Quinoline, preparation derivatives

Amino group of 3-(4-aminobutyl)-2,3,4,4u,5,6-hexahydro-l//-pyrazino [l,2-u]quinoline, prepared from 3-[4-phthalimidobutyl) derivative by treatment with H2NNH2 H2O in boiling EtOH, was acylated with 2-fluorenecarbonyl chloride in the presence of NEt3 in CHCI3 (97MIP12). 

The traditional unpredictably violent nature of the Skraup reaction (preparation of quinoline and derivatives by treating anilines with glycerol, sulfuric acid and an oxidant, usually nitrobenzene) is attributed to lack of stirring and adequate temperature control in many published descriptions [1], A reaction on 450 1 scale, in which sulfuric acid was added to a stirred mixture of aniline, glycerol, nitrobenzene, ferrous sulfate and water, went out of control soon after the addition. A 150 mm rupture disk blew out first, followed by the manhole cover of the vessel. The violent reaction was attributed to doubling the scale of the reaction, an unusually high ambient temperature (reaction contents at 32°C) and the accidental addition of excess acid. Experiment showed that a critical temperature of 120°C was attained immediately on addition of excess acid under these conditions [2],... 

Other esters such as the benzoyl,108 stearoyl,101 oleoyl,101 can be prepared by treating xylan with the appropriate chloride in the presence of sodium hydroxide, potassium hydroxide, pyridine or quinoline. These derivatives have not been characterized, perhaps because of their insoluble nature. 

As for quinolines, isoquinoline derivatives can be prepared by ring transformation of other heterocycles. For instance, oxazole-4-carboxylic ester 74, obtained from phthalic anhydride and isocyanoacetic ester, is converted into the l-isoquinolone-3-carboxylic ester 75 in an acidic medium, probably by hydrolysis to the enaminocarboxylic acid 76 followed by cyclization. 

In several synthetic endeavors to ion-receptor molecules, the simple tris(hydroxyphenyl) benzene 233, the more complex quinoline-containing derivative 239, and the related 243 have been prepared by combined DoM-Negishi cross-coupling strategies (Scheme 14.45 and Scheme 14.46). In the Negishi approach (Scheme 14.45), the 1 3 cross-coupling reaction between 231 and 232,... 

Seven-membered heterocyclic annellated quinolines and derivatives, often exhibit valuable biological activities, thus 228a and 228b were synthesized from 3-acetyl-4-(methylthio)quinolin-2(li4)-one 227 and the products were fully characterized (13RCI1209). A synthetic strategy to prepare a new class of compound, 5H-pyrrolo[2,l-[Pg.556]

On acetylation it gives acetanilide. Nitrated with some decomposition to a mixture of 2-and 4-nitroanilines. It is basic and gives water-soluble salts with mineral acids. Heating aniline sulphate at 190 C gives sulphanilic add. When heated with alkyl chlorides or aliphatic alcohols mono- and di-alkyl derivatives are obtained, e.g. dimethylaniline. Treatment with trichloroethylene gives phenylglycine. With glycerol and sulphuric acid (Skraup s reaction) quinoline is obtained, while quinaldine can be prepared by the reaction between aniline, paraldehyde and hydrochloric acid. 

Little is known quantitatively about substituent effects in the nitration of derivatives of azanaphthalenes. In preparative experiments 4-hydroxy-quinoline, -cinnoline, and -quinazoline give the 6- and 8-nitro compounds, but with nitric acid alone 4-hydroxyquinoline and 2,4-di-hydroxyquinoline react at With nitric acid, 4-hydroxycinnoline... 

Synthesis and Properties. Polyquinolines are formed by the step-growth polymerization of o-aminophenyl (aryl) ketone monomers and ketone monomers with alpha hydrogens (mosdy acetophenone derivatives). Both AA—BB and AB-type polyquinolines are known as well as a number of copolymers. Polyquinolines have often been prepared by the Friedlander reaction (88), which involves either an acid- or a base-catalyzed condensation of an (9-amino aromatic aldehyde or ketone with a ketomethylene compound, producing quinoline. Surveys of monomers and their syntheses and properties have beenpubhshed (89—91). 

Polymers. Quinoline and its derivatives may be added to or incorporated in polymers to introduce ion-exchange properties (see Ion exchange). For example, phenol—formaldehyde polymers have been treated with quinoline, quinaldine, or lepidine (81) (see Phenolic resins). Resins with variable basic exchange capacities have been prepared by treating Amherlites with 2-methylquinoline (82). 

Uses. Isoquinoline and isoquinoline derivatives are usehil as corrosion inhibitors, antioxidants, pesticides, and catalysts. They are used in plating baths and misceUaneous appHcations, such as in photography, polymers, and azo dyes (qv). Numerous derivatives have been prepared and evaluated as pharmaceuticals. Isoquinoline is a main component in quinoline stiH residue bases, which are sold as corrosion inhibitors and acid inhibitors for pickling iron and steel. 

The cinchona alkaloids on degradation break down into derivatives of (1) quinoline and (2) quinuclidine and the synthesis of any one of them involves the preparation of each of these two halves in a form suitable for combination. 

These substances differ structurally from niquidine (VI) by the substitution in the latter of a propylidene chain at C. Ainley and King having already found that d- and Z-dihydroquinicinols (VIII) which are y-substituted piperidine derivatives, were inactive, it appeared from these two sets of results that the strongly basic centre should not be separated by more than two carbon atoms frorn the point of attachment to the quinoline nucleus. King and Work therefore prepared a series of... 

Work also prepared a series of carbinolamines and polyamines without a quinoline nucleus but, in other respects, conforming in type and range of molecular weight, with quinoline compounds known to possess plasmocidal activity. As none of these were active, it seems clear that the quinoline nucleus in the cinchona alkaloids and in certain synthetic anti-malarials is a potent factor in the production of plasmocidal action. Later the same author made (1942) a series of lepidylamine derivatives of the form R. Q. CHj. NH[CH2] . NEtj, which were found to be inactive, in spite of their similarity to the active examples of the type R. Q. NH[CH2] . NEt2 prepared by Magidson and Rubtzow. Rubtzow (1939) has also shown that an isomeride of dihydroquinine (II) with the quinuclidine nucleus attached via the carbinol group at C in the quinoline nucleus was inactive in an infection of Plasmodium prcecox in finches. 

The preparation and use of derivatized Meldrum s acid has led to an alternative preparation of 2-substituted quinolines (49 and 50) and the preparation of pyridopyrimidines (52). When Meldrum s acid derivatives are used (as shown in this example) decarboxylation occurred under the cyclization conditions. Three component coupling has been used to readily assemble the desired 3-anilino-acrylate from reaction of Meldrum s acid, (EtO)3CH and an aniline (e.g. 54 or 55).< ... 

A number of dihydroquinolines have been prepared by treating aniline derivatives with acetone or mesityl oxide in the presence of iodine. In these cases aromatization to the fully unsaturated quinoline would require the loss of methane, a process known as the Riehm quinoline synthesis. Such Skraup/Doebner-von Miller-type reactions are often low yielding due to large amounts of competing polymerization. For example, aniline 37 reacts with mesityl oxide to give dihydroquinolines 39, albeit in low yield. ... 

Examples from preparative chemistry indicate the possible occurrence of special alpha-e ects in several other cases. The different reaction of 2- and 4-ethoxy quinolines with a thiol yielding carbostyril and a 4-arylthio derivative, respectively, may indicate the intervention of structures such as 17 in the transition state of the 2-isomer. 

The isomeric 2-substituted 4,9-dioxo-4,9-dihydrooxazolo[5,4- ]quinolines 15 were prepared in the same way starting from corresponding 6-chloro derivative (91CCC1919). 

Aminothiazolo[5,4-/]quinoline 27 and its acetyl derivative are effective as inhibitors of fogging in the preparation of photographic emulsions by both the acid and the NH4OH processes (51JPJ553). 

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