Cesium carbonate catalyzed efficient synthesis of quinazoline-2,4(1H,3H)-diones using carbon dioxide and 2-aminobenzonitriles

Abstract

An efficient protocol for the synthesis of quinazoline-2,4(1H,3H)-diones derivatives from 2-aminobenzonitriles with carbon dioxide using catalytic amount of cesium carbonate has been developed. 6,7-Dimethoxyquinazoline-2,4(1H,3H)-dione, which is one of the key intermediate for the synthesis of several drugs (Prazosin, Bunazosin and Doxazosin) was synthesized. The effect of different reaction parameters like influences of bases, solvent, temperature, CO₂ pressure and reaction time were investigated for the title reaction.     

Synthesis of 5′-azido- and 5′-amino-2′,5′-dideoxynucleosides from quinazoline-2,4(1H,3H)-diones

Quinazoline-2,4(1H,3H)-diones 4 were silylated and condensed with methyl 5-azido-2,5-dideoxy-3-O-(4-methylbenzoyl)-α,β-D-erythro-pentofuranoside (3) using trimethylsilyl trifluoromethanesulfonate (TMS triflate) as the catalyst to afford the corresponding 5′-azidonucleosides 5 . 1-(5-Azido-2,5-dideoxy-α-D-erythro-pentofuranosyl)quinazoline-2,4(1H,3H)-diones 6 and the corresponding β anomers were obtained by treating 5 with sodium methoxide in methanol at room temperature. 6-Methyl-1-(5-amino-2,5-dideoxy-β-D-erythro-pentofuranosyl)quinazoline-2,4(1H,3H)-dione (8) was obtained by treatment of the corresponding azido derivative 7 with triphenylphosphine in pyridine, followed by hydrolysis with ammonium hydroxide.     

Reaction of 3-aminoquinoline-2,4-diones with nitrourea. Synthetic route to novel 3-ureidoquinoline-2,4-diones and imidazo[4,5-c]quinoline-2,4-diones

1-Unsubstituted 3-alkyl/aryl-3-amino-1H,3H-quinoline-2,4-diones react with 1-substituted and 1,1-disubstituted ureas in boiling acetic acid to give 2,6-dihydro-imidazo[1,5-c]quinazoline-3,5-diones. In contrast, the reaction of these amines with nitrourea in dioxane affords novel 3-alkyl/aryl-3-ureido-1H,3H-quinoline-2,4-diones or 9b-hydroxy-3a-alkyl/aryl-3,3a,5,9b-tetrahydro-1H-imidazo[4,5-c]quinoline-2,4-diones, which can smoothly be dehydrated to 3a-alkyl/aryl-3,3a-dihydro-5H-imidazo[4,5-c]quinoline-2,4-diones. All three types of products can be converted to 2,6-dihydro-imidazo[1,5-c]quinazoline-3,5-diones by refluxing in acetic acid.     

One-Step Synthesis of Furo[2,3-d]Pyrimidine-2,4(1H,3H)-Diones Using the Can-Mediated Furan Ring Formation

The reaction of 1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione with various alkenes or terminal alkynes in the presence of cerium(IV) ammonium nitrate (CAN) afforded the corresponding 5,6-dihydrofuro[2,3-d]pyrimidine-2,4(1H,3H)-diones or furo[2,3-d]pyrimidine-2,4(1H,3H)-diones in moderate to good yields.     

Unprecedented reactivity of 3-amino-1H,3H-quinoline-2,4-diones with urea: an efficient synthesis of 2,6-dihydro-imidazo[1,5-c]quinazoline-3,5-diones

Substituted 3-amino-1H,3H-quinoline-2,4-diones react with urea in acetic acid to give novel 2,6-dihydro-imidazo[1,5-c]quinazoline-3,5-diones in high yields. The same compounds were obtained, albeit with small yields, from 3-chloro-1H,3H-quinoline-2,4-diones and urea. In the proposed reaction mechanism, a molecular rearrangement of the primarily formed mono-substituted urea takes place. The prepared 2,6-dihydro-imidazo[1,5-c]quinazoline-3,5-diones were characterized by their ¹H, ¹³C, ¹⁵N NMR and IR spectra and atmospheric pressure chemical ionisation mass spectra.     

3-aryl(alkyl)quinazoline-2,4(1<Emphasis Type="Italic">H</Emphasis>,3<Emphasis Type="Italic">H</Emphasis>)-diones and their alkyl derivatives

Two-stage reaction of methyl anthranilate with aryl(alkyl) isocyanates in keeping with the quantumchemical calculations and XRD analysis resulted in 3-aryl(alkyl)quinazoline-2,4(1H,3H)-diones that by treatment with alkyl halides, phenacyl bromides, esters and amides of chloroacetic acid were converted into the corresponding 1-alkyl derivatives.     

A one-step preparation of pyrido[3,4-d]pyrimidine ring system by reaction of 5-formyl-1,3,6-trimethyl-pyrimidine-2,4(1H,3H)-dione with primary amines

6,7-Dihydropyrido[3,4-d]pyrimidine-2,4(1H,3H)-diones were obtained in high yields from the reaction of 5-formyl-1,3,6-trimethylpyrimidine-2,4(1H,3H)-dione ( 1 ) and primary amines. For this pyridopyrimidine synthesis the following reaction pathway is proposed; the [1,5]-hydrogen shift of 1 gives a 5,6-dihydro-5,6-dimethylenepyrimidine-2,4(1H,3H)-dione intermediate. The cycloaddition reaction of the intermediate with aldimines from 1 and the primary amines affords 5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine-2,4(1H,3H)-diones, which are dehydrated to the final products.     

Reaction of 3-chloroquinoline-2,4-diones with ethanolamine and rearrangement of the reaction products

The reaction of tertiary α-chloroketones with ethanolamine has not been hitherto described in the literature. Herein, we describe the reaction of tertiary 3-chloroquinoline-2,4-diones with ethanolamine to give novel 3-(2-hydroxyethylamino)quinoline-2,4-diones. These compounds provide 3-(2-oxooxazolidin-3-yl)quinoline-2,4(1H,3H)-diones and new compounds with dimeric character after reaction with triphosgene. Molecular rearrangement proceeds during the reaction of 3-(2-hydroxyethylamino)quinoline-2,4-diones with isocyanic acid. Three types of reaction products arise: 2-(2-hydroxyethyl)imidazo[1,5-c]quinazoline-3,5-diones, 3-(2-hydroxyethyl)-3,3a-dihydro-2H-imidazo[4,5-]quinoline-4(5H)diones and primarily 5-hydroxy-1-(hydroxyethyl)-1′H-spiro[imidazolidine-5,3′-indole]-2,2′-diones. The reaction mechanism and product stereochemistry are discussed. The ¹H, ¹³C and ¹⁵N NMR spectra of the prepared compounds were measured, and all resonances were assigned from appropriate two-dimensional experiments.     

Retro-ene reactions in heterocyclic synthesis. IV. A new synthetic method for 6-hydroxypyrimidin-4(3H)-ones and 1,3,5-triazine-2,4(1H,3H)-diones

N-t-Butylbenzamidines 1 reacted with diphenyl phenylmalonate or diphenyl methylmalonate to give 6-hydroxypyrimidin-4(3H)-ones 4 or 5. Amidines 1 on reaction with diphenyl imidodicarboxylate afforded 1,3,5-triazine-2,4(1H, 3H)-diones 8.     

Facile synthesis of 3-substituted quinazoline-2,4-dione and 2,3-di-substituted quinazolinone derivatives

3-Substituted quinazoline-2,4(1H,3H)-dione and 2,3-di-substituted quinazolineone derivatives attract considerable interest due to their pharmacological properties. In this paper, we report the synthesis of N-substituted-3-nitrophthalimide derivatives II?CIII, the reactions of phthalimide III with amines, hydrazines, and amino acid derivatives to synthesise a small library of 3-substituted-5-nitroquinazoline-2,4(1H,3H)-diones IV?CXIV and 2,3-di-substituted-6-nitro-quinazolineones XVIII?CXIX.     

Synthesis of novel 1,3-oxazino[6,5-b]indole-2,4-(3H,9H)-dione and 2H-1,3,5-oxadiazino[3,2-a]indole-2,4-(3H)-dione from oxindoles

Two novel tricyclic ring systems were designed as serine protease inhibitors and synthesized from oxindoles; the first series, 1,3-oxazino[6,5-b]indole-2,4-(3H,9H)-diones, were prepared from 2,3-dihydro-2-oxo-(1H)-indole-3-carboxamides and phosgene in tetrahydrofuran with triethylamine. The second, a 2H-1,3,5-oxadiazino[3,2-a]indole-2,4-(3H)-dione was made using a similar cyclization on 2,3-dihydro-2-oxo-N-phenyl-(1H)-indole-1-carboxamide.     

Nitrogen bridgehead compounds. Part 88. Synthesis of 3H, 7H-[1,4]diazepino[3,4-b]quinazoline-3,7-diones

3H,7H-[1,4]Diazepino[3,4-b]quinazolone-3,7-diones 9, 11 were synthesized starting from 2-(1-bromo-ethyl)quinazolin-4(3H)-ones 3 and 17 via 2-[1-(4-methoxyphenylamino)ethyl]quinazolin-4(3H)-ones 4 and 18. Cyclization of 3-[2-(1-bromoethyl)-4-oxo-3,4-dihydroquinazolin-3-yl)propionic acid 14 by the action of triethylamine provided the first representative of the tricyclic 7H-[1,4]oxazepino[3,4-b]quinazoline-3,7-dione system, compound 15. The new tricyclic derivatives 9, 11 and 15 are characterized by uv, ir and ¹H nmr spectroscopy.     

Chemical fixation of CO2: efficient synthesis of quinazoline-2,4(1H, 3H)-diones catalyzed by guanidines under solvent-free conditions

Guanidines were proved to be efficient catalysts for the chemical fixation of carbon dioxide with 2-aminobenzonitriles under solvent-free conditions. Notably, the catalysts with low loading worked well for a variety of 2-aminobenzonitriles. As a result, quinazoline-2,4(1H, 3H)-diones by employing present protocol were obtained in good yields under mild conditions. This process represents an alternative approach for the greener chemical fixation of CO₂ to afford valuable compounds.     

Synthesis of thietanyl-substituted pyrimidine-2,4(1H,3H)-dions

Reactions of 6-methylpyrimidine-2,4(1H,3H)-dione or 5-hydroxy-6-methyl-pyrimidine-2,4(1H,3H)-dione with 2-chloromethylthiirane afforded the corresponding substituted 1-(thietan-3-yl)pyrimidine-2,4(1H,3H)-diones. The calculations in the framework of approximations PBE/3z, B3LYP/6-31G++(d,p) and MP2/6-31G++(d,p) showed that the alkylation occurred at the atom N¹ of the pyrimidine ring.     

New organic nitrates. II. Synthesis of 2H-pyrido[2,3-e]-1,3-oxazine-2,4(3H)-diones, 2H-pyrido[4,3-e]-1,3-oxazine-2,4(3H)-diones, 2H-pyrido[4,3-e]-1,3-oxazin-4(3H)-ones, 2H-thieno[2,3-e]-1,3-oxazin-4(3H)-ones and 2H-thieno[3,4-e]-1,3-oxazin-2,4(3H)-diones

The preparation and the physico-chemical characterization of 2H-pyrido[2,3-e]-1,3-oxazine-2,4(3H)-diones, 2H-pyrido[4,3-e]-1,3-oxazine-2,4(3H)-diones, 2H-pyrido[4,3-e]-1,3-oxazin-4(3H)-ones, 2H-thieno[2,3-e]-1,3-oxazin-4(3H)-ones and 2H-thieno[3,4-e]-1,3-oxazine-2,4(3H)-diones are reported.     

Pyrrolo [1,2-a] [1,3,5] triazine-2,4(1H, 3H)-diones. III—Fragementation under electron-impact

The mass spectra of eight pyrrolo[1,2-a][1,3,5]triazie-2,4(1H, 3H)-diones have been examined. An unusual feature in the fragmentation of those compounds having a 7-alkoxycarbonyl function, namely loss of the whole ester grouping with concomitant hydrogen rearrangement, is discussed.     

The synthesis and spectroscopic properties of 3-(2′,4′-Xylyl)-1H,3H-quinazoline-2,4-diones

The synthesis of 3-(2′,4′-xylyl)-1H,3H-quinazoline-2,4-diones ( 1a, 9a-j ) has been accomplished. Their pmr and ir spectra data for all compounds are presented.     

Synthesis, chemical properties, and antimicrobial activity of 2- and 2,3-substituted [(tetrahydro-2,4-dioxopyrimidin-1(2H)-yl)phenoxy]naphthalene-1,4-diones

Abstract  

Mono- and disubstituted [(tetrahydro-2,4-dioxopyrimidin-1(2H)-yl)phenoxy]naphthalene-1,4-diones were synthesized by the reaction of dihydro-1-(3-hydroxy- and 4-hydroxyphenyl)pyrimidine-2,4(1H,3H)-diones and their 5- and 6-methyl derivatives with 2,3-dichloro-1,4-naphthoquinone. Their stability in alkaline and acidic media was investigated. Four of the compounds exhibited good antimicrobial activity against Staphylococcus aureus, Mycobacterium luteum, Candida tenuis, and Aspergillus niger.     

New [f]-fused xanthines: Synthesis of 1,3-dipropyl-1H,3H-pyrazino,pyrido, pyrimido and pyrrolo[2, 1-f]purine-2,4-diones

Synthesis of 1,3-dipropyl-1H,3H-pyrazino, pyrido, pyrimido and pyrrolo[2,1-f]purine-2,4-diones, starting from 5,6-diamino-1,3-dipropylpyrimidine-2,4-dione 1 and 6-chloro-1,3-dipropylpyrimidine-2,4-dione 14 is described. A new synthetic approach to 1,3-dipropyl-1H,3H-pyrido(or pyrazino)[1′,2′-1,2]pyrimido[4,5-d]pyrimidine-2,4,5-triones 19 e, f, h has been also developed.     

Pyrano[4,3-d]pyrimidinium salts 4. Transformations of 5,7-diaryl-1,3-dimethyl-2,4-dioxo-1H,3H-pyrano[4,3-d]pyrimidinium bromides under the action of phenylhydrazines and aromatic acid hydrazides

Reactions of 5,7-diaryl-1,3-dimethyl-2,4-dioxo-1H,3H-pyrano[4,3-d]pyrimidinium bromides with phenylhydrazines and aromatic acid hydrazides have been studied. The reaction of the salts indicated with phenylhydrazine at ∼20 °C results in the pyrylium ring opening, whereas elevated temperature leads to recyclization products, i.e., 1,3-dimethylpyrido[4,3-d]pyrimidine-2,4(1H,3H)-diones. The reactions of the starting bromides with m-carboxyphenylhydrazine and aromatic acid hydrazides lead to 6-(R-amino)-1,3-dimethyl-2,4-dioxo-1H,3H-pyrido[4,3-d]-pyrimidinium salts.