Collidine, halogenation

Bis(sym-collidine)halogen(l) hexafluorophosphate. 15,30 17,155 18,49 19,29 20,33 Bromoalkenes. This reagent transforms a-diazo esters into a-bromo-a, p-unsaturated esters at low temperatures. 

Mono-substitution occurs most readily in the stepwise replacement of the halogen substituents of 2,4,6-trichloro-s-triazine with aqueous methanol and sodium bicarbonate (30°, 30 min), the monomethoxy derivative (324) is obtained on heating (65°, 30 min), the disubstitu-ted derivative is formed and on brief heating (65°) with the more basic sodium carbonate or methanolic sodium hydroxide (25°, 3 hr) complete methoxylation (320) occurs. Ethanolic ethoxide (25°, 1 hr) or sodium carbonate (35°) is sufficient to give complete ethoxy-dechlorination. The corresponding phenoxy derivatives are obtained on treatment with one (0°), two (15°, 1 hr), or three equivalents (25-70°, 3 hr) of various sodium phenoxides in aqueous acetone. The stepwise reaction with phenols, alcohols, or thiols proceeds in better yield in organic solvents (acetone or chloroform) with collidine or 2,6-lutidine as acid acceptors than in aqueous sodium bicarbonate. ... 

Electrophilic iodine reagents have also been employed in iodocyclization. Several salts of pyridine complexes with I+ such as bis(pyiidinium)iodonium tetrafluoroborate and bis(collidine)iodonium hexafluorophosphate have proven especially effective.61 y-Hydroxy- and d-hydroxyalkcncs can be cyclized to tetrahydrofuran and tetrahydropyran derivatives, respectively, by positive halogen reagents.62 (see entries 6 and 8 in Scheme... 

Low molecular weight aromatic ethers have been prepared principally by the condensation of phenolate salts with aromatic halides 82). The Ullmann condensation (81), which employs copper or its salts as catalysts has been used in most cases in the laboratory. Recently a modification of the Ullmann condensation which consists of heating copper (1) oxide, the free phenol, and the aromatic halide in s-collidine has been reported (3). This method is recommended for alkali-sensitive aromatic compounds. In addition, reaction of phenolate salts with copper (1) oxide and the aromatic halide in boiling N,N-dimethyl formamide is described. When the halogen is activated by electronegative groups as in -chloroni-... 

Cyclization of allylic alcohols to form epoxides has been particularly problematical, and the reactions have been more of mechanistic than of synthetic interest. For reactions conducted under basic conditions, it is possible that epoxide formation involves initial halogen addition followed by nucleophilic displacement to form the epoxide. Early examples of direct formation of epoxides from allylic alcohols with sodium hypobromite," bromine and 1.5 M NaOH,12 and r-butyl hypochlorite13 have been reviewed previously.fr Recently it has been shown that allylic alcohols can be cyclized effectively with bis(jym-collidine)iodine(I) perchlorate (equation 3).14 An unusual example of epoxide formation competing with other cyclization types is shown in equation (4).15 In this case, an allylic benzyl ether competes effectively with a -/-hydroxyl group as the nucleophile. 

Cyclizations of (3,7-un saturated acids form -lactones (4-exo cyclization) when the reactions are conducted under conditions of kinetic control.1 - The most common procedure for (3-lactone formation, developed by Barnett, involves halolactonization in a two-phase system using an aqueous solution of the carboxylate salt of the substrate with the halogen (Br2 or I2) added in an organic solvent.18 Cyclization with bis(, ym-collidine)iodine(I) perchlorate provides a higher yield than the Barnett procedure in cases where cyclization is not favored by geminal a-substitution (Table 2, entries 1 and 2).14 Iodo- and bromo-... 

It is possible to halogenate selectively at the methyl position of alkylpyridines to give halogenoalkylpyridines. Low to moderate yields of fluoromethylpyridines are obtained on fluorination of 2- and 4-methyl pyridines with (V-fluoro-bis[(trifluoromethyl)sulfonyl]imide 52 in the presence of sodium carbonate in dichloromethane <1996T15>. 2-Methylpyridine is fluorinated in 20% yield and 4-methylpyridine in 72% yield under these conditions. Reagent 52 also effects the selective fluorination of 2,4,6-collidine to give the 2-fluoromethylated product in moderate yield (Equation 35). 

The trienone (74), either by reaction with diazomethane and pyrolysis of the derived pyrazoline or by treatment with dimethylsulphoxonium methylide anion, yielded28 the 1 a,2 -methylene derivative (75). Epoxidation followed by the action of hydrogen chloride gave (77). The methylene bridge was re-formed by the reaction of collidine, the product being (76). Halogenated steroids of use in determining the metabolic fate of 16-chloro-oestrone methyl ethers and of chlormadinone acetate have been synthesized.29... 

Positive halogen complexes with pyridine bases are known as versatile halogenating reagents. Bis(sym-collidine)iodine(I) tetrafluoroborate (59) in dimethyl sulfoxide is a potential reagent for the direct conversion of alkenes to a-iodo carbonyl compounds (Scheme 6). The oxidation involves the... 

The electrophilic aromatic substitution of the pyridine ring continues to be explored as a way to prepare substituted pyridines. Bw-( 5y w-collidine)-iodine(I) and bromine (I) are effective iodinating or brominating agents, respectively, of pyridinols, although the di- or tri-halogenated products are obtained <97TL2467>. lodination of 3-pyridinol produces 5-hydroxy-... 

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