Quinazoline nitro

Little is known quantitatively about substituent effects in the nitration of derivatives of azanaphthalenes. In preparative experiments 4-hydroxy-quinoline, -cinnoline, and -quinazoline give the 6- and 8-nitro compounds, but with nitric acid alone 4-hydroxyquinoline and 2,4-di-hydroxyquinoline react at With nitric acid, 4-hydroxycinnoline... 

Quinazoline-2,4( 1 H,3H)-dione, 7-nitro-synthesis, 3, 110 Quinazolihediones mass spectra, 2, 22 polymers, 1, 298 Quinazoline-2,4( 1 H,3 H)-diones synthesis, 3, 106 O-trimethylsilylation, 3, 91 Quiriazolines addition reactions, 3, 73... 

The stabilizing influence in the hydrated cation is the amidinium resonance. If a solution of the cation is neutralized, a short-lived hydrated neutral molecule (4) (half-life 9 sec at pH 10) is obtained with an ultraviolet spectrum similar to that of the hydrated cation but shifted to longer wavelengths (5 m/ ). Supporting evidence can be derived from the anhydrous nature of the cation of 4-nitroiso-quinoline (pK 1.35), in which the nitro group has a similar electronic influence to that of the ring nitrogen atom N-I in quinazoline and where amidinium resonance is not possible. 

Of greater versatility is an extension of Albert and Royer s acridine synthesis. The first successful use of this in the quinazoline series was for the removal of the chlorine atom in 2-chloro-4-phenylquin-azoline, although it had been used previously to prepare 8-nitro-6-methoxyquinazoline in very poor yield. The 4-chloroquinazoline is converted to its 4-(A -toluene-p-sulfonylhydrazino) quinazoline hydrochloride derivative which is decomposed with alkali in aqueous ethylene glycol at lOO C (Scheme 13). The yields are high (60-70%) when R is Me, Cl, OMe but low when R is NO2, and in the latter case it is preferable to use dilute sodium carbonate as the base. This reaction is unsatisfactory if the unsubstituted pyrimidine ring is unstable towards alkali, as in 1,3,8-triazanaphthalene where the pyrimi-... 

Hydroxy- and 8-nitro-4-chloroquinazolines have been incorporated into the nucleotide of vitamin B12. These quinazoline-containing vitamin analogs stimulated the growth of cobalamine requiring cultures. ... 

Quinazolin-4-one and its 6-nitro derivative were both shown to exist predominantly in the o-quinonoid form (cf. 96) by ultraviolet spectral comparisons of the parent compound with the 0-methyl derivative and with the two A -methyl analogs, The existence of quinazolin-2- and -4-ones in an oxo-type structure was demonstrated in 1952 by using solid-state infrared data and later confirmed by... 

Morley and Simpson prepared quaternary salts from 4-phenoxy-quinazoline and 6- and 7-nitro-derivatives of 4-anilino- and 4-acet-amido-quinazohne. 6-Nitro-4-aminoquinazoline, however, could not be quatemized under the fairly mild conditions used by the... 

Reaction of 2-aminopyridine and 2,3,4,5,6-pentafluoro- and 5-nitro-2-fluorobenzoyl chloride in CH2CI2 in the presence of (/-Pr)2EtN at room temperature afforded 1,2,3,4-tetrafluoro- and 8-nitro-l l//-pyrido[2,l-6]-quinazolin-11-ones, respectively (01TL1851). 

Nitration of 3,4-dimethoxypropiophenone (91) affords the nitro derivative 92, and catalytic reduction leads to the aminoketone (93). This is then converted to the corresponding formamide by means of formic-acetic anhydride. Treatment with ammonia Completes Construction of the quinazoline ring. 

The pyridazine ring of 111 is formed from [4+2] atom fragments in the cyclization of 3-amino-2-chloromethyl-quinazolin-4-one with activated acrylthioamides. The saturated pyridazine ring of 111 aromatized spontaneously to give 112 (Equation 12). Reaction with io-nitrostyrene yielded the 3-nitro analogue of 112 <2003MOL401>. 

CPB1073, 2003CPB1109>, and 4-amino-7-fluoro-6-nitro-quinazolines 156 <19%JME918, 2005JME5337> have all undergone amination reaction with aliphatic amines. 

Alkoxylation in the benzene ring of quinazolines and quinazolinones is readily achieved in the presence of an ortho-nitro group, and even in the absence of a nitro group, displacement of fluorine is still quite facile. Examples of haloquinazolines to have been alkoxylated include 5-chloro-8-nitro-4(3//)-quinazolinone 187 <2005BMC5613>, 7-chloro-6-nitro-4(377)-quinazolinone 188 <1996JME267>, 4-arylamino-7-fluoro-6-nitroquinazolines 189... 

Several similar ring-closing strategies have also been published, such as the in situ reduction of the nitro group in 107 followed by condensation of the resulting amino group with the acetyl carbonyl to produce quinazoline 108 in 46% yield <99H2193>. The acetyl transfer product 109 was also produced (32%). 

H NMR spectra of 117/-pyrido[2,l-b]quinazolin-l 1 -one (27) and its 2-amino, 3-amino, 2-methoxy, 8-nitro, 9-methyl, and 3-chloro derivatives were measured using DMSO-d6 (83MI3). 

Amino-6,7,8,9-tetrahydro-l l//-pyrido[2,l -b]quinazolin-l 1 -one was prepared by catalytic hydrogenation of the 3-nitro derivative over Raney nickel in ethanol [91KFZ(11)28]. 

I h, then room temperature gave the 2-nitro derivative [85IJC(B)336]. Bromination of 1,2,3,4,6,7,8,9-octahydro-l 17/-pyrido[2,l -6]quinazolin-... 

Vielsmeier-Haack formylation of 2-nitro-6,7,8,9-tetrahydro-l 1 //-pyrido-[2,l-b]quinazolin-l 1-one (120, R = 2-N02) (84JHC219) and 1,2,3,4,6,7,8,9-octahydro-ll//-pyrido[2,l-6]quinazolin-l 1-one and its 8- and 9-methyl derivatives (87JHC1045) with a mixture of phosphoryl chloride and dimethyl-formamide at 15-20°C gave 6-formyl-2-nitro-5,7,8,9-tetrahydro- (122) and 6-formyl-l,2,3,4,5,7,8,9-octahydro-ll//-pyrido[2,l-b]quinazolin-ll-ones. 

Cyclization of 2-[(3-acetamido-2-pyridyl)amino]benzoic acid (202) in 0.5 N sulfuric acid gave 6-amino-ll//-pyrido[2,l-h]quinazolin-ll-one (203) (84MI3). 2-[(6-Methyl-, 5-nitro-, and 3-nitro-2-pyridyl)amino]benzoic acids were cyclized into 9-methyl, 8-nitro, and 6-nitro-l 1 //-pyrido[2,l -ujquina-zolin-ll-ones, respectively, by the action of 80% sulfuric acid. Ethyl 2-(2-pyridylamino)benzoate, prepared in the reaction of 2-chloropyridine and ethyl anthranilate in boiling toluene for 10 h, afforded ll//-pyrido[2,l-b]-quinazolin-ll-one (27) on heating at 200-210°C for 0.5 h (92MI2). 

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