Bromination by bromine

Pyrido[2, l-6]quinazolinone (analogous to 204) and its 2,8-dinitro derivative were brominated by bromine in acetic acid, but the products are of unknown structure. Reaction with a mixture of phosphoryl chloride and... 

Not only were the reaction rates for bromination by bromine and by hypobromous acid very similar, but the corresponding activation energies (determined over a 20 °C range) were between 11.8 and 12.6 (for Br2) and 12.5 and 12.7 (for HOBr). Thus all this kinetic data is consistent with the rapid formation of an intermediate which is identical for both brominating reagents, and from which the slow loss of a proton subsequently occurs. 

In view of this apparent resistance of triazolium to bromination with electrophilic bromine, it is interesting to discover that 1,3-dimethyl-1,2,3-triazolium tosylate (71) was 4-brominated by bromine and NBS. When the 4-bromo salt (72) is dissolved in base, an equilibrium is established containing unbrominated salt (71) and 4,5-dibromo salt (73). Presumably, base converts 72 into an ylid, which is further brominated by 72. A similar product mixture was obtained from the isomeric 5-bromo tosylate (74) [69ACS(B)2733 71ACS(B)249] (Scheme 27). 

Propionaldehyde was brominated by bromine and the propanoilbromide was obtained. Then propanoilbromide reacted with methanol and hydrobromic acid yielding 1,2-dibromo-l-methoxypropane. 

Vapor-phase bromination of benzothiazole affords the 2-bromo derivative whereas attempts to perform the bromination by bromine in acetic acid solution yield only perbromides which on heating in alcoholic solution give substitution products containing bromine in the benzo ring. Chlorination in the 2-position results when benzothiazole is heated at 160 °C with phosphorus pentachloride in a sealed tube. 

The oxidation of bromide by hydrogen peroxide is a two-electron process that results in electrophilic bromination of organic substrates as opposed to radical bromination. This reactivity was established from the products of bromination of 2,3-dimethoxytoluene in which ring-substituted bromo-2,3-dimethoxytoluene is the sole product (26). The product of bromination by bromine radical, 2,3-dimethoxybenzyl bromide (27), was not observed. 

Apart from early reports on the bromination of quinazolinones which gave undefined products, reports dealing with the direct introduction of a halogen into a quinazoline nucleus via the electrophilic reaction are scarce, probably because these derivatives are more easily accessible by cyclization of appropriate halogen-substituted precursors (cf. Section 6.3.1.1.1.). Quinazolin-4(3//)-one can be brominated by bromine in aqueous potassium bromide solution... 

Methoxyphenazine 5-oxide or 10-oxide are brominated by bromine in acetic acid to yield 1-bromo compounds. 

Pyrido[2,3-t/]pyridazine resists bromination by bromine/silver(I) sulfate in sulfuric acid or by bromine/65 % oleum, but can be converted into the 3-bromo derivative 6 via the 3,4-dibromide and subsequent dehydrobromination, which is best effected by pyrolysis.83... 

Similarly ester (XXXV) undergoes bromination (by bromine) at both the vacant sites in the five-membered ring [263]. 

Direct bromination by bromine in acetic acid or in chloroform allows the synthesis of 2-bromo-, 2,5-dibromo-, 2,3,5-tribromo- and 2,3,4,5-tetrabromo-thiophenes [104, 105]. Microwave-assisted mono-, di-, tri- and tetrabrominations of thiophene have been described [83]. An example of 2,4,5-tribromination of 3-hexylthiophene using bromine in acetic acid is shown in Scheme 68 [106]. 

Bromo-3-methylthiophene-2-carbonyl chloride was required as an intermediate for the synthesis of an insecticide, 5-(4-bromo-3-methylthien-2-yl)-3-(2-chloro-6-fluorophenyl)-l-methyl-l//-l,2,4-triazole (XR-693) [113]. 3-Methyl-thiophene was selected as a starting material it could be selectively 2-brominated with NBS or exhaustively brominated by bromine to 2,3,5-tribromo-4-methyl-thiophene as shown in Scheme 73 [113]. 

The enol group in 164 was functionalized, and various derivatives were prepared, e.g., the methyl ether, the mesylate (see also U.S. Patent 3,985,737), the alkoxycarbonyloxy compounds, and the enamines (U.S. Patents 4,065,618, 4,065,621). The purpose of making these enol derivatives was activation of the 8-methyl group in the crotonic ester moiety for allylic halogenation. After extensive experimentation, it was found that the optimal activation of the methyl group was achieved in the morpholinoenamine (165). When this compound was subjected to allylic bromination by bromine in the presence of pyridine at — 20°C, the bro-momethyl derivative (166) was isolated in high yield. Hydrolysis of the... 

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