Synthesis of Quinoline

In yet another solventless cyclisation reaction using montmorillonite KIO clay under MWI condition, readily available 2 -aminochalcones provide easy 

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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. 

Oxidation. The synthesis of quinolinic acid and its subsequent decarboxylation to nicotinic acid [59-67-6] (7) has been accompHshed direcdy in 79% yield using a nitric—sulfuric acid mixture above 220°C (25). A wide variety of oxidants have been used in the preparation of quinoline N-oxide. This substrate has proved to be useful in the preparation of 2-chloroquinoline [612-62-4] and 4-chloroquinoline [611 -35-8] using sulfuryl chloride (26). The oxidized nitrogen is readily reduced with DMSO (27) (see Amine oxides). 

In their general synthesis of quinoline-2,5,8(lf/)-triones, Avendano and coworkers use this modified protocol to access the key 2,5-dimethoxyanilide systems 11 required in their synthetic plan." For more examples, see reference 11 and references cited within. 

The Pfitzinger reaction entails the synthesis of quinoline-4-carboxylic acids 2 via condensation of isatic acids formed from isatins 1 and a-methylene carbonyl compounds in the presence of strong aqueous bases. Subsequent decarboxylation can afford the corresponding quinolines. " ... 

The Skraup reaction involves the synthesis of quinoline 3 from the reaction of aniline 1 and glycerol 2 in the presence of a strong acid and an oxidant. 

The palladium-catalyzed reaction of o-iodoanilides with terminal acetylenic carbinols provides a facile route to the synthesis of quinolines using readily available starting materials (93TL1625). When o-iodoanilide 126 was stirred with acetylenic carbinol 127 in the presence of bis-triphenyl phosphine palladium(ll) chloride in triethylamine at room temperature for 24 h, the substituted alkynol 128 was obtained in 65% yield. On cyclization of 128 with sodium ethoxide in ethanol, 2-substituted quinoline 129 was obtained in excellent yield. 

Cacchi and Palmier (83T3373) investigated a new entry into the quinoline skeleton by palladium-catalyzed Michael-type reactions. They found that phenyl mercurial 134 was a useful intermediate for the synthesis of quinoline derivatives, and that by selecting the reaction conditions the oxidation level of the heterocyclic ring in the quinoline skeleton can be varied. On such example is shown in Scheme 16. PdCla-catalyzed coupling between organomercurial reagent 134 and enone 135 delivered adduct 136 which was subsequently cyclized to quinoline 137 under acidic conditions. 

Most of the nitrobenzene (=97%) produced is used to make aniline. Other uses include synthesis of quinoline, benzidine, and as a solvent for cellulose ethers. 

Imino Diels-Alder reactions catalyzed by indium trichloride (InCIs). Facile synthesis of quinoline and phenanthridinone derivatives [106]... 

For the synthesis of quinolines and isoquinolines the classical approaches are the Skraup and the Bischler-Napieralski reactions. The reaction of substituted anilines with different carbonyl compounds in acid medium has been reported to be accelerated under microwave irradiation to give differently substituted quinolines and dihydro quinolines [137]. Although the yields are much better and the conditions are milder than under conventional heating, the acidity of the medium may prevent the preparation of acid-sensitive compounds. Thus, alternative approaches have been investigated. Substituted anilines and alkyl vinyl ketones reacted under microwave irradiation on the surface of sihca gel doped with InCU without solvent [137] to furnish good yields of quinohnes 213 (Scheme 77). 

Scheme 19 Synthesis of quinolines by iron(III)-catalyzed three-component coupling/hydroaryla-tion of aldehydes, alkynes, and amines...

Comb copolymers, 7 610t Combed yarn, 11 178 Combes synthesis, of quinolines, 21 189 Combicat, 7 387, 392 Combinational libraries, 7 382 characterization, 7 404-405 composition gradient libraries, 7 407 design, 7 399-400 fabrication, 7 414-419 temperature gradient libraries, 7 407—408 thickness gradient libraries, 7 406 Combination electrodes, 14 30 Combination vaccines, 25 504-505 Combinatorial biology, 16 414 Combinatorial biosynthesis, 15 301-302, 305... 

Conrad-Limpach-Knorr synthesis, of quinolines, 21 189 Conrad recycling process, 21 455 Conradson carbon test method, 11 705, 721 Consensus materials standards, 15 743 Consent decree protocols, in the United States, 11 692-694 Consent decrees, 11 689-690 Consequence analysis, 21 860-861 Consequence modeling, 13 165-166 Conservation applications, high performance fibers in, 13 398 Conservation of energy, 21 290 Conservation of mass, 11 737, 738-739 Conservation, of resources, 24 164-167 Conservation scientists, 11 398-399 Consistent force field, 16 744 Consolidants, in fine art examination/ conservation, 11 410... 

In the Skraup synthesis of quinoline the principal difficulty has always been the violence with which the reaction generally takes place it occasionally proceeds relatively smoothly, but in the majority of cases gets beyond control, with consequent loss of material through the condenser. By the addition of ferrous sulfate, which undoubtedly functions as an oxygen carrier, the reaction is extended over a longer period of time. It is thus possible to work with much larger quantities of material when ferrous sulfate is employed. 

Abstract Asymmetric total synthesis of marine natural product, nakadomarin A, is described and as further extension, a novel synthesis of quinoline and indole ring system by ring closing metathesis is also described. 

Novel Synthesis of Quinolines and Indoles Using Ring Closing Metathesis... 

Friedlander synthesis org chem A synthesis of quinolines the method is usually catalyzed by bases and consists of condensation of an aromatic p-amino-carbonyl derivative with a compound containing a methylene group in the alpha position to the carbonyl. fred.lan dar. sin-tha-sas ... 

Conrad, M. Limpach, L. Ber. Dtsch. Chem. Ges. 1887, 20, 944. Max Conrad (1848—1920), born in Munich, Germany, was a professor of the University of Wiirz-burg, where he collaborated with Leonhard Lhnpach (1852—1933) on the synthesis of quinoline derivatives. 

Synthesis of quinolines by nucleophilic substitution of nitrogen atom in oxime derivatives was described by Narasaka and coworkers. /3-Aryl ketone oximes 297 in the presence of trifluoroacetic anhydride and 4-chloranil afforded quinolines 298 in 72-82% yield (equation 128). However, interaction of oxime 299 with 48% HBr at 105 °C proceeded with elimination of hydroxyimino group and gave 2,3-dimethoxynaphtho[l,2-fc]quinolizinium bromide (300) in 45% yield (equation 129). ... 

Synthesis of Quinolines Substituted in the Carbocyclic Ring via Directed Mktalation... 

Makioka Y, Shindo T, Taniguchi Y, Takaki K, Fujiwara Y (1995) Ytterbium(III) triflate catalyzed synthesis of quinolinic derivatives from V-arylaldimincs and vinyl ethers. Synthesis 801-804... 

Friedlander Hetero-Annulation for the Synthesis of Quinoline Derivatives... 251... 

The main methods used for the synthesis of quinolines, isoquinolines and their derivatives... 

Since most anilines are derived from nitro intermediates the reduction of the aromatic nitro group followed by cyclization of the aniline in situ has offered a direct approach to the synthesis of quinolines. The ort/io-nitro cinnamic acid derivatives 28 undergo cyclization, where R corresponds to R , respectively, when treated with zinc in near-critical water at 250 °C... 

In the original Doebner-von Miller synthesis of quinolines an arylamine condenses with two molecules of an aldehyde most of the variants have been dealt with in Section 2.08.2.2.3.ii since the intermediate (often used directly) is an a,-unsaturated aldehyde. Two further major variations, the Beyer modification and the Doebner cinchoninic acid synthesis, will be dealt with here, since intermediates are rarely isolated. 

The Friedlander synthesis of quinolines has been adapted to give derivatives of compounds (279) and (280). The isomeric quinoline aldehydes (284) and (285) react with various ketones to give (286) and (287) (77CR(C)(284)459, 82JHC1289). Compound (286) has also been obtained starting from the Schiff s base derivative of (284) (81JHC925). 

Since then, similar reactions have been reported by different authors examples include the synthesis of quinolines [180] or even pyrroles [181] or enamines from chiral amines [182]. Indoles can also participate in these reactions [183]. 

This reaction is particularly useful in the Fricdlander quinoline synthesis, the use of which has been limited hy the inaccessibility of o-aminobenzaldehydes. Thus a one-pot synthesis of quinolines is now possible by reduction of an o-nitrobenz-aldehyde with the reagent in the presence of an a-mcthylene ketone. 

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