Quinazoline-containing compounds

Cyclization and rearrangement reactions such as the Dimroth rearrangement have played an important role in the synthesis of quinazoline-containing compounds. For example, Reddy and co-workers applied the Dimroth... 

In the construction of C=N bond-containing compounds, such as nitrogen heterocycles, the aza-Wittig methodology has received increased attention as the method of choice [7]. Thus, an easy access to optically active (-)-vasicinone (7-15), a pyr-rolo[2,l-fc]quinazoline alkaloid which is used in indigenous medicine [8], was... 

The reactions of isatoic anhydrides with various nitrogen-containing compounds of the acyclic, alicyclic, and heterocyclic series leading to derivatives of quinazoline have been studied most widely. Here two approaches to the synthesis of compounds of this group were developed 1) The initially formed derivatives of anthranilic acid were converted in situ into the heterocyclic compounds 2) the derivatives were isolated and cyclized separately into the required products. For example, the amino derivative 109 was obtained with a yield of 56% by the first method with the action of ammonia followed by phosphorus oxychloride on a mixture of the anhydrides 107 and 108 [63],... 

CN/CC replacements were also observed when the pyrimidine ring is part of a bicyclic system. Reaction of quinazoline with active methylene compounds, containing the cyano group (malonitrile, ethyl cyanoacetate, phenylacetonitrile) gave 2-amino-3-R-quinoline (R = CN, C02Et, Ph) (72CPB1544) (Scheme 12). The reaction has to be carried out in the absence of a base. When base is used, no ring transformation was observed only dimer formation and SnH substitution at C-4 was found. 

A special class of synthesis is the utilization of retro-Diels-Alder (RDA) reactions. A double RDA sequence was used to prepare the pyrimido[l,2-A]pyridazin-3-one 118. In this versatile method both reactants of the parent compound were constructed from cyclopentadiene. The parent compound 117 contains two norbornene units and decomposes on heating in toluene in a double RDA reaction leaving two double bonds in the target heterocycle. Similarily, the parent compound 119 decomposes in a single RDA reaction to yield the benzologue, pyridazino[6,l-3]-quinazolin-10-one 120 (Scheme 13) <2000SL67>. 

Quinazoline alkaloids contain more than 100 compounds. They have been isolated from animal and plant sources. The plant family Rutaceae is especially rich in these alkaloids. Typical quinazoline alkaloids include, for example, arborine, glomerin, homoglomerin, glycerine, glycosminine, febrifugine and... 

Catalytic hydrogenation of l,2,3,4-tetrahydro-ll//-pyrido[2,l-6]quina-zolin-ll-one and its 6-, 7-, 8-, and 9-methyl derivatives over Pd/C catalyst in ethanol gave 1,2,3,4,6,7,8,9-octahydro-ll //- derivatives (87JMC1543). A solution of a 1 1 mixture of 9-methyl-l,2,3,4-tetrahydro-ll/f-pyrido-[2,l-6]quinazolin-11 -one (73) and 2-benzyl-9-methyl-l,2,3,4-tetrahydro-ll//-dipyrido[l,2-a 4,3-catalyst yielded a complex reaction mixture containing 15% of 9-methyl-l,2,3,4,6,7,8,9-octahydro-ll//-pyrido[2,l-/)]quinanolizin-Tl-one and other products (87T1157). The double bonds of the pyridine of compound 73 was also saturated by intermolecular catalytic hydrogen transfer from 2-(4-cyclohexenyl)-l,2,3,4,5,6,7,8-octahydroquinazolin-4-one in the presence of Pd/C catalyst [85H(23)3095]. 

Rhodium-catalyzed hydroformylation of -(substituted amino)benzyl-amines (387, X = H2) and -(substituted amino)benzamides (387, R = H, X = O) in the presence of rhodium(II) acetate dimer and triphenylphos-phine in deoxygenated ethyl acetate gave a 7 3 mixture of 1,2,3,4,4 ,5-hexahydro-6//-pyrido[l,2-a]quinazolines (388, X = H2,0) and isomeric 3-methyl-l,2,3,3fl,4,5-hexahydropyrrolo[l,2-a]quinazolines (389, X = H2, O) (94AJC1061). The methyl derivative of benzylamine 387 (R = Me, X = H2) afforded a mixture of diastereoisomers 390 and 391 (X = H2). Their ratio depended on the reaction time. Longer reaction times gave more 391 (X = H2), containing the methyl group in an equatorial position. Compound 390 isomerized into 391 (X = H2), under the aforementioned conditions. The benzamide derivative (387, R = Me, X = O) yielded only one isomer (391, X = O), independent of the reaction period. 

The fluorescence and phosphorescence of quinazoline, 6-chloro-4-phenyl-and 6-chloro-l-methyl-4-phenylquinazolin-2(lH)-one were recorded in ethanol containing 1% of concentrated sulfuric acid. The luminescence of these compounds on thin-layer chromatography (TLC) plates saturated with ethanol was reported. 4-Morpholino- and 4-piperidino-6-methoxy-2-phenyl-quinazoline also have luminescent properties, and the ultraviolet fluorescence in the crystals and in hexane or benzene solution was discussed. The time and wavelength resolved emission from quinazoline vapor at low pressures was studied with a pulsed frequency double-dye laser and were compared with those of quinoxaline and cinnoline. ... 

Irradiation of aqueous solutions of (5)-tryptophan at pH 6-9 containing a photosensitizer (e.g., eosin) caused destruction of the amino acid and formation of N -formylkynurenine as the major product. Similar irradiation in dilute ammonia at pH 8-9 gave an optically active compound in 13% yield, which was shown to be 4-(2 -amino-2 -carboxyethyl)quinazoline (12). 

In analogy to the procedures described in the preceding sections, a-halo ketones and heterocyclic compounds containing thiohydrazide functions can also be used in the syntheses of 7/f-l,2,4-triazolo[3,4-/)][l,3,4]thiadiazines,61,52 irnidazo[2,3-7>][l,3,4]thiadiazines,63 pyrimido-[l,2-6][l,3,4]thiadiazines,64 and 6/f-l,3,4-thiadiazino[2,3-6]quinazolines.65... 

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