\makeatletter
\@ifundefined{HCode}
{\documentclass[screen,CRCHIM,Unicode,Thematic,published]{cedram} 
\newenvironment{noXML}{}{}
\def\tsup#1{$^{{#1}}$}
\def\tsub#1{$_{{#1}}$}
\def\thead{\noalign{\relax}\hline}
\def\tbody{\noalign{\relax}}
\def\endthead{\noalign{\relax}\hline}
\def\tabnote#1{\vskip4pt\parbox{.83\linewidth}{#1}}
\def\tpar#1{\\{\centering
  \vspace*{3pt}#1}}
\RequirePackage{etoolbox}
\def\jobid{crchim20230961}
\def\inlinefig#1{\includegraphics{#1}}
\newenvironment{xxcenter}{\begin{center}}{\end{center}}
\def\xsection#1{}
%\graphicspath{{/tmp/\jobid_figs/web/}}
\graphicspath{{./figures/}}
\usepackage[T1]{fontenc}
\usepackage{comment}
\newcounter{runlevel}
\usepackage{upgreek}
\let\MakeYrStrItalic\relax
\def\Smallskip{\smallskip}
\csdef{Seqnsplit}{\\}
\def\refinput#1{}
\def\back#1{}
\def\xmorerows#1#2{#2}
\def\0{\phantom{0}}
\def\mn{\phantom{$-$}}
\def\hyphen{\mbox{-}}
\newenvironment{inftab}{}{}
\usepackage{multirow} 
\def\nrow#1{\@tempcnta #1\relax%
\advance\@tempcnta by 1\relax%
\xdef\lenrow{\the\@tempcnta}}
\def\morerows#1#2{\nrow{#1}\multirow{\lenrow}{*}{#2}}
\def\botline{\\\hline}
\def\Lbreak{\newline}
\def\ubreak{\break}
\def\xvarnothing{\emptyset}
\DOI{10.5802/crchim.273}
\datereceived{2023-10-30}
\daterevised{2023-11-10}
\dateaccepted{2023-11-10}
\ItHasTeXPublished
}
{\documentclass[crchim]{article}
\def\CDRsupplementaryTwotypes#1#2{}
\def\CDRdoi{10.5802/crchim.273} 
\def\href#1#2{\url{#1}}
\def\xsection#1{}
\newenvironment{xxcenter}{}{}
\def\tpar#1{\Tg</p>\Tg<p>#1}
\def\xmorerows#1#2{\morerows{#1}{#2}}
\def\Smallskip{}
\let\newline\break
\def\ubreak{}
\let\xvarnothing\emptyset
\makeatletter
}
\makeatother

\usepackage[T1]{fontenc}
\usepackage{upgreek}

\dateposted{2024-03-29}
\begin{document}

\begin{noXML}

%\makeatletter
%\def\TITREspecial{\relax}
%\def\cdr@specialtitle@english{French Women in Chemistry in 2024}
%%\def\cdr@specialtitle@french{Les chimistes fran\c{c}aises en 2024}
%\makeatother

\title{A new generation of
ecocatalysts$^{\text{\textregistered}}$---from Invasive Alien Species
to sustainable and biosourced glyceryl fatty esters}

\alttitle{Une nouvelle g\'{e}n\'{e}ration
d'\'{e}cocatalyseurs$^{\text{\textregistered}}$\ --- des esp\`{e}ces
exotiques envahissantes aux esters de glyc\'{e}ryle d'acides gras
durables  et biosourc\'{e}s}

\author{\firstname{Arthur} \lastname{Lasbleiz}}
\address{Laboratory of Bio-inspired Chemistry and Ecological
Innovations, UMR 5021, University of Montpellier - CNRS, 34790 Grabels,
France}

\author{\firstname{Franck} \lastname{Pelissier}\CDRorcid{0000-0002-0621-2384}}
\addressSameAs{1}{Laboratory of Bio-inspired Chemistry and Ecological
Innovations, UMR 5021, University of Montpellier - CNRS, 34790 Grabels,
France}

\author{\firstname{Jean-Hugues} \lastname{Renault}\CDRorcid{0000-0002-8705-7258}}
\address{Universit\'{e} de Reims Champagne-Ardenne, CNRS, ICMR 7312,
51097, Reims, France}

\author{\firstname{Claire M.} \lastname{Grison}\CDRorcid{0000-0002-3179-2093}}
\addressSameAs{1}{Laboratory of Bio-inspired Chemistry and Ecological
Innovations, UMR 5021, University of Montpellier - CNRS, 34790 Grabels,
France}

\author{\firstname{Yves-Marie} \lastname{Legrand}\CDRorcid{0000-0002-0334-1666}}
\addressSameAs{1}{Laboratory of Bio-inspired Chemistry and Ecological
Innovations, UMR 5021, University of Montpellier - CNRS, 34790 Grabels,
France}

\author{\firstname{Claude} \lastname{Grison}\CDRorcid{0000-0002-2687-1520}\IsCorresp}
\addressSameAs{1}{Laboratory of Bio-inspired Chemistry and Ecological
Innovations, UMR 5021, University of Montpellier - CNRS, 34790 Grabels,
France}
\email[C. Grison]{claude.grison@cnrs.fr}

\keywords{\kwd{Invasive Alien
Species}\kwd{Ecocatalysts$^{\text{\textregistered}}$}
\kwd{Transesterification}\kwd{Glyceryl
esters}\kwd{Sustainable chemistry}}

\altkeywords{\kwd{Esp\`{e}ces Exotiques
Envahissantes}\kwd{\'{E}cocatalyseurs$^{\text{\textregistered}}$}
\kwd{Transest\'{e}rification}\kwd{Esters de glyc\'{e}ryle}\kwd{Chimie durable}}

\thanks{French National Centre for Scientific Research (CNRS)}

\dedicatory{This article is dedicated to Professor Philippe Coutrot in
recognition of his significant contributions in~the organic chemistry
of biomolecules}

\shortrunauthors

\begin{abstract}
A new generation of ecocatalysts$^{\text{\textregistered}}$\ derived
from Invasive Alien Species (IAS) (\textit{Fallopia japonica} and
\textit{Arundo donax}) was used as starting material for the
preparation of novel biosourced catalysts. The preparation of these
ecocatalysts$^{\text{\textregistered}}$\ is a new way to support the
management of IAS. These catalysts were characterized by microwave
plasma atomic emission spectrometry (MP-AES) and X-ray powder
diffraction (XRPD), which revealed basic properties. After calculating
Pearson's correlations to evaluate the relative importance of reaction
parameters, a design of experiments (DoE) was implemented to synthesize
glyceryl caprylate and oleate with a high selectivity. These molecules
constitute emollients and non-ionic emulsifiers of high industrial
interest. The ecocatalysts$^{\text{\textregistered}}$\ were efficient
and recyclable for the transesterification of methyl and ethyl fatty
esters, leading to high yields (66--83\%). These
ecocatalysts$^{\text{\textregistered}}$\ are an alternative to usual
base catalysts previously reported for the transesterification of
methyl caprylate, methyl oleate and ethyl caprylate with glycerol,
which are often non-recyclable, not systematically selective and
require questionable preparation conditions. 
\end{abstract}

\begin{altabstract}
Une nouvelle g\'{e}n\'{e}ration
d'\'{e}cocatalyseurs$^{\text{\textregistered}}$\ d\'{e}riv\'{e}s
d'Esp\`{e}ces Exotiques Envahissantes (EEE) (\textit{Fallopia japonica}
et \textit{Arundo donax}) a \'{e}t\'{e} utilis\'{e}e comme mat\'{e}riau
de d\'{e}part pour la pr\'{e}paration de nouveaux catalyseurs
biosourc\'{e}s. La pr\'{e}paration de ces
\'{e}cocatalyseurs$^{\text{\textregistered}}$\ est une nouvelle
fa\c{c}on de g\'{e}rer les EEE. Ces catalyseurs, caract\'{e}ris\'{e}s
par spectrom\'{e}trie d'\'{e}mission atomique par plasma micro-ondes
(MP-AES) et par diffraction des rayons X sur poudre (DRXP), ont
r\'{e}v\'{e}l\'{e} poss\'{e}der des propri\'{e}t\'{e}s basiques.
Apr\`{e}s avoir calcul\'{e} des corr\'{e}lations de Pearson
\'{e}valuant l'importance relative des param\`{e}tres r\'{e}actionnels,
un plan d'exp\'{e}riences (DoE) a \'{e}t\'{e} mis en \oe{}uvre pour
synth\'{e}tiser le caprylate et l'ol\'{e}ate de glyc\'{e}ryle avec une
grande s\'{e}lectivit\'{e}. Ces mol\'{e}cules constituent des
\'{e}mollients et des \'{e}mulsifiants non ioniques de fort
int\'{e}r\^{e}t industriel. Les
\'{e}cocatalyseurs$^{\text{\textregistered}}$\ ont \'{e}t\'{e} efficaces
et recyclables pour la transest\'{e}rification d'esters m\'{e}thyliques
et \'{e}thyliques d'acides gras, conduisant \`{a} des rendements
\'{e}lev\'{e}s (66--83\%). Ces
\'{e}cocatalyseurs$^{\text{\textregistered}}$\ sont une excellente
alternative aux catalyseurs standards rapport\'{e}s dans la
bibliographie pour la transest\'{e}rification du caprylate de
m\'{e}thyle, de l'ol\'{e}ate de m\'{e}thyle et du caprylate
d'\'{e}thyle avec le glyc\'{e}rol, qui sont souvent non recyclables,
peu s\'{e}lectifs et requi\`{e}rent des conditions de pr\'{e}paration
critiquables du point de vue environnemental.
\end{altabstract}

\maketitle

\twocolumngrid

\end{noXML}

\section{Introduction}\label{sec1}

According to recent data from IPBES (Intergovernmental Science-Policy
Platform on Biodiversity and Ecosystem Services), 60\% of species
extinctions are due to Invasive Alien Species (IAS)~\cite{1}. These
latter constitute one of the five main causes of biodiversity loss on a
global scale and cost 400 billion dollars each year. IAS profoundly and
negatively affect biodiversity, economy, food security, water security,
and human health. Among them, the Japanese knotweed, or
\textit{Fallopia japonica}, is one of the most fearsome plant species.
It is widely established in wetlands in Europe, Oceania, North and
South America~\cite{2}. The \mbox{uncontrolled} development of 
\textit{F.~japonica} strongly impacts the biological diversity of
wetlands, on uses, the weakening of banks and hinders flood management.
\textit{Arundo donax}, also called the giant reed and present in
temperate and tropical areas~\cite{3}, is another demonstrative
example. Its long, fibrous, interconnected root mats constitute a
frightening obstacle to ecosystems and affect the functioning of
wetlands. The growth of \textit{A.~donax} is 2--5 times faster than
native competitors, and its vegetative reproduction allows it to
quickly invade new areas and completely supplant native vegetation.
Finally, \textit{A.~donax} is extremely flammable, increasing the
likelihood and intensity of wildfires.

While they constitute the largest reservoirs of carbonaceous organic
matter, wetlands contribute to mitigating extreme climatic phenomena
(floods and droughts), water purification, and preserving biodiversity.
Thus, the rapid disappearance of wetlands, which no longer ensure their
regulatory action, is worryingly reducing the resilience of
neighbouring ecosystems. Over the past ten years, wetland managers have
made considerable efforts to try to eradicate IAS. The technique is
frequently based on the extraction of rhizomes. This method is
destructive, expensive and has a major limitation: the slightest
residue of rhizomes or roots can grow uncontrollably. The various
eradication operations seem so far illusory. Today, it is more
realistic to study the implementation of solutions to refrain the
proliferation of IAS rather than aiming for their eradication. Thus,
for example, a less destructive management of the proliferation of
invasive species, \textit{F.~japonica} and \textit{A.~donax}, is being
studied: rather than extracting the rhizomes at the cost of significant
and inconclusive efforts, repeated mowing of the aerial parts could
deplete the plant. This technique affects the vegetative dynamics of
the species and allows native species to recreate habitats. These
experiments must be designed over several years to assess the process
efficiency of management control for each species. It is therefore
essential to find an economically viable valorization of the harvested
parts to support the ecological study. To do so and particularly to
limit IAS in wetlands over the long term, the Grison group is studying
the transformation of harvested aerial parts into essential raw
materials for sustainable chemistry (Figure~\ref{fig1}).
Their particular physiology and vegetative dynamics bear witness to an
unusual mineral composition~\cite{4}. They \mbox{complete} the family
of biosourced metal catalysts, called
ecocatalysts$^{\text{\textregistered}}$~\cite{5,6,7,8}.

Recently, we showed that ecocatalysts$^{\text{\textregistered}}$\ 
derived from \textit{F.~japonica} were composed of fairchildite, a
double carbonate of potassium and calcium,
K\tsub{2}Ca(CO\tsub{3})\tsub{2}. This original structure led to very
good results in the Michael addition of di-activated methylene to
cyclic enones~\cite{9}. The study was here extended to a reaction of
industrial interest, the transesterification of alkyl esters with
glycerol. This new application led to the green and biosourced
synthesis of emollients and non-ionic emulsifiers, glyceryl caprylates
and oleates. The structure and reactivity of
ecocatalysts$^{\text{\textregistered}}$\ derived from
\textit{F.~japonica} and \textit{A.~donax} were compared. After a
detailed study of the different parameters influencing the conversion
and selectivity of transesterification reactions, the design of an
experimental plan was carried out to optimize the reaction conditions.
The method was then studied on larger quantities through a scale-up
study.

\begin{figure*}
{\vspace*{-2pt}}
\includegraphics{fig01}
{\vspace*{-2pt}}
\caption{\label{fig1}From the management of IAS in wetlands to green
synthesis of glyceryl esters. (a) \textit{F.~japonica} and (b)
\textit{A.~donax}~\cite{10}; (c,~d) massive harvests of aerial
parts; (e) transformation of aerial parts into
ecocatalysts$^{\text{\textregistered}}$; (f) synthesis of glyceryl
esters using ecocatalysts$^{\text{\textregistered}}$. Pictures taken by
the authors.}
\end{figure*}

\section{Results and discussion}\label{sec2}
\subsection{Characterisation of ecocatalysts$^{\text{\textregistered}}$}
\label{ssec21}

Ecocatalysts$^{\text{\textregistered}}$, Eco1-E-FA-JA and Eco1-E-AR-DO,
were prepared from aerial parts of \textit{F.~japonica} and
\textit{A.~donax}, including stems, leaves and petioles. The harvested
parts were ground and thermally treated under airflow, directly
characterised by MP-AES and XRPD and used as catalysts for the
transesterification of methyl and ethyl fatty esters.

\subsubsection{Elemental composition of 
ecocatalysts$^{\text{\textregistered}}$}\label{sssec211}

Metallic compositions of ecocatalysts$^{\text{\textregistered}}$,
resulting from the thermal treatment of aerial parts of
\textit{F.~japonica} (Eco1-E-FA-JA) and \textit{A.~donax}
(Eco1-E-AR-DO), were studied by MP-AES analyses. Assays were performed
in triplicate for each sample to determine the standard deviation of
the measurement (Table~\ref{tab1}). The results showed that potassium
was the major mineral element in each
ecocatalysts$^{\text{\textregistered}}$. These values were
significantly higher than the average values of native plants present
in the wetlands where the harvests were carried out (potassium content
usually around 3--5\%). It should be noted that Eco1-E-FA-JA exhibited
a high magnesium level, which is consistent with the high level of
chlorophyll in the leaf biomass of \textit{F.~japonica}~\cite{11}.

%tab1
\begin{table*}
\caption{\label{tab1}Elemental composition of Eco1-E-FA-JA and
Eco1-E-AR-DO determined by MP-AES.}
\vspace*{-4pt}
\begin{tabular}{ccccccc}
\thead
\xmorerows{1}{Ecocatalysts$^{\text{\textregistered}}$} & 
\multicolumn{6}{c}{Composition (wt\% (\%RSD))} \\\cline{2-7}
& Ca & Fe & Mg & Na & K & Al \\
\endthead
\morerows{1}{Eco1-E-FA-JA} & 9.09 & 0.28 & 3.90 & 0.10 & \textbf{30.16} & 0.13 \\
                           & (0.57) & (4.33) & (0.5)\0 & (0.66) & (0.7) & (3.52)\vspace*{4pt} \\
\morerows{1}{Eco1-E-AR-DO} & 2.71 & 0.05 & 1.49 & 0.12 & \textbf{37.16} & 0.03 \\ 
                           & (2.29) & (2.93) & (4.07) & (0.63) & \0(0.48) & (1.10)
\botline
\end{tabular}
{\vspace*{-5pt}}
\end{table*}

\subsubsection{XRPD analysis of
ecocatalysts$^{\text{\textregistered}}$}\label{sssec222}

The structures of Eco1-E-FA-JA and Eco1-E-AR-DO were investigated by
XRPD (Table~\ref{tab2}, Figures S1 and S2 in ESI). The two
ecocatalysts$^{\text{\textregistered}}$\ presented mostly crystalline
potassium salts; neutral crystalline potassium salts were similar but
the basic ones differed. Indeed, Eco1-E-AR-DO exhibited
K\tsub{2}CO\tsub{3}, while Eco1-E-FA-JA revealed the presence of
KMgPO\tsub{4}$\cdot$6H\tsub{2}O, crystallized as struvite-K.
Surprisingly no crystalline phase of fairchildite,
K\tsub{2}Ca(CO\tsub{3})\tsub{2}, could be detected within Eco1-E-FA-JA,
as it had been previously observed~\cite{9}. The difference of
structure between the two ecocatalysts$^{\text{\textregistered}}$,
which both derived from the same plant species \textit{F.~japonica},
might be due to different locations and dates of \mbox{collection}.
Nevertheless, the presence of struvite-K was of high interest since
phosphates possess stronger basic properties than carbonates.

\break
The basicity of the two ecocatalysts$^{\text{\textregistered}}$\ was
hence assessed and gave high pH values of 12 for Eco1-E-AR-DO and 11.5
for Eco1-E-FA-JA (Table~\ref{tab2}). 

These two catalysts being therefore slightly different, it was
particularly interesting to compare their reactivity in the
basic-catalyzed transesterification of triglycerides.

\vspace*{-10pt}
\subsection{Application of the
ecocatalysts$^{\text{\textregistered}}$\ in the transesterification of
triglycerides} \label{ssec22}

The preparation of glyceryl esters is based on three possible
strategies (Scheme~\ref{sch1}):
\vspace*{20pt}
 		

\begin{scheme*}
\includegraphics{sc01}
{\vspace*{15pt}}
\caption{\label{sch1}General routes for the synthesis of glyceryl
esters from literature and envisaged strategies for the
transesterification of alkyl esters with glycerol using ecocatalysis.}
{\vspace*{-4pt}}
\end{scheme*}


%tab2
\begin{table*}
\caption{\label{tab2}Crystalline species of potassium salts
Eco1-E-AR-DO and Eco1-E-FA-JA determined by XRPD and pH of a suspension
of ecocatalysts$^{\text{\textregistered}}$\ in water}
\begin{tabular}{cccccccc}
\thead
\xmorerows{1}{Ecocatalysts$^{\text{\textregistered}}$} &
\multicolumn{6}{c}{Crystalline species} & 
\xmorerows{1}{pH$^{*}$} \\\cline{2-7}
& KCl & K\tsub{2}SO\tsub{4} & K\tsub{2}CO\tsub{3} &
K\tsub{2}Ca(CO\tsub{3})\tsub{2} & KMgPO\tsub{4}{${\cdot}$}6H\tsub{2}O &
CaCO\tsub{3} & \\
\endthead
\raisebox{-.8pc}{Eco1-E-AR-DO} & \raisebox{-1.8pc}{\inlinefig{fx01}} & 
\raisebox{-1.8pc}{\inlinefig{fx02}} & 
\raisebox{-1.8pc}{\inlinefig{fx03}}\vspace*{4pt} & 
\raisebox{-.8pc}{-} & \raisebox{-.8pc}{-} & \raisebox{-.8pc}{-} 
& \raisebox{-.8pc}{12} \\
\raisebox{-.8pc}{Eco1-E-FA-JA} & \raisebox{-1.8pc}{\inlinefig{fx04}} & 
\raisebox{-1.8pc}{\inlinefig{fx05}} & \raisebox{-.8pc}{-} & 
\raisebox{-.8pc}{-} & \raisebox{-1.8pc}{\inlinefig{fx06}} & 
\raisebox{-1.8pc}{\inlinefig{fx07}}\vspace*{2pt} & \raisebox{-.8pc}{11.5}
\botline
\end{tabular}
\tabnote{$^{*}$pH was measured after stirring 100~mg of
ecocatalyst$^{\text{\textregistered}}$\ in 1~mL of distilled water for
15~min and decanting.}
{\vspace*{-12pt}}
\end{table*}

\break
\medskip\noindent
$\bullet$\ Hydrolysis of a triglyceride.\newline
\textbf{(Strategy 1)}: This strategy may seem attractive because it is direct.
However, the hydrolysis of a triglyceride into a monoglyceride is very
difficult to control as hydrolysis is increasingly rapid as the fatty
chains of the triglyceride are hydrolyzed~\cite{12,13}. The literature
is therefore mainly based on enzymatic hydrolysis using specific
lipases, which are more suited to this situation~\cite{14,15}. However,
the selectivities remain moderate ({${>}$}50\%) and the reactions are
described on small quantities of substrates.


\medskip\noindent
$\bullet$\ Esterification of an activated fatty acid.\newline
\textbf{(Strategy 2)}: This sequenced method requires the prior hydrolysis of the
triglyceride into fatty acid, followed by the activation of the acid to
carry out the esterification. Various activation methods are described:
activation of the fatty acid partner by Br\o{}nsted acids such as
APTS~\cite{16}, Zn or Ti salts supported on zeolite~\cite{17,18},
tungsten nanoparticles in ionic liquid~\cite{19}, cobalt salts
supported on hydroxyapatite~\cite{20}, activation by
enzymes~\cite{21,22,23}, formation of fatty acid
chlorides~\cite{24,25,26,27,28}, or acid \mbox{anhydrides~\cite{29,30}.} Using
\mbox{glycerol} as a nucleophile leads to unsatisfactory results despite the
variety of activation agents (drastic conditions in terms of
temperature and/or reaction time), and masked forms of glycerol have
been described to improve conversion and selectivity. Thus,
isopropylidene glycerol~\cite{30,31}, glycidol~\cite{32,33,34,35,36},
epichlorohydrin~\cite{37} or 3-chloro-1,2-propanediol~\cite{38} have
been reported. This strategy is hardly compatible with the principles
of green chemistry (protection/deprotection sequences of the masked
form of glycerol, toxic reagent, moderate or even low overall yields).

\smallskip\noindent
$\bullet$\ Transesterification of a methyl or ethyl fatty ester.\newline
\textbf{(Strategy 3)}: This strategy is probably the best compromise between
efficiency and number of reaction steps. The key intermediate here is
the fatty methyl ester (eventually an ethyl ester), widely described
since the emergence of biodiesel. However, only a few examples of
monoglyceride formation from fatty esters are described in the
literature. Among them, the preparation of glyceryl oleate and
caprylate has been reported using sodium carbonate for 5~h at
180~\textdegree C~\cite{39}. The yield is not specified, but the
reaction conditions show that using alkaline carbonates makes it
possible to facilitate the transesterification under reasonable
reaction conditions in terms of duration and temperature. Our recent
work showed that the ecocatalyst$^{\text{\textregistered}}$\ derived
from \textit{F.~japonica} presented a reactivity that could be higher
than the alkaline carbonates reactivity~\cite{4}. These encouraging
results led us to revisit this third strategy through the
transesterification of methyl and ethyl esters with glycerol in
caprylic and oleic series (Scheme~\ref{sch1}).

\subsubsection{Optimization of the transesterification conditions of
methyl caprylate \textbf{1} with glycerol}\label{sssec221}

The preparation of glyceryl caprylate \textbf{2} by transesterification
of methyl caprylate \textbf{1} with glycerol was chosen as the first
model reaction. The solvent-free reaction was promoted under microwave
activation. Glycerol plays the role of nucleophile as well as a heating
source absorbing microwaves (Figure~\ref{fig2}). A fine study of the
reaction conditions was carried out with Eco1-E-AR-DO. The influence of
four parameters were investigated on the conversion and the selectivity
of the reaction: temperature, reaction time, catalyst loading and the
quantity of glycerol. The detailed results are summarised in the 
Table~S1 of the ESI. Given the number and range of \mbox{experiments,}
Pearson's correlations were calculated to statistically analyze these
data (Figure~\ref{fig2}a). Correlation values greater than 0.50 and
$p$-values less than 0.05 were considered (in bold in
Figure~\ref{fig2}a). The correlation matrix showing only the
correlation of the four parameters and the two responses of the system
highlights two statistically significant correlations: conversion rate
and selectivity with the catalytic loading and the quantity of
glycerol. Both conversion rate and selectivity were positively
correlated to the catalytic loading. The influence of glycerol was more
complicated: conversion rate was negatively correlated to the quantity
of glycerol while selectivity was positively correlated. The
correlation coefficient of ${-}$0.44 between the conversion rate and the
quantity of glycerol was considered, although it does not meet the
selectivity criteria. The use of ten equivalents of glycerol was thus
chosen, which was a compromise to achieve a sufficient conversion rate
without affecting the selectivity. Experimental conditions that take
into account these initial results have been tested. Indeed, the
transesterification of methyl caprylate~\textbf{1} with glycerol (10
equiv) at 150~\textdegree C for 1~h using \mbox{Eco1-E-AR-DO} (0.5 equiv in
potassium) led to an excellent yield (Figure~\ref{fig2}b). The use of
Eco1-E-FA-JA led to excellent results as well (92\% of conversion and
96\% of selectivity).\looseness=-1

\begin{figure*}
{\vspace*{-1pt}}
\includegraphics{fig02}
{\vspace*{-1pt}}
\caption{\label{fig2}(a) Pearson's correlation matrix of the
experimental variables from 16 experiments for determining the key
parameters of the transesterification of methyl caprylate \textbf{1}
with glycerol using Eco1-E-AR-DO, at a small scale (values in bold
correspond to a $p$-value {${<}$} 0.05); (b) best conditions found at
different scales. $^{*}$methyl caprylate \textbf{1} (1 equiv), glycerol
(10 equiv) and ecocatalyst\protect$^{\text{\textregistered}}$ (0.5
equiv in potassium), $^{\yen}$conversion and selectivity were established
using an HPLC-QDa calibration curve; (c) recycling studies of
Eco1-E-AR-DO at the intermediate scale.}
{\vspace*{-1pt}}
\end{figure*}

The recyclability of Eco1-E-AR-DO was then studied on a larger scale
(8.5~mmol), called the intermediate scale, to allow distillation of the
crude mixture. Distillation of a mixture of glycerol and glyceryl
caprylate \textbf{2} under reduced pressure (145~\textdegree C, 
0.04~mbar) was used to recover the ecocatalyst$^{\text{\textregistered}}$\ as
the distillation residue. Eco1-E-AR-DO was reactivated by thermal
treatment and reused, giving comparable yields during at least 4
reaction cycles (Figure~\ref{fig2}c). \looseness=-1

The MW-transesterification was scaled up on a larger scale (85~mmol),
called the large scale, using a specific set-up. The reaction was
performed with Eco1-E-AR-DO on a pilot MW 1 L reactor equipped with a
distillation apparatus. MeOH was distilled to shift the equilibrium
while the temperature of the reaction mixture was maintained at
160~\textdegree C, with a high absorbance of MW power. Good conversion
(81\%) and selectivity (81\%) could be preserved at such a scale.
%\looseness=-1

\break
Depending on the scale of the reaction, the method used here led to
yields ranging from 66\% to 89\%. In the literature, the
transesterification of methyl caprylate \textbf{1} with glycerol was
described using a Ba--Al oxides catalyst at 140~\textdegree C for 16~h,
leading to a 96\% yield~\cite{40}. This reaction required a long
reaction time and the use of a Ba--Al oxide catalyst, which is
questionable from an environmental point of view~\cite{41}, while our
method relied on a biosourced catalyst and a shorter reaction time
which could be decreased to 1~h or 2~h according to the reaction scale.

Two work-up conditions were studied to separate glycerol and glyceryl
caprylate \textbf{2} (Figure~S3 in ESI). The first one relies on a
conventional treatment by adding water to remove glycerol, followed by
a liquid-liquid extraction of glyceryl caprylate \textbf{2} with
Me-THF. Glyceryl caprylate \textbf{2} (100~g) could be obtained with
high purity (less than 1 wt\% of glycerol) (Table~\ref{tab3}). 

Based on a cloud point experiment, an alternative work-up was
investigated to avoid the use of solvent and prevent waste formation.
Glyceryl caprylate~\textbf{2} was added to a brine solution, and the
mixture was stirred at 60~\textdegree C. Cloud points were determined
visually by noting the formation of two phases: brine water/glycerol
and glyceryl caprylate~\textbf{2}, which were \mbox{easily} separated by hot
decantation. This method led to an excellent separation with only 4
wt\% of glycerol.

\subsubsection{Extension of the method to the transesterification of
methyl oleate \textbf{3} with glycerol}\label{xsssec222}

The best conditions obtained during the synthesis of methyl caprylate
\textbf{1} (150~\textdegree C, 10 equiv glycerol, 0.5~equiv in
potassium, 1~h, microwave activation) were transposed to the
transesterification of methyl oleate~\textbf{3}. However, the
conversion rate collapsed to 5\%, probably due to the lengthening of
the carbon chain. Eco1-E-FA-JA appeared far more efficient to achieve
this reaction with significant conversion (Figure~\ref{fig3}b).

\begin{figure*}
{\vspace*{-2pt}}
\includegraphics{fig03}
{\vspace*{-2pt}}
\caption{\label{fig3}(a) Pearson's correlation matrix of the
experimental variables from 16 experiments for determining the key
parameters of the transesterification of methyl oleate \textbf{3} with
glycerol using Eco1-E-FA-JA (values in bold correspond to a $p$-value
{${<}$} 0.05). (b) Transposed conditions from transesterification of
methyl caprylate \textbf{1} and examples of conditions used for the
Pearson's correlation matrix, $^{*}$methyl oleate \textbf{3} (17~mmol,
1 equiv), glycerol (10 equiv) and
ecocatalyst$^{\text{\textregistered}}$\ (0.5 equiv in potassium), MW
activation, $^{\yen}$conversions and selectivity were established using
an HPLC-ELSD calibration curve.}
\end{figure*}

%tab3
\begin{table*}
\caption{\label{tab3}Industrial specifications~\cite{42} and properties
of glyceryl caprylate \textbf{2} obtained by extraction with
H\tsub{2}O/Me-THF}
\begin{tabular}{ccc}
\thead
& Industrial specifications & Sample properties \\
\endthead
Acid value (mg KOH/g) & {${<}$}2.5 & {${<}$}2.5 \\ 
Peroxide value (m equiv/kg) & {${<}$}1 & 0.6 \\ 
Free glycerol (\%)          & {${<}$}2.5 & {${<}$}1 \\ 
Monoglycerides (\%)         & {${>}$}80 & {${>}$}90 \\ 
Diglycerides (\%)           & {${<}$}20 & {${<}$}10 \\ 
Triglycerides (\%)          & {${<}$}5 & {${<}$}0.1 \\ 
Methanol (ppm)              & - & {${<}$}0.4 
\botline
\end{tabular}
{\vspace*{-14pt}}
\end{table*}

A new set of experiments was then conducted to improve the conversion
rate and the selectivity by studying the reaction time, the temperature
and the catalytic loading (Figure~\ref{fig3}a). Results were again
statistically analyzed by calculating Pearson's correlations, which
showed time and temperature were positively correlated to the
conversion rate (correlation coefficient {${>}$} 0.5 and $p$-value
{${<}$} 0.05). Moreover, the conversion was negatively correlated to the
selectivity. For instance, an increase of the temperature led to a
conversion rate of 88\% but with a selectivity of only 45\%
selectivity, which can be explained by the beginning of glycerol
polymerization.

A design of experiment (DoE) approach was carried out to determine the
optimal settings of the transesterification reaction parameters for the
production of glyceryl monooleate~\textbf{4}~\cite{43}.

The experimental space, shown in Table~\ref{tab5},
was defined by the
upper and lower limits of three parameters: the temperature of the
reaction (160--170~\textdegree C), which was limited to 170~\textdegree
C to avoid the glycerol polymerization side reaction, the reaction time
(40--80~min) and the quantity of Eco1-E-FA-JA  (0.25--0.5~equiv in~K)
(Table~\ref{tab5}). The studied response was the yield in glyceryl
monooleate \textbf{4}. A design matrix was generated using Modde 13.0
software according to full fractional design, resulting in 11
experimental points that included 2\tsup{3} factor points and three
replications at the middle point to evaluate the reproducibility. A
polynomial model (see Figure~\ref{fig4}b for the corresponding
equation) for the glyceryl monooleate~\textbf{4} yield was obtained
with a satisfying $R^{2}$ (0.954) and an acceptable fit between
prediction and experimental data ($Q^{2} = 0.800$).
Figure~\ref{fig4}a highlights that increasing the reaction time and
quantity of Ecocatalyst$^{\text{\textregistered}}$\ significantly
positively impacts glyceryl monooleate \textbf{4} synthesis. The other
studied parameters have no significant impact. As shown by the contour
plots of Figure~\ref{fig4}b, the hotspot is located in the top
right-hand area ({i.e.} Eco1-E-FA-JA at 0.5 equiv in potassium and
170~\textdegree C), these optimum conditions allowing the prediction of
a theoretical yield of 77\%. These optimized experimental parameters
were then tested in triplicate, leading to a repeatable yield of 82\%,
slightly higher than the yield predicted by the DoE model.

\begin{figure*}
{\vspace*{1pt}}
\includegraphics{fig04}
{\vspace*{1pt}}
\caption{\label{fig4}(a) Regression coefficients of the model and (b)
the associated model equation with normalized coefficients; (c)
response contour of yield for the transesterification of methyl oleate
\textbf{3} with glycerol; (d)~theoretical and experimental yields
obtained using optimum conditions determined by DoE. $^{\yen}$Yields in
glyceryl oleate \textbf{4} were established using an HPLC-ELSD
calibration curve.}
{\vspace*{1pt}}
\end{figure*}

This result can be advantageously compared to the literature data
regarding performances and soft reaction conditions (Table~\ref{tab4}).
The same reaction was described either with glycerol or using
isopropylidene glycerol. The use of glycerol relied on chemical
activation by P1 phosphazene~\cite{44} or Mg oxides~\cite{45} at high
temperature or during long reaction time. Isopropylidene glycerol was
used in enzymatic catalysis in a hazardous solvent (hexane) and
required a strong acid-catalyzed deprotection step~\cite{46}. The
solvent-free way of synthesis presented here, which needs low reaction
times and the use of an eco-friendly catalyst, is particularly
attractive from a sustainable point of view. 

\begin{figure*}
{\vspace*{2pt}}
\includegraphics{fig05}
{\vspace*{2pt}}
\caption{\label{fig5}(a) Pearson's correlation matrix of the
experimental variables from 12 experiments for determining the key
parameters of the transesterification of ethyl caprylate \textbf{5}
with glycerol (values in bold correspond to a $p$-value {${<}$} 0.05);
(b) examples of conditions used for Pearson's correlations. $^{*}$Ethyl
caprylate \textbf{5} (17~mmol, 1 equiv), glycerol (10 equiv) and
ecocatalyst$^{\text{\textregistered}}$, under MW activation,
$^{\yen}$conversions and selectivity were established using HPLC-ELSD and
HPLC-PDA ($\lambda = 211.3$ nm) calibration curves.}
{\vspace*{2pt}}
\end{figure*}

%tab4
\begin{table*}
\caption{\label{tab4}Comparison of processes from literature and using
ecocatalysis
\vspace*{4pt}\tpar{\protect\inlinefig{fx08}}\vspace*{-6pt}}
\tabcolsep=4pt
\begin{tabular}{ccccc}
\thead
\raisebox{-.5pc}{\inlinefig{fx09}}\raisebox{-.8pc}{} & Reactant & Conditions & Yield in 4 & Ref. \\ 
\endthead 
Glycerol & Ecocatalyst$^{\text{\textregistered}}$ &
\parbox[t]{9pc}{\centering 170~\textdegree C (MW), 1.3~h without
solvent} & \mn82\% & Present work\vspace*{2pt} \\
Glycerol & Phosphazene P1 & rt, 16~h in DMSO & \mn87\% & \cite{44} \\
Glycerol & Mg salts & 220~\textdegree C, 5~h & {${>}$}60\% & \cite{45} \\
\morerows{1}{Isopropylidene glycerol} & \morerows{1}{Lipase EC 3.1.1.3} & 
(1)~65~\textdegree C, 48~h in hexane & 
\morerows{1}{\mn88\%} & \morerows{1}{\cite{46}} \\
&&(2)~HCl (50\% v/v) & &
\botline 
\end{tabular} 
{\vspace*{2pt}}
\end{table*}

%tab5
\begin{table}[b]
\caption{\label{tab5}Factors and their values used for the experimental
design.}
{\vspace*{-2pt}}
\begin{tabular}{ccc}
\thead
\xmorerows{1}{Factors} & \multicolumn{2}{c}{Levels} \\ \cline{2-3}
& ${-}$1 & ${+}$1 \\
\endthead
Temperature & 160~\textdegree C & 170~\textdegree C \\
Time & 40~min & 80~min \\
Eco1-E-FA-JA (equiv K) & 0.25 & 0.5
\botline
\end{tabular}
{\vspace*{-2pt}}
\end{table}

\subsubsection{Transesterification of ethyl caprylate \textbf{5} by
glycerol}\label{sssec223}

The transesterification of ethyl caprylate \textbf{5} by glycerol
presents a specific interest in producing 100\% biosourced monoglyceryl
esters. Indeed, ethyl caprylate \textbf{5} is derived from the
transesterification of triglyceride by ethanol rather than by methanol,
which is petroleum-based and neurotoxic. However, ethyl caprylate
\textbf{5} is less reactive than methyl caprylate \textbf{1}. The
transesterification of ethyl caprylate \textbf{5} by glycerol therefore
required a specific study. The strategy previously used for methyl
caprylate \textbf{1} and oleate \textbf{3} was transposed identically.
First, the influence of the reaction time, temperature and catalyst
loading on the conversion rate and the selectivity was investigated
using Pearson's correlations (Figure~\ref{fig5}a). The correlation
matrix highlights that selectivity shows negative correlations with the
reaction time and the catalytic loading, suggesting that decreasing the
quantity of ecocatalyst$^{\text{\textregistered}}$\ increases the
selectivity (Figure~\ref{fig5}b). The reaction time and catalytic
loading are positively correlated with the conversion rate and
temperature is positively correlated with the selectivity, but their
values of correlation coefficient are not statistically significant
($p$-value {${>}$} 0.05).

The optimal reaction conditions of ethyl caprylate \textbf{5}
transesterification were then determined by DoE with regards to three
key parameters: the temperature of the reaction (150--160~\textdegree
C), the reaction time (15--30~min) and the loading of
ecocatalyst$^{\text{\textregistered}}$\ Eco1-E-FA-JA (0.025--0.05
equiv). The response was the yield in glyceryl monocaprylate
\textbf{2}. The same simple systematic design (full factorial design
with 11 experimental points) was used to estimate the main effects and
potential interactions. The coefficient values of the polynomial
response model ($R^{2} = 0.905$ and $Q^{2} = 0.677$) are all
significantly positive, except for the interaction between temperature
and \mbox{reaction} time, meaning that an increase in the temperature, time
and catalyst tends to increase the yield in glyceryl monocaprylate
\textbf{2} (Figure~\ref{fig6}a and~b). Figure~\ref{fig6}c
shows that the hotspot---again located at the top right-hand zone
({i.e.} Eco1-E-FA-JA at 0.05 equiv in potassium and 160~\textdegree
C)---indicates that these optimum conditions predict a theoretical
yield of~70\%.

\begin{figure*}
\includegraphics{fig06}
\caption{\label{fig6}(a) Regression coefficients of the model and the
associated model equation with normalized coefficients; (b) response
contour of yield for the transesterification of ethyl caprylate
\textbf{5} with glycerol ${}^{\yen}$isolated yield.}
\end{figure*}

This prediction was confirmed experimentally, with an isolated yield of
67\% of glyceryl monocaprylate \textbf{2}, slightly lower than the
yield predicted by the 2\tsup{3} full factorial design model.

In an attempt to obtain better results, the increase of each parameter
independently was tested. It led to similar results, with no increase
of the yield \mbox{(Table~S9)}. To our knowledge, no similar synthesis were
reported in the literature except in a patent, which claims the
possibility of carrying out the same reaction by enzymatic catalysis,
but without quantitative performance indicators~\cite{47}.

\section{Conclusion}\label{sec3}

In conclusion, we exploited two wetland Invasive Alien Species (IAS),
\textit{Arundo donax} and \textit{Fallopia japonica}, by transforming
these unwanted plant species into valuable resources,
ecocatalysts$^{\text{\textregistered}}$. Their characterization showed
an interesting mineral composition favoring transesterifications in a
basic medium. These ecocatalysts$^{\text{\textregistered}}$\ are
eco-friendly and harmless catalysts, which have proven to be very
effective for the preparation of glyceryl caprylate and oleate. Using
statistical tools such as Pearson's correlations and DoE, good to
excellent selectivities and yields were obtained under microwave
activation, without solvent and with a high degree of naturalness.
Finally, this study encourages the valorization of IAS, which aims to
explore disruptive solutions to support the management of IAS through
their transformation into new useful eco-materials for sustainable
chemistry processes.

\section{Experimental part}\label{sec4}
\subsection{Preparation of ecocatalysts$^{\text{\textregistered}}$}

Aerial parts of \textit{F.~japonica} were harvested in April 2023, in
the wetlands of Clapices, Aulas (South of France) by BIOINSPIR company.
Aerial parts of \textit{A.~donax} were harvested in November 2021, in
Montferrier-sur-Lez (South of France).
Ecocatalysts$^{\text{\textregistered}}$\ were prepared from aerial
parts of the harvested plants, which were first dried in an oven at
30~\textdegree C, ground and then thermally treated in an oven under
airflow. The following temperature program was used: 20~\textdegree
C--350~\textdegree C in 1~h,  350~\textdegree C--550~\textdegree C in
1~h, then 4~h at 550~\textdegree C.\looseness=-1

\subsection{Characterization of
ecocatalysts$^{\text{\textregistered}}$}

Mineral composition of the ecocatalysts$^{\text{\textregistered}}$\ was
determined using an Agilent 4200 Microwave \mbox{Plasma-Atomic} Emission
Spectrometer (MP-AES) coupled with an SPS4 autosampler. The samples
were digested in 6~mL of reversed aqua regia [hydrochloric acid
(37\%)/nitric acid (65\%) $=$\ 1:2] under an Anton Paar Multiwave Go
microwave-assisted digestion, with the following program:
20~\textdegree C--164~\textdegree C in 20~min then 10~min isothermal at
164~\textdegree C. Samples were filtered and then diluted to 0.2
g$\cdot$L$^{-1}$ in nitric acid (1\%). Three blanks were recorded for
each step of the dilute procedure. Three analyses were carried out for
each sample to determine the standard deviation of the measurement.
X-ray diffraction (XRD) analyses were performed on samples dried at
110~\textdegree C for 2~h by using a BRUKER diffractometer (D8 advance,
with a Cu K${\alpha}$ radiation $\lambda = 1.54086$~\AA{}) equipped
with a LynxEye detector.

\subsection{Procedure for the preparation of glyceryl monocaprylate
\textbf{2} from methyl caprylate \textbf{1}}
\subsubsection{Small scale procedure}

Methyl caprylate \textbf{1} (0.85~mmol), glycerol (8.5~mmol) and
Eco1-E-AR-DO (0.425~mmol of potassium) were stirred in a 10~mL
microwave reactor. A microwave oven (CEM Discover 2.0) was programmed
as follows: temperature gradient from rt to 150~\textdegree C in 2~min,
then constant temperature for 1~h. The reaction mixture was filtered
using a sintered glass filter (porosity 4) and washed 3 times with
isopropanol. The reaction was placed in a 100~mL volumetric flask and
analyzed by HPLC-QDa by ion extraction in Single Ion Recording (SIR)\break
mode.

\subsubsection{Intermediate scale procedure}

This procedure allowed the study of the
ecocatalyst$^{\text{\textregistered}}$\ recyclability. Methyl caprylate
\textbf{1} (8.5~mmol), glycerol (85~mmol) and Eco1-E-AR-DO (4.25~mmol
of potassium) were stirred in a 20~mL microwave reactor. A microwave
oven (CEM Discover 2.0) was programmed as follows: temperature gradient
from rt to 150~\textdegree C in 2~min, then constant temperature for 
2~h. The reaction mixture was filtered using a sintered glass filter
(porosity 4), washed with isopropanol and analyzed by HPLC-QDa by ion
extraction in Single Ion Recording (SIR)\break mode. 

\subsubsection{Large scale procedure}

Methyl caprylate \textbf{1} (595~mmol), glycerol (5.95~mol) and
Eco1-E-AR-DO (59.5~mmol of potassium) were stirred in a 1~L flask. A
microwave oven (CEM MARS 6) was programmed as follows: temperature
gradient from rt to 160~\textdegree C in 10~min, then constant
temperature for 1~h. During the reaction, the produced methanol was
distilled at atmospheric pressure. The reaction mixture was filtered
using a sintered glass filter (porosity 4), washed with isopropanol and
analyzed by HPLC-QDa by ion extraction in Single Ion Recording (SIR)
mode. 

\subsection{Procedure for the preparation of glyceryl monooleate
\textbf{4} from methyl oleate \textbf{3}}

{\vspace*{2pt}}

In a typical procedure, methyl oleate \textbf{3} (17~mmol), glycerol
(170~mmol) and Eco1-E-FA-JA (8.5~mmol of potassium) were stirred in a
50~mL flask. A microwave oven (CEM Discover 2.0) was programmed as
follows: temperature gradient from rt to 150~\textdegree C in 5~min,
then constant temperature for 1~h 20. During the reaction, the produced
methanol was distilled under a vacuum (20~mbar). The reaction mixture
was filtered using a sintered glass filter (porosity 4) and washed 3
times with isopropanol. The reaction was placed in a 250~mL volumetric
flask, diluted 8 times and analyzed by HPLC-PDA and HPLC-ELSD.

{\vspace*{2pt}}

\subsection{Statistical studies for the preparation of glyceryl
monooleate \textbf{4} from methyl oleate \textbf{3}}

{\vspace*{2pt}}

\subsubsection{Design of experiments}

{\vspace*{2pt}}

Using the Modde 13.0 software, a DoE was performed using the following
factors to optimize the experimental conditions for the preparation of
glyceryl monooleate \textbf{4} from methyl oleate \textbf{3} using
\mbox{Eco1-E-FA-JA.}

A first-order polynomial equation including correlation terms was used
to find the relationship between the factors and the response surface
(Equation~(\ref{eq1})): 
{\begin{equation}\label{eq1}
Y = \alpha _{0} + \displaystyle \sum _{i} \alpha _{i}X_{i} + 
                  \displaystyle \sum _{i,j}\alpha _{ij}X_{i}X_{j},
\end{equation}}\noindent
where $Y$ is the response (yield), $X_{i}$ are the factors,
$\alpha_{0}$ is the constant term of the equation, $\alpha_{i}$ are
the linear coefficients and $\alpha_{ij}$ are the interaction
coefficients. The factors and their values are reported in Table~\ref{tab6}.

The coefficients were determined using Multiple Linear Regressions
(MLR). The validity of the model was assessed by analysis of the
variance (ANOVA), $R^{2}$, $Q^{2}$ and the lack of fit. A full
2\tsup{3} factorial design, with 3 replicated centered points to
evaluate the reproducibility, was used to fit the model. This design
required 11 experiments. The results are presented in Table~S5 of the
ESI. The order of the experiments was randomized to avoid bias. The
yields were obtained by using a calibration curve in HPLC. To obtain a
good fit between the dataset and the polynomial equation, the
correlation term Temperature $\times$ Catalyst was removed from the
\mbox{initial} \mbox{polynomial} equation. The analysis of variance shows a good
correlation between the obtained yield and the factors. The $p$-value
of the regression model ($p = 0.002<0.05$) shows that the regression is
statistically significant. The lack of fit ($p = 0.571>0.05$) shows
that the model has low replicate errors. The model gives a very good
coefficient of determination ($R^{2} = 0.954$) and a good
cross-validation coefficient\break ($Q_{2} = 0.800$).

%tab6
\begin{table}
\caption{\label{tab6}Factors and their values used for the experimental
design}
\begin{tabular}{ccc}
\thead
\xmorerows{1}{Factors} & \multicolumn{2}{c}{Levels} \\ \cline{2-3}
& ${-}$1 & ${+}$1 \\
\endthead
Temperature & 150~\textdegree C & 160~\textdegree C \\
Time & 15~min & 30~min \\
Eco1-E-FA-JA (equiv K) & 0.025 & 0.05
\botline
\end{tabular}
\end{table}

\subsection{Procedure for the preparation of glyceryl monocaprylate
\textbf{2} from ethyl caprylate \textbf{5}}

In a typical procedure, ethyl caprylate \textbf{5} (17~mmol), glycerol
(170~mmol) and Eco1-E-FA-JA (0.85~mmol of K) were stirred in a 50~mL
flask. A microwave oven (CEM Discover 2.0) was programmed as follows:
temperature gradient from room temperature to 160~\textdegree C in
5~min, then constant temperature for 30~min. During the reaction, the
methanol produced was distilled under vacuum (220 mbar). The reaction
mixture was filtered using a sintered glass filter (porosity 4) and
washed 3 times with isopropanol. The reaction was placed in a 250~mL
volumetric flask, diluted 8 times with isopropanol and analyzed by
HPLC-PDA and HPLC-ELSD.

\subsection{Statistical studies for the preparation of glyceryl
monocaprylate \textbf{2} from ethyl caprylate \textbf{5}}
\subsubsection{Design of experiments}

A DoE was performed using the following factors to optimize the
experimental conditions for the preparation of glyceryl monocaprylate
\textbf{2} from ethyl caprylate \textbf{5} using Eco1-E-FA-JA.

As in the previous DoE, a first-order polynomial equation including
correlation terms was used to find the relationship between the factors
and the response surface (Equation~(\ref{eq2})): 
{\begin{equation}\label{eq2}
Y = \alpha _{0} + \displaystyle \sum _{i} \alpha _{i}X_{i} + 
                  \displaystyle \sum _{i,j} \alpha _{ij}X_{i}X_{j},
\end{equation}}\noindent
where $Y$ is the response (yield), $X_{i}$ are the factors, 
$\alpha_{0}$ is the constant term of the equation, $\alpha_{i}$ are the
linear coefficients and $\alpha_{ij}$ are the interaction coefficients.

The coefficients were determined using Multiple Linear Regressions
(MLR). The validity of the model was assessed by analysis of the
variance (ANOVA), $R^{2}$, $Q^{2}$ and the lack of fit. A full
2\tsup{3} factorial design, with 3 replicated centered points to
evaluate the reproducibility, was used to fit the model. Such a design
required 11 experiments. The results are reported in Table S5 of the
ESI. The correlation terms Temperature $\times$ Catalyst and Time
$\times$ Catalyst were removed from the initial polynomial equation to
obtain a good fit between the dataset and the polynomial equation. The
analysis of variance shows a good correlation between the obtained
yield and the factors. The $p$-value of the regression model ($p =
0.003 < 0.05$) and the lack of fit ($p = 0.124 > 0.05$) confirm the
statistical significance. Moreover, the model gives a good coefficient
of determination ($R_{2} = 0.905$) and an acceptable cross-validation
coefficient ($Q_{2} = 0.677$).

\section*{Declaration of interests}

The authors do not work for, advise, own shares in, or receive funds
from any organization that could benefit from this article, and have
declared no affiliations other than their research organizations.

\section*{Acknowledgements}

The authors thank the French National Centre for Scientific Research
(CNRS) for financial support (International program between CNRS and
University of Arizona). The authors also thank Professor Laurent Debelle
for the fruitful discussions concerning the statistical tests carried
out in this work.

\back{}

\section*{Supplementary data}

Supporting information for this article is available on the journal's
website under \printDOI\ or from the author.

\CDRsupplementaryTwotypes{supplementary-material}{\cdrattach{crchim-273-suppl.pdf}}

\bibliographystyle{crchim}
\bibliography{crchim20230961}
\refinput{crchim20230961-reference.tex}

\end{document}
