Nitriles Reissert compounds

By reacting quinoline first with benzoyl chloride and then with aqueous potassium cyanide, the corresponding Reissert compound is obtained. The reaction is normally carried out in one operation using a two-phase system plus a phase transfer catalyst. The N-benzoy group can then be removed by heating with sodium hydroxide solution, and the reaction is continued to hydrolyse the nitrile function to the acid ... 

The previously described Reissert compounds (94) can be converted back to the original heterocycles (91) by sodium hydroxide or, more usefully, by sodium hydride to the nitrile substituted heterocycles (100) <92CPB5137>. Under acidic conditions fission of the dihydropyrimidine ring occurs to give the triazole (101). V-Nitration of the tetrahydro[ 1,2,5]oxadiazolo[3,4-6]pyrazine (102) gives the explosive dinitro compound (67) (Scheme 7) <85J0C5123>. 

Isoquinoline, potassium cyanide, and an alkyl- or arylsulfonyl chloride reacted to yield 2-arylsulfonyl- an 2-alkyIsulfonyl-l,2-dihydroisoquinaldonitriles (62). As is the case with Reissert compounds these analogs do not exhibit any nitrile absorption in the... 

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... 

The anion of the Reissert compound (62.1) reacts at or below room temperature with an aldimine or an isothiocyanate by cycloaddition, and then displacement of the nitrile to form a tricyclic isoquinoline. The chemistry of Reissert compounds has been reviewed [2488, 2959a], as have the synthetic uses of isothiocyanates [3990]. 

The ester group of a carbamate is annulated to a neighbouring nitrile (of a Reissert compound) on reaction with an araldehyde under strongly basic con> ditions (the CN group is eliminated). A better yield of this type of compound was obtained by another method (Chapter 98). 

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... 

TMSCN//7-toluenesulfonyl chloride is much more effective than TMSCN/benzoyl chloride for the preparation of Reissert compounds from pyridazine and methylpyridazines 4-methylpyridazine reacts exclusively at N-2/C-3. Some of the Reissert compounds undergo facile tautomerism on silica gel, but treatment of the crude compounds with DBU provides an efficient synthesis of 3-cyanopyridazines in about 75% overall yield (Scheme 20). With sodium borohydride instead of DBU, competing reductions give a mixture of the pyridazine and tetrahydropyridazine nitriles <86H(24)793>. 

Another procedure for converting carbonyl chlorides into aldehydes proceeds by way of Reissert compounds.3448 Reissert found that 1-benzoyl-1,2-dihydro-2-quinolinecarbonitrile is formed in very good yield when benzoyl chloride reacts with quinoline in the presence of aqueous potassium cyanide, the technique being that of a Schotten-Baumann reaction the nitrile can then be hydrolysed to benzaldehyde and quinaldic acid by acid. 

The Reissert reaction of quinoline of MesSiCN/RCOCl can be conducted in an enantioselective fashion in the presence of a chiral BINAP-based catalyst to give enantiomeric nitriles of type 23 [91]. The Reissert compounds 23 are hydrolysed in an acid medium giving aldehydes and quinoline-2-carboxylic acid 24 ... 

Reductive oxidation of />-nitrotoluene to -aminobenzaldehyde, 31, 6 Reformatsky reaction, 37, 38 Reissert s compound, 38, 58 Reissert reaction, 38, 58 Replacement, benzenesulfonate groups by bromine atoms, 31, 82 bromine, by a thiol group, 30, 35 by fluorine, 36, 40 chlorine, by an amino group, 31,45 by a thiol group, 32, 101 by iodine, 30, 11 by methoxyl, 32, 79 by nitrile, 36, 50 in an imido-chloride group by an anilino group, 31, 48 chlorine and nitro by ethoxyl radicals, 32,68... 

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