Isoquinoline Reissert compounds

The most frequently used method for the preparation of isoquinoline Reissert compounds is treatment of an isoquinoline with acyl chloride and potassium cyanide in water or in a dichloromethane-water solvent system. Though this method could be successfully applied in a great number of syntheses, it has also some disadvantages. First, the starting isoquinoline and the Reissert compound formed in the reaction are usually insoluble in water. Second, in the case of reactive acyl halides the hydrolysis of this reaction partner may became dominant. Third, the hydroxide ion present could compete with the cyanide ion as a nucleophile to produce a pseudobase instead of Reissert compound. To decrease the pseudobase formation phase-transfer catalysts have been used successfully in the case of the dichloromethane-water solvent system, resulting in considerably increased yields of the Reissert compound. To avoid the hydrolysis of reactive acid halides in some cases nonaqueous media have been applied, e.g., acetonitrile, acetone, dioxane, benzene, while utilizing hydrogen cyanide or trimethylsilyl cyanide as reactants instead of potassium cyanide. 

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). 

Skiles and Cava have investigated the alkylation method of isoquinoline Reissert compounds (76), performing a comparative study on the alkylation of... 

Among the great number of different approaches for the synthesis of phthal-ideisoquinoline alkaloids the application of Reissert compounds, developed first by Kerekes et al. (42,43), proved to be one of the most efficient and suitable methods (Scheme 24). Treatment of isoquinoline Reissert compounds 26 or 28 with sodium hydride in dimethylformamide resulted in the formation of the corresponding Reissert anions, which were reacted with dimethoxy- or meth-ylenedioxy-substituted o-formylbenzoic acid ester derivatives 178 and 179, respectively. The presumed mechanism of this reaction involves an initial reaction... 

Although the number and variety of isoquinolines investigated does not approach that of the quinoline series, it would appear that the synthesis of isoquinoline Reissert compounds is general when the methylene chloride-water solvent system is used. A possible exception is 1-substituted isoquinolines where a steric effect, similar to that... 

Treatment of the isoquinoline Reissert compound 8 or 2 (R = 3,4,5-(OCH3)3CeH2) with benzoyl peroxide in boiling benzene gave l-cyanoisoquinoline. In contrast 7 was essentially unchanged under these conditions. 

Most work has been in the isoquinoline area, principally because of the usefulness of isoquinoline Reissert compounds in the synthesis of isoquinoline alkaloids. Aside from 5-chloro- and 3-acetylaminomethylquinoline and a few halo, methyl, and carbomethoxyisoquinolines, all the substituted quinoline or isoquinoline Reissert compounds have involved oxygen-type functions in one or more of positions 4-, 5-, 6-, 7-, and 8- of the isoquinoline... 

The sulfuric acid-catalyzed condensation of the isoquinoline Reissert compound 2 (R = Ph) with 1-p-anisyl-l-phenylethylene proceeds as described for the condensation with 1,1-diphenylethylenetogive 20. The hydrochloric acid-catalyzed condensation of 2 (R = C H OMe-p) with 2- and 4-vinyl-pyridine gave 21 C5H4N = 2- and 4-pyridyl, respectively). ... 

The anion (26) derived from the isoquinoline Reissert compound (2) and the related anions derived from other Reissert compounds have most generally been generated by the use of sodium hydride in dimethylformamide. ... 

The anion of the isoquinoline Reissert compound (26) has also been alkylated with a wide variety of other alkyl... 

Treatment of the isoquinoline Reissert compound (2) with sodium hydride in dimethylformamide, with 50% aqueous sodium hydroxide-TEBA chloride, or with 50% aqueous sodium hydroxide-TBA chloride and an activated aryl halide, such as 2,4-dinitrofluorobenzene, 2-bromo-3-nitropyridine, 4-nitrochlorobenzene, t-butyl 2-chloro-5-nitrobenzoate, ... 

A variety of other, nonaromatic, aldehydes with 26 have also given the expected esters.Ferrocenecarboxaldehyde has been allowed to react with the anions of both the quinoline and isoquinoline Reissert compound. Benzaldehyde and other aromatic aldehydes have been condensed with the anion of the phthalazine Reissert compound. 

At the time of the last review it was noted that the condensation of ketones with the Reissert anion was a relatively unsatisfactory reaction. It has now been shown that acetone, acetophenone, cyclohexanone, and several N-substituted 4-piperidones ° react with the isoquinoline Reissert compound in the presence of 50% aqueous sodium hydroxide-acetonitrile containing TEB A chloride. Isatin, A(-benzyl-3-piperidone, ° and a variety of N-substituted 4-piperidones ° "° also react with isoquinoline or... 

A variety of isoquinoline Reissert compounds (2) have been caused to undergo rearrangement of the acyl group from nitrogen to carbon by treatment with sodium hydride in dimethylformamide to give ketones of type similar manner, the bis-Reissert compound 14... 

The anion (26) of the isoquinoline Reissert compound (2) has been used in a Michael-type reaction. Thus, reaction of 26, generated with phenyllithium, with ethyl cinnamate and substituted cinnamates give rise to 63, dimethyl acetylenedicarboxylate yields 64, and 2- and 4-vinylpyridines give rise to 65. Use of cinnamonitrile in this sequence leads to the isolation of 66. The enol ester, vinyl acetate reacts with the isoquinoline Reissert compound in aqueous sodium hydroxide containing TEBA chloride to surprisingly give 67. ... 

Sodium borohydride reduction of alkylated isoquinoline Reissert compounds (27) gives rise to 1-alkylisoquinolines (28) and provides an alternative to base hydrolysis for this conversion." Sodium borohydride reduction of the perchlorate salts of Reissert compounds (19 R = Ar, X- CIO4) leads to the iV-benzyl-l,2,3,4-tetrahydroisoquinaldamides70. ... 

The addition of hypochlorous acid to the 3,4-position of the isoquinoline Reissert compound (2 R = Ph) takes place to give the chlorohydrin 71." Use of A -chlorosuccinimide in ethanolic dioxane gave the 0-ethyl derivative. Various reactions of the chlorohydrin led to isochromenes and a rearranged isoquinoline." ... 

The anion of the isoquinoline Reissert compound (26) has also been alkylated with a wide variety of other alkyl halides.519-35 38 48-62-66,90 93 The alkylation product from 26 and allyl chloride undergoes isomerization to 38 on base-catalyzed hydrolysis.90 The phthalazine Reissert compound (3) has also been alkylated, in the presence of sodium hydride, with methyl iodide39 and with benzyl halides40 to give, after hydrolysis, 1-substituted phthalazines. A phthalazine analog of 34 (n = 3) has been prepared.1511 An additional example of the alkylation of the quinoline Reissert compound in the 4-position has appeared.943... 

Isoquinoline Reissert compounds react with 1,1-diarylethenes in the presence of acid to give 3//-pyrroles (122, Scheme 45).6,118 The mechanism of related reactions has been discussed in detail.118 ... 

A base-catalyzed intramolecular nucleophilic substitution reaction on isoquinoline Reissert compounds (222) is the basis of a benzo[a]quinolizidine synthesis developed by Popp et al. (Scheme 42) <72JHC541>. 

A series of bisbenzylisoquinolines has been prepared through alkylation of 6,7-disubstituted isoquinoline Reissert compounds with diaryl ethers such as 8, 9, and 10. ... 

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