Bromine in pyridine

As foretold in the introduction, ring formation via attack on a double bond in the endo-trig mode is not well exemplified. The palladium(II) catalyzed oxidative cyclization of o-aminostyrenes to indoles has been described (78JA5800). The treatment of o-methyl-selenocinnamates with bromine in pyridine gives excellent yields of benzoselenophene-2-carboxylates (Scheme 10a) (77BSF157). The base promoted conversion of dienoic thioamides to 2-aminothiophenes is another synthetically useful example of this type (Scheme 10b) (73RTC1331). 

Bromine in pyridine largely dibrominated 2-amino- and 2-hydroxy-1,3-diazulenes (35), although some mono- and tri-bromo products were also detected (88BCJ2690). 

Bromination of (-)-(5 )-benzyl methyl sulfoxide 34 with bromine in pyridine affords a mixture of two regioisomers a-bromomethyl benzyl sulfoxide 328 and a-bromobenzyl methyl sulfoxide 329, in a molar ratio of 3 2 (325). Oxidation of thp latter gives the corresponding sulfone (-)-(S)-330, the absolute configuration of which was determined by X-ray analysis. In this context, it is interesting to point out that the formation of the sulfoxide 328 is accompanied by retention at sulfur, whereas 329 is formed with inversion at sulfur. 

Sulfonation of indole with pyridinium-A -sulfonate yields indolyl-3-sulfonic acid, and bromine in pyridine at 0 °C affords 3-bromoindole (Scheme 7.4). Acetylation with a heated mixture of acetic anhydride and acetic acid gives 1,3-diacetylindole. Methylation requires heating with methyl iodide in DMF (A,A-dimethylformamide) at 80-90 C and yields 3-methylindole. This compound reacts further, giving 2,3-dimethylindole and finally l,2,3,3-tetramethyl-3Ff-indoleninium iodide. 

The reaction of 1,5-naphthyridine (1) with bromine in chloroform does not yield any brominated products (54JCS1879). However, treatment of (1) with bromine in oleum was found to give a mixture of the 3-bromo- (13) and the 3,7-dibromo-l,5-naphthyridines (14) in 10% and 35% yield respectively (65JOC1607, 67LA(707)242). With bromine in pyridine the yields were 27% of (13) and 10% of (14) (68JOC1384), and application of this procedure to 1,6-naphthyridine (2) gave a mixture of 3-bromo- (15), 8-bromo- (16) and 3,8-dibromo-... 

Examples of neighboring group participation in isoxazole bromination have been reported. When the isoxazolylpropanol (80) was treated with bromine in pyridine, it gave the spiro (furan-2,5-isoxazole) (81) (74BAU2566). The corresponding propenoic acid gave 82 [76JCS(P1)1694], whereas a similar process accounts for the reaction of... 

An alternative route is the reaction of iodine or bromine in pyridine with liquid sulfur dioxide at 20°C, which gives good to high yields of sulfites (106). 

Azaborines have received a little attention in recent years, particularly 1,2,3-diazaborines (67) [75ACS(B)1036 76MI2 84MI1] (Scheme 58). Bromine in pyridine converted 5-ethyl-1,2-dimethyl-1,2-dihydro-1,2,3-borazine into a mixture of 4- and 6-monobromo derivatives, and the 4,6-dibromo compound. With iodine monochloride the 4-iodo or 4,6-diiodo products formed, depending on the mole ratio of iodine monochloride to substrate [75ACS(B)461]. 

Halogenation of the 3-hydroxypyridines follows the pattern set by the 3-aminopyridines in that substitution takes place at the 2-position. Chlorination with hydrochloric acid and hydrogen peroxide,102 bromination with one equivalent of bromine in pyridine,192 and iodination with iodine and sodium carbonate102 all give the 2-halo-3-hydroxypyridine. Chelation and formation of a cyclic transition state does not appear a likely possibility in these reactions. Under more vigorous conditions or with an excess of the halogen, 2,6-disubstitu-tion162,183 and 2,4,6-trisubstitution can occur.162... 

Ring closure of acylamines prepared from ethylenediamine also yields imidazoles,88 but this reaction will be discussed in Section II, E as formation of the 1 2- and 2 3-bonds. When 2,2 -dipyridyl compounds react with methylene iodide,84 bromine in pyridine, or p-toluenesulfonyl chloride in pyridine,85 imidazolium salts are produced. 

Several papers on the chemistry of longifolene derivatives have been published. These include the conversion of the two half-esters (225) and (226) into the same olefinic ester (227) with Pb(OAc)4-Cu(OAc)2, the reaction of longifolene (228) with mercuric acetate followed by iodine chloride to give (229) and (230), and the reaction of longicyclene (231) with bromine in pyridine and iodine chloride-pyridine complex in acetic acid to yield (232) and (233) respectively. 

Ortho esters may be brominated in pyridine solution. The reaction takes place rapidly at 10-30° to give good yields of a-bromoortho esters. Higher yields are obtained when a mixture of carbon tetrachloride and pyridine is used as solvent. The reaction fails for ethyl orthoisobutyrate. Two a-hydrogen atoms of ethyl orthoacetate have been replaced by bromine atoms to give ethyl orthodibromoacetate (53%). ... 

Perelman et aV of Eli Lilly and Co. found that the 19-nor-A -sleroid (1,19-nor-A < -androstene-17 3-ol-3-one) can be dehydrogenated smoothly to the 19-nor-A -3-ketosteroid (2) by reaction with bromine in pyridine or, more conveniently. 

A 2 N soln. of ethylmagnesium bromide added at -35° to a stirred ethereal suspension of CuBr, after 0.5 hr. propyne added at -35°, the temp, allowed to rise to -15° and stirred 1.5 hrs., a soln. of mercuric bromide in tetrahydrofuran added at -30° with stirring, which is continued 2 hrs. at room temp., cooled to -30°, hexamethylphosphoramide followed by bromine in pyridine added, and allowed to warm to room temp. product. Y 77%. F. e. s. J. F. Normant et al., Synthesis 1974, 803. 

Methyl-3-pyridinol is brominated in pyridine to give 2-bromo- and then 2,4-dibromo-6-methyl-3-pyridinol. lodination with sodium iododichloride gives 2-iodo-6-methyl-3-pyridinol. lodination of 2-(/7-substituted phenyl)-3-pyri-dinols (Xn-665 R = H, CHj, C Hs, CH(CH3)2. C(CH3)3, Q, OCHj) gives 2-aiyl-6-iodo-3-pyridinols. This should be contrasted with nitration of these pyridinols, which occurs first on the phenyl group " (Section II1.2.D.,... 

Hydroxypyridine with bromine in pyridine gives 2-bromo-3-hydroxy-or 2,6-dibromo-3-hydroxypyridine, depending on the proportion of bromine used, but in water the product is 2,4,6-tribromo-3-hydroxypyridineS . In mildly alkaline solution iodination of 3-hydroxypyridine gives 3-hydroxy-... 

Dihydroxy-, 2-ethoxy-4-hydroxy- and 4-ethoxy-2-hydroxy-pyridine with bromine in pyridine are substituted at C(3) first, whereas 2,4-diethoxy-pyridine gives 5-bromo-2,4-diethoxypyridine. 2,4-Dihydroxypyridine exists predominantly as 4-hydroxy-2-pyridone, and bromination at C(3) is thought to require the presence of the structure 0 C—C=G—OH or 0 C—C=aOR. 

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