α-Aminophosphonates, Phosphinates, and Phosphine Oxides as Extraction and Precipitation Agents for Rare Earth Metals, Thorium, and Uranium : A Review

This is a self-archived version of an original article. This version may differ from the original in pagination and typographic details. Author(s): Title: Year: Version: Copyright: Rights: Rights url: Please cite the original version: CC BY 4.0 https://creativecommons.org/licenses/by/4.0/ α-Aminophosphonates, Phosphinates, and Phosphine Oxides as Extraction and Precipitation Agents for Rare Earth Metals, Thorium, and Uranium : A Review © 2022 by the authors. Licensee MDPI, Basel, Switzerland. Published version Kukkonen, Esa; Virtanen, Emilia; Moilanen, Jani Kukkonen, E., Virtanen, E., & Moilanen, J. (2022). α-Aminophosphonates, Phosphinates, and Phosphine Oxides as Extraction and Precipitation Agents for Rare Earth Metals, Thorium, and Uranium : A Review. Molecules, 27(11), Article 3465. https://doi.org/10.3390/molecules27113465 2022 Molecules 2022, 27, 3465. https://doi.org/10.3390/molecules27113465 www.mdpi.com/journal/molecules Review α-Aminophosphonates, Phosphinates, and Phosphine Oxides as Extraction and Precipitation Agents for Rare Earth Metals, Thorium, and Uranium: A Review Esa Kukkonen, Emilia Josefiina Virtanen and Jani Olavi Moilanen * Department of Chemistry, Nanoscience Centre, University of Jyväskylä, P.O. Box 35, FI-40014 Jyväskylä, Finland; [email protected] (E.K.); emilia.j.virtane[email protected]i (E.J.V.) * Correspondence: jani.o.moilane[email protected]; Tel.: +358-408-054-849 Abstract: α-Aminophosphonates, -phosphinates, and -phosphine oxides are a group of organophosphorus compounds that were investigated as extraction agents for rare earth (RE) metals and actinoids for the first time in the 1960s. However, more systematic investigations of their extraction properties towards REs and actinoids were not started until the 2010s. Indeed, recent studies have shown that these α-amino-functionalized compounds can outperform the commercial organophosphorus extraction agents in RE separations. They have also proven to be very efficient extraction and precipitation agents for recovering Th and U from RE concentrates. These actinoids coexist with REs in some of the commercially important RE-containing minerals. The efficient separation and purification of REs is becoming more and more important every year as these elements have a pivotal role in many existing technologies. If one also considers the facile synthesis of α-amino-functionalized organophosphorus extractants and precipitation agents, it is expected that they will be increasingly utilized in the extraction chemistry of REs and actinoids in the future. This review collates α-aminophosphonates, -phosphinates, and -phosphine oxides that have been utilized in the separation chemistry of REs and actinoids, including their most relevant synthetic routes and molecular properties. Their extraction and precipitation properties towards REs and actinoids are also discussed. Keywords: α-aminophosphonates; α-aminophosphinates; α-aminophosphine oxides; rare earth elements; actinoids; separation; recovery; extraction; precipitation 1. Introduction Organophosphorus compounds are one of the main commercial extractants used to separate rare earth elements (RE; lanthanoids, Sc, and Y) in solvent extraction on an industrial scale [1]. The solvent extraction is based on two immiscible liquid phases, one of which is the (acidic) aqueous phase containing REs to be separated, and the other is an organic phase including extractants. Many factors, such as the selectivity and loading capacity of extractants, number of extraction, scrubbing, and stripping cycles, and back-extraction of the extracted metal, affect the efficiency of the extraction process, but in a simplified picture, it is the coordination affinity of the extractant towards metal ions that determines the extraction degree and separation of metal ions into different fractions [2,3]. Because the coordination affinity is dictated by the molecular structure of the extractant, a plethora of different organophosphorus extractants have been developed and investigated for the separation of REs by now [1,4,5]. Apart from solvent extraction, organophosphorus compounds have also been utilized in other separation methods to recover and separate REs. Illustrative examples of such methods are fractional precipitation and solidphase extraction [6–9]. Organophosphorus extractants are usually classified into neutral and acidic compounds, the latter of which contains at least one acidic proton. They can also be divided Citation: Kukkonen, E.; Virtanen, E.J.; Moilanen, J.O. α -Aminophosphonates, Phosphinates, and Phosphine Oxides as Extraction and Precipitation Agents for Rare Earth Metals, Thorium, and Uranium: A Review. Molecules 2022, 27, 3465. https://doi.org/10.3390/ molecules27113465 Academic Editor: Jakub Adamek Received: 5 May 2022 Accepted: 25 May 2022 Published: 27 May 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. C opyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditi ons of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Molecules 2022, 27, 3465 2 of 29 into four different subgroups, which are phosphates ((RO)3P(O)), phosphonates ((RO)2P(O)R′, phosphinates ((RO)P(O)R′2), and phosphine oxides (P(O)R′3), according to their functional groups (R = H, organic substituent; R′ = organic substituent) [3,10]. The basicity of organophosphorus extractants containing P=O and P-O-R bonds varies with the number of O atoms connected to the P atom; phosphine oxides are the most basic with one substituted oxygen atom, followed by phosphinates, phosphonates, and phosphates. An increase in the basicity is accompanied by an increase in the coordination strength of the extractant. Thus, phosphine oxides are usually the most efficient extractants for REs, but the separation of REs may be weaker with phosphine oxides as they may extract REs too effectively without significant separation compared to phosphinates, phosphonates, and phosphates. The introduction of an amino group into organophosphorus compounds opens further synthetic strategies to modify their molecular structures, coordination affinity, and extraction properties [5]. For example, substituting H atoms of the amino group with new coordinating arms or long alkyl chains can increase the extractant’s affinity towards REs or its lipophilicity, respectively [5,11]. Illustrative examples of organophosphorus extractants containing the amino group are α-aminophosphonates consisting of amino and phosphonate moieties with the general formula of (RO)2P(O)CR′2NR″2. The R–R″ substituents can vary from H atoms to substituted hydrocarbons containing additional functional groups, making α-aminophosphonates versatile and modifiable chemical species. Replacing one of the -OR moieties of α-aminophosphonates with hydrocarbon gives α-aminophosphinates ((RO)P(O)(R′)CR″2NR‴2), whereas the replacement of two of the -OR moieties leads to α-aminophosphine oxides ((RO)2P(O)CR′2NR″2). As a group, these three families of α-amino-functionalized organophosphorus compounds can be classified as a subclass of organophosphorus extraction and precipitation agents that not only bear similar functional groups (P=O and amino moiety in the α position), but also have their distinct features (P-O-R vs. P-R bonds) that contribute to their complexation, extraction, and precipitation properties towards REs and actinoids (Scheme 1) [5]. Importantly, some of the α-amino-functionalized organophosphorus compounds have been proven to be better extractants for REs and actinoids than commercial extractants. Scheme 1. Versatile frameworks of α-amino-functionalized organophosphorus extractants and precipitation agents that can be tailored for the extraction chemistry of REs and actinoids. REs play a pivotal role in several applications utilized today. Illustrative examples of such applications are ceramics [12], alloys [13], photonics [14], catalysis [15], and permanent magnets [16]. Importantly, the latter are used in electric vehicles and wind turbines, which are key players in the green technology revolution contributing to fossil-fuel-free traffic and energy production, respectively [17]. Due to the suitability of REs for a wide range of applications, it has been predicted that the demand and price of REs will significantly increase in the future. As a matter of fact, the average price of Nd, the most crucial Molecules 2022, 27, 3465 3 of 29 element in Nd-based permanent magnets, has already increased from ~50 EUR/kg to a peak value of ~200 EUR/kg during the years 2018–2022 [18]. The increased demand and rise in prices of REs along with the environmental issues have considerably driven the development of separation methods, including solvent extraction, fractional precipitation and crystallization, electrolysis, and solid-phase extraction for recovering and separating REs from ores, raffinates, waste streams, and from each other during the last decade [1,19– 21]. Despite the numerous efforts to utilize various waste streams as sources for REs, the main sources of REs are still ores, such as bastnäsite, monazite, and xenotime, as well as RE-bearing clay. The main ores of REs can also contain actinoids, such as U and Th. In particular, the content of Th can be up to 0.3 wt% and 20.0 wt% in bastnäsite and monazite, respectively, whereas U is typically found from bastnäsite (0.09 wt%) and xenotime (0.0– 5.0 wt%), and sometimes from monazite, in which its content can be as high as 16 wt% [22,23]. Th has been proposed as a valuable alternative to the conventional uranium-based nuclear fuel for future nuclear reactors because it is more abundant than U, and overcomes many problems related to uranium-based nuclear fuel [24,25]. Therefore, the selective separation of actinoids from REs not only secures RE concentrates free of radioactive elements but also aims for the full valorization of RE ore by recovering every element from it. Scope of the Review Taking into account all the above-mentioned, α-aminophosphonate-, α-aminophosphinate-, and α-aminophosphine oxide-based extractants and precipitation agents have strong potential to develop the extraction chemistry of REs and actinoids that are critical elements for modern society. Thus, this review aims to illustrate the essential aspects of the chemistry of α-amino-functionalized organophosphorus compounds used for recovering REs and actinoids, as well as to discuss their extraction, precipitation, and separation properties towards the aforementioned elements. Liao et al. have reviewed the subject before [5], but with a strong focus on their own work and the separation of Ce(IV) and Th(IV) from other REs. Moreover, Chistyakov et al. briefly mentioned α-aminophosphonates in their review revolving around organophosphorus extractants [4]. Compared to the previously published reviews, we will take a strong molecular approach. The review is divided into seven sections, which are: an introduction (Section 1), the history (Section 2), synthesis (Section 3), and characterization (Section 4) of α-amino-functionalized organophosphorus compounds and their complexes by IR, compositions of extracted and precipitated complexes in solution phase (Section 5), extraction and precipitation properties of α-amino-functionalized organophosphorus compounds towards REs and actinoids (Section 6), and conclusions and future perspectives (Section 7). The review covers the relevant literature on the subject published from the 1960s to March 2022, but all α-aminofunctionalized organophosphorus compounds used as sorption materials in the solidphase extraction of REs and actinoids are excluded from this review [26–29]. 2. The Short History of α-Aminophosphonates, -Phosphinates, and -Phosphine Oxides as Extraction and Precipitation Agents Scheme 2 shows all α-aminophosphonates, -phosphinates, and -phosphine oxides studied in the extraction chemistry of REs, Th, and U from the 1960s to March 2022. Among these compounds, α-aminophosphonates 1–20 have dominated the field since the 1960s and, in particular, during the last ten years. In sharp contrast, there is only one acidic α-aminophosphinate 21 investigated so far, and the studies performed for α-aminophosphine oxides 22–32 were mainly done at the beginning of the 2010s, with the exception of one study that was published in 2020. Molecules 2022, 27, 3465 4 of 29 Scheme 2. Structures of the α-aminophosphonates (1–20), -phosphinate (21), and -phosphine oxides (22–32) studied for RE and actinoid separation. The first extraction studies of REs and actinoids with α-aminophosphonates can be traced back to the 1960s and 1970s when Jagodic et al. investigated the extraction of REs and actinoids from the aqueous phase to the organic phase with mono-octyl ester of α-anilinobenzylphosphonic acid (1, MOABP) [30]. Later on, Jagodic et al. shifted their focus to the carboxylic derivative of MOABP, namely α-(2-carboxyanilino)benzylphosphonic acid (2, MOCABP), which was designed to extract divalent metals in addition to triand tetravalent metals. During the studies, Jagodic et al. not only proved the good extraction ability of MOCABP towards divalent metals from acidic solutions, but they also showed that MOCABP was a slightly better extractant for trivalent REs compared to MOABP [30–33]. After the pioneering work of Jagodic et al., interest in α-aminophosphonate-, α-aminophosphinateand α-aminophosphine oxide-based extractants remained rather low, and it was not until the beginning of the 2000s that Fedorenko et al. published two papers focusing on calix[4]resorcinarenes, whose upper rims were functionalized with four αaminophosphonate arms (3–6) [34,35]. The studies demonstrated that the four α- Molecules 2022, 27, 3465 5 of 29 aminophosphonate arms facilitated the polydentate coordination of REs, leading to more efficient extraction of La(III) and Lu(III) compared to the extraction properties of O,O-diethyl[(4-nitrophenyl)aminobenzyl] phosphonate 7. The synthesized calix[4]resorcinarenes functioned as neutral extractants because the deprotonation reaction of the phenolic protons of calix[4]resorcinarenes did not occur under the extraction conditions as proven by NMR studies. Additionally, by changing the length of the alkyl chain in the phosphonate moiety and the number of counterions (sodium picrate) in the extraction process, Jagodic et al. were able to vary the metal–ligand ratio of the extracted complexes from 1:1 to 1:2. In 2009, Cherkasov et al. synthesized a family of new α-aminophosphine oxides (22–28) with one or two phosphine oxide groups and one new α-aminophosphonate (8) and investigated their extraction properties towards Sc(III). They showed that the twoarmed phosphine oxides were more selective compared to one-armed ones, albeit the degree of extraction of Sc(III) was rather similar for all investigated compounds. In summary, these three studies indicated that the polydentate extractants can outperform the monodentate ones bearing similar coordinating groups, not only in selectivity but also in efficiency, by a variable margin [11]. The 2010s, particularly the late 2010s, were a renaissance in the chemistry of α-aminofunctionalized organophosphorus compounds targeted for extracting REs and actinoids. In 2012, Cherkasov et al. published three different α-aminophosphine oxides 22, 29, and 31 and investigated their efficiency to extract Nd(III), Sm(III), Dy(III), Yb(III), and Lu(III) from different acidic solutions (hydrochloric, nitric, or perchloric acid) to different organic phases (toluene, chloroform, or methylene chloride). Because the syntheses of 29 and 31 were challenging, their extraction studies were only carried out in perchloric acid containing Lu(III). Cherkasov et al. found out that the extraction efficiency of the synthesized extractants strongly depended on the nature of the acidic solution [36]. The extraction efficiencies of 29 and 31 were comparable with 22 in perchloric acid. In 2013, Cherkasov et al. performed extraction studies for Sc(III), Y(III), La(III), Ce(III), Nd(III), Sm(III), Gd(III), Lu(III), and U(IV) using bisphosphorylated azapodand 30 as an extractant without and with bis(pentadecyl)phosphoric acid to investigate the synergistic effect of two extractants [37]. These two studies were followed by the discovery of Cextrant 230 (11), which was patented in 2017 by Liao et al. [38]. Cextrant 230 turned out to be an efficient extractant to recover +4 oxidation state ions, such as Ce(IV) and Th(IV), from the RE mixtures containing La(III), Gd(III), and Yb(III) in sulfate media [39]. To explain the superior affinity of Cextrant 230 towards Ce(IV), Liao et al. compared the extraction ability between Cextrant 230 and di-(2-ethylhexyl) 2-ethylhexyl phosphonate (DEHEHP). Cextrant 230 and DEHEHP are very similar phosphonates containing one P-C, one P=O, and two P-O-C bonds, but the latter does not have an amino group. Based on the studies, they proposed that the better extraction ability of Cextrant 230 originates from its additional nitrogen atom, which can coordinate to the metal ion. However, the role of the nitrogen as a coordinating atom during the complexation has remained controversial to some extent (see below). In the late 2010s and early 2020s, Liao et al. synthesized derivatives of Cextrant 230 by varying substituents in the amino group (9) [40] or methyl bridge (12) [41], or by converting the derivatives to acidic extractants (10, 13, 14) [42–44]. In the similar extraction conditions used for Cextrant 230, the derivatives 12 and 9 showed similar extraction properties to Cextrant 230 towards REs and actinoids, as the extraction efficiency of metal ions decreased in the following order Ce(IV) > Th(IV) > Sc(III) > other RE(III). Interestingly, among 9, 11, and 12, the last one was much more selective towards Ce(IV) than Sc(III) and Th(IV) [39–41,45]. Liao et al. concluded that the bigger ionic radius of Th(IV) hinders the simultaneous coordination of the P=O group and the nitrogen atom [41]. The extraction efficiency of an acidic extractant can show strong pH dependency, as was observed for 10, 13, and 14 [42–44]. These three acidic extractants were mainly developed to separate heavier lanthanoids, which has been a challenge for commercial organophosphorus extractants such as 2-ethylhexylphosphoric acid mono-2-ethylhexyl ester (HEHEHP) and di-(2-ethylhexyl)phosphoric acid (D2EHPA). Indeed, the three Molecules 2022, 27, 3465 6 of 29 aforementioned α-aminophosphonate extractants performed better on the separation of adjacent heavier lanthanoids than the commercial ones. The synergistic extraction properties of 10, 13, and 14 were also investigated with di-(2,4,4′-trimethylpentyl) phosphinic acid (Cyanex272), D2EHPA, and HEHEHP, respectively [46–48]. Compared to the solvent extraction containing only one extractant, the synergistic system can have several advantages, including better extraction efficiency, selectivity, and rate, improved solubility and stability of extracted complexes, a lower tendency to emulsification, and the formation of a third layer [46–49]. The synergistic studies were carried out for 10, 13, and 14 because Liao et al. aimed to enhance the challenging separation of heavier lanthanoids. In all three studies, they proved that the synergistic systems outperform the extraction efficiencies of single extractants, but the results for RE separation varied. To the best of our knowledge, only one acidic α-aminophosphinate-based extractant (21) has been published so far in 2022 [50]. The development of this new extractant was driven by the findings from the previous studies carried out for the α-amino-functionalized organophosphorus extractants, which showed that most of the time, the α-aminofunctionalized counterparts outperform traditional commercial extractants. Liao et al. compared the extraction performance of 21 to its structural analogue di-(2ethylhexyl)phosphinic acid (P227). Although 21 did not separate the studied heavier REs as well as P227, 21 reached the extraction equilibrium in less than 5 min, and heavy REs loaded in the organic phase with 21 were easy to strip with inorganic acids within the pH range of 0 to 2 depending on the ionic radius of the REs. Prior to this study, in 2020, Liao et al. developed α-aminophosphine oxide 32 using the same reasoning as for 21, but they also aimed for a higher extraction performance with 32 due to the strong basicity of the P=O group. Just like Cextrant 230, 32 extracted Ce(IV) effectively from the sulfate medium, but it was also easy to strip from the organic phase [51]. α-Aminophosphonates have also been used as precipitation agents for REs and actinoids [9]. In 2021, Moilanen et al. published a study focusing on the double-armed αaminophosphonates (15–20) with short alkyl chains to increase their water solubility. The good water solubility of the investigated compounds enabled the precipitation of actinoids and REs directly from the acidic water phase, resulting in the very good separation of Sc(III), U(VI), and Th(IV) from REs, although the separation of the adjacent REs was minor. It is evident from the above text that the extraction chemistry of REs and actinoids with α-amino-functionalized organophosphorus compounds that function either as extractants or precipitation agents evolved slowly at first, but during the last ten years, considerable progress has been made. In particular, the studies have shown that the extraction properties of α-amino-functionalized organophosphorus compounds can readily be changed by modifying their molecular frameworks with the well-established synthetic methods developed for the organophosphorus compounds. 3. Synthesis of α-Aminophosphonates, -Phosphinates, and -Phosphine Oxides So far, three different synthetic approaches—Kabachnik–Fields, Pudovik, and Mannich—have been used to synthesize the α-aminophosphonates, α-aminophosphinates, and α-aminophosphine oxides studied in the extraction and separation chemistry of REs, Th, and U (Scheme 2 and Table 1). Among the utilized methods, the Kabachnik–Fields method has been the most used one. Molecules 2022, 27, 3465 7 of 29 Table 1. Synthesis strategies, separation methods, and studied metals for the α-aminophosphonate, -phosphinate, and -phosphine oxide extractants. Extractant Synthesis Strategy Separation Method Studied REs and Actinoids Ref. 1 MOABP Pudovik Solvent extraction Y( III ), La( III ), Ce( III ), Eu( III ), Pr( III ), Tb( III ), Th( IV ), U( IV ), U( VI ) [31–33,52–55] 2 MOCABP Pudovik Solvent extraction La(III), Ce(III), Eu(III), Pr(III) [30–33] 3–5 Mannich a Solvent extraction La(III), Lu(III) [34,35] 6 Mannich a Solvent extraction La(III) [34] 7 Pudovik Solvent extraction La(III) [35] 8 Kabachnik–Fields Solvent extraction Sc(III) [11] 9 DEHAMP Kabachnik–Fields Solvent extraction Sc(III), La(III), Ce(IV), Gd(III), Yb(III), Th(IV) [40] 10 HEHHAP Kabachnik–Fields Solvent extraction, synergistic solvent extraction with Cyanex272 La(III), Ce(III), Pr(III), Nd(III), Sm(III), Eu(III), Gd(III), Tb(III), Dy(III), Ho(III), Y(III), Er(III), Tm(III), Yb(III), Lu(III) [44,48] 11 Cextrant 230 Kabachnik–Fields Solvent extraction Sc( III ), La( III ), Ce( IV ), Gd( III ), Yb( III ), Th( IV ), U( VI ) [39,45,56] 12 DEHAPP Kabachnik–Fields Solvent extraction Sc(III), La(III), Ce(III), Ce( IV ), Gd(III), Y(III), Yb(III), Th(IV) [41] 13 HEHAPP Kabachnik–Fields Solvent extraction, synergistic solvent extraction with D2EHPA La( III ), Ce( III ), Pr( III ), Nd( III ), Sm( III ), Eu( III ), Gd(III), Tb(III), Dy(III), Ho(III), Y(III), Er(III), Tm(III), Yb(III), Lu(III) [42,46] 14 HEHAMP Kabachnik–Fields Solvent extraction, synergistic solvent extraction with HEHEHP Sc(III), La(III), Pr(III), Nd(III), Sm(III), Eu(III), Gd(III), Tb(III), Dy(III), Ho(III), Y(III), Er(III), Tm(III), Yb(III), Lu(III) [43,47] 15–20 Kabachnik–Fields Precipitation Sc( III ), La( III ), Ce( III ), Pr( III ), Nd( III ), Sm( III ), Eu(III), Gd(III), Tb(III), Dy(III), Ho(III), Y(III), Er(III), Tm(III), Yb(III), Lu(III), Th(IV), U(VI) [9] 21 EEAMPA Kabachnik–Fields Solvent extraction La( III ), Ce( III ), Pr( III ), Nd( III ), Sm( III ), Eu( III ), Gd(III), Tb(III), Dy(III), Ho(III), Y(III), Er(III), Tm( III ), Yb( III ), Lu( III ) [50] 22 Kabachnik–Fields Solvent extraction Sc( III ), Nd( III ), Sm( III ), Dy( III ), Yb( III ), Lu( III ) [11,36] 23–28 Kabachnik–Fields Solvent extraction Sc( III ) [11] 29, 31 Kabachnik–Fields Solvent extraction Lu( III ) [36] 30 Kabachnik–Fields Solvent extraction Sc( III ), La( III ), Ce( III ), Nd( III ), Sm( III ), Gd( III ), Y( III ), Lu( III ), U( VI ) [37] 32 DEHAPO Kabachnik–Fields Solvent extraction La(III), Ce(IV), Gd(III), Yb(III), Th(IV) [51] a The aminophosphonate moiety was synthesized with Kabachnik–Fields reaction. The Kabachnik–Fields reaction includes a condensation reaction between primary or secondary amine, aldehyde or ketone, and either phosphite, phosphinate, or phosphine oxide resulting in α-aminophosphonates, -phosphinates, or -phosphine oxides, respectively (Scheme 3) [57,58]. This acid-catalyzed condensation reaction is advantageous to the synthesis of the aforementioned compounds for five reasons. (1) It is a simple one-pot reaction. (2) A variety of reagents with different substituents can be used in the reaction. (3) The basicity of the synthesized compound can be modified by varying the nature of amine and phosphorus groups; tertiary amines are more basic than secondary amines, Molecules 2022, 27, 3465 8 of 29 and the number of P-O-R groups influences the basicity of the P=O group. (4) Lipophilicity and steric bulk of the compound can be altered via the substituents R1–R6. (5) More than one coordinating phosphonate, phosphinate, or phosphine oxide group can be attached to the compound by changing the stoichiometry of reagents [59]. Scheme 3. The general route for Kabachnik–Fields reaction for α-aminophosphonates, -phosphinates, and -phosphine oxides. Substituents R1–R6 can be either H, alkyl, or aryl substituents. α-Aminophosphonates 8–14 together with α-aminophosphinate 21 and α-aminophosphine oxides 22–32 were synthesized using the same procedure, by refluxing the reagents either in benzene, toluene, or acetonitrile and using p-toluenesulfonic acid as the acid catalyst [11,36,37,39–44,50,51]. The progress of the reaction was monitored by measuring the amount of water formed into the Dean–Stark trap. The reaction was complete when the formation of water was no longer observed. Unreacted catalytic p-toluenesulfonic acid was removed from the solution by reacting it with K2CO3 under reflux conditions. Finally, the solution was washed with water to separate the formed potassium tosylate and other impurities and dried with MgSO4, yielding oily compounds [60,61]. For 2-ethylhexyl ((2-ethylhexylamino) methyl) phosphonic acid (EEAMPA) 21 and bis(2-ethylhexyl) ((2-ethylhexylamino)methyl) phosphine oxide (DEHAPO) 32, the phosphorous moieties were synthesized first by forming a Grignard reagent from 2-ethylhexyl bromide by mixing it with magnesium powder in THF and refluxing for 2 h, yielding (2ethylhexyl)magnesium bromide. For compound 21, the synthesized (2-ethylhexyl)magnesium bromide was reacted with triethylphosphite, yielding diethyl 2-ethylhexylphosphonite, which was then converted into ethyl 2-ethylhexylphosphinate by treating it with 6 M HCl [50]. In the case of 32, (2-ethylhexyl)magnesium bromide was reacted with diethylphosphite, yielding bis(2-ethylhexyl)phosphine oxide. After the phosphorous moieties were synthesized, the reaction proceeded through the pathway described above, by refluxing the amine, phosphine, and aldehyde reagents in toluene. To obtain the hydroxyl group, the ethyl group in 21 was hydrolyzed with KOH in ethanol using KI as a catalyst [51]. Heptylaminomethyl phosphonic acid 2-ethylhexyl ester (HEHHAP) 10 was synthesized by hydrolyzing di(2-ethylhexyl)-N-heptylaminomethyl phosphonate (DEHAMP) 9 with NaOH in boiling ethanol for 6 h [44]. After removing the solvent, dissolving the sodium salt into toluene, and treating the solution with an acid, an oily product (10) was obtained. By using the same hydrolysis procedure, 2-ethylhexyl-3-(2-ethylhexylamino)pentan-3-yl phosphonic acid (HEHAPP) 13 and (2-ethylhexylamino)methyl phosphonic acid mono-2-ethylhexyl ester (HEHAMP) 14 were obtained from di(2-ethylhexyl) (2-((2-ethylhexyl) amino) propan-2-yl) phosphonate (DEHAPP) 12 and di(2-ethylhexyl) (2-((2-ethylhexyl)amino)methyl) phosphonate (Cextrant 230) 11, respectively [42,43]. α-Aminobisphosphonates 15–20 were synthesized using water as a solvent and HCl as a catalyst instead of organic solvents and p-toluenesulfonic acid [9]. To obtain Molecules 2022, 27, 3465 15 of 29 Table 3. Reported chemical compositions of RE complexes of α-aminophosphonate, -phosphinate, and -phosphine oxide extractants and precipitation agents in solution. For compounds with acidic protons, HL and L denote the protonated and deprotonated versions of compounds, respectively. Complex Acid Diluent Ref. 1 U( VI )O 2 L 2 U(IV)L 4 H2SO4 Ligroin Recryst. from ethanol [52] 1 ML3∙HL/ML2∙HL2 (M=Eu, Tb) HCl, HNO3, and HClO 4 Ligroin [53] 1 ML3HL (M=Ln, Eu) HCl, HClO 4 Petroleum ether, CHCl 3, CCl 4 [31] 1 Ce(III)L 3 ∙2HL HCl CHCl 3 , benzene [33] 1 Ce(III)L 3 ∙HL HCl CCl 4 , cyclohexane [33] 1 PrL 3 ∙HL HCl CHCl 3 , benzene, CCl 4 [33] 1 PrL 3 HCl cyclohexane [33] 2 ML 3 ∙HL (M=Ln, Eu) HCl CHCl 3 [31] 2 Ce(III)L 3 ∙2HL HCl CHCl 3 [33] 2 PrL 3 HCl CHCl 3 [33] 3 LaLX 3 - CHCl 3 [35] 3 LuL 2 X 3 or LuLX 3 * - CHCl 3 [35] 4 LaL 2 X 3 or LaLX 3 * - CHCl 3 [35] 4 LuL 2 X 3 or LuLX 3 * - CHCl 3 [35] 5 LaL 2 X 3 or LaLX 3 * - CHCl 3 [35] 5 LuL 2 X 3 - CHCl 3 [35] 6 LaL 2 Pic 3 - CHCl 3 [34] 7 LaLX 3 - CHCl 3 [35] 9 Ce(IV)(SO 4 ) 2 ∙ 2L H 2 SO 4 heptane [40] 9 Th(HSO 4 ) 2 SO 4 ∙ L H 2 SO 4 heptane [40] 10 MClH 2 L 4 (M=Lu, Yb) HCl heptane [44] 10 + Cyanex272 MH 2 Cl 2 A 2 B (A=10, M=Yb, Lu) HCl heptane [48] 11 Ce( IV )(HSO 4 ) 2 SO 4 ∙ 2L H 2 SO 4 heptane [39] 11 Th(HSO 4 ) 2 SO 4 ∙ L H 2 SO 4 heptane [39] 11 Sc(HSO 4 )SO 4 ∙ 2L H 2 SO 4 heptane [45] 11 UO 2 SO 4 ∙ 2L H 2 SO 4 heptane [56] 12 Ce( IV )(HSO 4 ) 2 SO 4 ∙ 2L H 2 SO 4 heptane [41] 13 ML 3 (M=La, Gd, Y, Lu) HCl heptane [42] 13 + D2EHPA LuCl 2 H 4 A 3 B 2 (A=13) HCl heptane [46] 14 MH 2 ClL 4 (M=Tm, Yb, Lu) HCl heptane [43] 14 + HEHEHP MA 2 B 4 (A=14, M=Lu, Yb, Tm, Er, Y, Ho) HCl heptane [47] 15 LuL(NO 3 ) 2 HNO 3 water [9] 15 LaL 2 (NO 3 ) HNO 3 water [9] 15 YL 3 HNO 3 water [9] 21 MHL 3 NO 3 (M=La, Nd, Gd, Lu) HNO3 heptane [50] 22 ScL 2 X 3 HClO 4 toluene [11] 32 Ce( IV )(HSO 4 ) 2 SO 4 ∙ L H 2 SO 4 heptane [51] * Compositions for LnX3 with the two different NaPic ratios: 1:250 for former and 10:1 for latter. Molecules 2022, 27, 3465 16 of 29 The investigations on the complexation of 1 and 2 were continued using the two αaminophosphonates in several organic solvents to extract Ce(III) and Pr(III) [33]. While the exact composition of the RE complexes of 1 varied, as the number of ligands on the second coordination sphere was found to be dependent on the solvent used, they always had a tri-ligand ML3 unit at their core as the earlier extraction studies suggested. Complex composition studies with 2 in chloroform came to the same conclusion: both Ce(III) and Pr(III) preferred a tri-ligand system, with the Ce(III) complex including two extractant ligands on the second coordination sphere while the Pr(III) complex had none (Table 3). In both cases, the phosphonic acid group of extractant is deprotonated instead of the carboxyl group that likely participates in the formation of hydrogen bonding interactions supporting the extraction process. Almost three decades later, the focus of the extraction studies moved to macrocyclic calix[4]resorcinarenes 5 and 6, which were functionalized with aminophosphonate groups [34]. While poor solubility prevented proper analysis of the La complex obtained with extractant 5, compound 6 was found to form a LaL2Pic3 complex, with the three picrate anions balancing the charge of the cationic RE metal. These anions also played an important role in making the metal complex sufficiently large to be able to effectively coordinate to the cavity of macrocyclic extractant. The calix[4]resorcinarene studies were continued by using compounds 3–5 in the extraction of La(III) and Lu(III) while also comparing the results to 7 to investigate the role of the macrocyclic structure [35]. The lanthanoid–ligand ratio of the complexes was found to be dependent on the relative amount of sodium picrate used: an excess of picrate anions led to the formation of LnL2X3 complexes in most cases, whereas a lesser amount of picrate (i.e., excess of metal ions) always gave LnLX3 complexes (Table 3). Additionally, by comparing the extraction constants of La(III) complexes of 3 and 7, it was concluded that the La(III) complex of 3 was stabilized by the macrocycle. Structurally similar extractants 9, 11, and 12 were used for the separation of the tetravalent Ce(IV) and Th(IV) from trivalent RE metals. The Ce(IV) and Th(IV) complexes of 9 were found to have the structures of Ce(SO4)2 ∙ 2L and Th(HSO4)2SO4 ∙ L, respectively, both containing sulfate anions from the acidic medium [40]. Unsurprisingly, the extracted complexes of 11—Ce(HSO4)2SO4 ∙ 2L and Th(HSO4)2SO4 ∙ L—were similar, with their only difference from 9 being the anions included in the Ce(IV) complex [39]. Further studies with 11 revealed that the extracted complexes of Sc(III) and U(VI)O2 also contain two ligands, Sc(HSO4)SO4 ∙ 2L and UO2SO4 ∙ 2L, respectively, while the number of HSO4− ions decreased due to the lower charge of the extracted cations [45,56]. The Ce(IV) complex of 12 was also found to have the same Ce(HSO4)2SO4 ∙ 2L composition as the complex of 11, while the Th(IV) complex was not investigated [41]. Studies on congeneric monoacidic α-aminophosphonates 10, 13, and 14, in turn, have concentrated on the extraction of trivalent lanthanoids. The complex formation of acidic α-aminophosphonate 10 was investigated with Yb(III) and Lu(III), and the RE complexes of the metals were found to have the composition of MClH2L4 [44]. The N-(2-ethylhexyl) congener 14 of 10 was found to form complexes with the same MClH2L4 composition with the trivalent Yb(III), Lu(III), and Tm(III) [43]. In both cases, two dimerized extractants were partially deprotonated before coordinating to the extracted metal. In contrast, compound 13 with di-ethylated α-carbon was found to form a simple ML3 complex with the trivalent La(III), Gd(III), Y(III), and Lu(III) [42]. In this case, the deprotonation of the extractant was complete and broke apart the dimerization of 13. Based on the results obtained with the aforementioned REs, all three studies generalized the observed compositions to concern all trivalent RE complexes of 10, 13, and 14. An interesting addition to the complex composition studies has been the research on synergistic extraction, where α-aminophosphonates are paired with another organophosphorus extractant. The Lu(III) complex of 13+D2EHPA was found to have the structure of LuCl2H4A3B2, where A depicts the amount of α-aminophosphonate and B the amount of D2EHPA [46]. The composition had the same amount of 13 as the ML3 complex of the pure α-aminophosphonate extractant, while also including two D2EHPA units, bringing Molecules 2022, 27, 3465 17 of 29 the total number of extractants from three to five. Furthermore, only one of the three αaminophosphonates is deprotonated in the synergistic extraction process while the other two, as well as the two D2EHPA units, stay in a neutral dimerized form. A similar trend was observed with the 14+HEHEHP pairing, as the synergistic system complex MA2B4 requires two units of 14 and four HEHEHPs to extract a single RE cation, whereas the RE complex of pure 14, MH2ClL4, only included four extractants in total. Both extractants of the synergistic system remain in a singly deprotonated dimer form [47]. In contrast, the 10+Cyanex272 complex MH2Cl2A2B contained one neutral dimer of 10 and one deprotonated Cyanex272, which means that the synergistic system leads to a lower total amount of extractant ligands when compared with the MClH2L4 complex of pure 10 (Table 3) [48]. A study on α-aminobis(phosphonates) determined the compositions of the complexes via 31P NMR titrations in D2O [9]. This method was successfully employed for 15 with Y(III), La(III), and Lu(III), and the results revealed the complex compositions of YL3, LaL2(NO3), and LuL(NO3)2, respectively. In each case, the extractant was in a zwitterionic form and coordinated in a bidentate manner to the extracted metal cation while NO3− ions and/or H2O most likely complemented the coordination sphere of the RE. In addition, each phosphonate group was only singly deprotonated due to the pH range of the experiments. Further attempts at determining the complexes for Sc(III) and Th(IV) were unsuccessful due to heavy precipitation of the formed complexes at low pH values. While the research towards new α-aminophosphonates seems ever-expanding, the RE extraction properties of α-aminophosphinates remain largely uncharted. The sole reported study so far used acidic α-aminophosphinate reagent 21 for the extraction of trivalent REs from nitric acid media [50]. The complex formation was studied for La(III), Nd(III), Gd(III), and Lu(III), and all their complexes were found to have the same MHL3NO3 composition, consisting of one individual deprotonated ligand and one singly deprotonated dimer for every RE cation. The extraction studies were expanded to α-aminophosphine oxides when compounds 22–28 were investigated for the extraction of Sc(III) and other selected RE metals. The composition of the Sc(III) complex of 22 in toluene was found to be ScL2X3, with X denoting acidic anions included to balance out the charge of the metal [11]. Attempts to use the bilogarithmic plots to investigate the Sm(III) complex of 22, as well as the complexes formed by 23, were unsuccessful, as the former resulted in a nonlinear graph and the latter to ambiguous conclusions. The other synthesized extractants were not researched further [11,36]. Phosphine oxide 32, in turn, was investigated for the extraction of Ce(IV). Unlike the Ce(HSO4)2SO4 ∙ 2L complexes of its α-aminophosphonate congeners 11 and 9, the composition of 32 was found to be Ce(HSO4)2SO4 ∙ L, including only a single unit of the extractant [51]. In general, the studies have shown that the (mono)acidic α-aminophosphonate and α-aminophosphinate extractants favor three to four coordinated ligands around each metal cation, form complexes through deprotonation of the acid or its dimer and act as the counterions for the cationic metal centers (Table 3). The neutral di-alkoxy α-aminophosphonates and α-aminophosphine oxides, on the other hand, are more likely to stay in the range of one to two ligands per metal. Moreover, the anions of the acidic solution are often involved in the extraction process, as the extracted complexes transferred to an organic phase must be charge-neutral. This, in turn, means that the complex compositions in different acidic media are inherently varied, and the importance of the counter anion is further underlined by the findings from the extraction experiments with sodium picrate and 3–5. The studies have also confirmed that the solvent of the organic phase can have an impact on the composition as well, despite not being a part of the complex itself. In short, the complex formation can be described as a complicated process with multiple experimental factors affecting the outcome of the extraction. Molecules 2022, 27, 3465 18 of 29 6. Extraction Ability of α-Aminophosphonates, -Phosphinates, and -Phosphine Oxides towards REs and Actinoids To compare the recovery and separation properties of extractants and precipitation agents, several parameters have been developed to quantify their performance. The key parameters are the distribution ratio D, separation factor SF, and synergistic enhancement coefficient R, the last of which only applies to synergistic systems containing two extractants [81]. The distribution ratio describes the extraction ability of a compound towards certain elements. In solvent extraction, it can be determined as the concentration of extracted metal in the organic phase [M]org divided by the concentration of the unextracted metal remaining in the aqueous phase [M]aq. In the case of precipitation processes, the organic phase concentration is replaced by the amount of precipitated metal [M]p and calculated as the difference between initial and final concentrations of the aqueous phase, as shown by Equation (1): 𝐷𝐷=[𝑀𝑀]𝑜𝑜𝑜𝑜𝑜𝑜 [𝑀𝑀]𝑎𝑎𝑎𝑎 𝑜𝑜𝑜𝑜 𝐷𝐷=[𝑀𝑀]𝑝𝑝 [𝑀𝑀]𝑎𝑎𝑎𝑎 =[𝑀𝑀]𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖−[𝑀𝑀]𝑎𝑎𝑎𝑎 [𝑀𝑀]𝑎𝑎𝑎𝑎 . (1) High values of distribution ratios indicate a strong transfer of metal ions from the water phase to the organic phase or strong precipitation, whereas values close to zero are a sign of poor transfer of metal ions [81]. The separation factor is calculated with Equation (2) as the quotient of the distribution ratios D of the two metals A and B: 𝑆𝑆𝑆𝑆 =𝐷𝐷𝐴𝐴 𝐷𝐷𝐵𝐵. (2) The parameter describes the ability of the extractant or precipitation agent to separate two metals from each other. Separation factor values close to unity are a sign of poor separation, while significantly higher or lower values indicate that the extractant or precipitation agent can be used to efficiently separate the two metals in question [81]. The second important parameter derived from the distribution ratios is the synergistic enhancement coefficient, which aims to quantify the potential improvement of a system using two extractants simultaneously [82]. This is done by comparing the extraction performance (i.e., distribution ratio) of the combinatory system DAB to the sum of the distribution ratios of the individual components (DA + DB) according to Equation (3): 𝑅𝑅=𝐷𝐷𝐴𝐴𝐵𝐵 𝐷𝐷𝐴𝐴+𝐷𝐷𝐵𝐵. (3) Consequently, enhancement coefficient values over 1 indicate a positive synergistic effect, whereas the opposite is a sign of negative competition between the two extractants. It should be noted that the values of D, SF, and R are dependent on several experimental conditions, such as temperature, pH, and concentration, all of which can affect the behavior of both the metal and the extractant itself. In addition to the distribution ratio D, separation factor SF, and synergistic enhancement coefficient R, another important factor measuring the performance of extractants is their loading capacity. This parameter is, simply, the maximum amount of metal that can be extracted under certain experimental conditions, and it is commonly reported in g/L or mol/L. It is therefore essential to pay close attention to the reported concentration of the extractant to determine whether the loading capacity values are directly comparable or not. 6.1. α-Aminophosphonates Octyl α-anilinobenzylphosphonic acid 1 and its ethyl analogue were the first α-aminophosphonates that were investigated for the solvent extraction of REs and actinoids. While the ethyl analogue was too water-soluble for the extraction of metals, 1 was found to be a very good extracting agent for binary and ternary systems containing radioactive Molecules 2022, 27, 3465 19 of 29 nuclei. Studies on U extraction in ligroin found that U(IV) was extracted quantitatively only between sulfuric acid concentrations of 2 M and 4 M, whereas U(VI) could be extracted with a broader range of 0.5–9 M acidity [52]. A follow-up study showed that 1 was able to separate U(VI) selectively from Eu(III) and Tb(III) when ligroin was used as an organic solvent, and the molarity of the aqueous phase was higher than 0.5 M [53]. According to the authors, the determined SFU/Eu and SFU/Tb were ~26,000 (Table 4). The full separation between Sr(II) (the source of the radioisotope of 88Y) and Y(III), as well as between 131Ba(II) and 140La(III), was also obtained in petroleum ether, keeping the hydrochloric acid molarity between 0.01 M and 0.1 M [54,55]. Table 4. Highest reported SF for the extraction of actinoids Th(IV) and U(VI) with α-amino-functionalized organophosphorus compounds. FP indicates full precipitation of the metal marked in parentheses, because of which the SF could not be determined. Extractant Ce(IV)/Th U/Eu Th/RE U/RE Th/Lu U/Th U/Lu Ref. 1 - 26,000 * - - - - - [53] a 11 14.7 - - - - - - [39] b 11 - - >1000 >1000 - - - [56] c 12 754.2 - - - - - - [41] d 15 - - - - 4.50 g FP(U) i FP(U) i [9] 16 - - - - 6.02 f, ^ 2.01 e 4.03 f, ^ [9] 17 - - - - 9.17 g 2.40 e 8.68 g [9] 18 - - - - 44.41 g FP(U) h FP(U) h [9] 19 - - - - FP(Lu) j FP(U) h FP(U) h [9] 20 - - - - FP(Th) j FP(U) e FP(U) e [9] 32 100.3 - - - - - - [51] k * Separation factor for U/Tb mentioned to be similar; ^ best SF with error smaller than the value; a 5 mM extractant 1, 0.1 mM Eu(III), 4 mM U(VI)O22+, 1 M H2SO4 ; b 0.1 M extractant 11, 0.01 M M(IV), 3 M H2SO4 ; c 0.1 M extractant 11, 0.01 M metals, 3.23 M H+ for Th/RE, 0.22 M or 3.23 M H+ for U/RE; d 0.048 M extractant 12, 6 mM Th, 5 mM Ce, 0.2134 M H2SO4; e 2.5 g/L extractant, 9 mg/L, pH 1; f 2.5 g/L extractant, 9 mg/L, pH 2; g 2.5 g/L extractant, 9 mg/L, pH 2.5; h 2.5 g/L extractant, 9 mg/L, pH 3; i 2.5 g/L extractant, 9 mg/L, pH 3.5; j 2.5 g/L extractant, 9 mg/L, pH 2.5; k 0.1 M extractant 32, 0.01 M M(IV), 0.9353 M H2SO4. The research on the carboxylic derivative (2) of 1 not only revealed that it is a better extractant for Eu(III) and Ln(III), but it was also more selective towards divalent transition metals than trivalent REs compared to 1 [30,31]. However, the solubility of 1 was much better in different organic solvents compared to 2, which was only well-soluble in CHCl3. Indeed, the studies in various organic solvents revealed distinguishable changes in the Eu(III) extraction behavior of 1, with increasing HCl concentration of the aqueous phase. The best extraction ability was maintained with petroleum ether and cyclohexane, with the increasing acid concentration compared to CCl4, benzene, and CHCl3 [32]. Both acidic α-aminophosphonates were also utilized to extract Ce(III) and Pr(III) from hydrochloric acid medium, but the differences in their extraction behavior were too small to allow efficient separation of the two metals from each other [33]. A study focusing on the extraction of La(III) with two α-aminophosphonates functionalized macrocyclic calix[4]resorcinarenes 5 and 6 reported that La(III) does not coordinate to nonfunctionalized calix[4]resorcinarenes, nor does it form complexes without the suitably sized lipophilic picrate counterions that fill the cavity of the calix[4]resorcinarene, as mentioned above [34]. The studies were continued with the extraction of La(III) and Lu(III) with compounds 3–5, and the influence of the relative amount of picrate anions on the extraction properties of 3–5 was also investigated [35]. Interestingly, in the presence of the excess of sodium picrate, the extraction efficiency of 3 towards La(III) was found to be higher than the extraction efficiency of 4 and 5 due to the change in the metal–ligand Molecules 2022, 27, 3465 20 of 29 ratio in the complex formation from 1:1 (3) to 1:2 (4 and 5). Contrary to La(III), 5 was the most efficient extractant for Lu(III). Importantly, all calix[4]resorcinarene–aminophosphonates were more efficient extractants than 7, indicating the strength of multiple coordinating arms in the extraction process. Several studies on α-aminophosphonates have concentrated on the extraction of Ce(IV) and Th(IV) from sulfuric acid leach of the bastnäsite ore using heptane as a diluent. Compound 9 effectively separated the aforementioned tetravalent metals and Sc(III) from the rest of the studied trivalent REs. The extraction of Th(IV) and Sc(III) was found to decrease sharply with increasing acidity, while the extraction of Ce(IV) remained practically complete in the sulfuric acid concentration of <4 M [40]. Comparable results were obtained for the structurally similar α-aminophosphonate 11, as Ce(IV) and Th(IV) were efficiently separated while the extraction of Th(IV) was more prone to changes in acid concentration. The extractant was successfully used to obtain RE products of high purity with high yields in a pilot test. It was subsequently patented and named as Cextrant 230 [39]. The extractant 12 performed similarly to 9 and 11 in the extraction studies because the most efficient metal separation occurred when the sulfuric acid concentration did not exceed 1 M [41]. However, a notable exception to the other two extractants was the low extractability of Th(IV) with 12, which enabled the efficient separation of Ce(IV) and Th(IV) (SFCe/Th = 754.2, Table 4). The increased selectivity was assigned to the steric effects arising from the larger ionic radius of Th(IV), hindering its effective coordination to 12. Compound 11 was further studied for the extraction of Sc(III) and U(VI). The extraction of Sc(III) from red mud was investigated with various acids, and the results showed that dilute sulfuric acid was by far the most efficient medium. Unfortunately, 11 was also found to extract significant amounts of other REs, as well as Ti(IV) and Fe(III), all of which are prevalent in red mud, but after a series of post-extraction treatment procedures, a purity of ~94% was achieved for the Sc2O3 product [45]. The results from the extraction studies of U(VI) and Th(IV) suggested that the separation of two actinoids from RE metals, Fe(III) and Al(III), is effective throughout the studied pH range of 0.22–3.23. U(VI) was best extracted and separated from REs at pH 0.22 with high SFU/RE > 1000. Moreover, U(VI) had a higher loading capacity (6.16 g/L vs. 4.08 g/L for 5% extractant in heptane) than Th(IV) (Table 5) [56]. Molecules 2022, 27, 3465 21 of 29 Table 5. Loading capacities of the α-amino-functionalized organophosphorus compounds used in RE and actinoid extraction studies, as reported in the original papers. Extractant Dilution Metal Acid Capacity Ref. 9 0.63 M in heptane 0.23 M Ce( IV ) (∑Ce 0.24 M) 0.02 M Th(IV) H2SO4 30.0 g/L Ce(IV) 24.4 g/L Th(IV) [40] 10 30% (v/v) in heptane 0.0985 M YbCl 3 0.0986 M LuCl 3 HCl 12.76 g/L Yb 15.43 g/L Lu [44] 11 30% (v/v) in heptane Ce(IV) & Th(IV) H2SO4 >30 g/L Ce( IV ) ~43 g/L Th(IV) [39,83] 11 30% (v/v) in heptane 0.064 M Sc H2SO4 3.85 g/L Sc [45] 11 5% ( v/v ) in heptane 8.08 mM Th( IV ) 21 mM U(VI) H2SO4 4.08 g/L Th( IV ) 6.16 g/L U(VI) [56] 12 30% (v/v) in heptane 0.29 M Ce(IV) H2SO4 31.43 g/L CeO2 [41] 13 30% (v/v) in heptane 0.1 M RE HCl 0.201 M Ho 0.205 M Er 0.216 M Yb 0.229 M Lu [42] 14 30% (v/v) in heptane 0.055 M YbCl3 * HCl 15.17 g/L Lu 14.46 g/L Yb 12.64 g/L Y [43] 14 + HEHEHP 30% (v/v) in heptane (1:1 extractant ratio) 96 mM Lu 92 mM Yb HCl 27.25 g/L Lu2O3 26.59 g/L Yb2O3 [47] 21 4 mM in heptane 0.4 mM RE HNO3 0.393 mM Ho 0.402 mM Er 0.422 mM Tm 0.435 mM Yb 0.450 mM Lu [50] 32 30% (v/v) in heptane 0.143 M Ce(IV) H2SO4 16.66 g/L CeO2 [51] * Used RE concentration only reported for Yb. The extraction and separation of trivalent REs from each other have also been investigated with monoacidic α-aminophosphonate reagents 10, 13, and 14. The extraction efficiency of 10 and 13 towards Y(III), La(III), Gd(III), Ho(III), Er(III), Tm(III), Yb(III), and Lu(III) decreased with increasing acid concentration [42,44]. A similar trend was observed for 14 when the extracted metals were Sc(III), Y(III), Ho(III), Er(III), Tm(III), Yb(III), and Lu(III), while the extractabilities of La(III) and Gd(III) were not strongly affected by the concentration of acid [43]. The best results were obtained with extractant 13, which has some of the highest reported separation factors among all the studied α-amino-functionalized organophosphorus extractants listed in Table 6. In general, the investigated α-aminophosphonate compounds have shown a better ability to separate adjacent heavy REs from each other than the commercially used extractants D2EHPA and HEHEHP [84]. Molecules 2022, 27, 3465 22 of 29 Table 6. Best reported SF for adjacent RE elements (excluding the radioactive promethium). Precipitation studies carried out for 15–20 were done in water, whereas heptane was used as a diluent in all solvent extraction experiments. The detailed experimental conditions are given below. Extractant Ce/La Pr/Ce Nd/Pr Sm/Nd Eu/Sm Gd/Eu Tb/Gd Dy/Tb Ho/Dy Er/Ho Tm/Er Yb/Tm Lu/Yb Y/Ho Er/Y Ref. 10 1.47 1.23 0.85 1.93 1.14 0.62 1.76 1.39 1.39 2.28 4.29 1.59 1.63 1.04 2.18 [44] a 10 - - - - - - - - 1.27 1.23 2.36 3.18 1.59 1.41 0.88 [48] b 10 + Cyanex272 - - - - - - - - 2.57 3.33 3.07 3.58 1.60 1.60 2.08 [48] c 12 135.1* - - - - - - - - - - - - - - [41] d 13 - - - - - - - - - 2.83 3.87 5.64 4.89 2.24 2.35 [42] e 13 + D2EHPA 0.72 1.31 0.93 0.92 1.03 0.97 1.01 1.13 1.03 1.45 2.58 2.77 1.77 1.35 0.93 ** [46] f 14 - - 1.43 1.35 1.11 1.19 1.44 1.07 1.32 1.78 1.93 1.36 1.24 1.13 1.58 [43] g 14 + HEHEHP - - 1.20 1.14 1.45 1.13 1.16 1.17 1.05 2.11 1.78 1.76 1.20 1.32 1.61 [47] h 15 2.56 m 2.06 l 1.16 l 1.41 m 1.28 m 1.22 m 1.01 n 2.67 l 1.28 m, ^ 2.00 l, ^ - 2.88 l 2.52 k - 3.02 l [9] 16 1.33 m, ^ 1.23 i 1.48 j 1.50 k 1.45 j, ^ 1.52 j, ^ 1.05 i 1.23 m 1.4 1 m 1.09 i - 1.77 m, ^ 1.30 n - 2.75 i [9] 17 2.92 j 1.36 k 1.75 j 1.44 l 1.76 l 1.41 l 0.84 l 1.51 l 1.44 l 1.18 l - 2.22 l, ^ 1.18 l - 3.33 m [9] 18 3.81 l 1.26 m 1.11 n 1.70 l 1.07 n, ^ 1.21 m 1.49 l 1.50 l 1.47 l 1.53 l - 3.60 k 2.32 n - 2.21 l [9] 19 2.11 l 2.18 k 1.54 k 2.04 k 1.20 n 1.42 k 1.14 k 1.06 k 1.12 k 1.57 n - 4.33 n FP(Lu) n - 1.87 n [9] 20 1.88 m 1.50 n 1.15 m 1.73 m 1.29 l 1.16 l 1.77 l 1.20 l 1.08 l 1.36 l - 1.94 l 2.33 n - 2.03 l [9] 21 1.54 2.57 1.09 1.43 1.62 0.92 1.83 1.56 1.35 1.71 1.97 2.37 1.63 1.68 1.00 [50] o 32 167.0 * - - - - - - - - - - - - - - [51] p D2EHPA 2.14 1.07 1.06 4.86 2.23 1.69 1.60 1.42 1.24 1.70 1.50 1.30 1.03 - - [84] q HEHEHP 1.30 1.09 1.17 2.00 1.96 1.46 2.35 1.62 2.58 1.25 1.33 1.12 1.13 - - [84] q * Ce(IV) was used instead of Ce(III); ** value for the reverse pairing reported; ^ best SF with error smaller than the value; a 0.1 M extractant 10, 2 mM RE, pH 4.5; b 0.1 M extractant 10, 1 mM RE, pH 2.5; c 0.05 M extractant 10 and 0.05 M Cyanex272, 1 mM RE, pH 2.5; d 0.048 M extractant 12, 5.1 mM La, 5 mM Ce, 0.2134 M H2SO4; e 0.05 M extractant 13, 5 mM RE, c(HCl): Tm/Er 2 M, Yb/Tm 4.1 M, Lu/Yb 3.7 M, Y/Ho 1 M, Er/Y 2.5 M, Er/Ho 2 M; f 0.05 M extractant (total, 1:1 molar ratio), 1 mM RE, 2.5 M H+; g 0.1 M extractant 14, 5 mM RE, pH 1.0; h 0.1 M extractant (total, χ = 0.5), 0.01 M RE, pH: Y/Ho 1.3, all others 1.0; i 2.5g/L extractant, 9 mg/L RE, pH 1; j 2.5g/L extractant, 9 mg/L RE, pH 2; k 2.5g/L extractant, 9 mg/L RE, pH 2.5; l 2.5g/L extractant, 9 mg/L RE, pH 3; m 2.5g/L extractant, 9 mg/L RE, pH 3.5; n 2.5g/L extractant, 9 mg/L RE, pH 4; o 4 mM extractant 21, 0.2 mM RE, pH 1.0; p 0.1 M extractant 32, 0.01 M RE, 0.4353 M H2SO4; q 0.2 M extractant in kerosene, 1 g/l RE, 0.1 M HCl. Molecules 2022, 27, 3465 23 of 29 While the majority of previous studies carried out for α-aminophosphonates have focused on solvent extraction, these compounds also work as precipitation agents. A series of α-aminobis(phosphonates) 15–20, with variable hydrocarbon chain lengths, was studied for the recovery of REs, Th(IV), and U(VI) by direct precipitation of the formed complexes from the nitric acid solution [9]. α-Aminobis(phosphonates) 18–20, with a longer hydrocarbon chain, separated Sc(III) and both actinoids from the rest of the investigated REs well in the pH range of 1–2. In this pH range, Sc(III), Th(IV), and U(VI) completely precipitated out from the nitric acid solution, while REs remained in the solution (Table 4). While similar trends in selectivity were observed for 15–17, their precipitation percentages did not surpass 60% at pH < 2, where the precipitation of other trivalent REs stayed under 10%. The synergistic extraction of REs by using binary mixtures of an acidic α-aminophosphonate and another acidic organophosphorus extractant has been studied as a potential way to improve either the selectivity of the system or the extractability of the metals of interest. For the 13+D2EHPA system, the separation factors for studied REs were found to be lower than with pure 13, but it still outperformed the separation efficiency of pure D2EHPA for heavier lanthanoids (Table 6) [46]. When comparing the separation factors of pure 14 and its synergistic system with HEHEHP under similar experimental conditions, the latter does not seem to bring a major improvement in performance over the former, as indicated by minor changes (less than ±0.4) in the determined separation factors (Table 6). However, the loading capacity of the synergistic system is almost doubled for Lu(III) and Yb(III) compared to pure 14 (Table 5), although it does not reach the Yb(III) capacity of pure HEHEHP (32.92 g/L) [47]. The separation factors determined for heavy lanthanoid separation with the 10+Cyanex272 system, on the other hand, showed general improvement over the separation factors obtained for pure 10 and Cyanex272. A closer inspection of data also reveals that out of these three synergistic systems studied, the binary mixture consisting of 10+Cyanex272 performed the best in heavy RE separation [48]. The highest synergistic enhancement factors reported in the aforementioned α-aminophosphonate studies are listed in Table 7. It should be noted that the best R values describe the enhancement obtained compared to the individual performance of two extractants, so it does not directly correlate to the best extraction capability of the system. Consequently, while the highest R values were obtained with α-aminophosphonate molar fractions of 0.5–0.6, the highest distribution ratios D of the two-component systems of 14 and 10 were found around molar fractions 0.3–0.4. This observation is consistent with the determined 1:2 extractant ratio of the metal complex of the former system but opposite to 10+Cyanex272′s 2:1 ratio [47,48]. Intriguingly, the maximum D of the 13+D2EHPA system was found at 0.8 and, while not in perfect agreement with the 3:2 complex composition, both ratios indicate that the α-aminophosphonate component played the more important role in the overall performance of the extraction process [46]. Table 7. The highest values of synergistic enhancement factors R reported for each system (and RE). The molar fraction χ of the α-aminophosphonate is included in parentheses. Extractant Ho Er Tm Yb Lu Y Ref. 13 + D2EHPA - - - - 3.96 (0.5) - [46] a 14 + HEHEHP 2.18 (0.4) 2.14 (0.5) 2.54 (0.5) 2.76 (0.5) 2.89 (0.5) 2.14 (0.5) [47] b 10 + Cyanex272 1.95 (0.4) 2.71 (0.6) 2.43 (0.6) 3.67 (0.5) 3.39 (0.5) - [48] c a 0.01 M Lu(III), 0.03 M extractant (sum), 0.6 M H+; b 0.02 M RE, 0.1 M extractant (sum), pH 2 ; c 3 mM RE, 0.03 M extractant (sum), pH 2.5. 6.2. α-Aminophosphinates Contrary to the better-explored α-aminophosphonates, only one RE extraction study has been reported for α-aminophosphinates so far [50]. The monoacidic α-aminophosphinate 21 extracted REs from nitrate medium similarly to monoacidic phosphonates 10, Molecules 2022, 27, 3465 24 of 29 13, and 14 because the extractabilities of REs increased with increasing pH. Only the light REs—La(III), Ce(III), Pr(III), Nd(III)—could not reach complete extraction, even at pH 4 or higher. Based on the determined separation factors for the adjacent heavy REs, 21 separated them better than the typical commercial extractants D2EHPA and HEHEHP, but it did not outperform its commercial phosphinic acid analogue P227 (Table 6). However, 21 reached the extraction equilibrium much faster, and its Lu(III) loading capacity of 0.45 mM was 1.5 times higher than P227′s 0.32 mM under the same experimental conditions. 6.3. α-Aminophosphine Oxides The research on α-aminophosphine oxides started with investigations on the possibility of using the compounds as extractants for Sc(III). A series of compounds 22–28, including also one α-aminophosphonate 8, was synthesized, and while most of them showed some capability for Sc(III) extraction, only the two best-performing reagents 22 and 23 were investigated further [11]. Both compounds were able to separate Sc(III) from a variety of diand trivalent metal ions; in particular, 22 was effective in 0.3 M nitric acid medium when toluene was used as a diluent. The selectivity of extractants towards Sc(III) was further confirmed in a follow-up study where the extraction of several trivalent lanthanoids was investigated as well [36]. The highest extraction degree (~80%) of REs was obtained from perchloric acid, surpassing the extraction degree (~30%) of two other acids, hydrochloric and nitric, by 50 percentage points when the acid concentration varied from 0.25 to 0.5 M. The extractability of the investigated REs followed the decreasing ionic radii of REs; Nd(III) was extracted the best, followed by Sm(III), Dy(III), Yb(III), and Lu(III). The synthesized α-aminophosphine oxide–azapodands 29 and 31 showed extraction properties towards Lu(III) similar to 22, but their more difficult synthetic procedure contradicted their usability in large-scale solvent extraction [36]. A follow-up study with a slightly smaller azapodand 30 in toluene showed that U(VI) and RE(III) ions, except Y(III), are extracted practically quantitatively from a perchloric acid solution at a pH of 4.7, whereas bis(pentadecyl)phosphoric acid extracted U(VI) and Lu(III) from hydrochloric acid more selectively compared to other studied REs at a low pH regime [37]. Synergistic studies in hydrochloric acid showed that, by combining 30 and bis(pentadecyl)phosphoric acid in a 1:2 ratio, the selectivity towards U(VI), Y(III), and Lu(III) can be increased at low (2.9) and high pH (5.0–5.5) regimes, while other RE ions extracted poorly (La(III), Ce(III), and Nd(III)) or moderately (Gd(III) and Sm(III)) from the aqueous phase. Like its α-aminophosphonate congener 11, α-aminophosphine oxide 32 was studied for the extraction of Ce(IV) from bastnäsite ore [51]. The extractant was found to have high selectivity towards Ce(IV), with SF exceeding 100 for all studied metal pairings, allowing the effective separation of Ce(IV) from Th(IV) and several REs. Although α-aminophosphonate 12 achieved better Ce(IV)/Th(IV) separation in dilute sulfuric acid, 32 was able to keep the separation relatively high despite increasing acidity. Compound 32 also outperformed 12 in the Ce(IV)/RE(III) separation in virtually all studied acid concentrations. However, the Ce(IV) loading capacity of 16.66 g/L was notably lower for 32 than for the three α-aminophosphonate extractants 9, 11, and 12, as all of them reached the loading capacities of 30 g/L or higher (Table 5). To summarize Section 6, the various α-amino-functionalized organophosphorus extractants have generally demonstrated good selectivity towards REs and actinoids, particularly U(VI), Th(IV), Ce(IV), and Sc(III). The studied systems have proven to outperform commercial extractants such as D2EHPA and HEHEHP in several aspects, with the improved separation of adjacent heavy REs as one of the most important highlights. While the experimental extraction data of α-aminophosphinates and phosphine oxides—SFs in particular—are still more scarce compared to the more studied α-aminophosphonates, the results so far indicate similar performance levels and encourage further studies on their extraction chemistry. The utilization of α-amino-functionalized organophosphorus compounds as part of synergistic extraction systems is another rather unexplored area with few but promising results.