Analogs of Reissert compounds

The reaction of adducts with alkali hydroxides have been studied for cyanoisochromenes 108, which are oxygen analogs of Reissert compounds described for the first time by Balaban and co-workers (87T409). In this case, sodium hydroxide, depending on its concentration in aqueous solutions and on the nature of R3 in 108, may act both as a base and as a... 

Several open-chain analogs of Reissert compounds have been prepared as part of the study of the mechanism of the acid-catalyzed h3 drolysis of Reissert compounds. A-Benzoyl-A-phenylglycinonitrile (49) has been prepared from glycolonitrile. Although the infrared and... 

I Shcherbakova, E. V. Kuznetsov, I. A. Yudilevich, O. E. Konpan, A. T. Balaban, A. H. Abolin, A. V. Polyakov, and Y. T. Struchkov, Oxygen analogs of Reissert compounds molecular structure and reactions with sodium hydroxide, Tetrahedron 44, 6217-6224 (1988). 

A Reissert compound has been prepared from 9-methoxyellipticine and both it and 10 give a fluoroborate salt of the type 19. The Reissert compound of 6,7-dimethoxyphthalazine has been used to prepare an azapa-paverine. The oxoaporphine alkaloid subsessiline has been synthesized using the Reissert compound of 5,6,7-trimethoxyisoquinoline. The reaction of vanillin Schiff bases with benzoyl cyanide yields open-chain analogs of Reissert compounds. a-Acylaminonitriles, which can be considered as open-chain Reissert compounds, have been converted to open-chain analogs of Reissert salts (5-imino-3,5-dihydrooxazole derivatives). - ... 

Stamegna and McEwen noted the presence of minor products such as a-benzamidostilbenes from the Stevens rearrangement of analogs of Reissert compounds. These minor products could be formed by recombination of radicals formed by homolysis. Further evidence for this was provided in that the minor products were observed for radical intermediates one would predict to be relatively stable (such as benzyl radicals), yet they were not observed if the radical intermediate was not expected to be stable (such as aryl radicals). 

Successful attempts have been made for the preparation of different emetine analogs 46). For example, 211 has been synthesized by the reaction of Reissert compound 26 with the protoemetine analog 212 (Scheme 26). 

The hydrochlorides of 64, 65, and 66 were obtained by reaction of iV-phenylbenzimidyl chloride and hydrogen cyanide with the appropriate heterocyclic base. As is typical of the Reissert compounds, these three compounds lack absorption peaks in the region 2200-2400 cm h To further the analogy to Reissert compounds, acid-catalyzed hydrolysis of 64, 65, and 66 gave benzaldehyde. Picolinio acid, quinaldic acid, and isoquinaldic acid, respectively, as well as aniline, are also obtained from the hydrolysis. Nitrobenzene oxidation of the three compounds gave pyridine-2-carboxamide, quinaldonitrile, and isoquinaldonitrile, respectively. ... 

Heterocyclic structures analogous to the intermediate complex result from azinium derivatives and amines, hydroxide or alkoxides, or Grignard reagents from quinazoline and orgahometallics, cyanide, bisulfite, etc. from various heterocycles with amide ion, metal hydrides,or lithium alkyls from A-acylazinium compounds and cyanide ion (Reissert compounds) many other examples are known. Factors favorable to nucleophilic addition rather than substitution reactions have been discussed by Albert, who has studied examples of easy covalent hydration of heterocycles. 

A reinvestigation of the experiments on the UV irradiation of l-acetyl-l,2-dihydroquinoline-2-carbonitriles (Reissert compounds) 561 unequivocally demonstrated that the rearrangement via the diradical intermediate 562 gave 4//-3,l-benzoxazines 563 and 565 rather than the benzazete derivatives described earlier. The yields and the type of products were strongly influenced by the substituent R at position 4 while irradiation of the unsubstituted quinoline 561 (R=H) gave 3,1-benzoxazine 563 in nearly quantitative yield, the amount of the corresponding methyl-substituted analog 565 that could be isolated was considerable lower, due to its irreversible isomerization via 562 to the stable cycloprop[/ ]indole derivative 564 (Scheme 107) <199811(49)121 >. 

Anhydro-5-aminooxazolium hydroxides (249), generated from Reissert compounds (248), combine with allcynes to afford pyrroloisoquinolines the reaction (Scheme 26) is analogous to that of munchnones with alkynes. 

Analogously, although the enhanced reactivity of quinoline derivatives (relative to pyridine counterparts) in nucleophilic additions such as the formation of pseudobases and Reissert compounds probably relates to the relatively lower energy of the LUMO in the quinoline derivatives, the radicals from these heterocycles, in which the corresponding orbitals are singly occupied, are anionic thus, reactivity toward nucleophiles is also unlikely to be important. 

The failure of pyridine and acridine to yield Reissert compounds has already been discussed. Although many of the arguments advanced for the failure of pyridine to yield a Reissert compound suffer from the fact that analogous compounds have been prepared from pyridine, no one yet appears to have found the proper conditions for formation of a pyridine Reissert compound. 

Treatment of the i r-benzyl isoquinolinium bromide with potassium cyanide gave 73. A similar compound was obtained from the ethiodide. Use of potassium thiocyanate in place of potassium cyanide also gave a similar compound. Treatment of 73 or the other analogs with ethanolic picric acid resulted in the liberation of the cyano or thiocyano group to give 2-benzyl- or 2-ethylisoquinolinium picrate. These compounds fail to react as typical Reissert compounds in the presence of phenyllithium or sodium hydride. 

Trisubstituted pynoles are obtained in 50-l(X)% yields by the addition of open chain analogs of a Reissert compound to the vinyltriphenylphosphonium cation, with subsequent cyclization by an intramolecular Wittig reaction and base-cataly elimination of HCN (Scheme 25). ... 

Most activity in this area has centered around the isolation of so-called pseudo-bases (82) in which the cyano group is replaced by a hydroxy group. Thus the pseudo-base is obtained, in addition to the normal Reissert compound, from S-nitroisoquinoline, " 3-methyl-5-nitroisoquinoline, 6-nitroquinoline, and phthalazine. Heating the pseudo-bases in alcohol gives rise to the ethers 83. A discussion of some of the chemistry and properties of the pseudo-bases has appeared. The formation of the pseudo-bases can be suppressed and that of the Reissert compounds increased by the use of a phase-transfer catalyst. Pseudo-bases have also been obtained in attempts to form Reissert compounds from 1,6-naphthyridine and 4,6-phenanthroline. 2-Phenyl-1,2,3-thiadiazole and benzoyl chloride in the presence of cyanide gave 84 and imidazo[l,5-a]pyrazines with acid chloride gave 85 in reactions analogous to the pseudo-base formation. 

The paper reporting the reaction of isoquinoline and potassium cyanide with dialkyl chlorophosphates and dialkyl chlorothiophosphates to give products of the type 114 has now appeared. These compounds can be alkylated in the same manner as a normal Reissert compound, and hydrolysis of the alkylation product gives 1-methylisoquinoline. A phthalazine analog (115) has also been prepared. ... 

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... 

Popp FD, Veeraraghavan S 1982 Synthesis of potential antineoplastic agents. XXVII. (Reissert compound studies. XLIV.). The ellipticine Reissert compounds as an intermediate in the syntheses of ellipticine analogs. J Heterocycl Chem 19 1275-1280... 

Use of equimolar amounts of acid chloride, trimethylsilyl cyanide, and quinazoline in the presence of a catalytic amount of aluminum trichloride results in the formation of mono-Reis-sert compounds 23 across the more reactive of the two C-N double bonds in quinazoline. When a chloroformate is employed instead of an acid chloride the corresponding Reissert analogs are obtained. ... 

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