Quinazolin simple substitutes

Chloromethyl)quinazoline 3-oxides, c.g. 8, react with ammonia and primary amines to yield 3//-1,4-benzodiazepine 4-oxides 10, sometimes accompanied by the simple substitution products 9.219 Dimethylamine220 and pyrrolidine221 react analogously, but other secondary amines afford only products of type 9. 

It has been proposed that the ring-expansion reaction is initiated by attack of the base at position 2 of the quinazoline oxide, which is rendered electron deficient by the inductive effect of the (V-oxide group. In fact, 2-(Chloromethyl)quinazolines, compounds that lack this feature, react with amines to give only simple substitution products.1133... 

Glycosminine (6) has been isolated from Glycosmis arborea (12,43) and Ruta species (48). The chemistry of this base and its syntheses have close parallels with the other simple substituted quinazolines. The structure was established by Pakrashi et al. (77). Physical data are as follows UV nm (log e)] 225... 

In practically all theories of the biosynthesis of quinazolines, anthranilic acid or an equivalent is regarded as one of the building blocks. Robinson 158) postulated that anthranilic acid (N-methylated where necessary), ammonia or amine, and formic acid or phenylacetic acid derived from phenylalanine units or their equivalents build up the simple substituted quinazoline derivatives. Thus vasicine (28) may be derived from anthranilic acid and proline, or closely related metabolites. Febrifugine (9) possibly could be formed from anthranilic acid, formic acid, ammonia, a Cj-unit, and lysine or equivalent compounds. For... 

Scheme L Mass spectrometric fragmentation of simple substituted quinazolines...

A small number of simple substituted quinazolines can be formed in the course of tryptophan degradation by microorganisms (131, 132). In Pseudomonas species, three pathways of tryptophan degradation are known the aromatic pathway in Ps. fluorescens, the quinoline pathway in Ps. acidovorans, and the quinazoline pathway in Ps. aeruginosa. Investigations with [P- C]-tryptophan have provided evidence for a new pathway from tryptophan through the intermediates, formylkynurenine and N-formylaminoacetophenone, forming 4-methylquinazoline with ammonia and free 2-aminoacetophenone. Reacylation of the product and cyclization with ammonia produces other derivatives of 4-methyl-quinazoline. 

Thermally promoted Claisen rearrangement of simple allyloxypyrimidines is difficult to effect, but is more common with quinazolines where it has been used to prepare allyl derivatives substituted in the carbocyclic ring < 1996HC(55) 1 >. An attempted amino-Claisen rearrangement of a 4-allylaminopyrimidine was unsuccessful <2005AJC368>. 

A -Aryl-A -(ethoxyearbonyl)iinidamides and 2-alkyl-l-aryl-3-(ethoxycarbonyl)isothioureas 12 cyclize thermally to yield 2-substituted quinazolin-4(3//)-ones 13. When an A-aryl-A -(ethoxy-carbonyl)imidamide is boiled briefly in quinoline, ethanol is evolved and the corresponding 2-arylquinazolin-4(3//)-one is formed in 49-88% yield. Presumably elimination of ethanol yields an imidoyl isocyanate which undergoes cyclization to form the 2-arylquinazolin-4(3//)-one. These cyclizations are most likely simple thermal processes, since they proceed equally well when diphenyl ether is used instead of quinoline or when the imidamide is heated at 50-70 C above its melting point in the absence of a solvent.This reaction is also suitable for the synthesis of benzo-fused quinazolin-4(3//)-ones. °... 

Reactions of benzodiazines show no exceptional features compared with the simple diazines. Reactivity towards electrophiles is less than in quinoline and isoquinoline. If S Ar reactions take place, they lead to substitution of the benzene ring. As a rule, nucleophilic substitution of benzodiazines occur in the diazine ring, particularly if substituted by halogen. The quinazoline system displays C-4 regioselectivity, e.g. in the reactions of 2,4-dichloroquinazoline with amines or alcohols ... 

Substituted-spiro-l,2-dihydroquinazolines were synthesized by direct reaction of 2-aminobenzophenones, isatin, or 1,2-diketone derivatives and ammonium acetate in the presence of dual role catalyst/solvent IL, 1-methylimidazoIium tri-fluoroacetate [HMIm]TFA.231. In the presence of the same IL, [HMImjTFA, a three-component condensation reaction between 2-aminobenzophenone derivatives, aromatic aldehydes, and ammonium acetate efficiently provides substituted quinazoline. The IL was separated from the reaction mixture by simple extraction and was recycled three times withont considerable loss in activity [115]. 

An interesting approach to chain-fluorinated quinazolines rehed on photochemical recyclization of 1,2,4-oxadiazole derivatives 697 (Scheme 146) [410]. The corresponding quinazolones 698 were obtained in 40-75 % yields when pyrene was used as a sensitizer. This is contrary to the data obtained for simple alkyl-substituted oxadiazoles, which gave highest yields of the products upon irradiation in the presence of triethylamine. 

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