2,2-Diethoxytetrahydrofuran

2,2-Diethoxytetrahydrofuran is a cyclic orthoester which can be reacted with diols to biodegradable polyorthoesters.

2,2-Diethoxytetrahydrofuran
Names
IUPAC name
2,2-Diethoxyoxolane
Identifiers
3D model (JSmol)
ECHA InfoCard 100.161.490
Properties
C8H16O3
Molar mass 160.213 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

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.[1] In the reaction the electrophilic ethyl cation attackes 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.

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.[2]

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.

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.[1]

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.

Polyorthoesters are used as embedding media for pharmaceuticals in depot drug dosage forms for controlled drug release by surface erosion under physiological conditions.[3]

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References
  1. H. Meerwein; P. Borner; O. Fuchs; H.J. Sasse; H. Schrodt; J. Spille (1956), "Reaktionen mit Alkylkationen", Chem. Ber. (in German), 89 (9), pp. 2060–2079, doi:10.1002/cber.19560890907
  2. US 4990631, K. Alster, "Reacting trialkyl orthoformate with boron trifluoride and lactone, then with alkoxide or alkanol and base"
  3. Jorge Heller (1997), A.J. Domb; J. Kost; D.M. Wiseman (eds.), "6. Poly (Ortho Esters)", Handbook of Biodegradable Polymers, Harwood Academic Press, pp. 99–118, ISBN 90-5702-153-6
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