Pierre Picot

Tobias Lange

Fabienne Testard

Frederic Gobeaux

Antoine Thill

Evidence and importance of intermediate nanostructures in the journey from molecular precursors to allophane and imogolite nanocrystals

à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

The alteration of volcanic minerals and glasses in slightly acidic conditions leads to the formation of imogolite and allophane [START_REF] Levard | Geology and mineralogy of imogolite-type materials[END_REF]. Imogolite is a tubular nanocrystal with a monodisperse diameter and a thin wall thickness of 5 Å. Its composition from the outside to the inside surface reads (HO) 3 Al 2 O 3 SiOH. Allophane has a less well-defined composition with a Si/Al ratio ranging from 0.5 to 1. A common characteristic of allophane is to have a hollow spherical shape with a wall thickness of also about 5 Å. In slightly acidic environments, Al and Si cations released from the primary minerals (quartz, feldspar, plagioclase, muscovite, biotite, amphibole, pyroxene. . . ) alteration form spontaneously hydroxyaluminosilicate (HAS) that have a very low solubility [START_REF] Schneider | The solubility of an hydroxyaluminosilicate[END_REF][START_REF] Exley | Reflections upon and recent insight into the mechanism of formation of hydroxyaluminosilicates and the therapeutic potential of silicic acid[END_REF]. It has been proposed to classify these resulting products into two types by their local structure, called HAS A and HAS B , depending on the concentration and ratio between Al and Si [START_REF] Exley | Reflections upon and recent insight into the mechanism of formation of hydroxyaluminosilicates and the therapeutic potential of silicic acid[END_REF]. For Si/Al < 1 mainly HAS A precipitates. Filterable HAS A solids are dominated by silicon coordinated through three Si -O -Al bonds (Q 0 (3Al)). Such coordination is typical of the so-called Imogolite Local Structure (ILS). Its very specific narrow 29 Si NMR signal at -79 ppm has been used to identify imogolite in soils [START_REF] Barron | Detection of imogolite in soils using solid state 29si nmr[END_REF]. HAS A compounds do not necessarily have the exact same local-structure as imogolite or allophane but we can hypothesize that HAS A precipitates can lead to an ILS through internal reorganization [START_REF] Yucelen | Formation of single-walled aluminosilicate nanotubes from molecular precursors and curved nanoscale intermediates[END_REF][START_REF] Thill | Nanozised tubular clay minerals; halloysite and imogolite, volume 7 of Developments in Clay Science, chapter From molecular precursor to imogolite nanotubes[END_REF]. Indeed, HAS A contains only octahedric coordinated aluminum Al V I associated with tetrahedric Si IV with the same Si/Al ratio as imogolite. The most thermodynamically stable structure for the smallest HAS A polycation consists of two Al V I octahedra that are edge bonded by two Al -µ 2 OH bonds and a Si IV tetrahedron with two Si -O -Al bonds [START_REF] Beardmore | What is the mechanism of formation of hydroxyaluminosilicates[END_REF]. The identification of nanostructured precipitates as an intermediate stage of imogolite formation has been very early recognized and the term proto-imogolite was used to describe them. For example, based on IR and diffraction data, Farmer et al. said in 1979 "Similarly, proto-imogolite can be presumed to incorporate orthosilicate groups attached to fragments of gibbsite-like sheets of aluminum hydroxides" [START_REF] Farmer | Characterization of the chemical structures of natural and synthetic aluminosilicate gels and sols by infrared spectroscopy[END_REF]. Proto-imogolite intermediates in the precipitation of aluminosilicate have not been the subject of many publications [START_REF] Lenhardt | Synthesis of short-range ordered aluminosilicates at ambient conditions[END_REF]. The low concentration of most of the standard imogolite synthesis protocols, their very small size and their high reactivity probably hinder their thorough characterization. Mukherjee et al. [START_REF] Mukherjee | Phenomenology of the growth of single-walled aluminosilicate and aluminogermanate nanotubes of precise dimensions[END_REF] and later Levard et al. [START_REF] Levard | Formation and growth mechanisms of imogolite-like aluminogermanate nanotubes[END_REF] have studied the formation of germanium based imogolite nanotubes and both observed that initial nanometric objects are also involved in the growth process. Mukherjee et al. initially considered these nanostructures as amorphous nanoparticles. Later, it has been recognized that, as for silicon-based imogolite, they already share the same local structure as the final nanotubes. Levard et al. demonstrated that the synthesis of germanium based imogolite is possible even at high concentration with a few days of growth [START_REF] Levard | Synthesis of large quantities of single-walled aluminogermanate nanotube[END_REF]. Based on the results of a combination of techniques (ICP, EXAFS, DLS, SAXS and cryo-TEM), they proposed a tile-like nanostructure that has the same local structure as the final nanotubes with a size of about 5 nm [START_REF] Levard | Formation and growth mechanisms of imogolite-like aluminogermanate nanotubes[END_REF]. Thill et al. showed the first cryo-TEM images of the proto-imogolite which tend to confirm such a tile-shape [START_REF] Thill | Nanozised tubular clay minerals; halloysite and imogolite, volume 7 of Developments in Clay Science, chapter From molecular precursor to imogolite nanotubes[END_REF][START_REF] Thill | Physico-chemical control over the single-or doublewall structure of aluminogermanate imogolite-like nanotubes[END_REF]. Yucelen et al. have studied the shape and the role of proto-imogolite in the formation of imogolite nanotubes of various diameters using a combination of NMR and ESI-MS techniques [START_REF] Yucelen | Formation of single-walled aluminosilicate nanotubes from molecular precursors and curved nanoscale intermediates[END_REF]. They demonstrate that anions are coordinated to hydroxyaluminosilicate curved polycations. DFT calculations on such tile-shaped nanostructures revealed that the type of anion attached to proto-imogolite modifies their curvature. Furthermore, they suggested that the type of acid used in the precipitation of imogolite nanotubes from aluminum and silicon alkoxide precursors controls the diameter of the final nanotubes in the same way as the curvature of proto-imogolite [START_REF] Yucelen | Shaping single-walled metal oxide nanotubes from precursors of controlled curvature[END_REF]. This seems to be in favor of the self-assembly process of the imogolite nanotubes already hypothesized by Thill and Yucelen in imogolite growth kinetics models [START_REF] Maillet | Growth kinetic of single and double-walled aluminogermanate imogolite-like nanotubes: An experimental and modeling approach[END_REF][START_REF] Yucelen | A generalized kinetic model for the formation and growth of single-walled metal oxide nanotubes[END_REF]. The formation of imogolite from proto-imogolite is considered a nucleation event [START_REF] Farmer | Synthetic imogolite: properties, synthesis, and possible applications[END_REF][START_REF] Bursill | Imogolite: An aluminosilicate nanotube material[END_REF][START_REF] Wilson | Tetrahedral rehydration during imogolite formation[END_REF]. It is generally performed at elevated temperature for several days. However, the origin and characteristics of the energy barrier associated with the nucleation event from proto-imogolite to imogolite or allophane have never been discussed to our knowledge. Using adsorption on mica surfaces at different stages of the synthesis process, Du et al. were able to observe the transition from protoimogolite to allophane and imogolite [START_REF] Du | Insights into the formation mechanism of imogolite from a full-range observation of its sol-gel growth[END_REF]. At a very early stage, the mica surface is covered with a layer of nanoparticles with a height of less than one nanometer. It has been interpreted as proto-imogolites adsorbed flat on the mica surface. Allophanes are observed in the initial growth stage as spherical objects with a height of more than 4 nm. Finally, nanotubes are observed with a typical elongated shape and height of 2 nm. The term open-ILS is introduced to refer to proto-imogolite before the growth stage. This notation is well suited to describe the tile shape of proto-imogolite being too small to close in the form of a nanotube or a nanosphere. In this line of thought, allophane and imogolite would be closed-ILSs that result from the assembly of several open-ILSs or their growth until they are large enough to close. The nucleation barrier can be hypothesized to occur in the transition from open-ILS to closed-ILS. It is reasonable to think that such a nucleation event can lead to several nanocrystal polymorphs which are allophanes (sphere), imogolites (nanotube) of various chiralities or less well-defined closed-ILS nanostructures or aggregates [START_REF] Thill | Physico-chemical control over the single-or doublewall structure of aluminogermanate imogolite-like nanotubes[END_REF][START_REF] Du | Insights into the formation mechanism of imogolite from a full-range observation of its sol-gel growth[END_REF][START_REF] Belloni | Why a 1:1 2D structure tend to roll? A thermodynalic perspective[END_REF][START_REF] Monet | Structural resolution of inorganic nanotubes with complex stoichiometry[END_REF]. Upon successful synthesis, imogolite is obtained in the form of very well dispersed perfectly transparent suspensions. Any turbidity would be due to the formation of large crystals of aluminum hydroxides (Gibbsite or Boehmite). These transparent dispersions however still contain non-tubular objects in various proportions.

Generally, imogolites are recovered by centrifugation after adding a concentrated salt solution or after increasing the pH [START_REF] Farmer | Synthetic imogolite: properties, synthesis, and possible applications[END_REF]. The result of this pH adjustment or addition of salt is the formation of nanotube bundles and aggregates that are then easily separated from water by centrifugation in the form of a concentrated gel. The relative height of the gel in the centrifuge tube in standard conditions was used by Farmer to compare the imogolite yield of different synthesis routes [START_REF] Farmer | Synthetic imogolite: properties, synthesis, and possible applications[END_REF], even though non-tubular nanostructures also take part in the formation of this gel. After separation, the gel is then redispersed with an acid and eventually dialyzed. The drawback of this method is that the aggregation/gelation steps lead to the formation of imogolite bundles that is not totally reversible. In addition, the effect of these steps on other closed-ILS nanostructures is not benign. Indeed, to eliminate the small non-tubular particles, some authors use chemical attack steps. It is known that acidification and other chemical digestion procedures are effective to get rid of non-tubular poorly crystallized products [START_REF] Wada | High resolution electron micrographs of imogolite[END_REF]. Therefore, authors using an acid redispersion stage of the gel are, at least in part, getting rid of some of the smallest non-tubular nanoparticles. When the proportion of non-tubular nanoparticles is huge, such a chemical purification step is very effective to retrieve nanotubes [START_REF] Koenderink | On the synthesis of colloidal imogolite fibers[END_REF][START_REF] Wada | Imogolite synthesis at 25 degree c[END_REF]. However, nothing can be inferred on the proportion and on the role of small closed-ILS nanostructures when such purification techniques have been used. Concentration procedures may be designed to preserve the nanotube dispersion state. For example, imogolite can be retrieved by filtration with a very small membrane cutoff (i.e. 8 -10 kD) [START_REF] Thill | Physico-chemical control over the single-or doublewall structure of aluminogermanate imogolite-like nanotubes[END_REF] or by evaporation [START_REF] Su | Properties of single-walled aluminosilicate nanotube/poly(vinyl alcohol) aqueous dispersions[END_REF]. In these cases, nanotubes and co-existing non-tubular products like allophane or other less welldefined closed-ILS nanostructures are also concentrated without compromising their stability. As no precipitation or acidic redispersion steps are required, resulting products contain well-dispersed nanotubes, but they can also contain a high amount of non-tubular closed-ILS. For such preserved samples, it is very difficult to assess the quantity or even the presence of non-tubular closed-ILS. Measurements by SAXS and IR spectroscopy cannot indicate the presence of non-tubular closed-ILS when their mass fraction is reduced to a few percent. However, at such low mass fraction, cryo-TEM can qualitatively reveal their presence in coexistence with very long nanotubes [START_REF] Yucelen | Shaping single-walled metal oxide nanotubes from precursors of controlled curvature[END_REF][START_REF] Su | Properties of single-walled aluminosilicate nanotube/poly(vinyl alcohol) aqueous dispersions[END_REF][START_REF] Farmer | Synthesis of imogolite: A tubular aluminium silicate polymer[END_REF]. When non-tubular closed-ILSs occur in high proportion, SAXS curves are deformed and their IR spectrum is modified [START_REF] Farmer | Synthetic imogolite: properties, synthesis, and possible applications[END_REF]. Knowing if these non-tubular closed-ILSs remaining after the growth stage are initial non reacted open-ILSs, allophanes or other types of non-tubular closed-ILSs is not yet resolved. Their characterization and quantification are very delicate [START_REF] Farmer | Synthetic imogolite: properties, synthesis, and possible applications[END_REF] even more because, as mentioned previously, the various protocols applied to retrieve the nanotubes may modify their proportion, sometimes intentionally. Recently, it was demonstrated that a size threshold exists in open-ILS for which the curvature changes from sphere-like to tube-like [START_REF] Thill | A mechanism for the sphere/tube shape transition of nanoparticles with an imogolite local structure (imogolite and allophane)[END_REF]. It is therefore important to characterize open-ILS nanostructures before the growth stage especially to compare their average size with the sphere-tube transition threshold. In this article, we illustrate the presence of remaining non-tubular nanostructures (closed-ILS) at the end of the growth stage for several samples by Cryo-TEM and ultrafiltration methods. To better understand their origin and role, we have explored the early stages of precipitation of Al and Si at different concentrations (millimolar and centimolar) and different NaOH injection speeds (fast and slow). Small Angle X-ray Scattering at the SWING beamline of synchrotron Soleil and Raman spectroscopy were used to continuously monitor the co-precipitation of Al and Si for several hours. After a growth stage at 90°C for 5 days, the dispersions were characterized by IR spectroscopy and laboratory SAXS experiments in order to assess the impact of the open-ILS structure on the final morphologies and proportions of closed-ILS.

Experimental

Cryo-TEM

Cryo-TEM observations of various typical samples were conducted at low temperature (-180 °C) on a JEOL 2010 FEG microscope operated at 200 kV. Images were recorded with a Gatan camera. A drop of the solution was deposited on a copper grid covered with a holey carbon film (Quantifoil R2/2) that was previously treated by a plasma glow discharge. Excess liquid on the grid was blotted out with filter paper and the grid was quickly plunged in liquid ethane to form a thin vitreous ice film. The whole process was performed using a Vitrobot apparatus (FEI Company).

Synthesis for synchrotron experiments

Chemicals were purchased from Sigma-Aldrich and used as received. The protocol was adapted for synchrotron SAXS monitoring from the one described by Farmer et al. [START_REF] Farmer | Synthesis of imogolite: A tubular aluminium silicate polymer[END_REF] The predefined volume of tetraethoxysilane (TEOS) needed to reach a Si/Al ratio of 0.55 was stored in a syringe connected to a first syringe pump. On a second syringe pump, the required volume of NaOH solution was prepared to be able to reach a OH/Al ratio of 2. A remote signal sent to the syringe pumps triggered the injection of these volumes to be fed into a 50 mL stirred solution of Al(ClO 4 ) 3 . The first pump injects the TEOS at 50 mL•min -1 . The second pump is programmed to inject 25 mL of NaOH at 50 mL•min -1 (fast injection) or 0.1 mL•min -1 (slow injection). The concentration of aluminum and silicon precursors, start of add time for TEOS and NaOH solutions and injection flowrate for the different syntheses are reported in Table 1. A peristaltic pump circulates the sample in a capillary placed in the X-ray beam. In the synthesis reactor, a pH-meter is continuously monitoring the pH and an optical fiber is used to collect the RAMAN spectrum. At the end of the SAXS experiment, the suspension is collected. The SAXS signal is measured again after at least 10 hours. The solution is then kept for five days at 90°C in an oven. Afterward, an 8 -10 kD membrane was used to concentrate the imogolite dispersion up to 10 g•L -1 by ultra-filtration. The final products are measured on a laboratory SAXS apparatus.

Dialysis

Dialysis membranes with a molecular weight cut-off (MWCO) of 8 -10 kD were purchased from Spectrumlabs. The membranes were soaked in deionized water for at least 30 min and abundantly rinsed before use. After filling them with the imogolite dispersion, they were closed with clips and immersed into deionized water. The water was renewed every 24 h for five days.

IR spectroscopy

An aliquot of the final products has been dried and KBr pellets were prepared by compressing approximately 1 mg of sample dispersed in 100 mg of KBr. FTIR spectra (200 scans) were collected in transmission from 4000 to 400 cm -1 with a resolution of 4 cm -1 (Vertex 70, Bruker). All spectra were treated using OPUS software and subtracted from KBr. The resulting curves were corrected using OPUS tools (water and CO 2 compensation, baseline correction).

Small Angle X-ray Scattering

Synchrotron SAXS experiments were conducted in air at the SWING line in SOLEIL Synchrotron equipped with an AVIEX170170 CDD detector, a monochromatic beam (λ = 0.827 Å) and a flux of 10 12 photon•s -1 . The detector count was normalized by the direct beam and the calibration was verified with water. Standard procedures were applied using the Foxtrot software (version 3.3.4) to subtract background scattering and to normalize the intensities. For millimolar conditions, a measurement of one second is made every 30 seconds. For the centimolar condition, several loops of 255 measurements of one second are acquired with 0.5 s of dead time between measurements. Lab Small Angle X-ray Scattering (SAXS) experiments were acquired under vacuum with a Xeuss 2.0 apparatus (Xenocs) equipped with a Pilatus3 R 1M detector (Dectris). The intensity is plotted against the scattering vector q = 4π • sin(θ) • λ -1 , with λ as the wavelength (0.1542 nm) and 2θ as the scattering angle. The sample-to-detector distance can be adjusted (used distances were 42.3; 53.7; 119.4 cm) and was calibrated with tetradecanol. The detector count was normalized by the direct beam and the calibration was verified with Lupolen. Standard procedures were applied using the open-source pySAXS software to subtract background scattering and to normalize the intensities. Samples were sealed in glass capillaries (diameter 1.5 mm, wall thickness 0.1 mm, WJM-Glas) or in Kapton capillaries (diameter 1.506 mm, wall thickness 41.9 µm, MicroLumen). Each sample was measured for one hour.

Raman

Raman data are recorded using the RXN1-785 Raman spectrometer from Kaiser Optical Systems, Inc. (KOSI) equipped with a near-IR laser diode working at 785 nm as excitation light, and with a CCD detector for providing fast and simultaneous full spectral collection of Raman data from 50 to 3450 cm -1 . The laser excitation is obtained in the sample using a remote probe head. The probe head is equipped with an immersion optic with a long fixed focal length (3 mm). The transmitted laser power at the sample position is 50 mW. A second optical fiber is used for the collection of the scattered Raman signals. One spectrum is recorded every 60 s in the cycle mode available with the HoloReact software developed by KOSI. This spectrum corresponds to ten spectra recorded with an integration time of 1 s and averaged.

Results and Discussion

Evidence of open-ILS and closed-ILS nanostructures

Very few direct observations of open-ILS before heat treatment are available in the literature [START_REF] Thill | Physico-chemical control over the single-or doublewall structure of aluminogermanate imogolite-like nanotubes[END_REF]. Only cryo-TEM observations enable the acquisition of unbiased images of non-tubular nano-objects during imogolite or allophane synthesis. Figure 1 shows several typical high-resolution cryo-TEM pictures of various samples. Figure 1A is the resulting suspension obtained after a growth stage at high temperature following a similar recipe as the one used by Du et al. for allophane synthesis [START_REF] Du | Structure of allophanes with varied si/al molar ratios and implications to their differentiation on mars[END_REF]. In this sample, all nano-objects are non-tubular. They consist of a mixture of closed hollow spherules (allophane) and tile-like curved opened objects (open-ILS) isolated, aggregated or stacked. An electrostatic interaction exists between protoimogolites due to the positively charged external (concave) surface and negatively charged internal (convex) surface [START_REF] Arancibia-Miranda | Use of isoelectric point and ph to evaluate the synthesis of a nanotubular aluminosilicate[END_REF]. A nice illustration of the existence of this attraction is obtained during the formation of Double-Walled nanotubes discovered by Maillet et al. in the case of germanium-based imogolite [START_REF] Thill | Physico-chemical control over the single-or doublewall structure of aluminogermanate imogolite-like nanotubes[END_REF][START_REF] Maillet | Evidence of double-walled al-ge imogolite-like nanotubes. a cryo-tem and saxs investigation[END_REF]. This attraction is active only for open-ILS nanostructures. In this case, the internal surface composed of Si -OH groups is still accessible to the bulk solvent and interaction with other surfaces is still possible. Once closed-ILS are obtained in the form of a nanotube, a nanosphere or a less well-defined nanostructure, mainly the external (concave) surface is able to interact, and repulsive electrostatic interactions dominate. Figure 1B illustrates the morphology of nanostructures in Figure 1: Cryo-TEM pictures of various products illustrating the shape of protoimogolites and their coexistence with imogolite and allophane. A) and B) allophane syntheses C) and D) imogolite synthesis at different magnifications. another allophane synthesis observed at a higher dilution. Some of the observed closed-ILSs have a very well-defined circular shape with a diameter of about 4 nm and could correspond to allophane. Others are less obviously completely closed or correspond to closed-ILSs with a less well-defined nanostructure. Figure 1C and D show high-resolution cryo-TEM images of a concentrated imogolite suspension.

The nanotubes have a diameter of about 2.4 nm. The nanotubes tend to have a parallel orientation. This is due to their strong electrostatic repulsion which, helps to trigger a liquid crystal organization at very low concentration [START_REF] Paineau | A liquid-crystalline hexagonal columnar phase in highly-dilute suspensions of imogolite nanotubes[END_REF]. In the space between the nanotubes, non-tubular nanostructures are observed, form aggregates between themselves and with the nanotubes. In Figure 1D, the structure of the non-tubular nanostructures is difficult to assess, but their shape and their interaction seem to correspond to closed-ILS. Finally, just by looking at various cryo-TEM pictures of final products obtained using ultrafiltration concentration and dialysis processes reveals that those non-tubular objects coexist with allophane or imogolite even at the end of the growth stage. This was already observed by Wada [START_REF] Du | Insights into the formation mechanism of imogolite from a full-range observation of its sol-gel growth[END_REF][START_REF] Wada | High resolution electron micrographs of imogolite[END_REF][START_REF] Koenderink | On the synthesis of colloidal imogolite fibers[END_REF]. We hypothesize that these non-tubular nanostructures are closed-ILS having a less well defined shape compared to allophane or imogolite. Their presence after a long lasting growth stage suggests that they that they are not able to evolve toward a tubular or spherical shape.

From molecular precursors to open-ILS

In order to better understand the formation kinetics of the proto-imogolites (open-ILS), we have followed the precipitation of molecular precursors in classical syntheses inspired by Farmer et al. [START_REF] Farmer | Synthesis of imogolite: A tubular aluminium silicate polymer[END_REF] using a combination of Small Angle X-ray Scattering and Raman spectroscopy (see conditions in Table 1). Scattered intensities as a function of the scattering vector q for three kinetic experiments are presented in Figure 2 at different times. In all conditions, the scattered intensity increases during NaOH injection. HO -triggers the replacement of aquo ligands in the first coordination shell of the Al 3+ cations. This favors the formation of polycations through nucleophilic attack by HO -ligands toward another Al 3+ cation. The growth of polycations induces an increase of the scattered intensity. Unlike imogolite or allophane where the monodisperse character induces oscillations in the scattered intensity, at this stage no characteristic size is noticeable. For kinetic 1, the scattered intensity displays a smooth q -2 trend that is typical of 2D objects. This is consistent with the expected scattering from tile shaped open-ILS [START_REF] Levard | Formation and growth mechanisms of imogolite-like aluminogermanate nanotubes[END_REF]. In the case of kinetic 2, the scattered intensity has a higher slope at low angle. This can be the signature of a more three-dimensional structure. This trend is even more pronounced for kinetic 3.

The scattered intensity at the smallest angle is proportional to the average mass of the polycations. To discuss the evolution of this average mass, Figure 3 compares the scattered intensity at the smallest measured angle I qmin normalized by the total concentration C tot = C Al + C Si for the three kinetic experiments. It is observed that for the slow injection rate of NaOH, the value of I qmin increases linearly up to 260 minutes i.e. when NaOH injection ends. The increase in average mass seems thus to be directly controlled by the injected volume of NaOH. After the end of NaOH injection, the signal continues to be monitored and it displays a small decrease of the maximum intensity. For kinetic 1 a total of 5.8 mM has been injected at a constant rate of 0.1 mL•min -1 . During this injection period, the pH barely changed from 4.1 to 4.8 at the end of the NaOH injection (figure S1). Therefore, almost all HO -are consumed to create Al -OH -Al bonds, which drives the growth of the polycations. At the end of the injection, a slight decrease in size (and pH) is probably due to the hydrolysis of some Al -OH -Al bonds releasing protons in the solution. For fast injection rates, I qmin also increases during NaOH injection. For millimolar concentration (kinetic 2), pH increases slightly more than in the case of slow injection with a final pH of 5. In this case also, almost all the hydroxyls are consumed to trigger the growth of Al polycations. The evolution of I qmin after the end of NaOH injection depends on concentration. For kinetic 2, I qmin decreases during the whole measurement session. For kinetic 3, I qmin quickly decreases and reaches a minimum value at about 38 minutes after the end of HO -injection (purple curve in Figure 2). Then, I qmin value increased very slowly while the pH continues to decrease. It is interesting to note that the speed of injection matters to control the maximum size of aluminum polycations. Indeed, with slow injection I qmin /C tot reaches a maximum value of 0.007 cm -1 •L•mol -1 while for kinetic 2 it reaches a twice larger value of 0.014 cm -1 •L•mol -1 . As I qmin /C tot is proportional to the average mass of the polycations, this means that upon fast injection much larger structures are obtained initially and they go through a restructuration and size decrease. On the contrary, for kinetic 1 the final size is smaller which probably means that during the NaOH injection both growth and internal restructuration are active, which limits the final polycations size when the hydrolysis ratio reaches 2. It is interesting to compare the size decrease of the polycations for kinetics 2 and 3 (fast NaOH injection). For both conditions, the same I qmin /C tot is reached after NaOH injection, but the size decrease is much faster for kinetic 3 (high concentration). Raman measurement at millimolar concentration is not meaningful because the concentration is too low to be detected. In the case of kinetic 3 however, it is possible to follow the hydrolysis of TEOS with time. Figure 4A shows Raman spectra at various times after TEOS injection of kinetic 3. At centimolar concentration, it is possible to follow the hydrolysis of TEOS that is injected 5 minutes before the NaOH solution. Indeed, when ethanol is released in solution, a peak is observed at 880 cm -1 (black arrow) [START_REF] Gnado | Raman spectra of oligomeric species obtained by tetraethoxysilane hydrolysis-polycondensation process[END_REF][START_REF] Marino | Micro-raman monitoring of solvent-free teos hydrolysis[END_REF]. In order to follow this hydrolysis, we calculate the area of this peak that is displayed in Figure 4B. The peak area of ethanol starts to exceed the background signal at 40 minutes (i.e. 35 minutes after TEOS injection) and its intensity continues to increase during the whole experiment. Therefore, depolymerization of Al occurs without a measurable signal of hydrolyzed Si. As the signal increases at least up to four times the background level, it means that less than 25% of TEOS has been hydrolyzed during the restructuring of the large Al polycations. It is also interesting to note that no peak at 695 cm -1 (gray arrow) is observed. This peak is characteristic of silicon condensation, i.e. the formation of Si -O -Si bonds [START_REF] Cleach | Ir and raman spectroscopic study of natural lawsonite[END_REF]. It suggests that when TEOS starts to be hydrolyzed, Si reacts first with the Al polycations and is not involved in a measurable self-condensation. The increase in size of the proto-imogolites between 38 minutes to the end of the experiments at 83 minutes and after an aging period of 10 hours may be driven by the slow continuous release of Si(OH) 4 during this period of time. For millimolar concentrations, it can be expected that the hydrolysis reactions occurred much faster due to the higher water to TEOS ratio. In such a case, the Si(OH) 4 species are available to interact with Al polycations earlier in the reaction. In this case, the depolymerization is slower than in the case of kinetic 3. The presence of Si from hydrolyzed TEOS seems to slow down the depolymerization of HA polycations.

Figure 5 compares the scattered intensity of the open-ILS prepared in the three different conditions at the end of aging period of 1 day for the millimolar conditions and 10 hours for the centimolar condition. In millimolar conditions, proto-imogolites have almost exactly the same scattering pattern at the end of aging time no matter the speed of NaOH injection. However, they have followed a very different formation mechanism. At slow NaOH injection rate, the condensation of Al is slowly driven by injection of HO -in a continuous and progressive way. At large injection rate, concentration gradient effects have led initially to a local over-condensation of Al polycations [START_REF] Hsu | Mechanisms of gibbsite crystallization from partially neutralized aluminum chlorure solutions[END_REF][START_REF] Bi | Studies on the mechanism of hydrolysis and polymerization of aluminum salts in aqueous solution: Correlations between the "core-links" model and "cage-like" keggin-al13 model[END_REF]. As soon as NaOH injection stops, the large obtained polycations are restructured and their average size decreases. A pH decrease is also noticed, which tends to prove that this depolymerization goes along with hydrolysis of Al -OH -Al bonds. As already discussed, the presence of Si during the depolymerization of Al polycations in kinetic 2 enables reaching a larger final size than kinetic 3.

In order to obtain a characteristic size of the nano-objects in the dispersion, we calculate a gyration radius R g using the following approximation (Guinier regime):

I(q) ≈ I qmin e -(Rg * q) 2 3 (1)
This approximation holds as q approaches 0 with qR g << 1. The proto-imogolites obtained during kinetic 3 with fast injection are obtained from the depolymerization of initial precipitate of larger size in absence of Si. The final scattered intensity of the polycations appears to be smaller than the one obtained at the end of aging for kinetic 1 and 2. After an aging period of 10 hours, we obtain a gyration radius of R g = 10 Å. Thill et al., using simplified mechanical models, evidenced that the shape of open-ILS depends on their characteristic size [START_REF] Thill | A mechanism for the sphere/tube shape transition of nanoparticles with an imogolite local structure (imogolite and allophane)[END_REF]. It exists a threshold size for which: i) if open-ILS are smaller they have a spherical shape and ii) if they are bigger they have a tubular shape. This sphere/tube transition threshold occurs at about 30 Å, i.e. three times greater than the size of Figure 4: A) Evolution of Raman spectrum with time for the centimolar concentration (kinetic 3) and B) evolution of the area of pic centered at 880 cm -1 . Gray arrow at 695 cm -1 and black one 880 cm -1 are respectively related to Si -O -Si bond and ethanol.

proto-imogolite for kinetic 3. Scattered intensities of kinetics 1 and 2 have not been measured at low enough angles to reach the Guinier regime. But the I qmin /C tot of the proto-imogolite after 24 hours of aging for kinetics 1 and 2 is about three times higher than kinetic 3. Molecular models of open-ILS, already described by Figure 5: Comparison of the scattered intensities normalized by the concentration for three different conditions after an aging period of 1 day for both millimolar concentrations (kinetics 1 and 2) and 10 hours for the centimolar concentration (kinetic 3). The dotted yellow line is a fit of the Guinier regime for kinetic 3 with I qmin = 0.001 cm -1 and R g = 10 Å. Green and gray curves are respectively scattered intensities of small proto-imogolites and a combination of small (25%) and large (75%) proto-imogolites.

Thill et al. [START_REF] Thill | Nanozised tubular clay minerals; halloysite and imogolite, volume 7 of Developments in Clay Science, chapter From molecular precursor to imogolite nanotubes[END_REF], are used to compute the scattered intensity using the Debye formula. A small open-ILS containing 152 atoms is displayed in Figure 5. Its border has an extended length of 20 Å. The computed scattered intensity of this small proto-imogolite compares well with the final scattered intensity of kinetic 3 (green curve) and is in agreement with the Guinier gyration radius of 10 Å. For kinetics 1 and 2, a larger model of 1092 atoms has to be used. This model has an extended border length of 45 Å. The scattered intensity of this model structure alone does not reproduce the trend of the experimental intensity. However, a mixture of 75% of large proto-imogolites and 25% of small proto-imogolites as depicted in Figure 5 is close to the experimental intensity (gray curve). The simulation of the scattered intensity of imogolite local structure molecular models can reproduce the shape of the scattered intensity. The size of the proto-imogolite is much smaller in the case of high concentration. For low concentration, a polydisperse distribution of protoimogolite is probable, with the larger ones having a size above the sphere/tube curvature transition proposed by Thill et al. [START_REF] Thill | Nanozised tubular clay minerals; halloysite and imogolite, volume 7 of Developments in Clay Science, chapter From molecular precursor to imogolite nanotubes[END_REF].

From open-ILS to closed-ILS

The three open-ILS (proto-imogolite) samples were put, for a growth stage, in an oven at 90°C for 5 days. The final products were dialyzed against MilliQ water and analyzed by IR spectroscopy and SAXS. Figure 6 shows the IR spectrum between 1200 and 350 cm -1 of the final dialyzed products for the three kinetic experiments (Table 1). Peaks around 1100 cm -1 and 700 cm -1 are related to perchlorate anions remaining after dialysis. The two products obtained at small concentration display a characteristic splitting of the Si -O stretching band at 990 and 935 cm -1 . This splitting occurs when the SiO 4 tetrahedra is deformed in a tubular structure. Indeed, in this case, the three Si -O -Al bonds are not equivalent and depend on the chirality of the nanotube. Below the sphere/tube transition, the curvature is the same in all directions and thus the Si -O -Al bonds are equivalent and no band splitting occurs. This is the case for kinetic 3 with a single band at 966 cm -1 . This absence of band splitting would be logical before the growth stage with a small R g value below the sphere/tube transition threshold. The fact that no such splitting occurs after the growth stage could be interpreted by the domination of a self-assembly and aggregation mechanism at constant curvature.

Small Angle X-ray Scattering of the three final products has been measured (Figure 7). Both materials issued from kinetics 1 and 2 display a signature of tubular objects that is well described by (14,0) zig-zag or [START_REF] Farmer | Characterization of the chemical structures of natural and synthetic aluminosilicate gels and sols by infrared spectroscopy[END_REF][START_REF] Farmer | Characterization of the chemical structures of natural and synthetic aluminosilicate gels and sols by infrared spectroscopy[END_REF] armchair nanotubes. On the contrary, the sample corresponding to kinetic 3 does not display clear oscillations characteristic of monodisperse imogolite nanotubes. It does not either correspond to the scattering of a hollow sphere. For the nanotube samples, it is possible to compare the experimental low angle scattering curves with calculations considering a mixture of nanotubes and open-ILS. We use a simple equation I mix = (αI tube + (1 -α)I proto ) * K + B g , where α controls the mixture of open-ILS and nanotubes, K is a proportionality parameter to adjust the concentration and B g is the background scattering. Taking into account the mass difference between the nanotube and the open-ILS, the weight fraction of proto-imogolite is directly proportional to α. An adjustment of the model to the experimental data enables the estimation of this mass fraction. For kinetic 1, we find a weight fraction of large proto-imogolite of 9%. For kinetic 2, the proportion increased to 20%. The In the following, we show that it is possible to eliminate part of the non-tubular closed-ILS in a poor imogolite synthesis using a large pore dialysis step. A sample containing more non-tubular nanostructures after the growth stage has been obtained by replacing Al(ClO 4 ) 3 with AlCl 3 for the aluminum precursor. Figure 8 displays the SAXS curves after a growth stage at 90°C for 5 days and dialysis against MilliQ water for two cut-off sizes: 8 kDa (black curve) and 100 kDa (red curve). The intensity of the first minimum around 0.2 Å-1 significantly decreases in the case of the larger pore size dialysis. Using the previous equation, we obtain a weight fraction of proto-imogolite of 50% for 8 kDa and 25% for 100 kDa. Figure S2 shows cryo-TEM images of the corresponding samples (top 8 kDa and bottom 100 kDa). At the 8 kDa cut-off, proto-imogolites are mainly isolated with a characteristic size below 5 nm whereas at the 100 kDa cut-off, no-isolated proto-imogolites are visible. On the contrary, they form aggregates of few tens of nanometers. No such aggregates seems to exist in the sample dialyzed at 8 kDa. SAXS enables a rough estimation of the weight fraction of non-tubular closed-ILS remaining in the dispersion after the growth stage. The shape of the Si -O stretching band in IR could be envisaged for a similar quantification. However, it seems more delicate than SAXS to interpret as part of the non-tubular closed-ILS can be larger than the sphere/tube transition threshold and thus contribute together with nanotubes to the splitting of the Si -O stretching band. Moreover, with this technique, it is also tough to compare synthesis obtained with different aluminum salts due to remaining anions that are infra-red active in this area (i.e. perchlorate anions) and could contribute to the splitting. Through this example, we show that it is possible to reduce the global proportion of non-tubular closed-ILS while maintaining the nanotube dispersion. However, for the moment, no method seems to be available to thoroughly remove non-tubular closed-ILSs while completely preserving both the integrity of the nanotubes and their dispersion state.

Conclusion and outlook

We have followed the early stages of the formation of hydroxyaluminosilicate nanostructures in an acidic environment and at a Si/Al ratio of 0.55 by synchrotron SAXS and Raman spectroscopy. Our results clearly confirm the important role of open-ILS (proto-imogolites) in the formation of nanostructured species (imogolite, allophane). The concentration and kinetics of TEOS hydrolysis with respect the formation and restructuring of Al polycations appear to be particularly important in the control of the average size of open-ILS. With typical synthesis conditions, this size can span both below (high concentration) and above (low concentration) the sphere/tube curvature transition that occurs at about 30 Å. Moreover, the rate of NaOH injection seems to be less important at least so long as a sufficient equilibration time (several hours) is allowed for the structure of open-ILS to stabilize at ambient temperature. The fact that no splitting of the stretching band of Si -O is observed in the IR spectra at high concentration is in favor of a selfassembly/aggregation mechanism of small proto-imogolites at constant curvature rather than a further growth of the open-ILS upon heating. The precise role of concentration, counter-ions, type of solvent and temperature in the control of the self-assembly of open-ILS has still been barely explored. These results call for further research in this direction in particular for better control of imogolite chirality, length and purity. Finally, while it is possible to reduce the concentration of non-tubular closed-ILS to a few percent in mass, no perfect method was found yet to fully remove them without compromising the dispersion and/or chemical integrity of the nanotubes.

Figure 2 :

 2 Figure 2: Scattered intensity at different time intervals for the three kinetic experiments. The first intensity and last intensity measured are respectively in green and red, intermediates ones are in black (for kinetics 1 and 2). Purple curve for kinetic 3 corresponds to scattered intensity at 38 min (when I qmin (see text) reaches a minimum value after NaOH injection). Colorful arrows indicate in which directions scattered intensity curves evolve with reaction time.

Figure 3 :

 3 Figure 3: Evolution of I qmin /C tot as a function of time. Injection of NaOH starts at 10 minutes for the three kinetics.

Figure 6 :

 6 Figure 6: IR spectrum of the final states for the three kinetic experiments.

Figure 7 :

 7 Figure 7: SAXS curves measured after the growth stage for the three kinetic experiments. Molecular structures used to compute the nanotube and large protoimogolite scattering are also displayed.

Figure 8 :

 8 Figure 8: SAXS curves of an imogolite synthesis dialyzed with an 8 kDa (red) and an 100 kDa (black) cut-off.

1 Figure S1 : 2 Figure

 1S12 Figure S1: Evolution of pH as a function of time. Injection of NaOH starts at 10 minutes for the three kinetics.

  et al., Koenderick et al. and more recently by Du et al. but cryo-TEM is providing an experimental insight of the presence of such nanostructures with minimal artifacts due to sample preparation

Table 1 :

 1 Conditions of the SAXS experiments for initial co-precipitation of Si (from TEOS) and Al (from Al(ClO 4 ) 3 ). Q N aOH is the flow rate of NaOH solution and times correspond to the beginning of addition.

	min)

Kinetic Al (mM) Si (mM) Q N aOH (mL•min -1 ) T N aOH (min) T T EOS (

Acknowledgements

The SWAXSlab plateform of NIMBE and LLB is acknowledged for the SAXS facility. We want to thank O. Taché for his help for the SAXS experiments in the SWAXS Lab. (Cryo-)TEM observations were made, thanks to "Investissements d'Avenir" LabEx PALM (ANR-10-LABX-0039-PALM). This work was also funded by the ANR grant BENALOR (ANR-20-CE09-0029). Sophie Charton is acknowledged for her collaboration on this project and for her work with Tobias Lange in Marcoule. Thibault Coradin is acknowledged for his help in supervising the work of Pierre Picot at the time of his PhD during which most experiments presented in this article were performed. The authors thank Dr. Mark Levenstein for reading the manuscript and making insightful comments.

Conflicts of interest

There are no conflicts to declare.


Lilian Geniller

Marc Taillefer

Florian Jaroschik

Alexis Prieto

Photocatalyzed amination of alkyl halides to access primary amines

We demonstrate that oxime ester derivatives can be used as both an XAT agent and an imine source under photocatalytic conditions allowing the radical amination of alkyl halides, resulting in the formation of a broad scope of imines. Hydrolysis of the latter gives a direct access to the corresponding primary amines. Mechanistically, the reaction is believed to proceed through the formation of aryl radical intermediates, which are responsible for the activation of alkyl halides via halogen atom transfer (XAT).

INTRODUCTION

Amines are ubiquitous in organic chemistry, as they constitute significant and essential chemicals for the conception of medicines and materials. 1 For instance, amino/nitrogen groups are present in more than 80% of the 200 best-selling drugs, highlighting the crucial role of such moieties in drug activity. 2 Among amines, primary amines are without any doubt the most interesting as they play a key role as starting reagents in a plethora of organic reactions. Consequently, the development of novel methods allowing their preparation are still sought after. 3 In this context, recent innovative strategies have been developed, including hydroaminations, 4 metal-catalyzed reductive amination, 5 and dehydrogenative couplings. 6 Even though such processes enable the valorization of various amine precursors, such as alkenes or alcohols, none of them allow the use of prevalent alkyl halides. Indeed, the syntheses of primary amines using alkyl halides are mainly restricted to traditional approaches, which present several drawbacks (Fig- ure 1A). While aminations using ammonia lead to a mixture of primary, secondary and tertiary amines, the other methods that rely on S N 2 reactions are exclusively effective with primary and secondary alkyl halides. 7 Moreover, the harsh conditions needed for some of them (e.g. the Delépine reaction 8 ) are deleterious for the functional group tolerance (Figure 1A). More recently, radical amination of alkyl halides has been envisaged as an alternative to the above-mentioned ionic methods. This would provide access to primary amines through the formation of readily hydrolysable imines. 9 To date, only two such protocols have been reported, in which carbon radicals are generated from alkyl iodides by halogen atom transfer (XAT) (Figure 1B). However, both protocols only offer a narrow range of imine scope. Furthermore, they are based on the use of well-established XAT promoters, such as Me 3 Sn • radical (known for its toxicity) 9a and less widespread α-amino radical (Figure 1B-C). 9b As these procedures require the presence of peroxides and in most cases high temperature, there is still a need for developing a general approach under mild reaction conditions.

A literature survey allowed us to discover that longneglected XAT promoters, such as aryl radicals, 10,11 recently proved to be effective for activating a large variety of alkyl iodides in copper-catalyzed coupling reactions. 12 Indeed, in comparison with heteroatom-based XAT promoters or αamino radicals, 13 the use of aryl radicals as XAT promoters is still in its early stage (Figure 1C). In parallel, an impressive number of photocatalyzed transformations has been recently developed using oxime derivatives prone to photolysis of the N-O bond by energy transfer (EnT), 14 including hydrofunctionalization 15 and 1,2-difunctionalization 16 of radical receptors (alkenes, propellanes, heterocycles, diazenes…), functionalization reactions, 17 multi-component reactions 18 and radical CH-functionalization. 19 Such reactions are particularly noteworthy as they can be performed under mild reaction conditions. In this context, we got especially interested in the use of readily-available oxime ester 1, which we believed would act both as an XAT promoter and an imine source (Figure 1D). 20 Indeed, based on literature precedents, 14-19 the reaction would start by the photoexcitation of the photocatalyst (PC), which would activate the oxime 1 by energy transfer (EnT). Then the excited oxime 1 would undergo N-O bond cleavage followed by a fast decarboxylative process that would result in the formation of radical intermediates I and II (Figure 1D). Then the aryl radical (I) would be involved in the thermodynamically favored XAT with alkyl iodides 2 (BDE of PhI = 65 kcal/mol and BDE of iPrI = 56 kcal/mol) 21 leading to the formation of alkyl radicals (III). Finally, the radical-radical coupling between radical intermediates II and III would afford the expected imines 3. Herein, we describe preliminary results demonstrating that the oxime 1 can be used for enhancing radical amination under photocatalyzed conditions, delivering a large variety of primary amine precursors 3 with excellent functional group tolerance.

RESULTS AND DISCUSSION

To implement our mechanistic proposal, the reaction was first performed with the oxime ester 1a and 1,1,1-Trifluoro-2iodoethane 2a as model substrates. The first experiments with those compounds were performed using 10 mol% of thioxanthone (TX) 22 as photocatalyst (PC) in EtOAc under 390 nm irradiation. In those conditions, the expected imine 3a was formed in a satisfying NMR yield of 67% (Table 1, entry 1). The replacement of TX by Ir-based or 4-CzIPN photocatalysts under blue light irradiation did not yield any improvements (Table 1, entries 2-3). When a lower quantity of 1a (1.5 equiv.) was used, the reaction delivered 3a in a slightly lower yield (Table 1, entry 4). Finally, the reaction was performed in various solvents (Table 1, entries 5-7). While in DCM or acetone no improvement was observed, the use of MeCN resulted in a significant increase of NMR yield (98%). Under these best conditions, in MeCN, product 3a could be isolated in a very good 84% yield. However, it is important to mention that such conditions also lead to the formation of a by-product stemming from reaction between the imine radical and the • CH 2 CN radical, generated by HAT. 18c Consequently, in the substrate scope exploration (see below) both solvents (EtOAc and MeCN) were employed.

The reaction was also investigated in the presence of various oximes 1 in MeCN, for which the aryl moieties that correspond to the XAT agents, were modified (Table 1, entries 8-10). Given that XATs are generally more effective with electron-rich XAT agents, 12 the reaction was first explored with oximes 1b and 1c bearing three methyl or two methoxy substituents, respectively. Unfortunately, the use of these oximes resulted in the formation of 3a in only moderate to insignificant yields (Table 1, entries 8-9). Interestingly, the oxime 1d bearing an electron-poor aryl moiety also provided 3a, albeit in low yield (Table 1, entry 10). Finally, control experiments showed that both the presence of thioxanthone and the exposure to light were essential for the reaction to proceed well ( With the optimized conditions in hand, we explored the scope of the amination reaction (Scheme 1). First, the reaction was investigated in the presence of various primary alkyl halides. Moderate to good yields were obtained for alkyl iodides of different chain lengths bearing cyano or trifluoromethyl groups (3a, c, d).

Scheme 1. Scope of the amination a a Reaction conditions: 1a (1 mmol), 2 (0.5 mmol) in MeCN or AcOEt (5 mL).

Yields refer to isolated products. In the case of bromoacetonitrile, product 3b was isolated in a good 61% yield. The reaction conditions were also compatible with alkyl iodides bearing nitro (3e), phosphonate (3f), silyl ether (3g) and phthalimide (3h) groups. A protected alkyne group was well tolerated (3i). In the case of the alkene containing ester substrate, the final product 3j was isolated in low 24% yield due to hydrolysis upon purification (NMR yield 50%). A primary amide precursor afforded compound 3k in good 55% yield. Finally, the use of ethyl iodo-or bromoacetate gave similar results, resulting in the formation of 3l in modest yields. Subsequently, a range of secondary halides were employed. Piperidines protected with Boc or benzoyl derivatives as well as an azetidine derivative led to the formation of 3m-3p in moderate yields. The propionate esters bearing alpha-halides gave moderate (bromide, 30%) and good (iodide 47%) results for product 3q. It is remarkable that this methodology can be extended to tertiary alkyl halides as shown for ethyl 2-iodo-2-methylpropionate and tBu-iodide, providing products 3r and 3s in 40% and 60% yields, respectively. The excellent functional group tolerance was further demonstrated in the late-stage transformation of several complex molecules. The imines derived from amino acids 3t, 3w, ibuprofen 3u or sugar derivative 3v were obtained in good 43 to 54% isolated yields. It should be noted that unactivated alkyl bromides, benzylbromide and 2-bromoacetophenone provided the corresponding imine products in yields lower than 10%, likely because phenyl radical cannot activate such bromides by XAT. Scheme 2. Scale up and mechanistic investigations.

Next, owing to the cost-effectiveness and mildness of the method, we envisaged to scale-up the reaction. For instance, a 10 mmol preparative-scale synthesis of 3f could be achieved without further optimization while still maintaining a high isolated yield of 54%, thus demonstrating the robustness of our protocol (Scheme 2A). We then turned our attention to the mechanistic elucidation (Scheme 2B-C). First, the crude reaction mixture of 1a with 2a under standard conditions was examined by GCMS analysis. We were pleased to observe every time the formation of iodobenzene (Scheme 2B). Moreover, the latter has been isolated upon purification in a nearly quantitative yield of 91%, which tends to prove that the transient aryl radical is well engaged in the XAT with alkyl iodides. Then, the reaction was performed in the presence of the radical scavenger 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO; 1 equiv) (Scheme 2C). In those conditions, the reaction allowed the formation of 3a in a poor yield of 6%, along with the formation of TEMPO adducts, which were detected by MS analysis. Indeed, TEMPO-Ph and TEMPO-CH 2 CF 3 as well as the imine dimer were identified. These results highlight the formation of both aryl and CH 2 CF 3 radicals.

Finally, we explored the hydrolysis of several imines 3 to the corresponding primary amines 4 or ammonium hydrochlorides 5 (Scheme 3). Following a reported procedure using PPTS, 9b the imine 3o could be converted to the corresponding amine 4o at room temperature in quantitative yield. Additionally, treating imines 3 with HCl gas in Et 2 O at room temperature provided the corresponding hydrochlorides 5 also in high yields. Pleasingly, chemical functions prone to hydrolysis such as esters or acetal were well tolerated during imines hydrolysis.

Scheme 3. Hydrolysis of imines 3 to primary amines 4 or ammonium hydrochlorides 5.

CONCLUSION

In summary, we have developed a general, effective and mild protocol to access primary amines starting from alkyl iodides/bromides and an oxime ester derivative. This two-step approach relies first on a photocatalyzed amination of alkyl halides furnishing imines, in which the oxime ester has the role of an XAT promoter and an imine source. The imines can secondly be easily hydrolyzed to give the corresponding pri-mary amines or their hydrochlorides. Overall, this strategy offers the possibility of using primary, secondary and tertiary alkyl halides bearing various functional groups and delivers expected amines in good yields.

EXPERIMENTAL SECTION

General information. 1 H, 13 C and 19 F spectra were recorded on a Bruker ® AC-400 MHz spectrometer (400 MHz, 101 MHz, and 376 MHz respectively) at ambient temperature. The peaks were internally referenced to residual undeuterated solvent signal (CDCl 3 : 7.26 ppm ( 1 H NMR), 77.16 ppm ( 13 C NMR)). The following abbreviations were used to explain multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad). All 19 F NMR spectra are reported in ppm relative to CFCl 3 . NMR yields were determined by using respectively trifluorotoluene or trifluoroanisole for 19 F NMR yields and trichloroethylene for 1 H NMR yields as internal standards. HRMS (Q-TOF) studies were performed on a JEOL JMS-DX300 spectrometer (3 keV, xenon) in a m-nitrobenzylalcohol matrix. All reactions were performed under an argon atmosphere in a sealed reaction vial. Reactions were monitored by analytical thin layer chromatography (TLC) using commercial sheets precoated (0.2 mm layer thickness) with silica gel 60F254 (Macherey-Nagel). Product purification by flash column chromatography was performed using Macherey-Nagel Silica Gel (40-63 μm). Solvents and reagents were obtained from commercial sources and used as received. Materials. Commercial grade reagents and solvents were purchased from Sigma-Aldrich, Fluka, Alfa Aesar, Fluorochem, SynQuest at the highest commercial quality and used without further purification, unless otherwise stated. Starting materials: Thioxanthone as well as the following alkyl halides 2a, 2b, 2d, 2k, 2l-Br, 2p, 2q, 2r, 2s are commercially available. They were purchased from Sigma-Aldrich, Alfa Aesar, Fluorochem, TCI Europe, and used without further purification. Starting materials 2c, 23 2e, 24 2f, 25 2g, 26 2h, 27 2i-2j, 26 2l-I, 28 2m-2o, 26 2t-2v, 26 2w 29 were synthesized according to described procedures. Photochemical equipment. Reactions were performed in the EvoluChemTM PhotoRedOx reactor fitted with the selected EvoluChem lights (450 nm -18W, relative irradiance 34 mW/cm 2 , SKU: HCK1012-XX-002) for reactions with (Ir[dF(CF3)ppy] 2 (dtbpy))PF 6 and Kessil PR160L lights (390 nm -40 W, relative irradiance 399mW/cm 2 ) for reactions with thioxanthone. The equipment was purchased from Interchim. The distance between the light reflection and the vessel has been measured to 2 cm. Synthesis of oxime 1a. Diphenylmethanone O-benzoyl oxime (1a): A round-bottom flask equipped with a stirring bar was charged with diphenylmethanone oxime (21.5 g, 109 mmol, 1.0 equiv.) and pyridine (17.6 mL, 218 mmol, 2.0 equiv.) in DCM (300 mL, 0.3 M) at 0 °C. Then, benzoyl chloride (13.9 mL, 120 mmol, 1.1 equiv.) was added dropwise and the reaction was left with stirring at 0 °C for 0.5 hour and then for 2.5 hours at room temperature. After dilution with H 2 O (mL), the layers were separated and the aqueous layer was extracted twice with DCM. The combined organic layers were washed with K 2 CO 3 , brine, dried (MgSO 4 ), filtered and evaporated. Purification by silca gel column chromatography (90% petroleum ether: 10% ethyl actetate) gave the products 1a in 86% yield (28.2 g) as a white solid. 1 H NMR (400 MHz, Chloroform-d) δ 7.87 -7.79 (m, 2H), 7.75 -7.67 (m, 2H), 7.58 -7.32 (m, 11H). Spectroscopic data obtained are consistent with the data reported in the literature. 30 Synthesis of oxime 1b. Diphenylmethanone O- (2,4,6trimethylbenzoyl) oxime (1b): A round-bottom flask equipped with a stirring bar was charged with diphenylmethanone oxime (2.0 g, 10 mmol, 1.0 equiv.) and pyridine (1.6 mL, 20 mmol, 2.0 equiv.) in DCM (30 mL, 0.3 M) at 0 °C. Then, 2,4,6trimethylbenzoyl chloride (1.8 mL, 11 mmol, 1.1 equiv.) was added dropwise and the reaction was left with stirring at 0 °C for 0.5 hour and then for 2.5 hours at room temperature. After dilution with H 2 O (mL), the layers were separated and the aqueous layer was extracted twice with DCM. The combined organic layers were washed with K 2 CO 3 , brine, dried (MgSO 4 ), filtered and evaporated. Purification by silca gel column chromatography (90% petroleum ether: 10% ethyl actetate) gave the products 1b in 74% yield (2.5 g) as a white solid. 1 H NMR (400 MHz, Chloroform-d) δ 7.65 (dd, J = 5.3, 3.2 Hz, 2H), 7.49 -7.29 (m, 8H), 6.79 (s, 2H), 2.25 (s, 3H), 2.20 (s, 6H). Spectroscopic data obtained are consistent with the data reported in the literature. 31 General procedure for the synthesis of oxime 1 (GP1). A round-bottom flask equipped with a stirring bar was charged with the corresponding benzoic acid (5.5 mmol, 1.1 equiv.) and one drop of DMF in DCM (15 mL, 0.3 M). Then, oxalyl chloride (635 µL, 7.5 mmol, 1.5 equiv.) was added dropwise at room temperature. The reaction was stirred for 1 hour at room temperature, then diluted in DCM (10 mL) and subsequently added to a solution of diphenylmethanone oxime (1.0 g, 5 mmol, 1.0 equiv.) and pyridine (0.8 mL, 10 mmol, 2.0 equiv.) in DCM (15 mL, 0.3 M) at 0 °C. The reaction was left with stirring at 0 °C for 0.5 hour and then for 2.5 hours at room temperature. After dilution with H 2 O (mL), the layers were separated and the aqueous layer was extracted twice with DCM. The combined organic layers were washed with K 2 CO 3 , brine, dried (MgSO 4 ), filtered and evaporated. Purification by silica gel column chromatography gave the products 1.

General procedure for the synthesis of imine 3 (GP2). In a vial, the corresponding alkyl iodide (0.5 mmol, 1 equiv.) was added to a solution of diphenylmethanone O-benzoyl oxime (301.3 mg, 1.0 mmol, 2 equiv.) and thioxanthone (10.6 mg, 0.05 mmol, 10 mol %) in AcOEt (5 mL). The reaction mixture was degassed via a freeze pump thaw procedure, and then placed in the EvoluChemTM PhotoRedOx reactor fitted with the Kessil PR160L -390 nm light. The reaction was stirred under light irradiation at room temperature for 18 h and then concentrated in vacuo. NEt 3 (approx. 0.3 mL) in DCM and SiO 2 were added to this solution and the volatiles were removed under reduced pressure, affording a powder which was loaded on column. Purification by silica gel column, pre-basified with NEt 3 using petroleum ether: EtOAc mixtures afforded the corresponding diaromatic imine products 3. Note: NEt3 was used as the product can be partially hydrolyzed by acidic silica, causing a slight decrease in the yield (approx. 5-10%). The amount of NEt 3 added to the eluent was approximately 1 ml for 300 ml of solvent. When NEt3 was used for TLC analysis, one Pasteur pipette drop was used for 10 ml of eluent. "Pre-basified" silica refers to silica gel, which have been soaked with 1-3% triethylamine in pentane prior to use.

Synthesis of amine 4m. Following a reported procedure. 9b A test tube equipped with a stirring bar was charged with 3m (40 mg, 0.11 mmol) and THF (1.9 mL) and H 2 O (0.1 mL) were added. Pyridinium p-toluene sulfonate (29 mg, 0.12 mmol) was added in a single portion. The reaction was stirred at room temperature until completion (determined by TLC). The reaction was then diluted with EtOAc (2 mL) and H 2 O (1 mL). The organic layer was separated and the aqueous layer was extracted with EtOAc (5 mL x 2). The combined organic phases were dried (MgSO 4 ), filtered, and evaporated. Crude mixture was purified using column chromatography (eluent DCM/MeOH 100:0 to 90:10) to give 4m as a solid (22 mg, 99%). 1 H NMR (400 MHz, CDCl 3 ) δ 3.98 (2H, br s), 2.91-2.80 (1H, m), 2.71-2.58 (2H, m), 1.94-1.67 (4H, m), 1.44 (9H, s), 1. 33-1.16 (2H, m). ). Spectroscopic data obtained are consistent with the data reported in the literature. 9b

General procedure for the synthesis of ammonium hydrochlorides 5 (GP3). HCl gas (generated from NaCl/H 2 SO 4 ) was bubbled in a vial containing a solution of the selected imine 3 (0.2 mmol, 1 equiv.) in wet Et 2 O (2 mL) until the appearance of a white solid. The reaction was stirred for 10 min (without HCl bubbling), and then concentrated in vacuo. The residue was dissolved in the minimum amount of DCM, followed by a slow addition of Et 2 O (solvent layering). During the solvent diffusion, a white solid precipitated. The organic layer was then removed with a pasteur pipette, and the white solid was washed several times with Et 2 O to provide the corresponding hydrochloride 5.

Characterization Data of Compounds. Diphenylmethanone O- (2,4-dimethoxybenzoyl) oxime (1c): The compound was obtained following GP1 using 2,4-dimethoxybenzoic acid (1.0 g). The title product was obtained by silica gel column chromatography (70% petroleum ether: 30% ethyl actetate) in 83% yield (1.5 g) as a white solid. 1 H NMR (400 MHz, Chloroform-d) δ 7.67 -7.62 (m, 3H), 7.49 -7.34 (m, 8H), 6.41 (dt, J = 5.1, 2.3 Hz, 2H), 3.81 (s, 3H), 3.66 (s, 3H). 13 C{ 1 H} NMR (101 MHz, Chloroform-d) δ 164.6, 164.6, 163.5, 161.5, 135.2, 134.0, 133.4, 130.8, 129.4, 129.2, 129.1, 128.4, 128.1, 111.0, 104.7, 99.0, 55.7, 55.5.

HRMS (ESI):

Calcd for C 22 H 20 NO 4 [M+H + , 100 %]: 362.1385, found 362.1387. 1-(4-((((diphenylmethylene)amino)oxy)carbonyl)phenyl)ethan-1one (1d): The compound was obtained following GP1 using 4acetylbenzoic acid (0.9 g). The title product was obtained by silica gel column chromatography (80% petroleum ether: 20% ethyl actetate) in 58% yield (1.0 g) as a white solid. 1 H NMR (400 MHz, Chloroform-d) δ 7.95 -7.92 (m, 1H), 7.89 -7.85 (m, 1H), 7.70 -7.66 (m, 1H), 7.55 -7.47 (m, 2H), 7.44 -7.38 (m, 2H), 2.61 (s, 2H). 13 C{ 1 H} NMR (101 MHz,166.3,163.0,140.5,134.5,132.8,132.8,131.4,130.0,130.0,129.3,128.9,128.6,128.5,128.4,[START_REF] Oukhatar | Straightforward and Mild Deprotection Methods of N-Mono-and N,N-Functionalised Bisaminal Cyclens[END_REF]0. HRMS (ESI): Calcd for C 22 H 18 NO 3 [M+H + , 100 %]: 344.1277, found 344.1281. 1,1-diphenyl-N-(2,2,2-trifluoroethyl)methanimine (3a): Following GP2 and purified by pre-basified silica gel column chromatography (98% petroleum ether: 2% AcOEt) to give the corresponding product as a colorless oil (111 mg, 84 %). 1 H NMR (400 MHz, CDCl 3 ) δ 7.73 -7.67 (m, 2H), 7.56 -7.42 (m, 4H), 7.37 (t, J = 7.4 Hz, 2H), 7.21 -7.16 (m, 2H), 3.89 (q, J = 9.5 Hz, 2H). 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 173. 1, 138.8, 135.8, 131.0, 129.3, 129.1, 128.9, 128.3, 127.5, 125.2 (q, J = 276.7 Hz), 55.2 (q, J = 30.9 Hz). 19 F NMR (377 MHz, Chloroform-d) δ -71.9 (t, J = 9.5 Hz). Spectroscopic data obtained are consistent with the data reported in the literature. 32 2-((diphenylmethylene)amino)acetonitrile (3b): Following GP2 and purified by pre-basified silica gel column chromatography (95% petroleum ether: 5% AcOEt) to give the corresponding product as a yellow oil (67 mg, 61 %). 1 H NMR (400 MHz, CDCl 3 ) δ 7.65 (ddd, J = 7.2, 3.1, 1.7 Hz, 2H), 7.56 -7.43 (m, 4H), 7.39 -7.34 (m, 2H), 7.20 -7.16 (m, 2H), 4.23 (s, 2H). 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 174. 4, 138.4, 135.0, 131.4, 129.6, 129.3, 129.0, 128.4, 127.4, 117.7, 41.4. Spectroscopic data obtained are consistent with the data reported in the literature. 33 3-((diphenylmethylene)amino)propanenitrile (3c): Following GP2 and purified by pre-basified silica gel column chromatography (90% petroleum ether: 10% AcOEt) to give the corresponding product as a yellow oil (56 mg, 48 %). 1 H NMR (400 MHz, CDCl 3 ) δ 2H),6H),7.19 (dd,J = 7.7,1.6 Hz,2H), 3.60 (t, J = 6.8 Hz, 2H), 2.74 (t, J = 6.8 Hz, 2H). 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 170.9, 139.1, 136.2, 130.6, 129.0, 128.9, 128.7, 128.3, 127.7, 119.0, 49.1, 20.0. Spectroscopic data obtained are consistent with the data reported in the literature. 34 1,1-diphenyl-N-(3,3,3-trifluoropropyl)methanimine (3d): Following GP2 except that thioxanthone was replaced by (Ir[dF(CF 3 )ppy] 2 (dtbpy))PF 6 (5.7 mg, 0.005 mmol, 1 mol%) and Kessil PR160L light (390 nm -40 W) was replaced by EvoluChem light (455 nm -18W) and purified by pre-basified silica gel column chromatography (99% petroleum ether: 1% AcOEt) to give the corresponding product as a colorless oil (69 mg, 50 %). 1 H NMR (400 MHz, CDCl 3 ) δ 7.64 -7.60 (m, 2H), 7.52 -7.28 (m, 6H), 7.20 -7.15 (m, 2H), 3.63 -3.56 (m, 2H), 2.64 -2.49 (m, 2H). 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 169.9, 139.6, 136.5, 130.4, 128.8, 128.5, 128.3, 127.6, 46.9 (d, J = 2.9 Hz), 35.6 (q, J = 27.5 Hz). 19 F NMR (377 MHz, Chloroform-d) δ -68.3 (t, J = 10.9 Hz). Spectroscopic data obtained are consistent with the data reported in the literature. 35 N-(4-nitrophenethyl)-1,1-diphenylmethanimine (3e): Following GP2 and purified by pre-basified silica gel column chromatography (80% petroleum ether: 20% AcOEt) to give the corresponding product as a brown oil (57 mg, 35 %). 1 H NMR (400 MHz, CDCl 3 ) δ 8.11 (dd,J = 6.5,4.6 Hz,2H),7.56 (dd,J = 8.3,1.2 Hz,2H),8H),2H), 3.67 (t, J = 6.9 Hz, 2H), 3.11 (t, J = 6.9 Hz, 2H). 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 169.3, 148.7, 146.6, 139.6, 136.6, 130.3, 130.0, 128.6, 128.4, 128.2, 127.7, 123.5, 54.6, 37.6 3f): Following GP2 and purified by pre-basified silica gel column chromatography (30% petroleum ether: 70% AcOEt) to give the corresponding product as a brown oil (86 mg, 50 %). 1 H NMR (400 MHz, CDCl 3 ) δ 7.61 -7.57 (m, 2H), 7.48 -7.29 (m, 6H), 7.18 -7.14 (m, 2H), 4.09 -3.99 (m, 4H), 3.67 -3.58 (m, 2H), 2.25 -2.14 (m, 2H), 1.24 (t, J = 7.1 Hz, 6H). 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 169.2 (d,J = 1.7 Hz),139.7,136.6,130.2,128.7,128.7,128.5,128.2,127.8,61.6 (d,J = 6.3 Hz),47.6 (d,J = 1.6 Hz),30.4,28.7,27.3,16.5 (d,J = 6.2 Hz). HRMS (ES+): Calcd for C 19 H 25 NO 3 P [M+H + , 100 %]: 346.1572, found 346.1578. N- (2-((tert-butyldimethylsilyl)oxy)ethyl)-1,1diphenylmethanimine (3g): Following GP2 and purified by prebasified silica gel column chromatography (99% petroleum ether: 1% AcOEt) to give the corresponding product as a colorless oil (69 mg, 41 %). 1 H NMR (400 MHz, CDCl 3 ) 7.63 -7.59 (m, 2H), 7.48 -7.29 (m, 6H), 7.21 -7.17 (m, 2H), 3.95 (t, J = 6.4 Hz, 2H), 3.53 (t, J = 6.4 Hz, 2H), 0.88 (s, 9H), 0.05 (s, 6H). 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 169.3, 140.1, 137.0, 130.0, 128.5, 128.4, 128.1, 63.9, 56.5, 26.1, 18.6, -5.1. HRMS (ESI): Calcd for C 21 H 30 NOSi [M+H + , 100 %]: 340.2091, found 340.2091. 2-(2-((diphenylmethylene)amino)ethyl)isoindoline-1,3-dione (3h): Following GP2 and purified by pre-basified silica gel column chromatography (80% petroleum ether: 20% AcOEt) to give the corresponding product as a yellow oil (83 mg, 47 %). 1 H NMR (400 MHz, CDCl 3 ) δ 7.82 (dt, J = 6.8, 3.4 Hz, 2H), 7.73 -7.64 (m, 2H), 7.60 -7.53 (m, 2H), 7.44 -7.25 (m, 6H), 7.13 -7.04 (m, 2H), 4.02 (t, J = 6.4 Hz, 2H), 3.69 (t, J = 6.4 Hz, 2H). 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 170.0, 168. 4, 139.6, 136.5, 133.9, 132.5, 132.3, 130.2, 130.1, 128.7, 128.6, 128.6, 128.4, 128.1, 127.7, 123.2, 51.6, 39. 1,1-diphenyl-N- (5-(trimethylsilyl)pent-4-yn-1-yl)methanimine (3i): Following GP2 and purified by pre-basified silica gel column chromatography (98% petroleum ether: 2% AcOEt) to give the corresponding product as a colorless oil (65 mg, 41 %). 1 H NMR (400 MHz, CDCl 3 ) δ 7.64 -7.59 (m, 2H), 7.50 -7.30 (m, 6H), 7.17 (dd, J = 7.8, 1.5 Hz, 2H), 3.45 (t, J = 6.7 Hz, 2H), 2.35 (t, J = 7.0 Hz, 2H), 1.91 (p, J = 7.0 Hz, 2H), 0.11 (s, 9H). 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 168.6, 139.9, 137.6, 137.0, 130.0, 128.6, 128.4, 128.1, 127.9, 107.3, 84.6, 52.6, 30.3, 17.9, 0.3. HRMS (ESI): Calcd for C 21 H 26 NSi [M+H + , 100 %]: 320.1829, found 320.1829. 2-((diphenylmethylene)amino)ethyl undec-10-enoate (3j): Following GP2 and purified by pre-basified silica gel column chromatography (95% petroleum ether: 5% AcOEt) to give the corresponding product as a colorless oil (47 mg, 24 %). 1 H NMR (400 MHz, CDCl 3 ) δ 7.63 -7.58 (m, 2H), 7.50 -7.29 (m, 6H), 7.17 (dd, J = 7.7, 1.6 Hz, 2H), 5.80 (ddt, J = 16.9, 10.2, 6.7 Hz, 1H), 5.03 -4.89 (m, 2H), 4.38 (t, J = 5.8 Hz, 2H), 3.61 (t, J = 5.8 Hz, 2H), 2.29 (t, J = 7.5 Hz, 2H), 2.02 (dd, J = 14.3, 6.9 Hz, 2H), 1.59 (dd, J = 14.5, 7.2 Hz, 2H), 1. 40 -1.19 (m, 10H). 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 174.0, 170.0, 139. 7, 139.3, 136.7, 130.2, 128.7, 128.6, 128.6, 128.2, 127.9, 114.3, 64.6, 52.6, 34.4, 33.9, 29.4, 29.3, 29.2, 29.2, 29.0, 25. 3k): Following GP2 and purified by pre-basified silica gel column chromatography (40% petroleum ether: 60% AcOEt) to give the corresponding product as a brown solid (66 mg, 55 %). 1 H NMR (400 MHz, CDCl 3 ) δ 7.64 (dd, J = 5.3, 3.4 Hz, 2H), 7.51 -7.41 (m, 4H), 7.40 -7.32 (m, 2H), 7.17 -7.11 (m, 2H), 6.22 (bs, 1H), 3.98 (s, 2H). 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 173. 7, 170.5, 138.9, 136.1, 130.9, 129.2, 129.1, 128.6, 128.4, 127.4, 56.7. Spectroscopic data obtained are consistent with the data reported in the literature. 36 Ethyl 2-((diphenylmethylene)amino)acetate (3l): Following GP2 and by pre-basified silica gel column chromatography (95% petroleum ether: 5% AcOEt) to give the corresponding product as a collorless oil (42 mg, 31 %). 1 H NMR (400 MHz, CDCl 3 ) δ 7.68 -7.64 (m, 2H), 7.50 -7.31 (m, 6H), 7.21 -7.17 (m, 2H), 4.21 (p, J = 7.1 Hz, 4H), 1.28 (t, J = 7.1 Hz, 3H). 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 172.0, 170. 8, 139.4, 136.1, 130.6, 128.9, 128.9, 128.8, 128.2, 127.8, 61.0, 55.9, 14.3. Spectroscopic data obtained are consistent with the data reported in the literature. 37 tert-butyl 4-((diphenylmethylene)amino)piperidine-1-carboxylate (3m): Following GP2 and purified by pre-basified silica gel column chromatography (90% petroleum ether: 10% AcOEt) to give the corresponding product as a colorless oil (80 mg, 44 %). 1 H NMR (400 MHz, CDCl 3 ) δ 7.59 (dd, J = 7.5, 6.2 Hz, 2H), 7.45 (t, J = 6.2 Hz, 3H), 3H),7.15 (dd,J = 7.5,1.7 Hz,2H),4.00 (bs,2H),1H), 2.87 (t, J = 11.0 Hz, 2H), 1.74 (ddd, J = 13.4, 11.9, 4.2 Hz, 2H), 1.58 (dd, J = 12.8, 3.1 Hz, 2H), 1.47 (s, 9H). 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 166. 7, 155.0, 140.0, 137.1, 130.0, 128.7, 128.5, 128.4, 128.1, 127.6, 79.4, 58.7, 41.9 (bs), 32.9, 28.6. Spectroscopic data obtained are consistent with the data reported in the literature. 38 (4-((diphenylmethylene)amino)piperidin-1-yl)(phenyl)methanone (3n): Following GP2 and purified by pre-basified silica gel column chromatography (80% petroleum ether: 20% AcOEt) to give the corresponding product as a yellow oil (100 mg, 54 %). 1 H NMR (400 MHz, CDCl 3 ) δ 2H),11H),2H),4.47 (bs,1H),3.81 (bs,1H),3.56 (tt,J = 8.5,4.1 Hz,1H),3.13 (bs,2H),4H). 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 170.3, 167.0, 139.8, 136.9, 136.4, 130.1, 129.5, 128.7, 128.5, 128.1, 127.5, 126.8, 58.2, 45.6 (bs), 40.1 (bs), 33.6 (bs), 32.8 (bs). HRMS (ESI): Calcd for C 25 H 25 N 2 O [M+H + , 100 %]: 369.1967, found 369.1961. 4-bromophenyl) (4-((diphenylmethylene)amino)piperidin-1yl)methanone (3o): Following GP2 and purified by pre-basified silica gel column chromatography (70% petroleum ether: 30% AcOEt) to give the corresponding product as a yellow oil (79 mg, 36 %). 1 H NMR (400 MHz, CDCl 3 ) δ 7.60 (dd,J = 8.2,1.4 Hz,2H),2H),3H),5H),2H),4.40 (bs,1H),3.75 (bs,1H),3.55 (tt,J = 8.4,4.1 Hz,1H),3.13 (bs,2H),4H). 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 169. 4, 167.2, 139.8, 136.9, 135.3, 131.8, 130.2, 128.7, 128.7, 128.5, 128.2, 127.5, 123.8, 58.0, 45.7 (bs), 40.2 (bs), 33.6 (bs), 32.7 (bs). HRMS (ESI): Calcd for C 25 H 24 BrN 2 O [M+H + , 100 %]: 447.1067, found 447.1066. tert-butyl 3-((diphenylmethylene)amino)azetidine-1-carboxylate (3p): Following GP2 and purified by pre-basified silica gel column chromatography (90% petroleum ether: 10% DCM) to give the corresponding product as a colorless oil (62 mg, 37 %). 1 H NMR (400 MHz, CDCl 3 ) δ 7.65 -7.61 (m, 2H), 7.48 -7.31 (m, 6H), 7.08 -7.04 (m, 2H), 4.27 -4.20 (m, 1H), 4.09 -3.99 (m, 4H), 1.43 (s, 9H). 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 170. 1, 156.4, 139.3, 136.8, 130.6, 129.0, 128.7, 128.7, 128.3, 127.7, 79.4, 50.7, 28.5 3q): Following GP2 and purified by pre-basified silica gel column chromatography (30% petroleum ether: 70% DCM) to give the corresponding product as a colorless oil (66 mg, 47 %). 1 H NMR (400 MHz, CDCl 3 ) δ 7.65 (ddd, J = 6.8, 3.6, 1.9 Hz, 2H), 6H),2H),3H),1.43 (d,J = 6.8 Hz,3H), 1.26 (t, J = 7.1 Hz, 3H). 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 173. 0, 169.8, 139.7, 136.4, 130.4, 128.9, 128.7, 128.7, 128.1, 127.8, 60.9, 60.8, 19.3, 14.3. Spectroscopic data obtained are consistent with the data reported in the literature. 39 Ethyl 2-((diphenylmethylene)amino)-2-methylpropanoate (3r): Following GP2 and purified by pre-basified silica gel column chromatography (99% petroleum ether: 1% AcOEt) to give the corresponding product as a colorless oil (60 mg, 40 %). 1 H NMR (400 MHz, CDCl 3 ) δ 7.57 -7.53 (m, 2H), 7.40 -7.27 (m, 6H), 7.15 (ddd, J = 3.5, 2.4, 1.5 Hz, 2H), 3.68 (q, J = 7.2 Hz, 2H), 1.53 (s, 6H), 1.11 (t, J = 7.2 Hz, 3H). 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 175. 5, 166.8, 141.3, 137.3, 130.0, 128.8, 128.6, 128.1, 127.8, 63.6, 60.4, 28.9, 13.9. HRMS (ESI): Calcd for C 19 H 22 NO 2 [M+H + , 100 %]: 296.1643, found 296.1645. 1-(tert-butyl) 2-(2-((diphenylmethylene)amino)ethyl) pyrrolidine-1,2-dicarboxylate (3t): Following GP2 and purified by prebasified silica gel column chromatography (80% petroleum ether: 20% AcOEt) to give the corresponding product as a yellow oil (112 mg, 53 % of a mixture of two rotamers). 1 H NMR (400 MHz, CDCl 3 ) δ 7.59 (d,J = 7.4 Hz,2H),7.40 (dddd,J = 30.4,25.5,14.2,6.8 Hz,6H),2H),1.93H),4.32 (dd,J = 8.6,3.1 Hz, 0.33H), 4.21 (dd, J = 8.6, 4.0 Hz, 0.61H), 3.61 (t, J = 5.9 Hz, 1.71H), 3.57 -3.46 (m, 0.98H), 3.46 -3.30 (m, 0.96H), 2.25 -2.07 (m, 1.01H), 2.04 -1.73 (m, 3.47H), 1.43 (s, 3H), 1.34 (s, 6H). 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 173.3, 173.0 170.1, 169.9, 154.5, 153.9, 139.7, 139.6, 136.6, 130.3, 130.2, 128.7, 128.7, 128.5, 128.1, 127.8, 127.8, 79.9, 79.8, 65.2, 59.2, 58.9, 52.5, 52.4, 46.6, 46.4, 31.0, 30.0, 28.5, 28.4, 24.3, 23.7 3u): Following GP2 and purified by pre-basified silica gel column chromatography (95% petroleum ether: 5% AcOEt) to give the corresponding product as a colorless oil (90 mg, 43 %). 1 H NMR (400 MHz, CDCl 3 ) δ 7.59 -7.55 (m, 2H), 7.42 -7.30 (m, 6H), 7.19 -7.15 (m, 2H), 7.05 -7.01 (m, 2H), 7.01 -6.97 (m, 2H), 4.40 (t, J = 5.7 Hz, 2H), 3.68 (q, J = 7.2 Hz, 1H), 3.56 (dd, J = 6.0, 5.4 Hz, 2H), 2.39 (d, J = 7.2 Hz, 2H), 1.86 -1.73 (m, 1H), 1.46 (d, J = 7.2 Hz, 3H), 0.87 (d, J = 6.6 Hz, 6H). 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 174. 8, 170.0, 140.5, 139.7, 138.0, 136.7, 130.2, 129.4, 128.6, 128.6, 128.2, 127.9, 127.3, 65.1, 52.5, 45.3, 45.2, 30.2, 22.5, 22.5, 18.9 N-((6-methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4yl)methyl)-1,1-diphenylmethanimine (3v): Following GP2 and purified by pre-basified silica gel column chromatography (95% petroleum ether: 5% AcOEt) to give the corresponding product as a yellow oil (99 mg, 54 %). 1 H NMR (400 MHz, CDCl 3 ) δ 2H),6H),7.16 (dd,J = 7.8,1.6 Hz,2H),4.96 (s,1H),4.91 (d,J = 5.9 Hz, 1H), 4.60 (d, J = 6.0 Hz, 1H), 4.50 (t, J = 7.4 Hz, 1H), 3.51 (dd, J = 7.4, 4.6 Hz, 2H), 3.19 (s, 3H), 1.52 (s, 3H), 1.35 (s, 3H). 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 169. 5, 139.7, 136.7, 130.2, 128.6, 128.1, 127.8, 112.3, 109.7, 87.5, 85.5, 82.9, 56.9, 54.7, 26.6, 25.2. HRMS (ESI): Calcd for C 22 H 26 NO 4 [M+H + , 100 %]: 368.1856, found 368.1862. Methyl (2-((diphenylmethylene)amino)acetyl)-L-phenylalaninate (3w): Following GP2 and purified by pre-basified silica gel column chromatography (70% petroleum ether: 30% AcOEt) to give the corresponding product as a yellow oil (89 mg, 45 %). 1 H NMR (400 MHz, CDCl 3 ) δ 7.93 (d,J = 8.2 Hz,1H),2H),4H),5H),2H),2H),5.00 (dt,J = 8.2,5.8 Hz,1H), 3.97 (d, J = 1.9 Hz, 2H), 3.75 (s, 3H), 3. 27 -3.15 (m, 2H). 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 172. 0, 170.6, 170.3, 138.7, 136.0, 130.8, 129.4, 129.1, 129.0, 128.8, 128.6, 128.3, 127.3, 127.2, 56.5, 52.7, 52.4, 38.1. HRMS (ESI): Calcd for C 25 H 25 N 2 O 3 [M+H + , 100 %]: 401.1860, found 401.1864. 2,2,2-trifluoroethan-1-amine hydrochloride (5a): Following GP3 to give the corresponding product as a white solid (23 mg, 85 %). 1 H NMR (400 MHz, DMSO) δ 9.23 (bs, 3H), 3.87 (q, J = 9.7 Hz, 2H). 13 C{ 1 H} NMR (101 MHz, DMSO) δ 123.8 (q, J = 277.6 Hz), 39.4 (q, J = 34.2 Hz). 19 F NMR (377 MHz, DMSO) δ -69.4 (d, J = 9.2 Hz). HRMS (ESI): Calcd for C 2 H 5 F 3 N [M+H + , 100 %]: 100.0369, found 100.0369. 2-aminoacetonitrile hydrochloride (5b): Following GP3 to give the corresponding product as a white solid (16 mg, 86 %). 1 H NMR (400 MHz, DMSO) δ 8.97 (s, 3H), 4.10 (s, 2H). 13 C{ 1 H} NMR (126 MHz, DMSO) δ 115. 4, 26.6. Spectroscopic data obtained are consistent with the data reported in the literature. 40 3,3,3-trifluoropropan-1-amine hydrochloride (5d): Following GP3 to give the corresponding product as a white solid (24 mg, 81 %). 1 H NMR (400 MHz, DMSO) δ 8.13 (s, 3H), 3.07 -3.00 (m, 2H), 2.73 -2.59 (m, 2H). 13 C{ 1 H} NMR (126 MHz, DMSO) δ 126.0 (q, J = 276.5 Hz), 32.5 (q, J = 3.7 Hz), 31.0 (q, J = 28.8 Hz). 19 F NMR (377 MHz, DMSO {H 1 }) δ -64.1 (s). Spectroscopic data obtained are consistent with the data reported in the literature. 41 Ethyl glycinate hydrochloride (5l): Following GP3 to give the corresponding product as a white solid (27 mg, 95 %). 1 H NMR (400 MHz, DMSO) δ 8.31 (bs, 3H), 4.21 (q, J = 7.1 Hz, 2H), 3.80 (s, 2H), 1.24 (t, J = 7.1 Hz, 3H). 13 C{ 1 H} NMR (101 MHz,DMSO) δ 167.6, 61.6, 14.0. Spectroscopic data obtained are consistent with the data reported in the literature. 42 (4-aminopiperidin-1-yl)(4-bromophenyl)methanone hydrochloride (5o): Following GP3 to give the corresponding product as a white solid (62 mg, 97 %). The NMR spectra of this compound are difficult to interpret because of their poor resolution. Consequently, only characteristic NMR signals are provided. 1 H NMR (400 MHz, DMSO) δ 7.60 (bs, 5H), 7.35 (d,J = 7.6 Hz,2H),4.41 (bs,1H),3.85 (bs,1H),2.97 (bs,2H), 2.00 (bs, 4H). 13 C{ 1 H} NMR (101 MHz, DMSO) δ 168. 0, 137.0, 135.2, 132.7, 131.5, 129.6, 129.0, 128.8, 128.6, 122.8, 57.9 6-methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4yl)methanamine hydrochloride (5v): Following GP3 to give the corresponding product as a white solid (42 mg, 87 %). 1 H NMR (400 MHz, DMSO) δ 8. 13 (bs,3H),4.98 (m,1H),1H),4.61 (d,J = 5.9 Hz,1H),4.27 (bs,1H),3.32 (s,3H),3.02 (bs,1H),2.77 (bs,1H),1.39 (s,3H),1.26 (s,3H). 13 C{ 1 H} NMR (101 MHz,DMSO) δ 111.6,109.2,84.3,83.0,81.2,54.9,42.1,26.2,24.6

ASSOCIATED CONTENT

Figure 1 .

 1 Figure 1. A/ Ionic methods for preparation of primary amines. B/ Radical approaches. C/ Uses of XAT promoters. D/ Our design plan for synthesis of primary amines via imines.

F

  NMR using α,α,α-trifluorotoluene as an internal standard c Isolated yield. TX = Thioxanthone. N.R. = No reaction.

Table 1 ,

 1 entries 11-12).

Table 1 .

 1 Optimization of the amination reaction a

	Entry	Deviations	Yields of 3a (%) b
	1	EtOAc	67
	2	EtOAc, (Ir[dF(CF 3 )ppy] 2 (dtbpy))PF 6 (1%), 455 nm	62
	3	EtOAc, 4-CzIPN (5%), 455 nm	39
	4	EtOAc, 1a (1.5 equiv.)	60
	5	DCM	58
	6	Acetone	65
	7	none	98 (84)
	8	1b instead of 1a	51
	9	1c instead of 1a	trace
	10	1d instead of 1a	18
	11	w/o TX	20
	12	w/o light	N.R.

  Calcd for C 21 H 19 N 2 O 2 [M+H + , 100 %]: 331.1441, found 331.1444. Diethyl (2-((diphenylmethylene)amino)ethyl)phosphonate (

. HRMS (ESI):

  Calcd for C 23 H 19 N 2 O 2 [M+H + , 100 %]: 355.1447, found 355.1437.

1. HRMS (ES+):

  1. HRMS (ESI): Calcd for C 26 H 34 NO 2 [M+H + , 100 %]: 392.2584, found 392.2584. 2-((diphenylmethylene)amino)acetamide (

  . HRMS (ES+): Calcd for C 21 H 25 N 2 O 2 [M+H + , 100 %]: 337.1916, found 337.1927. Ethyl 2-((diphenylmethylene)amino)propanoate (

  . HRMS (ESI): Calcd for C 28 H 32 NO 2 [M+H + , 100 %]: 414.2428, found 414.2422.

  . HRMS (ESI): Calcd for C 12 H 16 BrN 2 O [M+H + , 100 %]: 283.0442, found 283.0441.

  . HRMS (ESI): Calcd for C 9 H 18 NO 4 [M+H + , 100 %]: 204.1230, found 204.1235.

ACKNOWLEDGMENT

This research was supported financially by a grant to L.G. from the French Ministry of Higher Education and Research delivered by the Doctoral school (ED 459) and the ICGM. We thank the Centre National de la Recherche Scientifique (CNRS), the Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), the Université de Montpellier for financial support. The authors also thank the Balard Plateform Analysis and Characterization (PAC Balard) facilites for technical support.

Data Availability Statement

The data underlying this study are available in the published article and its Supporting Information.

Safety Statement

Caution! Ultraviolet light is damaging to biological tissues. Caution is required whenworking with the lamp and protective eyewear must be used at all times.

Supporting Information Statement

The Supporting Information is available free of charge on the ACS Publications website. General information; Synthesis of oxime 1; Optimization of the amination; Mechanistic investigations; NMR Spectra of compounds 1, 3, 5; General optimization of the amination (Table S1); Set up on 0.5 mmol scale (FigureS1); Set up on 10 mmol scale (FigureS2)

AUTHOR INFORMATION Corresponding Author

* Alexis Prieto -ICGM, Univ Montpellier, CNRS, ENSCM, 34000 Montpellier, France orcid.org/0000-0002-2922-4652 Email: alexis.prieto@enscm.fr Authors Lilian Geniller -ICGM, Univ Montpellier, CNRS, ENSCM, 34000 Montpellier, France Marc Taillefer -ICGM, Univ Montpellier, CNRS, ENSCM, 34000 Montpellier, France Florian Jaroschik -ICGM, Univ Montpellier, CNRS, ENSCM, 34000 Montpellier, France

Notes

The authors declare no competing financial interest.