2.6- Dibromo pyridine, amination

The inferior activation in the 3- or 6eto-position is illustrated by the very large difference in reactivity in the following aminations and alkoxylations. In the reaction of 2-chloro-5-iodopyridine or 2,3-dibromopyridine (cf. 295) with boiling methanolic methoxide, only the 2-halogen is displaced as is also the case in the amination of 2-chloro-3,5-diiodopyridine and of 2,3,6-tribromopyridine. 4-Amination of 3,4-dibromo-, 2,3,4,5-tetrabromo-, and 3-bromo-4-chloro-pyridine occurred. Only 2-amination (aqueous NH3, 190°, 36 hr) occurred with 2,3-dichloropyridine (295) and only 4-ethoxyla-tion (alcoholic ethoxide, 160°, 4 hr) with 3,4-dichloropyridine. ... 

Complex 10 is prepared by substitution of [TcNBr2(PPh3 )2]. The Tc-N bond length of the tertiary amine N atom coordinated trans to the nitrido ligand is 2.47(1) A and of the pyridine N atoms coordinated cis is 2.141 av. A. The thioether sulfur atom is not coordinated in the solid, but the H NMR spectrum shows that in solution there is an equilibrium between the dibromo form and one in which Br is expelled and the thioether sulfur is coordinated [62]. 

The inherent difference in the reactivity of the 2-, and 3-positions of the pyridine ring was also exploited in an industrial application of the carbonylative coupling of pyridines. 2,5-Dibromo-3-methylpyridine was converted into the 2-monoamides using different amines with a 98 2 selectivity. Keys to the success of the coupling, which was run on the 100 kg scale, were the use of DBU as base and the replacement of the phosphine in the catalyst with 2,2 -bipyridine.84 The carbonylation of 3,5-... 

When 3-chloro- or 3-bromopyridine is heated with lithium piperidide and piperidine in boiling ether, 156 is formed, which reacts further with piperidine to give a mixture of 3- and 4-piperidinopyridine in the ratio of 48 52. No 2,3-pyridyne intermediate is apparently produced under these conditions.388 Such an intermediate is probably involved in the reaction of potassium amide in liquid ammonia with 3-bromo-4-ethoxypyridine, which gives 2-amino-4-ethoxypyridine (55-60%). The reaction is, however, complicated by the fact that 2-amino-5-bromo-4-ethoxypyridine (15-20%) and 4-ethoxypyridine (25%) are also obtained.387 The formation of these two by-products may proceed by the preliminary disproportionation of some 3-bromo-4-ethoxy-pyridine to 3,5-dibromo-4-ethoxypyridine and 4-ethoxypyridine.388 The remarkable observation that both 2-amino-6-ethoxypyridine (157) (85%) and 4-amino-2-ethoxypyridine (158) (15%) are formed during the amination of 2-bromo-6-ethoxypyridine367 still requires explanation. No such rearrangement is observed with lithium piperidide.3880... 

The novel preparation of 5-cyano[n](2,4)pyridinophane-6-ones [n = 6 (5%), 7 (11%), 8 (63%), 9 (71%)] was conducted by allowing cyanoacetatoamide to react with cycloalk-2-enones <05OBC638>. Pd-Catalyzed amination of either 3,5-dibromo- or 3,5-dichloropyridine with linear polyamines led to the formation of a new family of pyridine-containing macrocycles (e.g. 6) possessing an exo -oriented pyridine iV-atoms <05HCA1983>. The treatment of 3,5-... 

Bromination of the compounds 63 using bromine in acetic acid provides the 8-bromo compounds 64. " Although a solution of N-bromosuccinimide in carbon tetrachloride does not brominate the amine 65 (R = H), it does brominate, in an unspecified yield, the carbamate 65 (R = C02Et). The position of substitution was identified as the 8-position on the basis of PMR evidence. There was no evidence of bromination of the methyl group. Bromination of a methyl phenyl compound, described without proof as 66, using bromine in carbon tetrachloride gave the dibromo compound 67. Treatment of 66 with iodine in pyridine gave the pyridinium salt 68, presumably by way of the iodomethyl compound. The orientation of these products remains to be established. 

The asymmetric bromination of (3-dicarbonyl compounds was accomplished using a catalytic amount of a chiral primary amine catalyst, with pyridine dicarboxylic acid (PDA) as the co-catalyst and 3,3-dibromo-5,5-dimethylcyclo-hexa-l,3-dione as the bromine source (Scheme 13.25) [55]. The substrate scope was quite broad and included cyclic and acyclic (3-ketoesters, acycfic p-diketones, and the cyclic ketones cyclopentanone and cyclohexanone. Additionally, the conditions for chlorination of (3-dicarbonyl compounds using the benzoylquinidine catalyst depicted in Scheme 13.15 were adapted for the bromination of two substrates [35]. 

---