2,2-Diethoxytetrahydrofuran

2,2-DETHF Struktur.svg 2,2-Diethoxyoxolane 52263-97-5 correct CAS 318092 633-422-4 correct FDA GD3AP58UTV 358290 CCOC1(CCCO1)OCC 1S/C8H16O3/c1-3-9-8(10-4-2)6-5-7-11-8/h3-7H2,1-2H3 HRKTYSDVSRVOIP-UHFFFAOYSA-N 8 16 3 2,2-Diethoxytetrahydrofuran is a cyclic orthoester which can be reacted with diols to biodegradable polyorthoesters. Preparation The synthesis of 2,2-diethoxytetrahydrofuran via γ-butyrolactone and the Meerwein salt (triethyloxonium tetrafluoroborate) in diethyl ether was first described by Hans Meerwein and co-workers.H. Meerwein P. Borner O. Fuchs H.J. Sasse H. Schrodt J. Spille Chem. Ber. Reaktionen mit Alkylkationen 89 9 2060–2079 1956 German 10.1002/cber.19560890907 In the reaction the electrophilic ethyl cation attacks the carbonyl oxygen and forms the stable but extraordinarily hygroscopic O-ethyl-γ-butyrolactonium tetrafluoroborate (melting point 42 °C). The compound dissolves in dichloromethane, chloroform and 1,2-dichloroethane but is insoluble in diethyl ether, benzene and tetrachloromethane. The onium salt reacts practically quantitatively with an ethanolate anion from sodium ethoxide in ethanol forming 2,2-diethoxytetrahydrofuran. 500px|Synthese von 2,2-Diethoxytetrahydrofuran nach Meerwein 2,2-Diethoxytetrahydrofuran can also be produced in a solvent-free one-pot reaction using γ-butyrolactone, orthoformic triethyl ester and gaseous boron trifluoride. This route avoids the use of diethyl ether and its side-products and sensible intermediates. US 4990631 Reacting trialkyl orthoformate with boron trifluoride and lactone, then with alkoxide or alkanol and base 1991-02-05 K. Alster Alza Corp. First diethoxymethylium tetrafluoroborate is formed from the triethyl orthoformate and boron trifluoride at −30 °C. This electrophilically attacks the carbonyl group of the γ-butyrolactone and the O-ethyl-γ-butyrolactonium tetrafluoroborate. The addition of sodium ethoxide leads to the final product, which is obtained after distillation in 69% overall yield. 500px|Synthese von 2,2-Diethoxytetrahydrofuran nach Alster The reaction proceeds under gentle conditions (<0 °C) and the almost quantitative addition of ethanolate to O-ethyl-γ-butyrolactonium tetrafluoroborate can also be catalyzed by bases such as ammonia and triethylamine. Properties 2,2-Diethoxytetrahydrofuran is a clear liquid which boils at 10 mm Hg vacuum at 60 - 61.5 °C according to the original literature. Application The cyclic orthoester 2,2-diethoxytetrahydrofuran is a reactive bifunctional monomer which forms biodegradable polyorthoesters of the type POE-I by transesterification with α, ω-diols. 500px|Synthese des Polyorthoester-Typs POE-I Polyorthoesters are used as embedding media for pharmaceuticals in depot drug dosage forms for controlled drug release by surface erosion under physiological conditions.Jorge Heller A.J. Domb J. Kost D.M. Wiseman Handbook of Biodegradable Polymers 6. Poly (Ortho Esters) Harwood Academic Press 99–118 90-5702-153-6 1997 References Category:Ortho esters Category:Tetrahydrofurans Category:Ethyl esters