The basicity gradient-driven migration of iodine: conferring regioflexibility on the substitution of fluoroarenes

Six different fluoroarenes were submitted to the same transformations. Direct deprotonation with alkyllithium or lithium dialkylamide as reagents and subsequent carboxylation afforded acids. These included 2,6-difluorobenzoic acid, 3,6-difluoro-2-iodobenzoic acid, 2-fluoro-6-iodobenzoic acid, 2-fluoro-3-iodobenzoic acid, 2,3-difluoro-4-iodobenzoic acid and 1-fluoro-2-naphthalenecarboxylic acid. If the aryllithium intermediate was trapped with iodine rather than with dry ice, an iodofluoroarene (2, 7, 12, 17, 19, and 24) was formed. Iodoarenes included 1,3-difluoro-2-iodobenzene, 1,4-difluoro-2,3-diiodobenzene, 1-fluoro-2,3-diiodobenzene, 2-fluoro-1,3-diiodobenzene, 2,3-difluoro-1,4-diiodobenzene, and 1-fluoro-2-iodonaphthalene. These, upon treatment with lithium diisopropylamide, underwent deprotonation and iodine migration. The resulting new aryllithium species was intercepted either by carboxylation, to give 2,6-difluoro-3-iodobenzoic acid, 2,5-difluoro-3,6-diiodobenzoic acid, 2-fluoro-3,6-diiodobenzoic acid, 2,3-difluoro-4,6-diiodobenzoic acid, and 1-fluoro-3-iodo-2-naphthalenecarboxylic acid, or by neutralization to produce the iodofluoroarenes which included 2,4-difluoro-1-iodobenzene, 1,4-difluoro-2,5-diiodobenzene, 2-fluoro-1,4-diiodobenzene, 1-fluoro-3-iodonaphthalene. The latter family of compds. was converted into another set of acids, which included 2,4-difluorobenzoic acid, 2,5-difluoro-4-iodobenzoic acid, 1-fluoro-3-naphthalenecarboxylic acid, by subsequent treatment with butyllithium or isopropylmagnesium chloride and carbon dioxide. [on SciFinder (R)]


Published in:
European Journal of Organic Chemistry, 19, 3351-3358
Year:
2002
Keywords:
Note:
CAN 138:237859 25-17 Benzene, Its Derivatives, and Condensed Benzenoid Compounds Institut de Chimie moleculaire et biologique Ecole Polytechnique Federale, BCh,Lausanne,Switz. Journal 1434-193X written in English. 75-77-4 (Chlorotrimethylsilane); 321-38-0 (1-Fluoronaphthalene); 348-52-7 (1-Fluoro-2-iodobenzene); 372-18-9 (1,3-Difluorobenzene); 462-06-6 (Fluorobenzene); 1121-86-4 (1-Fluoro-3-iodobenzene); 2265-92-1 (1,4-Difluoro-2-iodobenzene); 64248-57-3 (1,2-Difluoro-3-iodobenzene) Role: RCT (Reactant), RACT (Reactant or reagent) (basicity gradient-driven migration of iodine: conferring regioflexibility on substitution of fluoroarenes); 385-00-2P (2,6-Difluorobenzoic acid); 2265-93-2P (2,4-Difluoro-1-iodobenzene); 13671-00-6P (2,6-Difluorobenzoic acid methyl ester); 13697-89-7P (1,3-Difluoro-2-iodobenzene); 147808-02-4P (2-Fluoro-1,4-diiodobenzene); 189095-25-8P (1,4-Difluoro-2,5-diiodobenzene); 447464-03-1P (2-Fluoro-3-iodobenzoic acid); 501432-99-1P (1,4-Difluoro-2,3-diiodobenzene); 501433-02-9P (1-Fluoro-2,3-diiodobenzene); 501433-05-2P (2,3-Difluoro-4-iodobenzoic acid); 501433-06-3P (2,3-Difluoro-1,4-diiodobenzene); 501433-08-5P; 501433-09-6P (1-Fluoro-2-iodonaphthalene); 501433-11-0P (1-Fluoro-3-iodonaphthalene); 501433-13-2P (3,6-Difluoro-2-iodobenzoic acid methyl ester); 501433-14-3P (2,6-Difluoro-3-iodobenzoic acid methyl ester); 501433-15-4P (2-Fluoro-3,4-diiodobenzoic acid methyl ester); 501433-16-5P ((2-Fluoro-3-iodophenyl)trimethylsilane) Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (basicity gradient-driven migration of iodine: conferring regioflexibility on substitution of fluoroarenes); 574-97-0P (1-Fluoro-2-naphthalenecarboxylic acid); 1583-58-0P (2,4-Difluorobenzoic acid); 13772-61-7P (1-Fluoro-3-naphthalenecarboxylic acid); 111771-08-5P (2-Fluoro-6-iodobenzoic acid); 124700-40-9P (2-Fluoro-4-iodobenzoic acid); 229178-74-9P (2,6-Difluoro-3-iodobenzoic acid); 333780-74-8P (2,3-Difluoro-5-iodobenzoic acid); 501432-98-0P (3,6-Difluoro-2-iodobenzoic acid); 501433-00-7P (2,5-Difluoro-3,6-diiodobenzoic acid); 501433-01-8P (2,5-Difluoro-4-iodobenzoic acid); 501433-03-0P (2-Fluoro-3,6-diiodobenzoic acid); 501433-04-1P (2-Fluoro-1,3-diiodobenzene); 501433-07-4P (2,3-Difluoro-4,6-diiodobenzoic acid); 501433-10-9P (1-Fluoro-3-iodo-2-naphthalenecarboxylic acid); 501433-12-1P; 501433-17-6P Role: SPN (Synthetic preparation), PREP (Preparation) (basicity gradient-driven migration of iodine: conferring regioflexibility on substitution of fluoroarenes)
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 Record created 2006-03-03, last modified 2018-01-27


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