The catalytic hydrogenation of quinazoline
The literature on the properties of quinazoline, with special attention to its preparation and its behavior on reduction, was reviewed. Quinazoline was prepared by a reaction sequence involving condensation of anthranilic acid with formamide to give 4-quinazolinone, followed by conversion of 4-quinazolinone to 4-chloroquinazoline by boiling with phosphorus pentachloride in phosphorus oxychloride, and then controlled hydrogenation of 4-chloroquinazoline. Quinazoline was hydrogenated using rhodium-on-alumina as catalyst under varied conditions. Four runs were made at low pressure (40-60 p. s. i. ) and room temperature; with aqueous hydrochloric acid; with anhydrous ethanolic hydrochloric acid; in glacial acetic acid; and under anhydrous neutral ethanol. In all these cases the only product found was 3,4-dihydroquinazoline, identified by its melting point and those of its HCl salt and picrate. Hydrogenation was also carried out at 2000 p. s. i. and 125 C. in anhydrous netrual ethanol. The bolatile products were identified as o-toluidine (2-24%), N^α-methyl-toluene-α, 2-diamine (20-66%), N^α, N^α-dimethyltoluene-α, 2-diamine (24-51%), and unidentified trace products (5-18%) (about 3% of total product is non-volatile). The N^α, N^α-dimethyltoluene-α, 2-diamine must result from reaction of N^α -methyltoluene-α, 2-diamine with methylamine produced by formation of o-toluidine; this reaction may be considered analogous to the conversion of alcohols to amines under similar conditions. The products were identified by gas chromatography, thin-layer chromatography, infrared and ultraviolet spectrometry, mass spectrometry, MNR spectrometry, elemental analysis and synthesis of authentic samples. The authentic samples of o-toluidine was obtained commercially. N^α-Methyltoluene-α, 2-diamine and N^α, N^α-dimethyltoluene-α, 2-diamine were both obtained by reaction of o-nitrobenzyl chloride with the appropriate amine, followed by catalytic reduction of the nitro group. Samples of several other possible products were also synthesized but the products were not found in the hynrogenation mixtures. N-Methyl- o-toluidine was obtained commercially. Toluene-α, 2-diamine and N^2-methyltoluene-α, 2-diamine (a new compound) were both prepared by the lithium aluminum hydride reduction of the corresponding amides, which were obtained by treating isatoic anhydride and N-methylisatoic anhydride, respectively, with aqueous ammonia. The synthesis of N-o-tolylmethanediamine was attempted by lithium aluminum hydride reduction of the corresponding urea and by a modified Mannich condensation, but it was found to be unstable.
College and Department
Physical and Mathematical Sciences; Chemistry and Biochemistry
BYU ScholarsArchive Citation
Young, Kitchener Barrie, "The catalytic hydrogenation of quinazoline" (1966). Theses and Dissertations. 8503.