Quinazolinium salts

The structures of 6,6-dimethyl-6,7-dihydropyrido[l,2-c]quinazolinium salt (142) (97AJC109), and 6-methyl-9,10-dimethoxy-4-phenyl-... 

A 6,6-dimethyl-6,7-dihydropyrido[l,2-c]quinazolinium salt was obtained from the reaction of 2-(2-aminophenyl)-pyridine and acetone <1997AJC109>. Reaction of 3-methyl-l,2,3,4-tetrahydroisoquinoline-l-acetamides 195 (R = H) with 36% aqueous CH20 gave 1,3,4,6,7,11 b-hcxahydro-2//-pyrirmido[6,1 - ]isoquinolin-2-oncs 153 and their 3-methyl derivatives <1997LA1165>. When the reaction was carried out in the presence of 37% aqueous NaOH, 3-hydroxymethyl derivatives 152 were obtained. Reactions with PhCHO were stereospecific affording only diastereomers 196 (Equation 41). 

Furthermore, a cycloreversion has been observed in the case of the thermally labile azoniaallene salts (61) (Z = O, S). When Z = S, this proceeds within an hour at room temperature to yield the aryl isothiocyanate and the charged cumulene (66) which is isolated as the acyliminium salt (67) <9ICB2537>. When Z = O and R = Ph, cycloreversion occurs at 83°C (refluxing 1,2-dichloroethane) to give the aryl isocyanate and (66), which is further cyclized to the quinazolinium salt (68) (Scheme 4) <89T5825>. 

Quinazolinium salts, e.g. (189) or its 4-oxo analogue, on treatment with diazoalkanes also undergo ring expansion to give 1,4-benzodiazepines (74BCJ343). 

Cyclization of 2-(pyrid-2-yl)benzenediazonium tetrafluoroborate (451) with alkyl or aryl nitriles afforded the pyrido[l, 2-c]quinazolinium salts 452 [72GEP(O)2043665]. 

Whereas the reaction of the linearly fused 117/-pyrido[2,l -h]quina-zolin-ll-one (27) with alkylating agents (dimethyl sulfate at 120°C, and tri-ethyloxonium tetrafluoroborate in methylene chloride at 20°C) gave exclusively 7V(5)-alkylated quaternary salts (107), that of the isomeric angularly fused 6//-pyrido[l,2-a]quinazolin-6-one (28) with the soft methyl iodide afforded only the iV(5)-methyl quaternary iodide (108, X = I). The reactions of 28 with the hard dimethyl sulfate and triethyloxonium tetrafluoroborate yielded a mixture of 5-methyl-6-oxo-6//-pyrido[l,2-a]quinazolinium salts (108) and 6-alkoxypyrido[l,2-a]quinazolinium salts (109) (90JHC2005). 

Nucleophilic substitution of 6-ethoxypyrido[l,2-a]quinazolinium tetra-fluoroborate (109, R = Et, X = BF4) with methanol in the presence of triethylamine or with pyrrolidine in acetonitrile at 0°C gave 6-methoxy (109, R = Me, X = BF4) and 6-pyrrolidinopyrido[l,2-a]quinazolinium salts (138), respectively (90JHC2005). When the latter reaction was carried out at ambient temperature, a ring-opened product (139) was obtained. 

Deprotonation of the quinazolinium salt 148 with NaH or KH gave the dienamine 149 which cycloadds to methylsulfonyl azide or trifluoromethanesulfonyl azide included in the reaction to afford a mixture of two sulfonyl-imino-substituted benzodiazepine derivatives 150 and 151 after a ring expansion mediated by the expulsion of N2 (Scheme 88) <2000EJ01577>. 

The transformation of quinazolinium salts into quinoline derivatives 88 by... 

Arylamino)-l-chloro-l-(dimethylamino)-2-azapropenylium salts 6, formed from the corresponding arylureas, phosphoryl chloride, and dimethylcyanamide cyclize spontaneously in ca. 40% yield to quinazolinium salts which are characterized as their perchlorates. ... 

The acid-catalyzed condensation of 2-bromopyridines with o-aminoace-tophenone in dilute acids afforded the pseudobases 299. These pseudobases underwent dehydration in concentrated sulfuric acid to give the pyr-ido[2,l-6]quinazolinium salts 300, but on dilution of the acid covalent hydration occurred, causing reversion to the pseudobases. 

The quaternary pyrrolo[2,l-i>]quinazolinium salt 404 yielded the bis compound 405 with triethyl orthoformate in nitrobenzene in the presence of triethylamine at 190°C. The active methylene group of 404 readily react with the 2-[(2-acetanilido)vinyl] derivatives of 3-alkylbenzoxazo-lium, benzthiazolium, naphtho[2,l-acetic anhydride at 100 ° C in the presence of triethylamine to give the cyanines 406. Reaction of 404 with 3-ethyl-5-(acetanilidometh-ylene)rhodanine in refluxing pyridine in the presence of triethylamine af-... 

The first example is shown in Scheme 35. Attempts to formylate p-substituted /-anilines resulting in dealkylation have already been mentioned (see Section II,B and Scheme 11). When such /-anilines as 105 are treated with A-methylformanilide in POCI3 solution, for example, a diazocine 106 is formed (95CC1463) When A-methylformanilide is used, p-formylation of the resultant diazocine also occurs to give 106, R = CHO. However, when an aliphatic amide is utilized, the quinazolinium salts 107 are formed (which are probably the kinetic products in the diazocine formation). When such bulky formylamines as A-formyldiisopropylamine or -indoline are... 

Several 4-substituted 3-methyl-3,4-dihydroquinazolines were obtained by addition of nucleophilic bases across the 3,4 double bond of the 3-methyl-quinazolinium cation, and carbon nucleophiles (e.g., acetyl acetone) added across the 3-4 double bond of 3-phenyl-2-oxo(or thio)-(lH)-quinazolinium salts in much the same way. ... 

Quaternization of the pyrimidine ring of quinazolines enhances its reactivity toward nucleophiles. This reactivity has been used to advantage for preparing 1,2,3,4-tetrahydro derivatives. Methylation of 4-phenylquinazoline occurred at N-1 and N-3 (7 1) and was the first example in which it was shown that alkylating at two different sites in quinazolines was possible. The l-methyl(and 3-methyl)quinazolinium salt that was formed was reduced with sodium borohydride to l-methyl(and 3-methyl)-4-phenyl-l,2,3,4-tetra-hydroquinazoline. Potassium permanganate oxidized the latter compound to l-methyl-4-phenylquinazolin-2(lH)-one. 

Aryl-l-methylquinazolinium salts (111) also reacted with diazomethane. In this case, however, two molecules of diazoalkane could react with the quinazolinium salt. In anhydrous medium at 10°C the 1,2-dihydro adduct (112) was formed together with a 1 1 mixture (24% yield) of the benzodiazepines 113 and 114. At lower temperatures —45°C), on the other hand, 114, from reaction with two molecules of diazomethane, was the only product... 

Scheme 1.167). There was no evidence for acylation of the oxazole ring. In contrast, formylation of 5-(4-dimethylaminophenyl)-2-(4-nitrophenyl)oxazole 615 effects Vilsmeier-Haack formylation of the oxazole ring as well as the electron-rich A, A -dimethylaniline. In this case, heterocyclization then leads to the observed quinazolinium salt 616. " ... 

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