From 4-Hydrazino-quinazoline

Formation from 4-Hydrazino-quinazoline. The interaction of 4-hydrazoquinazoline 

Physical Properties.—A study of the u.v. spectra and acid-base equilibria of a-acylamino-N-heterocycles has included measurements for 2-acylamino-l,3,4-thiadiazoles. The formation of their sodium salts is accompanied by a strong bathochromic displacement in the near-u.v. band. The ionization constants indicate that the stability of the anions depends on both the electron-attracting 

In an extensive investigation of the r-electron structure of N- and S-hetero-cycles, the application of fundamental PPP MO calculations and n.m.r. and u.v. spectral measurements have provided information concerning the changes in the TT-electron distribution due to 2-amino- and 2-formyl-substituents in 1,3,4-thiadiazole derivatives. Energy barriers to rotation of the dimethylamino-group in 1,3,4-thiadiazoles have been determined (see p. 427). 

Chemical Properties.—Alkylation. Methylation of 2-amino-5-benzoyl-l,3,4-thiadiazole and its derivatives has been systematically examined. The direction of methylation, which occurs at the N-3 atom of the ring and the exocyclic amino-group, is influenced by the structure of the substrate, the nature of the reagent (Mel, Me2S04, or CH2N2), and the reaction conditions. 2-(Substituted amino)-l,3,4-thiadiazoline-5-thiones (104) are 5-methylated to (105) by one equivalent of methyl iodide, in the presence or absence of alkali. Further methylation occurs at N-3 or N-4, but may lead to mixtures, the composition of which depends on the ratio of the reactants and on the degree of substitution of the 2-amino-group in (105). At 190 C, (105 R = R = Me) isomerizes to (106)  

The interaction of l,3,4-thiadiazolidine-2,5-dithione with bromo-mono-saccharides is comparable with its alkylation. Treatment with 2 moles of 2,3,4,6-tetra-O-acetyl-a-D-glucopyranosyl bromide ( a-acetobromoglucose . ABG) yields a mixture of the (acetylated) 55 -bis(glucoside) (108) and SN-bh- 

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A series of novel l-substituted-4-phenyl-l,2,3-triazolo(4,3-a)quinazolin-5(4H)-ones 1 were synthesized by the cyclization of 2-hydrazino-3-phenyl-quinazolin-4(3H) 2 with various one carbon donors. The starting material 2-hydrazino-3-phenylquinazolin-4(3H)-one 2, was synthesized from aniline 7 by a novel innovative route. When tested for their in vivo Hi-antihistaminic activity on conscious guinea pigs all the test compounds protected the animals from histamine-induced bronchospasm significantly, whereas the compound l-methyl-4-phenyl-l,2,3-triazolo(4,3-a)quinazolin-5(4H)-one lb (percentage protection 70.7%) was found to be equipotent with the reference standard chlorpheniramine maleate (percentage protection 71%). These compounds show negligible sedation (5%) when compared to the reference standard (26%). Hence they could serve as prototype molecules for future development [1,4,5]. 

A one-pot preparation of pyrrolo[l,2-a]quinazoline libraries with three points of diversification by condensation of a-cyano-ketones and 2-hydrazino-benzoic acids has been developed by Hulme and coworkers (Scheme 6.252) [439]. The protocol simply involved heating a solution of equimolar amounts of the two building blocks in acetic acid at 150 °C for 5 min. In many cases, the final products precipitated directly from the reaction mixture. In such cases, simple washing with diethyl ether yielded the products in >95% purity. A 63-member library was prepared by employing seven a-cyano-ketones and nine 2-hydrazino-benzoic acids. 

Quite similarly, the reaction product obtained from 2-benzylthio-3-phenylquinazolin-4(3H)-thione and hydrazine should be assigned the structure 2-anilino-3-aminoquinazoline-4(3//)-hydrazone instead of the reported 2-hydrazino-3-phenyl quinazoline-4(3//)hydrazone (Scheme III.23) (70IJC1055). 

The synthesis of 3,7-dimethylimidazo[4,5- ]quinazoline-6,8(5//,7//)-dione and imidazo[4,5- ]qui-nazoline-6,8(5/7,7/7)-dione, the 1-methyl and 1,9-dimethylated versions (155) of //n-benzoxanthine, respectively, has been achieved using an approach (Equation (75)) based upon an imidazole ring assembly on 7-chloro-3-methyl-6-nitroquinazoline-2,4(l//,3//)-dione, effected by treatment with NH3 or MeNH2 followed by reductive cyclization in HC02H <84JHC79l>. In this same investigation, the 9-(formylamino)-/m-benzoxanthine derivatives (156) were obtained from 7-hydrazino-6-nitro-quinazoline-2,4(l//,3//)-dione precursors. 

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