Isoquinoline ring oxidation

The one report of a true [3-1-3] cyclization occurs in the only reported synthesis of the pyrazino[2,3-c]isoquinoline ring system. The isoquinolino fused derivative (451) was isolated from dimerization of an intermediate iminoquinone formed by air oxidation of the unstable 4-amino-2-methyltetrahydroisoquinolin-l-one (450) 75JOC1760). 

Treatment of isoquinoline tV-oxide (55) with sodium hydride in dimethyl sulfoxide results in ring expansion, albeit in poor yield, to the 3//-3-benzazepine 56, along with a trace of naphthalene (0.8%), and much tar.26... 

The photochemical ring expansion of A-oxides when applied to isoquinoline 2-oxides leads to 1,3-benzoxazepines 5.2122 The yield was reported for 5b only. 

Isoquinoline 2-oxide was converted by bromine in acetic anhydride in the presence of sodium acetate into the 4-bromo 2-oxide, presumably via an addition-elimination process (84MI2). Metallic derivatives have been used occasionally to prepare bromoisoquinolines, as in the formaton of 79, a process accompanied by ring-opening [87JCS(PI)1865]. 

The most reactive position for base-catalyzed hydrogen exchange of the 1-oxide derivatives of quinoline and isoquinoline is the position adjacent to the heteroatom and nearest the fused benzene ring. Thus for isoquinoline 1-oxide the positionalreactivity is given by 1 > >3 > > 4,... 

The Reissert-Henze and the Feely-Beavers-Tani reactions are considered together in this section because of their similarity. The former involves cyanation of acyloxy (formed in situ) (Scheme 113), and the latter alkoxy (Scheme 114), quaternary salts. The Reissert-Henze reaction is a facile, fairly general reaction for quinoline and isoquinoline AT-oxides (Table 19) with cyanation occurring a to the ring nitrogen. Certain substituents inhibit reaction, for example a 1-methyl group (equation 125), and others undergo replacement (Scheme 130) (81H(15)98l). Reaction of 1-methylisoquinoline 2-oxide with benzoyl chloride... 

The photolysis of quinoline AT-oxides in protic media mainly leads to carbostyrils (Scheme 120) (63ACS1461) while in aprotic media ring expansion and contraction products are obtained (69ACS2149, 71TL1311). Isoquinoline TV-oxides behave similarly (Scheme 120)... 

When the sodium salt of 1-methylcorypalline (165 R = CH3) was oxidized in acetonitrile, a good yield of carbon-carbon dimer (69%) was obtained, in which only one of the enantiomeric pairs was obtained.251 The results were explained by proposing a surface mechanism in which the isoquinoline rings are adsorbed in a planar fashion. If the reacting molecules are adsorbed on the surface with methyl groups projecting upward, only those... 

The isoquinoline ring undergoes attack by the nucleophilic aluminum hydride anion in much the same manner as the pyridine ring to produce 1,2-dihydroisoquinolines,91,92 although tetrahydroisoquino-lines have been reported as products even though no proton source was apparently present.92 (For a probable mechanism see Section IV,B.) The reduction of isoquinoline A-oxide by lithium aluminum hydride was also reported to yield the 1,2-dihydroisoquinoline.93... 

Other isoquinoline alkaloids are derived from the biogenetic key compound 81 by further transformations, mainly by oxidative phenol coupling of the isoquinoline ring and on the benzyl residue. A number of structural types of isoquinoline alkaloids are known, e.g. the systems 82-87 (for individual examples and further details, see textbooks of natural products). 

Af-Oxide chemistry in these bicyclic systems largely parallels the processes described for pyridine 7V-oxide, with the additional possibility of benzene ring electrophilic susbstitution, for example mixed acid nitration of quinoline A -oxide takes place at C-5 and C-8 via the O-protonated species, but at C-4 at lower acid strength nitration of isoquinoline A/ -oxide takes place at C-5. ... 

Isoquinolines Containing Basic Functions on the Ring and Their Hydrogenated Derivatives Isoquinolines Containing Oxidized Nitrogen Functions and Their Hydrogenated Derivatives... 

Phosphorus oxide chloride/poly phosphoric acid Pictet-Gams isoquinoline ring closure with C-aryl migration... 

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