Reductive Amination of Ketones with Benzylamine Over Gold Supported on Different Oxides

Reductive amination of cyclohexanone with benzylamine was investigated at 100 °C under 30 bar hydrogen in toluene with five different gold catalysts prepared by deposition–precipitation method and supported on TiO2, La2O3/TiO2, CeO2/TiO2, La2O3 and CeO2. Size of metallic gold varied in the range of 2.6–3.6 nm. The best catalysts in reductive amination of cyclohexanone with benzylamine were 4 wt% Au/TiO2 and 4 wt% Au/CeO2/TiO2 giving 72% and 79% yield of the desired amine. The most acidic and basic catalysts were also unselective and exhibited low activity towards imine hydrogenation. The best catalyst 4 wt% Au/CeO2/TiO2 gave in reductive amination of propiophenone 56% selectivity to the corresponding amine at 20% conversion in 5 h.

Hydroamination of alkynes has been conducted using titanium indenyl complexes. In the first step of the reaction 1-phenylpropyne reacted with benzylamine with [Ind 2 TiMe 2 ] complex as a catalyst at 105 °C in 2 h in toluene followed by hydrogenation of imine in methanol for 20 h using NaBH 3 CN as a reducing agent in the presence of ZnCl 2 at 25 °C giving N-benzyl-1-phenylpropan-1-amine. As a result a mixture of regio-isomers was obtained [1]. In addition, α-ethyl-N-(phenylmethyl)benzenemethaneamine was produced via ethylmagnesiation (EtMgCl) of the corresponding imine in the presence of a homogeneous catalyst, zirconocene dichloride (di(cyclopentadienyl)zirconium(IV) dichloride, Cp 2 ZrCl 2 ) in tetrahydrofuran under argon atmosphere giving 90% yield at 20 °C after 8 h [2].
N-benzyl-1-phenylpropan-1-amine with 86% yield after 3 h at room temperature has been synthesized via reductive allylation of N-benzylbenzamide using a homogeneous iridium complex as a catalyst in dichloromethane [4]. In addition, N-alkylation of aromatic alcohols over non-noble metal catalysts for production of amines such as via hydrogen borrowing mechanism [8], was done with benzyl alcohol and cyclohexylamine as reactants over NiCuFeO in xylene under reflux giving 89% yield of cyclohexylbenzenemethaneamine in 24 h.
Heterogeneous catalysts, such as Pd/C, Pt/C and Rh/C [5] and Au/TiO 2 [6] have been used in reductive amination of ketones. In particular Pd/C, Pt/C and Rh/C [5] were active in amination of aldehydes and ketones in the absence of hydrogen, requiring, however, high pressure of CO. Reductive amination of benzaldehyde with p-anisidine was performed in the presence of 95 bar CO at 140 °C in tetrahydrofuran over Rh/C catalyst giving 50% of the corresponding amine after 42 h [5]. A carbon based solid acid catalyst of the overall composition CH 0.6 O 0.35 S 0.14 prepared by sulfonation of naphthalene with sulfuric acid at 200-300 °C [9] was used in reductive amination of cyclohexanone with benzylamine allowing 90% yield of N-benzylcyclohexyamine in 10 min at room temperature with NaBH 4 as a reducing agent [10]. Au/TiO 2 was reported as an efficient catalyst for reductive amination of cyclohexanone with benzylamine at 60 °C in tert-butanol using formic acid as a hydrogen source [6]. Unsupported ionic liquid (carboxymethyl)-1-methyl-1H-imidazol-3-ium-bis(trifluoromethyl)sulfonyl)amine has also been applied as a catalyst in the same reaction using formic acid and triethylamine as hydrogen sources at 40 °C in acetonitrile as a solvent [3]. The authors [3] achieved the yield of amine of 30% after 5 h.
Imines have been hydrogenated using isopropanol as a hydrogen source in transfer hydrogenation and Funk's iron complex together with Fe(acac) 3 as a catalyst under nitrogen atmosphere at 110 °C under 48 h facilitating formation of N(E)-N-(1-phenylpropylidene)-benzenemethaneamine with 98% yield [11].
Based on a recent study [6], describing Au/TiO 2 and formic acid as a catalyst and a hydrogen source in reductive amination of cyclohexanone with benzylamine, it was decided to explore catalytic behavior of different Au supported catalysts in reductive amination of cyclohexanone and propiophenone with benzylamine using instead of formic acid as a hydrogen source molecular hydrogen, which has clear advantages in the case of industrial implementation compared to formic acid, namely lower costs and no CO 2 release. ) were prepared by the deposition-precipitation method with urea, previously described in ref. [12]. Gold(III) chloride trihydrate (Merck) was used as a gold precursor. The nominal gold content in all catalysts was 4 wt%. After the gold deposition and drying procedure, the materials were treated in a reducing atmosphere (H 2 ) at 300 °C for 1 h.

Catalyst Preparation and Characterization
The specific surface area (S BET ) of the supports and catalysts was measured by nitrogen adsorption method ("TriStar 3000" analyzer, Micromeritics, USA). The phase composition of the materials was studied by XRD (Philips XPert PRO diffractometer). The measured diffractograms were analyzed with the ICDD-2013 powder diffraction database and Inorganic Crystal Structure Database (ICSD) [13]. Catalysts morphology and the gold cluster size were investigated by transmission electron microscopy and scanning transmission electron microscopy-High Angle Annular Dark Field (JEOL JEM-2100F). The gold content was measured by energy dispersive spectroscopy (JEOL JEM-2100F with an Oxford INCA X-sight system detector) and inductively coupled plasma optical emission spectrometry (Perkin Elmer ICP-OES Optima 3300 DV spectrometer). The electronic state of gold on the support surface was determined by XPS (SPECS Surface Nano Analysis GmbH, Berlin, Germany). The concentration of basic and acid sites, and their distribution in supports and catalysts were investigated by temperature programmed desorption (TPD) of CO 2 (Autochem 2900 1 3 apparatus) and NH3 (Chemosorb-chemisorption analyzer), respectively.
Details on the catalysts preparation and characterization are reported in the Electronic supplementary material.

Catalyst Testing
Reductive amination of cyclohexanone (Sigma Aldrich ≥ 99.5%) and propiophenone (Kebo Lab > 99%) with benzylamine (Fluka ≥ 99%), was performed in an autoclave using toluene as a solvent. In a typical experiment 6.6 mmol of ketone and 6.6 mmol of benzylamine in 50 ml solvent were mixed with 100 mg of catalyst. Thereafter, the reactor was flushed with hydrogen and after reaching the desired temperature and pressure, the reaction was started. The stirring rate was 900 rpm and small catalyst particles, below 63 µm were used to suppress the external and internal mass transfer limitations. The samples were taken from the reactor and analyzed by GC equipped with a FID detector and a capillary column, HP-5 (length 30 m, internal diameter 320 µm, film thickness 0.50 µm) with the following temperature programme: 100 °C (5 min)-5 °C/min-320 °C (5 min). The products were confirmed by GC-MS.
Vibrational frequencies were also calculated in order to obtain thermodynamic data of the stabilities.

Catalyst Characterization Results
The phase composition of the studied catalysts was investigated by XRD (Fig. 1). Analysis of diffractograms of 4wt%Au/TiO 2 , 4wt%Au/La 2 O 3 /TiO 2 , 4wt%Au/CeO 2 /TiO 2 and their corresponding supports (Fig. 1a, b, c) showed absence of any diffraction peaks characteristic for gold, ceria or lanthana, implying that their size is lower than 3-4 nm (i.e. sensitivity of XRD) or that they are X-ray amorphous. For these samples, only reflections characteristic of titania (P25) were observed [21]. Previously, this was also reaffirmed by XRD-SR [22], where the reflections related to additives (CeO 2 ) were only detected for 4wt%Au/CeO 2 / TiO 2 .
The XRD pattern of CeO 2 ( Fig. 1d) revealed all of the major characteristic peaks of CeO 2 corresponding to the (111), (200), (220), (400), (311), (222) and (420) planes, which are very close to the face centered cubic CeO 2 crystal [23] indicating the cubic fluorite structure (JCPDS file No: 81-0792). No changes in the phase composition or the support structure were detected after gold deposition. Moreover, no reflections related to the Au NPs were observed as mentioned above.
The highest specific surface area (S BET ) was measured for 4 wt%Au/TiO 2 being 50 m 2 /g cat ( Table 1). Loading of 4 wt% Au on TiO 2 decreased its surface area by 15%. Both addition of CeO 2 and La 2 O 3 decreased the specific surface area of 4wt%Au/La 2 O 3 /TiO 2 and 4wt%Au/CeO 2 /TiO 2 in comparison with 4wt%Au/TiO 2 . The lowest specific surface area was determined for 4wt%Au/La 2 O 3 and 4wt%Au/CeO 2 . In comparison with data reported by Demidova et al. [28] the S BET of La 2 O 3 and CeO 2 are much lower than in the current work, however, following the same trends.
The mean size of gold particle was determined by TEM (Table 1, Electronic supplementary material, Figure  S1). The largest value was measured for 4wt%Au/La 2 O 3 , which also exhibited the lowest specific surface area. On the other hand, the average gold particle sizes for other studied catalysts were in the narrow range of 2.6-2.9 nm. Morphology of different catalysts was also investigated ( Fig. S1). In particular, 4 wt% Au/TiO 2 exhibited irregular shape particles in the range of 10-35 nm (Fig. S1a). Morphology of 4 wt% Au/CeO 2 /TiO 2 and 4 wt% Au/La 2 O 3 / TiO 2 did not change remarkably after ceria and lanthana modification because to their small amounts (Fig. S1 b, c).  It is noted in the literature [28][29][30] that the acid-base properties of the support play a very important role in the amination of oxygen-containing compounds. The acidic and basic properties of supports and respective gold catalysts were investigated by NH 3 -TPD (  Fig. 3).
Three types of acid sites with different strength and concentrations were observed for the initial supports ( Table 2, Fig. 2). Among the used supports, unmodified titania has the highest acidity, characterized by the presence of both weak and medium strong Brønsted acid sites (acidic OH groups), according to [31][32][33]. The presence of strong acid sites may be due to the existence of Lewis (aprotic sites-tetrahedral coordinated Ti 4+ ) and/or Brønsted sites. The total acidity of ceria and lanthana was 1.5 and 2.1 fold lower than the acidity of titania. The main difference is in the concentration of weak acid sites the amount of which for TiO 2 is 2.3 fold higher than for CeO 2 and La 2 O 3 , both latter ones exhibiting the same amounts. In contrast to ceria, the concentration of medium and strong acid sites for lanthana was slightly higher than for titania.
After modification of the pristine titania surface with ceria and lanthana, a decrease in the concentration of both weak and medium acidic centers was observed, which is caused by dehydration of the surface under high temperature (550 °C) during preparation. In the case of the Cemodified material, the concentration of strong acid centers increases almost two fold, compared to modification with lanthana, for which a sevenfold decrease in the concentration of strong acid sites was observed. It should be noticed that on the contrary to lanthana ceria is a reducible oxide with variable valence states. It can be suggested that after modification of titania with ceria, new Lewis acid sites Ce 4+ /Ce 3+ can be formed, which presence being indirectly confirmed by TPR [34]. Deposition of gold on the supports   Fig. 1e). For all other studied catalysts, acidity alteration was much less noticeable and was not associated with changes in the phase composition according to XRD (Fig. 1). For 4wt%Au/TiO 2 the amount of weak sites moderately increased, while the concentration of medium sites slightly decreased, at the same time strong acid sites almost vanished. Similar trends in the change of support acidity after the introduction of the metal were previously discussed [35][36][37]. The origin of such changes was related to the mutual influence of the support and the metal crystallites on each other through their interactions at the catalyst preparation step. Furthermore, it was found [38][39][40][41] that during the gold deposition, the support surface is protonated, which leads to formation of additional OH groups, which can remain on the surface even after drying and redox pretreatments. Moreover, a part of the acid sites previously present on the surface can be blocked by formed gold nanoparticles. The amount of blocked sites depends on the nanoparticles size. Moreover, acidity can also affect the particle size, as previously found [42]. For Ce-modified titania catalysts, a decrease in the amount of strong acid sites after deposition of gold was also observed. In this case, however, the concentration of weak and medium acid sites increases. For 4wt%Au/La 2 O 3 /TiO 2 and 4wt%Au/CeO 2 the concentration of strong acid sites significant increased. When comparing XPS (Table 4) and NH 3 -TPD (Table 2) data, it can be assumed that a part of these sites (39 µmol/g) is due to the presence of Au + , which are Lewis acid sites, while another part is associated with Brønsted acidity and belongs to the support or the modifier. As for the acid sites of weak and medium strength, the amount of weak ones decreased for 4wt%Au/La 2 O 3 /TiO 2 and increased for 4wt%Au/CeO 2 , while that of medium strong sites varied opposite to the weak ones.
According to the literature [43][44][45][46] CO 2 adsorption on metal-oxide materials results in formation of various carbonate species (bicarbonate, bidentate and monodentate carbonates), which are desorbed at different temperatures giving information about the strength and nature of the basic sites. CO 2 desorption in the low-temperature range (25-200 °C) is usually associated with the interactions of CO 2 with surface hydroxyl groups, which are basic sites of weak strengths. Medium strong basicity is related to the presence of metaloxide pairs, in this case CO 2 desorption is observed in the range of 200-400 °C. Desorption peaks appearing in the range of 400-600 °C are caused by monodentate carbonate species formed on low-coordination oxygen anions which correspond to strong basic sites.
Three types of basic sites of different strength and concentrations were observed on the surface of studied supports in similar temperature ranges mentioned above (Table 3, Fig. 3). Among the used supports, CeO 2 and La-modified titania possess the highest and approximately the same basicity, with a small difference in the distribution of the basic sites in strength. For ceria weak/medium/strong site ratio is 2:2:1, while for La 2 O 3 /TiO 2 , the ratio is 3:3:1. Titania and lanthana have intermediate basicity, for them the W/M/S ratio is 6:10:1 and 2:1:1, respectively. The lowest basicity was determined for Ce-modified titania, with the predominant contribution of the basic sites of medium strength (W/M/S ratio is 9:13:1).
Similar to acidic properties, after gold deposition a redistribution of basic sites was observed. For almost all studied catalysts, except 4wt%Au/TiO 2 , a significant increase in the concentration of the basic sites was  observed compared to the corresponding supports, while the number of strong basic sites increased for all materials without any exception. Since the acid-base properties of materials are interrelated, such changes could occur for the reasons described above for acidity. The 18-fold increase in the basicity of 4wt%Au/La 2 O 3 after gold deposition should be noted separately, associated with changes in the phase composition as described above for acidity.
Moreover, CO 2 desorption can be originated from carbonates, which are incorporated in the structure of lanthanum hydroxycarbonate. Thus, evaluation of basic sites is not straightforward, as these residual carbonates contribute to the overall released CO 2 in addition to carbon dioxide desorbed from basic sites. Furthermore, these data explain the formation of Au n d− sites (38%, Table 4, Fig. 4a) due to increased interactions between gold and the support accompanied by changes in the structure and phase composition of the support. XPS was used to determine the electronic state of gold. XPS spectra of Au4 f are shown in Fig. 4. A relative atomic concentration of various electronic states of gold, as well as the corresponding binding energies (BE), identified according to the literature [25][26][27][28][29][30][31][32][33][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61] are given in Table 4. Relative values of the various gold states depend strongly on the support nature. On the surfaces of all studied materials, most of gold (50-81%) is in a metallic state with BE (Au4 f7/2 ) in the range of 84.1-84.3 eV, part of gold (12-21%) is present as Au + with BE (Au4 f7/2 ) in the range of 85.0-85.3 eV. In the case of unmodified and Ce-modified samples, another state related to Au 3+ with BE of Au4 f7/2 = 86.1 and 86.2 eV appears in XPS spectra (11 and 12%, respectively). It is notable that for 4wt%Au/La 2 O 3 and 4wt%Au/CeO 2 within BE range 83.3-83.5 eV, related to Au n d− states (38 and 22%, respectively), was observed. Such a shift towards lower BE as compared with the metallic state can be explained by several reasons. A negative particle charge may occur due to an electron transfer from the support to gold [54,55,60]. Another possible explanation is stronger interactions between gold and the support accompanied by local changes in the structure and phase composition of the support [43,44,48]. Finally, the particle shape determined by the size of gold nanoparticles may also be a reason of a lower BE shift [57].

Reductive Amination of Cyclohexanone
The results revealed that imines 1C/1D were instantaneously formed already after mixing of cyclohexanone with benzylamine at room temperature. According to GC analysis high conversion of cyclohexanone was obtained already after few minutes when a mixture of reactants and a solvent was prepared. Since the imine formation kinetics was very rapid, it was not quantified. Two different imines were formed, 1C and 1D (Table 5, Fig. 5) with D being the main product in line with quantum mechanical calculations for the Gibbs free energy also showing that this product is more stable than 1C by 19.5 kJ/mol at DFT/B3LYP/DNP level (Fig. 6). Standard thermodynamic quantities in the range 275-475 are shown in Table 6. At 298.15 K, the Gibb's free energy was 620.3 and 614.4 kJ/mol for the two conformers of the 1D structure and 613.8 and 618.0 kJ/mol for 1C.
The product distribution in amination was analyzed by NMR for 4wt% Au/TiO 2 ( Table 5). Besides the anticipated products the mixture contained also 9% unreacted cyclohexanone. The molar ratio between unreacted benzylamine to cyclohexanone was 0.44 showing that amine not only reacts with a ketone, but also undergoes self-condensation forming E-(N)-benzyl-1-phenylmethanimine (Table 5). Kinetics of amine formation over different catalysts is shown in Fig. 7.
The results illustrate that the lowest produced total concentration is obtained for 4wt%Au/La 2 O 3 /TiO 2 , which exhibited also a high amount of strong acid sites ( Table 2). The highest initial rate for amine formation was obtained by 4wt%Au/TiO 2 followed by 4wt%Au/CeO 2 /TiO 2 ( Table 7). The initial formation rates for three other catalysts were very small resulting also in low conversion after 4 h (Fig. 7). The three most active catalysts, 4wt%Au/TiO 2 , 4wt%Au/CeO 2 / TiO 2 and 4wt%Au/La 2 O 3 /TiO 2 were retaining their activity also after 1 h reaction time resulting in 72%, 79% and 27% yield of N-benzylcyclohexanamine after 4 h. The concentration of amine increased in the liquid phase for other catalysts as follows: 4wt%Au/CeO 2 < 4wt%Au/La 2 O 3 < 4wt%Au/ TiO 2 < 4wt%Au/CeO 2 /TiO 2 .
It is important to note here that rather high yields of amine were obtained with the supported gold catalysts containing small gold particle, below 3 nm (Tables 1 and 7). As a comparison with literature, relatively large gold particles, 8.4 nm were active in reductive amination of aldehydes over gold supported on mesoporous silica functionalized by an amine [62]. In that work [62] the reduction was, however, performed at room temperature with a slight excess of the stoichiometric reducing agent, dimethylphenylsilane in 2-propanol as a solvent.
When using molecular hydrogen as a reducing agent, Au/ SiO 2 -SO 3 H catalyst with 4.1 nm gold particles was rather inactive in reductive amination of furfural with aniline under 50 bar hydrogen at room temperature in ethyl acetate, giving mainly imine and only 3% yield of amine in 8 h [63]. In the latter study the gold particle size was rather large, 4.1 nm, which can decrease the hydrogenation rate as activity of gold catalysts is typically very sensitive to the cluster size. Moreover, a low BE of 83.4 eV indicated the presence of Au δ− [63], while in the current work gold was mainly in the metallic state ( Table 4).
The catalyst giving the highest yield for the desired amine, i.e. 4wt%Au/CeO 2 /TiO 2 contained twofold more basic sites and 1.3 fold more acidic sites in comparison with 4wt%Au/TiO 2 (Tables 2, 3). A lower amine yield was obtained with 4wt%Au/LaO 2 /TiO 2 which also exhibited 2.5 fold strong acid sites in comparison with 4wt%Au/CeO 2 / TiO 2 . When comparing the amount of strong acid sites for these catalysts and the corresponding amine yields, it can be stated that a lower amount of strong acid sites was beneficial for amine production. It can also be noted that a large fraction of metallic gold exists in 4wt%Au/TiO 2 and 4wt%Au/CeO 2 /TiO 2 and 4wt%Au/La 2 O 3 /TiO 2 , The latter one exhibited a lower activity compared to the two former ones, despite a larger amount of metallic gold. 4wt%Au/TiO 2 was more active, but less selective than 4wt%Au/CeO 2 /TiO 2 .  Conversion 91% . 5 The reaction scheme for the reductive amination of cyclohexanone with benzylamine. Notation is in Table 5 In addition to imine and amine, several other products were also identified by NMR (Table 5). No cyclohexanol was observed in the reaction mixture after 4 h for reductive amination of cyclohexanone with benzylamine in toluene on 4wt%Au/TiO 2 opposite to the results where reductive amination was performed in water using a homogeneous reducing agent, such as NaBH 4 and water as a solvent [64]. Absence of cyclohexanol among the products in reductive amination of cyclohexanone with benzylamine in the current work can be partially explained by low ability of metallic gold, produced via reduction with hydrogen at 300 °C, to dissociate hydrogen [65].
Low activity of 4wt%Au/La 2 O 3 /TiO 2 is related to its high acidity and basicity. From the mechanistic point of view reductive amination of ketones proceeds differently than amination of alcohols through borrowing hydrogen. In the latter case some acidity is required for dehydrogenation of an alcohol and formation of a corresponding aldehyde. For reductive amination of ketones, it has been stated that the carbonyl bond is activated by homogeneous Lewis acid catalysts, forming an aminol followed by activation of the imine towards nucleophilic attack [64]. Furthermore, it was proposed in ref. [65] for reductive amination of benzaldehyde with aniline using heterogeneous B(OSO 3 H) 3 /SiO 2 as a catalyst, that Brønsted acidity plays a role in increasing the electrophilic character of the carbonyl compound leading to formation of an intermediate which further dehydrates to imine.   Selectivity in amination has also been correlated with electronegativity of the support metal ions in [28,30]. The results of [28] in amination of myrtenol showed that gold supported on La 2 O 3 and CeO 2 exhibited low conversion and selectivity to secondary amines, whereas in N-alkylation of aniline with benzyl alcohol the selectivity to secondary amine was slightly higher with Ti 4+ ion in comparison to Ce 4+ ion [30]. The electronegativity of Ti 4+ , Ce 4+ and La 3+ is decreasing as follows: 14, 10 and 8.23, respectively [28,30]. In reductive amination of cyclohexanone with benzylamine the highest amine yield was obtained over 4wt%Au/TiO 2 with the highest support ion electronegativity in comparison to CeO 2 and La 2 O 3 , which gave low amine yields. The best catalysts in the current work are Au/TiO 2 and Au/CeO 2 /TiO 2 which could also be related to their high electronegativity.
As a comparison the yields of N-benzylcyclohexanamine produced via reductive amination (Table 8, entries 1-3) and N-alkylation of cyclohexylamine with benzylalcohol (Table 8, entry 4) with the current results (Table 8, entry 5) agree very well with the work of Liang et al. [6]. In the latter work it was reported that a commercial 1 wt% Au/ TiO 2 with 2-3 nm Au particles was very active and selective for production of N-benzylcyclohexanamine using 1:4 molar ratio of cyclohexanone to benzylamine with formic acid as a reductant at 60 °C in tert-butanol as a solvent giving after 5 h 97% yield of amine [6]. The TOF for formation of N-benzylcyclohexanimine, defined as moles of formed amine divided by moles of the surface gold over 1 wt% Au/TiO 2 [6] was 1.1 s −1 , while in the current work it was 52 s −1 . The main difference between these studies is the use of formic acid as a reducing agent [3,6], whereas hydrogen was applied in the current study. The gold particle size was about the same in the current work and in [6]. In addition to formic acid [3,6], also NaBH 4 [10] has been used as a reducing agent for production of N-cyclohexylbenzylamine as illustrated in Table 8. Furthermore, N-alkylation of cyclohexylamine with benzylalcohol is rather slow reaction, although giving a high yield of the desired product (Table 8, entry 4). Thus it can be concluded that Au/CeO 2 /TiO 2 using hydrogen as a reducing agent can be considered as a viable alternative to chemical reducing agents.

Reductive Amination of Propiophenone
In reductive amination of propiophenone with benzylamine the initial reaction mixture was analyzed by GC-MS showing that a small fraction of propiophenone has already reacted to the corresponding imine, α-ethyl-N-(phenylmethyl)benzenemethaneimine (2C/2D) at room temperature. Together with this imine a small amount of E-(N)-benzyl-1-phenylmethanimine was also present in the initial mixture and the molar ratio between the unreacted benzylamine to propiophenone was 0.48. Reductive amination of propiophenone over 4wt%Au/ CeO 2 /TiO 2 resulted in 20% conversion after 4 h ( Table 9, Fig. 8). The ratio of unreacted benzylamine to propiophenone over this catalyst was 0.5 showing the benzylamine reacts not only with propiophenone. The yield of the Table 9 NMR results from the reaction mixture obtained from reductive amination of propiophenone reaction with benzylamine over 4 wt% Au/ CeO 2 /TiO 2 in cyclohexane as a solvent, 100 °C, 30 bar hydrogen after 5 h (a) Benzylamine amount and its product are excluded from cyclohexanone yield calculation desired amine was 11.2% corresponding to TOF of 6.3 s −1 for formation of amine. The formed imines (2C/2D) were to a substantial extent hydrogenated to the corresponding amine (2E) over 4wt%Au/CeO 2 /TiO 2 . The final amine selectivity at 20% conversion was 56%, defined as the yield of amine divided by converted propiophenone determined based on NMR analysis It is known that especially Brønsted acidity promoted the reaction between aniline and furfural under 50 bar hydrogen at room temperature in ethyl acetate [50], when the imine was formed in the first step followed by hydrogenation to corresponding amine.
Hydrogenation of the carbonyl bond in ketone was very minor, 2% yield, over 4wt%Au/CeO 2 /TiO 2 catalyst in comparison to formation of imine with subsequent hydrogenation to amine, which was analogous to the case of cyclohexanone reductive amination. In addition to the desired imines, amines and phenyl-1-propanol, minor amounts of unidentified side products were formed (Table 9).

Conclusions
Several gold catalysts supported on TiO 2 , La 2 O 3 , CeO 2 , and mixed oxides, La 2 O 3 /TiO 2 , CeO 2 /TiO 2 were prepared by deposition-precipitation method and investigated in reductive amination of cyclohexanone and propiophenone using molecular hydrogen as a reducing agent. Typically Au was present as small particles, below 3 nm in all other catalysts except Au/CeO 2 which had a slightly larger cluster size. According to XPS gold mainly the metallic state after prereduction with hydrogen at 300 °C. The lowest fraction of metallic Au was present in Au/La 2 O 3 catalysts.
The catalytic results revealed that the most promising catalysts in reductive amination of cyclohexanone with benzylamine at 100 °C under 30 bar hydrogen using toluene as a solvent namely 4 wt% Au/CeO 2 /TiO 2 exhibited mainly weak and medium strong acid sites. On the other hand, 4 wt% Au/ La 2 O 3 /TiO 2 was very unselective catalyst giving only 27% yield of N-benzylcyclohexanamine at 89% conversion. This catalyst contained mainly strong acid sites. The best catalyst in amination of cyclohexanone, 4 wt% Au/CeO 2 /TiO 2 , was also tested in reductive amination of propiophenone giving 56% selectivity to corresponding amine at 20% conversion in 5 h. Fig. 8 The reaction scheme in the reductive amination of propiophenone with benzylamine over 4wt% Au/CeO 2 /TiO 2 .The notation is the same as in NMR results (Table 9)