dihydroacenaphthylene‐spiro‐tetrakis(4‐hydroxyquinolin‐2(1H)‐ones)

Reaction of four equivalents of 4‐hydroxyquinolin‐2(1H)‐ones with one equivalent of acenaphthoquinone in absolute ethanol, containing catalytic triethylamine, gave 3,3′,3″,3?‐(1,2‐dihydroacenaphthylene)‐1,1,2,2‐tetrayl‐tetrakis(4‐hydroxyquinolin‐2(1H)‐ones) in a good to excellent yields. The structures of the products were elucidated by ¹H NMR, ¹³C NMR, NMR, IR, mass spectra, and elemental analyses.     

Preparation of 6‐azaoxindole (6‐azaindol‐2(3H)‐one) and substituted derivatives

A general synthesis of 6‐azaoxindoles, substituted in the 3‐ and 5‐position, has been developed starting from 4‐methoxycarbomethyl‐3‐nitropyridine, via hydrogenation of the nitro group and cyclisation of the resulting 3‐amino‐4‐methoxycarbomethyl‐pyridine.     

Unanticipated Heterocyclization from Reaction of Hydrazine Hydrate and/or Hydrazine Dihydrochloride with 1‐Ethyl‐4‐hydroxyquinolin‐2(1H)‐one

Unexpectedly, the reaction of 1‐ethyl‐4‐hydroxyquinolin‐2(1H)‐one ( 1 ) with hydrazine hydrate and/or hydrazine dihydrochloride led to three different products. In addition to the expected quninolinylhydrazine, two heteropentacycles, diquinopyrrole and diquinopyridazine, were afforded, depending on reaction conditions. The structure of the new products was established upon their spectral and analytical data.     

Convenient synthesis of some 2‐substituted 4(3H)‐quinazolinone derivatives

A series of 2‐substituted‐4(3H)‐quinazolinones 13‐20 has been synthesized in good yields using the reaction of double lithiated 2‐methylquinazolinone‐4 with a variety of aromatic aldehydes. They have been easily transformed in high yields into the corresponding 2‐substituted conjugated derivatives 21‐28 bearing terminal aryl groups by F₃CCOOH mediated dehydration.     

Synthesis of 2‐aminoquinazolinc‐4(3H)‐one derivatives as potential potassium channel openers

Starting from 2‐thioxoquinazolin‐4‐one, the synthesis of 2‐amino‐4(3H)‐one derivatives, structurally related to potassium channels openers pinacidil and diazoxide, is described.     

Synthesis and further studies of chemical transformation of the 2‐aryl‐3‐halogenoquinolin‐4(1H)‐one derivatives

The C‐3 brominated and iodinated derivatives were prepared from the corresponding 2‐arylquinolin‐4(1H)‐ones and their NMe‐4‐oxo derivatives using pyridinium tribromide in acetic acid or iodine‐Na₂CO₃ mixture in THF. The results of further studies of chemical transformation of the prepared α‐haloenones and preliminary antitumour activity of the 3‐bromo NH‐4‐oxo and NMe‐4‐oxo derivatives are also described.     

CuBr‐catalysed one‐pot multicomponent synthesis of 3‐substituted 2‐thioxo‐2,3‐dihydroquinazolin‐4(1H)‐one derivatives

A novel methodology is presented for the synthesis of 3‐substituted 2‐thioxo‐2,3‐dihydroquinazolin‐4(1H)‐one derivatives based on an efficient tandem multicomponent reaction using copper bromide as catalyst. This methodology is based on the multicomponent one‐pot reaction of methyl 2‐bromobenzoate, phenylisothiocyanate derivatives and sodium azide in the presence of copper bromide and l ‐proline under basic conditions. To show the generality of the method, various phenylisothiocyanates bearing electron‐donating or electron‐withdrawing functionalities were used and the desired products were obtained in high isolated yields.     

Synthesis and biological activities of quinolone analogues: Pyridazino[3,4‐b]quinoxalin‐4‐one

Quinolone analogues I‐VI with pyridazino[3,4‐b]quinoxaline ring system were synthesized form the (l‐alkylhydrzino)quinoxalina N‐oxides 1 via oxidation of pyridazino[3,4‐b]quinoxalines 2,3,5,7 , quinoxalino[2,3‐c]cinnolines 4 , and 1,2‐dizepino[3,4‐b]quinoxalines 6 . The biological activities of quinolone analogues IVa (N₁‐methyl‐C₃‐methyl), Va (N₁‐methyl‐C₃‐ethyl), and VI (N₁‐methyl‐C₃‐H) were superior to those of quinolone analogues I (N₁‐ethyl‐C₃‐carboxyl), 26b (N₁‐ethyl‐C₃‐carboxylate), and IIIc,d [N₁‐alkyl‐C₃‐(CH₂)₃COOC₂H₅].     

Synthesis of 3‐Acetyl‐4‐hydroxy‐1‐phenylpyridin‐2(1H)‐one Derivatives

The cyclization of aryl ketone anilides 3 with diethyl malonate to affords 4‐hydroxy‐6‐phenyl‐6H‐pyrano[3,2‐c]‐pyridin‐2,5‐diones 4 in good yields. 3‐Acetyl‐4‐hydroxy‐1‐phenylpyridin‐2(1H)‐ones 5 are obtained by ring‐opening reaction of 4‐hydroxy‐6‐phenyl‐6H‐pyrano[3,2‐c]‐pyridin‐2,5‐diones 4 in the presence of 1,2‐diethylene glycol. The reaction of 3‐acetyl‐4‐hydroxy‐1‐phenylpyridin‐2(1H)‐ones 5 with hydroxylamine hydrochloride produces 4‐hydroxy‐3‐[N‐hydroxyethanimidoyl]‐1‐phenylpyridin‐2(1H)‐ones 6 from which 3‐alkyloxyiminoacetyl‐4‐hydroxy‐1‐phenylpyridin‐2(1H)‐ones 7 are obtained by reacting with alkyl bromides or iodides in the presence of anhydrous potassium carbonate with moderate yields. The similar compounds can be synthesized on refluxing 3‐acetyl‐4‐hydroxy‐1‐phenylpyridin‐2(1H)‐ones 5 with substituted hydroxylamine hydrochloride in the presence of sodium bicarbonate with good yields. Most of the synthesized compounds are characterized by IR and NMR spectroscopic methods.     

Syntheses of some new 1H‐pyrazole,pyridazin‐3(2H)‐one,and oxazin‐4‐one derivatives

The new 1H‐pyrazole‐3‐carboxylic acid 2 , pyridazin‐3(2H)‐one 3 , and their various derivatives were prepared by the reactions of the 4‐benzoyl‐5‐phenyl‐2,3‐dihydro‐2,3‐furandione 1 and 2,5‐dichlorophenylhydrazine. Pyrazolo[3,4‐d]pyridazine 7 was obtained from cyclization of the pyrazole‐3‐carboxylic acid 2 with 2,5‐dichlorophenylhydrazine. The reaction of 1 and pyrazole‐3‐carbonitriles 6 gave the new oxazin‐4‐one 9 derivatives. The structures of compounds were characterized on the basis of elemental analyses, mass, IR, ¹H, and ¹³C NMR spectra. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:8–12, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20170     

15N NMR spectra of some 3‐substituted 4(1H)‐quinolinones and their 1‐methyl derivatives

¹⁵N NMR spectral data for 3‐substituted (chloro, bromo, acetyl, carboxy, carboethoxy, methylsulfanyl, methylsulfinyl, N,N‐dimethylsulfamoyl, nitro) 4(1H)‐quinolinones and their 1‐methyl derivatives are presented. Copyright © 2003 John Wiley & Sons, Ltd.     

Synthesis and stereochemical studies of 2‐substituted thiazolidine‐4‐carboxamide derivatives

A series of new 2‐substituted thiazolidine‐4‐carboxamide derivatives which have potentially useful immunological properties, have been synthesized in a stereoselective manner by coupling 2‐subsituted thiazolidine‐4‐carboxylic acids with amines or amino esters. The structure of these compounds was established by combination of NMR methods and by X‐ray analysis.     

Synthesis of new 1‐phenylthieno[1,2,4]triazolo[4,3‐a]pyrimidin‐5(4H)‐one derivatives

A series of novel 1‐phenylthieno[1,2,4]triazolo[4,3‐a]pyrimidin‐5(4H)‐one derivatives 5 and 6 were synthesized by oxidative cyclization of thienopyrimidinonyl hydrazones using iodobenzene diacetate. J. Heterocyclic Chem., (2011).     

1‐[(1‐Ethoxypropylidene)amino]‐2‐ethyl‐4‐(4‐hydroxybenzyl)imidazol‐5(4H)‐one

The racemic title compound, C₁₇H₂₃N₃O₃, isolated from the reaction of l ‐(−)‐tyrosine hydrazide with triethyl orthopropionate in the presence of a catalytic quantity of p‐toluenesulfonic acid (p‐TsOH), crystallizes with Z′ = 1 in a centrosymmetric monoclinic unit cell. The molecule contains two planar fragments, viz. the benzene and imidazole rings, linked by two C—C single bonds. The dihedral angle between the two planes is 59.54 (5)° and the molecule adopts a synclinal conformation. The HOMA (harmonic oscillator model of aromaticity) index, calculated for the benzene ring, demonstrates no substantial interaction between the two π‐electron delocalization regions in the molecule. In the crystal structure, there is an O—H...N hydrogen bond that links the molecules along the c axis.     

Synthesis and Antimicrobial Activity of 4‐(10H‐Phenothiazin‐2‐yl)‐pyrimidin‐2(1H)‐one/thione Derivatives

A series of chalcones 3a , 3b , 3c , 3d containing phenothiazine nucleus were prepared by Claisen–Schmidt condensation. The chalcones on treatment with urea, thiourea, phenyl urea, and phenyl thiourea in alcoholic KOH yielded compounds 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i , 4j , 4k , 4l , 4m , 4n , 4o , 4p , and the structures of these compounds were confirmed by spectral and elemental analyses. The newly synthesized compounds were evaluated for antimicrobial activity.     

Synthesis and Herbicidal Activities of 3‐(4‐Chloro‐2‐fluoro‐5‐substituted phenyl)benzo[d][1,2,3]triazin‐4(3H)‐one Derivatives

A series of 3‐phenyl benzo[d][1,2,3]triazin‐4(3H)‐one derivatives were synthesized through the condensation of phenol E and alkyl (alkenyl, alkynyl) chlorides (bromides, iodide) or alkyl chloroacetates or N‐alkyl chloroacetamides using K₂CO₃ as the acid acceptor in N,N‐dimethylformamide. Phenol E was prepared from starting material, 5‐amino‐2‐chloro‐4‐fluorophenyl ethyl carbonate, in four steps involving in amidation, reduction, diazotization, and deprotecting‐group reaction. The herbicidal activities of the title compounds were tested against two dicotyledonous plants and two monocotyledonous plants, in which some of them exhibited high herbicidal activities against two dicotyledonous plants in preemergence and postemergence treatments. Moreover, when the dosage was decreased to 180 and 90 g/ha, compounds F1 , F8 , and F9 showed highly selective inhibitory activities against amaranth pigweed, alfalfa, asteraceae, field sowthistle, morning glory, purslane, and velvetleaf in postemergence treatment but had no herbicidal efficacy on rape except F1 , suggesting that it be possible to find a kind of herbicides to inhibit dicotyledonous weeds in the field of dicotyledonous crops with the same genus as aforementioned weeds.     

非催化条件下合成取代2,3-二氢-4(1H)-喹唑啉酮衍生物的研究

在乙醇/水混合溶剂中,回流条件下,无需使用催化剂,靛红酸酐、芳香醛和铵盐或伯胺三组分"一锅法"反应,可合成单取代和双取代的2,3-二氢-4(1H)-喹唑啉酮。考察了溶剂对产率的影响,结果表明,当乙醇/水体积比为1∶3时,产品产率较高。产物的结构通过熔点、IR、1H NMR和元素分析进行测定和结构表征。