Reissert compounds acid hydrolysis

How might quinoline be converted into quinoline-2-car-boxylic acid via a Reissert compound and hydrolysis ... 

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. ... 

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. 

Acid-catalyzed hydrolysis of Reissert compounds results in an aldehyde, a formal reduction product of the acyl halide utilized in the Reissert compound formation (11). The mechanism of the reaction according to McEwen and Cobb (3), is shown in Scheme 2. 

A hydrogen attached to a pyridine or pyridine 1-oxide nucleus cannot be replaced directly by cyanide however, addition of cyanide to various quaternary salts constitutes an important class of reactions of synthetic importance. Before surveying these reactions in detail, the four main classes are outlined. In 1905, Reissert reported the first example, the reaction of quinoline with benzoyl chloride in aqueous potassium cyanide (Scheme 111) (05CB1603). This yielded a crystalline product, C17H12N2O, a Reissert compound (176) which afforded benzaldehyde and quinaldinic acid on acid hydrolysis (Scheme 111). Kaufmann (09CB3776) treated a 1 -methylquinolinium salt with aqueous potassium cyanide and observed 1,4-rather than 1,2-addition (Scheme 112), the Reissert-Kaufmann reaction. Reissert compounds are well known in the quinoline and isoquinoline series, but only rarely have even small yields been found in the pyridine series. On the other hand, cyanide ions add 1,4 with ease to pyridinium salts that have an electron withdrawing substituent at C-3. 

In the early days, greatest interest was focused on the acid-catalyzed hydrolysis (by hydrochloric acid in the presence of 2,4-dinitrophenylhydrazine) of Reissert compounds to aldehydes and the corresponding heterocyclic carboxylic acid derivatives. This reaction is fairly general for compounds of quinoline (178) and isoquinoline (179) (Table 18), but it is not applicable to pyridines as they rarely form Reissert compounds. The 3-hydroxyquino-line Reissert compound does not yield benzaldehyde, probably because acylation of the 3-hydroxy group prevents formation of the required cyclic intermediate (180). Some nitroquinolines and isoquinolines give low yields of benzaldehyde. Rather curiously, disub-stituted quinoline Reissert compounds yield less of the aldehyde than of the corresponding... 

The mechanism proposed495-497 for the acid-catalyzed hydrolysis of Reissert compounds (l-acyl-l,2-dihydro-2-cyanoquinolines or 2-acyl-1,2-dihydro-1-cyanoisoquinolines) invokes a mesoionic oxazolinium... 

Phthalazine has been reported to give the compound 6 which, as noted in subsequent sections, behaves as a normal Reissert compound on acid-catalyzed hydrolysis and alkylation. ... 

In the early work on Reissert compounds the reaction that attracted the greatest attention was the acid-catalyzed hydrolysis to aldehydes plus the corresponding heterocyclic carboxylic acid or acid derivative. 

The acid-catalyzed hydrolysis continues to be used as a highly satisfactory method for the synthesis of quinaldic acids. The reaction of Reissert compound (7) with hydrobromic acid in acetic acid gave near quantitative yields of quinaldic acid hydrobromide with no contamination from other acid derivatives and would appear to be the method of choice for this conversion. This method has subsequently been used to produce high yields of benzo(/)quinoline-3-carboxylic acid and phthalazine-1-carboxylic acid. ... 

On the basis of the mechanism for the acid-catalyzed hydrolysis of Reissert compounds it can be reasoned that such compounds might function as acylating agents towards carbonium ions. Studies toward this end have been reported. 

As noted in Section III, C, a pure sample of 46 has now been obtained and this does not give benzaldehyde on acid hydrolysis.Other dihydro Reissert compounds (52, R = H and R = OCH3) have been prepared bj reaction of the appropriate 3,4-dihydroisoquinoline with... 

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. 

Reissert reaction. Formation of l-acyl-2-cya-no-l,2-dihydroquinoline derivatives (Reissert compounds) by reaction of acid chlorides with quinoline and potassium cyanide hydrolysis of these compounds yields aldehydes and quinaldic acid. 

Except for a demonstration that the phthalazine Reissert compound (3 R = Ph) behaves normally in giving benzaldehyde on acid-catalyzed hydrolysis, no new reports have appeared of Reissert compounds being used in aldehyde synthesis. Acid-catalyzed hydrolysis has been used, however, in some cases to prepare heterocyclic carboxylic acids. Thus in addition to the preparation of isoquinaldic acid, phthalazine-1-carboxyIic acid and 15 have been prepared from 3(R = Ph) and 11, respectively. Acid-catalyzed hydrolysis of 16 occurs with cyclization to give 17. A series of Reissert compounds derived from substituted 3-aminoquinolines have been converted to the corresponding quinaldic acids by acid-catalyzed hydrolysis. ... 

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... 

Treatment of isoquinoline with sulphuryl chloride and potassium cyanide gives 4-chloro-l-cyanoisoquinoline and l-carbamoyl-3-cyanoisoquinoline, the relative yields of the two products depending upon the proportion of reagents. The Reissert compound from 4-methylisoquinoline gives the bromohydrin (172), and this, on treatment with aqueous sodium hydroxide, affords the benzoylimino-compound (173). Hydrolysis of the latter with dilute hydrochloric acid yields 4-methylisocoumarin (174) (Scheme 71). ... 

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