Quinazolinium derivative

Amino-5-deoxy-D-xylopyranose (17) has the structure of a cyclic a-amino alcohol and should, accordingly, react with nucleophiles, leading to a-amino alkylation. " These reactions generally proceed under acid catalysis, and are only applicable to 17 if they provide rapid formation of stable products otherwise, rearrangement to 22 results. The condensation of 17 with o-aminobenzaldehyde at pH 5 gives the quinazolinium derivative (36), isolated as a red, crystalline picrate. This reaction serves as a specific chromatographic indicator for 16 17. 

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). 

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... 

Reaction of quinazoline with phenacyl bromides and subsequently with dimethyl acetylenedicarboxylate or ethyl propiolate in propylene oxide at ambient temperature gave the pyrrolo[l,2-c]quinazolines 47. The latter are formed in a [3 + 2] dipolar cycloaddition between the quinazolinium ylides 46, generated in situ, and the acetylene derivatives. 

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 reaction proceeds according to the principles of the r-amino effect (Scheme 11). A wide range of substituted benzyl derivatives followed this pathway. Debenzylation rather than decyanoethylation occurred—a fact attributable to the stabilization of the iminium cation that occurs in the former process, whereas destabilization would result in the latter. Furthermore, the reaction gave low yields with cation-destabilizing benzyl groups such as nitro- and difluoro-substituted derivatives. In the absence of the para-methyl group, normal para-formylation occurred and the perfluoro-phenylmethyl derivative (27, Ar = QH5) formylated normally in the ortho position. The quinazolinium intermediate 29 was mooted (see type 3 reactions for more information on this reaction). 

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. 

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