Synthesis and characterization of some new 4-heteroaryl quinazoline and fused triazolo quinazoline derivatives (original) (raw)
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2011
The behavior of 2-ethoxy-4-chloroquinazoline 2 towards various nitrogen nucleophiles, namely: thiosemicarbazide, sodium azide, glucosamine, ethanol, and hydrazine hydrate has been discussed. Also, the behavior of 4-(2-ethoxyquinazolin-4-yl)thiosemicarba- zide towards one-carbon, for example, ethyl chloroformate, and two-carbon donors, for example, ethyl chloroacetate and diethyl oxalate has been investigated. On the other hand, new 5-ethoxy-2-substituted[1,2,4]-triazolo-[1,5-c]quinazoline derivatives have been obtained by ring closure accompanied with Dimroth rearrangement through the interaction of compound 2 with hydrazides of acetic, benzoic, crotonic, cinnamic, 2-furoic, and phthalimidoacetic acids. Structures of the novel products were confirmed by elemental, IR, MS, and 1H-NMR spectral analyses.
2012
The interactions of 2-ethoxy(4H)-3,1-benzoxazin-4-one (1) with various nitrogen nucleophiles such as ammonium acetate, hydrazine hydrate, ethanolamine, p-phenylenediamine, o-phenylenediamine, o- tolidine, dapsone, 2-aminophenol, 4-aminophenol, 4-aminobenzoic acid and 2-aminonicotinic acid have been discussed. The reactions of 2-thoxy-(3H)-quinazolin-4-one with ethyl chloroformate, phosphorus pentasulfide, chloroacetyl chloride and phosphorus oxychloride have also been investigated. Similar reactions of 2-ethoxy-4-chloroquinazoline with hydrazine hydrate and thiosemicarbazide have been introduced. Aminolysis of the 2-ethoxy group in some of the thiadiazoloquinazolinone derivatives has been attempted. The interactions of these aminolized derivatives and the 3-aminoquinazolinone with chloroacetyl chloride have been studied. All of the synthesized derivatives have been used in a wide range as starting materials for the synthesis of novel quinazoline and/or quinazolinones which have biological activity. The structures of all these products, obtained by heterocyclic ring opening and ring closure, were inferred by the IR, MS, 1H NMR spectral as well as elemental analyses.
Synthesis of New Quinazoline Derivatives
Heterocyclic Communications, 2004
New quinazoline derivatives were prepared by the reaction of 4-hydroxy-quinazoline with alkyl halides under phase transfer-catalysis conditions. The hydroxy group was readily converted into a thiol function by treating with phosphorus pentasulfide in pyridine and the subsequent alkylation of the thiol group was carried out under PTC conditions. Chlorination of 4-hydroxyquinazoline was carried out with phosphorus oxychloride. Branching of alkylamino side chains to the 4-OH, 4-S, and 4-C1 quinazolines has resulted in the synthesis of several compounds identified by 'H NMR. Introduction: Quinazoline derivatives have been reported to possess depressant, anticonvulsant and muscle relaxant properties as well as anti-inflammatory, antihypertonic, antibacterial, antifungal, analgesic and spasmolytic activities [1-6]. Attention was also drawn to this heterocyclic moiety with the aim to use it as possible pharmacophore, especially in case of tyrosine kinase inhibitors and adenosine antagonists [7]. Within the frame of our ongoing research devoted to chemosensitizers [8-11], we intended to prepare new derivatives belonging to this series. Results and discussion: At first, 4-hydroxy-quinazoline, 1_, was used as starting material. Alkylation was carried out under phase transfer catalysis (PTC) conditions with tetrabutylammoniumbromide (TBAB) as catalyst. In spite of the tautomeric equilibrium between N(3) and C(4), only small amounts of O-alkylated derivatives were identified but not isolated. Hence, substitution at the nitrogen atom in position 3 gave compounds 2 as the major product. Subsequently, the OH functional group was modified. On the one hand, the 4-thio-quinazoline 3 was prepared by treating 1 with phosphorus pentasulfide in pyridine. Alkylation of the thione only gave 4-alkylthioquinazoline derivatives 4 as already observed with thioacridines [12] or thioquinolines [13]. Dimers 5 were also prepared alkylating 3 with α,ω-alkyldihalides.
Chemical and Process Engineering Research, 2011
The 2-{[5-(2-Amino-4-oxoquinazolin-3(4H)-yl)-1,3,4-thiadiazol-2-yl]methyl}-1H-isoindole-1,3(2H)-dione 1 was synthesized and allowed to react with each of p-methoxybenzaldehyde, p-methoxyacetophenone and chloroacetyl chloride to produce the Schiff bases 2 and 3 and 2-chloro-N-(3-{5-[(1,3-dioxo-1,3-dihydro-2Hisoindol-2-yl)methyl]-1,3,4-thiadiazol-2-yl}-4-oxo-3,4-dihydroquinazolin-2-yl)acetamide 6, respectively. The products 2 and 3 were reacted with phenyl isothiocyanate to afford 4 and 5. Derivative 6 was reacted with various nucleophiles, namely: thioglycolic acid, ethyl glycinate and 2-aminoethanol giving 7-9 respectively. In turn, the derivative 8 was reacted with α-bromoglucose tetraacetate affording product 8a whereas 9 was reacted with p-acetylaminobenzenesulfonyl chloride affording derivative 9a. Moreover, the reactions of the derivative 6 with potassium thiocyanate, potassium cyanate, malonitrile, ethyl cyanoacetate and ammonium acetate gave derivatives 10-15, respectively. All the synthesized derivatives were confirmed by the IR, mass, 1 H-NMR and elemental analysis.
Maher A. El-Hashash, Sameh A. Rizk, Fakhry A. El-Bassiouny Khalid M. Darwish , 2012
2-Ethoxy-4(3H) quinazolinone 1 was synthesized and allowed to react with various halides, namely: alkyl, benzyl, allyl, acyl, haloacetyl, crotonyl, benzoyl, 2-furoyl and 1-naphthalenesulphonyl halides affording quinazoline and quinazolinone derivatives. The reactions of compound 1 with phosphorus oxychloride, phosphorus pentasulfide, ethyl chloroformate, ethyl chloroacetate, α-bromoglucose tetraacetate, p-acylaminobenzenesulfonyl chloride, acrylonitrile, chalcone and chalcone oxide were also investigated. Depending on the reaction condition and reactant halide, the type of substituent (alkyl, acyl, aroyl, etc.) that will reside on either of the expected positions (3 or 4) on the quinazoline moiety can control the reaction pathway for synthesis of the promising products. The significant role of solvent responsible for determining both the reaction pathway and type of products synthesized was also discussed. Some derivatives were chosen for biological screening test against Gram (-ive) and Gram (+ive) bacteria and two strains of fungi.
Synthesis and Biochemical Evaluation of Some Novel Anti-inflammatory Quinazolines
2011
This study was carried out to synthesis of some novel of anti-inflammatory triazoloquinazoline and triazinoquinazoline derivatives. When compound 2 was reacted with sulfa merazine the thioureido derivative 3 was obtained. Refluxing of compound 3 with hydrazine hydrate in ethanol afforded the N-aminoquinazoline derivative 4. When compound 4 was reacted with aromatic aldehydes with aromatic aldehydes in acetic acid containing fused sodium acetate, triazoloquinazoline derivatives 5 – 7 were produced. In a similar manner, acetic anhydride and/or 2- chlorobenzoylcholoride were reacted with compound 4 to furnish the triazoloquinazoline derivatives 8, 9, respectively. In addition, the corresponding triazinoquinazoline derivative 11 was obtained via reaction of compound 4 with ethyl chloroacetate. The triazoloquinazoline 16 was obtained in good yield via reaction of 4 with diethyloxalate. The results of the pharmacological study indicated that some of the derivatives which were tested, espe...
ChemInform, 2011
A series of 3-(4-substituted benzylidene)-4-N-ethoxyphthalimido-6-phenyl-3,4-dihydro-2H-[1,2,4]triazino[2,3c]quinazolin-2-one 6a-d and 3-[3-(4-substituted benzylidene-5-phenyl-2-N-ethoxyphthalimido-3,3a-dihydro-2Hpyrazolo[3,4-d][1,3]thiazol-6(5H)-yl)]-2-phenylquinazolin-4(3H)-one 11a-d have been designed and synthesized starting from benzoxazine 1. The structure of all synthesized compounds has been established by IR, 1 H and 13 C NMR and mass spectral studies. These compounds have been screened for antimicrobial activities in order to evaluate the possibility of the derivatives to be used as potential chemotherapeutic agents.
Synthesis and Biological Activity of Some New Substituted Quinazolin-4(3H)-Ones
Egyptian journal of chemistry, 2011
(4-AMINOPHENYL)-2-benzyl-4-oxo-3,4-dihydroquinazoline 1a and 3-(4-aminophenyl)-2-benzyl-6-bromo-4-oxo-3, 4 dihydroquinazoline 1b were prepared and diazotized by nitrous acid to give ″2a, b″. The diazonium chloride derivatives were converted to the corresponding 3-arylhydrazono derivatives on treatment with active methylene compounds namely acetylacetone, ethyl acetoacetate and/or ethyl cyanoacetate. The hydrazono derivatives were converted to the corresponding pyrimidino derivatives ″6a-f″, pyrazolo derivatives ″7a-d″ and pyrazoline derivatives ″8a-d″ and ″9a-f″ in order to study their antimicrobial activity. A significant level of activity of the new products was observed.
A Novel Approach Towards Development of Quinazoline
2013
Objective: To synthesize and evaluate the analgesic and anti-inflammatory activities of pyrazoline bearing 4(3H)-quinazolinone derivatives. Methods: Synthesis of Chalcone (3a-3j) involves the Claisen-Schmidt condensation of equimolar quantities of substituted acetophenone with aromatic aldehyde in the presence of aqueous alkali (10%). Comp. (3a-3j) undergoes cyloaddition reaction with semicarbazide HCl in the presence of suitable solvent to yield comp. (4a-4j). It undergoes addition cyclization reaction with anthranillic acid to yield final comp. (6a-6j). Acute toxicity study of synthesized compound was found according to OECD guidelines 423. The test compound do not showed any toxicity up to 200mg/kg dose. Mortality was not observed during the course of study. The analgesic and anti-inflammatory activity of all synthesized compounds were carried by using hot plate method and Carrageenan induced Rat Paw Edema Method respectively. Results: All compounds synthesized are obtained in crystalline form with good practical yield. The purity and homogeneity of compounds synthesized were determined by sharp melting points and TLC method. The chemical structures were confirmed by FTIR, 1 HNMR, and Mass spectrum. Conclusion: The synthesized compound 6b, 6d, 6e, 6i and 6j showed good analgesic and anti-inflammatory activities whereas others showed significant activities.
Synthesis of Some Novel Quinazoline Derivatives Having Anti-Cancer Activity
Global journal of pharmacy & pharmaceutical sciences, 2017
General procedures Synthesis of 2-aryl-3-amino-4(3H) quinazolinone from anthranilic acid: Anthranilic acid (0.1mol, 13.71gm) was dissolved in 30ml of dry pyridine by stirring slowly at room temperature. The solution was cooled to 0 °C and a solution of an aromatic acid chloride (4-Chlorobenzoyl chloride) (0.02mole) in 30ml of dry pyridine was added slowly with constant stirring [4,5]. After this addition the reaction mixture was further stirred for half an hour at room temperature and set aside for 1h.