Isoquinolines rearrangement

Antimony pentachloride complexes of A-oxides of pyridine, quinoline and isoquinoline rearrange on heating to give the corresponding pyrid-2-one, carbostyril or isocarbostyril, e.g. Scheme 118 (81T1871). 

Gabriel-Colman Rearrangement (Phthalimidoacetic Ester- Isoquinoline Rearrangement, Gabriel Isoquinoline Synthesis)... 

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GABRIEL COLMAN Rearrangement Synthesis of isoquinolines by rearrangement ol phthahmides. 

The Gabriel-Colman rearrangement entails reaction of the enolate of a maleimidyl acetate (2) to provide isoquinoline 1,4-diol 3. ... 

The Gabriel-Colman reaction has been used to prepare 3-alkyl isoquinoline 1,4-diols. Phthalimides 8 and 9 rearrange as expected when treated with alkoxides. Further treatment with sodium ethoxide results in decarboxylation and the expected isoquinolinone 1,4-diols 12 and 13. 

In 1968, the aforementioned reaction was repeated and found to produce a rearranged product (11). This was the first report of aryl migration with the Pictet-Gams conditions. The expected product was l-methyl-3-phenyl isoquinoline, but only 1-methyl-4-isoquinoline (11) was observed. Interestingly, the authors did not suggest a mechanism for the formation of the isolated product. 

Although this isoquinoline at first bears little structural resemblance to morphine (108), careful rearrangement of the structure (A) shows the narcotic to possess the benzylisoquinoline fragment within its framework. Indeed, research on the biogenesis of morphine has shown that the molecule is formed by oxidative coupling of a phenol closely related to papaverine. 

Ethyl 1 -phenyl-1,8b-dihydroazirino[2,l- ]isoquinoline-3-carboxylate (2), obtained by decomposition of azide 1 (see Section 3.2.1.1.1.1.) in the presence of triethyl phosphite, on heating under reflux in toluene, rearranges quantitatively to the 3//-3-benzazepine 3.82... 

Substituted isoquinoline (V-acylimines 6 undergo a photochemical rearrangement to 1-acyl-1//-1,3-benzodiazepines 7.164... 

It is necessary to hold the reaction temperature below —5° in order to prevent 1,2-rearrangement of the Reissert anion to 1-benzoyliso-quinoline [Isoquinoline, 1-benzoyl-].5... 

Thus, cycloprop [c] isoquinolines 101 obtained by a stereo specific 1,1-cycloaddition of nitrile ylides 100 undergo two distinct thermal (80 °C) rearrangements depending on the substituents in the cyclopropane ring (equations 35 and 36)52. 

The (diphenylmethylene)aminocyclobutenecarboxylates 109 obtained by rearrangement of the DMPA-H adducts of 1-Me, 2-Me, contain a 2-azadiene unit and a cyclobutene moiety. Indeed, the parent compound 109 a reacted with 4-phenyl-l,2,4-triazoline-3,5-dione (PTAD, [80]) at room temperature in a [4-1-2] cycloaddition mode to yield the tricyclic tetraazaundecene 132 in almost quantitative yield (Scheme 44) [8]. As substituted cyclobutenes, compounds 109 should be capable of opening up to the corresponding butadienes [1, 2b, 811. When compounds 109 were subjected to flash vacuum pyrolysis, the dihydro-isoquinolines 135 were obtained, presumably via the expected ring-opened intermediates 133, which subsequently underwent bn electrocyclization followed by a 1,5-shift, as is common for other 3-aza-l,3,5-hexatrienes [82]. 

Rare-earth exchanged [Ce ", La ", Sm"" and RE (RE = La/Ce/Pr/Nd)] Na-Y zeolites, K-10 montmorillonite clay and amorphous silica-alumina have also been employed as solid acid catalysts for the vapour-phase Beckmann rearrangement of salicylaldoxime 245 to benzoxazole 248 (equation 74) and of cinnamaldoxime to isoquinoline . Under appropriate reaction conditions on zeolites, salicyl aldoxime 245 undergoes E-Z isomerization followed by Beckmann rearrangement and leads to the formation of benzoxazole 248 as the major product. Fragmentation product 247 and primary amide 246 are formed as minor compounds. When catalysts with both Br0nsted and Lewis acidity were used, a correlation between the amount of Br0nsted acid sites and benzoxazole 248 yields was observed. 

Aromatic donble bonds may also be nsed effectively to trap the electrophilic intermediate (electrophilic aromatic snbstitntion). The Beckmann rearrangement-cyclization seqnence has fonnd ntihty in the synthesis of the isoquinoline nucleus . ... 

Phenethyl ketone oximes have been cyclized by a Beckmann rearrangement to isoquinolines 477 (equation 205), but quinoline derivatives 478 can also be obtained as a result of a formal displacement at the nitrogen atom of the oxime (equation 206). 

The Neber rearrangement has been used as a valuable synthetic tool to introduce an a-amino group relative to a ketone and it has been used as a key step in the synthesis of a large array of heterocycles, including imidazoles, oxazoles, isoquinolines and pyrazines and has been reviewed long ago °° . ... 

Isoquinoline Reissert compounds of type 12 could be easily converted to the corresponding 1-cyanoisoquinolines (13) by simple base treatment (4,5) (Scheme 3). This transformation also takes place with high yields when type 12 compounds are oxidized with molecular oxygen in a two-phase system in the presence of phase-transfer catalysts (12-14). It should be mentioned that similar oxidation of dihydro Reissert compounds of type 14 afforded the corresponding dihydroisocarbostyril derivatives (15) (12-14). Base treatment of isoquinoline Reissert eompounds followed by intramolecular rearrangement, due to the absence of a proper intermolecular reaction partner, results in 1-acylisoquinoline derivatives (18) (3). 

When the conjugation is further extended, as in the triene-conjugated nitrile ylides (347), it is interesting that 1,1-cycloaddition still appears to be the favored primary process. In the case of the cis isomers 347 [R R =Me, Ph or (CH2)3 R = Ph, Me, C02Me] the proximate products (348) were not isolated but rearranged spontaneously via an aza-Cope process to give the bridged isoquinolines (349) in moderate yield (20-65%) (60,206). 

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