Nitrene, quinazolin

A photolytic study with a 5-azidotetrazole derivative also led to the formation of a tetrazolo[l,5-/z]quinazoline compound, although the yield was fairly low. Araki et al. published findings that irradiation of 110 in aqueous medium resulted in formation of the mesoionic enolate 112 in 8% yield <2000JHC1129> (Scheme 20). The authors concluded that the formation of the tricyclic structure can be rationalized by an intramolecular insertion of the triplet nitrene formed from 110 to a C-H bond of an ortho-methyl group to give at first intermediate 111, which was converted under the applied reaction conditions to produce 112. 

Oxidation of the 1-aminoquinazolinones (44) with lead tetraacetate culminated in the intramolecular addition of the resulting N-nitrene intermediate to the triple bond to give the pyrrolo[2, l-b]quinazoline (45) [85CC544 86JCS(P1)1215]. The pyrrole ring of 47 was also formed by cyclization of 2-methyl-3-phenacylquinazolin-4-one (46) with dilute aqueous alkali followed by fusion (86T4481). 

Synthesis of pyrido[ 1,2-bJquinazolines through formation of the azole ring from properly substituted quinazoline precursors is also known (61AP556). Thus, the cyclodehydrobromination of the 2-(4-bromo-butyl)quinazolin-4-one (445) with alkali was claimed to give only the linearly annulated 1,2,3,4-tetrahydropyrido[ 1,2-6]quinazolin-4-ones (446) (61AP556). Oxidation of the 3-amino-2-(butyn-l-yl)quinazolin-4-ones (447) with lead tetraacetate led to intramolecular addition of the produced /V-nitrene intermediate to the triple bond to give 449 [86JC S(P 1) 1215]. 

Argon matrix photolysis of tetrazolo[l,5-a]quinazoline/2-azidoquinazoline (96) gave a nitrene (97) which was observable by ESR, UV, and IR spectroscopy.81 The reactions of this nitrene were characterized and included fragmentation to radical species (98), rearrangement to cycloheptatetraene (99), and ring opening to a new nitrene (100). 

The 1,3-diazines have also been prepared by a reaction of enamines and S, S -dimethyl-A (A arylbenzimidoyl)sulfimides 360 in boiling tetraline220,221. The mechanism of the ring formation probably involves a thermal cleavage of the imidoylsulfimides 360 into imidoylnitrenes 361 and dimethyl sulfide. The nitrene can then react with the enamine to give an aziridine intermediate 362 which rearranges to a 3,4-dihydroquinazoline 363. Subsequent elimination of amine yields the quinazoline 364220. 

Furthermore, 6-chloro-l,3-dimethyl-5-vinyluracils are readily transformed into the 6-azido derivatives. UV irradiation in acetone leads, under denitrogenation, to nitrenes, which insert into the sidechain to give pyr-rolo[2,3-acetone solvent to afford, under 6ir-electron cyclization, benzo[/z]quinazoline-diones (85UP1). 

Alkyl-2-phenylquinazolines 9 are readily available by reaction of 5,S -dimethyl-A-(A-aryl-benzimidoyl)sulfimides 7 with enamines 8 in refluxing Tetralin (1,2,3,4-tetrahydronaphthalene). The mechanism of quinazoline ring formation probably involves a thermal cleavage of the imidoylsulfimides into imidoyl nitrenes, nitrene addition to the enamine double bond and subsequent rearrangement of the aziridine intermediate thus formed to the final product 9. Small amounts (10-15%) of 4-unsubstituted quinazolines 10 are obtained as byproducts. The formation of these byproducts involves a known intramolecular rearrangement of the benz-imidoylsulfimides employed. ... 

Trifluoromethyl)quinazolin-4(3//)-one (6) is formed quantitatively from a-azido-a-phenyl-/1-trifluoroethyl isocyanate (3) via a nitrene intermediate 4 which undergoes rearrangement to a-(A -phenylimino)- 8-trifluoroethyl isocyanate (5) followed by cyclization to 6 (cf. p 58). °... 

Preparation.—Direct Insertion. The oxidation of 2,4-dinitrobenzenesuiphen-amide with [Pb(OAc)4] in CH2CI2 generates a nitrene which, in the presence of alkenes, gives aziridines. With /ra 5-l-phenylpropene, [200 R = 2,4-(N02)2C6H3] (64%) was formed, which could be reduced with NaBH4 to (200 R = H) (56%). Nitrenes produced by the oxidation of A(-aminophthalimide or 3-amino-2-methyl-4-quinazoline with [Pb(OAc)4] yield 6-azabicyclo[3.1.0]-hexanes, e.g. (201), in the presence of variously substituted cyclopentenes. 

A novel and interesting route to 2-aryl-4-oxo-benzo[c/][l,3]oxazines (392) is furnished by the thermal reaction of o-azidobenzoic acid with benzaldehydes (Scheme 151). The reaction is thought to proceed via a novel type of cycloadduct (391) rather than via a nitrene, as the temperature required ca. 110 °C) is significantly below that at which the azide decomposes (145 C). Yields are good, the reaction works with electron-rich and electron-poor aldehydes, and ort o-azidobenzamides react similarly, giving quinazoline derivatives (see p. 256)."° ... 

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. 

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