Quinazoline N-oxides

The use of oximes as nucleophiles can be quite perplexing in view of the fact that nitrogen or oxygen may react. Alkylation of hydroxylamines can therefore be a very complex process which is largely dependent on the steric factors associated with the educts. Reproducible and predictable results are obtained in intramolecular reactions between oximes and electrophilic carbon atoms. Amides, halides, nitriles, and ketones have been used as electrophiles, and various heterocycles such as quinazoline N-oxide, benzodiayepines, and isoxazoles have been obtained in excellent yields under appropriate reaction conditions. 

Dimethylamino)-2,3,4,4a-tetrahydro-l//-pyrido[l,2-a]quinazoline N-oxide (181) converted to l,2,3,4-tetrahydro-6//-pyrido[2,l-a]quinazolin-6-one (140) by the action of light via 182 and the elimination of dimethyl-amine [92ZN(B)1333],... 

Then, studies on the chemistry of these compounds revealed that the structures of the presumed benzoheptoxdiazines(20) had been erroneously assigned, and that they were in fact quinazoline N-oxides (22). The reaction products were then reassigned structure (23), rather than structure (21). 

At this point the demands of other projects forced the abandonment of this synthetic work, and that would have been the end of the story but for a remarkable stroke of good fortune almost 2 years later. Duringa lab cleanup in 1957 Sternbach s assistant, Earl Reeder, came across a small quantity of a crystalline compound that had been formed from the reaction of the quinazoline N-oxide (24) with methylamine in 1955, but had not been sent for biological testing. To tie up loose ends the... 

These compounds show the typical reactions of heterocyclic N-oxides and their structure was proved by methylation which takes place on N-1. Quinazoline 3-oxide is soluble in water and melts at 155°C. It has basic properties and its pKa value in water is 1.47. ... 

Quaternary salt formation in 4-quinazoline 3-oxide and its 4-amino and 4-methyl derivatives has been studied by Adachi. These N-oxides, prepared by reaction of the simple quinazoline with hydroxylamine, react with ethyl iodide at N-1, although only in the case of the 4-amino derivative could the ethiodide be purified. The salts are degraded by alkali yielding derivatives of ethylaniline [Eq. (4)]. 

Heterocyclic compounds that have water bound covalently across a C=N bond behave as secondary alcohols. When subjected to very gentle oxidative conditions, they are converted into the corresponding 0x0 compounds. Potassium permanganate in 0. IN sodium hydroxide at room temperature has been used to oxidize 2- and 6-hydroxypteri-dine to 2,4- and 6,7-dihydroxypteridine, respectively. In contrast, 4-hydroxypteridine was not attacked by this reagent even at 100°. Hydrogen peroxide in acid solution was used to oxidize quinazoline quinazoline 3-oxide 1,3,5-, 1,3,7-, and 1,3,8-triazanaphthalene and pteridine (which hydrate across the 3,4-double bond in the... 

Covalent hydration has been demonstrated in the following families of compounds 1,6-naphthyridines, quinazolines, quinazoline. 3-oxides, four families of l,3,x-triazanapththalenes, both l,4,x-triazanaphthalenes, pteridines and some other tetraazanaphthalenes, and 8-azapurines these compounds are discussed in that order. In general, for any particular compound (e.g. 6-hydroxypteridine) the highest ratio of the hydrated to the anhydrous species follows the order cation > neutral species > anion. In some cases, however, anion formation is possible only when the species are hydrated, e.g. pteridine cf. 21 and N-methyl-hydroxypteridines (Section III, E, 1, d). Table V in ref. 10 should be consulted for the extent of hydration in the substances discussed here. 

H-l,4-Benzodiazepin 7-Chlor-2-hydroxy-5-(2-thienyl)- -4-oxid E9d, 401 (2-CH2Cl — 4-Het — 6-Br — quinazolin — 3-oxid/NaOH) lOH-Phenothiazine 3-Chlor-9-methyl-l-nitro- E9a, 536 [6-SH —2-R —anilin 4- 3,5-Cl2 — 1,2-(N02)2 — benzene] Thioformimidsaure N-(4-Nitro-phenyl)- -chlorid-phenylester E4, 548 (R —NH —CHO + SOCl2/ R—SCI)... 

Ref. 45, l4N spectra, originally referred to internal CH3N02, recalculated with solvent shifts for CH3N02 from Table VII the screening of quinazoline I-N-oxide, a compound hereto unknown, is calculated from the additivity rules for the nitrogen screening of azine N-oxides. 

The chemical shifts of quinazoline 1-oxide, 3-oxide, and 1,3-dioxide were reported and were correlated with 7c-charge densities at the N-oxide nitrogen atom calculated by the MO-SCF-PPP method. 

The oximes of aminoaldehydes yield the N-3 oxides of (fused) pyrimidines. Thus, several methoxy derivatives of trans-2-aminobenzaldoximes, heated at 140°C in triethyl orthoformate, gave good yields of the corresponding methoxy derivatives of quinazoline 3-oxide (88). Ultraviolet light rearranged these products to quinazolin-4-ones. (The cis forms of these aldehydes produced only benzoxadiazepines.) The same aldehydes, heated in decalin with... 

The past year has seen the publication of Comprehensive Organic Chemistry, one volume of which contains much information on the six-membered ring systems to be reviewed in this article a monograph on the chemistry of condensed pyrazines has also appeared. Reviews on 1,4-thiazines, l,3-benzothiazines," pyridazines, benzo[c]cinnolines, quinazolines, purines, pyrrolo[3,2-c]quino-lines, 1,10-phenanthroline and its complexes, polyaza-phenanthrenes, and 1,9- and 1,10-diaza-anthracenes have been published. Other specialist reviews are devoted to catalytic methods of obtaining pyridine bases pyridine N-oxides the stereochemistry of quinolizines, indolizines, and pyrrolizines benzothiazinone dioxides 2-quinazolones and their cyclic homologues (e.g. 

Treatment of the quinazoline 3-oxide (142) with hydrazine leads via fission of the N(3)—C(4) bond to the formation of the 2-hydroxyamino-l,4,5-benzotriazocine (29), as illustrated in Scheme 30 <73CPB2375>. A similar ring expansion was reported in the formation of 4,1,5-benzoxadiazocin-2-one oxime (143) by treatment of the same starting material with hydroxylamine <70JHC1429>. 

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