It is a light yellow crystalline solid that is soluble in water. The fusion of anthranilic acid with urea gave 1,2,3,4tetrahydro2,4dioxoquinazoline see scheme 14. The quinazoline skeleton appears in many alkaloids, most commonly in the form of 43hquinazolinone moieties. Design, synthesis, computer modeling and analgesic. In this study, a new series of quinazoline derivatives 326 was synthesized and characterized via physicochemical and spectral means. Typically, quinazolin43hones are prepared from an anthranilic acid or its derivative, e.
Using the conditions disclosed herein, a small library of substituted quinazolin43hones has been generated with high yields figure1. Microwaves in drug discovery and multistep synthesis. Methods for the synthesis of quinazoline and quinazolinone derivatives benzoylene urea some methods were reported for the synthesis of quinazolines and quinazolinones are as follows. Quinazolines are nitrogen containing heterocyclic scaffolds and have showed a wide range biological activities, such as anticancer. Synthesis of some new quinazolinone derivatives and. The niementowski quinazoline synthesis is the chemical reaction of anthranilic acids with amides to form 4oxo3, 4dihydroquinazolines. In alkaline medium, where the anhydrous neutral species of quinazoline were predominantly undergo oxidation with kmno 4 furnished a high yield of 3,4dihydro4oxo quinazoline was also formed. The action of alkylating agents on 12 carboxyethyl1h,3h quinazoline2,4dione was utilized to synthesize corresponding esters. Several biological activities were reported for fused tricyclic quinazoline derivatives 8, 9 among which deoxyvasicinone is highly interesting and has been.
Abstract four new diaza analogues 14, 15, 23, and 24 of the conformationally constrained aminobutyrophenone derivatives qf0104b 5 and. The observed dipole moment of quinazoline in benzene is 2. Synthesis of nheterocycles benzofused nheterocycles synthesis of quinazolines. Synthesis, characterization and antimicrobial studies of. Methyl, ethyl, isopropyl, benzyl, tbutyl and phenyl magnesium halides and phenyl lithium also add across the 3, 4 double bond to give the corresponding 4 substituted 3, 4dihydroquinazolines. Synthesis and biological evaluation of new quinazoline and.
Research has demonstrated that the niementowski quinazoline synthesis could be employed for the creation of potential egfrinhibiting molecules. All synthesized compounds are confirmed by uv, ir, mass and h1nmr. The preparation of the quinazoline came many years later when bischler and lang obtained it by decarboxylation of the 2carboxy derivative. Synthesis of novel quinazoline4one derivatives and their. Name reactions name reactions and reagents in organic. An efficient cucatalyzed synthesis of quinazolines via the cn bond formation reactions between nh bonds of amidines and csp 3h bonds adjacent to sulfur or nitrogen atoms in the commonly used solvents, such as dmso, dmf, dma, nmp or tmeda, followed by intramolecular cc bond formation reactions was developed for the first time. Synthesis, characterization, and anticancer activity of new.
Shakhidoyatov chemistry of heterocyclic compounds volume 35, pages 821 824 1999cite this article. Seven new quinazoline derivatives are synthesized by three steps. The use of oxygen as an oxidant combined with the transitionmetal, additive and solventfree. The bioactive assays showed that most of the compounds exhibited moderate antimicrobial activities against the tested strains. Niementowski quinoline synthesis wikipedia niementowski quinazoline synthesis wikipedia. Synthesis of chalcone incorporated quinazoline derivatives as. Helmy sakr m 2016 design, synthesis, computer modeling and.
Oxidation catalytic hydrogenation of quinazoline stopped after the absorption of one molecules of hydrogen and. Synthesis of two bifunctional ligands for the quest threehybrid system. Synthesis of some novel quinazoline derivatives having. These studies are connected with our work on the synthesis of original heterocycliccompounds with potential pharmaceutical value. Quinazolin4ones with 2, 3disubstitution is reported to. Synthesis of quinazoline compounds various methods were reported for the synthesis of oxoquinazolines. Review article chemical characteristics, synthetic methods. Quinazoline in 1905 riedel obtained a patent describing a synthesis of quinazoline from onitrobenzaldehyde through reaction with formamide to the onitrobenzylidenediformamide. A new rapid and versatile approach using ionic liquiddmso as a chemical reagent for the synthesis of fused heterocyclic compounds in a highly efficient way is described.
Synthesis and anticancer activity of new quinazoline derivatives. A highly employed method for 43hquinazolinone synthesis is based on acylation of anthranilic acid with acyl chloride. Synthesis of new 1,2,3triazol4ylquinazoline nucleoside and. Synthesis and antimicrobial activity of some new quinazoline. Design and synthesis of imidazobenzimidazo 1, 2c quinazoline. Niementowski quinazoline synthesis, cheminform on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. May 19, 2017 reaction of 5aminotetrazole triethylammonium salt and 2fluoro6chlorobenzaldehyde resulted in the formation of 6chlorotetrazolo1,5a quinazoline instead of the expected azomethine. The hydrolysis and hydrazinolysis of the last were accomplished. Synthesis of 6chlorotetrazolo1,5 a quinazoline and 6. C8h6n2 and various methods have been worked out for their synthesis. It is a mancude organic heterobicyclic parent, a member of quinazolines, an azaarene and an orthofused heteroarene. More than three fourth of the bioactive drugs available in the market are all hetero cycles. Quinazoline is a mancude organic heterobicyclic parent that is naphthalene in which the carbon atoms at positions 1 and 3 have been replaced by nitrogen atoms.
Isatoic anhydride, acid hydrazides or ammonium acetate and aromatic aldehydes in the presence of nhalosulfonamides. Unfortunately, classic chemical synthesis does not provide an opportunity for the formation of n. Synthesis and antimicrobial activity of some new quinazoline derivatives dhaval j. Microwave assisted synthesis and molecular docking studies. Compounds 1 and 2 demonstrated a remarkable antiproliferative effect, with an ic 50 value of 6. I 43hquinazolinones 1 and related quinazolines 2 are classes. A brief survey about biological importance of quinazoline and thier derivatives revealed that a large number of publications began to appear after 1960s. Synthesis of 6aryl5 h quinazolino4,3 b quinazolin8. A novel series of n,o,s heterocyclic compounds incorporated at position. Quinazolines are a large group of naturally occurring and semisynthetic heterocyclic compounds. We also report the synthesis of a modest selection of 5,6dihydropyrimidin43hones from. Dakhil department of chemistry, faculty of science, university of benghazi, benghazi, libya a r t i c l e i n f o a b s t r a c t article history. Inspired by the high yields obtained using formic acid, a further study of 43h quinazolinones synthesis, as a possible niementowski reaction, was carried out using different aromatic and heteroaromatic carboxylic acid, amine and carboxylic acid were mixed and irradiated under microwaves to yield 2,3disubstituted43h quinazolinones 1al.
Chemical profiling of a streptomyces griseus strain isolated from an old building with moisture damage led to the discovery of two novel phenoxazinones, chandrananimycin d 1 and pitucamycin 2, along with the known grixazone b 3. This reaction employs mild reaction conditions, is metalfree and utilizes readily available starting materials making it a more viable reaction for scale up synthesis and ligand diversity. The journal of organic chemistry 2000, 65 6, 17431749. Recently, many efforts have been focused by chemists on the modification of quinazoline ring for development of pharmaceutical and clinical compounds. Files are available under licenses specified on their description page. This novel procedure has the advantages of high yields, being metalfree and having a mild reaction condition. When the effervescence ceased, the precipitate obtained was filtered and washed with water. The interest of microwaves in drug discovery and multistep synthesis is exposed with the aim of describing our strategy. Niementowski was een voornaam scheikundige in zijn tijd. Synthesis of quinazolinones and quinazolines request pdf. It is an aromatic heterocycle with a bicyclic structure consisting of two fused sixmembered aromatic rings, a benzene ring and a pyrimidine ring. Nmr, esi hrms, and hplc purity spectra of compounds 8aa8gd pdf.
Pitucamycin represents an unprecedented hybrid molecule composed of a phenoxazinone and an enaminomycinlike epoxyquinone moiety. Synthesis of some new quinazolinone derivatives and evaluation. We aimed to modify the procedure reported till now using ionic liquids which can be applicable not only for fused quinazoline but to a wide range of fused heterocycles such as substituted thienopyrimidine, pyridothienopyrimidines, triazinoquinazolines as well as quinazolines. Up to now more than 120 alkaloids belonging to this class have been isolated and structurally characterized from. These named traditional reactions were performed using microwave assisted synthesis on samsung domestic microwave, 1. The heterocyclic fused rings quinazoline and quinazolinone have drawn a huge consideration owing to their expanded applications in the field of pharmaceutical chemistry. Jan 24, 2007 the invention concerns quinazoline derivatives of formula i. Unexpected coppercatalyzed cascade synthesis of quinazoline derivatives zhongyan chen, jiuxi chen, miaochang liu, jinchang ding, wenxia gao, xiaobo huang and huayue wu college of chemistry and materials engineering, wenzhou university, wenzhou 325035, china, email. Also known as 1,3diazanaphthalene, quinazoline received its name from being an aza derivative of quinoline. Synthesis, quinazolines, antibacterial, antifungal.
A simple and efficient approach for the synthesis of 2aminoquinazoline derivatives in moderate to good yields. Unexpected coppercatalyzed cascade synthesis of quinazoline. General procedure for coppercatalyzed synthesis of quinazoline derivatives 3aj p5. Subsequent ring closure with acetic anhydride afford corresponding 1,3benzoxazin4one benzoxazinone which will be treated with different amines to give 43hquinazolinone derivatives. Oct 17, 2012 3substituted quinazoline2,41h,3hdione and 2,3disubstituted quinazolineone derivatives attract considerable interest due to their pharmacological properties.
Quinazoline and condensed quinazoline exhibit potent central nervous system cns activities like antianxiety, analgesic, antiinflammatory 10and anticonvulsant 11. Synthesis and antihypertensive activity of some quinazoline. The synthesized compounds were characterized by spectral methods. Synthesis and reactivity of some novel quinazoline. Synthesis and reactions of some new quinazoline derivatives for. Numerous quinazoline derivatives have been found to possess a broad spectrum of biological. Syhthesis following methods were reported for the synthesis of oxoquinazolines. Facile synthesis of 3substituted quinazoline2,4dione and 2. Analgesic activity of some new quinazoline derivatives. Jun 03, 20 owing to the significant biological activities, quinazoline derivatives have drawn more and more attention in the synthesis and bioactivities research. A new route toward 4substituted pyrazino2,1b quinazoline 3,6dione systems. Review article chemical characteristics, synthetic methods, and biological potential of quinazoline and quinazolinone derivatives mohammadasif department of pharmacy, grd pg institute of management and technology, dehradun, uttarakhand, india. Quinazoline derivatives have been very well known for antihypertensive activity. A sustainable synthesis of quinazoline and 2aminoquinoline via acceptorless dehydrogenative annulation is catalyzed by earthabundant welldefined manganese complexes bearing nns ligands.
An efficient construction of quinazolin43hones under. Quinazoline derivatives are well known to have a diverse array of therapeutic activities. Synthesis of quinazoline derivatives and their biological. Reduction of this with zinc and dilute acetic acid gave quinozoline in.
Molecular iodine catalyses a benzylic sp 3 ch bond amination of 2aminobenzaldehydes and 2aminobenzophenones with benzylamines to provide quinazolines in very good yields. Treatment of 2amino5methylbenzoic acid with butyl isothiocyanate resulted in the new 2thioxoquinazolin4one 3. A simple and efficient approach for the synthesis of 2. The iodinecatalyzed reaction of 22aminophenylquinazolin43hones and benzaldehydes was treated in ionic liquids, giving a series of 6aryl5hquinazolino4,3bquinazolin86hone derivatives in high yields. Owing to the significant biological activities, quinazoline derivatives have drawn more and more attention in the synthesis and bioactivities research. The thermal transformation of an anthranilic acid into 4. Biological activities of quinazolines diverse biological activities were attributed to compounds possessing a quinazoline ring system. Nmr, esihrms, and hplc purity spectra of compounds 8aa8gd pdf. Oct 10, 20 a series of novel 1methyl3substituted quinazoline 2,4dione derivatives was designed, synthesized, and evaluated for their antimicrobial activities against six strains of bacteria and five fungi in vitro. In recent years, the synthesis of quinazolines and its derivatives has become a hot spot in organic synthetic chemistry due to their broad biological and medicinal activities, such as. Synthesis of quinazoline derivatives containing veratrole and. Chemical characteristics, synthetic methods, and biological. Quinazoline and quinazolinone are reported for their diversified biological activities and compounds with different substitutions bring together to knowledge of a target with understanding of the molecule types that might.
Reduction of this with zinc and dilute acetic acid gave quinozoline in good yield. Polyphosphoric acid effected the conversion of 12carboxyethylquinazolinedione to 1,3,7trioxopyrido1,2,3k,jquinazoline. Introduction quinazoline nucleus has attracted attention of medicinal chemists, due to wide spectr um of biological activities exhibited by them. Synthesis, characterisation and biological evaluation of. Recent advances in 43 h quinazolinone syntheses rsc. The hydrocarbonylation of 2nallylaminomethylanilines 125a and 125b catalyzed by a rh complex resulted in the formation of quinazolines 126 and 127, respectively, in good yields equation 16. Hydrogenation of the obtained quinazoline afforded 6chloro4,5dihydrotetrazolo1,5a quinazoline. Acaaddemmiicc ss ciieenncess international journal of. The reaction yield in such conditions is variable and sometimes low yields were. Quinazoline derivatives with antitubercular activity. The first known synthesis of quinazoline was reported in 1895 by august bischler and lang through the decarboxylation of the 2carboxy derivative quinazoline 2carboxylic acid. Niementowski quinazoline synthesis essay niementowski quinazoline synthesis essay inflammatory dermatoses dissertations denizmen dissertation essayer futur indicatif. Ebscohost serves thousands of libraries with premium essays, articles and other content including synthesis of novel quinazoline 4one derivatives and their acyclonucleoside analogs.
The use of oxygen as an oxidant combined with the transitionmetal, additive and solvent. Synthesis and evaluation of antioxidant properties of some synthesized quinazoline and 1,4diazepine derivatives pratibha sharma, premansh dudhe, ashok kumar. Synthesis of quinazoline derivatives containing veratrole and benzo15crown5 moieties. Synthesis, characterization and biological screening of quinazoline 4one analogs introduction hetero cyclic chemistry research reached in all areas of drug discovery in recent days. Quinazoline has become a popular topic up of two fused sixmembered simple aromatic rings, a benzene ring and a pyrimidine ring having due to its manifold uses. All the title compounds 10a 10r were evaluated for cytotoxic activity against four human cancer cell lines mgc803, ec109, mcf7 and hgc27 using mtt assay in vitro.
The synergy of combined use of dmso and bronsted acid. Synthesis of some novel quinazoline derivatives having anticancer activity. Coppercatalyzed annulation of amidines for quinazoline. The essence of the synthesis is given in equation 8. In 1903, siegmund gabriel reported the synthesis of the parent quinazoline from onitrobenzylamine, which was reduced with hydrogen iodide and red phosphorus to 2aminobenzylamine. Supporting information highly efficient coppercatalyzed cascade. A novel series of quinazolines were synthesised by cyclisation reaction of anthranilic acid with urea to get 2,4 di hydroxy quinazoline 2. Stefan niementowski zjovkva, 4 augustus 1866 warschau, juli 1925 was een pools scheikundige. A series of novel 1,2,3triazolequinazoline derivatives were synthesized in five steps starting from anthranilamide by conventional methods.
Quinazolinone derivatives are an important class of these heterocyclic compounds that has been shown to display a broadrange of biological. Synthesis, cytotoxic activity evaluation of novel 1,2,3. Design, synthesis, and evaluation of novel 1methyl3. All structured data from the file and property namespaces is available under the creative commons cc0 license. A novel approach to the synthesis of quinazoline alkaloids has been developed by means of the rhodiumcatalyzed hydroformylationcyclocondensation of diaminoalkenes 71. The pasty mass obtained was diluted with 50ml of water and treated with aqueous sodium bicarbonate solution. Synthesis, characterization, and anticancer activity of. Synthesis of some novel quinazoline derivatives having anti. This method offers the advantages of proceeding in neutral conditions, giving high to excellent isolated yields 8392% for niementowski synthesis with easy workup procedure. In this paper, we report the synthesis of nsubstituted3nitrophthalimide derivatives iiiii, the reactions of phthalimide iii with amines, hydrazines, and amino acid derivatives to synthesise a small library of 3substituted5. Ep 1667992 b1 quinazoline derivatives the lens free.
Synthesis and antiinflammatory screening of some quinazoline and. Aug, 2016 in this research, a facile, effective and onepot synthesis of new quinazoline41hone derivatives is reported. A more satisfactory synthesis of quinazoline was subsequently devised by gabriel in 1903. Two new synthesized and characterized quinazoline schiff bases 1 and 2 were investigated for anticancer activity against mcf7 human breast cancer cell line. Stephen j baker, steven m firestine, david smithrud, frank salinas, stephen j benkovic. Synthesis and evaluation of antioxidant properties of some. Design and synthesis of imidazobenzimidazo1,2cquinazoline. Niementowski synthesis an overview sciencedirect topics.
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