Synthesis of 3-arylamino-4(3H)quinazolinone derivatives from 1-acetyl- or 1-ethoxycarbonylmethylene-2-arylhydrazines

By reacting 1-acetyl- or 1-ethoxycarbonylehloromethylene-2-arylhydrazines ( 2a-c ) with anthranilic acids (1a-b) the corresponding C-acetyl- or C-ethoxyearbonylcarbohydrazonamide derivatives (3a-d) were obtained. Ring closure of the carbohydrazonamides with acetic anhydride afforded 2-carboethoxy- or 2-acetyl-3-arylamino-4(3H)quinazolinones ( 4a-d ). The ester derivatives undergo basic hydrolysis with decarboxylation to 3-arylamino-4(3H)quinazolinones ( 5a-b ).     

2-Aryl-4(3H)quinazolinones

Reaction of isatoic anhydride with benzamides is shown to produce 2-aryl-4(3H)quinazolinones. The quinazolinones carrying a 2-(o-hydroxyphenyl) group are obtained in high yields.     

Convenient preparation of N-substituted 2-amino-4H-3,l-benzoxazin-4-ones and 3-substituted 2,4(1H,3H)-quinazolinediones

Room temperature treatment of 2-(3-arylureido)benzoic acids ( 1 ) and methyl 2-(3-alkyl-, or 3-arylureido)- benzoates ( 2 ) with concentrated sulfuric acid leads to N-substituted 2-amino-4H-3,l-benzoxazin-4-ones ( 3 ) in generally very good yields. The isomeric 3-substituted 2,4(1H,3H)-quinazolinediones ( 4 ) are conveniently made in high yield by the action of aqueous-ethanolic sodium hydoxide on 2.     

Synthesis of 1-Substituted 4(1H)-Quinazolinones Under Solvent-Free Conditions

Abstract

Heating a mixture of 2-(N-alkylamino)benzoic acids, triethyl orthoformate, and ammonium acetate under solvent-free conditions generated 1-substituted 4(1H)-quinazolinones in 73?99% yields. Moreover, a possible reaction pathway was proposed.     

Synthesis of N-(o- and p-Alkenylphenyl)-Substituted Quinazolin-4-ones

Alkenylphenyl-substituted quinazolinones were prepared by reactions of 2-methyl-4H-3,1-benzoxazin-4-one with o- and p-alkenylanilines.     

Synthesis of some new 3-pyrazolyl-substituted-4(3H)quinazolinones

N-(1-Phenyl-3-methylpyrazol-5-yl)-o-aminobenzamide reacted with orthoesters to yield some new 3-pyrazolyl-substituted-4(3H)quinazolinones (VIIa,b,c,d). An alternative synthesis of Vllb was accomplished by reaction of acetylanthranyl with l-phenyl-3-methyl-5-aminopyrazole.     

Synthesis of 4(3H)-quinazolinones from derivatives of methyl 2-isothiocyanatobenzoate

Ethyl N-(2-methoxycarbonylphenyl)thiocarbamate ( 2), N -(2-ethoxycarbonylphenyl)-4-methoxythiobenz-amide ( 3b ), and 2-(4-methoxyphenyl)-4H-3,1-benzothiazin-4-one ( 4a ), react with nucleophilic reagents containing at least one primary amino group to yield a variety of 2-substituted and 2,4-disubstituted 4(3H)quinazolinones, as well as some tricyclic and tetracyclic products.     

Nickel boride mediated reductive desulfurization of 2‐thioxo‐4(3H)‐quinazolinones: A new synthesis of quinazolin‐4(3H)‐ones and 2,3‐dihydro‐4(1H)‐quinazolinones

A novel one‐pot approach for the synthesis of aryl substituted quinazolin‐4(3H)‐ones and 2,3‐dihydro‐4(1H)‐quinazolinones has been reported based on the reductive desulfurization of 3‐aryl‐2‐thioxo‐4(3H)‐quinazolinones with nickel boride in dry methanol at ambient temperature.     

Synthesis and transformations of 2- and 4-(2-Methylquinolin-4-ylamino)benzoic acids and ethyl 4-(2-methylquinolin-4-ylamino)benzoates and their fluorescent properties

2- and 4-(2-Methylquinolin-4-ylamino)benzoic acids and ethyl 4-(2-methylquinolin-4-ylamino)-benzoates having a substituent in the 6(8)-position of the quinoline ring were synthesized by reaction of the corresponding substituted 4-chloro-2-methylquinolines with 2- and 4-aminobenzoic acids and ethyl 4-aminobenzoate. Intramolecular cyclization of 2-(2-methylquinolin-4-ylamino)benzoic acids in concentrated sulfuric acid gave 7-hydroxy-6-methyldibenzo[b,h][1,6]naphthyridines, and ethyl 4-(2-methylquinolin-4-ylamino)benzoates were converted into 4-(2-methylquinolin-4-ylamino)benzoic acids by alkaline hydrolysis.     

Chinazolincarbonsäuren. XII. Mitteilung. Synthese von [2-(Ethoxycarbonyl)-3,4-dihydro-4-oxochinazolin-3-yl]-, [2-(Ethoxycarbonyl)chinazolin-4-yloxy]- und (5,6,7,8-Tetrahydro-2-phenylchinazolin-4-ylthio)alkansäure-estern

Quinazolinecarboxylic Acids. Synthesis of Alkyl [2-(Ethoxycarbonyl)-3,4-dihydro-4-oxoquinazolin-3-yl]-, [2-(Ethoxycarbonyl)quinazolin-4-yloxy]- and (5,6,7,8-Tetrahydro-2-phenylquinazolin-4-ylthio)alkanoates The [(2-aminobenzoyl)amino]alkanoic acids and their esters 1 showed a different reaction behaviour with diethyl oxalate. Compound 1 (n = 2,3) was converted into the quinazolinylalkanoates 3 . o-Aminohippurate yielded with ethyl (chloroformyl)formate a mixture of the amide 4 and the cyclized quinazolinone 7b . Ethyl 3,4-dihydro-4-oxoquinazoline-2-carboxylate ( 6 ) reacted with 2-bromoalkanoates, in the presence of NaH, to the [2-(ethoxycarbonyl)-3,4-dihydro-4-oxoquinazolin-3-y1]acetates 7 in the case of alkyl bromoacetate, and to the O-alkylated derivatives 8 with the ethyl 2-bromopropionate and -butyrate. 2-Aminobenzamide ( 5 ) gave with ethyl 3-(chloroformyl)-2-propenoate and methyl 3-(chloroformyl)propionate the amides 9 or 11 , respectively, and not the expected quinazolinones. The cyclized product 12 was obtained from 11 and ethyl bromoacetate. Tetrahydroquinazolin-4(3H)-thione 14 was synthesized by the reaction of 13 with NH₃, and it was alkylated at the S-atom with bromoalkanoates to 15 . The hydrazide 16 was synthesized from 15b with hydrazine hydrate.     

Synthesis and base-catalyzed cleavage of 1-aryl-4,9-dioxo-1H-naphtho[2,3-d][1,2,3]triazole 2-oxides

A method was developed for the synthesis of 1H-1-arylnaphtho[2,3-d][1,2,3]triazole-4,9-dione 2-oxides based on 2-arylamino-3-chloro-1,4-naphthoquinones. The reaction of 1H-1-arylnaphtho[2,3-d][1,2,3]triazole-4,9-dione 2-oxides with an ethanolic alkali solution affords 2-{[1-(aryl)-2-oxido-1H-1,2,3-triazol-4-yl]carbonyl}benzoic acids.     

Synthesis and characterization of bromoquinazolinone substituted spiro[isobenzofuran-1,9′-xanthene]-3-ones

Some new bromoquinazolinone substituted fluoran compounds were synthesized by the reaction of the keto acid, 2-(4-diethylamino-2-hydroxybenzoyl)benzoic acid with different 3-(3/4-hydroxyphenyl)-2-methyl/phenylbromo-4(3H) quinazolinones in the presence of a dehydration condensing agent like sulfuric acid. Various quinazolinones were prepared by reacting different monobromo/dibromobenzoxazine-4-ones with 3-aminophenol or 4-aminophenol in the presence of pyridine as a solvent. All the synthesized fluoran compounds were identified by conventional methods such as melting point, IR, ¹H NMR, ¹³C NMR, elemental analysis and UV-visible spectroscopy in organic solvents and 95% acetic acid. All these colorless fluorans develop a color in contact with electron accepting compounds.     

Synthesis of 4-Amino-3,5-dicyano-arylpyrazoles,Part 2: Isolation and Characterization of By-Products

Reaction of (dicyanomethylidene-hydrazino)benzoic acids with chloroacetonitrile, under basic conditions, gave cyanomethyl-3-(7-amino-3,5-dicyano-1H-pyrazolo[4,3-d]pyrimidin-1-yl-benzoates and para-substituted cyanomethyl benzoates, in addition to the expected cyanomethyl 3-(4-amino-3,5-dicyano-1H-pyrazol-1-yl)-benzoates.     

A facile synthesis of 3-substituted 2-cyanoquinazolin-4(3H)-ones and 3-alkyl-2-cyanothieno[3,2-d]pyrimidin-4(3H)-ones via 1,2,3-dithiazoles

The reaction of methyl anthranilate with 4,5-dichloro-1,2,3-dithiazolium chloride (Appel's salt) in the presence of pyridine (2 equivalents) in dichloromethane at room temperature gave methyl N-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)anthranilate ( 3a ) (50% yield), which reacted with sterically less hindered primary alkylamines to give directly 3-alkyl-2-cyanoquinazolin-4(3H)-ones 5 in moderate to good yields. With tert-butylamine, N-(2-methoxycarbonylphenyl)iminocyanomethyl N-(tert-butyl) disulfide 7 and methyl 2-(N-cyanothioformamido)anthranilate ( 8 ) were isolated in 33% and 59% yields, respectively. The cyano group of quinazoline 5a (R = CH₃) is readily displaced by various nucleophiles to give 2-substituted quinazolinones 11–19 , which indicates that compounds 5 can be utilized as starting materials for the synthesis of new 2-substituted quinazolines. Similarly 3-alkyl-2-cyanomieno[3,2,-d]pyrimidin-4(3H)-ones 22 were prepared from methyl 3-[N-(4-chloro-5H-1,2,3-dimiazol-5-ylidene)]-2-thiophencarboxylate ( 21 ) in moderate to good yields.     

Cyclic hydroxamic acids derived from quinazoliue

The action of various acylating agents on 2-aminobenzohydroxamic acid afforded 3-hydroxy-4(3H)quinazolinones (hydroxamic acids) as well as several ethers and esters from them were prepared and their spectroscopic properties analyzed. Secondary amines, as well as one equivalent of alkali, on 2-halomethyl-3-hydroxy-4(3H)quinazolinone lead to the formation of a dimer(XI). In this respect the behaviour of secondary amines is different from that of primary amines. Some new 3-hydroxy-2-4(1H,3H)-quinazolidinediones are described.     

Some reactions of 2-(4-substitutedphenyl)-2-(N-methyl-N-4-substitutedbenzamido) acetic acids

In situ generated 2,4-diaryl substituted münchnones from 2-(4-substitutedphenyl)-2-(N-methyl-N-4-substitutedbenzamido)acetic acids react with acetic anhydride in the presence of 2-nitromethylene thiazolidine, which is most likely acting as a base, and unexpectedly undergo a Dakin–West type reaction and a concurrent autoxidation reaction leading to the formation of (E)-1-(N,4-dimethylbenzamido)-1-(4-fluorophenyl)prop-1-en-2-yl acetate, 4-substitutedphenyl-N-methyl-N-(4-substitutedbenzoyl) benzamides and p-substituted benzoic acids. In addition, a novel and efficient access to N-acyl urea derivatives is described by the reaction between 2-(4-substitutedphenyl)-2-(N-methyl-N-4-substitutedbenzamido)acetic acids and cyclohexyl, isopropyl carbodiimides in the presence of a base. The structures of all new products were identified on the basis of NMR and IR spectra, along with X-ray diffraction data and HRMS measurements.     

Synthesis of some derivatives of imidazo[1,2-a]pyridine,pyrazolo[1,5-b]imidazole,and 4-(3H)quinazolinone from α-ketohydrazidoyl bromides

α-Aroyl-N-arylhydrazidoyl bromides 1 react with 2-aminopyridine in ethanol and give 2-aryl-3-arylazo-imidazo[1,2-α]pyridines 2 in 60-75% yield. The reaction of 1 with 3-phenyl-5-aminopyrazole in ethanol leads to 2,6-diaryl-3-arylazo-1H-pyrazolo[1,5-b]imidazoles 3 in almost quantitative yield. Also, 1 react with anthran-ilic acid in the presence of triethylamine giving 3-arylamino-2-aroyl-4-(3H)quinazolinones 4 in 80-85% yield. The structures of the products were assigned and confirmed on the basis of their elemental analysis and electronic absorption, infrared and nmr spectra.     

Synthesis and reactions of 3-carbethoxy and 3-aroyl-3,4-dihydro-1h-2,3-benzoxazin-1-ones

A series of 3-substituted 3,4-dihydro-1H-2,3-benzoxazin-1-ones (IV) (Scheme I) was prepared by reaction of 2-bromomethylbenzoyl chlorides (II) with N-hydroxyethylcarbamate (III) or with benzohydroxamic acids. Acid hydrolysis of 3-carbethoxy (IVa) and 3-benzoyl derivatives (IVb) afforded a mixture of 2-(hydroxyaminomethyl)benzoic acid (V) and 2,3-dihydro-2-hydroxy-1H-1-isoindolinone (VII). Compound IVa reacted with ethanol, amines or hydrazine to yield the ethyl ester X, amides XIV (Scheme II) and the hydrazide XII of 2-(N-carbethoxy-N-hydroxy-aminomethyl)benzoic acid. Diazotization of the hydrazide XII afforded the unstable azide XIII which did not undergo the Curtius reaction but gave the benzoxazinone IVa by loss of hydrazoic acid.     

Aquachlororuthenium(III) catalysis in the oxidation of substituted 4-oxo-4-arylbutanoic acids by bromate in acid medium: a kinetic and mechanistic study and validity of linear free-energy relationships

Ru(III) acts an efficient catalyst in the oxidation of substituted 4-oxo-4-arylbutanoic acids (4-oxo acids) by bromate in sulfuric acid medium, giving the corresponding benzoic acids in quantitative yields. The reaction shows first-order dependence in both [bromate] and [H₂SO₄], and a non-linear dependence on both [oxo acid] and [catalyst]. Changing solvent from H₂O to D₂O increases the rate. The rate is not affected by ionic strength but decreases with increase in dielectric constant of the medium. Electron-releasing substituents in the phenyl ring of the substrate greatly accelerate the rate, whereas the retardation by electron-withdrawing substituents, though perceptible, is small. The linear free-energy relationship is characterized by smooth curves in Hammett plots of log k versus σ; however, linear plots are obtained with excellent correlation coefficients at all the studied temperatures, when Brown’s σ⁺ values are used. The reaction constant is negative and decreases with increase in temperature. From the intersection of the lines in the Hammett and Arrhenius plots, the isokinetic relationship is evaluated. A mechanism involving a cyclic oxidant–substrate–catalyst ternary complex is proposed, in which both C–C bond-breaking and C–O bond formation are involved, and the oxidation state of Ru(III) remains unchanged. A rate law explaining all the kinetic results has been derived and verified. The reaction is an example of neighboring group participation in intramolecular catalysis and is potentially useful for the synthesis of substituted benzoic acids.     

Synthesis of some substituted dibenzodiazepinones and pyridobenzodiazepinones

Some fluoro- and iodo-derivative of 5-[[4-[(4-diisobutylamino)butyl]-1-phenyl]acetyl]-10,11-dihydro-5H-dibenzo[b,e][1,4]diazepin-1l-one and 11-[[4-[(dialkylamino)butyl]-1-phenyl]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-ones 6 (Scheme 1) and their analogues were synthesized. The synthesis of dibenzodiazepinones 1 (Scheme 1) is based on the reaction between 1,4-phenylenediamine and substituted benzoic acids. The intermediate pyridobenzodiazepinones 3 (Scheme 1) were prepared by condensation of 2-chloro-3-aminopyridine with methyl anthranilate and its chlorine derivative. The condensation of 4-[(halo)alkyl]phenylacetyl chloride with dibenzodiazepinones and pyridobenzodiazepinones followed by the reaction of mono- or dialkyl- or dialkenylamine provides 6 (Scheme 1).