Quinoxalines and Quinazolines

Synthesis of b-SFs-quinoxalines was described by Beier and coworkers (12EJ02123) utihzing l,2-diamino-4-SF5-benzene (61) as a precursor for 

Beier and Pastyrikova (13M1411) reported that SFs-substituted benzi-soxazoles such as 78a (see Section 2.5) can be used as precursors for the synthesis of other SFs-substituted heterocycles, such as quinolines (see Section 2.7) as well as for a synthesis of quinazohnes. For example, reduction of ben-zisoxazole 78a using iron in aqueous AcOFl resulted in an excellent yield of ori/jo-aminobenzophenone 100. Reaction of benzophenone 100 with excess benzylamine provided the corresponding intermediate imine (not shown), which in the presence of i-BuOOH and catalytic iodine gave 

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Diprotonated pyrimidines, quinoxalines, and quinazolines (HetAr +CH=CH2) have been reported to exhibit an unusual regioelectronic effect that controls the addition reaction thus, depending on the ring position of the vinyl substituent, either conjugate or Markovnikov addition occurs on reaction with benzene, giving rise to either HetArCH2CH2Ph or HetArCH(Ph)-Me. The mode of addition has been shown to correlate well to NBO calculated charges. ... 

The dioxygenase-catalyzed oxidation of heterocyclic arenes occurs predominantly in a carbocycHc ring of the substrate [7], exemplified by the conversion by P. putida UV4 of quinoline, isoquinoline, quinoxaline, and quinazoline to the cw-diol products shown in Fig. 35 [57], but a recent report of the formation of cw-diol 46 (Fig. 36) by oxidation of 2-chloroquinoline by P putida [58] suggests the possibility that furtber products of this t) may become available as new chiral starting materials for synthetic applications. 

Figure 35 Oxidations of quinoline, isoquinoline, quinoxaline, and quinazoline by P. putida.

The compounds to be discussed are the quinolines, isoquinolines, cinnolines, quinazolines, quinoxalines, and phthalazines. Once again, this is a family of compounds for which much qualitative, but little quantitative information is available. 

Isolated and benzo-fused diazine rings are key structural elements in many natural and synthetic compounds of current interest. This contribution relates highlights from many of the studies on the diazines pyridazine, pyrimidine, pyrazine, and their benzo-fused derivatives cinnoline, phthalazine, quinazoline, quinoxaline, and phenazine published in English in the journal literature during 1996, as covered by Chem. Abstr. through volume 126, issue 5. 

Syntheses of fused mesoionic heterocycles such as [l,2,3]triazolo[l,5-a]-quinoline, -quinazoline, -quinoxaline, and -benzotriazine derivatives have been described <02T3185>. Cyclizations of alkyl 2-benzoylamino-(4,5-dicyano-1 //-1,2,3-triazol-1 -yl)propenoates gave [1,2,3]triazolo[l, 5-a]pyrazines <02H(56)353>. Reaction of triethyl N-( 1 -ethy 1-2-methy 1-4-nitro-l//-imidazol-5-yl)phosphorimidate with aryl isocyanates provided a route to 2-aryI-2//,4//-imidazo[4,5-fif][l,2,3]triazoles <02JCS(P 1)1968>. 2-(A,A-Diphenylamino)-4-hydrazino-6-... 

The reactivities of several azanaphthalene anion-radicals, alter polaro-graphic generation, are discussed by van der Meer.122,123 This includes the radicals of quinazoline and cinnoline whose ESR spectra do not appear to have been reported. The stability of carbon-halogen bonds in various azine anion-radicals, including quinoxaline and quinoline, has been discussed, as has the reactivity of quinoline anions toward alkyl halides.92,182 In the latter reaction alkylation occurs at the 1,2- and 2,4-positions. Heteroarylation of a range of electron-rich substrates by azine anion-radicals has been reported.183 No mechanism is implied in the available abstract, but the apparent electrophilicity on the part of the azine anions is surprising. 

Nitrogen Heterocycles.- Reactions of iminophosphoranes have been used to prepare a wide range of heterocycles. Examples of compounds prepared by intramolecular aza-Wittig reactions include 3,4-dihydroquinazolines (191) and quinazolines (192), quinazoline derivatives (e.g. 193),pyrrolo( 1,2-a)quinoxalines (194), indolo[3,2-clquinolines (195), and indolo[l,2-c]quinazolines (196),"8 imidazolinones (197),"9 quinazolinones (198),"9, 120 pyrido[2,3-d]pyrimidine derivatives (199), 21 and 4,5-dihydropyrazolo(3,4-d]pyrimidine derivatives (200). 22 Tributyl(cyclohepta-1,3,5-trienylimino)phosphorane (201), prepared by thermal isomerization of the 2,4,6-derivative, reacts with a,p-unsaturated ketones to give 9H-cyclohepta[b]pyridine derivatives (202). 23 a synthesis of (2,4)pyridinophanes (204) by the reaction of N-vinyliminophosphoranes (203) with a,P-unsaturated ketones has been reported. 24... 

The fluorescence and phosphorescence of quinazoline, 6-chloro-4-phenyl-and 6-chloro-l-methyl-4-phenylquinazolin-2(lH)-one were recorded in ethanol containing 1% of concentrated sulfuric acid. The luminescence of these compounds on thin-layer chromatography (TLC) plates saturated with ethanol was reported. 4-Morpholino- and 4-piperidino-6-methoxy-2-phenyl-quinazoline also have luminescent properties, and the ultraviolet fluorescence in the crystals and in hexane or benzene solution was discussed. The time and wavelength resolved emission from quinazoline vapor at low pressures was studied with a pulsed frequency double-dye laser and were compared with those of quinoxaline and cinnoline. ... 

The polarographic reduction of quinoxaline and its derivatives has been studied by a number of workers. Half-wave electrode potentials are pH dependent and over the pH range of 1 to 10, Ei has been reported to vary from —0.254 to -0.863 The half-wave electrode potential in anhydrous dimethylformamide is — l.bOV for quinoxaline, —1.06 V for cinnoline, —1.41V for phthalazine, and —1.22 V for quinazoline. The benzodiazines are more easily reduced than the corresponding diazines, thus pyrazine has a half-wave electrode potential of -1.57V. Pyridine with a half-wave potential of —2.15 V is still more difficult to reduce. The reversible reduction potential of quinoxaline as determined by cyclic voltammetry is -1.097 V. The observed energy differences between azine and radical anion are well correlated with the results of CNDO and SCF iT-electron calculations. 

Polyazines are polymers with six-membered heteroaromatic rings in the main chain, whereby these rings contain at least one tertiary nitrogen. Compounds which can be conceived by partial hydrogenation of the hetero rings are related to these. Of the very great number of possible different compounds, those with quinoxaline (I), quinazoline dione (II), triazine (III), melamine (IV), and isocyanurate (V) groups have found use in industry ... 

By far the main part of the studies involves aromatic azides, however. These are the object of unrelenting interest. During the period considered, some reference works have been published, including a wide-scope review on the detection and role of intermediates, another one on pyr-idineazides and an account on the relation between nitrenes, carbenes, diradicals and zwitterions in the thermal and photochemical reaction operating in the decomposition of aromatic and heterocyclic azides. A recent, nice example illustrates the variety of paths followed. Thus, tetra-zolo[l,5-a]quinoxaline and tetrazolo[5.1-c]quinazoline equilibrate thermally with the corresponding azides. 

Pyridazines, Cinnolines, and Phthalazines Pyrimidines and Quinazolines Pyrazines, Quinoxalines, and Phenazines Purines, Pteridines, and Related Systems Other Systems with Two Nitrogen Atoms Oxazines, Thiazines, and their Benzo-derivatives... 

When two fused six-membered rings (naphthalene analogues) are considered, possibilities become very numerous, partly on account of the reduced symmetry of naphthalene, compared with benzene, and also because of the larger number of positions available for substitution. Thus, there are two monoazanaphthalenes, quinoline (8) and isoquinoline (9), four benzodiazines [cinnoline (10), phthalazine (11), quinazoline (12) and quinoxaline(13)], with the two nitrogen atoms in the same ring, and six naphthyridines (e.g. (14), named and... 

Unlike the other diazanaphthalenes (i.e., naphthyridines/ cinno-line, phthalazinc/ and quinoxaline), quinazoline shows abnormal behavior when converted into its cation. This anomaly was first discovered by Albert et who noticed that 4-methylquinazoline was a w eaker base (tenfold) than quinazoline (see Table I). This was... 

Pyrimidine-2-thiones (e.g., 206) have been shown to exist as such by comparison of their ultraviolet spectra with those of both alkylated forms.The ultraviolet spectra of pyrimidine-4-thiones are different from those of 4-alkylthiopyrimidines, therefore the former compounds exist as 207 and/or 208, the predominant form not having been determined. Infrared spectral evidence suggests that quinazoline-4-thione exists as 209 and/or 210 and has been used recently to demonstrate the thione formulation for pyrimidine-2- and -4-thione, pyrazine-2-thione, and quinoxaline-2-thione. In view of this work, the report that X-ray crystallographic evidence supports the mer-... 

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