Supported Palladium Nanoparticle Catalyzed α-Alkylation of Ketones

Sep 13, 2017 - Fax: +91-1894-230433. ... Phosphine-Free NNN-Manganese Complex Catalyzed α-Alkylation of Ketones with Primary Alcohols and ...
0 downloads 0 Views 6MB Size
Research Article Cite This: ACS Sustainable Chem. Eng. 2017, 5, 9683-9691

pubs.acs.org/journal/ascecg

Supported Palladium Nanoparticle Catalyzed α‑Alkylation of Ketones Using Alcohols as Alkylating Agents C. Bal Reddy, Richa Bharti, Sandeep Kumar, and Pralay Das* Natural Product Chemistry & Process Development Division, CSIR−Institute of Himalayan Bioresource Technology, Palampur 176061, HP, India Academy of Scientific & Innovative Research, New Delhi 110025, India

Downloaded via UNIV OF CALIFORNIA SANTA BARBARA on June 26, 2018 at 20:02:32 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.

S Supporting Information *

ABSTRACT: Polymer stabilized palladium (Pd@PS) nanoparticles (NPs) catalyzed α-alkylation of acyclic, cyclic, and aliphatic ketones were performed with methanol, ethanol, and long chain alkyl and benzyl alcohols. The heterogeneous catalyst, Pd@PS, was found to be highly active for most challenging small chain alkyl alcohols such as methanol and ethanol in alkylation reaction following oxidation, condensation, and reduction approaches.

KEYWORDS: Palladium nanoparticles, Heterogeneous catalyst, Alkylation, Ketones, Alcohols



INTRODUCTION α-Alkylation of ketones is the most versatile carbon−carbon bond formation reaction in organic synthesis. These reactions are conventionally performed using toxic alkyl halides as alkylating agents in the presence of strong bases.1,2 In recent years alcohols have been directly used as greener alkylating agents over alkyl halides in transition metal catalyzed αalkylation of ketones using a hydrogen borrowing strategy as a promising alternative approach.3−6 Inspired by the work of Grigg et al., who used alcohols as alkylating agents,7,8 many groups have envisioned a variety of alkylation methods using iridium,9−15 ruthenium,16−20 rhodium,21,22 and other transition metal catalysts.23−31 Methanol is an important feed stock chemical, and its dehydrogenation reactions are a valuable but challenging goal. Beller and Grutzmacher independently reported Ru-catalyzed dehydrogenation of methanol to hydrogen and carbon dioxide.32,33 Krische et al. reported Ir-catalyzed coupling of methanol with allenes34 and Glorius et al. reported activation of methanol for C−N bond formation reaction.35 In addition, the activation of methanol in α-methylation reactions was carried out under expensive homogeneous [Cp*RhCl2]2, [Cp*RuCl2]2, and iridium complexes (Scheme 1, reaction b).12−14,20,21 Like methanol, the dehydrogenation of ethanol for α-ethylation of ketones has also been described rarely. The only reported process for α-ethylation of ketones using ethanol (only one example) utilized a stoichiometric amount of catalyst (100 mmol) and excess of solvent (ethanol 4 mL).23 Among the reported methods, limited approaches are available for alkylation reactions of ketones under heterogeneous palladium catalyzed conditions (Pd/C,29,31 Pd/AlO© 2017 American Chemical Society

Scheme 1. Comparative Studies of the Research

(OH),27 Pd/Viologen,28 and Pd−Si−Pr−Ni Xantphos/SiO2 catalyst30). Even though, these methods were restricted to benzyl and long chain aliphatic alcohols with the requirement of a hydrogen acceptor29 and high temperature.31 Yet, there is no single report available where palladium catalyst has been Received: March 15, 2017 Revised: August 29, 2017 Published: September 13, 2017 9683

DOI: 10.1021/acssuschemeng.7b00789 ACS Sustainable Chem. Eng. 2017, 5, 9683−9691

Research Article

ACS Sustainable Chemistry & Engineering used efficiently for α-alkylation of ketones with methanol or ethanol under milder conditions. Since then, our group has been actively engaged in the development of heterogeneous transition metal NPs as catalyst and their applications in oxidative transformations of methanol,36 ethanol,37 and other challenging reactions.38−41 Herein, for the first time we present Pd@PS NPs catalyzed αalkylation reaction of ketones using small chain alcohols such as methanol and ethanol as well as long chain alkyl/benzyl alcohols as alkylating agents following oxidation, condensation, and reduction approaches (Scheme 1c).



Figure 1. (a) SEM image of the prepared Pd@PS catalyst. (b) SEMEDX conforming the presence of palladium on the surface.

PREPARATION OF THE Pd@PS CATALYST A 1 g portion of Amberlite IRA 900 resin (chloride form) was taken into a 100 mL round-bottom flask containing 30 mg of NaBH4 and 5 mL of water. The mixture was stirred at room temperature for 6 h, then the resin was washed with water until pH became neutral, and washed with acetone. The resin beads (borohydride exchanged) were dried under reduced pressure. The dried borohydride exchanged resin beads (solid surface) (1 g) were added to the solution of palladium acetate (10 mg) in DMF (3 mL) at 100 °C. The resulting mixture was heated for 1 h or until the dark brown color of the solution became colorless and simultaneously white solid beads were turned into blackish. After cooling, the beads were filtered through a cotton bed, washed with water and acetone, and dried under reduced pressure. The amount of palladium present in the catalyst was found to be 0.47 wt %.

Figure 2. (a, b) Low field TEM images of the Pd@PS catalyst at 20 nm scale.



CATALYST CHARACTERIZATIONS Scanning electron microscopy (SEM) was performed on E1010 ion sputter Hitachi, Japan. Transition electron microscopy (TEM) was conducted using JEOL 2100F and tecnai, twin 200 Kv (FEI, Netherlands). To prepare the TEM specimen, the samples were sonicated in water and then dispersed on a carbon coated copper grid (Microscopy sciences). The crystal structure of the catalyst was determined by powder X-ray diffraction (XRD) measurements in 2 theta range 10−90° on X’PERT Pro, equipped with x’Celerator solid state detector. The composition of the catalyst was analyzed by performing Xray photoelectron spectroscopy (XPS) on X-ray photoelectron spectrometer from prevac, Polland. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) was carried out on the instrument, ARCOS Spectro, Germany.

Figure 3. (a) Bright field TEM image of the Pd@PS catalyst at 5 nm scale. (b) Particle size distribution histogram calculated from a.



RESULTS AND DISCUSSION The formation of palladium NPs at the polymer surface was analyzed by SEM and energy dispersive X-ray (EDX) indicating the presence of palladium at the analyzed region (Figure 1). The low field TEM images of Pd@PS further confirmed the impregnation of palladium NPs over the polymer matrix at 20 nm scale (Figure 2) as well as at 5 nm scale (Figure 3a). The histogram representing the particle size distribution of the Pd NPs was drawn from Figure 3a by measuring the size with the help of image-J software and a larger number of particles was found ranging from 1 to 5 nm with largest average number in the range 1−3 nm (Figure 3b). The high resolution-TEM (HR-TEM) bright field image of Pd@PS represented the crystallographic orientation of the Pd NPs. The crystalline feature of Pd NPs having d-spacing of 0.22 and 0.19 nm corresponding to (111) and (200) reflection planes, respectively (Figure 4a). The inset picture shows the

Figure 4. (a) HR-TEM image showing lattice fringe spacing. (b) Single crystal of Pd@PS. (c) Fast Fourier transform (FFT) pattern of selected region from part a.

fast Fourier transformation pattern (FFT) from a selected region of HR-TEM, and the diffraction pattern also confirms the presence of a cubic (111) plane (Figure 4). 9684

DOI: 10.1021/acssuschemeng.7b00789 ACS Sustainable Chem. Eng. 2017, 5, 9683−9691

Research Article

ACS Sustainable Chemistry & Engineering

carbon, and nitrogen elements. The XPS spectrum of palladium showed two peaks at different binding energies, 334.48 and 340.12 eV, corresponding to Pd 3d3/2 and 3d5/2 respectively and in compliance with the reported values for Pd(0) (Figure 7). The Pd@PS catalyst was found to be recyclable up to four runs (Figure 8), and negligible leaching of Pd was detected by ICP-AES analysis (Figure 9). The TEM analysis of Pd@PS catalyst after four runs also showed the presence of Pd NPs (Figure 8b). The heterogeneity of the active Pd species on Pd@ PS was confirmed by the hot filtration (Figure 10) and Hg (0) poisoning test. We started our investigation using α-tetralone as a model substrate, and all the related parameters were extensively investigated to get the highest yield of the product. Initially, we explored different bases (K2CO3, Cs2CO3, K3PO4, KOH, NaOH, NaOtBu, and KOtBu) already reported in various alkylation reactions. Also, in our previous studies, the oxidative coupling reactions of methanol and ethanol were performed efficiently using KOtBu/NaOtBu, as base.36,37,42 Likewise, in this report KOtBu was found to be the most suitable for ethanol and methanol oxidation in the presence of Pd@PS catalyst (Table 1, entries 1−11). With these initial results, we further optimized the base loadings to get good yield of the product (Table 1, entries 12−17). We were pleased to observe that the use of 3 equiv of KOtBu gave the highest yield of the product (Table 1, entries 15 and 16). The reaction was also carried out at different temperatures and 110 °C was found to be the optimal temperature (Table 1, entries 15 and 19). The alkylation reactions involve multistep processes where the alcohols have to be used as alkylating as well as reducing agents. Also, the in situ produced aldehydes, oxidation products of methanol and ethanol are high volatile and less stable. Hence, it is necessary to optimize the amount of methanol and ethanol required for efficient alkylation. For this purpose, different concentrations of ethanol or methanol in combination with other solvents were also investigated. Among these, combinations of 2.5 mL ethanol/methanol and 0.5 mL of toluene gave the best results (Table 1, entries 15−20). Furthermore, screening of catalyst loadings indicated that Pd@PS (3 mol % Pd and wt % of Pd is 0.47%) gave a good result (Table 1, entries 10, 15, and 18). To check the reaction atmospheric conditions, we further carried out the reaction under O2 and N2 (Table 1, entries 21 and 22) which resulted in lowering the yield indicated that traces air present in the vial is beneficial for

The selected area electron diffraction (SAED) pattern of Pd@PS showed the diffraction rings corresponding to the (111), (200), (220), and (311) crystallographic planes (Figure 5).

Figure 5. Typical selected area electron-diffraction pattern of the palladium NPs.

The Pd@PS catalyst was further characterized by powder Xray diffraction (pXRD). The XRD of the polymer support (PS) was also carried out and compared with the XRD of the Pd@PS catalyst. The XRD of the Pd@PS catalyst showed two peaks at ∼40° and ∼45° corresponding to Pd (111) and Pd (200) planes, respectively (Figure 6), which are also in accordance with the planes obtained from SAED.

Figure 6. X-ray diffraction pattern (XRD) of PS and Pd@PS catalyst.

X-ray photoelectron spectroscopy (XPS) applied to determine the composition of Pd@PS catalyst. The full spectrum of XPS showed the presence of palladium, oxygen,

Figure 7. (a) XPS full spectrum of Pd@PS. (b) Pd 3d XPS spectra. 9685

DOI: 10.1021/acssuschemeng.7b00789 ACS Sustainable Chem. Eng. 2017, 5, 9683−9691

Research Article

ACS Sustainable Chemistry & Engineering

Figure 8. Recyclability experiment of Pd@PS catalyst.

Table 1. Optimization of Reaction Conditionsa

Figure 9. ICP-AES analysis of reaction mixture at different cycles.

Figure 10. Hot filtration test for the catalyst Pd@PS.

the conversion (Table 1, entries 15 and 16). The reaction was also tested with some other palladium catalysts such as Pd/ C29,31 and Pd(OAc)2. However, these catalysts afforded the desired product albeit in low yield under standard conditions (Table 1, entries 24 and 25). The reaction was also carried out in absence of the catalyst under different base concentrations and resulted in negligible/traces of product (Table 1, entries 26 and 27). Gratifyingly, we were delighted to observe that the desired product could be achieved in 82% yield when carried out with Pd@PS (3 mol % Pd), 3 equiv of KOtBu in mixture of ethanol/methanol and toluene (2.5:0.5 mL) solvent at 110 °C for 48 h. Next, we explored the potential use of Pd@PS catalyst for methylation reaction of different aryl ketones with methanol under the pre-optimized reaction conditions (Scheme 2). 4-

s no.

[Pd] (mol %)

base (equiv)

R−OH

yield (%)b

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15c 16c 17c 18c 19d 20e 21f 22g 23h 24 25 26 27

Pd@PS (3) Pd@PS (3) Pd@PS (3) Pd@PS (3) Pd@PS (3) Pd@PS (3) Pd@PS (3) Pd@PS (3) Pd@PS (3) Pd@PS (2) Pd@PS (3) Pd@PS (3) Pd@PS (3) Pd@PS (3) Pd@PS (3) Pd@PS (3) Pd@PS (3) Pd@PS (4) Pd@PS (3) Pd@PS (3) Pd@PS (3) Pd@PS (3) Pd@PS (3) Pd/C (3) Pd(OAc)2 (3)

K2CO3 (3) K2CO3 (3) KOH (3) KOH (3) K3PO4 (3) NaOH (3) Cs2CO3 (5) NaOtBu (3) NaOtBu (3) KOtBu (3) KOtBu (2) KOtBu (1) KOtBu (1.5) KOtBu (2.5) KOtBu (3) KOtBu (3) KOtBu (4) KOtBu (3) KOtBu (3) KOtBu (3) KOtBu (3) KOtBu (3) KOtBu (3) KOtBu (3) KOtBu (3) KOtBu (3) KOtBu (5)

EtOH MeOH EtOH MeOH EtOH EtOH EtOH EtOH MeOH EtOH EtOH EtOH EtOH EtOH EtOH MeOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH

35 15 40 20 14 42 10 78 65 75 77 25 30 65 82 72 80 81 55 (66) 75 45 20 50 46 55 traces traces

a

Reaction conditions: 1a (0.34 mmol), 2a (2.5 mL), base (3 equiv), catalyst (3 mol % Pd), at 110 °C for 48 h in a closed 30 mL reaction vial. bIsolated yields. c0.5 mL toluene was used as solvent. dReaction at 90 °C, yield in the parentheses was for the reaction with 2 mL ethanol at 110 °C. e0.5 mL dioxane was used as solvent. fReaction carried out under O2 (balloon). gReaction carried out under N2 flash. hReaction carried in the presence of 4 Å molecular sieves.

Methyl-1-tetralone and 7-methoxy-1-tetralone were found to be excellent substrates for the corresponding methylated products 3b (diastereomeric mixture) and 3c synthesis in 75 and 61% yields, respectively. Surprisingly, dimethylation was observed 9686

DOI: 10.1021/acssuschemeng.7b00789 ACS Sustainable Chem. Eng. 2017, 5, 9683−9691

Research Article

ACS Sustainable Chemistry & Engineering Scheme 2. Pd@PS Catalyzed α-Methylation of Ketonesa

methylation product 3h in 62% yield along with the conjugate addition product 3h′ in 30% yield. In addition, the halogen substituted 4-chloro-2-phenylacetophenone also furnished the desired methylation product 3i in 60% yield under standard reaction conditions (Scheme 2). Subsequently, we explored the alkylation by using ethanol as alkylating agent under standard reaction conditions. Various aryl ketones were allowed to react with ethanol and all the reactions proceeded efficiently to afford the desired ethylated products in good to excellent yields (Scheme 3). Substituted Scheme 3. Pd@PS Catalyzed α-Ethylation of Ketonesa

a

Reaction conditions: ketone 4 (1 equiv), ethanol 5 (2.5 mL), KOtBu (3 equiv), Pd@PS (3 mol % Pd), and toluene (0.5 mL) in a closed 30 mL reaction vial. Conversion/yield (%).

tetralones such as 4-methyl-1-tetralone and 6-methoxy-1tetralone were found to be active to furnish the desired ethylated products 6b (diastereomeric mixture) and 6c in 72 and 60% yields, respectively. A seven-member ring fused ketone, benzosuberone was attempted under the same conditions and 6d was obtained in 71% yield. The compatibility of the reaction was further explored for various substituted acetophenones. The electroneutral and -rich acetophenones gave the desired butyrophenones 6e−6i in good yields. Interestingly, no orthosubstitution effect was observed in the reaction as the substrates 2,5-dimethoxy and 2,4-dimethyl acetophenones produced 6j and 6k in 82% and 76% yields, respectively. 3,4,5-Trimethoxy acetophenone was also tried to get the desired substituted butyrophenone 6l in 50% yield. Aliphatic cyclic ketone, cyclohexanone, was also found to be reactive under the standard reaction condition and produced diethylated product 6m in 39% yield. Amino substituted acetophenone underwent a smooth transformation into corresponding product 6n exclusively in 76% yield. Apart from acetophenone, 2-phenylacetophenone also participated in the reaction to give 6o in 78% yield.

a Reaction conditions: 1 (1 equiv), 2 (2.5 mL), KOtBu (3 equiv), Pd@ PS (3 mol % Pd), toluene (0.5 mL), at 110 °C in a closed 30 mL reaction vial. d.r = diasteriomeric ratio. Isolated yields. bAt 140 °C.

when 2,5-dimethoxy acetophenone and acetophenone were used as substrates with methanol and furnished 3d and 3e in 68 and 50% yields correspondingly. During the dimethylation process of acetophenone, the initial methylation of acetophenone produced in situ propiophenone which was further involved in the conjugate addition to give the product 3e′ in 30% yield. Interestingly, butyro- and propio-phenones also reacted with methanol and the desired products 3f and 3g were formed exclusively in 65 and 55% yields with the conjugate addition products 3f′ and 3g′ in 20 and 40% yields. Furthermore, the reaction of 2-phenyl acetophenone under standard reaction conditions with methanol gave the desired α9687

DOI: 10.1021/acssuschemeng.7b00789 ACS Sustainable Chem. Eng. 2017, 5, 9683−9691

Research Article

ACS Sustainable Chemistry & Engineering To check the viability and scope of the present method, the alkylation with other alkyl and benzyl alcohols was also investigated (Scheme 4). When acetophenone and p-methyl acetophenone were treated with butanol, the desired alkylation products 9a and 9b were obtained in 79 and 86% yields, respectively.

Scheme 5. Mechanistic Investigations

Scheme 4. Pd@PS Catalyzed α-Alkylation/Benzylation of Ketonesa

Scheme 6. Possible Reaction Mechanism for Alkylation under Air

a

Reaction conditions: 7 (1 equiv), KOtBu (3 equiv), Pd@PS (3 mol % Pd), at 110 °C in a closed 30 mL reaction vial. Conversion/Yield (%). b Butanol/toluene (1:1 mL). cThree equiv of corresponding benzyl alcohols and toluene (2 mL) were used. dSmall amount of conjugate addition product (ESI, compound 9da).

In addition, the alkylation reaction of acetophenone (1 equiv) with 3-methoxy and 4-methyl benzyl alcohols (3 equiv) were efficiently carried out under standard reaction conditions affording 9c and 9d in 78 and 75% yields. Furthermore, 1napthalene methanol also participated in the similar reaction and gave corresponding alkylation product 9e in 82% yield. Under the optimized conditions, aliphatic ketone such as isobutylmethylketone also effectively participated in the alkylation reaction with 4-methylbenzylalcohol and 3-methoxybenzylalcohol and gave 9f and 9g in moderate yield. Controlled experiments were performed to obtain the mechanistic insight. The reaction of propiophenone with methanol was carried out under the standard reaction conditions and the product 3g′ was observed that might conclude for the α-methenylation with formaldehyde and subsequent conjugate addition by an enolate (Scheme 5). When the product 3g′ was treated under similar optimized conditions, no further reaction occurred. Moreover, when the unsaturated ketone 7d was subjected to the standard reaction conditions, reduction of CC was observed to form 9d through the hydrogen transfer by the Pd−H and the excess alcohol used in the reaction (Scheme 5). Based on our previous reports and other metal catalyzed alkylation reactions under air,42−46 the possible mechanism involved the coordination of O2 to palladium surface to produce I and then in the presence of excess alcohols (methanol and ethanol) produce alkoxy palladium intermediate II (Scheme 6). This intermediate after Pd−H elimination gave

the aldehyde III to couple with the ketone to produce unsaturated ketone IV. The further reduction took place by the transfer hydrogenation with Pd−H to give the intermediates V which rearranged to produce VI. The intermediate VI in the presence of excess alcohol and base gave the desired alkylated ketone VII (Scheme 6). Recyclability Experiment. The recyclability experiment for Pd@PS catalyst was carried out by choosing α-tetralone as model substrate (Figure 8a). The reaction of α-tetralone and ethanol was carried out under optimized reaction conditions. After complition of the reaction, the catalyst was filtered and washed with water, acetone and dried over reduced pressure. The dried catalyst was further utilized for the next cycle and found that the catalyst was recycled up to four times with negligible leaching (