Readily Scalable Methodology for the Synthesis of Nonsymmetric Glyceryl Diethers by a Tandem Acid-/Base-Catalyzed Process

Article abstract of DOI:10.1021/acs.oprd.9b00411

A useful optimized synthetic methodology has been designed for the synthesis of nonsymmetric glyceryl diethers from epichlorohydrin. A tandem process combining a cheap, heterogeneous, and fully recoverable acid catalyst and alkaline hydroxide is used for the synthesis of a variety of glycerol-derived ethers bearing different alkyl substituents in 1 and 3 positions. Different heterogeneous acid catalysts have been tested for the reaction of epichlorohydrin with several alcohols, the best results being obtained with readily available recoverable and inexpensive montmorillonite-K10 and Nafion NR50. For the second reaction step, potassium hydroxide is used. In all the cases, good yields of the desired glyceryl diethers are obtained in smooth reaction conditions, always with total conversion of epichlorohydrin and without the need of intermediate purification. Scale-up of the tandem process has been carried out with good results.

Full text of DOI:10.1021/acs.oprd.9b00411

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Full Paper
A readily scalable methodology for the synthesis of non-symmetric
glyceryl diethers by a tandem acid/base catalyzed process
Alejandro Leal-Duaso, Sara Gracia-Barberán, Jose A. Mayoral, Jose Ignacio Garcia, and Elísabet Pires
Org. Process Res. Dev., Just Accepted Manuscript • DOI: 10.1021/acs.oprd.9b00411 • Publication Date (Web): 30 Dec 2019
Downloaded from pubs.acs.org on December 31, 2019
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A readily scalable methodology for the synthesis of
non-symmetric glyceryl diethers by a tandem
acid/base catalyzed process.
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Alejandro Leal-Duaso,a,b Sara Gracia-Barberán,a José A. Mayoral,a
a,b
José I. García,b Elisabet Pires,*
a
Departamento de Química Orgánica. Facultad de Ciencias.
Universidad de Zaragoza. c/ Pedro Cerbuna 12. 50009 Zaragoza
(Spain).
b
Instituto de Síntesis Química y Catálisis Homogénea (ISQCH)
CSIC-Universidad de Zaragoza. c/ Pedro Cerbuna 12. 50009
Zaragoza (Spain).
KEYWORDS Heterogeneous acid catalysis, glycerol, glyceryl ethers,
green solvent.
ABSTRACT: A useful optimized synthetic methodology has been
designed for the obtaining of non-symmetric glyceryl diethers from
epichlorohydrin. A tandem process combining a cheap, heterogeneous
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and fully recoverable acid catalyst and alkaline hydroxide is used
for the synthesis of a variety of glycerol-derived ethers bearing
different alkyl substituents in 1 and 3 positions. Different
heterogeneous acid catalysts have been tested for the reaction of
epichlorohydrin with several alcohols, the best results being
obtained with readily available recoverable and inexpensive
Montmorillonite-K10 and Nafion® NR50. For the second reaction step
potassium hydroxide is used. In all the cases, good yields of the
desired glyceryl diethers are obtained in smooth reaction
conditions, always with total conversion of epichlorohydrin and
without the need of intermediate purification. Scale up of the
tandem process has been carried out with good results.
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INTRODUCTION
Green Chemistry focusses on the production of chemicals improving
the sustainability and safety of the synthetic processes, reducing
the generation of by-products and minimizing risks.1 One of the
outstanding aspects related to Green Chemistry is the development
of green solvents, able to substitute conventional ones, which
have a non-renewable origin, and usually present negative
features, such as volatility, flammability and toxicity.
In the last decades, different families of neoteric solvents have
arisen such as bio-based solvents, fluorinated solvents, ionic
liquids, deep eutectic solvents, supercritical fluids, gas-
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expanded liquids, switchable solvents, etc.2–6 Bio-based solvents
are attracting a great attention due to their chemical similarity
with conventional organic solvents, and their favorable features,
mainly their bio-based origin, biodegradability and low toxicity.7
Among the different proposals, glycerol and its derivatives such
as esters, ethers, carbonates and ketals present very interesting
properties.8 These compounds have been used as solvents and
additives in cleaning, cosmetic, food and pharmaceutical
industry.9–13
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The use of glycerol itself or its derivatives as solvents is
supported by the readily availability of glycerol as it appears to
be the concomitant product in the biodiesel preparation from
vegetable oils.14 Thus valorization of glycerol has attracted a
great attention both in academic and industrial fields.15,16
Glyceryl ethers stand out with respect to other glycerol
derivatives due to their chemical stability, especially to
oxidation,17 their tunable physical-chemical properties, mainly
polarity, viscosity and interfacial characteristics, as a function
of their substituents,18,19 their low volatility and flammability,
interesting hydrotropy,20,21 and low acute ecotoxicity.22–24
Different synthetic procedures for the obtaining of glyceryl
ethers have been proposed using glycerol as starting material,
including substitutions, alkylations, etherifications with alcohol
or alkenes, telomerization reactions, etc.25 However, controlling
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