Pyridine 2,5-dibromo

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. ... 

Pyridines which failed to produce detectable quantities of 2,2 -bipyridines include 2-aminopyridine, 3-aminopyridine, 3,5-dibromo-pyridine, and ethyl isonicotinate. 2,2 -Bipyridine failed to give any 2,2 6, 2 6",2" -quaterpyridine, and this is discussed in a later section. 

A second reaction which is very often used for the preparation of phthalonitriles, although the yields are usually not reproducible, is the Rosenmund-von Braun reaction (see Houben-Weyl, Vol. E5, p 1460).106 107 Herein, a benzene derivative with a 1,2-dibromidc or 1,2-dich-loride unit is treated with copper(I) cyanide in dimethylformamidc or pyridine. During this reaction the formation of the respective copper phthalocyanine often occurs. This can be used as an easy procedure for the exclusive synthesis of copper phthalocyanines (see Section 2.1.1.7.),1 os-109 but can also lead to problems if the phthalonitrile is required as the product. For example, if l,2-dibromo-4-trifluoromethyl-benzene is subjected to a Rosenmund-von Braun reaction no 4-trifluoromethylphthalonitrile but only copper tetra(tri-fluoromethyljphthalocyanine is isolated.110... 

A useful method of synthesis of 5-bromo- and 5,8-dibromo-3-methoxy-2-phenylimidazo[ 1,2-a]pyridines has involved quenching the lithium derivatives with bromine (83S987). 

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]. 

H n.m.r.spectrum of compound 64 showed the well-known allylic coupling 111 between the protons on C-4 and C-6 and C-4 and C-6. On reacting with silver fluoride and pyridine, 2,3,4,l, 3, 4 -hexa-0-acetyl-6,6 -dibromo-6,6 -dideoxysucrose, like the 6,6 -diiodo derivative (63), gave the corresponding 6,6 -dideoxy-5,5 -diene derivative.96... 

Alkoxycarbonylation of 2,3-dichloro-5-(methoxymethyl)pyridine (78) took place regioselectively at C(2) to give ester 79 [79], Aminocarbonylation of 2,5-dibromo-3-methylpyridine also proceeded preferentially at C(2) to give amide 80 despite the steric hindrance of the 3-methyl group [80]. 

All of the sulfone diols were able to form oligomers in the second step of the reaction sequence, the Ullmann ether synthesis. As with the synthesis of the mono(bromophenoxy)phenol products, two methods were used to form the dibromo materials. Method A used pyridine, potassium carbonate and cuprous iodide, while Method B employed collidine and cuprous oxide with the dibromobenzene and higher molecular weight diol (IV). The major difference between the syntheses of the mono(bromophenoxy)phenols described earlier and these lies in the stoichiometry of the reactions. In order to... 

Brominated Monomer/Oligomer Mixtures from IV (V). The brominated sulfone monomer/oligomer mixtures were preparedby two different methods. Method A A mixture of pyridine (70mL), IV (11.5 mmol), dibromobenzene (26.96g, 115 mmol), anhydrous potassium carbonate (7.94g, 57.5 mmol) and cuprous iodide (0.13g, 0.7 mmol) was heated at reflux under nitrogen for 24h. After cooling to room temperature, the reaction mixture was acidified with IN HC1 and the aqueous solution extracted with ether. The organic phase was reduced in volume to a brown gum which was washed several times with hexane and then dried to give a 75-95% yield of the dibromo product. 

The pyrolysis of 2-(2-azido-3,5-dibromobenzoyl)pyridine (118, R = R = Br) in 1,2,4-trichlorobenzene for 24 h yielded 2,4-dibromo-ll-oxopyrido[l,2-b]cinnolin-6-ium hydroxide inner salt (119, R = R = Br) in 85% yield (74JHC125). The pyrolysis in boiling toluene gave a ca. 1 1 mixture of 5,7-dibromo-3-(2-pyridyl)-2,l-benzisoxazole (120, R = R = Br) and the foregoing tricyclic derivative. 

A In the absence of a Lewis acid, bromine adds across the 3,4-double bond of coumarin to give 3,4-dibromo-3,4-dihydrocoumarin. In the presence of pyridine a dehydrobromination reaction takes place, leading to 3-bromocoumarin as the favoured product (Scheme 5.4). 

Bromo substituents in the 6- and 6 -positions of 2,2 -bipyridines are particularly reactive, being readily converted to amino,cyano, ° al-koxyl, hydrazino, chloro, and hydrogen groups and by way of the corresponding lithio derivatives to carboxyl, methyl, aldehyde or alkylcarbonyl, and other groupings. 6,6 -Dibromo-2,2 -bi-pyridine also reacts with the disodium derivatives of polyethylene glycols to give crown ethers akin to 100, and 6,6 -bis(chloromethyl)-2,2 -bi-pyridine " and the derived 6,6 -bis(mercaptomethyl)-2,2 -bipyridine... 

Bromination of pyridine is much easier than chlorination. Vapour phase bromination over pumice or charcoal has been studied extensively (B-67MI20500) and, as with chlorination, orientation varies with change in temperature. At 300 °C, pyridine yields chiefly 3-bromo-and 3,5-dibromo-pyridine (electrophilic attack), whilst at 500 °C 2-bromo- and 2,6-dibromo-pyridine predominate (free radical attack). At intermediate temperatures, mixtures of these products are found. Similarly, bromination of quinoline over pumice at 300 °C affords the 3-bromo product, but at higher temperatures (450 °C) the 2-bromo isomer is obtained (77HC(32-1)319). Mixtures of 3-bromo- and 3,5-dibromo-pyridine may be produced by heating a pyridine-bromine complex at 200 °C, by addition of bromine to pyridine hydrochloride under reflux, and by heating pyridine hydrochloride perbromide at 160-170 °C (B-67MI20500). 

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