Fluorine-Containing Heterocycles: XII. Fluorine-Containing Quinazolin-4-ones and Azolo[a]quinazolinone Derivatives

Abstract

Methods for the synthesis of fluorine-containing derivatives of 2-imino-1,3-diphenylquinazolin-4-one, imidazo[1,2-a]quinazolin-5-one, pyrazolo[1,5-a]quinazolin-5-one, and [1,2,4]triazolo[1,5-a]quinazolin-5-one were developed on the basis of the reaction of tetrafluorobenzoyl chloride with N,N'-diphenylguanidine and aminoazoles. * For communication XI, see [1].Fused quinazolin-4-one derivatives attract strong interest from the viewpoint of their potential biological activity. Antibacterial, antitoxoplasmatic, antihypertensive, and antihistaminic agents, phosphodiesterase inhibitors, and compounds possessing other kinds of biological activity have been revealed among quinazolin-4-one derivatives [2][3][4][5][6][7][8]. A known procedure for building up such heterocyclic systems is based on cyclization of 2-halo-substituted benzoyl chlorides with difunctional nitrogen-centered nucleophiles [4,[9][10][11]. This approach was not applied previously to the synthesis of fused imidazo-, pyrazolo[a]-and triazolo[a]-quinazolinones. There are published data only on the preparation of triazolo[a]quinazolinone derivatives via transformations of quinazolinones having a sulfanyl, hydrazino, thiosemicarbazido, or S-methylisothiosemicarbazido group in the 2-position [2,5,[12][13][14][15].In continuation of our studies on the synthesis of fused fluorine-containing nitrogen heterocycles, we have developed a general procedure for the preparation of fluorinated triazolo-, pyrazolo-, and imidazo[a]-quinazolinones by reaction of tetrafluorobenzoyl chloride with difunctional N,N'-dinucleophiles. By acylation of N,N'-diphenylguanidine (II) with tetrafluorobenzoyl chloride (I) in boiling toluene we obtained N, N'-diphenyl-N-(2,3,4,5-tetrafluorobenzoyl)-guanidine (III) (Scheme 1). The 1 H NMR spectrum of III confirmed the presence in its molecule of two

Copper‐Catalyzed One‐Pot Synthesis of Imidazo/Benzoimidazoquinazolinones by Sequential Ullmann‐Type Coupling and Intramolecular CH Amidation

“…[4,5] Although the reported methods are effective, the tedious procedures required greatly limit the construction of diverse molecules, which prevents the development of potent biologically active molecules. The transition-metal-catalyzed formation of N-heterocycles continues to be an active area of research.…”

Stable N-Heterocyclic Carbenes with the N,N′-Diarylquinazolin-4-one Backbone: Improved Synthesis, Electronic Properties, and Reactivity

“…This behavior has been observed by Lipunova and co-workers before. 8 The F/H substitution is ultimately supported by the molecular structure of 7b (Figure 4) determined by X-ray diffraction. Bond lengths and angles are in the range typically observed for organic amines with Csp 3 substituents.…”

“…A number of N -arylation reactions have been reported in the context of NHC synthesis. Lipunova, Zhang, and Thompson reported approaches to cationic carbene precursors of type B (Chart ) via nucleophilic aromatic substitutions as the crucial step for C–N bond formation. However, these protocols require harsh conditions, prolonged reaction times, and the use of transition metal additives for Ullmann-type coupling reactions.…”

Synthesis of β-functionalized ethyl polyfluoroaryl sulfides, sulfoxides, and sulfones underlain by pentafluorobenzoic acid

“…The building blocks containing acyl chloride groups, on the one hand, may be easily converted into versatile other functional groups, and on the other hand, provide a possibility of additional fusion of heterocycle and going over to tricyclic structures, also interesting for the synthesis of potential biologically active substances. The possibility of heterocyclization of polyfluorobenzoic acids chlorides was demonstrated in [30,31].…”