Boron tribromide mediated debenzylation of benzylamino and benzyloxy groups

The treatment of 2(or 4)-benzylamino substituted quinolines, 9-benzylaminoacridine, 2-benzylaminopyridine, a 4-benzyloxyquinoline, and an N-benzyloxyamidine with BBr₃ yields the corresponding amino or hydroxy substituted compounds. The scope and limitations of this novel reaction are discussed.     

Selective debenzylation of benzyl esters by silica-supported sodium hydrogen sulphate

A new debenzylation of benzyl esters by silica-supported sodium hydrogen sulfate is described. The debenzylation could be achieved selectively and efficiently in good to excellent yields without affecting sensitive functional groups such as nitro, unsaturated bonds, and ethyl ester.     

A new DMAP-catalyzed and microwave-assisted approach for introducing heteroarylamino substituents at position-4 of the quinazoline ring

We report herein a new methodology for synthesizing quinazoline derivatives bearing a heteroarylamino moiety at position-4 of the quinazoline ring. As an alternative to the Buchwald–Hartwig cross-coupling reaction, which appears, until now, as the only efficient way to react 4-chloroquinazolines with numerous amino nitrogen-containing heterocycles displaying poor nucleophilicity, we developed a DMAP-catalyzed reaction involving microwave irradiation. Optimization of the reaction conditions led to the use of 30 mol % of DMAP in toluene, using a monomode microwave reactor and sealed vials. Moreover, the S_NAr reaction intermediate salt was isolated and fully characterized. Finally, the procedure was extended to two different 2-substituted-quinazoline series and also to various anilines, demonstrating that this approach was a general efficient way to access to such 4-substituted quinazoline scaffolds of high pharmaceutical interest.     

Selective debenzylation of aromatic benzyl ethers by silica-supported sodium hydrogen sulfate

A new debenzylation of aromatic benzyl ethers by silica-supported sodium hydrogen sulfate is described. The process proceeds selectively and efficiently in good to excellent yields without affecting sensitive functional groups such as nitro, COOMe, aldehyde, ketone, and tosyl.     

Three-point variation of a gefinitib quinazoline core

A versatile four-step process describing the controlled systematic variation of a key quinazoline core from one intermediate is highlighted.     

Specific features of the reactions of quinazoline and its 4-hydroxy and 4-chloro substituted derivatives with C-nucleophiles

Reactions of quinazoline 1 with indole, pyrogallol and 1-phenyl-3-methylpyrazol-5-one in the presence of acid led to C-4 adducts 2, 3 and 5. Adduct 4 is formed by heating 1 with 1,3-dimethylbarbituric acid without acid catalysis. 1-Phenyl-3-methylpyrazol-5-one reacts with 1 without acid catalysis to form dipyrazolylmethane 6. 4-Chloroquinazoline 8 reacts with 1-phenyl-3-methylpyrazol-5-one to form 4-(1-phenyl-3-methyl-5-oxopyrazol-4-yl) quinazoline 9 and dipyrazolylmethane 6. Heating 8 with 2-methylindole leads to the formation of 4-(2-methylindol-3-yl) quinazoline 10 and tris(2-methylindol-3-yl)methane 11.     

Formation of new organoselenium heterocycles and ring reduction of 10-membered heterocycles into seven-membered heterocycles

Reacting 2,4-bis(phenyl)-1,3-diselenadiphosphetane-2,4-diselenide [{PhP(Se)(μ-Se)}₂], Woollins’ reagent, with an equivalent of aromatic diol in refluxing toluene afforded 10-membered phosphorus-selenium heterocycles 1 and 2 with an O-P(Se)-Se-Se-P(Se)-O linkage. Two equivalents of aromatic diol and Woollins’ reagent in refluxing toluene gave seven-membered phosphorus-selenium heterocycles 3 and 4 with an O-P(Se)-O linkage together with 10-membered phosphorus-selenium heterocycles 1 and 2. It was also found that the diphosphorus species O-P(Se)-Se-Se-P(Se)-O rings 1 and 2 could be readily ring contracted into the monophosphorus rings 3 and 4 in almost quantitative yields via further reaction with another equivalent of corresponding aromatic diol. One representative X-ray structure is reported.     

Solid-phase synthesis of benzazoles,quinazolines, and quinazolinones using an alkoxyamine linker

An alkoxyamine linker was applied for the solid-phase synthesis of benzazoles, quinazolines, and quinazolinones. Aromatic aldehydes were anchored by aldoxime linkage. After some reactions on a solid support, the products were cleaved with paraformaldehyde under the acidic conditions to afford the corresponding aldehydes, which were subsequently subjected to oxidative coupling with 2-substituted anilines under air atmosphere to give the desired compounds.     

A microwave improvement in the synthesis of the quinazoline scaffold

A rapid and efficient microwave-assisted protocol is described that greatly improves a recent synthetic method developed for quinazoline synthesis. The synthetic protocol is based on the use of cycles of microwave irradiation. The optimization process is reported and the experimental results are compared with those of the conventional synthetic route.     

Stable deep blue organic light emitting diodes with CIE of y < 0.10 based on quinazoline and carbazole units

Achieving stable deep blue organic light emitting diodes (OLEDs) with narrow full width at half maximum (FWHM) and color gamut in the range of the commission International de L’Eclairage (CIE) of y ≤ 0.10 is still challenging in display and lighting applications. In this investigation, three donor-acceptor (D-A) deep-blue emitters were designed and synthesized via integrating asymmetric quinazoline (PQ) acceptor with weak donating carbazole (Cz) donor. The effect of the position and number of Cz group in PQ unit are investigated, which is also first examples for systematic research about the effect of different position of asymmetric PQ as acceptor on deep OLEDs. Their bandgaps of 3.12∼3.19 eV and the singlet state energy levels of 3.12∼3.19 eV were found to be sufficiently large to achieve deep blue light. As expected, these emitters-based OLEDs exhibit deep blue emission with the maximum wavelength ≤ 450 nm and narrow FWHM ≈ 60 nm. Especially, a CIE of y = 0.080 was achieved for 4PQ-Cz-based OLED. Significantly, the deep blue electroluminescence (EL) spectra of these three emitters-based OLEDs are very stable and the corresponding CIE coordinates deviation (ΔCIE (x, y)) can be negligible under the applied voltage ranging from 5 V to 9 V.     

The synthesis of 2-amino-4(3H)-quinazolinones and related heterocycles via a mild electrocyclization of aryl guanidines

A new method for the preparation of 2-amino-4(3H)-quinazolinones and similar fused heterocycles is described. Simply warming a mixture of an aryl guanidine and carbonyl diimidazole in acetonitrile results in formation of a putative N-amidinoisocyanate intermediate which undergoes a 6π-electron electrocyclic reaction with the aryl ring to generate the quinazolinone ring system. The mild conditions are compatible with a variety of functional groups, and the reaction is shown to be successful on multigram scale.     

Fused ring aziridines as a facile entry into triazole fused tricyclic and bicyclic heterocycles

The intramolecular dipolar cycloaddition of an azide with an alkyne has provided a useful entry into triazole fused tricyclic heterocycles containing both the triazole ring and the oxazolidin-2-one ring system. The requisite azido-alkynes have been prepared via a two-step sequence from fused ring aziridines. A series of 6-12 membered rings containing both the oxazolidinone and triazole rings have been prepared. These ring systems have been designed as conformationally restrained analogs of RNA-binding oxazolidinones.     

Investigation of the oxidative cleavage of butyl rubber by selective catalysis

Selective oxidizing cleavage of carbon-carbon double bonds of unsaturated polymers leads to bifunctional oligomers. It is shown, using ruthenium tetroxide in catalytic amount in conjunction with a peracid as co-oxidizing agent, that efficient cleavage of butyl rubber double bonds can be obtained without side reaction. The procedure can be used for analytical as well as for synthetic purpose.     

Low temperature electrochemistry as a mechanistic probe for the partial reduction of heterocycles

The reduction of a series of electron deficient aromatic heterocycles has been examined using electrochemical techniques: the analysis was performed under anhydrous conditions at low temperature, so as to mimic typical synthetic reducing conditions.     

Synthesis,characterization, crystal structure,and DNA-binding of ruthenium(II) complexes of heterocyclic nitrogen ligands resulting from a benzimidazole-based quinazoline derivative

The reaction of cis-[RuCl₂(dmso)₄] with [6-(2-pyridinyl)-5,6-dihydrobenzimidazo[1,2-c]quinazoline] (L) afforded in pure form a blue ruthenium(II) complex, [Ru(L¹)₂] (1), where the original L changed to [2-(1H-benzoimidazol-2-yl)-phenyl]-pyridin-2-ylmethylene-amine (HL¹ ). Treatment of RuCl₃?·?3H₂O with L in dry tetrahydrofuran in inert atmosphere led to a green ruthenium(II) complex, trans-[RuCl₂(L²)₂] (2), where L was oxidized in situ to the neutral species 6-pyridin-yl-benzo[4,5]imidazo[1,2-c]quinazoline (L² ). Complex 2 was also obtained from the reaction of RuCl₃?·?3H₂O with L² in dry ethanol. Complexes 1 and 2 have been characterized by physico-chemical and spectroscopic tools, and 1 has been structurally characterized by single-crystal X-ray crystallography. The electrochemical behavior of the complexes shows the Ru(III)/Ru(II) couple at different potentials with quasi-reversible voltammograms. The interaction of these complexes with calf thymus DNA by using absorption and emission spectral studies allowed determination of the binding constant K _b and the linear Stern–Volmer quenching constant K _SV.     

Biomimetic Asymmetric Reduction of Quinazolinones with Chiral and Regenerable NAD(P)H Models

A facile approach to chiral dihydroquinazolinone derivatives has been described via biomimetic asymmetric reduction of quinazolinones with chiral and regenerable NAD(P)H models. The utility of this method was demonstrated by a concise synthesis of the bromodomain protein divalent inhibitor.     

Investigation of nitrogen- and sulfur-containing heterocycles

The chlorine atom in 4-chloro-6,7-dihydro-8H-pyrimido[5,4-b][1,4-oxazin-7-ones is replaced by amine residues and mercapto and methoxy groups and can also be removed in the presence of Pd/C. Pyrimidooxazin-7-ones are alkylated in the 8 position, while, depending on the conditions, the 4-mercapto derivatives are alkylated either at the mercapto group or simultaneously at the mercapto group and in the 8 position.     

Investigation of nitrogen- and sulfur-containing heterocycles

The reaction of 5-amino-4-chloro- and -4-methoxy-6~mercaptopyrimidines with 4-methoxy-, 4-amino-, and 2,4-diethoxyphenacyl chlorides has yielded 5-amino-4-chloro- and -4-methoxy-6-phenacylthiopyrimidines. The reaction of 2, 5-diamino-4-methyl-6-mercaptopyrimidine with 4-methoxyphenacyl chloride has yielded 2-amino-6-hydroxy-6-(4-methoxyphenyl)-4-methyl-5, 6-dihydropyrimido[4, 5-b]-1,4-thiazine, and that with 4-aminophenacyl chloride has yielded the corresponding 7H-pyrimido[4, 5-b]-1,4-thiazine.For part IV, see [1].     

Investigation of nitrogen- and sulfur-containing heterocycles

The reaction of (3-amino-6-chloro-2-pyridylmercapto)oxalacetic ester with ammonia, benzylamine, morpholine, and piperidine yielded amides, while the reaction of the ester with hydrazine hydrate gave [2-(ethoxycarbonylmethylthio)-3-pyridyl]oxamic acid hydrazide. The benzylamide and morpholide of this acid were obtained by treatment of 2-chloro-6-hydroxy-6,7-di(ethoxycarbonyl)dihydropyridothiazine with the appropriate amines. The reaction of 2-mercapto-3-amino-6-chloropyridine with chlorooxalacetic ester in the presence of alkali yielded potassium [2-(ethoxycarbonylmethylthio)-3-pyridyl]oxamate.See [1] for communication XXI.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1502–1505, November, 1971.     

Investigation of nitrogen- and sulfur-containing heterocycles

Catalytic hydrogenation of cyanoacetyl-, -cyanopropionyl-, and cyanobutyrylurethanes in aqueous media in the presence of Raney nickel and the hydrochlorides of o- and p-toluidines, o- and p-alkoxyphenylamines, p-aminoacetophenone, ethyl p-aminobenzoate, and ethyl p-aminophenylacetate, and in the presence of sodium p-aminosalicylate and acetic acid gave the corresponding -arylaminoacryloyl(or -alkylacryloyl)urethanes, which were converted, without isolation in the pure state, to 1-aryl- and 1-aryl-5-alkyluracils by heating in dilute alkali solutions.See [1] for communication XXV.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1280–1282, September, 1974.