Quinoline amination

Cu(C9HgN ](Na)2 mw 403.88, N 27.75%, yel-green crysts tnp — explodes at 197—200° bums in flame sol in ethylenediamine with violet color freeing some (Sfi-quinoline darkens in warm acid. It is insensitive to impact. It was prepd by dissolving Cu azide in an iso-quinoline amine soln in ale, by the addn of... 

In contrast, nitrogen-containing bases are contained in many crude-oil fractions. In a typical starting material, 25 35 % of the nitrogen compounds have basic character. The sensitivity of solid acids towards these poisons correlates directly with their basicity. For example, pyridine, quinoline, amines, and indoles are basic, while pyrrole and carbazole are nonbasic. These poisons are best removed by hydrogenation, together with sulfur and most of the heavy metal poisons. 

Doebner-von Miller reaction Condensation of an aromatic amine with an aldehyde or ketone in the presence of hydrochloric acid to form a quinoline derivative. A general method, thus aniline and ethanal give 2-methyl-quinoline (quinaldine) and p-phenetidine. 

The mixed amines are dissolved in hydrochloric acid and zinc chloride solution added. The quinoline chlorozincate, (C H7N)2,HtZnCl, crystallises out, being almost insoluble in water, while the aniline chlorozincate remains in solution. The quinoline chlorozincate is then filtered off and decomposed by alkalis, and the liberated quinoline extracted with ether or steam-distilled. 

B) Methiodi s. Members of Classes (i), (ii) and (iv) combine wdth methyl iodide (some very vigorously) to form quaternary methiodides. It is best to add the amine to an excess of methyl iodide dissolved in about twice its volume of methanol, allow any spontaneous reaction to subside, and then boil under reflux for 30 minutes (extend to 1 hour for Class (iv) except pyridine and quinoline). The methiodide may crystallise when the reaction-mixture cools if not, evaporate the latter to small bulk or to dryness, and recrystallise, (M.ps., pp. 553-554 )... 

Quinoline derivatives may be synthesised by heating aii aromatic amine with an aldehyde or a mixture of aldehydes in the presence of concentrated hydrochloric or sulphuric acid this synthesis is known as the Doebner - Miller reaction. Thus aniline and paraldehyde afford 2-methylquinohne or quinaldine. 

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. 

Supplement 1953 3242-3457 Hydroxy-carboxylic acids, 190 In i doxylic acid, 226. Carbonyl-carboxylic acids, 284. i Sulphonic acids, 386 Quinoline sul-phonic acid, 390. Amines, 419 2-Aminopyridine, 428. Amino-carboxylic acids, 541 Tryp- tophane, 545. Hydrazines, 563. Azo. compounds, 572. Diazo compounds, 590. ... 

Because of these difficulties, special mechanisms were proposed for the 4-nitrations of 2,6-lutidine i-oxide and quinoline i-oxide, and for the nitration of the weakly basic anilines.However, recent remeasurements of the temperature coefficient of Hq, and use of the new values in the above calculations reconciles experimental and calculated activation parameters and so removes difficulties in the way of accepting the mechanisms of nitration as involving the very small equilibrium concentrations of the free bases. Despite this resolution of the difficulty some problems about these reactions do remain, especially when the very short life times of the molecules of unprotonated amines in nitration solutions are considered... 

Aniline [AMINES - AMINES, AROMATIC - ANILINE AND ITS DERIVATIVES] (Vol 2) -for quinolines [QUINOLINES AND ISOQUINOLINES] (Vol 20)... 

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). 

Phenols. Phenols are unreactive toward chloroformates at room temperature and at elevated temperatures the yields of carbonates are relatively poor (< 10%) in the absence of catalysis. Many catalysts have been claimed in the patent Hterature that lead to high yields of carbonates from phenol and chloroformates. The use of catalyst is even more essential in the reaction of phenols and aryl chloroformates. Among the catalysts claimed are amphoteric metals or thek haUdes (16), magnesium haUdes (17), magnesium or manganese (18), secondary or tertiary amines such as imidazole (19), pyridine, quinoline, picoline (20—22), heterocycHc basic compounds (23) and carbonamides, thiocarbonamides, phosphoroamides, and sulfonamides (24). 

Friedlander synthesis, 2, 444 as antipyretic, 1, 172 Quinoline-4-carboxylic acids amination, 2, 236 Beyer synthesis, 2, 475 Pfitzinger synthesis, 2, 446... 

CHICHIBABIN Aminalion a Amination ol pyridines quinolines and older N deterocycles... 

Other secondary amines such as pyrrolidine, di- -butylamine, tetrahydro-quinoline, n-benzylamine, and piperidine were also found to be capable of effecting this reduction. Interestingly, morpholine does not reduce enamines as readily (47) and its acid-catalyzed reaction with norbornanone was reported (45) to give only the corresponding enamine (93), although trace amounts of the reduction product were detected when cyclohexanone was treated with morpholine under these conditions (47a). The yield of morpholine reduction product was increased by using higher temperatures. 

The lithium- -propylamine reducing system has been found capable of reducing julolidine (113) to /d -tetrahydrojulolidine (114, 66% yield) and 1-methyl-1,2,3,4-tctrahydroquinoline to a mixture of enamines (87% yield), l-methyl-J -octahydroquinoline (115) and 1-methyl-al -octahydro-quinoline (116) 102). This route to enamines of bicyclic and tricyclic systems avoids hydroxylation, which occurs during mercuric acetate oxidation of certain bicyclic and tricyclic tertiary amines 62,85 see Section III.A). 

The Knorr quinoline synthesis refers to the formation of a-hydroxyquinolines 4 from P-ketoesters 2 and aryl amines 1. The reaction usually requires heating well above 100°C. However, some cases do exist when the cyclization takes place in the presence of a catalytic amount of mineral acid at temperatures as low as -10 °C. The intermediate anilide 3 undergoes cyclization by dehydration with concentrated sulfuric acid. The reaction is conceptually close to the Doebner-Miller and Gould-Jacobs reactions. ... 

The idea that dichlorocarbene is an intermediate in the basic hydrolysis of chloroform is now one hundred years old. It was first suggested by Geuther in 1862 to explain the formation of carbon monoxide, in addition to formate ions, in the reaction of chloroform (and similarly, bromoform) with alkali. At the end of the last century Nef interpreted several well-known reactions involving chloroform and a base in terms of the intermediate formation of dichlorocarbene. These reactions included the ring expansion of pyrroles to pyridines and of indoles to quinolines, as well as the Hofmann carbylamine test for primary amines and the Reimer-Tiemann formylation of phenols. 

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