Iodo pyridines

In 2006 Maes and co-workers described the intramolecular Pd-catalyzed amination of A-(2-chloropyridin-3-yl)pyr-idazin-3-amine and A-(3-bromopyridin-2-yl)pyridazin-3-amine which involves intramolecular coordination of Pd(ll) to the N-2 nitrogen of the A-arylpyridazin-3-amine entity (Equation 8). A-(2-Chloropyridin-3-yl)pyridazin-3-amine and A-(3-bromopyridin-2-yl)pyridazin-3-amine are intermediates in the auto tandem amination of 2-chloro-3-iodo-pyridine and 2,3-dibromopyridine with pyridazin-3-amine, respectively <2004CC2466, 2006JOC260>. In the former case the ring closure proceeds partly via an SNAr process. 

Thus, reaction of 3-chloro-, 3-bromo- and 3-iodo-pyridine with potassium amide in liquid ammonia give in each case the same mixture of 3- and 4-aminopyridine, showing the intermediacy of... 

An interesting double amination of 2-chloro-3-iodo-pyridine (16) with 2-aminopyridine (17) catalyzed by Pd/BINAP or Pd/Xantphos, which gives dipyridoimidazoles (18), was described by B. U. W. Maes and co-workers. 2-Aminopyrazine was also found to be a capable coupling partner.70 The mechanism is most likely an initial amination at the 3-iodo position followed by an intramolecular amination at the 2-chloro position. 

Chloro- and bromoaminopyridines are oxidized by persulfuric acid at 0° to their nitro derivatives thus, 3-chloro-, and 3-bromo-4-aminopyridine are converted to the respective 3-halo-4-nitropyridines. However, 4-araino-3-iodo-pyridine is not oxidized under these conditions. 4-Amino-2,3,5,6-tetrafluoro-pyridine is difficult to oxidize and requires refluxing peroxytrifiuoroacetic acid for 22 hours in order to yield the 4-nitro derivative. Potassium bromate has been used to oxidize S-amino-3-methyl-2-pyridone, but the product was not a nitro compound instead 3-hydroxy-6-methyl-2-aza-l,4-benzoquinone-4-(2,6-di-hydroxy-5-methyl-3-pyridyl)imine (IX-S7) was obtained. ... 

It is not surprising that, of the halogenopyridines, only the 3-substituted compounds can be successfully nitrated. 3-Bromo- and 3-iodo-pyridine give 5-nitro derivatives226. 

Den Hertog and his co-workers have found that amination of 2-chloro-, 2-bromo-, and 2-iodo-pyridine with H2N yields only... 

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. 

Rhodium (i 5-Cyclopentadienyl)-iodo-pyridin-trifluoromethyl-XIII/9b. 348 (F3C—RhR] + Py)... 

It has been reported that the furoindole (361) underwent Diels-Alder reactions with DMAD, N-phenylmaleimide and benzyne to give the expected products <84JOC45l8>. Treatment of 3-chloro-4-iodo-pyridine with t-butyllithium followed by addition of (361) led to a mixture of the isomeric Diels-Alder adducts (362) and (363) in 15% yield. Deoxygenation and desulfonylation of (362) and (363), gave a readily separable mixture of the pyridocarbazole alkaloids ellipticine (364), and isoellipticine (365), respectively (Scheme 14) <84JOC45l8,83TL5435>. 

Ni(II)-catalyzed reductive cross-coupling of iodo-pyridines, iodo-isoquino-lines, and iodo-pyrimidines with a-chloronitriles (23 examples 37—82% yields, 72—92% ee) (2015JAC10480). The sole example of coupling to 6-iodoimidazo[l,2-fl]pyridine (244) generated 245 in a respectable 63% yield with 97% ee after purification by recrystaUization. 

Pyridine and iodine react in the vapour phase, giving small amounts of 3,5-di- and pentaiodopyridine. The use of iodine monochloride does not improve the yield, and considerable amounts of 2-chloropyridine result . Molten pyridine hydrochloride reacts with iodine to give some penta-iodopyridine , but the yield is better v when the very stable pyridine hydrochloride-iodine complex is heated at 280-290°. At 280° the hydrochloride is said also to form, with iodine or iodine monochloride, 2-pyridyl-pyridinium chloride, via 2-halogenation . Iodine in 50 per cent oleum at 300-320° converts pyridine into 3-iodo- (18 per cent) and some 3,5-di-iodo-pyridine, and 2-picoline at 200-210° gives 5-iodo-2-methylpyridine. It is probable that the oleum functions here rather like the aluminium chloride in the experiments discussed above, generating the reactive iodine cation . 

The halogenopyridines are susceptible to nucleophilic substitution (p. 210), and quaternary salts from pyridine and 2-chloro-, -bromo- and -iodo-pyridine have been described 24, 2-Halogenopyridines and -quinolines react... 

Reaction of 2-chloro- or 2-iodo-pyridine with potassamide in liquid ammonia , or of 2-fluoropyridine with lithium piperidide in ether results in direct substitution without pyridyne intermediates. The reaction of 3-fluoropyridine with potassamide in liquid ammonia at —33° takes a surprising course . Evidently the base abstracts a proton from the 4-... 

Aminopyridine 1-oxide has been diazotized and, by use of the Sandmeyer reaction, converted into 4-chloro- and 4-bromo-pyridine l-oxide" . 4-Iodo-pyridine 1-oxides have also been prepared through the diazonium reac-tion i . 

Methyl-5-(4-pyridyl)-7-aza- 2-Araino-3-iodo-6-methyl-,S- (4-pyridyl)pyridine Trimethylsilylethyne. Pd(PPh,)jCl4, Cut 96,40 ... 

Note 2. Under acidic conditions and in the presence of water, the 18,20-hemiacetal formed from the 18-iodo-18,20-ether is transformed into a dimeric anhydro product, resistant to further oxidation. Pyridine is added to prevent this transformation. 

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