3.4- Dihydroquinolines, formation

The reduction of quinoline with either lithium or sodium in liquid ammonia produces only 1,4-dihydroquinoline . Formation of 1,2-dihydroisoquinolines was observed in the reduction of quaternary isoquinoline salts with sodium hydrosulphite ", lithium aluminium hydride " , NaBH4 , dialkylaluminohydrides or on treatment with a Grignard reagent . 

This is an example of the Doebner synthesis of quinoline-4-carboxylic acids (cinchoninic acids) the reaction consists in the condensation of an aromatic amine with pyruvic acid and an aldehj de. The mechanism is probably similar to that given for the Doebner-Miller sj nthesis of quinaldiiie (Section V,2), involving the intermediate formation of a dihydroquinoline derivative, which is subsequently dehydrogenated by the Schiff s base derived from the aromatic amine and aldehyde. 

Schwarz et al. in agreement with Shukla observed the formation of 2-Oxo-l, 2-dihydroquinoline, 8-hydroxy-2-oxo-l, 2-dihydroquinoline, 8-hydroxycoumarin, and 2,3-dihydroxy-phenylpropionic acid were found as intermediates of quinoline transformation by P. fluorescens 3 and P. putida 86 [325], They compared that metabolic pathway with the one obtained for Rhodococcus strain B1 (Fig. 22). This bacterium was unable to yield denitrogenated metabolites (i.e., 2-oxo-l, 2-dihydroquinoline, 6-hydroxy-2-oxo-l, 2-dihydroquinoline, and 5-hydroxy-6-(3-carboxy-3-oxopropenyl)-lH-2-pyridone). 

The first step in any of the degradation pathways is the formation of 2-quinolinone/2-hydroxyquinoline/2-oxo-l, 2-dihydroquinoline and quinoline2-oxidoreductase has been shown to be responsible for this initial metabolic reaction [318], When the oxidation is carried out by a dioxygenase, it resulted in the formation of ds-hydrodiol derivatives and when oxidation is carried out by a monooxygenase monohydroxilated derivatives are formed, via the arene oxide intermediates [323],... 

An efficient high yielding synthesis of 3-substituted 2,3-dihydroquinolin-4-ones 90 was developed by using a one-pot sequential multi-catalytic process <06TL4365>. The scheme below shows the one-pot sequential multi-catalytic Stetter reaction of aldehyde 91 and a, (3-unsaturated esters 92, resulting in the formation of the desired dihydroquinolines 90. 

PEPTIDE-BOND FORMATION FROM 1-ETHOXYCARBONYL-2-ETHOXY-1,2-DIHYDROQUINOLINE-MEDIATED REACTIONS OF /V-ALKOXYCARBONYLAMINO ACIDS... 

The formation of cyclic nitrones (150) from pericyclic mechanism. Kinetic and computational studies have provided evidence for the involvement of a novel pseudo-pericyclic electrocyclization in the conversion of o-vinylphenyl isocyanates into quinolin-2-ones. " Such reactions have also provided evidence of torquoselectivity in a 6jt system. Hash vacuum thermolysis of triazoles (151) has been found to afford dihydroquinolines (155), presumably by generation of a-oxoketenimines (152) which can undergo a [1,5]-hydrogen shift to the o-quinoid imines (153)7(154) and subsequent electrocyclization (see Scheme 57). 

Reduction of quinolines in acid solution at a lead cathode or by dissolving zinc leads to attack on the heterocyclic ring with the formation of 4,4-coupled products, together with the tetrahydroquinoline [82,83]. In the case of 2- and 4-methyl substituted quinolines, dimeric products are obtained in 10 90 % yields. In these processes, dimerization of the one-electron addition product is in competition with further reduction to give the 1,4-dihydroquinoline, The latter is an enamine and it... 

A novel approach to the construction of the duocarmycin core has involved the formation of the cyclopropane ring and the five-membered C-ring by an intramolecular ring contraction <1998CPB400, 2004OL2953>. Thus, treatment of the dihydroquinoline 210 with potassium carbonate in methanol gives the tetracyclic product 211 (Equation 141). 

EEDQ is a valuable reagent for carboxyl activation in the coupling of amino acids [55]. Ideal d-a pairings of various reactive moieties facilitate the formation of the semicarbonate intermediates. Of course, a major driving force for this transformation is the aromatization of the dihydroquinoline system. 

Very recently, Fujii and Ohno developed a route for the synthesis of dihydroquinoline and chromene derivatives under mild reaction conditions. Hydroarylation leads to a highly selective formation of six-membered rings, depending on the carbon (terminal or central allenic) that reacts with the aryl moiety [50]. 

Treatment of quinoline with sodium gives mainly 2,3 -biquinolyl, the formation of which can possibly be explained as initial reduction followed by reaction of the dihydroquinoline anion with another molecule of quinoline (379). Quinoxaline derivatives in an ether solvent are reduced by sodium to the corresponding anti-aromatic doubly charged anions, e.g. (380) (85JA1501). 

The use of Sc(OTf)3 as the catalyst facilitated the Skraup synthesis of 1,2-dihydroquinolines from anilines and a variety of dialkyl ketones at mild conditions (room temperature). Nevertheless, an elevated temperature was necessary if acetophenone was employed in the cyclo condensation with anilines [109]. Microwave dielectric heating at 150 °C for 50 min was sufficient to bring about the formation of the desired 1,2-dihydroisoquinolines (Scheme 40). 

During the synthesis of such compounds, the epoxide is often installed at an early stage for example, dihydroquinoline 31 (Scheme 18) is readily epoxidized with MCPBA, and subsequent formation of the bis-alkynyl iodides followed by bis-intramolecular Stille coupling occurs with complete chemoselectivity <2006ARK261>. 

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