An efficient synthesis of quinazoline derivatives with the aid of low‐valent titanium reagent

Quinazolin‐4(3H)‐ones, 1,2‐dihydroquinazolin‐4(3H)‐ones, 3,4‐dihydroquinazolines, imidazo[1,2‐c]‐quinazolines and 5,6‐dihydroimidazo[1,2‐c]quinazolines were synthesized by the novel reductive reaction of nitro group, N‐H bond and ortho‐ester, aldehydes or ketones promoted by the low‐valent titanium reagent (TiCl₄‐Zn system). The structures of these compounds were characterized by elemental analysis, IR and ¹HNMR spectra and further confirmed by single crystal X‐ray diffraction analysis.     

An efficient synthesis of pyrrolo[1,2‐a]quinazolin‐5(1H)‐one derivatives with the aid of low‐valent titanium reagent

A short and facile synthesis of 2,3,3a,4‐tetrahydropyrrolo[1,2‐a]quinazolin‐5(1H)‐ones and 2,3,3a,4‐tetrahydropyrrolo[1,2‐a]quinazoline‐1,5‐diones in good yields via the novel reductive cyclization of 2‐nitrobenzamides with haloketones or 4‐oxopentanoic acid promoted by low‐valent titanium reagent is described. J. Heterocyclic Chem., (2011).     

A facile synthesis of substituted 3‐amino‐1H‐quinazoline‐2,4‐diones

A new synthesis of a series of 3‐amino‐1H‐quinazoline‐2,4‐diones is described. The 1H‐quinazoline‐2,4‐dione 10 was made starting with fluorobenzoic acid in three high yielding steps. The key step of this synthesis involved the generation of the dianion of urea 7 and the subsequent intramolecular nucleophilic displacement of the 2‐fluoro to form the quinazolinedione ring. The 3‐amino moiety was incorporated using (2,4‐dinitro‐phenyl)‐hydroxylamine as the aminating reagent.     

One‐pot Syntheses of Some New 2,4(1H,3H)‐quinazolinedione Derivatives in the Absence of Catalyst

A facile, rapid and one‐pot procedure for the synthesis of some new 2,4(1H ,3H )‐quinazolinediones is described. The method involves the one‐pot condensation of isatoic anhydride, primary amine and carbonyl diimidazole (CDI) in the absence of organic or inorganic catalyst. It affords the corresponding product in high yield.     

Reduction of 3‐Aminoquinoline‐2,4(1H,3H)‐diones and Deamination of the Reaction Products

3‐Aminoquinoline‐2,4‐diones were stereoselectively reduced with NaBH₄ to give cis‐3‐amino‐3,4‐dihydro‐4‐hydroxyquinolin‐2(1H)‐ones. Using triphosgene (=bis(trichloromethyl) carbonate), these compounds were converted to 3,3a‐dihydrooxazolo[4,5‐c]quinoline‐2,4(5H,9bH)‐diones. The deamination of the reduction products using HNO₂ afforded mixtures of several compounds, from which 3‐alkyl/aryl‐2,3‐dihydro‐1H‐indol‐2‐ones and their 3‐hydroxy and 3‐nitro derivatives were isolated as the products of the molecular rearrangement.     

Synthesis of quinazolinophanes containing bridgehead nitrogen atoms from quinazoline‐2,4(1H, 3H)‐dione

Quinazoline‐2,4(1H,3H)‐dione (1) reacts with α,ω‐dihaloalkanes to generate three types of quinazolinophanes. When the number of carbon atoms in the dihaloalkanes is 9 , a mixture of all the three types of quinazolinophanes ( 2 ), ( 3 ) and ( 4 ) was produced; and when the number of carbon atoms in the dihaloalkane used is from 4 to 7, a mixture of only two types of quinazolinophanes ( 2 ) and ( 3 ) were produced. When the number of carbon atoms of the dihaloalkane used is odd ( 5, 7 and 9 ), the different structural types of quinazolinophanes produced were easily identifiable and distinguishable on the basis of ¹³C NMR and mass spectral data.     

One‐pot three‐component synthesis of novel 2‐(3‐nitro‐phenyl)‐quinazoline‐4‐carboxylic acid derivatives

A simple and easy synthesis of 2‐(3‐nitro‐phenyl)‐quinazoline‐4‐carboxylic acid ( 3 ) has been successfully developed through a one‐pot three‐component condensation reaction of (2‐amino‐phenyl)‐oxo‐acetic acid sodium salt ( 1 ) obtained from the hydrolysis of isatin with ammonium acetate and 3‐nitrobenzaldehyde. Some novel quinazoline‐ester derivatives 4‐7 were then obtained by the reaction between the new compound 3 and various alcohols. Then, quinazoline‐amide derivatives 10‐14 were synthesized from the reaction of various amines and 2‐(3‐nitro‐phenyl)‐quinazoline‐4‐carbonyl chloride ( 8 ), obtained by the reaction of compound 3 with SOCl₂. Finally, some novel quinazoline‐azo derivatives 17‐19 were synthesized by the coupling reaction between β‐dicarbonyl compounds and the novel amino‐quinazoline derivative compound 15 , obtained by reduction of nitro‐quinazoline derivative compound 11 . Thus, a new series of quinazoline‐4‐carboxylic acid, ester, amide, and azo derivatives was synthesized and fully characterized by ¹H NMR, ¹³C NMR, IR, and mass spectrometry analysis.     

A novel one‐pot procedure for preparation of some new condensed pyrido[2,3‐d]pyrimidine(1H,3H)‐2,4‐diones

A novel one‐pot procedure for preparation of some new condensed pyrido[2,3‐d]pyrimidine(1H,3H)‐2,4‐diones based on condensation of ninhydrin, alkyl cyanoacetate, and 6‐aminouracil derivatives has been reported. The reactions were carried out in refluxed ethanol and were completed in less than 2 h. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:16–18, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20242     

Traceless synthesis of quinazoline‐2,4‐diones by curtius rearrangement reaction using poly(ethylene glycol) as soluble polymeric support

We have developed an efficient method to synthesize various quinazoline‐2,4‐diones using poly‐(ethylene glycol) as soluble polymeric support. The procedure of this reaction included: formation of acyl azide, efficient Curtius rearrangement, nucleophlic addition with amines to produce ureas, cyclization and concurrent cleavage of the resulted six‐membered heterocycle from PEG‐support in excellent yields. This method is mild and manipulation is easy.     

Synthesis of 3‐thiocyanato‐1H,3H‐quinoline‐2,4‐diones

4‐Hydroxy‐1H‐quinolin‐2‐ones ( 1 ) react with thiocyanogen in acetic acid to the corresponding 3‐thiocyanato‐1H,3H‐quinoline‐2,4‐diones ( 2 ) in good yields. In some cases, 3‐bromo‐1H,3H‐quinoline‐2,4‐diones ( 4 ) were isolated as minor reaction products. Compounds 2 are very reactive towards nucleophiles and easily hydrolyze to the corresponding 4‐hydroxy‐1H‐quinoline‐2‐ones ( 1 ).     

Retro‐ene reactions in heterocyclic synthesis. v. a novel synthetic method for 1,3,5‐triazine‐2,4(1H,3H)‐diones

N‐t‐Butylamidines 1 on heating with diphenyl carbonate ( 2 ) at 150‐180° gave the 1,3,5‐triazine‐2,4(1H,3H)‐dione derivatives 5 . Acylation of amidines 1 and cyclocondensation of the resulting carbamates 3 gave [1,3,5,7]tetrazocine‐2,6‐dione derivatives 4 , and subsequent retro‐ene reaction and ring contraction afforded triazine derivatives 5 .     

Efficient Synthesis of (3E)‐3‐[Amino(aryl)methylidene]chromane‐2,4‐diones (=(3E)‐3‐[Amino(aryl)methylene]‐2H‐1‐benzopyran‐2,4(3H)‐diones) via a Three‐Component Reaction

The Michael‐type addition of a 4‐hydroxycoumarin (=4‐hydroxy‐2H‐1‐benzopyran‐2‐one) 1 to a β‐nitrostyrene (=(2‐nitroethenyl)benzene) 2 in the presence of AcONH₄ leads to substituted (3E)‐3‐[amino(aryl)methylidene]chroman‐2,4‐diones (=(3E)‐3‐[amino(aryl)methylene]‐2H‐1‐benzopyran‐2,4(3H)‐diones) 4 (Table 1). High yields, short reaction time, and easy workup are advantages of this novel one‐pot three‐component reaction.     

One‐pot inimer promoted ROCP synthesis of branched copolyesters using α‐hydroxy‐γ‐butyrolactone as the branching reagent

An array of branched poly(?‐caprolactone)s was successfully synthesized using an one‐pot inimer promoted ring‐opening multibranching copolymerization (ROCP) reaction. The biorenewable, commercially available yet unexploited comonomer and initiator 2‐hydroxy‐γ‐butyrolactone was chosen as the inimer to extend the use of 5‐membered lactones to branched structures and simultaneously avoiding the typical tedious work involved in the inimer preparation. Reactions were carried out both in bulk and in solution using stannous octoate (Sn(Oct)₂) as the catalyst. Polymerizations with inimer equivalents varying from 0.01 to 0.2 were conducted which resulted in polymers with a degree of branching ranging from 0.049 to 0.124. Detailed ROCP kinetics of different inimer systems were compared to illustrate the branch formation mechanism. The resulting polymer structures were confirmed by ¹H, ¹³C, and ₁H‐₁₃C HSQC NMR and SEC (RI detector and triple detectors). The thermal properties of polymers with different degree of branching were investigated by DSC, confirming the branch formation. Through this work, we have extended the current use of the non‐homopolymerizable γ‐butyrolactone to the branched polymers and thoroughly examined its behaviors in ROCP. © 2016 The Authors. Journal of Polymer Science Part A: Polymer Chemistry Published by Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1908–1918     

One‐pot synthesis of novel 2′‐deoxyuridine derivatives containing α‐aminophosphonate moieties

A series of α‐aminophosphonate derivatives of 2′‐deoxyuridine ( 8a–k ) have been prepared from 5′‐O‐tert‐butyldimethylsilyl‐3′‐amino‐2′, 3′‐dideoxyuridine in good yields. The structures of all the products were confirmed by ¹H NMR, ³¹P NMR, ³¹C NMR, and IR spectroscopy, and mass spectrometry and elemental analyses. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:230–235, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20288     

Palladium‐Catalyzed Cyclization Reaction of o‐Haloanilines,CO2 and Isocyanides: Access to Quinazoline‐2,4(1H,3H)‐diones

Quinazoline‐2,4(1H,3H)‐diones are core structural subunits frequently found in many biologically important compounds. The reaction of 2‐​aminobenzonitrile and CO₂, which was frequently studied, only provided N3‐unsubstituted quinazoline‐2,4(1H,3H)‐dione compounds. Herein we report palladium‐catalyzed cyclization reactions of o‐haloanilines, CO₂ and isocyanides to prepare N3‐substituted quinazoline‐2,4(1H,3H)‐diones. Electron‐rich o‐bromoanilines participated in the cyclization reaction using Cs₂CO₃ at high temperature, and electron‐deficient o‐bromoaniline or o‐iodoaniline substrates conducted the reaction using CsF as base to deliver corresponding quinazoline‐2,4(1H,3H)‐dione products in good yields.