Quinoline Reissert reaction

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... 

In the Reissert reaction, 1-benzoylquinolinium ions (formed in situ from quinolines and PhCOCl) and cyanide ions give Reissert compounds thus, quinoline itself forms (313). These Reissert compounds are hydrolyzed by dilute alkali to, for example, quinoline-2-carboxylic acids and benzaldehyde. Isoquinolines also form Reissert compounds (e.g. 314). 

Reactions of quinoline Reissert compounds were less satisfactory than those of the corresponding isoquinolines. The hydrochloride of 64 with DMAD gave 65 in only 7% yield in methylene chloride ethanol, and 10% in DMF. From a study of the mechanism of the 1,3-dipolar addition of Reissert salts to arylpropiolate esters, McEwen et a/.499 concluded that a concerted cyclization was more probable than a two-step process. 

Shibasaki and co-workers applied (BINOL)Al(III)-derived catalyst 5a, previously developed for the cyanation of aldehydes [28], to the asymmetric Strecker reaction. This catalyst proved to be highly enantioselective for both aromatic and a,p-unsaturated acyclic aldimines (>86% ee for most substrates) (Scheme 8) [63-65]. Aliphatic aldimines underwent cyanide addition with lower levels of enantioselectivity (70-80% ee). A significant distinction of 5 relative to other catalysts is, undoubtedly, its successful application to the hydrocyanation of quinolines and isoquinolines, followed by in situ protection of the sensitive cx-amino nitrile formed (this variant of the Strecker reaction is also known as the Reissert reaction [66]). Thus, Shibasaki has shown that high enantioselectivities (>80% ee for most substrates) and good yields are generally obtainable in the Reissert reaction catalyzed by 5b [67,68]. When applied to 1-substituted... 

Sodium cyanide in DMF at 120 °C has been used for the decarboxylation of 1-substituted-4-oxoquinoline-3-carboxylic acids <94TL(35)8303>. Quinoline Reissert adducts have been epoxidized at the 3,4-bond. Its reaction with amine nucleophiles gave regiospecifically substituted 1,2,3,4-tetrahydroquinolines <95H(41)897>. Successive Claissen rearrangements of 2-(8-quinolinoxymethyl)-3-(8-quinolinoxy)-l-propene gave a product which shows excellent ability to extract heavy metal ions <95TL(36)5567>. An Eschenmoser approach has been used in a facile synthesis of monofunctional and difunctional A -substituted-4-alkylidenequinolines (54) (Scheme 39) <95S(St)56>. 

When first reported in 1905, the Reissert reaction demonstrated the addition of KCN to quinoline in the presence of benzoyl chloride, but many new modifications since then have employed other nucleophiles and catalytic promotion by a Lewis acid. Shibasaki reported in 2001 the first catalytic enantioselective Reissert-type reaction. Optimized reaction conditions involving an electron-rich aromatic acid chloride in a low-polarity solvent, and use of catalyst 14, were found to suppress the racemic pathway and resulted in good enantioselectivity (Scheme 2) <2001JA6801>. 

A chiral auxiliary-mediated Reissert reaction has been demonstrated. Though the diastereomeric ratios are not as high as hoped, the conditions are simple and the products are easily separated by flash chromatography (Equation 63) <2005TL2983>. A catalytic version of the asymmetric Reissert reaction with quinolines, isoquinolines, and pyridines has been developed by Shibasaki and co-workers <2005PAC2047, 2004JA11808>. 

The Reissert reaction with quinoline-1-oxide which was noted in the previous review has now been extended to a number of additional heterocyclic iV-oxides but is considered to be beyond the scope of this review. 

High yields of a-cyanoazines are obtained from pyridine, quinoline or isoquinoline (V-oxides and TMS-CN in acetonitrile/triethylamine or in DMF, and so in THF in the presence of tetrabutylammoni-um fluoride. In another variation TMS-CN together with dimethylcarbamoyl chloride is used. Mechanistically these transformations should be similar to the Reissert reaction and may run through intermediates of type (18) and (19 Scheme 22) ... 

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. 

Asymmetric acylcyanation of quinolines (Reissert-type reaction) with 2-furoyl chloride and TMSCN is successfully performed by using the chiral catalyst 168 (Scheme 10.243) [658]. In this reaction the sterically more demanding complex 168b exceeds 168a in enantioselectivity. 

In the introduction of a sidechain to C-2 of the quinoline nucleus via 1,2-addition (extended Reissert reaction) to form an adduct with a A -(p-methoxybenzyl) group, the rearomatization step can be initiated by oxidative C—N bond cleavage with CAN7... 

Petasis reaction on quinoline following an analogous course to the Reissert reaction is catalyzed by the thiourea 196, water and NaHCOs are facilitating additives. ... 

Hydrogenation of several 6- and 7-substituted quinoline Reissert compounds (1) in the presence of Raney nickel leads to the 2-aminomethyl-1,2,3,4-tetrahydroquinoline derivatives 68.114 A similar reduction of the Reissert compound derived from benzo[/]quinoline, followed by reaction of the crude product with carbon disulfide, gave the diazacyclopentaphenan-threne derivative 69.115... 

Cyanadons. Aluminum complexes of BINOLs (1) that are armed at C-3 and C-3 with diarylphosphine oxide groups possess both Lewis acid and base centers. Asymmetric cyanation of aldehydes and mines with MeaSiCN, and of quinolines and isoquinolines in a manner analogous to the Reissert reaction is successful (ee 70-90%). The asymmetric Strecker synthesis is applicable to conjugated aldimines and the higher reactivity of Me SiCN than HCN in the presence of 10 mol% of PhOH enables its use in catalytic amount while supplying stoichiometric HCN as the cyanide source. 

Quinoline adds cyanide [as KCN or (CH3)3SiCN] in the 2-position in the presence of acylating agents, usually C6H5COCI or CICOOR, producing A-acyl-2-cyano-l,2-dihydroquinolines 23 Reissert reaction) ... 

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 ... 

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