Zur Photochemie von 1H‐ und 2H‐Indazolen in saurer Lösung

Abstract

It is shown that I Hand 2H-indazoles (cf: Scheme2) on protonation ( 0 , l~ H2S04 in water or alcoholic solution) give analogous indazolium ions (see Fig. 1 and 2) which on irradiation undergo heterolytic cleavage of the N(l), N(2) bond whereby aromatic nitrenium ions in the singlet ground state are formed (cf: Scheme 13). If the para position of these nitrenium ions is not occupied by a substituent (e.g. a methyl group) they are readily trapped by nucleophiles present (e.g. water, alcohols, chloride ions) to yield the corresponding 5-substituted 2-amino-benzaldehydes or acetophenones (cf: Schemes 4-10). Photolysis of indazole (4) and 3-methyl-indazole (5) in 0,75 N H$O, in alcoholic solutions gives in addition minor amounts of the corresponding 3-substituted 2-amino-benzaldehydes and acetophenones, respectively (cf: Schemes 6 and 8 and Table 2). Phenylnitrenium ions carrying a methyl group in the para position give in aqueous sulfuric acid mainly the reduction products, i.e. 2-amino-5-methyl-benzaldehydes (cf: Schemes I 1 and 12 and Table 3). In methanolic sulfuric acid, in addition to the reduction products, 6-methoxy substituted benzaldehydes are found (cf: Schemes I 1 and 12 and Table 3) which are presumably formed by an addition-elimination mechanism (cf: Scheme 18). It is assumed that precursors of the reduction products are the corresponding nitrenium ions in the triplet ground state. Singlet-triplet conversion of the nitrenium ions may become efficient when addition of nucleophiles to the singlet nitrenium ions is reversible (cf: Scheme 22) thus, enhancing the probability of conversion or when conjugation in the singlet nitrenium ions is disturbed by steric effects (cJ Scheme 20) thus, destabilizing the singlet state relative to the triplet state.

Practical Large-Scale Synthesis of Endothelin Receptor Antagonist S-0139

“…A survey of the literature revealed no reliable and practical procedure for 15 although its protected forms have been reported recently as an intermediate for the synthesis of camptothecin analogues . Initially, aminohydroxybenzaldehyde 15 was prepared by photoreaction of indazole; however, the photoreaction was an obvious drawback for the large-scale preparation. From these initial experiments, we concluded that 15 had not been available presumably owing to its lability.…”

Photolyse von 3‐Methyl‐2, 1‐benzisoxazol (3‐Methylanthranil) und 2‐Azido‐acetophenon in Gegenwart von Schwefelsäure und Benzolderivaten

“…C 80,82 H 7,64 N 5,75% 2.5. Bestrahlung (5) [lo]. KR.-Destillation bei 1 10-120"/10-3 Torr lieferte 103 mg (6,6%) 5i vom Smp.…”