Reissert compounds amides

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. 

Using the original conditions for the formation of Reissert compounds the triazolopyrimidine (91 R = H) undergoes ring fission producing the triazole (92) and the amide (93) (Scheme 6). Under... 

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. 

As in the previous chapter, the material will be organized according to substrate category, starting with the carboxylic acids themselves and then moving on to the various derivatives. The methods have been placed generally in sections corresponding to the immediate precursors of the aldehydes. Thus, the hydrolysis of Reissert compounds appears under amides as opposed to acyl chlorides, and the Sonn-Muller appears under imidoyl chlorides and not amides. 

As mentioned above, there are two particular types of amide which can be induced to decompose to aldehydes without requiring reducing agents. They are the Reissert compounds, to be discussed first, and the sulfonylhydrazides involved in the McFadyen-Stevens method, to be discussed second. 

Attempted rearrangement of 4-chloro-2-(4-methoxybenzoyl)dihydro-isoquinaldonitrile with sodium hydride in dimethylformamide led to a product whose structure was 59 or 60. Treatment of the 8-benzoyloxy-Reissert compound 61 with sodium hydride in dimethylformamide resulted in attack of the anion at the ester rather than the amide carbonyl to give 62. ... 

Reaction of the Reissert compound of 4-methylquinoline with sodium hydride in dimethylformamide and acrylonitrile at 0° led to rearrangement to 4-methyl-2-benzoylquinoline, while reaction at — 30° led to 67a and 676. Use of sodium amide-liquid ammonia gave an improve yield of 67a and 67b. Reaction of 3 with potassium t-butoxide in dimethyl sulfoxide and acrylonitrile gave 67c. ... 

Treatment of the Reissert compound derived from 4-chloroisoquinoline with phosphorus pentachloride yielded 4-chloro-l-cyanoisoquinoline. Similar treatment of the benzo[/]quinoline Reissert compound gave a mixture of nitrile and amide." The Reissert compound from 2-bromo-benzo[/]quinoline with thionyl chloride gives 2-bromo-3-cyanobenzo-[/]quinoline." Oxidation of a Reissert compound in the presence of 50% sodium hydroxide and a phase transfer catalyst also gives the isoquinaldonitrile. ... 

Treatment of the compounds 78 with various alkyl halides in the presence of sodium hydride results in 1-alkylation as with normal Reissert com-pounds. ° Acylation has also been reported under these conditions. Under a variety of conditions, however, 78 does not react with benzaldehyde. Acid hydrolysis of 80 gave tetrahydroquinaldic acid, while acid hydrolysis of the alkylated dihydroisoquinoline-Reissert compounds gave the amino acids 81. By first complexing the alkylated dihydroisoquinoline-Reissert compound with zinc chloride in ether and then hydrolyzing the complex, the nitrile was hydrolyzed to an acid, but the amide group was left intact. The perchlorate salts of dihydroisoquinoline-Reissert compounds have also been prepared, and sodium borohydride reduction proceeds in the same manner as reduction of the Reissert salt to... 

Reissert compounds of the type 33 (n = 330,49 and 430) undergo an intramolecular alkylation on treatment with sodium hydride in dimethyl-formamide to give the tricyclic compounds (34). A similar reaction also takes place in the quinoline series.30 When 33 (n = 3) and isopropyl bromide are treated with sodium hydride, cyclization to 34 (n = 3) takes place rather than alkylation with the isopropyl bromide however, treatment of 33(n = 3) and carbon disulfide-methyl iodide with sodium hydride gives 35 rather than cyclization.30 Alkaline peroxide converts the nitrile 34 (n = 3) into an amide, and acid or base hydrolysis gives 4-(l-isoquinolyl)butyric acid.30... 

The Reissert compound, l-cyano-iV,A(-diethyl-l,2-dihydro-2-phthalazinecarbox-amide (126) with benzaldehyde in an alkaline medium gave l-(a-hydroxy-benzyl)phthalazine (128), allegedly via the intermediate (127) (PhCHO, NaOH, H2O, MeCN, PhCHjEtaNCl, 20°C, 2 h 15%). ... 

The Reissert compound 12 undergoes add hydrolysis to give isoquinoline-l-carboxyhc acid and an aldehyde R-CH=0. This disproportionation reaction presumably involves formation of an amino-oxazolium ion 13 and its ring-cleavage to the amide 14 and the aldehyde. 

---