Deuterated Malonamide Synthesis for Fundamental Research on Solvent Extraction Systems

ABSTRACT Malonamide derivatives, which are the most extensively investigated extractants for solvent extraction of lanthanides, actinides, and platinum group metal ions, were deuterated by using Pd/C and Rh/C catalysts in a D2O/2-propanol mixture. This method replaces 1H atoms in the malonamides with 2H atoms at a controllable deuteration rate. The maximum rate reached about 75%, determined by nuclear magnetic resonance and electrospray ionization – mass spectrometry. The extraction behavior of metal ions by the malonamides was unchanged by the deuteration. Deuterated malonamides are a powerful tool for fundamental research on solvent extraction systems and for structural analysis of organic phases. The large difference in the cross section of coherent neutron scattering between 1H and 2H leads to a large difference in neutron scattering length density of malonamide derivatives before and after the deuteration. Therefore, using deuterated malonamides in small-angle neutron scattering and neutron reflectivity studies may help to reveal the microscopic structure of the specific solute species in the bulk organic phase and at the liquid–liquid interface, respectively. In this paper, we report the advantage of the deuterated malonamides for a contrast-matching method in the SANS experiment. This deuteration method could be generalized and extended to a wide variety of extractant molecules.


Introduction
Malonamides are among the most extensively investigated extractants for solvent extraction. [1][2][3][4] They undergo bidentate coordination to actinide and lanthanide ions via two carbonyl oxygen atoms. [5] Various malonamides have been developed by changing the length of the four alkyl chains bound to the nitrogen atoms of the two amide groups, and of the central alkyl/alkyl-ether chain on the α-carbon. [6] These modifications of the chemical structure produce changes in solute architectures not only at the molecular scale in the metalligand complexes but also at the supramolecular scale in multi-molecular structures, such as inverted micelles or reversed aggregates. Both types of change strongly affect the kinetics, selectivity, efficiency, and phase stability during solvent extraction. [7][8][9][10] N,N′-Dimethyl-N,N′-dioctylhexylethoxymalonamide (DMDOHEMA) in aliphatic diluent (n-dodecane) has been proposed for use in the nuclear chemical industry to separate actinides from high-level radioactive liquid waste by DIAMide Extraction (DIAMEX). [11][12][13] DMDOHEMA shows high solubility in organic solvents and high stability to hydrolysis and radiolysis. [14] Malonamides are currently studied in the more conventional industrial field of hydrometallurgical recycling of rare-earth elements and platinum group metals. [15][16][17][18][19] Solvent extraction systems using malonamides occasionally also provide interesting fundamental insights. For example, Poirot et al. [20] reported that the organic phase of DMDOHEMA in n-heptane in contact with HNO 3 forms solute aggregates, enabling the extraction of both Nd(III) and Pd(II), whereas no aggregates are formed in toluene leading to the extraction of Pd(II) only. Moussaoui et al. reported a synergistic effect using dihexylamine (DHA) with N,N,N′,N′-tetrahexylmalonamide (THMA) in the solvent extraction of Pd(II). [21] They demonstrated that the molar ratio of DHA to THMA in the organic phase governed the kinetics of Pd(II) extraction. Investigating the solute architectures in the bulk organic phase and at the liquid-liquid (L-L) interface should give key insights into understanding metal ion transfer and the mechanism of the solvent extractions. Nuclear magnetic resonance (NMR) and crystal structure analyses have been widely used to investigate metal-ligand coordination chemistry, whereas small-angle X-ray scattering and small-angle neutron scattering (SANS) are used to observe supramolecular organization formed by the complexes, ligands, acids, and water molecules. [22,23] Additionally, neutron reflectivity (NR) measurements provide the ligand topology, such as orientation and association at the L-L interface, and the nanoscale concentration profiles of each solute across the L-L interface. Scoppola et al. evaluated the interfacial potential energy across the oil-water interface, governing both the kinetics and selectivity of the metal ion transfer, based on the local concentration profiles. [24] Using deuterated malonamide derivatives containing deuterium ( 2 H, D) atoms instead of protium ( 1 H) atoms can have major advantages for fundamental research using SANS, NR, and NMR. Because of the large difference in the scattering cross-section between 1 H and 2 H, deuterated molecules are important in techniques that use neutrons. In particular, contrast-variation SANS and NR techniques [25] using deuterated malonamides may provide a partial scattering function (self-correlation function) for each solute, i.e., metal-ligand complex, uncoordinated ligand, and modifier, in the bulk organic phase and at the L-L interface. The structural information obtained should help advance the fundamental science of solvent extraction systems. Deuterated material synthesis is generally achieved by either bottom-up synthesis starting from available deuterated synthons or by post-synthetic methods directly applied to hydrogenated molecules, on which 1 H/ 2 H exchange is performed. Bottom-up methods are usually used to prepare deuterated extractants because the deuterated positions and deuteration rates can be controlled easily; however, these methods have multiple steps, often resulting in low yields. [26] 1 H/ 2 H exchange is widely used in pharmaceutical chemistry to prepare specific drugs or standards, and it is cost-effective and fast compared with bottom-up methods, although specific site labelling is difficult. [27,28] 1 H/ 2 H exchange uses the multiple different kinds of metals on carbon as catalysts. For example, Pd/C is usually used for deuterating aliphatic compounds and Pt/C is used for aromatic compounds, and a mixture of both produces a synergistic effect on the labelling efficiency. [27,28] It is generally known that the synthesis atmosphere, namely the gas, also has an important effect on the total deuteration rate. However, Yamada et al. [29] successfully demonstrated that deuteration of saturated fatty acids can achieve high deuterium exchange and high yields under mild conditions using a Pt/C catalyst in 2-PrOH/D 2 O without the external addition of hydrogen gas for catalyst activation. [28] The post-synthetic method has never been used to prepare deuterated extractants, including malonamide derivatives.
In this study, we report the synthesis of deuterated malonamide derivative isomers, namely THMA and N,N′-dibutyl-N,N′-dimethyl-2-tetradecylmalonamide (DBMA) using Pd/C and Rh/C catalysts with a D 2 O/2-PrOH mixture. [29][30][31] The reaction yield is calculated from the mass balance, and the deuteration rate of each 1 H atom in malonamide molecules is determined using NMR. Additionally, the effect of the deuterium atom on the extraction efficiency of various metal ions in an acidic solution is investigated through solvent extraction using the malonamide derivatives in toluene. Finally, SANS experiments with deuterated and non-deuterated DBMA extractants in n-heptane are performed using contrast matching method. [25] These results highlight the advantage of using deuterated malonamides over non-deuterated molecules to describe supramolecular organization with reducing the incoherent scattering contribution.

Synthesis of deuterated malonamides
The deuteration reactions were performed under heating at 140 and 180°C and at pressures of 0.3 and 0.9 MPa according to literature procedures proposed by Modutlwa et al. [31] Figure 1 shows the synthesis schemes of N,N,N′,N′tetrakis(hexyl-d 13 )malonamide-d 2 (THMA-d n ) and N,N′-bis(butyl-d 9 )-N,N′bis(methyl-d 3 )-2-(tetradecyl-d 29 )malonamide-d 1 (DBMA-d n ). In the general procedure, the malonamide (5.0 g, 11.4 mmol), Pd/C (5.0 g, corresponding to 500 mg Pd), and Rh/C (10 g, corresponding to 500 mg Rh) were added to a stainless steel reactor (TPR1-VS1-300, Taiatsu Techno Corp., Tokyo, Japan) [34] that could withstand pressures up to 20 MPa, and then they were dissolved and dispersed in D 2 O (100 cm 3 , 5.54 mol)/2-PrOH (100 cm 3 , 1.31 mol). The mixture was degassed with argon and heated at 140°C under stirring in an aluminum bead bath for 48 h. After cooling to room temperature (23 ± 3°C), the residue was filtered through Celite to remove Pd/C and Rh/C and was washed at least twice with ethanol (50 cm 3 ). The remaining solvent was evaporated under reduced pressure, and a light-yellow oil and white precipitate were obtained for both THMA and DBMA. This kind of precipitate is not generally observed in other similar deuterations. 1 H NMR and X-ray fluorescence measurements (Supplementary Information) showed that the precipitate consisted of the malonamide and Rh. Therefore, this unexpected byproduct appeared to be related to the specific interactions between the malonamides and Rh. The resulting oil was redissolved in a tiny amount of chloroform and purified by column chromatography using chloroform as an eluent. The solvent was evaporated under reduced pressure, and the desired deuterated malonamides were obtained as a transparent yellow liquid. The compounds were identified by 1 H NMR, 2 H NMR, 13 C NMR, infrared (IR) spectra, and electrospray ionization-mass spectrometry (ESI-MS). The ESI-MS 1 H, 2 H, and 13 C NMR spectra were recorded at 400, 61.4, and 100 MHz, respectively using a 400 MHz NMR spectrometer (JMTC-400/54/JJ/YH, JEOL Ltd., Tokyo, Japan). The IR spectra were measured using an IR spectrometer (FT/ IR-6100All, JASCO Corporation, Tokyo, Japan) with a dedicated sample card cell (ST-IR Card Type 1, Thermo Fisher Scientific, Inc., Waltham, MA). The ESI-MS spectra were recorded on aESI-MS mass spectrometer (EXTREMA -MS-100P, JASCO Corporation). The deuteration rate of malonamides was evaluated from the integral value of the 1 H NMR signals arising from the deuterated malonamide and the 1,4-dioxane internal standard. Each deuterated malonamide (50-60 mg) and 1,4-dioxane (about 10 mg), which were precisely measured and placed in the same vial together for each tare, were dissolved in CDCl 3 (0.6 cm 3 ) containing tetramethylsilane (TMS; internal standard for chemical shift) leading to comparable 1 H NMR signal-to-noise ratios. THMA-d n , 1

Metal ion extraction procedure
The extraction experiments were performed using the batch method. The extracting organic phases were prepared by dissolving each malonamide (THMA-h 54 , DBMA-h 54 THMA-d n , and DBMA-d n ) in toluene to reach a concentration of 0.3 M. The aqueous phase was prepared by mixing a 1000 ppm metal cation stock solution, containing Pd(II), La(III), Nd(III), Eu(III), Dy(III), Fe(III), Co(II), Ni(II), Cu(II), and Zn(II), with 15.6 M HNO 3 solution to obtain a 0.5 mM metal cation and 3 M HNO 3 solution. Equal volumes of both phases were mixed and shaken (1800 rpm) at 20°C for 120 min. The temperature was maintained during phase equilibration using a temperaturecontrolled air bath (FMC-100, EYELA, Tokyo, Japan). After phase separation by centrifugation at 5000 rpm for 5 min, the metal ion concentration was measured by inductively coupled plasma-optical emission spectrometry (ICP-OES; Agilent 5800, Agilent Technologies, Santa Clara, CA). For ICP-OES measurements, the aqueous phases before and after extraction were diluted with a 0.5 M HNO 3 solution containing 10 ppm Y internal standard. The metal ion concentration was determined using a calibration curve of 0.1-100 ppm metal ions. The relative standard deviations in all ICP-OES measurements were less than 5%. The extraction yield, E, of the metal ions was calculated by where subscripts in and eq denote the initial and equilibrium conditions, respectively. All extraction experiments were repeated three times, and the standard errors of the E value were less than 5%.

SANS measurements
SANS measurements were performed with the SANS-J diffractometer installed at Japan Research Reactor-3 (JRR-3; 20 MW), Japan Atomic Energy Agency (JAEA), Tokai, Japan. [35,36] With a velocity selector, cold neutrons were monochromatized to a wavelength, λ, of 0.65 nm with a wavelength distribution, Δλ/λ, of 0.15. The incident beam was defined using a 20 × 20 mm aperture 10 m upstream of the samples and an aperture 15 mm in diameter at the sample position. The scattered neutrons were detected with two twodimensional position-sensitive 3 He detectors: one was 650 × 680 mm (length × width) and consisted of 95-tube 3 He detectors 8 mm in diameter and the other was 650 × 385 mm (length × width) and consisted of 48-tube 3 He detectors 8 mm in diameter. The two sample-to-detector distances, L, of the larger detector were set to 4.0 and 2.0 m along the beam path of the incident neutrons, whereas that of the smaller detector was set to 0.96 m, where the scattering angle 2θ was set as 6° for L = 4.0 m and 13.4° for L = 2.0 m to observe the scattered neutrons over a wide q region. Here q = 4πsinθ/λ is the magnitude of the scattering vector. These configurations of SANS-J allowed us to cover a q range of 0.07 < q (nm −1 ) < 4. The scattering data recorded with the two-dimensional detectors were circularly averaged. The scattering intensity distribution, corrected for counting efficiency, instrumental background, and air scattering, was plotted as a function of q. The intensity scale was converted to the absolute intensity units (cm −1 ) by using a secondary standard of an irradiated Al plate. Cell scattering was subtracted from that of samples by considering the transmittance of the neutrons in each sample. The scattered intensity distribution obtained is designated as I(q) hereafter. Incoherent scattering, estimated from the theory proposed by Shibayama et al., [37] was subtracted from the SANS profiles of samples (a) and (c) (described below). SANS experiments were carried out with DBMA in n-heptane to demonstrate the advantages of contrast matching, [25] which is a well-defined unique technique in neutron scattering.

Scattering length density
The scattering length density (SLDs; ρ) of extractant molecules for each deuteration rate was calculated by where b i and V is the coherent neutron scattering length of the atomic nuclei and the molecular volume, respectively. [25] Here V is given by where M and d are molecular weight and density of the extractant molecule, respectively. N A is Avogadro's number.

Results and discussion
To optimize the deuteration reaction conditions, the effects of the reaction temperature and reagent amount on the deuteration rate and yield were examined. Table 1 lists the reagent amounts, heating temperatures, deuteration rate, and yields for the deuteration of THMA-h 54 and DBMA-h 54 . At a reaction temperature of 180°C, no THMA-d n was obtained (entry 1, Table 1). At 180°C, an increase in the internal pressure of the stainless-steel reactor from 0.1 MPa to 0.3 MPa was observed, which caused the decomposition of THMA during the reaction. Consequently, to avoid decomposition, the reaction temperature was set to 140°C for the other reactions (entries 2-9). The effect of the D 2 O to 2-PrOH volume ratio was then investigated (entries 2, 3, 6, and 7). A higher deuteration rate was obtained at a ratio of 4 (entries 2 and 6) than at a ratio of 1 (entries 3 and 7). For THMA-h 54 (entries 3-5) and DBMA-h 54 (entries 7-9), the initial solvent volume ratio was kept constant and equal to 1, and the solvent to catalyst (Pd/C and Rh/C) ratio was 0.5 mol·g −1 , but the initial reaction conditions were scaled up, increasing with the entry number. The total volumes for entries 5 and 9 were 8-10 times larger than those for entries 3 and 7. Increasing the reaction scale decreased the malonamide deuteration rate from 65.3% to 33.6% for THMA-d n and from 58.9% to 28.8% for DBMA-d n . This may be attributed to the inhomogeneous dispersion of Pd/C and Rh/C powder over the whole volume of the mixture, despite mechanical stirring. Macroscopic aggregates of Pd/C and Rh/C were observed in the reaction systems and contained the majority of the catalyst. Thus, as the quantity of catalyst increased, increasingly large aggregates were formed, thereby decreasing their specific surface area and their reactivity, resulting in a lower deuteration rate. However, the yield of deuterated malonamides did not depend on the reaction scale, and it remained above 60% for THMA-d n and 50% for DBMA-d n . Figure 2 shows the SLD values of THMA-d n and DBMA-d n plotted as a function of the deuteration rates (entries 2-9, Table 1), as well as those of DBMA-h 54 , THMA-h 54 , DBMA-d 54 , and THMA-d 54 . Controlling the deuteration rate of the malonamides via the initial feed amounts allowed the neutron SLDs of the malonamides to be optimized.  Table 1.   Figures 3 and 4 show the 1 H NMR spectra for THMA and DBMA, respectively, before and after the deuteration reaction (top (a) and middle (b) charts, respectively) and 2 H NMR spectra after the deuteration reaction (bottom (c) charts). The chemical structures shown at the top of the figures show the deuteration rate of each 1 H atom. All spectroscopic data, i.e., 1 H, 2 H, and 13 C NMR, and IR and ESI-MS, for each deuterated malonamide are summarized in the Supplementary Information. For the deuteration of THMA-h 54 , the peaks that arose from the 1 H atoms of THMA-d n were observed at the same chemical shift as THMA-h 54 (Figures 3a,b). The deuteration rate of THMA-d n was evaluated from the ratio of the integral value of the peaks between the 1,4-dioxane internal standard and THMA-d n . The deuteration rates of the 1 H atoms in THMA-d n ranged from 31.9% to 40.3% for entry 4, and the average deuteration rate of THMA-d n overall was 34.9% (Figure 3). This indicated that all hydrogen positions underwent 1 H/ 2 H exchange during the deuteration reactions of THMA-h 54 . However, the preferential positions for atom exchange were the terminal and central 1 H atoms, as indicated by the higher deuteration rates at the no.1 and no.5 positions (≈40%) compared with the other positions. For the deuteration of DBMA, the chemical shifts of all peaks arising from the DBMA hydrogen atoms were the same for the non-deuterated and deuterated molecules (Figures 4a,b), as well as the case of THMA. The chemical structure of DBMA with the average deuteration rate values for each hydrogen, evaluated from the ratios of the integral value of the NMR peaks between 1,4-dioxane and DBMA-d n , is shown at the top of Figure 4. The deuteration rate of the hydrogens of DBMA-d n ranged from 38.6% to 70.8% (entry 8, Table 1), indicating different behaviors in the deuteration reactions of THMA and DBMA. The THMA-d n average deuteration rate was 34.9%, whereas the average deuteration rate of DBMA-d n was 45.8%. The deuteration rate of the 1 H in the no. 7 positions was particularly high (70.8%) compared with the other positions. Several stereochemical and chemical effects can explain these differences. Modutlwa et al. reported that Pd and Rh may coordinate with organic compounds via amide, amine, and carboxylic acid functional groups during the deuteration reaction. [31,38,39] Thus, specific 1 H atoms close to these functional groups may get closer to the active Pd and Rh, leading to facile 1 H/ 2 H exchange through the neighboring effect. Consequently, the distance between a hydrogen atom on the malonamide and the Pd/Rh in the single complex may affect the deuteration. Additionally, the alkyl chain steric structure of the malonamide is also related to the distance between the Pd/Rh and the hydrogens; 1 H atoms on terminal methyl groups are more accessible and can easily undergo 1 H/ 2 H exchange. The combination of these effects may explain the differences in deuteration rates at different hydrogen positions for THMA and DBMA.
The average deuteration rate at the position no. 2 of DBMA is ca. 42% as shown in Figure 4. Here attention needs to be paid to the distribution of the deuteration rate at the position no. 2 when planning in neutron scattering experiments. The distribution of the deuteration rate in the long alkyl chain (tetradecyl group) of DBMA may produces an inhomogeneous SLD profile for neutrons across the single DBMA molecule. The large distribution rate tends to cause a difficulty for the success of the contrast-variation SANS and NR experiments. Although it is practically impossible to evaluate the distribution rate from 1 H and 2 H NMR spectra, we speculate that the deuteration rate in the tetradecyl group agrees within 4% by taking into account the given deuteration rate at the positions no. 1-3 of DBMA (see Figure 4). Additionally, it is generally known that the deuteration reaction used in this study, i.e., 1 H/ 2 H exchange method using Pd/C and Rh/C catalysts in a D 2 O/ 2-PrOH mixture, does not provide a large distribution of the deuteration rate within an alkyl chain. [29,31] Therefore, DBMA-d n obtained here is available for the contrast-variation SANS and NR experiments. Figure 5 shows the IR spectra of THMA and DBMA before and after the deuteration reaction, corresponding to entry 4 and 8, respectively. The most important feature of the IR spectra of both THMA-d n and DBMA-d n was the peak at 2100-2200 cm −1 originating from C-2 H stretching vibrations (υ C-2H ). This is directly related to the 1 H/ 2 H exchange effect because the increase in atomic mass causes a shift in the frequency of the chemical bond toward a lower wavenumber. [40] Moreover, a peak corresponding to the C-2 H bending vibration (δ C-2H ) was observed at 1300-1430 cm −1 . Simultaneously, C -H stretching and bending vibration peaks were also observed at 2850-2960 cm −1 (υ C-H ) and 1400-1465 cm −1 (δ C-H ), respectively. This is because the deuteration of THMA-d n and DBMA-d n was not total (deuteration rates of 34.9% for entry 4 and 45.8% for entry 8, respectively). In addition, no change in the C=O stretching vibration peak (υ C=O ) was observed (1600-1700 cm −1 ), suggesting that neither THMA-d n nor DBMA-d n showed changes around the C=O group, which is the main group that coordinates with the metal ions. Therefore, the extraction properties of both THMA-d n and DBMA-d n after deuteration were expected to remain unchanged.
Solvent extraction experiments with non-deuterated and deuterated malonamides (entries 4 and 8, Table 1) in toluene were performed to highlight the effect of deuteration on extraction yield, E. Table 2 Table 1) and (b) DBMA-h 54 and DBMAd n (entry 8, Table 1).  Co, Ni, Cu, and Zn). For the non-deuterated malonamides, THMA-h 54 and DBMA-h 54 , the E values were consistent with previous reports. [21,33] Comparing non-deuterated and deuterated malonamides indicated that the presence of deuterium atoms in the malonamides did not affect the extraction efficiency. The difference in E was lower than 3% for all metal ions examined among the extractants, except for Pd(II) with DBMA, where the difference was 4.7%, although this was close to the error margin of E determination, estimated to be 5%. This result suggests that deuteration had no substantial effect on the extraction equilibria. We concluded that the deuterated malonamides obtained by our method could be used in a wide variety of fundamental studies with, for example, neutron scattering techniques or NMR. SANS measurements were performed using DBMA-d 25 (entry 8, Table 1) to demonstrate the advantage of the deuterated malonamides. Figure 6 shows the SANS profiles in absolute units obtained for the sample solutions (a) to (d), where the details of the sample solutions have been described in the Experimental section. DBMA molecules form associates in an aliphatic solvent due to dipole-dipole interactions among the polar head groups and hydrogen bonding between the carbonyl oxygens and the hydrogens bonded to the amide alpha carbons. [8,41,42] The SANS profiles of (a) 0. factor of the DBMA associates. At q > 1.0 nm −1 , the scattering intensity started to decrease according to the power law scattering, I(q) ~ q −1 . The characteristic q position, which starts to decrease in intensity at this position, q c , (indicated by thick arrows), depends on the average size of the associates, because of q c ~1/R. The average radius, R, was evaluated as 1.3 nm for both DBMA-h 54 and DBMA-d 25 by using Guinier's law [25] assuming that shape of the associates was spherical. A Guinier plot, i.e., lnI(q) vs. q 2 , gives linear curves for qR g <1 (R g is the average radius of gyration), enabling the determination of R and I(q = 0) from the slope and intercept, respectively. Note that R 2 = (5/3)R g 2 . The value of I(q = 0) is generally given by the product of the solute volume fraction, φ, the volume of the solute (scatterer), V s , and the square of difference between the solute and solvent SLD, (ρ solutes − ρ solvent ) 2 , In samples (a) and (c), φ and V s are same, whereas ρ solutes and ρ solvent correspond to ρ DBMA-h54 and ρ n-heptane-d16 for (a) and ρ DBMA-d25 and ρ n-heptane-d16 for (c), respectively. ρ DBMA-h54 ( = 0.104 × 10 10 cm −2 ), ρ DBMA-d25 ( = 3.47 × 10 10 cm −2 ), and ρ n-heptane-d16 ( = 6.18 × 10 10 cm −2 ) are the SLDs of DBMA-h 54 , DBMA-d 25 , and n-heptane-d 16 , respectively. Thus, the larger I(q = 0) value for sample (a) than for sample (c) is attributed to the difference between ρ solutes and ρ solvent . In the case of a conventional SANS measurement for investigating the malonamide associates in a deuterated solvent, it is thus better to use non-deuterated malonamide compared to the deuterated ones in order to obtain the higher scattering intensity.
In the SANS experiments, contrast matching is a unique technique, allowing the scattering contributions from a specific component to be detected in isolation. Similar to Figure 2, the SLD value of the n-heptaned 16 /n-heptane-h 16 mixture changes linearly as a function of the volume ratio from ρ n-heptane-d16 (= −0.547 × 10 10 cm −2 ) to ρ n-heptane-d16 . Therefore, ρ DBMA-h54 and ρ DBMA-d25 agree with the SLD of n-heptane-d 16 /n-heptaneh 16 = 0.096/0.904 and 0.597/0.403 (v/v), respectively. In these cases, (ρ solutes − ρ solvent ) 2 should be zero, and hence, the disappearance of the small-angle scattering contribution of the DBMA associates should be observed on the scattering profiles. SANS profiles obtained for these sample solutions ((b), filled circles) and ((d), open circles) changed dramatically from (a) and (c) and showed an almost constant scattering intensity as a function of q. The constant small-angle scattering intensities in (b) and (d) are attributed to incoherent scattering, which generally acts as noise in SANS experiments. 1 H atom possesses a huge incoherent scattering cross section (80.26 barn; 1 barn = 100 fm 2 ); thus, sample (b) shows the highest noise level because it has a higher 1 H content than sample (d). Increasing the deuteration rate of the malonamide molecule decreases the 1 H content in the solvent mixture at the contrast matching point (ρ solutes = ρ solvent ). Accordingly, using a deuterated extractant, such as DBMA-d 25 , provides a lower background intensity. The lower incoherent scattering (noise) level may help to observe the scattering contribution of the hydrophilic species, such as metal ions, water, and acid molecules in the organic phase, which are likely to be hidden by the scattering contribution of the extractants in a conventional SANS measurement. This is one of the main advantages of using a deuterated extractant in a SANS experiment. Additionally, deuterated extractants may have another advantage in SANS measurements. The SLDs of two non-deuterated extractants, such as THMA-h 54 and DBMAh 54 , or an additional modifier, such as an alcohol, tend to be similar. Labelling one molecule with the present deuteration procedure to increase its SLD could help to distinguish the scattering contribution of the coextractant or modifier from that of the malonamide by using contrast matching method. [43] Conclusion Direct deuteration (post-synthetic) of two malonamides, THMA and DBMA, was performed under mild conditions using Pd/C and Rh/C as catalysts. To our knowledge, this is the first report that post-synthetic deuteration methods have been applied to malonamide derivative extractants. We demonstrated that the deuteration rate could be controlled by changing the initial feed amount, and the rates reached over 79% for THMA and 73% for DBMA. The deuteration rate of each 1 H atom in the malonamides varied according to its position in relation to the functional groups. Classical deuteration methods starting from deuterated raw materials are more costly and less efficient, but allow better control of deuterated positions and deuteration rates. The direct deuteration method used in this study has a major advantage, in particular, for malonamides because classical synthesis schemes starting from deuterated reagents often require multiple steps, resulting in low yields. [32] The deuteration rates of each hydrogen atom were explained by the combination of chemical and stereochemical effects related to the distance from the catalysts (e.g., neighboring effect) and the position in the molecule (e.g., accessibility and lability/acidity). The efficiency of the deuterated malonamides solubilized in toluene for metal ion extraction was investigated in typical solvent extraction experiments. The extraction efficiencies of malonamide molecules before and after the deuteration were consistent, with a maximum difference of 5% in extraction yield. To our knowledge, these isotopic effects related to the extractant have not been studied and may require further investigation. The deuterated extractants are expected to be invaluable in SANS, NR, and NMR experiments, and thus are expected to contribute to fundamental research on solvent extraction systems. The deuteration method reported in this study could be generalized beyond malonamides to a wide variety of extractants, e.g., N,N,N′,N′-tetraoctyl diglycolamide (TODGA), [44,45] N,N,N′,N′,N′′,N′′hexaoctylnitrilotriacetamide (HONTA), [44,46] and N,N-dioctylbutylamide (DOBA). [47]