3- Iodoquinolines

Only a little 3,5-di- and penta-iodopyridine is obtained when pyridine reacts with iodine in the vapour phase. Treatment of pyridine with iodine in 50% oleum furnishes 3-iodo-(18%) and some 3,5-di-iodo-pyridine. This is probably the result of electrophilic substitution by I+, with oleum performing in the role already discussed (57JCS387). The products of iodination of quinoline are not well defined however, a reviewer (77HC(32-1)319) has pointed out that one such product (formed by heating quinoline with iodine and potassium iodide at 160-170 °C in the presence of mercury(II) chloride) has a melting point identical with that of 3-iodoquinoline. 

The carbonylative cross-coupling was successfully extended to organofluorosilanes by Hiyama. TVN -Dimethyl-2-imidazolidmone was found to be the most effective solvent for the carbonylative Hiyama-coupling, which was run in the presence of potassium fluoride. 3-Iodoquinoline, for example, reacted smoothly with 2-(ethyldifluorosilyl)-thiophene (7.68.) under an ambient pressure of carbon monoxide to give the desired ketone in 78% isolated yield.89... 

This observation opens up the way for another transformation the copper catalyzed halogen exchange reaction on aromatic systems. When not only a catalytic, but a stoichiometric amount of iodide was added to 3-bromoquinoline in the presence of the copper catalyst system (7.83.), it was converted smoothly to 3-iodoquinoline, which was isolated from the reaction mixture in 95% yield.105... 

As part of their study on gastric (H+/K+)-ATPase inhibitors, Kang et al. developed a simple and convenient synthetic approach to 1,2,3-trisubstituted pyrrolo[3,2-c]quinolines by means of Pd-catalyzed heteroannulation of 4-amino-3-iodoquinoline derivatives with internal alkynes [76]. The following scheme shows an example of a reaction using 4-arylamino-3-iodoquinoline derivative 180 with alkyne 181 to provide 1-arylpyrrolo [3,2-c]quinoline 182, illustrating the possibility of introducing diverse substituents to 1-arylpyrrolo[3,2-c]quinolines. In addition, a Pd-catalyzed domino hydroarylation/ cyclization process was reported to form substituted quinolines [77]. Thus, 3-arylquino-lines were prepared in 56-74% yield when 3,3-diethyl-l-phenyl-1-propyne and aryl iodide were refluxed in ionic liquid, 1-butyl-3-methylimidazolium tetrafluoroborate [(bmim)BF4 ],in the presence of HCO2H, EtjN, and palladium catalyst. Meanwhile,... 

Ketones are formed from pyridylzinc halides on acylation with acid chlorides or anhydrides in reactions with benzoyl chloride or benzoic anhydride, pyridyl ketones (307) are formed in moderate yields. Reactions with 3-iodoquinoline gave the 3-benzoyl derivative 308. Organostannanes may be a better choice for ketone formation (see above). 

Reddy et al. [41] developed a method for the synthesis of substituted quinolines 12 from 2-aminoaiylketones (via l-(2-aminoaiyl)-2-yn-l-ols 11) using mild and simple reaction conditions. They used different iodine sources (Ij, NIS, and ICl) and I2 was found to work efficiently for the synthesis of 3-iodoquinolines (Scheme 10.9). 

Some articles have described synthesis of 3-trifluoromethylquinoline (271) [161-165]. Catalytic oxidative trifluoromethylation of 3-qunolineboronic acid (270) resulted in 3-trifluoromethylquinoline in 49 % yield [161]. Use Togni s reagent (272) in reaction with boronic acids 270 resulted in increase yield of 271 up to 53 % [162]. 3-Trifluoromethylquinoline was also obtained by reaction of boronic acids 270 with CF3I [163] or with trifluoromethyl sulfonium salts [164] in 87 % yield. Interaction of 3-iodoquinoline (273) with sodium trifluoromethyl formate at presence Cu and AgjO also led to compound 271 [165] (Scheme 80). 

Propyl-3-iodoquinoline has been transfonned into 2-propyl-3-(trifluoromethyl) quinoline by action of ClCF2C02Me, Cul, and KF on reflux in DMF [75], An interesting example of highly selective trifluoromethylation of 6-methylquinoline by means of the iridium-catalyzed reaction is presented in Scheme 49 [76],... 

The Suzuki -coupling, as well as dehalogenation and carboxylation reactions of 2-trifluoromethyl-3-iodoquinolines have been studied (Scheme 77) [68]. 

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