Thesis (Ph. D.)--Columbia University. / Biography. Includes bibliographical references.

Thesis. / Includes bibliographical references.

Thesis. / Includes bibliographical references.

Thesis (Ph. D.)--Columbia University, 1938. / Vita. Bibliography: p. [46-47].

Thesis (PH. D.)--Columbia University, 1938. / Vita. Bibliography: p. [46]-[47].

Thesis (Ph. D.)--Columbia University, 1935. / Vita. Bibliography: p. 39-41.

Thesis (Ph. D.)--Columbia University, 1923. / Vita. Bibliography: p. [36]-37.

Thesis (Ph. D.)--Columbia University, 1924. / Vita. Bibliography: p. [37]-39.

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.

I. The quinazolines, a branch of the benzodiazine class of aromatic nitrogen hetercycles, do not occur to any great extent in naturally occurring compounds. The discovery of the antimalarial febrifugine and its structure elucidation led to the preparation and investigation of a host of new quinazolines in the search for new and more effective antimalarials. Most of the present body of information governing the quinazolines arose out of these synthetic studies. The present study has been accomplished with a four-fold purpose in mind: (1) to investigate the susceptibility of chloroquinazolines to nucleophilic displacement reactions by thiols or their salts, (2) to expand the present body of knowledge concerning the chemistry of the quinazolines, (3) to investigate the susceptibility of sulfides of quinazolines to oxidation to sulfoxides and sulfones, and (4) to prepare new compounds of potential chemotherapeutic value. A procedure for the preparation of 4-chloroquinazoline was worked out and thiol displacements were carried out on this material as well as the 2,4-dichloroquinazoline and 2-chloro-4(3H)-quinazolinone. Twenty-six new thioethers were prepared. Oxidation of these thioethers yielded the oxo derivatives in all but two instances. 4-Methylthioquinazoline was oxidized to 2(1H)-oxoquinazoline- 4-sulfonic acid and 4-phenylthioquinazoline yielded the 2(1H)-oxo-4-phenylsulfinylquinazoline. 4(3H)-Quinazolinethione when treated with dimethyl-sulfate yielded the 1-methyl derivative. When 2-benzyl-thio- 4(3H)-quinazolinone was treated with dimethyl sulfoxide it was converted into 2-benzylthio-3-methylthio-4- quinazolinone. 4-n-Butylthioquinazoline, when treated with per-benzoic acid, yielded 3-(4'-quinazolyl)-4(3H)-quinazolinone. II. Investigations on 2-chloromethyl-4-methyl-quinazoline 3-oxide using primary amines yielded the simple displacement products. Work carried out on 6-chloro- 2-chloromethyl-4-phenylquinazoline 3-oxide with primary amine displacements yielded the simple products and also a ring expanded 1,4-benzodiazepine 4-oxide. This phase of the investigation has been carried out with the following purposes in mind: (1) to examine the conditions under which 6-chloro-2-chloromethyl-4- phenylquinazoline 3-oxide and related analogs rearrange to the 1,4-benzodiazepine 4-oxide, (2) to determine if a similar rearrangement will occur when thiols are used, (3) to investigate the possible rearrangement of the amine and thiol displacement products of 2-chloromethyl- 4-methylquinazoline 3-oxide and the 6-bromo analog, and (4) to examine the possible rearrangement of the 2-alkyl-aminomethylquinazolines. Although a number of conditions were employed, the aminomethylquinazolines were found not to rearrange to the diazepines. Thiol displacements yielded the simple displacement products in each case studied. Amine displacements on 2-chloromethyl-4-methylquinazoline 3- oxides yield simple displacement products. With the 6-bromo-2-chloromethyl-4-methylquinazoline 3-oxide and simple amines the diazepine is formed. Dilute solutions of both the quinazolines and the diazepines change on standing in daylight at room temperature but the products have not been identified.