Subject Reissert compounds

The chemistry of Reissert compounds has been the subject of numerous general reviews (3-10). In 1973 Popp gave a summary on the use of Reissert compounds in the synthesis of isoquinoline alkaloids and related compounds (7). We now wish to summarize new results that have appeared from 1973 to the end of 1985 for the application of Reissert compounds in the synthesis of isoquinoline as well as indole alkaloids. 

The chemistry of iV-acyldihydroquinaldonitriles (1) and N-acyldihydroisoquinaldonitriles (2) (Reissert compounds) was the subject of an excellent review in 1955. The purpose of the present... 

The previous review noted the formation of Reissert compounds from less than half the quinolines investigated and stated that ... the ease of formation of Reissert compounds is dependent upon steric as well as electronic factors, since the presence of substituents in the 2- and 8-positions of quinoline inhibits the formation of. .. Reissert compounds. That a steric factor does indeed exist is evidenced by the fact that from a total of seven 2-substituted and nine 8-substituted quinolines subjected to the reaction none has yielded a Reissert compound. Using the methylene chloride-water solvent system, however, Reissert compounds have been prepared from 3-, 4-, 5-, 6-, and 7-substituted quinolines and from disubstituted quinolines. Quinolines having various substituents in these positions, including all those previously reported as not giving Reissert compounds, gave positive results in this solvent system. In addition to Reissert compound formation, hydroxyquinolines were esterified and aminoquinolines were converted to the amides. 

A group of Reissert compounds containing various A-acyl groups were subjected to hydrolysis under similar conditions to give the aldehyde-2-,4-dinitrophenylhydrazone. ... 

The chemistry of Reissert compounds, for example, N-acyldihydroquin-aldonitriles (1) and Af-acyldihydroisoquinaldonitriles (2), was the subject of a review in an earlier volume of this series. The application of Reissert compounds to the synthesis of isoquinoline alkaloids and related compounds... 

The 1,6-naphthyridine-6-oxide (126) and 1,6-naphthyridine-1,6-dioxide (127) form the 5-cyano (128) and 2,5-dicyano (130) compounds, respectively, when subjected to Reissert reaction conditions.52 The 5-oxo isomer (129) is a by-product in the 6-oxide reaction. Cyano-l,6-naphthyridines are obtained when the 1,6-di-JV-oxide (127) is treated with potassium cyanide in the presence of potassium ferricyanide.76-77 Methanolic potassium cyanide yields the 5-cyano-, 5-carboxamido-, and 2-methoxy-l,6-naphthyridines (128, 131, and 132, respectively) when reacted with 1,6-naphthyridine 1,6-dioxide (127).78... 

Dechlorination of 4-chloro-6-methylthieno[2,3-d]pyrimidine 164 with zinc in ethanol and acetic acid at 80°C gave compound 165. The latter was subjected to the Reissert reaction using two equivalents each of tributyltin cyanide and acyl chloride in dichloromethane at room temperature. With benzoyl chloride the mono-Reissert adduct 166 was obtained, whereas with acetyl chloride the di-Reissert product 167 (86JHC545). 

When the iV-alkoxypyridinyl compound is subjected to cyanide, it imdergoes the Reissert-Henze reaction to afford the 2-cyano-derivative with loss of the alkoxy group. Ethylation of W-oxide 311 with diethylsulfate afforded intermediate 312, which was treated with cyanide to afford the corresponding cyano-pyridine 313, an intermediate used in the synthesis of 5-adenosylmethionine decarboxylase inhibitor 314. ... 

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