Chemical Properties

Abstract

It is well known that the 2- and 4-positions of the quinoline molecule show a great resistance to electrophilic substitutions, owing to the strong electron-withdrawing effect of the ring nitrogen, and that a representative electrophile of the nitronium cation attacks the 5- and 8-positions of the molecule to produce 5- and 8-nitroquinolines under rather drastic nitration conditions. In 1943, E. Ochiai speculated on the basis of his brilliant work on aromatic amine chemistry that N-oxygenation of quinoline would alter the reactivities of this aromatic ring system owing to the expected electron-donating resonance effect of the N-oxide group. In fact, he and his coworkers demonstrated credibly that the 4-position of quinoline 1-oxide was easily nitrated in an excellent yield under a milder nitration condition than that chosen for the free quinoline base (Ochiai, Ishikawa and Sai, 1943; Ochiai, 1953). The synthesis of 4-nitroquinoline 1-oxide was thus brought about, although it was beyond imagination in those days that this yellow nitro compound, painted on the skin or injected, had a potent ability to produce malignant tumors in a wide variety of animals. It may be not too much to say that Ochiai’s ideas about the electronic effect of the N-oxide group gave birth to the chemistry of new classes of heteroaromatic amines, such as pyridines, quinolines, and many other nitrogen-containing aromatic compounds. Numerous studies along these lines, mainly by Ochiai and his school, were recently reviewed by Ochiai himself in a monograph entitled “Aromatic Amine Oxides” (1967) which gives the whole story of the organic and physical chemistry of aromatic amine oxides, including 4-nitroquinoline 1-oxide. This chapter will be devoted to a review of the chemical properties of substituted 4-nitroquinoline 1-oxide. The 4-nitroquinoline 1-oxide derivatives reported in the literature are listed in Table 1.