Bicyclo orthoesters and amide acetals were prepared from the corresponding triols or diethanolamine using -difluoroalkylamines. The reaction proceeds under milder conditions compared with the conventional methods. 4-tert-Butyl-1-(4-ethynylphenyl)trioxabicyclo[2.2.2]octane, a new class of insecticide, was prepared from a triol in 3 steps using a difluoroalkylamine.Key words: bicyclo orthoesters, bicyclo amide acetals, -difluoroalkylamines, protecting group, polymer Bicyclo orthoesters have been used by organic chemists as a protecting group for carboxylic acids.1 However, they have recently attracted the attention of a wide range of chemists because bicyclo orthoesters such as 1,4-disubstituted 2,4,6-trioxabicyclo[2.2.2]octanes have been found to be a highly potent insecticide.2 Moreover, it was found that bicyclo orthoesters polymerize reversibly to offer an environment-friendly recycling system for polymer materials.3 The bicyclo orthoesters were prepared by transetherification from the corresponding trialkyl orthocarboxylates and triols. 4 However, the reaction is reversible and is performed at high temperature over a long period to obtain the products. 4 The bicyclo orthoesters were also prepared by acid-catalyzed isomerization of the carboxylate esters of hydroxymethyloxetanes.1,5 However, severe reaction conditions are required for the preparation of the starting hydroxymethyloxetanes.5 Therefore, more facile and convenient methods are required for the synthesis of bicyclo orthoesters. Recently, we found that the reaction of -difluoroalkylamines with 2-aminoalcohols, 2-aminothiols, and 1,3-diamines proceeds rapidly to give five-membered heterocyclic compounds under mild conditions.6 During the course of the study, we found that the reaction of the difluoroalkylamines with triols proceeds quickly to give bicyclo orthoesters under mild conditions (Equation 1). Various difluoroalkylamines can be prepared from the corresponding carboxylic amides in two steps.6 When 1,1,1-tris(hydroxymethyl)ethane 1 was allowed to react with N,N-diethyl--difluorobenzylamine (DFBA) in DMF, the reaction was completed at r.t. in 2 h to give 4-methyl-1-phenyl-2,6,7-trioxabicyclo[2.2.2]octane 5 in 66% yield (Table 1). Under the same conditions, the tbutyl group substituted bicyclo orthoester 6 was obtained from 1 in 70% yield with N-(1,1-difluoro-2,2-dimethylpropyl)pyrrolidine instead of DFBA. On the other hand, a benzoyloxy group substituted triol 2 is less soluble in DMF and its reaction with DFBA was not completed under the same conditions. Therefore, the reaction was performed in CDCl 3 and was followed by NMR. Consequently, the reaction was completed in 1 h at 50 °C and the corresponding bicyclo orthoester 7 was obtained in 62% yield. Bis-bicyclo orthoester of dipentaerythritol 3 was previously prepared by transetherification using triethyl orthopropionate. The reaction was performed at high temperature (180-200 °C) for 6 h, and the desired bifunctional bicyclo orthoester was obtained in only 1.4% yield.4...
Dioxane derivatives R 0470Facile Synthesis of Bicyclo Orthoesters and Bicyclo Amide Acetals Using α,α-Difluoroalkylamines. -Reaction of triols of type (I) with α,α-difluoroalkylamines offers a simple synthesis of bicyclic orthoesters. Diethanolamine gives bicyclic orthoamides (VI) under similar conditions. The process is used in the synthesis of the highly potent insecticide (XI). -(TANGE, S.; FUKUHARA, T.; HARA*, S.; Synthesis 2008, 20, 3219-3222; Grad. Sch. Eng., Hokkaido Univ., Kita, Sapporo 060, Japan; Eng.) -Mais 09-153
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