Quinoline, 4-methyl

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. 

Derivatives. Small amounts of alkyl quiaolines are present ia the tars resulting from the carbonization and Hquefaction of coal (111). Good yields of 4-methyl quinoline, 4,6-dimethyl quinoline [826-77-7], and 4,8-dimethyl quinoline [13362-80-6] are obtained from 4-(diethylamino)-2-butanone and the appropriate aniline. This approach is a promising addition to the traditional syntheses discussed eadier (112). Vlaylacetylene reacts with mercuric chloride and either aniline or -toluidine to yield 4-methyl- and 4,6-dimethyl quinoline, respectively (113). 

Of the total tar bases in U.K. coke-oven and CVR tars, pyridine makes up about 2%, 2-methyl pyridine 1.5%, 3- and 4-methylpyridines about 2%, and ethylpyridine and dimethylpyridines 6%. Primary bases, anilines and methylanilines, account for about 2% of the bases in coke-oven and CVR tars and 3.5% of the bases in low temperature tars. The main basic components in coke-oven tars are quinoline (16—20% of the total), isoquinoline (4—5%), and methyl quinolines. These dicycHc bases are less prominent in CVR and low temperature tars, in which only a minority of the basic constituents have been identified. 

Methyl-4-phenyl thiazole-2)( 1-methyl quinoline-4)monomethine cyanine iodide, formation. 40... 

Quinaldine (2-methyl-quinoline) (2) 2-methyl-4(lH)-quinolinone (3) 3 -hydroxy-2-methyl-4( 1 H)quinolinone (4) N-acetylanthranilic acid (5) Anthranilic acid (6) Catechol (1) Quinoline (2) 2(lH)quinolinone (3) 8-hydroxy-2(lH)quinolinone (4) 8-hydroxycoumarin (5) 2, 3-dihydroxyphenylpropionic acid... 

Renault et al. cyclized 7V-(3-methylphenyl)aminomethylenemalonate (757, R = Me, R1 = H) in a mixture of acetic anhydride and concentrated sulfuric acid to give a mixture of 5- and 7-methyl-quinoline-3-carboxylates (758 and 759, R = Me, R1 = H) (76MI3). The ratio of the 5- and 7-methyl isomers was determined by H-NMR (see Table VI). Mapara and Desai reported that only the 5-methyl isomer (758, R = Me, R1 = H) was obtained, in 74% yield, under similar conditions (54JIC951). 

Methoxy-3-isobutylpyrazine 176 (Structure 4.53) is found in galbanum oil obtained from Ferula galbaniflua. 2,4-disubstituted pyridines 177, N,N-dimeth-ylated amino compounds 178, alkyl pyrazines 179, quinoline 180 and methyl quinolines 181 were isolated from fig leaf absolute [64]. 

Aminoenone (87), when heated with phosphoryl chloride, cyclizes to 2-(trif uoro-methyl)quinoline, rather than the expected 4-isomer.126 A series of crossover experiments using different perfluoroalkyl and aniline moieties suggest an amine exchange process. A 1,3-diaminoallyl cation (88), i.e. a vinylogous formidinimn salt, is proposed to act as turntable in the process. 

In a reaction which is mechanistically related to the Skraup reaction an a,/ -unsaturated carbonyl compound, generated by way of an acid-catalysed aldol condensation, reacts with a primary aromatic amine in the presence of acid to yield a quinoline derivative (Doebner-Miller reaction). For example, when aniline is heated with paraldehyde (which depolymerises to acetaldehyde during the reaction) in the presence of hydrochloric acid the final product is 2-methyl-quinoline (101) (quinaldine, Expt 8.40). Retrosynthetic analysis for the 1,2-dihydroquinoline reveals crotonaldedhyde as the unsaturated carbonyl component which is in turn formed from acetaldehyde (see Section 5.18.2, p. 799). 

Kitamura, C. Maeda, N. Kamada, N. Ouchi, M. Yoneda, A. Synthesis of 2-(substituted methyl) quinolin-8-ols and their complexation with Sn(II)./. Chem. Soc. Perkin Trans. 1 2000, 781-785. 

Steric hindrance from substituents at the 8-position of a 2-methyl-quinoline inhibits reactions of the nitrogen atom. The quinoline 323 only reacts with DMAD at 200° and yields 324 as sole product.375 In the case of 2,4,6,8-tetramethylquinoline, the analog of 324 and also its presumed precursor (325) formed by proton addition to an intermediate carbanion (cf. Scheme 6) were isolated along with 328.379 This last could be formed via an intermediate (cf. Scheme 6) undergoing proton transfer to 326, cyclization to a phenol (327), and addition to another mole of DMAD.379 2,8-Dimethylquinoline in tetrahydrofuran with DMAD yielded some of the phenol corresponding to 327 379... 

Methoxyquinoline is regioselectively oxidized at the methyl group by a chelate-directed palladium-catalyzed C-H bond activation <2004JA2300>. 8-Methylquinoline is selectively oxidized at the methyl position on treatment with palladium(ll) acetate followed by the oxidant phenyliodinium diacetate in acetic acid. The reaction proceeds via formation of a palladacycle (Scheme 4). Performing the reaction in methanol leads to isolation of 8-(methoxy-methyl)quinoline in 77% yield. 

The reaction of quinoline with [( 5-Cp )Rh(AN)3]2+ gives the rjl(N)-coordinated complex 121 (88OM2250). If this reaction occurs in acetone or acetonitrile containing traces of water, the product is [( 75-Cp )Rh (quinoline)(/x-OH)]2(BF4)2. The reaction of isoquinoline with [( 5-Cp ) Rh(AN)3]2+ or [( 5-Cp )Rh(/ -xylene)]2+ gives complex 122. 2-Methyl quinoline gives a mixture of products 123 and 124. In 124 coordination is fulfilled via the benzene ring. 

Using a model of the quinoline ligand we can measure the H4 —H5 separation as being 2.49 A. Check this in the two structures of cis-[Pt(quinoline)(3-methyl-quinoline)Cl2] that you have refined. Given this distance and Eq. 17.19.2 we can calculate the H2 —Hg and H2 -H2 separations ... 

Methyl-quinolin-8-yloxymethyl derivatives, (IV), prepared by Carson (3) were effective as bradykinin agonists/antagonists and used in the management of pain and inflammation. 

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