Supported Palladium Nanoparticle Catalyzed Î±-Alkylation of Ketones

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Supported Palladium Nanoparticles Catalyzed #Alkylation of Ketones using Alcohols as Alkylating Agents Chennayala Bal Reddy, Richa Bharti, Sandeep Kumar, and Pralay Das ACS Sustainable Chem. Eng., Just Accepted Manuscript • DOI: 10.1021/ acssuschemeng.7b00789 • Publication Date (Web): 13 Sep 2017 Downloaded from http://pubs.acs.org on September 14, 2017

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ACS Sustainable Chemistry & Engineering

Supported Palladium Nanoparticles Catalyzed αAlkylation of Ketones using Alcohols as Alkylating Agents C. Bal Reddy,†,‡ Richa Bharti,†,‡ Sandeep Kumar,†,‡ 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 * Corresponding author: E-mail: [email protected], [email protected]

ABSTRACT: Polymer stabilized palladium (Pd@PS) nanoparticles (NPs) catalyzed α-alkylation of acyclic, cyclic and aliphatic ketones were performed with methanol, ethanol, 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.

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 presence of strong bases.1-2 In recent years alcohols have been directly used as greener ACS Paragon Plus Environment


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alkylating agents over alkyl halides in transition metal catalyzed α-alkylation of ketones using 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 valuable but challenging goal. Beller and Grutzmacher independently reported Ru-catalyzed dehydrogenation of methanol to hydrogen and carbon dioxide.32,33 Kriche et al. reported Ircatalysed coupling of methanol with allenes34 and Glorious et al. reported activation of methanol for C-N bond formation reaction.35 In addition, the activation of methanol in α-methylation reactions were 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 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(OH)27, Pd/Viologen28 and Pd–Si–Pr–NiXantphos/SiO2 catalyst30). Even though, these methods were restricted to benzyl and long chain aliphatic alcohols with the requirement of hydrogen accepter29 and high temperature.31 Yet, there is no single report available where palladium catalyst has been used efficiently for α-alkylation of ketones with methanol or ethanol under milder conditions. Scheme 1. Comparative studies of the research

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Since, 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 ethanol37 and other challenging reactions.38-41 Herein, first time we present Pd@PS NPs catalyzed αalkylation reaction of ketones using small chain alcohols such as methanol, ethanol as well as long chain alkyl/ benzyl alcohols as alkylating agents following oxidation, condensation and reduction approaches (Scheme 1c). Preparation of the Pd@PS catalyst 1g 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 till 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 oC. The resulting mixture was heated for 1 h or till the dark brown color of the solution changed into colorless and simultaneously white solid beads were turned into blackish. After cooling, the beads were filtered through a cotton bed, washed with water and


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acetone, and dried under reduced pressure. The amount of palladium present in the catalyst was found to be 0.47 wt%. 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 1090º on X’PERT Pro, equipped with x’Celerator solid state detector. The composition of the catalyst was analyzed by performing X-ray 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. Results and discussion The formation of palladium NPs at the polymer surface was analyzed by SEM and the energy dispersive X-ray (EDX) indicating the presence of palladium at the analyzed region (Figure 1a, 1b).

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


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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 (a and b)] as well as at 5 nm scale [Fig 3 (a)]. The histogram representing the particle size distribution of the Pd NPs as drawn from Figure 3a, by measuring the size with the help of image-J software and found larger number of particles ranging from 1-5 nm with largest average number in 1-3 nm (Figure 3b).

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

Figure 3. (a) Bright field TEM image of the Pd@PS catalyst at 5 nm scale, (b) Particle size distribution histogram calculated from (a). 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 nm and 0.19 nm corresponding to (111) and (200) reflection planes respectively (Figure 4a). The inset picture showed the fast Fourier transformation pattern (FFT) from a selected


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region of HR-TEM and the diffraction pattern also confirms the presence of cubic (111) plane (Figure 4).

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 4a. 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 X-ray 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 ~40º and ~45º corresponding to Pd (111) and Pd (200) planes respectively (Figure 6) which are also in accordance with the planes obtained from SAED.


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Figure 6. X- ray diffraction pattern (XRD) of PS and Pd@PS catalyst. X-ray photoelectron spectroscopy (XPS) was applied to determine the composition of Pd@PS catalyst. The full spectrum of XPS showed the presence of palladium, oxygen, 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 are in compliance with the reported values for Pd(0) (Figure 7). The Pd@PS catalyst was found to be recyclable up to 4 runs (Figure 8) and negligible leaching of Pd was detected by ICP-AES analysis (Figure 9). The TEM analysis of Pd@PS catalyst after 4 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.

Figure 7. (a) XPS full spectrum of Pd@PS (b) Pd 3d XPS spectra. We started our investigation using α-tetralone as model substrate and all the related parameters were extensively investigated to get the highest yield of the product. Initially, we explored


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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 by using KOtBu/ NaOtBu as base.36,37,42 Table 1. Optimization of reaction conditionsa O

O

R Catalyst, Base +

1a S.No

R OH 2a

[Pd] (mol%)

Solvent 110 °C, 48 h Air (traces)

3a, R = Me 6a, R = Et

Base (equiv.)

R-OH

Yield(%)b

1

Pd@PS (3)

K2CO3 (3)

EtOH

35

2

Pd@PS (3)

K2CO3 (3)

MeOH

15

3

Pd@PS (3)

KOH (3)

EtOH

40

4

Pd@PS (3)

KOH (3)

MeOH

20

5

Pd@PS (3)

K3PO4 (3)

EtOH

14

6

Pd@PS (3)

NaOH (3)

EtOH

42

7

Pd@PS (3)

Cs2CO3 (5)

EtOH

10

8

Pd@PS (3)

NaOtBu (3)

EtOH

78

9

Pd@PS (3)

NaOtBu (3)

MeOH

65

10

Pd@PS (2)

KOtBu (3)

EtOH

75

11

Pd@PS (3)

KOtBu (2)

EtOH

77

12

Pd@PS (3)

KOtBu (1)

EtOH

25

13

Pd@PS (3)

KOtBu (1.5)

EtOH

30

14

Pd@PS (3)

KOtBu (2.5)

EtOH

65

15c

Pd@PS (3)

KOtBu (3)

EtOH

82

16c

Pd@PS (3)

KOtBu (3)

MeOH

72

17c

Pd@PS (3)

KOtBu (4)

EtOH

80

18c

Pd@PS (4)

KOtBu (3)

EtOH

81

19d

Pd@PS (3)

KOtBu (3)

EtOH

55 (66)

20e

Pd@PS (3)

KOtBu (3)

EtOH

75

21f

Pd@PS (3)

KOtBu (3)

EtOH

45


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22g

Pd@PS (3)

KOtBu (3)

EtOH

20

23h

Pd@PS (3)

KOtBu (3)

EtOH

50

24

Pd/C (3)

KOtBu (3)

EtOH

46

25

Pd(OAc)2 (3)

KOtBu (3)

EtOH

55

-

KOtBu (3)

EtOH

traces

-

KOtBu (5)

EtOH

traces

26 27 a

Reaction conditions: 1a (0.34 mmol), 2a (2.5 mL), base (3 equiv), catalyst (3 mol % Pd), at 110 ºC for 48 h in a closed 30 mL reaction vial. bIsolated yields. c0.5 mL toluene was used as solvent. dReaction at 90 oC, yield in the parenthesis was for the reaction with 2 mL ethanol at 110 o C. e0.5 mL dioxane was used as solvent. fReaction carried out under O2 (balloon). gReaction carried out under N2 flash. hReaction carried in presence of 4 Å molecular sieves. Likewise, in this report KOtBu was found to be the most suitable for ethanol and methanol oxidation in 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 o

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 the good result (Table1, entry 10, 15 and 18). To check the reaction atmospheric condition, 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


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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 ºC for 48 hrs. 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-Methyl-1tetralone 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 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 di-methylation 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 propiophenones 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 α-methylation product 3h in 62% yield along with the conjugate addition product 3h' in 30% yield. In addition, the halogen substituted 4-chloro-2-


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phenylacetophenone also furnished the desired methylation product 3i in 60% yield under standard reaction conditions (Scheme 2). Scheme 2. Pd@PS catalyzed α-methylation of ketonesa


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a

Reaction conditions: 1 (1 equiv.), 2 (2.5 mL), KOtBu (3 equiv.), Pd@PS (3 mol% Pd), toluene (0.5 mL), at 110 oC in a closed 30 mL reaction vial. d.r = diasteriomeric ratio. Isolated yields. bAt 140 oC. 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 tetralones such as 4-methyl-1-tetralone and 6-methoxy-1-tetralone 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. 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), toluene (0.5 mL) in a closed 30 mL reaction vial. Conversion/yield (%).


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The compatibility of the reaction was further explored for various substituted acetophenones. The electro-neutral and rich acetophenones gave the desired butyrophenones 6e-6i in good yields. Interestingly, no ortho substitution 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 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. To check viability and scope of the present method, the alkylation with other alkyl and benzyl alcohols were also investigated (Scheme 4). When acetophenone and p-methyl acetophenone treated with butanol, the desired alkylation products 9a and 9b were obtained in 79 and 86% yields respectively. Scheme 4. Pd@PS catalyzed α-alkylation/benzylation of ketonesa


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a

Reaction conditions: 7 (1 equiv.), KOtBu (3 equiv.), Pd@PS (3 mol% Pd), at 110 oC in a closed 30 mL reaction vial. Conversion/Yield (%). bButanol/toluene (1:1 mL). c3 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, 1-napthalene 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 was also effectively participated in the alkylation reaction with 4-methylbenzylalcohol and 3-methoxybenzylalcohol and gave 9f and 9g in moderate yields. 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 3gˈ was observed that might conclude for the α-methenylation with formaldehyde and subsequent conjugate addition by an enolate (Scheme 5). Scheme 5. Mechanistic investigations O-K+

O

Conjugate addition

Reduction O

O

O Pd@PS, KOtBu

1g O

3g' O

MeOH/Toluene (2.5:0.5 ml) 48 h, 110 oC O

7d

+ 3g

3g' O

Pd@PS, KOtBu MeOH/Toluene 48 h, 120 oC Pd@PS, KOtBu MeOH/Toluene (2.5:0.5 ml) 24 h, 110 oC

O

3g O

H

H 9d, 75%


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When the product 3gˈ was treated under the similar optimized conditions and 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 PdH 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 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 presence of excess alcohol and base gave the desired alkylated ketone VII (Scheme 6).

Scheme 6. Possible reaction mechanism for alkylation under air.


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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 futher utilized for the next cycle and found that the catalyst was recycled upto four times with negligible leaching (< 2 ppm) of the palladium. This is further confirmed by ICP-AES analysis of the resulting solutions at different cycles. The TEM experiment of the Pd@PS catalyst after 4th cycle was also performed to check the morphology of the catalyst and found that the palladium NPs were ranging 1-5 nm in size (Figure 8b). The histogram revealed that the average particles size of NPs is in the range of 2-3 nm (Figure 8c).

Figure 8. Recyclability experiment of Pd@PS catalyst ICP-AES analysis ICP-AES analysis was performed for the reaction mixture using α-tetralone and ethanol as substrates under optimized reaction conditions. After completion of the reaction, the reaction mixture was subjected to complete acid digestion and was analyzed by ICP-AES at different cycles. Gratifyingly, the overall leaching of the palladium after 4 cycles was only < 2 ppm (Figure 9).


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Figure 9. ICP-AES analysis of reaction mixture at different cycles. Hot filtration test Hot filtration test is mainly used to differentiate the heterogeneous surface catalysis and solution phase catalysis. Hence, we performed the hot filtration test to determine the catalytic active species involved in the reaction. We have carried out the reaction between α-tetralone and ethanol under standard reaction conditions, after 35% of the product 6a formation, the solid catalyst (Pd@PS) was filtered off, and the reaction was further continued for

48 h. There is no

gradual increase in the yield of the product indicating the absence of catalytic active species in the solution for fruitful conversion. While the same reaction when performed unperturbed under standard reaction conditions, gave 6a in 82% yield. On the basis of these experiments we concluded that the reaction takes place in truly heterogeneous manner and the catalytic active species involved in the reaction are Pd(0) (Figure 10).

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


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Mercury test Mercury drop experiment was generally used to confirm the catalytic active species in the solution and the heterogeneity of the catalyst. When a drop of mercury was added to a heterogeneously catalyzed reaction, amalgamation on the catalytic surface takes place and hence the reaction doesn’t occur whereas mercury doesn’t have any effect on the homogeneously catalyzed reaction. The same experiment was carried out for the present catalytic reaction. When a drop of mercury was added to the reaction mixture of α-tetralone and ethanol under standard reaction conditions, no product formation was observed indicating that the no leached palladium was present in the reaction mixture (which also correlated with ICP-AES data). The amalgamation on the catalytic surface (Pd@PS) inhibited the reaction which established that the catalysis was truly heterogeneous and the catalytic active species in the solution are Pd(0). General method and materials Reagents of high quality were purchased from Sigma Aldrich, Tech Chem Solutions, Loba Chemie and Sd Fine-chem Ltd. Amberlite® IRA 900 Cl− resin (PS) used as support (Chloride form) was purchased from Acros Organics. Thin layer chromatography was performed using pre coated silica gel plates 60F254 (Merck) in UV light detector. GC–MS analysis was carried out on a Shimadzu (QP 2010) series GC–MS (Tokyo, Japan), equipped with a FID, AOC 5000 auto sampler, DB-5MS capillary column (30 m 9 0.25 mm i.d. with film thickness 0.25 lm). ESI-MS spectra were determined using a Waters micro mass Q-TOF Ultima Spectrometer. Germany. 1H and

13

C NMR spectra were recorded using a Bruker Avance 600 spectrometer operating at 600

MHz (1H) and 150 MHz (13C) and Bruker Avance 300 spectrometer operating at 300 MHz (1H) and 75 MHz (13C) spectra were recorded at 25 ºC in CDCl3 [residual CHCl3 (δH 7.26 ppm) or CDCl3 (δC 77.00 ppm)]. Chemical shifts were recorded in δ (ppm) relative to the TMS and NMR


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solvent signal, coupling constants (J) are given in Hz and multiplicities of signals are reported as follows: s, singlet; d, doublet; t, triplet; m, multiplet; br, broad singlet. General procedure for alkylation reaction

2-Methyl-3,4-dihydronaphthalen-1(2H)-one (3a): α-Tetralone (0.34 mmol, 1 equiv.), KOtBu (2.05 mmol, 3 equiv.) and Pd@PS (229 mg, 3 mol% Pd, 0.03 equiv.) were charged in a 30 mL reaction tube and methanol (2.5 mL), toluene (0.5 mL) was added to it. The reaction tube was closed with the teflon screw cap and heated at 110 oC for 48 hrs under air (traces) present in the vial. The complition of the reaction was monitered by TLC, the reaction mixture was allow to cool to room temperature and diluted with water 2 mL and extracted with EtOAc. The crude was concentrated under vacuum and purified by column chromatography on silica gel (hxane 100%) affording the desired product 3a as colourless liquid (39 mg) in 72 % of yield; 1H NMR (300 MHz, CDCl3) δ = 1.29 (d, J = 6.2 Hz, 3H), 1.82-1.92 (m, 1H), 2.18-2.24 (m, 1H), 2.56-2.62 (m, 1H), 2.99-3.06 (m, 2H), 7.24 (d, J = 7.4 Hz, 1H), 7.28-7.33 (t, J = 7.5 Hz, 1H), 7.44-7.49 (t, J = 7.3 Hz, 1H), 8.05 (d, J = 7.6 Hz, 1H);

13

C NMR (75 MHz, CDCl3) δ =

15.3, 28.7, 31.3, 42.5, 126.4, 127.3, 128.6, 132.3, 133.0, 144.1, 200.6; GC-MS m/z = 160. CONCLUSIONS In conclusion, Pd@PS NPs were found to be highly efficient catalyst for α-alkylation of ketones with small chain alkyl alcohols such as methanol and ethanol under hydrogen accepter free condition. To see viablity and scope of the present method, different long chain alkyl and benzyl alcohols were also used successfully and ended with similar products. The steps involved in the reaction are facile oxidation of alcohols, sequential participation in condensation and reduction reaction to achieve the desired products through oxidation, condensation and reduction


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approaches. The negligible leaching of Pd and recyclibility of the catalyst reflects overall efficiency of the method and catalyst. ASSOCIATED CONTENT Supporting Information 1

HNMR, 13CNMR spectra and GC-MS, ESI-MS data. The Supporting Information is available

free of charge on the ACS Publications website as PDF file. AUTHOR INFORMATION * Corresponding Author * E-mail: [email protected], [email protected], Fax: +91-1894-230433. Notes The authors declare no competing financial interest ACKNOWLEDGMENT We are grateful to the director CSIR-IHBT for providing necessary facilities during the course of the work. We thank Dr. G. Saini, AIRF, JNU-New Delhi, India for the TEM; Biotechnology Division, CSIR-IHBT for SEM and EDS analysis; We thank CSIR, New Delhi for financial support as part of XII Five Year Plan programme under the title ORIGIN (CSC-0108). C. B. R, R. B and S. K. thanks CSIR and UGC, New Delhi for awarding fellowship. REFERENCES 1. Caine, D. In Comprehensive Organic Synthesis (Eds.: Trost, B. M., Fleming, I.) Pergamon Press: Oxford, 1991; Vol. 3, pp 1-63. 2. Otera, J. Modern Carbonyl Chemistry; Ed.; Wiley- VCH: Weinheim, 2000.


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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


3. Guillena, G.; Ramon, D. J.; Yus, M. Alcohols as electrophiles in C-C bond-forming reactions: The hydrogen autotransfer process. Angew. Chem. Int. Ed. 2007, 46, 23582364. 4. Gunanathan, C.; Milstein, D. Applications of acceptorless dehydrogenation and related transformations in chemical synthesis. Science. 2013, 341, 249. 5. Schranck, J.; Tlili, A.; Beller, M. More sustainable formation of C-N and C-C bonds for the synthesis of N-heterocycles. Angew. Chem. Int. Ed. 2013, 52, 7642-7644. 6. Obora, Y. Recent advances in α-Alkylation reactions using alcohols with hydrogen borrowing methodologies. ACS Catal. 2014, 4, 3172-3981. 7. Bibby,C. E.; Grigg,R.; Price, R. Oxidation of ethanol by cobalt, iron, and rhodium complexes. J. Chem. Soc. Dalton Trans. 1977, 872-876. 8. Lçfberg, C.; Grigg, R.; Keep, A.; Derrick, A.; Sridharan, V.; Kilner, C. Sequential onepot bimetallic Ir(III)/Pd(0) catalysed mono-/bisalkylation and spirocyclisation processes of 1,3-dimethylbarbituric acid and allenes. Chem. Commun. 2006, 5000-5002 and reference no.6 cited therein. 9. Taguchi, K.; Nakagawa, H.; Hirabayashi, T.; Sakaguchi S.; Ishii, Y. An Efficient Direct α-Alkylation of Ketones with Primary Alcohols Catalyzed by [Ir(cod)Cl]2/PPh3/KOH System without Solvent. J. Am. Chem. Soc. 2004, 126, 72-73. 10. Bhat, S.; Sridharan, V. Iridium catalysed chemoselective alkylation of 2’aminoacetophenone with primary benzyl type alcohols under microwave conditions. Chem. Commun. 2012, 48, 4701-4703.


21


1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 22 of 27

11. Li, F.; Ma, J.; Wang, N. α‑Alkylation of ketones with primary alcohols catalyzed by a Cp*Ir complex bearing a functional bipyridonate ligand. J. Org. Chem. 2014, 79, 1044710455. 12. Ogawa, S., Obora, Y.

Iridium-catalyzed selective α-methylation of ketones with

methanol. Chem. Commun. 2014, 50, 2491-2493. 13. Shen, D.; Poole, D. L.; Shotton, C. C.; Kornahrens, A. F.; Healy, M. P.; Donohoe, T. J. Hydrogen-borrowing and interrupted-hydrogen-borrowing reactions of ketones and methanol catalyzed by iridium. Angew. Chem., Int. Ed. 2015, 54, 1642-1645. 14. Quan, X.; Kerdphon, S.; Andersson, P. G. C-C Coupling of ketones with methanol catalyzed by a N-heterocyclic carbene–phosphine iridium complex. Chem. - Eur. J. 2015, 21, 3576-3579. 15. Frost, J. R.; Cheong, C. B.; Akhtar, W. M.; Caputo, D. F. J.; Stevenson, N. G.; Donohoe, T. J. Strategic Application and Transformation of ortho-Disubstituted Phenyl and Cyclopropyl Ketones To Expand the Scope of Hydrogen Borrowing Catalysis. J. Am. Chem. Soc. 2015, 137, 15664-15667. 16. Cho, C. S.; Kim, B. T.; Kim, T. J.; Shim, S. C. Ruthenium-catalyzed regioselective αalkylation of ketones with primary alcohols. Tetrahedron Lett. 2002, 43, 7987-7989. 17. Martinez, R.; Brand, G. J.; R.; Ramon, D. J.; Yus, M. [Ru(DMSO)4]Cl2 catalyzes the αalkylation of ketones by alcohols. Tetrahedron Lett. 2005, 46, 3683.


22

Page 23 of 27

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


18. Martinez, R.; Ramon, D. J.; Yus, M. Easy a-alkylation of ketones with alcohols through a hydrogen autotransfer process catalyzed by RuCl2(DMSO)4. Tetrahedron. 2006, 62, 8988-9001. 19. Kuwahara, T.; Fukuyama, T.; Ryu, I. RuHCl(CO)(PPh3)3‑Catalyzed r‑Alkylation of Ketones with Primary Alcohols. Org. Lett. 2012, 14, 4703-4705. 20. Dang, T. T.; Seayad, A. M. A Convenient Ruthenium-Catalysed α-Methylation of Carbonyl Compounds using Methanol. Adv.Synth. Catal. 2016, 358, 3373-3380. 21. Chan, L. K. M.; Poole, D. L.; Shen, D.; Healy, M. P.; Donohoe, T. J. Rhodium-Catalyzed Ketone Methylation Using Methanol Under Mild Conditions: Formation of α-Branched Products. Angew. Chem., Int. Ed. 2014, 53, 761-765. 22. Li, Y.; Xue, D.; Lu, W.; Wang, C.; Liu, Z.-T.; Xiao, J. DMF as carbon source: Rhcatalyzed α‑methylation of ketones. Org. Lett. 2014, 16, 66-69. 23. Alonso, F.; Riente, P.; Yus, M. Alcohols for the α-Alkylation of Methyl Ketones and Indirect Aza-Wittig Reaction Promoted by Nickel Nanoparticles. Eur. J. Org. Chem. 2008, 4908-4914. 24. Chaudhari, C.; Siddiki, S. M. A. H.; Shimizu, K-I. Self-coupling of secondary alcohols and α-alkylation of methyl ketones with secondary alcohols by Pt/CeO2 Catalyst. Top Catal. 2014, 57, 1042-1048. 25. Cui, X.; Zhang, Y.; Shi, F.; Deng, Y. Organic Ligand-Free Alkylation of Amines, Carboxamides, Sulfonamides, and Ketones by Using Alcohols Catalyzed by Heterogeneous Ag/Mo Oxides. Chem. Eur. J. 2011, 17, 1021-1028.


23


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Page 24 of 27

26. Dixit, M.; Mishra, M.; Joshi, P. A.; Shah, D. O. Clean borrowing hydrogen methodology using hydrotalcite supported copper catalyst. Catal. Commun. 2013, 33, 80-83. 27. Kwon, M. S.; Kim, N.; Seo, S. H.; Park, I. S.; Cheedrala, R. K.; Park, J. Recyclable Palladium Catalyst for Highly Selective a Alkylation of Ketones with Alcohols. Angew. Chem., Int. Ed. 2005, 44, 6913-6915. 28. Yamada, Y. M. A.; Uozumi, Y. A Solid-Phase Self-Organized Catalyst of Nanopalladium with Main-Chain Viologen Polymers: r-Alkylation ofKetones with Primary Alcohols. Org. Lett. 2006, 8, 1375-1378. 29. Cho, C. S. palladium-catalyzed route for α-alkylation of ketones by primary alcohols. J. Mol. Catal. A; Chem. 2005, 240, 55-60. 30. Dang, T. T.; Shan, S. P.; Ramalingam, B.; Seayad, A. M. An efficient heterogenized palladium catalyst for N-alkylation of amines and α-alkylation of ketones using alcohols RSC Adv., 2015, 5, 42399-42406. 31. Xu, G.; Li, Q.; Feng, J.; Liu, Q.; Zhang, Z.; Wang, X.; Zhang, X.; Mu, X. Direct αAlkylation of Ketones with Alcohols in Water. ChemSusChem, 2014, 7, 105-109. 32. Nielsen, M.; Alberico, E.; Baumann, W.; Drexler, H.-J.; Junge, H.; Gladiali S.; Beller, M. Low-temperature aqueous-phase methanol dehydrogenation to hydrogen and carbon dioxide. Nature. 2013, 495, 85-89. 33. Rodriguez-Lugo, R. E.; Trincado, M.; Vogt, M.; Tewes, F.; Santiso-Quinones G.; Grutzmacher, H. A homogeneous transition metal complex for clean hydrogen production from methanol–water mixtures. Nat. Chem. 2013, 5, 342-347.


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Page 25 of 27

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


34. Moran, J.; Preetz, A.; Mesch,R. A.; Krische, M. J. Iridium-catalysed direct C–C coupling of methanol and allenes. Nat. Chem. 2011, 3, 287-290. 35. Ortega, N.; Richter, C.; Glorius, F. N-Formylation of Amines by Methanol Activation. Org. Lett. 2013, 15, 1776-1779. 36. Guha, N. R.; Bhattacharjee, D.; Das, P. Polystyrene trimethyl ammonium chloride impregnated Rh(0) (Rh@PMe3NCl) as a catalyst and methylating agent for esterification of alcohols through selective oxidation of methanol. Catal. Sci. Technol. 2015, 5, 25752580. 37. Guha, N. R.; Sharma, S.; Bhattacherjee, D.; Thakur, V.; Bharti, R.; Reddy, C. B.; Das, P. Oxidative “reverse-esterification” of ethanol with benzyl/alkyl alcohols or aldehydes catalyzed by supported rhodium nanoparticles. Green Chem. 2016, 18, 1206-1211. 38. Das, P.; Sharma, D.; Shil, A. K.; Kumari, A. Solid-Supported Rhodium(0) Nano/Microparticles: An Efficient Ligand-Free Heterogeneous Catalyst for MicrowaveAssisted Suzuki–Miyaura Cross-Coupling Reaction Tetrahedron Lett. 2011, 52, 11761178. 39. Guha, N. R. ; Reddy, C. B.; Aggarwal, N.; Sharma, D.; Shil, A. K.; Bandna; Das, P. Solid-Supported

Rhodium(0)

Nano-/Microparticles:

An

Efficient

Ligand-Free

Heterogeneous Catalyst for Microwave-Assisted Suzuki–Miyaura Cross-Coupling Reaction. Adv. Synth. Catal. 2012, 354, 2911-2915. 40. Shil, A. K.; Das, P. Solid supported platinum(0) nanoparticles catalyzed chemo-selective reduction of nitroarenes to N-arylhydroxylamines. Green Chem. 2013, 15, 3421-3428.


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41. Shil, A. K.; Kumar, S.; Reddy, C. B.; Dadhwal, S.; Thakur, V.; Das. P. Supported Palladium Nanoparticle-Catalyzed Carboxylation of Aryl Halides, Alkenylsilanes, and Organoboronic Acids Employing Oxalic Acid as the C1 Source. Org. Lett. 2015, 17, 5352-5355. 42. Kumar, S.; Chaudhary, A.; Bandna, Bhattacherjee, D.; Thakur, V.; Das, P. Supported palladium nanoparticles as switchable catalyst for aldehyde conjugate/s and acetate ester syntheses from alcohols. New J. Chem., 2017, 41, 3242-3245. 43. Ma, X.; Su, C.; Xu, X. N-Alkylation by Hydrogen Auto transfer Reactions. Top. Curr. Chem. 2016, 374, 27. 44. Liao, S.; Yu, K.; Xu, Q. Copper-catalyzed C-alkylation of secondary alcohols and methyl ketones with alcohols employing the aerobic relay race methodology. Org. Biomol. Chem. 2012, 10, 2973–2978. 45. Liu, C.; Liao, S.; Xu, Q. Discovery and mechanistic studies of a general air-promoted metal-catalyzed aerobic N-alkylation reaction of amides and amines with alcohols. J. Org. Chem. 2011, 76, 5759–5773. 46. Li, Q.; Fan, S.; Xu, Q. Copper-catalyzed N-alkylation of amides and amines with alcohols employing the aerobic relay race methodology. Org. Biomol. Chem. 2012, 10, 2966–2972.


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For Table of Contents Use Only

Synopsis Low cost, easy to handle and highly reactive Pd@PS catalyst was developed and applied for alkylation of ketones with alcohols.


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Supported Palladium Nanoparticle Catalyzed Î±-Alkylation of Ketones

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