8-Iodoquinoline

Fig. 16 Examples of current dips (a) 2-iodoquinoline (1.6 mM) with benzenethiolate ions (44 mM) (b) 2-iodoquinoline (5.2 mM) with diethylphosphite ions (100mM). Scan rate, 0.2Vs . Example of trace crossing (c) 4-chlorobenzonitrile (1.55mM) with diethylphosphite ions (663 mM). Scan rate, 0.215 Vs . In liq. NHj/O.l m KBr at — 40°C. (Adapted from Amatore et a ., 1980a,b.)...

Due to their successful synthesis of 2-(4 -chlorophenyl)-4-iodoquinoline from the corresponding precursor acetylene, Arcadi et al. (99T13233) developed a one-step synthesis of 2,4-disubstituted quinolines via palladium-catalyzed coupling reactions. An example is the Heck reaction of 4-iodoquinoline (131) with a-acetamidoacrylate (132). This one-pot synthesis yielded adduct 133 in 50% overall yield after purification via flash chromatography. 

Treatment of 4-arylamino-8-iodoquinoline 268 with propargyl alcohol in presence of iodo(phenyl)bis(triphenylphosphine) palladium and copper (I)iodide afforded 269 which upon catalytic reduction using Linder s catalyst gave 4//-pyrrolo[3,2,l-(/]quinoline 270 (97H2395) (Scheme 48). 

Halogen exchange with metallic derivatives provides a powerful means of introducing iodine into specific quinoline sites. It has proved possible to prepare 2-, 3-, and 4-iodoquinolines from the trimethylstannyl [82H(19)168] or lithium derivatives [86S670]. Protected 2-aminoquinoline, lithiated at C-3, was quenched with iodine to give a 90% yield of the 3-iodo derivative (86S670). 

Other indoles that have been prepared using the Sonogashira coupling and cyclization sequence include 5,7-difluoroindole and 5,6,7-trifluoroindole [219], 4-, 5-, and 7-methoxyindoles and 5-, 6-, and 7-(triisopropylsilyl)oxyindoles [220], the 5,6-dichloroindole SB 242784, a compound in development for the treatment of osteoporosis [221], 5-azaindoles [222], 7-azaindoles [160], 2,2-biindolyls [223,176], 2-octylindole for use in a synthesis of carazostatin [224], chiral indole precursors for syntheses of carbazoquinocins A and D [225], a series of 5,7-disubstituted indoles [226], a pyrrolo[2,3-eJindole [226], an indolo[7,6-g]indole [227], pyrrolo[3,2,l-y]quinolines from 4-arylamino-8-iodoquinolines [228], optically active indol-2-ylarylcarbinols [229], 2-alkynylindoles [176], 7-substituted indoles via the lithiation of the intermediate 2-alkynylaniline derivative [230], and a variety of 2,5,6-trisubstituted indoles [231], This latter study employs tetrabutylammonium fluoride, instead of Cul or alkoxide, to effect the final cyclization of 215 to indoles 216 as summarized here. 

The synthesis of the heterocyclic diiodides can be tricky (Scheme 8). Direct iodination of quinoline was reported by Kiamuddin et al. [59] to give 5,8-di-iodoquinoline. Their procedure did not furnish any products according to Bunz et al., but classical electrophilic iodination leads to a single product that was identified not to be the 5,8-isomer but 3,6-diiodoquinoline, according to the X-ray crystal structure of a diethynylated derivative [60]. 

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. 

Closely related are the cyanine dyes, for example cyanine (62) itself, which is formed from the ethiodide salts of lepidine and 4-iodoquinoline in the presence of base (Scheme 51). Analogous monomethine cyanines can have the quinoline nuclei linked 2,2 (pseudocyanines) and 2,4 (isocyanines). Quinaldine ethiodide on condensation With ethyl orthoformate gives the 2,2 -linked trimethine cyanine (carbocyanine) (63), known as pinacyanol (Scheme 51). 

The palladium catalysed sequential alkylation-alkenylation of 5-iodoquinoline leads to the formation of the quinolooxepin ring system (5.20.), The process, closely related to the Catellani reaction,19 runs through an ort/zo-alkylation - Heck reaction sequence. The preparation of a series of benzoxepines has also been achieved in this manner, starting from such iodobenzene derivatives, where one of the or/7 o-positions was blocked by substitution.20... 

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... 

ChIoro-8-hydroxy-7-iodoquinoline [130-26-7] M 305.5, m 178-179 . Crystd from abs EtOH. 

---