Quinolines Skraup synthesis

Naphtho[l,2-h]pyrylium salts, 5,6-dihydro-2,4-diphenyl-synthesis, 3, 869 Naphtho[2,l-h]pyrylium salts synthesis, 3, 866 Naphthoquinolines, tetrahydro-synthesis, 2, 469 N aphtho[ 1,2-7]quinolines Skraup synthesis, 2, 467... 

Gyclization. Aniline, nitrobenzene, and glycerol react under acid catalysis (Skraup synthesis) to form quinoline [91-22-5] (27). 

Finally, some results obtained from indazoles substituted in the carbocycle are of interest, even though in these cases the reaction does not involve the heterocyclic moiety (Section 4.04.2.3.2(ii)). For example, pyrazolo[3,4-/]- (566) and pyrazolo[4,3-/]-quinolines (567) have been obtained from aminoindazoles by the Skraup synthesis (76JHC899). Diethylethoxy-methylenemalonate can also be used to give (566 R = C02Et, R = OH) (77JHC1175). Pyrazolo-[4,3-/]- and -[4,3-g]-quinazolones (568) and (569) have been obtained from the reaction of formamide with 5-amino-4-methoxycarbonyl- and 6-amino-5-carboxyindazole, respectively (81CB1624). 

Quinoline, 2,4-bis(dimethylamino)-synthesis, 2, 419, 469 Quinoline, 3-bromo-bromination, 2, 319 oxidation, 2, 325 Skraup synthesis, 2, 467 Quinoline, 5-bromo-bromination, 2, 319 nucleophilic substitution, 2, 324 Quinoline, 6-bromo-nucleophilic substitution, 2, 324 Quinoline, 8-bromo-bromination, 2, 319 N-oxide... 

Skraup synthesis starting from 4- and 5-aminobenzothiadiazole afforded only angularly annelated products thiadiazolo[5,4-/i]- and [4,5-/]quinoline, respectively. Attempts to cyclize 4-chloro-5-aminobenzothiadiazole failed (37LA38). 

The Friedlander quinoline synthesis is particular useful for the preparation of 3-substituted quinolines, which are less accessible by other routes. A drawback however is the fact that the required o-atninobenzaldehydes or o-aminoarylketones are not as easy to prepare as, e.g., the anilines that are required for the Skraup synthesis. 

By reaction of a primary aromatic amine—e.g. aniline 1—with glycerol 2, and a subsequent oxidation of the intermediate product 4, quinoline 5 or a quinoline derivative can be obtained.As in the case of the related Friedlander quinoline synthesis, there are also some variants known for the Skraup synthesis, where the quinoline skeleton is constructed in similar ways using different starting materials. ... 

A second similar synthesis, due to Doebner and Miller, leads to the formation of substituted quinolines. The simplest example is the production of quinaldine from aniline and paraldehyde by heating with concentrated hydrochloric acid. The course of the reaction is closely related to that of the Skraup synthesis by route II. There the aniline reacts with acrolein, here with crotonaldehyde, which is easily formed under the conditions which prevail ... 

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. 

Skraup synthesis org chem A method for the preparation of commercial synthetic quinoline by heating aniline and glycerol in the presence of sulfuric acid and an oxidizing agent to form pyridine unsubstituted quinolines. skraup sin-tha-sas slaked lime See calcium hydroxide. slakt iTm )... 

The initial product is a dihydroquinoline it is formed via Michael-like addition, then an electrophilic aromatic substitution that is facilitated by the electron-donating amine function. A mild oxidizing agent is required to form the aromatic quinoline. The Skraup synthesis can be used with substituted anilines, provided these substituents are not strongly electron withdrawing and are not acid sensitive. 

Benzo[/i]quinolines hydrogenation, 2, 329 Skraup synthesis, 2, 467 structure, 2, 110 synthesis, 2, 468 from benzindoline, 2, 491 from propargylnaphthylamines, 2, 416 Benzoquinolinium cations metabolism, 1, 234 Benzoquinolinium salts Beyer synthesis, 2, 474 Benzoquinolinones synthesis, 2, 448... 

The simplest member of the quinoline family is quinoline itself. It is a hygroscopic, yellowish oily liquid that is slightly soluble in water, soluble in alcohol, ether, carbon disulfide, and readily soluble in many other organic solvents. It can be obtained through the distillation of coal tar [2]. Quinoline can be prepared from aniline with acrolein under heated sulfuric acid (the Skraup synthesis [3-6], shown in Scheme 1) [ 1]. Isoquinoline was also isolated from coal tar in 1885 [2]. Both of these bases have been known about for a long time. 

Scheme 1 Synthesis of quinoline, starting from acrolein and aniline (Skraup synthesis) [7]...

The classical Skraup synthesis of quinolines is exemplified by the reaction of aniline 6.3 with glycerol 6.4 under acidic/oxidative conditions to produce quinoline 6.1. 

An important use of the traditional Skraup synthesis is to make 6-methoxy-8-nitroquinoline from an aromatic amine with only one free ortho position, glycerol, the usual concentrated sulfuric acid, and the oxidant arsenic pentoxide. Though the reported procedure uses 588 grams of As2Os, which might disconcert many chemists, it works well and the product can be turned into other quinolines by reduction of the nitro group, diazotization, and nucleophilic substitution (Chapter 23). 

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