Highly Efficient Liquid-Phase Hydrogenation of Naringin Using A

materials

Article Highly Efﬁcient Liquid-Phase Hydrogenation of Naringin Using a Recyclable Pd/C Catalyst

Jiamin Zhao, Ying Yuan, Xiuhong Meng, Linhai Duan * and Rujin Zhou *

Department of Chemical Engineering, Guangdong University of Petrochemical Technology, Maoming 525000, China; [email protected] (J.Z.); [email protected] (Y.Y.); [email protected] (X.M.) * Correspondence: [email protected] (L.D.); [email protected] (R.Z.); Tel.: +86-668-298-1080 (L.D.)

Received: 3 December 2018; Accepted: 18 December 2018; Published: 24 December 2018

Abstract: A highly efﬁcient liquid-phase hydrogenation reaction using a recyclable palladium on carbon (Pd/C) catalyst has been used for the transformation of naringin to its corresponding dihydrochalcone. The effects of various solvents on the hydrogenation process were studied, with water being identiﬁed as the optimal solvent. The analysis also revealed that sodium hydroxide (NaOH) can accumulate on the surface of the Pd/C catalyst in alcoholic solvents, leading to its inactivation. The higher solubility of NaOH in water implies that it remains in solution and does not accumulate on the Pd/C catalyst surface, ensuring the catalytic activity and stability.

Keywords: Pd/C; Catalyst; Hydrogenation; Naringin; Dihydrochalcone

1. Introduction There has been significant interest in dihydrochalcones (DHC) since Horwits reported their strong sweetness in 1963 [1]; these heterocycles are also known to exhibit antioxidant or antidiabetic activities [2,3]. For example, Chao et al. [4] used phlorizin as a DHC template to develop three antidiabetic drugs approved by the Food and Drug Administration (FDA) and the European Medicine Agency (EMA) [5]. Snijman et al. [6] reported that the dihydrochalcones aspalathin and nothofagin exhibit strong antioxidant activities, implying that they are ingested into the human body as intact glycosides. Janvier et al. [7] gained approval for using the dihydrochalcone neohesperidin as a food additive (E959) in Europe. Naringin is a flavanone occurring as the major component of exocarpium and pomelo, which are cultivated widely in south China [8–10]. Therefore, processes to convert naringin to value-added products on an industrial scale must be developed. Naringin dihydrochalcone (NDC) can be prepared from naringin via a two-step alkali- mediated hydrogenation reaction at high pressures [11]. First, NaOH(aq) or (KOH(aq)) is used as a base for ring-opening of the tetrahydropyran-4-one fragment of naringin to afford the corresponding chalcone intermediate with an (E)-alkene bond. Second, selective hydrogenation of this alkene bond using Pd/C (or Raney nickel) catalyst at high hydrogen pressures yield the dihydrochalcone product; the reaction scheme is shown in Scheme1. The key feature of this reaction is the selective hydrogenation of the C=C bond of the DHC intermediate over its C=O functionality. An ideal process would involve hydrogenation at medium-to-low hydrogen pressures at an ambient temperature using a heterogeneous catalyst that can be easily recovered and recycled [12,13]. Pd/C has often been used as a catalyst to selectively reduce the C=C bond of α, β-unsaturated carbonyl compounds, and the efficacy and mechanism of this reaction has been proven by experimental and theoretical results [14–16] and studies [17–19].

Materials 2019, 12, 46; doi:10.3390/ma12010046 www.mdpi.com/journal/materials Materials 2019, 12, 46 2 of 11 Materials 2017, 10, x FOR PEER REVIEW 2 of 12

SchemeScheme 1. The 1. The reaction reaction scheme scheme of hy ofdrogenation hydrogenation of ofnaringin. naringin.

TheThe choice choice of anan appropriate appropriate solvent solvent is critical is critical for the for success the ofsuccess hydrogenation of hydrogenation using heterogeneous using heterogeneouscatalysis; the catalysis; physical propertiesthe physical of properties solvents can of solvents significantly can significantly influence the influence yield and the distribution yield and of distributionthe hydrogenated of the hydrogenated products. An products. ideal solvent An idea in al catalyticsolvent in reaction a catalytic can reaction dissolve can the soliddissolve reactants the solidand reactants products and effectively, products enhance effectively, conversion enhance rates, conversion and ensure rates, that theand catalyst ensure surfacethat the remains catalyst free surfaceof inhibitors remains [20 free]. Alcohols of inhibitors (e.g., [20]. methanol Alcohols or ethanol)(e.g., methanol are the mostor ethanol) widely are used the solventsmost widely for reported used solventsheterogeneous for reported catalytic heterogeneous hydrogenation catalytic reactions hydr [21ogenation]. Wei et reactions al. [22] have [21]. shownWei et that al. Pd[22] catalysts have shownexhibit that higher Pd catalysts activity exhibit for hydrogenation higher activity reactions for hydrogenation in toluene and reactions ethanol, in than toluene in DMF, and acetonitrile, ethanol, thanor water.in DMF, However, acetonitrile, Ma et or al. water. [23,24] However, reported that Ma water et al. was [23,24] a more reported effective that solvent water for was liquid-phase a more effectivehydrodechlorination solvent for liquid-phase of chlorophenols hydrodechlorination catalyzed by Raney of chlorophenols nickel. However, catalyzed there has by been Raney little nickel. research However,on the effects there ofhas different been little solvents research on liquid-phase on the effects catalytic of different hydrogenation solvents on of naringin.liquid-phase catalytic hydrogenationIn this study, of naringin. our primary aim was to develop a practical process for catalytic hydrogenation ofIn naringin this study, to afford our primary naringin aim dihydrochalcone was to develop usinga practical Pd/C process as a recyclable for catalytic heterogeneous hydrogenation catalyst. of naringinThis was to afford achieved naringin by studying dihydrochalcone the effects using of different Pd/C as solvents a recyclable and theheterogeneous influence of catalyst. water content This wason achieved the yield by of studying hydrogenation. the effects The of effects different of solventssolvents and the reaction influence conditions of water on content the structure on the of yieldthe recoveredof hydrogenation. Pd/C catalyst The effects was also of studiedsolvents using and transmissionreaction conditions electron on microscopy the structure (TEM), of X-raythe recoveredphotoelectron Pd/C spectroscopycatalyst was (XPS),also studied etc. using transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), etc. 2. Experimental Section 2. Experimental Section 2.1. Materials and Methods 2.1. MaterialsThe 732 and cation Methods exchange resin was purchased from Shape Chemical, Shanghai, China. Naringin wasThe obtained 732 cation from exchange the National resin Institute was purchased for the Controlfrom Shape of Pharmaceutical Chemical, Shanghai, and Biological China. Naringin Products in wasBeijing, obtained China. from Other the National chemicals Institute of analytical for the gradeControl were of Pharmaceutical purchased from and Sigma-Aldrich, Biological Products St. Louis, in MO,Beijing, USA. China. Other chemicals of analytical grade were purchased from Sigma-Aldrich, St. Louis, MO, USA.TEM characterization was performed using a Hitachi HT-7700 microscope (Hitachi Corporation, Tokyo,TEM Japan).characterization High-resolution was performed TEM (HRTEM) using wasa performedHitachi HT-7700 using amicroscope Tecnai G2 F30(Hitachi S-Twin Corporation,microscope Tokyo, (Thermo Japan). Fisher High-resolution Scientific, MA, USA)TEM (HRTEM) operated at was an accelerationperformed using voltage a Tecnai of 300 G2 kV. F30 S-TwinThe microscope surface composition(Thermo Fisher of theScientific, catalyst MA, was USA) analyzed operated using at XPS an acceleration (Thermo Escalab voltage 250Xi of 300 XPS) kV.(Thermo Fisher Scientific, MA, USA) with Al Kα radiation, operated at 15 kV and 14.9 mA, as the excitationThe surface source. composition Binding energy of the valuescatalyst were was referenced analyzed tousing the CXPS (1s) (Thermo peak at 285.0Escalab eV. 250Xi XPS) (Thermo Fisher Scientific, MA, USA) with Al Kα radiation, operated at 15 kV and 14.9 mA, as the 2.2. Preparation of Pd/C Catalyst excitation source. Binding energy values were referenced to the C (1s) peak at 285.0 eV. The 10 wt % Pd/C catalyst was prepared by adding 0.2 g of activated carbon to 40 mL of water 2.2.containing Preparation 0.11 of Pd/C g Na Catalyst2PdCl4 (Sigma-Aldrich, St. Louis, MO, USA). After sonication for 10 min and stirring for 4 h, NH ·H O (Sigma-Aldrich, St. Louis, MO, USA) was added dropwise to the solution The 10 wt% Pd/C3 catalyst2 was prepared by adding 0.2 g of activated carbon to 40 mL of water for adjusting pH to 8.5. Next, the Pd adsorbed on activated carbon was reduced by adding 10 mL of containing 0.11 g Na2PdCl4 (Sigma-Aldrich, St. Louis, MO, USA). After sonication for 10 min and stirring for 4 h, NH3·H2O (Sigma-Aldrich, St. Louis, MO, USA) was added dropwise to the solution for adjusting pH to 8.5. Next, the Pd adsorbed on activated carbon was reduced by adding 10 mL of

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freshly prepared 0.08 mol L-1 NaBH4 (Sigma-Aldrich, St. Louis, MO, USA) solution. The mixture was further stirred for 12 h. Finally, the Pd/C was washed and collected by several rounds of centrifugation and the ﬁnal product was dried under vacuum for 12 h.

2.3. Procedures Used to Carry Out Hydrogenation Reactions Liquid-phase hydrogenation was performed in a 250-mL Hastelloy autoclave (Parr, Illinois, USA) fitted with a mechanical stirrer and an electric temperature controller. In a typical reaction, the reactor was loaded with 0.50 g of the reduced heterogeneous Pd/C catalyst and 150 mL of an aqueous solution containing 5.0 g of naringin and 0.6 g of NaOH (Sigma-Aldrich, St. Louis, MO, USA). The reactor was purged with H2 to remove air and was then pressurized to 1.5 MPa using H2. The reactor was then heated to 40 ◦C and stirred at 600 rpm for 10–14 h. The reaction mixture was then filtered to recover the heterogeneous catalyst and the filtrate was passed through a type 732 cation exchanger (Shape Chemical, Shanghai, China) (to exchange Na+ for H+ cations). This resulted in crystallization of the dihydrochalcone product from the solution, and the crystals were collected using vacuum filtration [8].

3. Results and Discussion

3.1. Characterization of Pd/C and the Product DHC The TEM images (Figure1) of the as-synthesized Pd/C indicated that Pd nanoparticles with diameters of 4.3 nm are dispersed uniformly on the carbon black. The X-ray diffraction (XRD) patterns of the Pd/C sample (Figure2a) exhibit three typical peaks at 2 θ = 40.1◦, 47.4◦, and 68.7◦, corresponding to the (111), (200), and (220) reﬂections, respectively, of crystalline Pd, which matches well with PDF 65-6174. The diameters of the Pd nanoparticles can also be measured by XRD using the Scherrer equation [25]: L = Kλ/β cos θ. Where λ is the X-ray wavelength in nanometer (nm), β is the peak width of the diffraction peak proﬁle at half maximum height resulting from small crystallite size in radians and K is a constant related to crystallite shape, normally taken as 0.89. The diameter of the Pd nanoparticle calculated using Scherrer equation is 0.41 nm, which is similar to the average particle size (0.43 nm) observed from TEM. The XPS spectrum of Pd/C (Figure2b) shows two symmetrical peaks assigned to the Pd 3d 5/2 and Pd 3d 3/2 core levels. The peaks at 335.9 and 341.4 eV are attributed to metallic Pd0, while those at 337.3 eV and 343.4 eV correspond to the Pd 2+ species. The percentage of metallic Pd0 was calculated from the relative areas under these peaks; metallic Pd0 was found to be the main metal species on the surface of the as-prepared catalyst (65 wt %). MaterialsMaterials2019, 122017, 46, 10, x FOR PEER REVIEW 4 of 12 4 of 11

(a) (b)

FigureFigure 1. Transmission 1. Transmission electron electron microscopy microscopy (TEM) images (TEM) of images 10 wt % of Pd/C 10 withwt% differentPd/C with magnifications different (a–c) magnifications (a–c) and size distribution of Pd particles (d). and size distributionMaterials 2017, 10 of, x PdFORparticles PEER REVIEW (d). 5 of 12

(a) (002) ) (200)

(220) Intensity (a.u. Intensity

40 45 50 55 60 65 70 2 Theta (deg.)

0 (b) Pd Pd0:Pd2+=1.83

Pd2+ Intensity (a.u.)

355 350 345 340 335 330 B.E.(eV)

Figure 2. (aFigure) XRD 2. and(a) XRD (b and) X-ray (b) X-ray photoelectron photoelectron spectroscopy spectroscopy (XPS) (XPS) patterns patterns of Pd/C. of Pd/C.

The product naringin hydrochalcone was characterized by infrared spectroscopy (IR) absorption (Figure 3). IR absorption at 3390 cm-1 (-OH), 2923.84 cm-1 (-CH3), 1631 cm-1 (conjugated -C=O), 1513 cm-1, 1438 cm-1 and 817 cm-1 (aromatic nucleus) were indicative of a hydroxylated dihydrochalcone, similar to the result of Tang et al. [8].

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The product naringin hydrochalcone was characterized by infrared spectroscopy (IR) absorption −1 −1 −1 (Figure3). IR absorption at 3390 cm (-OH), 2923.84 cm (-CH3), 1631 cm (conjugated -C=O), 1513 cm−1, 1438 cm−1 and 817 cm−1 (aromatic nucleus) were indicative of a hydroxylated Materialsdihydrochalcone, 2017, 10, x FOR similar PEER REVIEW to the result of Tang et al. [8]. 6 of 12

100

60 -CH 50 3 T (%)

20 aromatic nucleus -OH -C=O 10

0 4000 3500 3000 2500 2000 1500 1000 500 Wave number (cm-1)

Figure 3. IRIR absorption absorption of naring naringinin hydrochalcone (DHC).

3.2. Solvent Effect on the Hydrogenation Reaction of Naringin over Pd/C Catalyst The hydrogenation of naringin overover Pd/CPd/C cataly catalystst was was examined examined in various solvents, including methanol, ethanol, iso-propanol, and n-hexane (Figure 44a).a). ItIt waswas foundfound thatthat naringinnaringin couldcould bebe hydrogenated in in all all these these solvents, solvents, with with DHC DHC yields yields depending depending strongly strongly on on the the solvent, solvent, according according to theto the following following order: order: methanol methanol > >ethanol ethanol > >iso-prop iso-propanolanol > > n-hexane n-hexane > > toluene. The Pd/CPd/C catalyst showed greater activity in alcoholic solvents than in n-hexane and toluene. Therefore, Therefore, protic solvents are betterbetter solventssolvents than than aprotic aprotic ones ones for for liquid-phase liquid-phase hydrogenation hydrogenation reactions reactions of naringin. of naringin. These resultsThese resultsare consistent are consistent with previous with reports,previous which reports, describe which that describe hydrogenation that hydrogenation of non-polar of substrates non-polar in polarsubstrates solvents in polar give solvents the best yieldsgive the of hydrogenatedbest yields of hydrogenated products [20,26 products]. The rates [20,26]. of these The hydrogenation rates of these hydrogenationreactions were alsoreactions dependent were onalso solvent dependent polarity, on withsolvent hydrogenation polarity, with reactions hydrogenation occurring reactions faster in occurringhigher-polarity faster solvents.in higher-polarity Indeed, for solvents. alcoholic Indeed, solvents, for DHCalcoholic yield solvents, was directly DHC proportional yield was directly to the ε µ proportionalorder of the normalized to the order empirical of the normalized parameter em (ETN),pirical dielectric parameter constant (ETN), ( ), dielectric and dipole constant moment (ε), ( and) of dipolethe solvents moment [23 ,(27μ), 28of]. the solvents [23,27,28]. Water, a highly polar protic solvent, can be used as an additive to increase the polarity of alcoholic solvents. Therefore, a series of mixed alcohol/water solvents were investigated to determine the impact of solvent polarity on hydrogenation reactions. A series of Pd/C-catalyzed hydrogenation reactions of naringin were performed in different mixed solvents, i.e., ethanol, 20 wt % water-ethanol (20/80, v/v), 50 wt % water-ethanol (50/50, v/v), 80 wt % water-ethanol (80/20, v/v), and water (Figure4b). These experiments revealed that the highest DHC yield was obtained using water as the solvent, followed by progressively lower DHC yields for 80 wt % water-ethanol, 50 wt % water-ethanol, 20 wt % water–ethanol, and ethanol. These results showed that the rate of hydrogenation increased with increasing polarity of the mixed ethanol-water solvents. Therefore, the rate of hydrogenation of naringin over the Pd/C catalyst can be increased signiﬁcantly by simply adding water to the alcoholic solvent.

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80 (a) methanol ethanol i-propanol n-hexane 60 toluene

40 Yield(%)

0 024681012 Time (hour)

(b) 80

40 Yield (%) Yield

0 0 2050 80 100 The proportion of water (%) FigureFigure 4.4. HydrogenationHydrogenation of naringinof naringin in different in different solvents solvents over 10 wt over % Pd/C 10 catalyst.wt% Pd/C (a) Hydrogenation catalyst. (a) Hydrogenationof naringin in variousof naringin solvents. in various (b) Hydrogenation solvents. (b) Hydrogenation of naringin in variousof naringin ethanol–water in various ethanol– mixtures. waterReaction mixtures. conditions: Reaction 150 mLconditions: of each solvent,150 mL 5of g each of naringin, solvent, solvent5 g of naringin, pH 12, 0.5 solvent g of 10 pH wt 12, % Pd/C(0),0.5 g of ◦ 10temperature wt% Pd/C(0), of 45 temperatureC, and H2 ofpressure 45 °C, ofand 1.5 H MPa.2 pressure of 1.5 MPa.

Water,The stability a highly and polar recyclability protic solvent, of the 10can wt be % used Pd/C as catalyst an additive used forto increase hydrogenation the polarity in water, of alcoholic50 wt % water-ethanol solvents. Therefore, (50/50, v /av ),series and ethanol of mixe wered thenalcohol/water investigated solvents (Figure 5were). In ethanol, investigated the initial to determineDHC yield the was impact 70 wt %of aftersolvent 12 h;polarity however, on thishydr yieldogenation dropped reactions. to 59 wt A %series on using of Pd/C-catalyzed Pd/C catalyst hydrogenationthat had been recycledreactions ﬁve of times.naringin However, were performed the DHC in yield different obtained mixed using solvents, water ori.e., water-ethanol ethanol, 20 wt%(50/50, water-ethanolv/v) as solvent (20/80, remained v/v), 50 almostwt% water-ethanol unchanged after (50/50, six v/v rounds), 80 wt% of catalyst water-ethanol recycling, (80/20, indicating v/v), andsuperior water stability (Figure of4b). the These Pd/C experiments catalyst in these revealed solvents. that Therefore,the highest we DHC concluded yield was that obtained water was using the waterbest solvent as the solvent, for performing followed Pd/C-catalyzed by progressively liquid-phase lower DHC hydrogenation yields for 80 wt of% naringin. water-ethanol, 50 wt% water-ethanol, 20 wt% water–ethanol, and ethanol. These results showed that the rate of hydrogenation increased with increasing polarity of the mixed ethanol-water solvents. Therefore, the rate of hydrogenation of naringin over the Pd/C catalyst can be increased significantly by simply adding water to the alcoholic solvent. The stability and recyclability of the 10 wt% Pd/C catalyst used for hydrogenation in water, 50 wt% water-ethanol (50/50, v/v), and ethanol were then investigated (Figure 5). In ethanol, the initial DHC yield was 70 wt% after 12 h; however, this yield dropped to 59 wt% on using Pd/C catalyst that had been recycled five times. However, the DHC yield obtained using water or water-ethanol (50/50, v/v) as solvent remained almost unchanged after six rounds of catalyst recycling, indicating superior stability of the Pd/C catalyst in these solvents. Therefore, we concluded that water was the best solvent for performing Pd/C-catalyzed liquid-phase hydrogenation of naringin.

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water 90 water-ethanol(50/50,v/v) ethanol

70 Yield(%)

50 123456 Resue time Figure 5. Repeated hydrogenation of naringin in water, water-ethanol, and ethanol.

3.3. The Influence Influence of Solvent on Pd/C Catalyst Structure Having shown that among the solvents studied, water is the optimal solvent for hydrogenation of naringin [[20,28–30],20,28–30], we used TEM and XPS studies to elucidate the solvent effect on the structure of the Pd/C catalyst. catalyst. The The recovere recoveredd 10 10 wt% wt % Pd/C Pd/C catalyst catalyst after after six six rounds rounds of ofuse use for for hydrogenation hydrogenation of ofnaringin naringin was was analyzed analyzed using using TEM. TEM. The The surface surface morp morphologieshologies of 10 of wt% 10 wt Pd/C % Pd/C catalyst catalyst that had that been had beenreused reused six times six times using using water water (Figure (Figure 6b)6 b)and and 50 50 wt% wt %water-ethanol water-ethanol (Figur (Figuree 66c)c) asas solventsolvent werewere almost identical to that ofof thethe originaloriginal Pd/CPd/C cata catalyst.lyst. On On the the other hand, when ethanol was used as the solvent,solvent, thethe morphologymorphology ofof thethe recoveredrecovered Pd/CPd/C catalyst changed significantly, significantly, with significantsignificant amounts of crystalline material deposited on its su surfacerface after six rounds of use in the hydrogenation reactions (Figure6 6d).d). To gain more information about the structural composition of this crystalline material, 10 wt % Pd/C catalysts recovered from ethanol–water (50/50) and ethanol reactions were subjected to XPS analysis. Table1 provides the XPS analysis results of the composition of fresh and reused Pd/C catalysts. This table shows the presence of Pd3d and O1s emissions at 336.39 eV and 532.60 eV, respectively, probably due to the presence of PdO. The biggest difference between catalyst samples recovered from hydrogenation reactions in water and ethanol was in their Pd3d and Na1s emissions. The Pd-to-Na ratios of a Pd/C catalyst recovered from hydrogenation reactions in water and ethanol were 1.79:1 and 0.38:1, respectively. This indicates that the crystalline material observed on the surface of the catalyst recovered from hydrogenation reactions in ethanol is probably NaOH. Therefore, the reduced catalytic activity of Pd/C in ethanol is due to NaOH blocking the catalytically active sites on the catalyst surface, preventing it from effectively absorbing hydrogen and the naringin substrate. However, when water is present, its higher polarity ensures that NaOH remains in solution, preventing the Pd/C catalyst surface from becoming deactivated.

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FigureFigure 6.6.TEM TEM images images of of the the Pd/C Pd/C catalysts catalysts fresh fresh (a), ( aftera), after 6 cycles 6 cycles of hydrogenation of hydrogenation in water in (waterb), after (b 6), cyclesafter 6 of cycles hydrogenation of hydrogenation in ethanol-water in ethanol-water (50/50) ((50/50)c), after ( 6c), cycles after of6 cycles hydrogenation of hydrogenation in ethanol in ( dethanol). (d).

To gain more informationTable 1. XPSabout analysis the structural of fresh and composition recycled Pd/C of catalysts.this crystalline material, 10 wt% Pd/C catalysts recovered fromArea ethanol–water (50/50) Centreand ethanol reactions were AT subjected (wt %) to XPS analysis.Peak _Table ID 1 provides the XPS analysis results of the composition of fresh and reused Pd/C Ethanol-Water Ethanol Ethanol-Water Ethanol Ethanol-Water Ethanol catalysts. This table shows the presence of Pd3d and O1s emissions at 336.39 eV and 532.60 eV, respectively,O1s probably 18,667 due to the 12,383presence of PdO. 532.60 The biggest 532.42 difference between 83.4 catalyst 83.63 samples Na1s 2700 3323 1071.52 1071.47 4.63 11.87 recoveredPd3d from hydrogenation 19,280 reactions 6107 in water 336.39 and ethanol was 336.11 in their Pd3d 11.96 and Na1s emissions. 4.5 The Pd-to-Na ratios of a Pd/C catalyst recovered from hydrogenation reactions in water and ethanol were 1.79:1 and 0.38:1, respectively. This indicates that the crystalline material observed on the 3.4. Optimal Reaction Conditions for Naringin Hydrogenation surface of the catalyst recovered from hydrogenation reactions in ethanol is probably NaOH. Therefore,The effects the reduced of reaction catalytic temperature, activity of pressure, Pd/C in ethanol pH, and is due catalyst to NaOH content blocking on the the DHC catalytically yield in hydrogenationactive sites on ofthe naringin catalyst were surface, then investigatedpreventing (Figureit from7 ).effectively Figure7a showsabsorbing that hydrogen the DHC yieldand inthe thesenaringin reactions substrate. increased However, up to when a maximum water is at presen hydrogent, its pressure higher polarity of 2.0 MPa, ensures with that no furtherNaOH increaseremains inin yieldsolution, at higher preventing pressures. the Pd/C Figure cataly7b showsst surface that from the optimal becoming temperature deactivated. for these hydrogenation reactions was 42–45 ◦C. Higher temperatures resulted in catalyst degradation, leading to lower DHC yields. Increasing the amountTable of1. catalystXPS analysis from of 2 fresh wt % and to 10recycled wt % signiﬁcantlyPd/C catalysts. increased the DHC yield, while the optimum basicity of the NaOH(aq)solvent was found to be pH 11.8 (Figure7d). The role Area Centre AT (wt%) of NaOHPeak on _ the ID reaction is to open heterocycles of naringin for forming the corresponding chalcone intermediate. If theEthanol-Water pH is lower thanEthanol 11, theEthanol-Water heterocycles cannotEthanol be opened.Ethanol-Water If the pHEthanol is too high, the glycosideO1s bonds on 18,667 naringin may12,383 be destroyed,532.60 and the532.42 corresponding 83.4 chalcone intermediate 83.63 Na1s 2700 3323 1071.52 1071.47 4.63 11.87 Pd3d 19,280 6107 336.39 336.11 11.96 4.5

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3.4. Optimal Reaction Conditions for Naringin Hydrogenation The effects of reaction temperature, pressure, pH, and catalyst content on the DHC yield in hydrogenation of naringin were then investigated (Figure 7). Figure 7a shows that the DHC yield in these reactions increased up to a maximum at hydrogen pressure of 2.0 MPa, with no further increase in yield at higher pressures. Figure 7b shows that the optimal temperature for these hydrogenation reactions was 42–45 °C. Higher temperatures resulted in catalyst degradation, leading to lower DHC yields. Increasing the amount of catalyst from 2 wt% to 10 wt% significantly increased the DHC yield, while the optimum basicity of the NaOH(aq)solvent was found to be pH 11.8Materials (Figure2019, 127d)., 46 The role of NaOH on the reaction is to open heterocycles of naringin for forming9 ofthe 11 corresponding chalcone intermediate. If the pH is lower than 11, the heterocycles cannot be opened. If the pH is too high, the glycoside bonds on naringin may be destroyed, and the corresponding chalconecannot be formed.intermediate These cannot results werebe formed. combined These to design results the were optimal combined conditions to for design this hydrogenation the optimal ◦ conditionsreaction: hydrogen for this reactionhydrogenation pressure reaction: of 2.0–2.5 hydrogen MPa, reaction reaction temperature pressure ofof 40–452.0–2.5C, MPa, pH 11.5–12.0,reaction temperatureand Pd/C catalyst of 40–45 loading °C, pH of 11.5–12.0, 8–10 mol wtand %. Pd/C catalyst loading of 8–10 mol wt%.

86 85 (b) (a) 84 80

82 75

70 80

Yield (%) Yield 65 (%) Yield 78

60 76

55 Reaction Pressure (MPa) 74 Reaction temperature (? ) 50 0.5 1.0 1.5 2.0 2.5 3.0 25 3 0 35 40 45 50

85 (c) (d) 80

80 70

75 Yield (%) Yield Yield (%) Yield 50

70 40

65 catalyst content (%) 30 pH

246810 8 9 10 11 12 13 1 4

Figure 7. EffectsEffects of of reaction reaction pressure ( a), temperature temperature ( b), catalyst content ( c), and pH ( d) on on the the DHC DHC yield. The Reaction conditions: 150 mL of each solven solvent,t, 5 g of naringin, solvent pH 12, 0.5 g of 10 wtwt% % Pd/C(0), temperature of 45 ◦C, and H pressure of 1.5 MPa. Pd/C(0), temperature of 45 °C, and H2 2pressure of 1.5 MPa. 4. Conclusions 4. Conclusions The effects of various solvent systems on the Pd/C-catalyzed liquid-phase hydrogenation of The effects of various solvent systems on the Pd/C-catalyzed liquid-phase hydrogenation of naringin have been investigated. Water was found to be the optimal solvent for affording the naringin have been investigated. Water was found to be the optimal solvent for affording the corresponding dihydrochalcone in good yield. The presence of water was critical for preventing corresponding dihydrochalcone in good yield. The presence of water was critical for preventing accumulation of NaOH on the surface of the Pd/C catalyst, which can lead to catalyst deactivation in accumulation of NaOH on the surface of the Pd/C catalyst, which can lead to catalyst deactivation in alcoholic solvents. An optimal high-yielding and scalable process was developed using a hydrogen alcoholic solvents. An optimal high-yielding and scalable process was developed using a hydrogen pressure of 2.0–2.5 MPa, a reaction temperature of 40–45 ◦C, an aqueous solvent of pH 11.5–12.0, and a pressure of 2.0–2.5 MPa, a reaction temperature of 40–45 °C, an aqueous solvent of pH 11.5–12.0, and recyclable Pd/C catalyst loading of 8–10 wt %. a recyclable Pd/C catalyst loading of 8–10 wt%. Author Contributions: L.D. and R.Z. conceived and designed the experiments; J.Z. carried out the laboratory work; Y.Y. and X.M. participated in data analysis. All authors gave ﬁnal approval for publication. Funding: This research was ﬁnancially supported by the National Natural Science Foundation of China (21476101).

Conﬂicts of Interest: The authors declare no conﬂict of interest.

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