Quinoline synthesis salts

Quaternary ammonium N-F reagents, 69, 2 salts, rearrangements of, 18, 4 Quinolines, synthesis of,... 

A wide variety of pyrvinium salts (1) have been prepared by treating a quinoline quaternary salt (41) with 2,5-dimethyl-l-phenylpyrrole-3-carboxaldehyde (40) [42,43]. The latter is obtained by a Paal-Knorr synthesis starting with 2,5-hex-anedione (37) and aniline [44,45] (Scheme 1). 

The lower temperature variation of this reaction initially forms an imine or an enamine. Friedel Crafts cyclization gives the 4-hydroxyquinoline in what is called the Conrad-Limpach reaction. xhis reaction generally gives the opposite regioisomeric product to that obtained by the Knorr quinoline synthesis. The initially formed product is usually the enamine (as in the formation of 248 from aniline and ethyl acetoacetate). 3 Under acidic conditions the iminium salt is formed and cyclized with the aromatic ring. A more efficient method simply heated 248 to 250°C in mineral oil, giving a 90% yield of 249. A variety of other functional groups can be tolerated in the molecule when this procedure is used. 

In 1923, Mills introduced thiazole for the first time in the synthesis of methine dyes through a somewhat indirect route. In order to demonstrate the 2,4 -cyanine mechanism of formation by quinoline and quinaldine quaternary salts reacting together, Mills used other pairs of quaternary salts as 2-methylthiazolium with either quinolinium or benzothiazolium (42, 43). 

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... 

Pyrimido[4,5-6]quinolinium salts pseudo bases - ring opening, 3, 208 Pyrimido[4,5-6]quinolinium salts, 4-chloro-hydrolysis, 3, 214 Pyrimido[4,5-6]quinolinones synthesis, 3, 228 Pyrimido[4,5 -6]quinolin-5-ones synthesis, 3, 221-222 Pyrimidothiadi azoles reactions, 6, 533 Pyrimidothiazines synthesis, 4, 527 Pyrimidothiazinones mass spectra, 2, 23... 

Halothiophenes, which are not activated through the presence of —I—M-substituents, undergo substitution smoothly under more forcing conditions with copper salts in pyridine or quinoline. Hence 3-cyanothiophene and 5-methyl-2-cyanothiophene have been obtained from the corresponding bromo compounds. 2-Bromothiophene reacts readily with aliphatic cuprous mercaptides in quinoline at 200°C to give thioethers in high yields. The use of the copper-catalyzed Williamson synthesis of alkoxythiophenes from iodo- or bromo-thiophenes and alcoholate has been mentioned before. The reaction of 2-bromothiophene with acetanilide in nitrobenzene in... 

Due to its commercial importance, the synthesis of copper phthalocyanine (PcCu) is the best investigated of all the phthalocyanines. Copper phthalocyanine is prepared from phthalonitrile and copper(I) chloride without solvent137 and also in a melt of urea.229,277 Additionally, the insertion of copper into metal-free phthalocyanine in butan-l-ol and pentan-l-ol is possible. The copper salts used in this case are copper(I) chloride112 and copper(II) acetate.290 Starting from copper(II) acetate, copper phthalocyanine can also be prepared in ethylene glycol.127 As mentioned above, copper phthalocyanine often occurs as a byproduct of the Rosenmund-von Braun reaction. To increase the yield of the phthalocyanine the solvent dimethylformamide can be substituted by quinoline. Due to the higher boiling point of quinoline, the copper phthalocyanine is the main product of the reaction of copper(I) cyanide and 1,2-dibromoben-zene.130... 

Hie reactions of 4-chloropyridines and quinolines 17 with benzotriazoles 18 in a modified Graebe-Ullman synthesis give excellent yields of Y arbolines and their benzo-fused derivatives 20. Excellent yields for preparation of the penultimate benzotriazole precursors 19 are reported as well. In the optimized one-pot conditions, the combined neat substrates are heated with microwave irradiation (MW) for short (7-10 min) durations. The crude 19 is treated with H4P2O7 and irradiated futher (4-6 min). The resultant y-carbolines 20 were methylated to form the quaternary salts. These were tested and found to lack DNA intercalation properties <96JOC5587>. 

The sonochemistry of the other alkali metals is less explored. The use of ultrasound to produce colloidal Na has early origins and was found to greatly facilitate the production of the radical anion salt of 5,6-benzo-quinoline (225) and to give higher yields with greater control in the synthesis of phenylsodium (226). In addition, the use of an ultrasonic cleaning bath to promote the formation of other aromatic radical anions from chunk Na in undried solvents has been reported (227). Luche has recently studied the ultrasonic dispersion of potassium in toluene or xylene and its use for the cyclization of a, o-difunctionalized alkanes and for other reactions (228). 

Its synthesis follows the usual pathway of coupling diazotized 4-chloroaniline onto 2,4-dihydroxy-quinoline and subsequently treating the product with a nickel (II) salt. 

Alternative synthetic approaches include enantioselective addition of the organometallic reagent to quinoline in the first step of the synthesis [16], the resolution of the racemic amines resulting from simple protonation of anions 1 (Scheme 2.1.5.1, Method C) by diastereomeric salts formation [17] or by enzymatic kinetic resolution [18], and the iridium-catalyzed enantioselective hydrogenation of 2-substituted quinolines [19]. All these methodologies would avoid the need for diastereomer separation later on, and give direct access to enantio-enriched QUINAPHOS derivatives bearing achiral or tropoisomeric diols. Current work in our laboratories is directed to the evaluation of these methods. 

The Balz-Schiemann synthesis can be applied not only to substituted anilines but also to aminobiphcnyls1,131 or amino-substituted fused polyaromatic compounds, such as naphthalene,1114,119,129 anthracene,136 phenanthrene,1135 acenaphthene,133 fluorene,1,131,134 benzanthracene,130 136 pyrene,136 chrysene,136 fluoranthene,131 fluorenone,1,131 anthra-quinone,1,137,139,140 benzanthrone,1,117,118 phenanthraquinone,138 or xanthone.132 Fluorinated pyridines,1,141"146 methylpyridincs,126,147 149 pyridinecarboxylic acids,150 quinolines,1,151 isoquinolines,152 quinazolone,1 thiazoles,153,154 isothiazoles,156 benzothiazoles,157 thiadiazoles,155 and thiophenes154 can also be obtained from the corresponding aminated heterocycles. Modified Balz-Schiemann methods are recommended for amino nitrogen-containing heterocycles, the diazonium salts of which are rather water-soluble and unstable (a violent explosion was reported for pyridine-3-diazonium tetrafluoroborate).159 These new techniques have also been specially adapted for pyrazol-, imidazol-, or triazolamines which fail to react under classical conditions.158... 

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