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\DOI{10.5802/crchim.293}
\datereceived{2023-09-30}
\daterevised{2023-12-20}
\dateaccepted{2024-01-24}
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\dateposted{2024-03-13}
\begin{document}

\begin{noXML}

%\makeatletter
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%\def\cdr@specialtitle@english{GDR Prom\'eth\'ee}
%%\def\cdr@specialtitle@french{GDR Prom\'eth\'ee}
%\makeatother

\CDRsetmeta{articletype}{review}

\title{Solvent extraction of uranium from an acidic medium for the
front-end of nuclear fuel cycle: from~mechanisms understanding to
innovative process design}

\alttitle{Extraction de l'uranium en milieu acide pour l'amont du cycle
du combustible nucl\'eaire : de la compr\'ehension des m\'ecanismes \`a la
conception de proc\'ed\'es innovants}

\author{\firstname{Fabrice} \lastname{Giusti}\CDRorcid{0000-0001-6416-2736}\IsCorresp}
\address{ICSM, Univ Montpellier, CEA, CNRS, ENSCM, Marcoule, France}
\email[F. Giusti]{fabrice.giusti@cea.fr}

\author{\firstname{Elise} \lastname{Guerinoni}\CDRorcid{0000-0002-5647-3881}}
\addressSameAs{1}{ICSM, Univ Montpellier, CEA, CNRS, ENSCM, Marcoule, France}

\author{\firstname{David} \lastname{Lemire}\CDRorcid{0009-0009-1020-1301}}
\addressSameAs{1}{ICSM, Univ Montpellier, CEA, CNRS, ENSCM, Marcoule, France}

\author{\firstname{Marine} \lastname{Thimot\'{e}e}}
\addressSameAs{1}{ICSM, Univ Montpellier, CEA, CNRS, ENSCM, Marcoule, France}

\author{\firstname{Guilhem} \lastname{Arrachart}\CDRorcid{0000-0002-5277-3967}\IsCorresp}
\addressSameAs{1}{ICSM, Univ Montpellier, CEA, CNRS, ENSCM, Marcoule, France}
\email[G. Arrachart]{guilhem.arrachart@cea.fr}

\author{\firstname{Sandrine} \lastname{Dourdain}\CDRorcid{0000-0003-4828-4092}}
\addressSameAs{1}{ICSM, Univ Montpellier, CEA, CNRS, ENSCM, Marcoule, France}

\author{\firstname{St\'ephane} \lastname{Pellet-Rostaing}\CDRorcid{0000-0003-3399-7153}}
\addressSameAs{1}{ICSM, Univ Montpellier, CEA, CNRS, ENSCM, Marcoule, France}

\shortrunauthors

\begin{abstract}
Despite the fact that methods for uranium extraction from an acidic
medium (sulfuric, phosphoric or nitric) are relatively robust
processes, the search for more efficient systems in terms of extraction
efficiency and selectivity with respect to competitor ions remains
relevant. To address this challenge, researchers have developed a wide
range of new extracting molecular agents that allow efficient and
selective liquid--liquid extraction of the target metal. After
delivering a synoptic reminder of the former hydrometallurgical
processes on which dogmas have been based, we present an exhaustive
report of the structures that have been designed, synthesized and
evaluated as useful hydrometallurgical tools for the extraction of
uranium focused on the front-end of the nuclear fuel cycle.~Moreover,
peculiar emphasis has been given to theoretical aspects related to
parameters, such as amphiphilic properties, which influence the
extraction mechanism involved in each system, be it mono- or
multifunctional ligand. Concluding remarks were afforded as consistent
milestones of a prospective and promising route for the next
hydrometallurgy including the influence of the stereochemistry. 
\end{abstract}

\begin{altabstract}
Bien que les m\'ethodes d'extraction de l'uranium \`a partir d'un milieu
acide (sulfurique, phosphorique ou nitrique) soient des processus
relativement robustes, la recherche de syst\`emes plus efficaces en
termes d'efficacit\'e d'extraction et de s\'electivit\'e par rapport aux ions
concurrents reste d'actualit\'e. Pour relever ce d\'efi, les chercheurs ont
d\'evelopp\'e une large gamme de nouveaux agents mol\'eculaires d'extraction
qui permettent une extraction liquide--liquide efficace et s\'elective du
m\'etal cible. Apr\`es un rappel synoptique des anciens proc\'ed\'es
hydrom\'etallurgiques sur lesquels les dogmes ont \'et\'e fond\'es, nous
pr\'esentons un rapport exhaustif des structures qui ont \'et\'e con\c{c}ues,
synth\'etis\'ees et \'evalu\'ees en tant qu'outils hydrom\'etallurgiques utiles
pour l'extraction de l'uranium ax\'ee sur l'amont du cycle du combustible
nucl\'eaire. En outre, une attention particuli\`ere a \'et\'e accord\'ee aux
aspects th\'eoriques li\'es aux param\`etres, tels que les propri\'et\'es
amphiphiles, qui influencent le m\'ecanisme d'extraction impliqu\'e dans
chaque syst\`eme, qu'il s'agisse d'un ligand monofonctionnel ou
multifonctionnel. Les remarques concluant cette revue ont \'et\'e
pr\'esent\'ees comme des jalons coh\'erents d'une voie prospective et
prometteuse pour l'hydrom\'etallurgie du futur, prenant en compte
l'influence de la st\'er\'eochimie des ligands.
\end{altabstract}

\keywords{\kwd{Uranium}
\kwd{Nuclear fuel cycle}
\kwd{Solvent extraction}
\kwd{Extractants synthesis}
\kwd{Chiral ligand}
\kwd{Mechanism}}

\altkeywords{\kwd{Uranium}
\kwd{Amont du nucl\'eaire}
\kwd{Extraction liquide--liquide}
\kwd{Synth\`ese d'extractants}
\kwd{Ligand chiral}
\kwd{M\'ecanisme}}

\maketitle

{\vspace*{1pc}}

\twocolumngrid

\end{noXML}

\section{Introduction}\label{sec1}

The nuclear fuel cycle includes the front-end steps (mining and
milling, conversion, enrichment, and fuel fabrication) that prepare
uranium for use in nuclear reactors and the back-end steps that manage
spent nuclear fuel (reprocessing and reuse and disposal). Uranium is,
in fact, the most widely used raw material as UOX fuel in nuclear
fission power plants, sometimes with Plutonium (MOX fuel). Uranium is
relatively abundant in the earth's crust and can be found in various
geological deposits (proterosoic unconformity, sandstones,
metasomatite, granite-related, carbonates, etc.)~\cite{1}, rivers
and seawater. It can be extracted in a variety of forms and
environments, ranging from very low grade to very high grade ores, as
well as from mines with a different primary product such as copper or
gold. \mbox{Uranium} resources are divided into conventional and
unconventional resources. Conventional resources are defined as
resources (pitchblende, uranite) from which uranium is recoverable as a
primary product, co-product or significant by-product. Unconventional
resources are those from which uranium can only be recovered as a minor
by-product. This is particularly the case for low-grade deposits such
as phosphate rock or phosphorite, which is mined primarily to produce
phosphorus pentoxide for fertilizer production, as well as non-ferrous
ores, carbonatite, black shale, rare earth elements (REE) deposits,
lignite, and even very low levels of uranium, such as in\break seawater.

Historically, uranium has been produced primarily by open pit and
underground mining techniques and then processed by conventional
uranium milling, leaching and separation from the leach solutions by
solvent extraction or ion exchange. Uranium can thus be recovered from
the ore using dynamic or heap leaching processes, in which the
preliminary crushed ore is either mixed with oxidizing acid or base
solutions in a tank, or placed on an engineered barrier sprayed with
acid or base. Other mining methods include in situ leaching (ISL),
which involves the extraction of uranium from the deposit using an acid
or alkaline solution directly injected into the confined underground
zone, followed by chemical treatment to purify it. Sulfuric acid is the
most common acid used in the leaching process because uranium sulfate
salt is readily soluble in the hexavalent state. An oxidizing agent
(sodium chlorate or manganese dioxide) is usually required because most
of ores contain tetravalent uranium, which is poorly soluble in the
acidic leach solutions. The resulting leach solutions consist of
complex acid sulfate solutions containing a wide variety of ions in
addition to uranium, including aluminum, calcium, iron, magnesium,
molybdenum, vanadium, etc., depending on the composition of the ore
being treated. It is therefore necessary to implement a stage for the
separation of the uranium present in a sulfuric acid phase. However,
uranium can also be found in a phosphoric acid phase if it comes from
wet-process phosphoric acid (WPA) or in a nitric acid phase if it comes
from the final purification before conversion and enrichment steps.

As a result, uranium can be present in different acidic environments
(sulfuric, phosphoric or nitric, etc.), which requires different
conditions for its extraction and recovery involving specific
extractants.

Despite the efficiency of the current systems, but due to some
drawbacks, the search for more efficient and selective systems for
uranium extraction and recovery with respect to competing ions is still\break
relevant.

Through this review, we present the research carried out to understand
and capture the mechanisms involved in the classical processes, but
also the search for new systems.

\section{Molecular systems for the extraction of \mbox{uranium} from
conventional ores}\label{sec2}

The marketable uranium product, Yellowcake, can be obtained through
various processes, depending on the origin of the ore from which it is
produced. Uranium ores are categorized into two types: primary or
conventional ores, which are the richest, and secondary ores, from
which uranium is sometimes extracted as a by-product. The primary
source of uranium production is obtained from conventional ores,
achieved through the utilization of sulfuric acid leach liquors. The
ore extracted from mine, whose fragments measure some centimeters or
more in diameter, is crushed and ground to the consistency of fine
sand. Since most of the conventional ores currently processed contain
around 0.02\% to 0.2\% recoverable uranium, it is necessary to process
500 to 5000~kg of ore for each every kilogram of uranium
recovered. Most uranium ore processing plants use wet milling, and the
resulting sludge is directed to a leaching circuit, where sulfuric acid
is added. Acid consumption does not depend on the uranium content of
the ore, but on the constituents of the gangue. Thus total acid
consumption can range from 10 kg H$_{2}$SO$_{4}$
per tonne of ore to over 100 kg/tonne. Leaching times vary from a few
hours to more than 24. For some ores, leaching times can be
considerably reduced by heating the pulp in tanks at temperatures of
between 40~\textdegree C to 60~\textdegree C. However, these processes
require purification of the leach liquor to effectively separate
uranium from competing elements such as iron (Fe), molybdenum (Mo),
zirconium (Zr), and others. Uranium is then selectively extracted from
the leach solutions by solvent extraction or ion exchange. The uranium
industry was the first {hydrometallurgical} industry to make extensive
use of both processes. 
In the \mbox{solvent} extraction process, the active
agent is generally an organic molecule diluted in a petroleum fraction
such as kerosene, which can selectively extract uranium ions by forming
an organic complex that is insoluble in water. The organic phase is
separated from the aqueous phase by continuous mixing and settling
techniques. The uranium is then re-extracted from the organic complex
by contacting it with a solution of inorganic salt, such as sodium
chloride or ammonium sulfate. Thus, the marketable uranium product
Yellowcake is precipitated from the re-extraction solution by adding
ammonia, soda, 
magnesium hydroxide or hydrogen peroxide, and the
resulting solid product is dried and packaged for shipment to a
refining facility.

Since current industrial processes predominantly use solvent extraction
to reach higher level of purification, this liquid--liquid extraction
process consists in contacting the leachate with an immiscible organic
solvent, a diluent loaded in lipophilic ligand. Through various
interactions (ionic, electrostatic, polar) with the metal cation at the
interface, liposoluble metal-ligand complexes are obtained that are
then spontaneously transferred from the aqueous leachate to the organic
phase. Recovery of the pure metal is then achieved during the
back-extraction or stripping step. Depending on the nature of the
metal, its release from the solvent can be induced by contact with an
aqueous phase that may contain either acid-base or water-soluble ligand
before the recovering step by precipitation or electrowinning. The
effectiveness of the stripping process is driven by the concentration
of the stripping reagent (H$^{+}$, HO$^{-}$, etc.) that must be
modulated according to the type (neutral or ionizable) of the
liposoluble\break extractant. 

Industrial uranium extraction began in 1955 with the development of the
DiAlkyl Phosphoric acid EXtraction (DAPEX) process, which utilized
di-2-ethylhexylphosphoric acid (HDEHP) as the extractant. This
pioneering solvent extraction process was developed and marketed for
uranium VI. However, owing to its limited selectivity when it came to
competing metals, especially iron, it has been replaced in 1957 by the
amine extraction (AMEX) process, which used a mixture of secondary
and tertiary amines (in particular Alamine 336, mainly composed of
tertiary amines) or more recently pure trialkylamine such as
trioctylamine~\cite{2}.

\section{Historical of AMEX and DAPEX processes in sulfuric
acid}\label{sec3}


AMEX and DAPEX processes were actually concomitantly developed at the
Oak Ridge National Laboratory (ORNL) during the 50's. First ideas
were about the designs of long alkyl chain polyamines but this concept
was quickly dropped for the benefits of alkylamines and phosphorous
derivatives~\cite{3}, Hence, numerous structures such as linear or
branched di- or trialkylamines, trialkylphosphines oxide, mono-, di- or
triesters of phosphinic, phosphonic or phosphoric acid were considered
for uranium extraction. However, only a few of them exhibited the
required properties allowing efficient large-scale processing, namely
AMEX and DAPEX, discussed below.

\subsection{The DAPEX process}\label{sec31}

The development of the DAPEX process at the ORNL relied on previous
results reported by other laboratories where affinity of
organophosphorus compounds towards uranium was extensively studied.
More specifically, in 1949, it was fortuitously found that the
hydrolysis products (mono- and dibutylphosphate) of the tri-$n$-butyl
phosphate (TBP) showed higher affinity than that of the parent compound
towards uranium in nitric media. Ensuing works allowed to set a first
uranium extraction process based on long-chain monoalkylphosphoric acid
at the pilot plant scale in 1954. A year earlier, dibutylphosphate was
claimed as a potential ligand for uranium extraction from
seawater~\cite{4}.

Consequently, at the ORNL, emphasis was put on the development of a
method involving the use of promising phosphate-based ligands. HDEHP
was quickly identified as a good candidate as it was a cheap
commercially available compound with very low water
solubility~\cite{4}.

Nevertheless, considering that neutral phosphorus derivatives such as
phosphine oxides could provide efficient and applicable extraction
properties, investigations were also carried out with a series of
symmetrical trialkylphosphine oxide (TAPO) in the same
laboratory~\cite{3}.

Extraction properties of HDEHP towards uranium contained in sulfuric
acid leachates were assessed with regards to (i) ions (sulfate, uranium
and other metals) and ligand concentrations, (ii) pH of the leachate,
(iii) nature of the diluent, (iv) temperature, (v) chemical structure
of the phase modifier, (vi) volumetric phase ratio (A:O) of aqueous
phase volume (A) to organic phase volume (O), (vii) required stripping
conditions and (viii) up-scaling feasibility~\cite{4,5}.

HDEHP is an ionizable acidic extractant that allows the transfer of
metal by cationic exchange, that is, ${n}$ protons are released in
aqueous phase by the extractant while ${m}$ metal cations are trapped
in the organic phase. Because this exchange verifies electroneutrality,
${n}$ and ${m}$ are correlated as follows:
{\begin{equation}\label{eq1}
n=k{\cdot}m
\end{equation}}\unskip
where $k$ is the cationic charge of the metal. HDEHP was known to
auto-associate depending on its concentration and the nature of the
diluent. It has been reported to form dimeric species in hexane, in the
0.025--2.1~mol${\cdot}$L$^{-1}$
concentration range and larger species at higher
concentration~\cite{6}. However, before that the properties of
HDEHP could be properly established, this transfer was assumed to obey
the equilibrium described as follow:
{\begin{eqnarray}\label{eq2}
&&{\mathrm{UO}}^{2+}_{2_{(\mathrm{aq})}}+
2\,\text{HOPO}(\mathrm{OR})_{2_{(\mathrm{org})}}\nonumber\\
&&\quad\rightleftharpoons ({\mathrm{UO}}_{2}^{2+})
(\mbox{}^-\mathrm{OPO}
(\mathrm{OR})_{2})_{2_{(\mathrm{org})}}
 +2\mathrm{H}^{+}_{(\mathrm{aq})}
\end{eqnarray}}\unskip

Considering that in the concerned range of concentration, activities
could be approximated by concentrations, the equilibrium constant was:
{\begin{equation}\label{eq3}
K_{\mathrm{ex}}=\frac{\left[({\mathrm{UO}}_{2}^{2+})
(\mbox{}^-\mathrm{OPO}
{(\mathrm{OR})_{2}})_{2_{(\mathrm{org})}}\right]_{\mathrm{eq}}\cdot 
{\left[({\mathrm{H}^{+}})_{(\mathrm{aq})}\right]}_{\mathrm{eq}}^{2}}
{\left[{\mathrm{UO}}^{2+}_{2_{(\mathrm{aq})}}\right]_{\mathrm{eq}}
\cdot {\left[\text{HOPO}(\mathrm{OR})_{2_{(\mathrm{org})}}\right]}_{\mathrm{eq}}^{2}}
\end{equation}}\unskip


Finally, the distribution coefficient of uranium, which is the ratio at
equilibrium of transferred uranium concentration to that of the metal
remaining in aqueous phase, could be expressed as:
{\begin{equation}\label{eq4}
D_{\mathrm{U}}=\frac{\left[\left({\mathrm{UO}}_{2}^{2+}\right)
(\mbox{}^-\mathrm{OPO}
{(\mathrm{OR})_{2}})_{2_{(\mathrm{org})}}\right]_{\mathrm{eq}}}
{\left[{\mathrm{UO}}^{2+}_{2_{(\mathrm{aq})}}\right]_{\mathrm{eq}}}
\end{equation}}\unskip
Experiments performed with various type of diluents (halohydrocarbons,
ethers, plain hydrocarbons, aromatics and fatty alcohols) keeping all
other parameters fixed (see above), showed that the best extraction
(e.g. highest $D_{\mathrm{U}}\sim 135$ at  298~K) was obtained in
kerosene.

Although fatty alcohols were found to drastically impair the extraction
of uranium, it was shown that the organic phase supplemented with v:v
2\% 2-ethylhexan-1-ol as a phase modifier (whose essential role is
discussed in later section) could maintain a good level of uranium
extraction (${D}_{\mathrm{U}} \sim 30$) without being subjected to the third
phase formation (see AMEX process) occurring in pure kerosene during
the stripping step. Thus, while operating with leachates partially
miming (pH ${=}$ 1, sulfate concentration range from 0.2 to
0.5~mol${\cdot}$L$^{-1}$, $4\times 10^{-3}$~mol${\cdot}$L$^{-1}$ 
uranium) those
recovered with ores processing, first optimal system for uranium
extraction could be defined as HDEHP solubilized at
0.1~mol${\cdot}$L$^{-1}$ in 98:2 v:v kerosene:2-ethylhexan-1-ol mixture.
The best uranium extraction performance could be achieved with this
mixture at 1:1 A:O at 298~K in short contact time
(${\sim}$2~min). 

Efficiency and selectivity of the uranium extraction enabled by
numerous other dialkylphosphates were evaluated for this system and
this was an unexpected opportunity to preliminary investigate the
structure-activity relationship (SAR) of the phosphoric diester ligand
(Table~\ref{tab1}).

\begin{table*}
\caption{\label{tab1}$D_{\mathrm{U}}$ obtained for a series of dialkyl phosphoric
esters at two concentrations of sulfate in the aqueous phase with
$[\mathrm{U}^{\mathrm{VI}}] =4\times 10^{-3}~\mathrm{mol}{\cdot}
\mathrm{L}^{-1}$}
\begin{tabular}{cccc}
\thead
\raisebox{.8pc}{}
\parbox[t]{4cm}{\centering Dialkyl phosphoric ester
$\mathrm{O}\leftarrow \mathrm{P}$ (OR)$_2$OH} &
Formula of R & 
\parbox[t]{2.6cm}{\centering $D_{\mathrm{U}}$ \mbox{(0.5~mol${\cdot}$L$^{-1}$\ $\mathrm{SO}_4^{2-}$)}} &  
\parbox[t]{2.6cm}{\centering $D_{\mathrm{U}}$ \mbox{(1.5~mol${\cdot}$L$^{-1}$\ $\mathrm{SO}_4^{2-}$)}}
\vspace*{.2pc}\\
\endthead
\raisebox{1.3pc}{}
\parbox{4cm}{\centering
Dioctyl hydrogen phosphate} & $n$-C$_{8}$H$_{17}$- & 450 & 57 \vspace*{.1pc}\\
\raisebox{2.3pc}{}
\parbox{4cm}{\centering
Bis(3,5,5-trimethylhexyl) hydrogen phosphate} & 
\parbox[c]{4cm}{\centering\inlinefig{fx01}} & 260 & 41\vspace*{.3pc} \\
\raisebox{2.5pc}{}
\parbox{4cm}{\centering
Bis(2-ethylhexyl) hydrogen phosphate (HDEHP)} & 
\parbox[c]{4cm}{\centering\inlinefig{fx02}} & 135 & 20\vspace*{.3pc} \\
\raisebox{2pc}{}
\parbox{4.5cm}{\centering
Bis(2,6-dimethylheptan-4-yl) hydrogen phosphate} & 
\parbox[c]{4.5cm}{\centering\inlinefig{fx03}} & \010 & \02\vspace*{.3pc}
\botline
\end{tabular}
\tabnote{Organic phase
was $0.1~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$ extractant in w:v
98:2~kerosene:ol, contact time was 2~min. with A:O ${=}$ 1:1. Data
extracted from  Blake \etal~\cite{5}.\vspace*{3pt}}
\end{table*}

Actually, ores leach liquors contain, in addition to uranium, many
other elements present in higher or even much higher concentrations
than those of uranium. Therefore, beside the affinity of the ligand
could be lower for those elements than for the uranium, most of them
might represent a cumbersome powerful competitor impairing the
extraction process.

For instance, with tests performed according to the conditions
previously established for U (VI) and with a
10$^{-2}$~mol${\cdot}$L$^{-1}$ single metal-containing solution,
significant extractions were observed for thorium (IV), titanium (IV),
iron (III), molybdenum (VI), Vanadium (IV) and cerium (IV) with $D_{\mathrm{M}}
= 26$ (Th ${=}$ Ti), 16, 6, 1.8, 1.1 (V ${=}$ Ce), respectively. These
results also underlined the benefit brought by the fast U extraction
equilibrium that should allow to circumvent the huge co-extraction of
ferric cations that could take place in real condition at contact time
longer than 2 min ($D_{\mathrm{Fe}} \sim 250$ at $t = 7.5$~h with
HDEHP). However, the iron extraction could be drastically lowered in
the presence of reducing agents that converted ferric ions in ferrous
one.

Stripping could be achieved at high mineral acid concentrations as well
as in basic condition with 10\% sodium carbonate, which was preferred
because of its cheap and fast implementation. Moreover, the uranium
carbonate complex is water-soluble whereas those of competitors mostly
precipitate, allowing thus to remove co-extracted contaminants from the
recovered uranium. Nonetheless, as mentioned above, the main issue was
the formation of the third phase that resulted from insolubility of
HDEHP sodium salt in both phases and that could be addressed by
supplying the kerosene with 2\% 2-ethylhexan-1-ol. Once again, SAR
could be explored for phase modifier and ligand. A significant impact
of both the branching and the length of the alkyl chain was typically
demonstrated but without place for some comprehensive explanations (see\break
Table~\ref{tab2}). 

\begin{table*}
\caption{\label{tab2}Structures of various alcohols tested as phase
modifiers and their respective amount needed in the diluent to prevent
the formation of third phase during the stripping\vspace*{-2pt}}
\begin{tabular}{ccc}
\thead
\raisebox{.8pc}{}
Alcohol & Formula & \parbox[t]{3cm}{\centering w:v\% needed as phase modifier}\vspace*{.2pc} \\
\endthead
\raisebox{1pc}{}
$n$-Octan-1-ol & \parbox[c]{5cm}{\centering\inlinefig{fx04}} & 0.9 \vspace*{.25pc}  \\
\raisebox{2pc}{}
2-Ethylhexanol & \parbox[c]{5cm}{\centering\inlinefig{fx05}} & 1 \vspace*{.25pc}\\
\raisebox{2pc}{}
$n$-Octan-2-ol & \parbox[c]{5cm}{\centering\inlinefig{fx06}} & 1 \vspace*{.25pc}\\
\raisebox{2pc}{}
4-Ethyloctan-1-ol & \parbox[c]{5cm}{\centering\inlinefig{fx07}} & 0.9 \vspace*{.25pc}\\
\raisebox{3pc}{}
\parbox{4cm}{\centering 3-Neopentyl-5,5-dimethyl hexanol} & \parbox[c]{5cm}{\centering\inlinefig{fx08}} & 1.5 \vspace*{.25pc}\\
\raisebox{2.8pc}{}
5-Ethyl-nonan-2-ol & \parbox[c]{5cm}{\centering\inlinefig{fx09}} & 2.5 \vspace*{.25pc}\\
\raisebox{2pc}{}
2,6,8-Trimethylnonan-4-ol & \parbox[c]{5cm}{\centering\inlinefig{fx10}} & 7.5 \vspace*{.25pc}\\
\raisebox{2.8pc}{}
7-Ethyl-2-methylundecan-4-ol & \parbox[c]{5cm}{\centering\inlinefig{fx11}} & 7.5 \vspace*{.25pc}\\
\raisebox{2.8pc}{}
3,9-Diethyl-tridecan-6-ol & \parbox[c]{5cm}{\centering\inlinefig{fx12}} & ${>}$12 \vspace*{.25pc}
\botline
\end{tabular}
\tabnote{Organic phase was
$0.1~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$ HDEHP in kerosene
modified by various w:v percentages of phase modifier. Aqueous phase
was 10\% Na$_{2}$CO$_{3}$
and contact were performed at A:O ${=}$ 1:1. Data extracted from
Blake \etal~\cite{4}.\vspace*{-2pt}}
\end{table*}

In a last stage, synthetic leachate liquors containing U, Fe and Al
were processed on a pilot scale to allow the recovery (after acidic
hydrolysis of carbonate salts and precipitation with ammonia and
finally after calcination) of 98\% U under its 78--84\% pure
U$_{3}$O$_{8}$ form.

Subsequent works focused on the use of neutral organophosphorus
compounds as phase modifiers. At variance with fatty alcohol, few
amount of trialkylphosphates, dialkylphosphonates or TAPO were found to
increase the $D_{\mathrm{U}}$ by several orders of magnitude when
compared to each respective $D_{\mathrm{U}}$ (ranging from 0 to 5.9 for
various TAPO tested at 0.3~mol${\cdot}$L$^{-1}$ in kerosene, for
instance) and to improve the \mbox{selectivity} towards U. TBP, dibutyl
butylphosphonate (DBBP) and tributylphosphine oxide (TBPO) provided the
strongest synergies (see Table~\ref{tab3}).

\begin{table*}
\caption{\label{tab3}Values of $D_{\mathrm{U}}$ obtained with DEHPH at
$0.1~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$ in kerosene modified by few
w:v\% of neutral organophosphorus compounds\vspace*{-2pt}}
\begin{tabular}{cccc}
\thead
\raisebox{.8pc}{}
Phase modifier & Formula & \parbox[t]{3cm}{\centering w:v\% needed as
phase modifier} & Synergic $D_{\mathrm{U}}$\vspace*{2pt} \\
\endthead
\raisebox{1pc}{}
Tri($n$-butyl)phosphite & \textbf{P(OBu)}$_{\mathbf{3}}$ & 7 & \0700 \\
\raisebox{2.3pc}{}
Tri($n$-butyl)phosphate (TBP) & \parbox[c]{5cm}{\centering\inlinefig{fx13}} & 2.2 & \0800 \vspace*{.3pc}\\
\raisebox{2.3pc}{}
Dibutyl butylphosphonate & \parbox[c]{5cm}{\centering\inlinefig{fx14}} & 1.4 & 3000 \vspace*{.3pc}\\
\raisebox{2.3pc}{}
Butyl dibutylphosphinate & \parbox[c]{5cm}{\centering\inlinefig{fx15}} & 0.9 & 2500 \vspace*{.3pc}\\
\raisebox{2.3pc}{}
Tributylphosphine oxide & \parbox[c]{5cm}{\centering\inlinefig{fx16}} & 1.1 & 7000 \vspace*{.3pc}
\botline
\end{tabular}
\tabnote{Aqueous phase was
$0.5~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$ SO$_4^{2-}$, 
0.004~mol${\cdot}$L$^{-1}$ U (VI),
pH ${=}$ 1. Time contact was 10~min with 1:1 O:A at 298~K.
Data extracted from Blake \etal~\cite{5}.\vspace*{-2pt}}
\end{table*}

This synergy was explained by Blake \etal~\cite{7} after
considering the revisited mechanism of U extraction mediated by HDEHP
where the ligand forms dimers in the organic diluent. At low levels
(maximum organic uranium concentration four times lower than that of
HDEHP)~\cite{6} of extraction the associated equilibrium became:
{\begin{eqnarray}\label{eq5}
&&\hspace*{-7pt}{\mathrm{UO}}^{2+}_{2_{(\mathrm{aq})}}+2\,{\left[\text{HOPO}
(\mathrm{OR})_{2}\right]_{2}}_{(\mathrm{org})} \rightleftharpoons  \nonumber\\
&&\hspace*{-7pt} 
({\mathrm{UO}}_{2}^{2+})
(\mbox{}^-\mathrm{OPO}
{(\mathrm{OR})_{2}},
{\text{HOPO}(\mathrm{OR})_{2}})_{2_{(\mathrm{org})}}+2{\mathrm{H}^{+}}_{(\mathrm{aq})}
\quad
\end{eqnarray}}\unskip

And at a high level of extraction, (minimum organic uranium
concentration more than four times higher than that of HDEHP)~\cite{6}
polymers responding to formula as
(UO$_{2}$)$_{n}$(R$_{2}$PO$_{4}$)$_{2n+2}$H$_{2}$ were formed in the
organic phase. In the presence of a neutral extractant like TAPO, this
did not happen as the neutral extractant played its role of
solubilizing agent to lead to
(UO$_{2}$(R$_{2}$PO$_{4}$)$_{4}$H$_{2}$)(R$_{3}$PO).

Indeed, neutral extractants do proceed via solvation of ionic species
and absolutely not by ionic \mbox{exchange.} In this case, the metal is
transferred to the organic phase with its counterions, water and acids.
The equilibrium of this transfer may be described\break  as:
{\fontsize{9.4}{12}\selectfont
\begin{eqnarray}\label{eq6}
{\mathrm{UO}}^{2+}_{2_{(\mathrm{aq})}}+{\mathrm{SO}}_{4}^{2-}+{n}{\mathrm{R}_{3}}
\mathrm{PO}_{(\mathrm{org})}\rightleftharpoons \mathrm{UO}_{2}
{\mathrm{SO}_{4}}{\left(\mathrm{R}_{3}\mathrm{PO}\right)_{{n}}}_{(\mathrm{org})}
\quad
\end{eqnarray}}\unskip
This points out the complexity of the involved synergy mechanism.

Although the processing of sulfuric leach liquors by DAPEX was formerly
applied at large scale and \mbox{remains} nowadays topic for
studies~\cite{8,9,10}, it has been progressively abandoned for the more
selective AMEX process~\cite{10}. 

\subsection{The AMEX process}\label{sec32}

As mentioned above, the development of the AMEX process took place in
the early 50's at the ORNL to be set at large scale at the end of the
same decade~\cite{2}. Conditions were optimized according to similar
approach as that followed for the DAPEX development. Tests were
performed on several hundred of various primary, secondary, tertiary
amines and tetraalkylammoniums (see some examples in
Figure~\ref{fig1}). The ligands were selected in respect of their
solubility in the organic diluent (before and after contact with acidic
leach liquors), their low ability to form a third phase and their
extraction properties.

\begin{figure*}[p]
\includegraphics{fig01}
\caption{\label{fig1}some structures (and related $D_{\mathrm{U}}$) of amines II
and amines III that were formerly assessed in the AMEX context.
Conditions were $0.1~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$\ $\mathrm{SO}_4^{2-}$,
pH 1, $4\times 10^{-3}~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$  U(VI),
phase ratio 1:1; $0.1~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$  amine in
kerosene. TP stands for third phase formation. \textbf{Amine II}: 
$N$,$N$-di(decyl)amine (\textbf{1}), bis(3,5,6,8-tetramethylnonyl)amine
(\textbf{2}), bis(2-isobutyl-3,5-dimethylhexyl)amine (\textbf{3}), 
$N$-(2-isobutyl-3,5-dimethylhexyl)decan-1-amine (\textbf{4}), 
$N$-(cyclohexylmethyl)-4-ethyl-2-(3-ethylpentyl)octan-1-amine
(\textbf{5}), 
4-ethyl-2-(3-ethylpentyl)-$N$-((2,4,6-trimethylcyclohexyl)methyl)octan-1-amine 
(\textbf{6}), $N$-benzyltetradecan-1-amine (\textbf{7}), 
$N$-(3-phenylpropyl)tetradecan-1-amine (\textbf{8}), 
$N$-benzyl-4-ethyl-2-isopropyloctan-1-amine (\textbf{9}), 
$N$-benzyl-4-ethyl-2-(3-ethylpentyl)octan-1-amine (\textbf{10}),
2-ethyl-$N$-(1-phenylethyl)hexan-1-amine  (\textbf{11}),
$N$-benzyl-2,5,7-trimethylnonan-4-amine (\textbf{12}),
2,5,7-trimethyl-$N$-(1-phenylethyl)nonan-4-amine  (\textbf{13}).
\textbf{Amine III}: trioctylamine (\textbf{14}),
$N$-decyl-$N$-methyldecan-1-amine  (\textbf{15}),
$N$,$N$-dibutyldodecan-1-amine \textbf{(16)},
$N$,$N$-dihexyldodecan-1-amine (\textbf{17}),  tridodecylamine
(\textbf{18}), $N$-dodecyl-$N$-methyldodecan-1-amine (\textbf{19}), 
$N$-benzyl-$N$-dodecyldodecan-1-amine (\textbf{20}),
tris(2-ethylhexyl)amine (\textbf{21}), 
tris(3,5,6,8-tetramethylnonyl)amine (\textbf{22}),
tris(5,5-dimethyl-3-neopentylhexyl)amine  (\textbf{23}). Data extracted
from Coleman \etal~\cite{2}.\looseness=-1}
\end{figure*}

Considering solubility and phase behavior, it was found that, once
protonated, only trialkylamines showed acceptable solubility in the
diluent. More precisely, branched trialkylammoniums were found to be
soluble in kerosene whereas linear one became soluble after supplying
the diluent with 3--5\% \mbox{tridecanol} as a phase modifier. In sulfuric
acid, this protonation could be described as follows:
{\begin{equation}\label{eq7}
{2\mathrm{R}_{3}}\mathrm{N}{:}_{\text{ org}}+\mathrm{H}_{2}\mathrm{S}\mathrm{O}_{4\text{ aq}}
\rightleftharpoons (\mathrm{R}_{3}\mathrm{NH})_{2}\mathrm{S}\mathrm{O}_{4\text{ org}}
\end{equation}}\unskip
With enough acid, a further protonation might occur:
{\begin{equation}\label{eq8}
(\mathrm{R}_{3}\mathrm{NH})_{2}\mathrm{S}\mathrm{O}_{4\text{ org}}+\mathrm{H}_{2}
\mathrm{S}\mathrm{O}_{4\text{ aq}}\rightleftharpoons 2\mathrm{R}_{3}
\mathrm{NH}{\cdot} \mathrm{HS}\mathrm{O}_{4\text{ org}}
\end{equation}}\unskip
Uranium was transferred in the organic phase either by complexation of
a neutral uranylsulfate (Equation~(\ref{eq9})) or by anion exchange 
(Equation~(\ref{eq10})):
{\begin{eqnarray}
&&(\mathrm{R}_{3}\mathrm{NH})_{2}\mathrm{S}\mathrm{O}_{4\text{ org}}+
\mathrm{UO}_{2}\mathrm{S}\mathrm{O}_{4\text{ aq}}\nonumber\\
&&\quad \rightleftharpoons 
(\mathrm{R}_{3}\mathrm{NH})_{2}\mathrm{U}\mathrm{O}_{2}
(\mathrm{S}\mathrm{O}_{4})_{2\text{ org}}\label{eq9} \Seqnsplit
&&(\mathrm{R}_{3}\mathrm{NH})_{2}\mathrm{S}\mathrm{O}_{4\text{ org}}+
\mathrm{UO}_{2}(\mathrm{S}\mathrm{O}_{4})_{2\text{ aq}}^{2-}\nonumber\\
&&\quad \rightleftharpoons (\mathrm{R}_{3}\mathrm{NH})_{2}\mathrm{U}\mathrm{O}_{2}
(\mathrm{S}\mathrm{O}_{4})_{2\text{ org}}+
\mathrm{S}{\mathrm{O}}_{4\text{ aq}}^{2-} \label{eq10}
\end{eqnarray}}\unskip

Efficiency of the extraction was shown to tightly depend on the
concentration of aqueous sulfate (too high sulfate concentration led to
uranium release), cationic competitors (molybdenum, vanadium, iron,
etc.), free amine sulfate, pH of the leachate (too low pH led to
ammonium salt hydrolysis) and the temperature (extraction decreased by
20 to 30\% for 10~\textdegree C temperature rise), while $D_{\mathrm{U}}$ was not
affected by the uranium concentration. Uranium:amine stoichiometry in
the transferred complexes could be determined as 1:6 with linear to
moderately branched secondary amines and as 1:4--5 with symmetrical
trialkylamines (1:4.7 for tri-$n$-octylamine, for instance) or highly
branched secondary amines. A mass law could be applied~\cite{2} showing
that $D_{\mathrm{U}}$ evolved proportionately to the activity of the uncomplexed
amine according to:
{\begin{equation}\label{eq11}
D_{\mathrm{U}}=K_{\mathrm{ex}}\left(a_{{\mathrm{R}_{3}}\text{Norg}}-n\cdot a_{\text{Uorg}}\right)
\end{equation}}\unskip
where ${n}$ varied between 4 and 6 according to the amine. The first
power of this relationship suggested that the activity of the amine
salt was nearly constant regardless of the initial amine concentration.
Assumptions concerning the formation of homogeneous aggregates were
readily discarded after analysis of the organic phase by light
scattering as only partial and heterogeneous aggregation was
evidenced~\cite{2}.

Again, dependence of $D_{\mathrm{U}}$ on the structure of amines, could not be
established with accuracy because the extracting properties were
claimed to be driven by solvent effects subsequently to comparative
studies carried out in kerosene, benzene and chloroform (partially
shown in this paper) that were not fully understood. Indeed, if
extraction was certainly mainly ruled by steric hindrance, basicity and
lipophilicity, the observed effects seemed to result from a complex
combination of these parameters. Moreover, it is interesting to note
that while the authors had tried to characterize the colloidal
properties of the system, they did not report some theories
establishing the link between chemical structure and supramolecular
assembly behavior. However, ignoring the supramolecular phenomena and
considering the $D_{\mathrm{U}}$ values measured in the same solvent, namely
kerosene (Figure~\ref{fig1}), it was obvious that extraction was
enhanced with a longer alkyl chain in the symmetrical linear
trialkylamine series. It became more difficult to give proper
explanations in the case of their dissymmetric isomers. In the branched
trialkylamine series, the presence of an ethyl group on position 2
(tris(2-ethylhexyl)amine \textbf{22}) generated a drastic decrease of
$D_{\mathrm{U}}$ while the highest level of extraction was reached with the
branched trialkylamine \textbf{22} carrying methyl groups on positions
3, 5, 6 and 8. Comparison with the $D_{\mathrm{U}}$ obtained for a trialkylamine
bearing two bulky neopentyl groups on the same position leads to
postulate that steric hindrance affects the process according to the
position and the nature of the branching. ${N}$-benzyl secondary
amine were the best extractants. For instance, the
${N}$-benzyl-4-ethyl-2-(3-ethylpentyl)octan-1-amine (\textbf{10})
showed exceptional efficiency in standard conditions ($D_{\mathrm{U}} = 8000$)
and was still extractant at very low pH ($D_{\mathrm{U}} = 1$ with
[H$_{2}$SO$_{4}$] ${=}$ 3~mol${\cdot}$L$^{-1}$), finally, any attempt
of rationalization based on the theoretical basicity of the tested
amines should be a failure.

Selectivity of extraction could also be tuned according to the amines
structure and the diluent. Some of the more promising and commercially
available secondary and tertiary amines were successfully used in the
AMEX process developed at large scale. For instance 90\% of the uranium
contained in the leach liquor could be extracted in countercurrent
extraction equipment.

Stripping was easily achieved by displacement of uranyl with either
chloride or nitrate ions, or alternatively by simple hydrolysis of the
ammonium salt. The precipitated uranium oxide was recovered as
predominant component presenting a few percent of contamination.

The main co-extracted competitors are molybdene (VI), vanadium (V) and
zirconium. At the time it was already known that vanadium (V) and
molybdene (VI) formed polymeric species incorporated in the organic
phase. This further but not trivial detail is discussed below.

\section{Current issues and progress in the AMEX process} \label{sec4}

Nowadays, the principle of the AMEX process is still the same but the
composition of the system has been lightly revisited as it consists in
a mixture of trialkylamines diluted in kerosene with 3\% tridecanol.
The mixture of trialkylamines, namely Alamine 336, is composed of
trioctylamine (TOA), trinonylamine and tridecylamine.

Despite its widespread application and economic efficiency, the AMEX
process also has drawbacks that warrant consideration: (i) the uranium
separation factor is not optimal when compared to competing elements
like Zr, Fe, Mo, and V, which are co-extracted~\cite{11,12}, (ii) it
requires the use of a volatile phase modifier to prevent the formation
of a third phase (organic phase splitting)~\cite{2}, (iii) the amine
extractants undergo degradation due to a radical reaction catalyzed by
the co-extracted vanadium in the presence of the phase
modifier~\cite{13}, (iv) industrial facilities require significant
quantities of organic diluent, typically kerosene, for solvent
extraction carried out in mixer-settlers. Additionally to the resulting
dysfunction, these issues have a high economical impact and must be
addressed. For instance, the Soma\"{i}r plant in Niger maintains an
inventory of approximately 900~m$^{3}$ of solvent, with 75\%
replacement annually due to issues such as cruds formation, organic
entrainment, and solvent evaporation. Moreover, in the same plant, a
50\% loss of TOA due to chemical decomposition was noted over a year of
activity~\cite{14}. Also, the selectivity with respect to
molybdenum(VI) is not optimal which results in a decrease of the
uranium extraction efficiency and of the loading capacity of the
amine~\cite{15}.

The degradation of tertiary amines by acidic hydrolysis and oxidation
by nitrate~\cite{16} or radical reaction in the presence of
vanadium(V)~\cite{13} is one of the main drawback of such systems. 

The amines degradation phenomenon has been thoroughly studied by 
Chagnes and his co-workers~\cite{13,14,17,18,19}. It results in the
appearance of growing concentration of dialkylamines and in the
decrease of uranium extraction efficiency. First, they tried to provide
a concrete solution with an applicability at large scale and showed by
computer modeling that the flow-sheet of the AMEX process could be
advantageously modified and optimized in order to delay the periodic
replacement of the degraded TOA~\cite{17}. All their subsequent works
allowed to clarify the mechanism of the TOA degradation, which involved
transferred vanadium (V) and/or chromium (VI), the phase modifier
(tridecanol) and the diluent (be it kerosene, TPH or $n$-dodecane). 

Oxidation of vanadium (IV) to vanadium (V) should be the root of the
problem since V$^{\mathrm{IV}}$ is not extracted in sulfuric media
whereas V$^{\mathrm{V}}$ is extracted. Chagnes \etal~properly monitored the
already known conversion (see Coleman \etal~\cite{2}), after
incorporation in 95:5 w:v $n$-dodecane:tridecanol mixture, of monomeric
V$^{\mathrm{V}}$ {to a polymeric species by} $^{51}$V nuclear magnetic
resonance (NMR) and Fourier Transform-Infra Red (FT-IR)
spectroscopies~\cite{14}. The first step is the formation of the
transferable vanadium.sulfate complex
$\mathrm{VO}_{2}\mathrm{SO}_{4}^{-}$ taking place in the aqueous phase.
The sulfate complex is then transferred by anion exchange into the
organic phase where it is not expected to form polynuclear species.
However, the formation of decavanadate
($\mathrm{HV}_{10}\mathrm{O}_{28}^{5-}$) was verified and assumed to
result from the colloidal properties of the organic phase. Actually,
trialkylammoniums form reverse-micelles in oily diluents and can
incorporate further components other than the targeted metal such as
water, salts and acids. Because the intrinsic properties (dielectric
constant, ionic strength, etc.) of the yielded aqueous core might be
significantly different from these of the sulfuric acid leach liquor,
some redox reactions that were forbidden in usual aqueous media were
instead allowed in reverse-assemblies.

\begin{figure*}[t!]
\vspace*{-2pt}
\includegraphics{fig02}
\vspace*{-3pt}
\caption{\label{fig2}(A) Schematic representation of the two mechanisms
of extractant degradation reported to occur in the AMEX process by 
Chagnes \etal~\cite{13,14}. Main degradation by-products are
tetradecanal (\textbf{24}), dioctylammonium  (\textbf{25}),
(E)-$N$,$N$-dioctyloct-1-en-1-aminium (\textbf{26}) and octanal
(\textbf{27}). (B)~Structures of phase  modifier assessed by
Chagnes \etal~\cite{18} with related values of the degradation kinetic
constant  $k$ observed before/after degassing of the organic phase by
nitrogen bubbling. Values are factors of  $10^{-7}$ and $k$ is
expressed in $\mathrm{s}^{-1}$. Tested alcohols were tridecan-1-ol, nonan-2-ol 
(\textbf{28}), 9-methylnonadecan-9-ol (\textbf{29}),
9-hexylnonadecan-9-ol (\textbf{30}),  10-octylicosan-10-ol
(\textbf{31}), 9-octylheptadecan-9-ol (\textbf{32}), 
3-methyl-1-phenylpentan-3-ol (\textbf{33}), 4-nonylphenol
(\textbf{34}), 
1,1,2,2,3,3,4,4,5,5,6,6,7,7,7-pentadecafluoroheptan-1-ol (\textbf{35}),
3,3,4,4,5,5,6,6,7,7,8,8-dodecafluoro-2-methyloctan-2-ol
(\textbf{36}).\vspace*{-3pt}}
\end{figure*}

Mechanism and kinetic of the degradation were investigated by
UV--visible spectroscopy monitoring of the V$^{\mathrm{IV}}$ appearance
in the aqueous phase (absorption of V$^{\mathrm{IV}}$ at
${\lambda}= 760$~nm) and degradation by-products contained in the
organic phase were identified by Gas Chromatography coupled to Mass
Spectrometer (CG--MS)~\cite{13}. Indeed, when the oxidation
occurred, the V$^{\mathrm{IV}}$ yielded after reduction of the
V$^{\mathrm{V}}$ was immediately released in the aqueous phase,
signaling the beginning of the phenomenon that was found to evolve
slowly. Its rate depended on the concentration of both V$^{\mathrm{V}}$
{and sulfuric acid in the aqueous phase, and of TOA and solubilized
dioxygen concentrations in the organic phase. Against all expectations,
the kinetic of oxidation depended only poorly on the concentration of
tridecanol whereas this latter was typically involved in the process.
Actually, decavanadate and/or
$\mathrm{V}^{\mathrm{V}}{\cdot}\mathrm{O}_{2}$ complex generated
radical oxidative species that reacted first with tridecanol to yield
tridecanal and then with TOA to produce mainly dioctylamine, octanal
and} $(E)$-$N$,$N$-dioctyloct-1-en-1-amine (Figure~\ref{fig2}A). The
role of phase modifier was more specifically studied in the context of
another works undertaken by the same team~\cite{18}. A series of either
commercially available or synthesized alcohols were tested as phase
modifier regarding the impact on the kinetic of TOA degradation.
Although SAR could not be established with accuracy, it was shown that
the kinetic of degradation became slower even extremely slower in the
presence of a long branched alkyl chain alcohol  (Figure~\ref{fig2}B).


Therefore, to optimize the AMEX process and enhance its efficiency, it
is essential to gain a deeper insight into the mechanisms of this
solvent \mbox{extraction} process and to focus on optimizing the composition
of extractants employed. This process uses extractant mixtures
consisting of a range of secondary and tertiary amines. While numerous
studies have investigated the extraction capabilities of these
secondary and tertiary amines, there has been a conspicuous lack of
research dedicated to comprehending their inherent properties. Notably,
most of these studies has addressed their aggregation characteristics,
which are a consequence of their amphiphilic nature.

\begin{figure*}[t!]
\vspace*{-1pt}
\includegraphics{fig03}
\vspace*{-1pt}
\caption{\label{fig3}(a) Snapshots issued from MD simulations performed
in $n$-dodecane presenting the complex UO$_{2}$(SO$_{4}$)$_{3}$(TOA)$_4$ 
with 3 $\mathrm{SO}_4^{2-}$ in the bidendate coordination. The uranium atom is
colored in green. {(b)} $k$ 3--weighted Fourier transformed
EXAFS spectra of U-SO$_4$-TOA complex. Insert: corresponding $k$
3--weighted EXAFS spectra~\cite{20}. Reproduced from Ref.~\cite{20}
with permission from the Royal Society of Chemistry.
\vspace*{-3pt}}
\end{figure*}


In the context of uranyl extraction in sulfuric acid solutions using
tertiary amine extractants, an in-depth examination of the
microstructure of uranyl complexes was conducted through a combination
of Extended X-ray Absorption Fine Structure (EXAFS) analysis and
Molecular Dynamics (MD) simulations~\cite{20}. The TOA extractant
was used as a reference for tertiary amines. The MD simulations and
classical fitting methods yielded consistent results, revealing an
unprecedented structure in the organic phase: the uranyl complex
consists of three sulfate anions coordinated to the uranyl cation
through U--O bonds in its first coordination shell (Figure~\ref{fig3}a).

Further analysis of the EXAFS spectra demonstrated that uranyl
trisulfate complexes exhibit dynamic behavior, transitioning between a
configuration in which all three sulfate ions are bidentate and another
configuration where two sulfate ions are bidentate, and one is
monodentate. The MD simulations corroborated these findings, providing
evidence that the configuration with three bidentate sulfate anions is
energetically more favorable than the alternative arrangement with two
bidentate and one monodentate sulfate ions (Figure~\ref{fig3}b). Behind
this sulfate coordination aspect, the distribution of exchangeable
hydrogen bonds observed through MD simulations also revealed a
significant interplay between the inner- and outer-sphere environments
of the uranyl complex.


The effect of alkyl chain configuration on the phase stability and the
aggregation properties of tertiary amines has further been
investigated~\cite{21}. The results showed that tertiary amines
with longer or slightly branched alkyl chains exhibit enhanced phase
stability and maintain their effectiveness in extracting uranium
(Figure~\ref{fig4}a). 

Through a combination of techniques such as small-angle scattering to
determine nanostructures in the organic phase and measurements of
oil--water surface tension, it has been revealed that these effects on
extraction and phase stability are linked to the presence of reverse
aggregates characterized by smaller polar core volumes and reduced
co-extraction of water. When the alkyl chains exhibit more pronounced
branching, they prevent the formation of a swollen reverse aggregates,
thereby hindering efficient extraction. This suggests that the
arrangement and packing of the alkyl chains directly influence the
efficiency of the solvent extraction system.\looseness=-1

\begin{figure*}[t!]
{\vspace*{-2pt}}
\includegraphics{fig04}
{\vspace*{-2pt}}
\caption{\label{fig4}(a) Illustration of effect of tertiary amines
alkyl chain length and branching on organic phase organization and
stability~\cite{21}. (b) Main thermodynamic contributions to the
uranium transfer energy plotted as a function of alkyl chains length
and branching~\cite{22}.}
{\vspace*{-2pt}}
\end{figure*}

Taking such a structural approach into account, this study has not only
demonstrated that smaller aggregates effectively prevent the formation
of a third phase but also elucidated how reduced attractive
interactions among these aggregates play a pivotal role in achieving
this outcome. 

An in-depth thermodynamic analysis, based on the ``ienaic'' approach,
also provided a comprehensive rationale for this phenomenon~\cite{22}.
It highlighted the significant impact of the alkyl chains on the
curvature free energy of the aggregates (Figure~\ref{fig4}b). Notably,
this curvature free energy emerges as a primary inhibitory factor
affecting the transfer free energy of uranium, primarily due to the
significant entropic contributions arising from the branching and
packing of the extractants.

It is worth noting that this study was conducted using commercially
available tertiary amines. However, for a more nuanced understanding,
we synthesized a family of branched TOA isomers with different degrees
of branching in terms of length, number, and location. Interesting
complementary conclusions could be established. This work will be
reported elsewhere~\cite{23}.

An eco-friendly solvent extraction process has been innovatively
developed for uranium extraction using diluent-free tri- and
tetraalkylammonium-based extractants. A series of ammonium mixtures
were systematically tested in absence of diluent to evaluate the
influence of ammonium cations and anions on extraction efficiency,
viscosity and phase separation~\cite{24}. 

Tetraalkylammoniums were readily accessible as they were commercially
available as chloride (Cl$^{-}$) or bis(trifluoromethanesulfonyl)imide
($\mathrm{N}(\mathrm{Tf})_{2}^{-}$) salts of ${N}$-methyltrioctylammonium and Aliquat
336 mixture (Figure~\ref{fig5}a). Trialkylammoinium-based ionic liquids
(ILs) required synthesis. They were easily obtained by neutralizing the
TOA diluted in ethanol with stoichiometric ($n = 0.5$ in
Equation~(\ref{eq12})) or half amount ($n = 1$ in 
Equation~(\ref{eq12})) of sulfuric
acid.
{\begin{equation}\label{eq12}
2{n}\mathrm{R}_{3}\mathrm{N}{:}_{\text{ org}}+\mathrm{H}_{2}\mathrm{S}
\mathrm{O}_{4\text{ aq}}\rightleftharpoons \left(\mathrm{R}_{3}
\mathrm{N}{:} \right)_{2{n}}
(\mathrm{H}_{2}\mathrm{S}\mathrm{O}_{4})_{\mathrm{org}}
\end{equation}}\unskip
Extensive evaporation and drying under reduce pressure led to the
expected sulfated IL. The complete protonation of the tertiary amines
could be accurate by $^{1}$H NMR spectroscopy. Metathesis, performed by
contacting an aqueous solution of an anion Y$^{-}$ with IL
Am$^{+}$X$^{-}$, followed by centrifugation and extensive washing
allowed the quantitative displacement of anion X$^{-}$ by anion Y$^{-}$
(Equation~(\ref{eq13})). 
{\begin{eqnarray}\label{eq13}
&&(\mathrm{R}_{3}\mathrm{N}{:})_{2{n}}(\mathrm{H}_{2}\mathrm{S}\mathrm{O}_{4})_{\mathrm{org}}+
2{n}\mathrm{N}(\mathrm{Tf})_{2\text{ aq}}^{-}\nonumber\\
&&\quad \rightleftharpoons 
\left[(\mathrm{R}_{3}\mathrm{NH})(\mathrm{N}(\mathrm{Tf})_{2})\right]_{2n\text{ org}}+
\mathrm{H}_{2-2{n}}\mathrm{S}\mathrm{O}_{4\text{ aq}}
\end{eqnarray}}\unskip

Numerous binary mixtures of each IL were yielded and their properties
were tuned according to the molar ratio of each partner, the nature and
the molar ratio of each counterion ($\mathrm{N}(\mathrm{Tf})_{2}^{-}$,
Cl$^{-}$, $\mathrm{HSO}_{4}^{-}$, $\mathrm{SO}_{4}^{2-}$)
(Figure~\ref{fig5}a). 

\begin{figure*}[t!]
\vspace*{-3pt}
\includegraphics{fig05}
\vspace*{-2pt}
\caption{\label{fig5}(a) Structure of the tested cations and anions.
(b) Distribution ratios of Uranium obtained for mixte ammoniums plotted
as a function of the molar ratio of the sulfate anion. The initial
aqueous solution (pH ${=}$ 1) contains
$0.1~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$ sulfuric acid,
$1~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$ ammonium sulfate, 
$250~\mathrm{mg}{\cdot}\mathrm{L}^{-1}$ U(VI).
It was contacted to the organic phase with an aqueous to organic volume
ratio A:O ${=}$ 2:1~\cite{24}.}
\vspace*{-2pt}
\end{figure*}

These systems have proven to be exceptionally effective and
straightforward to implement, as they employ the same chemical
components as those employed in the AMEX process. As presented in
Figure~\ref{fig5}b, distribution ratios of uranium obtained with some
of these ammoniums salts and mixtures allow either comparable or much
higher extraction than the classical TOA extractant (taken as reference
for the AMEX process). Uranium extraction increases with sulfates
concentrations, which is consistent with the recognized extraction
mechanisms for such systems~\cite{20}. An interesting synergistic
behavior with the molar ratio of one ammonium to another was further
investigated as it could be \mbox{advantageously} \mbox{considered} to adjust
\mbox{physicochemical} properties of the final solvent (as viscosity or
density)~\cite{25}. Furthermore, it has been established that adopting
such alternatives not only serves to avoid the formation of a third
phase and subsequent extractant degradation but also leads to a
remarkable reduction in solvent evaporation losses. To provide a
comprehensive evaluation of their sustainability, a comparative life
cycle assessment (LCA) was carried out between this novel system and
the conventional solvent~\cite{24}. The results indicate that the new
system is 18 times less environmentally impactful. 

Beyond focusing on the improvement of some historical and well
established processes that still need optimization, developing new
methods and/or new tools is certainly the more innovative and
attractive alternative intended by organic chemists. This point is
discussed in the following section.

\section{Development of new ligands working in \mbox{sulfuric}
media}\label{sec5}

The development of new, more efficient extractants than those currently
used in the AMEX and DAPEX processes is an important issue for the
uranium mining industry. Knowing that these processes are based on
trialkylated tertiary amines for AMEX and organophosphorus compounds
(HDEHP and tri-$n$-butylphosphate (TBP)) for DAPEX, various studies have
investigated the possibility of combining amine or amido to
organophosphorus functional group to offer bifunctional extractants.
These molecules are designed to have at least two distinct functional
groups that enable them to selectively bind and extract uranium from a
complex mixture in order to improve the efficiency and selectivity.

Organophosphorus compounds are very widely used in the context of
separation chemistry in hydrometallurgy. The classification of
organophosphorus extractants can vary based on different criteria, such
as their structural features, chemical properties, or extraction
mechanisms~\cite{26}.

The coordination strength of the organophosphorous extractant can be
enhanced with an increase in their basicity. This can be achieved by
varying the oxidation state of phosphorus. Phosphines [R$_{3}$P],
for instance, are generally more basic than phosphine oxides
[R$_{3}$P(O)] due to the presence of an electron pair on the
phosphorus atom in phosphines. The number of O atoms linked to the P
atom plays also a role in the basicity of the phosphine oxides
(R$_{3}$P(O)). Indeed, these compounds with one substituted oxygen atom
are more basic than phosphinates [(R$'$O)P(O)R$_{2}$], phosphonates
[(R$'$O)$_{2}$P(O)R], and finally phosphates [(R$'$O)$_{3}$P(O)].
The nature of the substituents (R) attached to the P atom can
significantly influence the basicity of the compound. By introducing
electron-donating groups or \mbox{electron-withdrawing} groups on the alkyl
groups attached to phosphorus, the overall electronic environment can
be altered and consequently, the basicity of the compound. Bulkier
substituents can decrease the basicity due to steric hindrance effects.
In addition, they are usually categorized into neutral (R$'=$ organic
moiety) and acidic compounds ($\mathrm{R}'=\mathrm{H}$ or
$\mathrm{R}'=\mathrm{H}$ and organic moiety).

Taking into account the versatility of organophospohorous compound,
their combination with amine allowed proposing various
${\upalpha}$-amino-functionalized organophosphorus compounds with a
strong potential for the extraction of lanthanides and actinides
including uranium~\cite{27,28}. 


One of the first systems based on the use of
${\upalpha}$-amino-functionalized organophosphorus extractant described
in the literature was proposed by Jagodi\'{c} and Grdeni\'{c} with the
use of ${N}$-substituted mono-esters of ${\upalpha}$-aminophosphonic
acid (ethyl and octyl mono-esters of $\upalpha$-anilinobenzylphosphonic
acid) (see Table~\ref{tab4} entry \#1) as complexing agents for the
extraction of various metal including uranium from sulfuric acid
solutions~\cite{29}. Interestingly, it turned out that this category of
extractant exhibits a different behaviour depending on the degree of
oxidation of uranium. Uranium (IV) is extracted at lower sulfuric acid
concentration while uranium (VI) is extracted over a wide concentration
range (0.25 to  $4.5~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$
H$_{2}${SO}$_{4}$).

An advantage of ${\upalpha}$-aminophosphonate-, phosphinate-, and
phosphine oxide-based extractants is that they can be easily
synthesized through Kabachnik--Fields, Mannich and Pudovik
pathway~\cite{30,31,32}.

The Kabachnik--Fields reaction is mainly used since it allows obtaining
${\upalpha}$-amino-functionalized organophosphorus derivatives in a
single step by a three-component condensation reaction involving a
carbonyl (aldehyde or ketone), an amine (primary or secondary amine)
and a phosphoryl compound (phosphite, phosphinate, or phosphine
oxide)~\cite{33}. 

\begin{table*}
\caption{\label{tab4}Extractant and related extraction condition for
the extraction of uranium from sulfuric acid solution\vspace*{-3pt}}
\fontsize{9}{11}\selectfont
\begin{tabular}{cccc}
\thead
Entry & Extractant struture & Extraction condition & Reference \\
\endthead
\raisebox{4pc}{}
\#1 & \parbox[c]{7cm}{\centering \inlinefig{fx17}} & \parbox[c]{4cm}{\centering Sn (II), UO$_{2}$ (II), VO (II), Sb(III), Bi(III), Ce(III), Ti(III), Fe(III), Ce(IV), Zr(IV), Sn(IV),\par Th(IV), Ti(IV), U(IV)\par  Neutral and H$_{2}$SO$_{4}$\ ${\geq}$ 1~mol${\cdot}$L$^{-1}$} &  \cite{29}\vspace*{.3pc} \\
\raisebox{4pc}{}
\#2 & \parbox[c]{7cm}{\centering \inlinefig{fx18}} & \parbox[c]{4cm}{\centering U(VI), Fe(III), Mo(VI), Ce(III), La(III), Gd(III), Yb(III), Nd(III), Ti(IV), Zr(IV)\par  H$_{2}$SO$_{4}$ 1~mol${\cdot}$L$^{-1}$ + Li$_{2}$SO$_{4}$ 1~mol${\cdot}$L$^{-1}$} & \cite{34}\vspace*{.5pc} \\
\raisebox{4pc}{}
\#3 & \parbox[c]{7cm}{\centering \inlinefig{fx19}} & \parbox[c]{4cm}{\centering Th(IV), U(VI), RE(III), Fe(III) and Al(III)\par  Leach solution of ion-adsorption rare earth (RE) ores by aluminum sulfate  H$_{2}$SO$_{4}$\ ${\leq}$ 1~mol${\cdot}$L$^{-1}$} & \cite{35} \vspace*{.3pc}\\
\raisebox{3.4pc}{}
\#4 & \parbox[c]{7cm}{\centering \inlinefig{fx20}} & \parbox[c]{4cm}{\centering Separation by precipitation of thorium, uranium, and scandium from RE} & \cite{36} \vspace*{.8pc}\\
\raisebox{3.3pc}{}
\#5 & \parbox[c]{7cm}{\centering \inlinefig{fx21}} & \parbox[c]{4cm}{\centering U(VI)\par Mo(VI), Zr(IV), Ti(IV), La(III), Ce(III) and Fe(III)  0.1~mol${\cdot}$L$^{-1}$ H$_{2}$SO$_{4}$} & \cite{37} \vspace*{.8pc}\\
\raisebox{5pc}{}
\#6 & \parbox[c]{7cm}{\centering \inlinefig{fx22}} & \parbox[c]{4cm}{\centering U(VI)\par   Mo(VI), Zr(IV), Ti(IV), La(III), Ce(III) and Fe(III)  0.1~mol${\cdot}$L$^{-1}$ H$_{2}$SO$_{4}$} & \cite{38}\vspace*{.3pc}
\botline
\end{tabular}
\end{table*}

According to this approach, Leydier \etal~proposed different amino
phosphine oxide type extractants for the extraction and recovery of
uranium from sulfuric acid~\cite{34}, The condensation of an aldehyde,
a dialkylamine, a dialkylphosphite or a dialkylphosphine oxide in the
presence of \textit{para}-toluene sulfonic acid in catalytic quantity
in toluene leads to aminophosphine oxide (Figure~\ref{fig6}). Among all
the extractants synthesized, an interest was demonstrated for the
(1-(bis(2-ethylhexyl)amino)-4,6,6-trimethylheptan-2-yl)dioctylphosphine
oxide ($\mathrm{R}_{1} = \mathrm{R}_{2} =$ Octyl; 
$\mathrm{R}_{3}=2$,4,4,-triMethylPentyl;  $\mathrm{R}_{4}
= 2$-EthylHexyl) (see Table~\ref{tab4} entry \#2). Indeed under the
conditions of the study this extractant shows extraction performance
for uranium much higher with much greater selectivity than HDEHP or TOA
used as a reference system.

\begin{figure*}[t!]
\includegraphics{fig06}
\caption{\label{fig6}Kabachnik--Fields pathway for the synthesis of
aminophosphine oxide extractant studied for the extraction and recovery
of uranium from sulfuric acid~\cite{34}.}
\end{figure*}


More recently, Liao and coworkers showed that neutral aminophosphonate
extractants exhibit high extraction ability towards high-valence metal\break
ions such as U(IV). Indeed, bis(2-ethylhexyl)
(((2-ethylhexyl)amino)methyl)phosphonate also~called Cextrant 230 (see
Table~\ref{tab4} entry \#3) can form a
UO$_{2}${SO}$_{4}{\cdot}2$[Cextrant 230] complex in which phosphoryl
oxygen atom are involved in the coordination of $\mathrm{UO}_{2}^{2+}$
{and the
extraction of U(VI) is an exothermic process~\cite{35}. It has been
shown that the extraction capacity can be influenced with steric
hindrance and that the Cextrant 230, which has a relatively low steric
hindrance, shows a strong affinity for high valence uranium.

Usually the amino phosphorylated-based extractants are functionalized
by long alkyl chains that can increase their lipophilicity in order to
facilitate the separation between the aqueous feed phase and the
organic phase. Recently, Moilanen and coworkers proposed water-soluble
aminobis(phosphonate) ligands (see Table~\ref{tab4} entry} \#4) as
precipitating agents for REEs, Th, and U allowing a selective
separation~\cite{36}.

Beyond organophosphorous extractant compounds, extractants with amino
or amido moieties have been also investigated for the extraction and
recovery of uranium from sulfuric leachates. The carbonyl oxygen atoms
of the amide groups and the nitrogen atom of the amino groups allow to
bind lanthanide and actinide ions. 

Iminodiamides which combine amides and amine functionalities have been
proposed for this purpose (see Table~\ref{tab4} entry \#5)~\cite{37}.
The chelating behaviour of the iminodiamides was evaluated through
complementary analysis (FT-IR, NMR, Mass spectroscopy) and molecular
modelling (DFT calculation) and the extraction performances showed the
potential of this system for the extraction of uranium at low
concentration in sulfuric acid.

In the same way, it could be demonstrated that iminodiamides could be
attached on calixarene \mbox{platform} leading calix[4]azacrowns (see
Table~\ref{tab4} entry \#6)~\cite{38}. Such macrocycle is able to
selectively extract uranium at low sulfuric acid concentration but in a
different way in comparison to the ``free'' iminodiamide. Indeed, the
stoichiometry of complexation is different with the demonstration of
complex 1:1 for the iminodiamide-functionalized calixarene while it was
found to be 2:1 for the iminodiamide. Also, a lower efficiency can be
noticed when the iminodiamide is tethered on calixarene.

\section{Molecular systems for the extraction of \mbox{uranium} from
unconventional ores}\label{6}

Wet process phosphoric acid is a potential source of uranium as
significant concentrations of uranium ranging from 20 to 
200~mg${\cdot}$L$^{-1}$ can be
found in phosphate rock. It represents an alternative resource for
uranium production as large quantities of phosphate rock are processed
annually to produce phosphoric acid~\cite{39,40,41,42,43,44}.

Several hydrometallurgical processes such as
precipitation~\cite{45,46}, membrane separation~\cite{47,48,49}, and
liquid--liquid extraction~\cite{50,51} have been investigated to remove
or recover uranium from the WPA. 

Among these processes, liquid--liquid extraction has emerged as the
benchmark technology for the industrial recovery of uranium from
phosphoric acid~\cite{44}.

Three processes have reached commercial status between the late 1970s
and 2000 with varying degrees of success:

\begin{enumerate}[(i)]
\item The URPHOS process (uranium from industrial phosphoric acid),
developed at the ORNL, using a synergistic combination of HDEHP and
trioctyl phosphine oxide (TOPO) as extractants for the recovery of
uranium(VI) from 4--$6~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$ phosphoric
acid solution~\cite{52}.

\item The OctylPhenyl Acid Phosphate (OPAP) process, also from ORNL but
using a mixture of mono- and dioctylphenylphosphoric acid as the
extractant for the recovery of uranium(IV) from WPA~\cite{53}.

\item The OctylPyroPhosphoric Acid (OPPA) process, developed by Dow for
the recovery of uranium(IV) by using octylpyrophosphoric acid as the
extractant~\cite{53}.
\end{enumerate}

In each of these processes, organophosphorus extractants are used, as
shown in Figure~\ref{fig7}. 

In the case of the URPHOS process, a mixture of a cationic exchanger
HDEHP with a solvating agent TOPO is used in the following proportions
$0.5~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$ {HDEHP +
$0.125~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$ {TOPO in aliphatic diluents.
Indeed, Hurst \etal~\cite{52} have shown that a
synergistic effect is observed for a HDEHP/TOPO ratio of 4/1 with a
significant increase in the uranium extraction compared to extractants
used independently.

\begin{figure*}[t!]
\includegraphics{fig07}
\caption{\label{fig7}Chemical structure of extractant involved in
URPHOS~\cite{52}, OPAP~\cite{53} and OPPA~\cite{54} processes.}
\end{figure*}

A number of studies have been carried out in order to gain a better
understanding of the mechanisms involved in this synergistic
extraction. Among the various mechanisms proposed to predict and gain
insights into synergism in solvent extraction, studies with a molecular
approach were usually proposed, explaining the extraction of species by
the mechanism of addition, substitution, and
solvation~\cite{55,56,57,58,59}. The possibility of pre-organizing a
mixture of extractant molecules has further been explored on the system
HDEHP/TOPO~\cite{60}. This concept encompasses scenarios such as
synergistic aggregation of the extractants, promoting molecular
interactions between extractant molecules and to enhancing the
\mbox{solubilization} into the reverse micelles. To examine this hypothesis,
the aggregates formed by the extractant molecules were characterized
with neutron and X-ray scattering, but also thermodynamically in order
to determine the critical aggregation concentation (CAC) for each ratio
of the mixture (Figure~\ref{fig8}). This unprecedent study revealed
that lower CAC, which can be related to favored micellar energy, is
concomittant with the synergistic extraction of uranium.

\begin{figure*}[t!]
\vspace*{-2pt}
\includegraphics{fig08}
\vspace*{-2pt}
\caption{\label{fig8}(a) SAXS data showing the aggregation of the
extractant molecule. The top inset shows the deduced aggregate
diameter. (b) CAC as a function of TOPO ratio determined from
tensiometry, SAXS and SANS~\cite{60}.}
\end{figure*}

Conducted in the absence of any cations, this innovative study further
demonstrated that there is no discernible preorganization of the
extractants, suggesting that the synergistic aggregation observed in
the presence of cations is a result of the chelation
mechanism~\cite{61}. Finally, the synergistic extraction of
uranium by HDEHP/TOPO was shown to be controlled by an entropic effect
(offering more configurations to extract), by a favored extractant
association (in presence of acid and cations), and by the curvature
energy of the aggregates, this latter depending on both the extractant
alkyl chains geometry (packing parameter) and the diluent penetration
in the apolar shell of the aggregates~\cite{62}. These results
were further confirmed on another extractant mixture thanks to a
complete thermodynamic balance perfomed with the so-called ineaic
approach~\cite{63,64}.

\section{Research on new extractants for uranium extraction from
phosphoric acid medium}\label{sec7}

In spite of the accomplishments in uranium recovery from WPA 
(4--$6~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$ phosphoric acid solution),
the three processes commercialized exhibit significant potential for
enhancement, prompting further research. The primary shortcomings of
these developed methods are classically an inadequate selectivity and
limited capacity.

Efforts have been dedicated to enhancements, particularly through the
exploration of novel extractant systems surpassing the efficiency of
URPHOS. The initial approach involved combining extractants in
different ways: (i) mixing cation exchangers with
TOPO~\cite{59,65,66,67}, (ii) integrating solvating agents with
HDEHP~\cite{68,69,70}, or (iii) new synergy
system \cite{71,72,73,74,75,76}.

However, the use of mixtures is limited by the need to control the
composition during the extraction phase, particularly when recycling
the extraction phase. To overcome this challenge, the search for
multifunctional molecules has become a priority with a particular focus
on autosynergistic molecules.

Such autosynergistic molecules refer to bifunctional extractants that
incorporate both a cationic exchanger and a solvating agent within
their structure.

For this purpose, the combination of phosphine oxide and phosphoric
acid groups has been proposed Figure~\ref{fig9}. 

\begin{figure*}[t!]
\includegraphics{fig09}
\vspace*{-2pt}
\caption{\label{fig9}Bifunctional molecule bearing a phosphine oxide
and phosphoric acid groups~\cite{75,77}.}
\vspace*{-2pt}
\end{figure*}

One of the first examples studied was proposed by Warshawsky}
\etal~using a $O$-methyldihexyl{\hbreak}phosphine oxide}
$O^{\prime}$-hexyl-2-ethyl phosphoric acid however a third-phase
formation occurs during the extraction (Figure~\ref{fig9}a)~\cite{75}.
In a comparable approach, molecules that contain a phosphoric acid
group, similar to HDEHP, and a phosphine oxide group, similar to TOPO,
have been described (Figure~\ref{fig9}b)~\cite{77}.

A number of different extractants were synthesized on the basis of a
reaction scheme (Figure~\ref{fig10}) involving di-$n$-octylphosphine oxide
or di(2-ethylhexyl)phosphine oxide obtained from di-$n$-butylphosphite
using the appropriate (alkyl)magnesium bromide. The introduction of an
alcohol group, which is then substituted in a chloride derivative,
allows an Arbuzov reaction to be carried out with a suitable trialkyl
phosphite (P(OR$'$)$_{3}$). The resulting
(dialkylphosphoryl)-methyl-(dialkylphosphonate) can then be treated to
become monosaponified or alkylated.

\begin{figure*}[t!]
\includegraphics{fig10}
\caption{\label{fig10}General synthesis of bifunctional molecules
bearing a combination of phosphine oxide and phosphoric acid
groups~\cite{77}.} 
\end{figure*}

These ``autosynergistic'' molecules show an increased extraction
efficiency for U(VI) compared to Fe(III) from concentrated phosphoric
acid solutions (5~mol${\cdot}$L$^{-1}$). This efficiency exceeds that
obtained by using two molecules in a synergistic ratio. Furthermore,
the selective extraction of uranium from phosphoric acid proves to be
superior to the HDEHP/TOPO system, even in the presence of numerous
impurities. With such an extractant it is possible to achieve a
distribution ratio for U(VI) that is more than 10 times higher than the
one achieved with the HDEHP/TOPO system. This superiority has been
confirmed by investigations on an authentic industrial phosphoric acid
solution.

The exploration of bifunctional molecules, involving the innovative
combination of a neutral donor and an acidic extractant, that achieve
the selective extraction of uranium from phosphoric acid has been
extended to other molecule families. A novel family of bifunctional
molecules has been successfully synthesized and extensively examined
for their capability to extract U(VI) from phosphoric solutions. This
approach is built upon amidophosphonic acid~\cite{78} and
amino-phosphonate functional groups~\cite{79}.

The reaction scheme depicted in Figure~\ref{fig11} illustrates the
straightforward synthesis of these bifunctional molecules, starting
with the amidation of $N$,$N$-dialkylamine with halogeno-acylchloride
followed by an Arbusov reaction with triethylphosphite to lead to the
${N}$,${N}$-dialkylcarbamoylalkylphosphonate. The complete or partial
hydrolysis of phosphonate respectively performed with
bromotrimethylsilane or sodium hydroxide results in phosphonic acids or
monophosphonate molecules. The possibility of \mbox{introducing} an alkyl
group on the methylenic bridge was also considered before the
hydrolysis step. Many structures have been synthesized according to
this approach and then subjected for the extraction and recovery of
uranium from phosphoric acid.\looseness=1

Taking a structure-activity perspective, a specific ligand named
butyl-1-[$N$,$N$-bis(2-ethylhexyl){\ubreak}carbamoyl]nonyl phosphonic acid
(DEHCNPB) has been subject to in-depth study due to its remarkable
performance in selectively extracting and quantitatively recovering
uranium~\cite{79,80}. These results stand in contrast to those of the
URPHOS reference system. Indeed, the extraction efficiency reaches
levels up to 90 times greater, and the selectivity is amplified by 150
times compared to the synergistic HDEHP/TOPO reference system.
Importantly, this enhanced performance is achieved without any
occurrence of third-phase formation during both the extraction and
back-extraction processes which is totally reached by using ammonium
carbonate.\looseness=1

\begin{figure*}[t!]
\includegraphics{fig11}
\caption{\label{fig11}General synthesis of bifunctional molecules
bearing a combination of amido and phosphoric acid groups and structure
of butyl-1-[$N$,$N$-bis(2-ethylhexyl)carbamoyl]nonyl phosphonic acid
(DEHCNPB)~\cite{78,79}.}
\end{figure*}

Currently, this extractant appears to be most effective for the
selective extraction and recovery of U(VI) from industrial phosphoric
acid solution.

Further advancement includes the design of a comprehensive flow sheet
and the ongoing development of a solvent extraction process using
DEHCNPB as the central molecule~\cite{81}.

As with the URPHOS reference system, mechanistic studies at the
molecular and supramolecular scale were investigated for the
DEHCNPB~\cite{79,80,82}.

Slope methods and electronspray ionization mass spectroscopy (ESI-MS)
analysis revealed the presence of complexes with four
DEHCNPB~\cite{82}. Density functional theory (DFT) coupled to IR
studies showed moreover that DEHCNPB molecules solely interact through
their phosphonate groups by forming hydrogen bond, while the amide
group does not participate to the association. The carbonyl group seems
to participate primarily by forming hydrogen bond in the outer
coordination sphere. Even if such an outer-sphere bond is not as strong
as an uranium-oxygen bond, it was supposed to stabilize the uranyl
complex and to favor the extraction of uranyl species. These effects
combined with the favorable aggregation properties of the system was
associated to the very high extraction efficiency of DEHCNPB toward
U(VI). 


Classical MD coupled with experimental data from Small-Angle Neutron
Scattering (SANS) and Small-Angle X-ray Scattering (SAXS) techniques
were further employed to elucidate the aggregation behavior of the
bifunctional extractant DEHCNPB~\cite{83}.

It showed that in the absence of uranium, the organic phase primarily
consists of dimers and trimers held together by hydrogen bonds formed
through the phosphonate groups, without any water molecules. However,
in the presence of uranium, it is observed that two to three extractant
molecules directly coordinate with the uranyl cation through their
phosphonate groups. Notably, uranyl remains partially hydrated in this
organic solution, with the amide groups of the extractants forming
hydrogen bonds with the water molecules bound to uranyl.

These intricate hydrogen bond networks surrounding the metallic cation
serve to stabilize the complexes and facilitate the extraction process.
These findings underline the significance of considering weak
interactions to understand extraction processes and highlight how
molecular simulations play a pivotal role in providing crucial insights
into the intricate chemistry of organic phases characterized by a
multitude of species.

\section{Molecular systems for the purification of uranium in nitric acid}\label{sec8}

Uranium refining and conversion, which transforms yellow cake into
different types of enriched uranium (uranium dioxide (UO$_{2}$),
natural metallic uranium (U), etc.), is one of the most important steps
in the nuclear fuel cycle, as it enables the purity levels required for
use in nuclear reactors to be achieved. Uranium purification process
consists of three sub-processes: dissolution, solvent extraction,
solvent regeneration. The yellow cake is first dissolved in nitric acid
to produce a feed solution of metal nitrates. Uranium is then
selectively extracted from this acidic feed with TBP diluted in
kerosene or another suitable hydrocarbon mixture. Finally, uranium is
stripped from the TBP extract in low acidified water to produce a
highly purified uranyl nitrate,
UO$_{2}${(NO}$_{3}$)$_{2}$ \cite{84,85}.\looseness=-1

Today, TBP extraction technology and processes are used worldwide for
the purification of uranium from nitric acid feed solution. The success
of TBP solvent extraction over other uranium purification processes is
due to the fact that TBP (i) is highly selective for uranium and
provides excellent decontamination from most impurities, (ii) is
relatively stable to degradation under conditions normally used for
uranium purification, (iii) has physicochemical properties tailored to
the process in terms of density, viscosity, corrosion, etc~\cite{86}.

In addition, TBP is one of the most versatile extractants, used at
various stages of the nuclear fuel cycle, most notably in the Plutonium
Uranium Reduction Extraction (PUREX) process for reprocessing spent
nuclear fuel. In the context of this back-end of the nuclear fuel
cycle, despite the performance of TBP, some drawbacks such as: (i) the
co-extraction of neptunium and technecium, (ii) the difficulty of
performing the back-extraction stage, with a necessary addition of
U(IV) and hydrazine to assure the change in the oxidation state of the
Pu(IV) to Pu(III), and (iii) the significant degradation of the TBP
through \mbox{radiolysis} and the water-solubility of the corresponding
degradation products, led researchers to develop alternative extraction
agents. Then, several research groups have carried out in-depth studies
on uranium extraction with TBP~\cite{87,88,89,90}.

If alternatives to TBP have been proposed in the context of the PUREX
process, some are also proposed for the upstream part of the
cycle \cite{51}. Naturally, several organophosphorus derivatives have
been proposed, such as HDEHP \cite{91,92}, TOPO \cite{93},
OPAP \cite{94}, mono-2-ethylhexyl (2-ethylhexyl)phosphonate
(PC88A) \cite{95}, cyanex compounds \cite{96,97,98}, but it is the
nitrogen-based extractants that have shown the most significant
results. Among them, amides and diamides \cite{99,100} and in particular
monoamides have a high potential \cite{101,102,103,104}. Symmetrical
and non-symmetrical monoamides with linear or branched chains have been
studied. Some of them are grouped in
Table~\ref{tab5} \cite{105,106,107,108,109}. The results of these
studies show that depending on the alkyl group on the monoamides, the
performance and selectivity of uranium extraction with respect to other
cations can be modulated.\looseness=-1


\begin{table*}
\caption{\label{tab5}General formula of $N$,$N$-dialkylamides used for
uranium extraction from nitric acid medium}
\fontsize{9}{12}\selectfont
\begin{tabular}{cccc}
\thead
\raisebox{3pc}{}
Name & \multicolumn{2}{c}{\parbox[c]{7cm}{\centering\inlinefig{fx23}}} & Reference \vspace*{.3pc}\\
\endthead
\raisebox{1.4pc}{}
${N}$,${N}$-di-2-ethylhexylacetamide & $\mathrm{R}_{1} = \mathrm{CH}_{3}$ & \parbox{3cm}{\centering $\mathrm{R}_{2} = \mathrm{R}_{3} = (\mathrm{C}_{4}\mathrm{H}_{9})$(C$_{2}\mathrm{H}_{5}$)CHCH$_{2}$}  & \cite{105} \vspace*{.5pc}\\
${N}$,${N}$-di-2-ethylhexylpropionamide & $\mathrm{R}_{1} = \mathrm{CH}_{3}$CH$_{2}$ & \parbox{3cm}{\centering $\mathrm{R}_{2} = \mathrm{R}_{3} = (\mathrm{C}_{4}\mathrm{H}_{9})$(C$_{2}\mathrm{H}_{5}$)CHCH$_{2}$} & \cite{105} \vspace*{.5pc}\\
\parbox{5cm}{\centering ${N}$,${N}$-di-2-ethylhexylbutyramide  (DEHBA)} & $\mathrm{R}_{1} = \mathrm{CH}_{3}$CH$_{2}$CH$_{2}$ & \parbox{3cm}{\centering $\mathrm{R}_{2} = \mathrm{R}_{3} = (\mathrm{C}_{4}\mathrm{H}_{9})$(C$_{2}\mathrm{H}_{5}$)CHCH$_{2}$} & \cite{105} \vspace*{.5pc}\\
\parbox{5cm}{\centering ${N}$,${N}$-di-2-ethylhexylisobutyramide  (DEHiBA)} & $\mathrm{R}_{1} = (\mathrm{C}\mathrm{H}_{3})_{2}$CH & \parbox{3cm}{\centering $\mathrm{R}_{2} = \mathrm{R}_{3} = (\mathrm{C}_{4}\mathrm{H}_{9})$(C$_{2}\mathrm{H}_{5}$)CHCH$_{2}$} & \cite{105,106,107,108} \vspace*{.5pc}\\
${N}$,${N}$-di-2-ethylhexylpivalamide & $\mathrm{R}_{1} = (\mathrm{C}\mathrm{H}_{3})_{3}$C & \parbox{3cm}{\centering $\mathrm{R}_{2} = \mathrm{R}_{3} = (\mathrm{C}_{4}\mathrm{H}_{9})$(C$_{2}\mathrm{H}_{5}$)CHCH$_{2}$} & \cite{105} \vspace*{.5pc}\\
${N}$,${N}$-dihexyloctanamide & $\mathrm{R}_{1} = \mathrm{C}_{8}\mathrm{H}_{17}$ & \parbox{3cm}{\centering $\mathrm{R}_{2} = \mathrm{R}_{3} = \mathrm{C}_{6}\mathrm{H}_{13}$} & \cite{108} \vspace*{.5pc}\\
\parbox{4cm}{\centering ${N}$-methyl-${N}$-octyl-2-ethylhexanamide} & $\mathrm{R}_{1} = (\mathrm{C}_{4}\mathrm{H}_{9})$(C$_{2}\mathrm{H}_{5}$)CHCH$_{2}$ & \parbox{3cm}{\centering $\mathrm{R}_{2} = \mathrm{C}_{8}\mathrm{H}_{17}$\ $\mathrm{R}_{3} = C\mathrm{H}_{3}$} & \cite{109}\vspace*{2pt}
\botline
\end{tabular}
\vspace*{2pt}
\end{table*}

Another approach is the design of multifunctional molecules; various
multifunctional compounds have shown promising properties
(Table~\ref{tab6}). For example, the combination of sulfur and nitrogen
functions with amidosulfoxide structures~\cite{110} as well as the
combination of phosphorus and nitrogen functions with
iminomethylenediphosphonic acids~\cite{111} or aminophosphonic acid
and aminophosphonate extractant~\cite{112} were suggested for the
extraction and purification of uranium from dilute or concentrated
nitric acid solutions. Recognizing the potential of this approach, the
multifunctional ligands proposed for the extraction of uranium from the
phosphoric medium such as amidophosphonates showed interest for the
purification of uranium from the nitric medium. The importance of the
presence of a biphosphonate moiety rather than a monophosphonate moiety
was demonstrated for high extraction efficiency and selectivity. In
addition, the bifunctional extractant was found to improve the uranium
loading capacity by a factor of about 1.3 compared to TBP and to have a
slightly lower solubility in the aqueous phase. As with TBP, uranium
extraction is favoured in high nitric acid concentrations, suggesting
that back-extraction at low acidity is also possible~\cite{113}. 

\begin{figure*}
\includegraphics{fig12}
\caption{\label{fig12}(a) U/Zr distribution coefficients and
corresponding separation factors for the alkylated and non-alkylated
extractants (Alk and NAlk) diluted at 0.5~mol${\cdot}$L$^{-1}$ in 
dodecane after contact with an aqueous phase: [HNO$_3$] ${=}$ 
4~mol${\cdot}$L$^{-1}$ [U] ${=}$ [Zr] ${=}$ 10~mmol${\cdot}$L$^{-1}$. 
(b)~Schematic illustration of the aggregates formed with Alk and
NAlk extractants according to their polar and apolar part
distribution~\cite{114}.}
\end{figure*}

\begin{table*}
\caption{\label{tab6}General formula of multifunctional molecules used
for uranium extraction from nitric acid medium}
\begin{tabular}{cccc}
\thead
Entry & Extractant struture & Extraction condition & Reference \\
\endthead
\raisebox{2.7pc}{}
\#1 & \parbox[c]{7.5cm}{\centering \inlinefig{fx24}} &  \parbox{4cm}{\centering [extractant] $= 0.5~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$ [U] $= 10^{-10}~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$;   [HNO$_{3}$] $= 0.5\mbox{--}9.5~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$} & \cite{110} \vspace*{.8pc}\\
\raisebox{2pc}{}
\#2 & \parbox[c]{7.5cm}{\centering \inlinefig{fx25}} &  \parbox{4cm}{\centering [extractant] $= 0.03\mbox{--}0.3~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$\par [U] $= 0.015~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$; pH ${=}$ 2} & \cite{111} \vspace*{.8pc}\\
\raisebox{4.8pc}{}
\#3 & \parbox[c]{7.5cm}{\centering \inlinefig{fx26}} &  \parbox{4cm}{\centering [extractant] $= 0.1~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$\ 
$[\mathrm{U}^{\mathrm{VI}}= \mathrm{Fe}^{\mathrm{III}} = 
\mathrm{Mo}^{\mathrm{VI}} = \mathrm{Ce}^{\mathrm{III}} = 
\mathrm{La}^{\mathrm{III}} = \mathrm{Gd}^{\mathrm{III}} = 
\mathrm{Yb}^{\mathrm{III}} = \mathrm{Nd}^{\mathrm{III}} = 
\mathrm{Ti}^{\mathrm{IV}} = \mathrm{Zr}^{\mathrm{IV}} = 
\mathrm{Th}^{\mathrm{IV}}] = 250~\mathrm{mg}{\cdot}\mathrm{L}^{-1}$;\break   [HNO$_{3}$] $=2~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$} & \cite{112} \vspace*{.8pc}\\
\raisebox{3.8pc}{}
\#4 & \parbox[c]{7.5cm}{\centering \inlinefig{fx27}} &
\parbox{4cm}{\centering [extractant]
$=0.2~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$\  $[\mathrm{U}^{\mathrm{VI}}=
\mathrm{Fe}^{\mathrm{III}} = \mathrm{Mo}^{\mathrm{VI}} =
\mathrm{V}^{\mathrm{III}} = \mathrm{Zr}^{\mathrm{IV}} =
\mathrm{Th}^{\mathrm{IV}}] = 1\times
10^{-3}~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$; \par  [HNO$_{3}$] $=
4~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$} & \cite{113}\vspace*{4pt}
\botline
\end{tabular}
\end{table*}


The extraction mechanisms of two bifunctional extractants, differing
only by the grafting of an alkyl chain between their two functions,
were studied at molecular and supramolecular scales to investigate the
origin of their very different separation factors for uranium and
zirconium (Figure~\ref{fig12}a)~\cite{114}. This investigation aimed
to uncover the reasons behind their significantly different separation
factors when it comes to uranium and zirconium. By scrutinizing the
complex structure through spectroscopic analyses, including FTIR,
ESI-MS, and EXAFS, it was established that the alkylation process does
not alter the chelation mechanism for uranium and zirconium. The
stoichiometries of the formed complexes remained identical for both
extractants, resulting in the formation of
UO$_{2}${L$_{2}${(NO}$_{3}$)$_{2}$ complexes and zirconium polynuclear
complexes upon extraction into the organic phase. Consequently, the
investigation shifted its focus to discerning the origins of
selectivity by examining the supramolecular self-assembly behavior of
these two bifunctional molecules.

SAXS and SANS showed that the most significant separation factors
between uranium (U) and zirconium (Zr) are achieved when smaller
aggregates are present (Figure~\ref{fig12}b). Consequently, this study
strongly suggests that the selectivity is governed by the
supramolecular self-assembly of the two extractant molecules. In the
case of the non-alkylated molecule, its larger packing parameter leads
to the formation of larger aggregates, akin to reverse micelles. These
larger aggregates have the ability to extract additional polar species
into their polar core through a solubilization effect, which, in turn,
reduces the separation factor between uranium and zirconium.


Here it has been demonstrated \textit{de novo} that the efficiency and
the selectivity of a liquid--liquid extraction process may rely on a
complex combination of various parameters, among which the colloidal
properties of the extraction system are certainly one of the main
contributors. However, ability to self-assemble is itself driven by a
peculiar combination of the lipophilic-hydrophilic balance of the
ligand, the composition of the aqueous phase, the solvophobic effect
and the geometry of the ligand~\cite{63,115,116,117}. As
the geometry of the ligand is tightly linked to its stereochemistry,
one interesting open insight was to investigate the SAR between
stereochemistry and complexation properties at supramolecular scale.
This aspect is discussed below.

\section{The influence of the ligands stereochemistry on the
liquid--liquid extraction process}\label{sec9}
\vspace*{-3pt}

\subsection{A foreword about significance of the stereoisomerism in the
context of hydrometallurgy}
\vspace*{-3pt}


By observing carefully all the ligands structures presented in previous
sections (see entries 3 and 4 \mbox{Table~\ref{tab4},} for instance) or in the
cited literature, the questioning about how extraction may be affected
by the stereochemistry of the ligand is perfectly understandable.
Indeed, branched alkyl chains and unsymetrically substituted methylene
bridges bring chirality and the possibility for isomery of position.
Therefore, some studies have been carried out to demonstrate the effect
of the diasteroisomerism and/or the regioisomerism on the solvent
exchange process. Nevertheless, as ambitious and challenging as they
were, these studies have only been sparsely reported during the last
four decades.

Pionnering works that concerned the use of two diastereosiomers
(cis-syn-cis- and cis-anti-cis-isomers) of dicyclohexano-18-crown-6
ether \mbox{(Figure~\ref{fig13}A)} in the context of uranium
extraction~\cite{118} and reprocessing~\cite{119}, were achieved during
the 80's and the 90's by different teams. It was found than the
cis-syn-cis-diastereoisomer had typical higher affinity for uranium
than that of its cis-anti-cis-diastereoisomer. This was explained by
the different orientation of the lone pairs of the oxygen atoms in both
isomers as reported by Wang \etal~\cite{118}, and a decade later, Dietz
\etal~\cite{120} considered rather the difference of free energy
reorganization needed for each complexed isomer. A year later, Tsukube
\etal~reported that the selectivity towards Ag (I) of a series of
tridendate pyridine podans (Figure~\ref{fig13}B) could be easily
adjusted by tuning the chirality of these derivatives~\cite{121}. Short
explanations were only given at the molecular scale. Finally, a major
step forward was done with the works of Wilden and We{\ss}ling who showed
that diastereoisomerism of some chiral diglycolamide (DGA) derivatives
(Figure~\ref{fig13}C) could significantly affect the organization of
the ligand and its interaction with other partners than the metal
cation (lanthanide or actinide), on the inner- and the outer-sphere of
coordination~\cite{122,123}.

\begin{figure*}[t!]
\vspace*{3pt}
\includegraphics{fig13}
\vspace*{3pt}
\caption{\label{fig13}(A)~Structure of the cis-syn-cis- (\textbf{37}) and
cis-anti-cis- (\textbf{38}) isomers of dicyclohexano-18-crown-6 ether
and respective uranium extraction equilibrium constant
$K_{\mathrm{ex}}$~\cite{118}. (B)~Structure of two diastereosiomers of a
chiral podand and respective silver extraction equilibrium constant
$K_{\mathrm{ex}}$~\cite{121}. (C)~Structure of some achiral and chiral
DGAs. $N$,$N$,$N'$,$N'$-tetraoctyldiglycolamide (TODGA) \textbf{41} and
$N$,$N$,$N'$,$N'$-tetradecyldiglycolamide (TDDGA) \textbf{42} are
achiral whereas their respective bis-C-methylated derivatives
TODGA-Me$_{2}$ and mTDDGA can be distinguished in cis-(or meso)
(\textbf{43} and \textbf{45}) and (\textbf{44} and \textbf{46})
trans-isomers. Americium coefficient distribution $D_{\mathrm{Am}}$
were obtained with extraction of
$10^{-5}~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$ of Am in
$4.3~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$ HNO$_{3}$ performed at
298~K, with $0.1~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$ ligand
in TPH~\cite{122}. Stability constants $\log {\beta}^{\prime}_{\mathrm{n}}$
for the complexation of Cm (III) was  measured in 2-propanol with 5~vol\%
H$_{2}$O and $10^{-2}~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$
HClO$_4$~\cite{123}. (D)~Structure of various DGAs and associated
samarium to lanthanum factor separation ($\mathrm{SF}_{\mathrm{Sm/Ln}}
=D_{\mathrm{Sm}}/D_{\mathrm{Ln}}$) determined by extraction of
$5\times 10^{-4}~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$  of lanthanides in
$3~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$ HCl with
$0.1~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$ ligand in Isopar L with 30
vol\% Exxal 13 at 298~K~\cite{124}.}
\vspace*{3pt}
\end{figure*}

Beside the influence of the DGAs chirality, the effect induced on the
liquid--liquid extraction (LLE) process by their regioisomerism was also
\mbox{highlighted} by Stamberga \etal~who assessed the intra-lanthanide
selectivity of several DGAs \mbox{derivatives} (Figure~\ref{fig13}D) whose
nitrogen substituents were either linear or branched alkyl
chains~\cite{124}. Although it was not the main goal of these
researches that focused more generally on the effect of chains lenght
and the position of the branching, conclusions about regioisomerism
could be established by comparing the results yielded by some of those
DGAs derivatives that carried regiomers of a same alkyl chains
($n$-octyl, 2-ethylhexyl for instance). Explanations were given at the
scale of the aggregate. Sterical hindrance and the interfacial
properties varying according to the considered compound were claimed as
the main parameters affecting differently the process. In the same way,
the studies undertook with linear and branched trialkylamines by our
team in the AMEX context (see Section~\ref{sec4}) comes to sustain these
conclusions.

To summarize, some ensuing questions would be: if both
diastereoisomerism and regioisomerism affect the process, which one is
predominant? How? Why? What are the challenges afforded by chirality in
the context of the fuel cycle?

\begin{figure*}[t!]
{\vspace*{-2pt}}
\includegraphics{fig14}
{\vspace*{-2pt}}
\caption{\label{fig14}Structure of the stereoisomers of DEHBA (a) and
EHOBA (b)~\cite{125,126}.}
{\vspace*{-2pt}}
\end{figure*}

The answer to the last question seems obvious if one considers that
some current and extensive work aims to replace advantageously the TBP
at the down-stream of the cycle by other ligands with more complex
structures (see Section~\ref{sec8}), thus potentially chiral as it is the
case of the ${N}$,${N}$-di(2-ethylhex-1-yl)butyramide (DEHBA)
(Table~\ref{tab5}) claimed as promising candidate.

Thus, in order to address the aforementioned resulting concerns, a
partnership was established some years ago between the CEA Marcoule
Atalante and the ICSM. Our first results and conclusions are briefly
reported in the following section.


\subsection{Impact of the stereochemistry of the DEHBA on the plutonium
(IV) extraction~\cite{125}}

The aims of this work was to: (i) clarify if the diastereoisomers and
the regioisomers of the DEHBA presented marked differences of
extraction properties towards uranium and plutonium, (ii)
understand and explain the mechanism involved. 

DEHBA is a ternary monoamide carrying two chiral centers and presenting
three stereoisomers, which are the ($R$,$R$)-DEHBA, its enantiomer
($S$,$S$)-DEHBA and the achiral meso ($R$,$S$)- or ($S$,$R$)-DEHBA
(Figure~\ref{fig14}).

This molecule is commonly obtained as an achiral mixture via a
Schotten--Baumann reaction starting from butyryl chloride and
commercially available diastereomeric mixture of
bis(2-ethylhexylamine). The first part of the project consisted of the
development of diastereopure ($S$,$S$)- and ($R$,$S$)-forms of both
the DEHBA and one of its regioisomer, namely the}
$N$-(2-ethylhexyl)-$N$-(octan-3-yl)butyramide,
(EHOBA) \cite{125,127}. The interest in providing EHOBA was to
access to a DEHBA isomer for which one ethyl side chain was closer to
the complexing amide function. Therefore, if there was one, the impact
of chirality was expected to be more pronounced for the EHOBA. The
synthesis of the diastereopure forms of the monoamides consisted to
react \mbox{activated} butyric acid with the diastereopure forms of the
$N$,$N$-dialkylamine. These latter were obtained after a
multi-steps synthesis. The diastereopure bis(2-ethylhexylamine) was
yielded after reaction of the enantiopure 2-ethylhexylamine with
enantiopure 3-(bromomethyl)heptane. Both synthons were derived from one
of the two enantiomers of 2-ethylhexanoic acid resolved by
diastereoselective recrystallization. The diastereopure
$N$-(2-ethylhexyl)octan-3-amine was obtained after reaction of the
enantiopure 2-ethylhexylamine with the racemic 3-bromooctane, followed
by resolution of both yielded diastereoisomers on a chromatography
column (Figure~\ref{fig15}).


\begin{figure*}[t!]
{\vspace*{-3pt}}
\includegraphics{fig15}
{\vspace*{-3pt}}
\caption{\label{fig15}Retrosynthetic scheme of the synthesis of
unresolved and diastereopure DEHBA (A) and EHOBA
(B). Butanoyl-X may be a butanoyl halide or a reactive
ester of butanoic acid. Unresolveld form of EHOBA is obtained from the
diastereoisomers mixture of $N$-(2-ethylhexyl)octan-3-amine, itself
yielded by condensation of racemic 2-ethylhexylamine with racemic
3-bromooctane~\cite{125,126,127,128}.}
\end{figure*}


Each diastereoisomers mixture and the diastereopure form of DEHBA and
EHOBA were evaluated in the context of U and Pu extraction in nitric
media. It was found that the stereochemistry of DEHBA did not affect U
extraction (not shown), whereas it impacted the extraction of Pu
(Figure~\ref{fig16}A). 

 
\begin{figure*}
\includegraphics{fig16}
{\vspace*{-3pt}}
\caption{\label{fig16}(A)~$D_{\mathrm{Pu}}$
obtained after extraction of a Pu solution
($[\mathrm{Pu}^{\mathrm{IV}}]_{\mathrm{aq,ini}}= 2.23\times 10^{-2}~\mathrm{mol}
{\cdot}\mathrm{L}^{-1}$,
$[\mathrm{HNO}_{3}]_{\mathrm{aq,ini}} = 4~\mathrm{mol}{\cdot}\mathrm{L}^{-1}$) by the various achiral mixtures (mix) or
diastereopure monoamides ([Ligand] $= 1.2~\mathrm{mol}{\cdot}\mathrm{L}^{{-1}}$)
in hydrogenated tetrapropylene (TPH) at
298~K with 1:1 A:O. The proportion of each type of complex
(inner- or outer-sphere) involved in the extraction mechanism was
determined UV--vis spectroscopy (not shown). (B)~Density
functional theory (DFT) model of Pu.monoamide inner- (left) and
outer-sphere complex. For simplification, the simulation was achieved
with the $N$,$N$-diethylpropanamide. Pu:ligand:nitrate stoichiometry
was also given for each type of complex~\cite{125}
(source: Figures~4b and~3 from Ref.~\cite{125} under licence CC BY-NC-ND).}
{\vspace*{-3pt}}
\end{figure*}

Effect on Pu extraction was shown to be more significant for the EHOBA
extractant as the branching is closer (${\upalpha}$ position) to the
complexing site. In both cases, this stereochemical effect could be
related to the formation of different inner or outer-sphere complexes
(Figure~\ref{fig16}B), which are demoted or promoted by steric
hindrance.

To summarize, ligands stereochemistry which intervenes at different
level in the solvent exchange process should be one of the major
concerns to be clarified and addressed for a better understanding of
the process. Moreover, once mastered, this key-parameter should allow
to finely adjust the process. This last statement paved the way for
further fundamental studies aiming to verify the impact of the
stereochemistry of branched ligands, be it commonly used at large scale
in hydrometallurgic process (HDEHP for instance) or at lab scale
(monoamides, amino- and amidophosphonates). These works are currently
under development at the ICSM.\looseness=-1
 

\section{Conclusion}\label{sec10}

As the uranium industry has expanded, research efforts have focused on
optimizing techniques, especially leaching and liquid/liquid extraction
in order to improve both the yield and selectivity toward the targeted
uranium as well as the environmental \mbox{footprint.} Future challenges
include recovering uranium from more complex resources, which may often
be of lower grade and at greater depth than the deposits currently
being processed. Thus, research has focused on the improvement of the
recovering of uranium from conventional and unconventional resources,
including sulfuric, phosphoric and nitric acid, as well as low-grade
ores and seawater. The uranium industry aims to develop this wide
variety of mining and processing techniques because uranium ores are
extremely diverse. For that, processing operations must be designed to
take into account the specific composition and mineralogical
\mbox{characteristics} of the ore to be treated. Extraction mechanisms of any
given extraction operation should be investigated to comprehensively
understand and quantify such variability. This understanding is
essential for the selection of a combination of unit operations that
can economically and environmentally accommodate this variability.

With the common goal of improving and understanding uranium extraction
processes, this review aimed to put in regards the various extractant
synthesis strategies and the mechanistic studies of uranium extraction
in sulfuric, phosphoric and nitric media. As evidenced by the
literature, these investigations are fundamental and should encompass a
comprehensive characterization that includes both molecular and
supramolecular descriptions of the organic phase structure. The alkyl
chains of the synthesized and examined extractants, along with those of
the diluent, were for instance modified to investigate their impact on
the organic phase structure, uranium extraction efficiency, and on the
third-phase formation. A study of a system in the absence of diluent
was also described, considering the analogy of such a system to ionic
liquid media. 

Overall, this review shows that synthesizing and studying new
extractants for uranium extraction remains essential for improving the
efficiency, selectivity, and sustainability of nuclear fuel production
while minimizing its environmental impact. These efforts are critical
to the continued growth and advancement of nuclear energy technologies.


\section*{Abbreviations}\label{sec11}

\begin{inftab}
\begin{tabular}{lp{5cm}}
\tbody
AMEX: & amine extraction\\
DAPEX: & dialkylphosphoric acid extraction\\
DBBP: & dibutyl butylphosphonate\\
DEHBA: & ${N}$,${N}$-di(2-ethylhex-1-yl)butyramide\\
DEHCNPB: & butyl-1-[${N}$,${N}$-bis(2-ethylhexyl)carbamoyl]nonyl phosphonic acid\\
DGA: & diglycolamide\\
\inftabbreak
$D_{\mathrm{U}}$: & uranium distribution coefficient\\
EHOBA: & ${N}$-(2-ethylhexyl)-${N}$-(octan-3-yl)butyramide \\
ESI-MS~: & \mbox{electrospray ionization mass} spectroscopy\\
EXAFS: & extended X-ray absorption fine structure analysis\\
FT-IR: &\mbox{Fourier-transform infrared} spectroscopy \\
HDEHP: & di-2-ethylhexylphosphoric acid\\
Ils: & ionic liquids\\
ISL: & in situ leaching\\
$K_{\mathrm{ex}}$: & \mbox{exchange equilibrium} constant\\
LCA: & life cycle assessment\\
LLE: & liquid--liquid extraction\\
MD: & molecular dynamics\\
MS: & mass spectroscopy\\
MOX: & mixture of oxides\\ 
NMR: & \mbox{nuclear magnetic resonance} spectroscopy\\
ORNL: & \mbox{Oak-Ridge National} Laboratory\\
OPAP: & octyl phenyl acid phosphate\\
OPPA: & octyl pyro phosphoric acid\\
PC88A: & mono-2-ethylhexyl \mbox{(2-ethylhexyl)phosphonate}\\
PUREX: & Plutonium Uranium Reduction\break EXtraction\\ 
REE: & rare earth element\\
SAR: & structure-activity relationship\\
SANS: & \mbox{Small-Angle Neutron} Scattering\\ 
SAXS: & Small-Angle X-ray Scattering\\
TAPO: & trialkylphosphine oxide\\
TBP: & tributylphosphate\\
TBPO: & tributylphosphine oxide\\
mTDDGA: & 2,$2'$-oxybis($N$,$N$-didecylpropanamide)\\
TDDGA: & $N$,$N$,$N'$,$N'$-tetradecyldiglycolamide \\
TOA: & trioctylamine\\
TODGA: & $N$,$N$,$N'$,$N'$-tetraoctyldiglycolamide\\
TODGA-Me2: & 2,2$'$-oxybis(${N}$,${N}$-dioctylpropanamide)\\
TOPO: & trioctylphosphine oxide\\
TPH: & hydrogenated tetrapropylene\\
UOX: & uranium oxide\\
URPHOS: & uranium from industrial phosphric acid\\
WPA: & wet-process phosphoric acid
\end{tabular}
\end{inftab}

\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 acknowledge the GDR PROMETHEE, the NEEDS program as well as
the CEA for their support. They also thank Tamir Sukhbaatar, Alexandre
Artese, Zijun Lu, Nicolas Felines, Julien Rey, Moheddine Wehbie, Olivia
Pecheur, Raphael Turgis, Antoine Leydier, Beatrice Baus-Lagarde, Thomas
Dumas, C\'{e}cile Marie, Manuel Miguirditchian, Thomas Zemb,
Jean-Francois Dufr\^{e}che, Magali Duvail for their fruitful
discussions and contributions on the subject of uranium extraction. The
authors are also grateful to the Editors Elsevier, American Chemical
Society, Taylord \& Francis, Royal Society of Chemistry and Wiley for
their applied copyright policy allowing free reproduction and/or
modification of all original figures (sometimes only for authors of the
original articles, please check those publishers' policies).

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