Quinaldine derivatives

Quinophthalones, made by the condensation of phthalic anhydride with quinaldine derivatives, are one snch gronp, exemplified by Cl Disperse Yellow 54 (2.17a) and Yellow 64 (2.17b) nsed for polyester, especially for transfer printing and also as solvent dyes. 

Quinophlhalones. Like the hydroxy azo dyes, quinophthalonc dyes can. in theory, exhibit tautoiuerism. The dyes are synthesized by the condensation of quinaldine derivatives with phthalic anhydride. Quinophlhalones provide important yellow dyes for the coloration of plastics and lor the coloration of polyester. 

Phenol and quinaldine derivatives (Table 88,B,C) as well as the indole derivatives are discussed here under urine metabolites. The expression plant growth regulators has become adopted in recent years for auxins, gibberellins and cytokinins, which are reaUy quite distinguishable from each other both chemically and in their physiological... 

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. 

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. 

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. 

Merocyanines with selenazolidine nuclei are obtained in 70 to 80°/o yield from the appropriate derivatives of lepidine or quinaldine (Scheme 79) (84). 

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). 

The reactivity of the 1-methyl group and of corresponding positions (i.e., a-carbon atoms) in other l-alkyl-j8-carbolines, analogous to that in a-picoline, quinaldine, and isoquinaldine, is due to the acidity of this center. Deprotonation yields a resonance-stabilized anion (288) which reacts readily with electrophilic reagents. Metallation with phenyl-lithium of the 1-methyl group of a l-methyl-j8-carboline derivative in which the indole nitrogen is protected, first described by Woodward... 

Quinophthalone (6.229) and its derivatives [86] also fall into the methine category, although they appear in the Colour Index under quinoline colouring matters. The parent compound was discovered in 1882 by Jacobsen, who condensed 2-methylquinoline (quinaldine) with phthalic anhydride. The product, quinoline yellow, is used as a solvent dye (Cl Solvent Yellow 33). The light fastness is improved by the presence of a hydroxy group in the quinoline ring system. Derivatives of this type provide greenish yellow disperse dyes for polyester. The moderate sublimation fastness of Cl Disperse Yellow 54 (6.230 R = H) is improved by the introduction of an adjacent bromine atom in Cl Disperse Yellow 64 (6.230 R = Br). 

Quinophthalone pigments have a polycyclic structure derived from quinaldine and phthalic anhydride. 

E. Jacobson in 1882 fused phthalic anhydride with quinoline bases obtained from coal tar, which also contained quinaldine (136). He thus received quinophthalone (137). Quinophthalone derivatives bearing sulfonic or carboxylic acid functions represent suitable anionic dyes. Derivatives carrying basic side chains containing quarternary nitrogen, on the other hand, provide cationic dyes. The compounds are used especially as disperse dyes [1]. 

The Skraup, Doebner-Miller, and Gould-Jacobs reactions for the syntheses of quinolines, quinaldines, and 4-hydroxyquinolines, respectively, were applied to 5-aminotropolone derivatives (e.g., 208, Scheme 50) to get pyridotropolones 209-211 (59NKZ75 68NKZ620) and other derivatives [52CI(L)471 60NKZ295]. These reactions illustrate the behavior of 5-aminotropolones as typical aromatic amines (55CRV9,... 

In the quinoline series, the 2- and 4-methyl derivatives (quinaldine and lepidine respectively) will also undergo condensations at the methyl groups. Use of an aldehyde gives the secondary alcohol, which may then be dehydrated to provide the styryl compound... 

JCS1641). The ease of deprotonation is in the order 4>2>3, but, possibly for steric reasons, the 2-methyl substituent is found to be the more reactive, as condensation of 2,4-dimethylquinoline with 2,4-dinitrobenzaldehyde rapidly gives the 2-styryl derivative the 2,4-distyryl compound is formed only on prolonged reflux. Quinaldine will take part in the Mannich reaction to give /3-aminoethylquinoline derivatives. Examples of the above reactions are shown in Scheme 42. 

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 aldehyde. The mechanism is probably similar to that given for the Doebner-Miller synthesis of quinaldine (Section V,2), involving the intermediate formation of a dihydroqulnoline derivative, which is subsequently dehydrogenated by the Schiff s base derived from the aromatic amine and aldehyde. 

Experiment 6.152 describes a synthesis of quinaldinic acid from quinaldine (2-methylquinoline). The method depends upon the reactive nature of the 2-methyl group in quinaldine which can readily be brominated using bromine in acetic acid. Hydrolysis of the resulting tribromo derivative by boiling with dilute sulphuric acid occurs smoothly to give the corresponding carboxylic acid in good yield. 

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). 

The uses of pyridine derivatives, such as aminopyridines, quinaldine, and acridine, together with quaternary salts and photochromic compounds are reviewed in CHEG-II(1996) <1996CHEC-II(5)245>. Pyridinium-based stilba-zolium cationic dyes 43 and 44 were induced to give intense fluorescence by anionic peptide amphiphiles <2006CC1073>. 

Vierfond et al. used thermal cyclization (79JHC753). The anion obtained by the reaction of quinaldine with phenyllithium was reacted with o-chlorobenzonitrile to afford imine 138, which cyclized at 235°C to give amino derivative 139 (32%). Another method is shown by the reaction of 140-142. The reaction of 140 with excess sodium diethyl malonate in hexamethylphosphoramide (HMPA) at 190°C gave cyclization product 141 (38%), which was converted to fully aromatic 142 by reaction with acetic anhydride (92%) (82JHC127). 

For the preparation of pyrido[2,3-d]pvrimidinc-2,4(l//,3//)-diones 28, an adaption of the Doebner-Miller quinaldine synthesis (cf. Houben-Weyl, Vol. E7a, p 363), can be used. The orientation of addition of oc,/5-unsaturated carbonyl compounds to pyrimidin-6-amines is governed by the attack of C5 of the pyrimidinamine at the carbon /5 to the carbonyl function.219 Besides pyrimidine-2,4,6-triamine,149 263 aminouracils are used as partners for the base-catalyzed reaction with a,/5-unsaturated ketones.148,219 264,570,571 Without the final oxidation step, which occurs mostly by air, the dihydro compounds are produced.265 Examples are the Michael additions of 4,4-dimethyl-l-phenylpent-l-en-3-one266 or of 1,3-diphenylprop-2-en-l-one264 to 6-amino-l,3-dimethylpyrimidine-2,4(l//,37T)-dione, which are followed by ring closure to give the corresponding pyrido[2,3-d]pyrimidme-2,4(l//,3//)-diones or their dihydro derivatives. 

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