{Palladium on carbon in PEG-400/cyclohexane: Recoverable and recyclable catalytic system for efficient decarbonylation of aldehydes} J. Serb. Chem. Soc. 87 (6) 669–675 (2022) Original scientific paper JSCS–5549 Published 28 April 2022 669 Palladium on carbon in PEG-400/cyclohexane: Recoverable and recyclable catalytic system for efficient decarbonylation of aldehydes NATAŠA TERZIĆ-JOVANOVIĆ1 and VLADIMIR AJDAČIĆ2*# 1University of Belgrade – Institute of Chemistry, Technology and Metallurgy, National Institute of the Republic of Serbia, Njegoševa 12, 11000 Belgrade, Serbia and 2Innovative Centre Ltd., Faculty of Chemistry, Studentski Trg 12–16, 11158 Belgrade, Serbia (Received 28 January, revised 28 February, accepted 7 March 2022) Abstract: A simple methodology for the decarbonylation of aldehydes catalysed by commercially available palladium on carbon in a green two-solvent system is reported. Various aromatic, aliphatic and heteroaromatic aldehydes were transformed to the corresponding decarbonylated products in good yields. Pro- duct isolation from the reaction mixture is simple in practice, and the catalyst can be reused three times. Keywords: green chemistry; defunctionalization; heterogeneous catalysis. INTRODUCTION The transformation of aldehydes into hydrocarbons (deformylation/decar- bonylation) promoted by enzymes,1 transition-metals2 or metal-free reagents3 is an important reaction in academic research4 and industry.5 The aldehyde group is an useful promoter of certain transformations, such as the Diels–Alder reaction, C–H activation, and domino oxa-Michael-aldol reaction, and its simple removal via decarbonylation after it has served its purpose has been extensively applied in numerous methodologies6 and in the synthesis of complex molecules and natural products.7 Some metals of the first, second and third transition series, including Ni,8 Ru,9 Rh,10 Pd11 and Ir12 as well as complexes thereof, efficiently perform the mentioned transformation (Fig. 1). However, the toxicity and high cost of these metals is a major drawback from an economic and environmental point of view. Therefore, the use of recyclable heterogeneous catalysts for decarbonyl- ation is both a greener and more economical alternative to homogeneous cat- alysis.13 * Corresponding author. E-mail: ajdacic@chem.bg.ac.rs # Serbian Chemical Society member. https://doi.org/10.2298/JSC220128024T ________________________________________________________________________________________________________________________ (CC) 2022 SCS. Available on line at www.shd.org.rs/JSCS/ 670 TERZIĆ-JOVANOVIĆ and AJDAČIĆ Fig. 1. Decarbonylation of aldehydes pro- moted by transition-metals. EXPERIMENTAL The general information Pd/C (10 wt.% loading) was purchased from Sigma Aldrich. Aldehydes were mostly obtained from commercial sources and used without further purification, except for the 1-ada- mantanecarboxaldehyde,14 1-adamantaneacetaldehyde,14 1-prop-2-yn-1-yl-1H-indole-3-carb- aldehyde15 and 1-benzyl-1H-indole-3-carbaldehyde,15 which were synthesized according to known procedures. Unless stated otherwise, solvents and other reagents were obtained from commercial sources and used without further purification. Dry-flash chromatography was per- formed on SiO2 (0.018–0.032 mm). 1H- and 13C-NMR spectra were recorded on a Bruker Ultrashield Avance III spectrometer (at 500 and 125 MHz, respectively) and Varian 400/54 Premium Shielded spectrometer (at 400 and 101 MHz, respectively) using CDCl3 (unless stated otherwise) as the solvent and tetramethylsilane (TMS) as an internal standard. The chemical shifts are expressed in ppm on the δ scale and they were calibrated relative to those of the solvent. GC–MS spectra of the synthesized compounds were acquired on an Agilent Technologies 7890A apparatus equipped with a DB-5 MS column (30 m×0.25 mm×0.25 μm), a 5975C MSD and FID detector. The selected values are as follows: carrier gas was He (1.0 mL/min), temperature linearly increased from 40–315 °C (10 °C/min), injection volume: 1 μL, temperature: 250 °C, temperature (FID detector): 300 °C, and EI mass spectra range: m/z 40–550. For determination of GC–MS yield, the internal standard (naphthalene) was added to the reaction mixture after the workup. General procedure for decarbonylation of aldehydes 2a–n Decarbonylation of biphenyl-4-carbaldehyde to biphenyl (2a) (CAS Reg. No. 92-52-4). Dry glass reaction tube purged with argon and equipped with a magnetic stir bar was charged with aldehyde (90 mg, 0.5 mmol), Pd/C (26 mg, 5 mol.% Pd), cyclohexane (750 μL) and PEG-400 (750 μL). The sealed tube was heated at 140 °C for 24 h. The reaction medium was then cooled to room temperature. The mixture of water and cyclohexane was then added to the reaction mixture. The layers were afterwards separated and the aqueous layer was washed with cyclohexane (5×5 mL). The organic layer was dried over Na2SO4, and the solvent was evaporated under reduced pressure. Compound 2a was obtained after dry-flash column chro- matography (SiO2:cyclohexane) as a white solid (69.0 mg, 90 %). Decarbonylation of 2-naphthaldehyde to naphthalene (2b) (CAS Reg. No. 91-20-3). Following the general procedure for decarbonylation, compound 2b was prepared from alde- hyde (78.0 mg, 0.5 mmol) using Pd/C (26.0 mg, 5 mol.% Pd) in a mixture of cyclohexane (750 μL) and PEG-400 (750 μL) and was obtained after dry-flash column chromatography (SiO2:cyclohexane) as a white solid (45.1 mg, 70 %). ________________________________________________________________________________________________________________________ (CC) 2022 SCS. Available on line at www.shd.org.rs/JSCS/ DECARBONYLATION OF ALDEHYDES 671 Decarbonylation of anthracene-9-carbaldehyde to anthracene (2c) (CAS Reg. No. 120- -12-7). Following the general procedure for decarbonylation, compound 2c was prepared from aldehyde (103.2 mg, 0.5 mmol) using Pd/C (26.0 mg, 5 mol % Pd) in a mixture of cyclohex- ane (750 μL) and PEG-400 (750 μL) and was obtained after dry-flash column chromatography (SiO2:cyclohexane) as a white crystalline solid (73.2 mg, 82 %). Decarbonylation of 4-nitrobenzaldehyde to nitrobenzene (2d) (CAS Reg. No. 98-95-3). Following the general procedure for decarbonylation, compound 2d was prepared from alde- hyde (75.6 mg, 0.5 mmol) using Pd/C (26.0 mg, 5 mol % Pd) in a mixture of cyclohexane (750 μL) and PEG-400 (750 μL) and was obtained as a yellow oil (GC–MS yield 90 % based on naphthalene). Decarbonylation of 5-fluoro-2-methoxybenzaldehyde to 4-fluoroanisol (2e) (CAS Reg. No. 459-60-9). Following the general procedure for decarbonylation, compound 2e was pre- pared from aldehyde (77 mg, 0.5 mmol) using Pd/C (26 mg, 5 mol % Pd) in a mixture of cyc- lohexane (750 μL) and PEG-400 (750 μL) (GC–MS yield 60 % based on methyl benzoate as standard). Decarbonylation of diphenylacetaldehyde to diphenylmethyl (2h) (CAS Reg. No. 101-81- -5). Following the general procedure for decarbonylation, compound 2h was prepared from aldehyde (89 μL, 0.5 mmol) using Pd/C (26.0 mg, 5 mol % Pd) in a mixture of cyclohexane (750 μL) and PEG-400 (750 μL) and was obtained after dry-flash column chromatography (SiO2:cyclohexane) as a colorless oil (78.1 mg, 93 %). Decarbonylation of 3-(1,3-benzodioxol-5-yl)-2-methylpropanal to dihydrosafrole (2i) (CAS Reg. No. 94-58-6). Following the general procedure for decarbonylation, compound 2i was prepared from aldehyde (83 μL, 0.5 mmol) using Pd/C (26 mg, 5 mol % Pd) in a mixture of cyclohexane (750 μL) and PEG-400 (750 μL) and was obtained after dry-flash column chromatography (SiO2:cyclohexane) as a colorless oil (59.3 mg, 72 %). Decarbonylation of 1-adamantanecarboxaldehyde to adamantane (2j) (CAS Reg. No. 281-23-2). Following the general procedure for decarbonylation, compound 2j was prepared from aldehyde (82.3 mg, 0.5 mmol) using Pd/C (26.0 mg, 5 mol % Pd) in a mixure of cyclo- hexane (750 μL) and PEG-400 (750 μL) and was obtained after dry-flash column chromato- graphy (SiO2:cyclohexane) as a colorless solid (67.3 mg, 84 %). Decarbonylation of 1-adamantaneacetaldehyde to 1-methyl adamantane (2k) (CAS Reg. No. 768-91-2). Following the general procedure for decarbonylation, compound 2k was pre- pared from aldehyde (89.1 mg, 0.5 mmol) using Pd/C (26.0 mg, 5 mol % Pd) in a mixure of cyclohexane (750 μL) and PEG-400 (750 μL) and was obtained after dry-flash column chro- matography (SiO2:cyclohexane) as a colorless solid (74.0 mg, 73 %). Decarbonylation of benzo[b]thiophene-3-carboxaldehyde to benzo[b]thiophene (2l) (CAS Reg. No. 95-15-8). Following the general procedure for decarbonylation, compound 2l was prepared from aldehyde (81.1 mg, 0.5 mmol) using Pd/C (26.0 mg, 5 mol % Pd) in a mix- ture of cyclohexane (750 μL) and PEG-400 (750 μL) and was obtained after dry-flash column chromatography (SiO2:cyclohexane) as a colorless solid (47.1 mg, 70 %). Decarbonylation of 1-prop-2-yn-1-yl-1H-indole-3-carbaldehyde to 1-prop-2-yn-1-yl- -1H-indole (2m) (CAS Reg. No. 19017-00-6). Following the general procedure for decarbonyl- ation, compound 2m was prepared from aldehyde (92.3 mg, 0.5 mmol) using Pd/C (26.1 mg, 5 mol % Pd) in a mixure of cyclohexane (750 μL) and PEG-400 (750 μL) and was obtained after dry-flash column chromatography (SiO2:cyclohexane) as a colorless solid (53.3 mg, 68 %). Decarbonylation of 1-benzyl-1H-indole-3-carbaldehyde to 1-benzyl-1H-indole (2n) (CAS Reg. No. 3377-71-7). Following the general procedure for decarbonylation, compound ________________________________________________________________________________________________________________________ (CC) 2022 SCS. Available on line at www.shd.org.rs/JSCS/ 672 TERZIĆ-JOVANOVIĆ and AJDAČIĆ 2n was prepared from aldehyde (89.2 mg, 0.5 mmol) using Pd/C (118.0 mg, 5 mol % Pd) in a mixture of cyclohexane (750 μL) and PEG-400 (750 μL) and was obtained after dry-flash col- umn chromatography (SiO2:cyclohexane) as a colorless solid (68.0 mg, 66 %). Spectral data of the compounds are given in Supplementary material to this paper Recycling of Pd/C and PEG-400 catalytic system for decarbonylation of aldehyde (1a) Dry glass reaction tube purged with argon and equipped with a magnetic stir bar was charged with aldehyde (1a, 90 mg, 0.5 mmol), Pd/C (26 mg, 5 mol % Pd), cyclohexane (750 μL) and PEG-400 (750 μL). The sealed tube was heated at 140 °C for 24 h. After the com- pletion of the reaction, the cyclohexane layer was decanted with a pipette and PEG-400 layer was washed with cyclohexane (5×2 mL). The formed residue (Pd/C in PEG-400) was used for next reaction cycles following the general reaction procedure. RESULTS AND DISCUSSION Herein we report the efficient decarbonylation of aromatic, heteroaromatic and aliphatic aldehydes mediated by palladium on carbon in ecologically acceptable solvents, cyclohexane and PEG-400. To determine the optimal react- ion conditions, biphenyl-4-carboxaldehyde (1а) was used as the model substrate (TABLE I). TABLE I. Optimization of reaction conditions Entry Solvent t / °C Time, h Yielda, % 1 H2O 160 24 trace 2 PEG-400 140 24 42 3 PEG-400 140 44 26 4 PEG-400/ cyclohexane (1:1, v,v) 140 24 90 aIsolated yield The initial conditions of 5 mol % palladium on carbon in H2O at 160 °C provided only trace amounts of the corresponding decarbonylated product (entry 1). When PEG-400 was used instead of H2O, the yield increased to 42 % (entry 2). Increasing the reaction time from 24 to 44 h led to a significant reduction in the yield (26 %, entry 3). After a detailed analysis of the reaction mixture, it was found that the reduced yield resulted from product evaporation. Finally, the addi- tion of cyclohexane as a co-solvent increased the yield to 90 %. To our surprise, after the reaction mixture had cooled, the catalyst particles were located exclusively in the PEG-400 layer (Fig. 2). The product was isolated by careful decantation of cyclohexane and addi- tional extraction of the PEG-400 layer with cyclohexane. The residual catalyst in PEG-400 was used successively three more times under the same reaction con- ditions, without a significant loss of activity (Fig. 3). ________________________________________________________________________________________________________________________ (CC) 2022 SCS. Available on line at www.shd.org.rs/JSCS/ DECARBONYLATION OF ALDEHYDES 673 Fig. 2. Reaction mixture after completion of the reaction. Employing the optimized decarbonylation conditions, the aldehyde substrate scope was investigated (Scheme 1). The non-functional polycyclic aromatic alde- hydes (1a–c) were efficiently decarbonylated and the corresponding products (2a–c) were obtained in good yields. Benzaldehyde bearing an electron-with- drawing substituent (NO2) 1d generated the desired product 2d in high yield. 2-Fluoro-4-methoxybenzaldehyde afforded the decarbonylated product 2e in moderate yield. In the case of 4-bromobenzaldehyde (1f) and 4-formylbenzoic acid (1g) there was no reaction. Fig. 3. Reusability of the Pd/C/PEG-400 catalytic system. The substrate scope was then extended to aliphatic aldehydes. The aliphatic aldehydes with an aromatic core successfully produced the desired products (2h, and i) in good to excellent yields. Furthermore, the methodology was applied to the sterically demanding aldehydes, adamantane-1-carbaldehyde (1j) and 1-ada- mantylacetaldehyde (1k). The decarbonylated products, adamantane (2j) and methyladamantane (2k) were isolated in good yields. The decarbonylation of several heterocyclic aldehydes was also explored under the optimal reaction con- ditions. The decarbonylation of benzo[b]thiophene-3-carboxaldehyde (1l) afforded the desired product benzo[b]thiophene (2l) in good yield. In addition, the N-sub- stituted indole derivates (1m and n) gave the corresponding decarbonylated pro- ducts (2m and n) in good yields. ________________________________________________________________________________________________________________________ (CC) 2022 SCS. Available on line at www.shd.org.rs/JSCS/ 674 TERZIĆ-JOVANOVIĆ and AJDAČIĆ Scheme 1. Substrate scope. CONCLUSION To conclude, the ligand-free palladium-on-carbon-catalysed decarbonylation of aldehydes in ecologically acceptable solvents as an alternative to homogene- ous catalysis was reported in this study. Various aldehydes were successfully decarbonylated in moderate to excellent yields. The formation of byproducts during the reaction and chromatography was not observed. Also, Pd/C and PEG- -400 system could be recycled and reused in at least four consecutive reaction cycles, without significant loss of catalytic activity. SUPPLEMENTARY MATERIAL Additional data and information are available electronically at the pages of journal website: https://www.shd-pub.org.rs/index.php/JSCS/article/view/11599, or from the corres- ponding author on request. Acknowledgments. This research was financially supported by the Ministry of Education, Science and Technological Development of Republic of Serbia (contract numbers: 451-03-9/ /2021-14/200168, 451-03-9/2021-14/200288 and 451-03-9/2021-14/200026) and Serbian Academy of Sciences and Arts under strategic projects programme-grant agreement No. 01- -2019-F65. ________________________________________________________________________________________________________________________ (CC) 2022 SCS. Available on line at www.shd.org.rs/JSCS/ DECARBONYLATION OF ALDEHYDES 675 И З В О Д ПАЛАДИЈУМ НА УГЉЕНИКУ У PEG-400/ЦИКЛОХЕКСАНУ: КАТАЛИТИЧКИ СИСТЕМ KOJИ СЕ МОЖЕ РЕЦИКЛИРАТИ И ПОНОВО УПОТРЕБИТИ ЗА ЕФИКАСНО ДЕКАРБОНИЛОВАЊЕ АЛДЕХИДА НАТАША ТЕРЗИЋ-ЈОВАНОВИЋ1 и ВЛАДИМИР АЈДАЧИЋ2 1Универзитету Београду, Институт за хемију, технологију и металургију (ИХТМ), Његошева 12, 11000 Београд и 2Иновациони центар Хемијског факултета, Студентски трг 12–16, 11000 Београд Развијена је једноставна метода за декарбониловање алдехида користећи комерци- јално доступни паладијум на угљенику уз употребу зелених растварача. Различити аро- матични, алифатични и хетероароматични алдехиди могу се трансформисати у декар- бониловане производе у добром приносу и без настајања споредних производа. Произ- води се једноставно изолоју из реакционе смеше, а исти катализатор се може употре- бити још три пута без значајног смањења приноса. (Примљено 28. јануара, ревидирано 28. фебруара, прихваћено 7. марта 2022) REFERENCES 1. N. Li, H. Nørgaard, D. M. Warui, S. J. Booker, C. Krebs, J. M. B., Jr., J. Am. Chem. Soc. 133 (2011) 6158 (https://doi.org/10.1021/ja2013517) 2. A. Modak, D. Maiti, Org. Biomol. Chem. 14 (2016) 21 (https://doi.org/10.1039/C5OB01949D) 3. V. Ajdačić, S. Stepanović, M. Zlatovića, M. Grudena, I. M. Opsenica, Synthesis 48 (2016) 4423 (https://doi.org/10.1055/s-0035-1562615) 4. A G. J. S. Dawes, E. L. Scott, J. Le Nôtre, J. P. M. Sanders, J. H. Bitter, Green Chem. 17 (2015) 3231(https://doi.org/10.1039/C5GC00023H) 5. U. K. Bagha, J. K. Satpathy, G. Mukherjee, C. V. Sastri, S. P. de Visser, Org. Biomol. Chem. 19 (2021) 1879 (https://doi.org/10.1039/D0OB02204G) 6. H. Lu, T.-Y. Yu, P.-F. Xu, H. Wei, Chem. Rev. 121 (2021) 365 (https://doi.org/10.1021/acs.chemrev.0c00153) 7. Ž. Selaković, A. M. Nikolić, V. Ajdačić, I. M. Opsenica, Eur. J. Org. Chem. (2022) (https://doi.org/10.1002/ejoc.202101265) 8. K. 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D’Alessandro, D. Taramelli, B. Solaja, J. Med. Chem. 59 (2016) 264 (https://doi.org/10.1021/acs.jmedchem.5b01374) 15. Y. Sawama, Y. Miki, H. Sajiki, Synlett 31 (2020) 699 (https://doi.org/10.1055/s-0040- 1707993). ________________________________________________________________________________________________________________________ (CC) 2022 SCS. Available on line at www.shd.org.rs/JSCS/ @Article{Terzic-Jovanovic2022, author = {Terzi{\'{c}}-Jovanovi{\'{c}}, Nata{\v{s}}a and Ajda{\v{c}}i{\'{c}}, Vladimir}, journal = {Journal of the Serbian Chemical Society}, title = {{Palladium on carbon in PEG-400/cyclohexane: Recoverable and recyclable catalytic system for efficient decarbonylation of aldehydes}}, year = {2022}, issn = {1820-7421}, month = {apr}, number = {6}, pages = {669--675}, volume = {87}, abstract = {A simple methodology for the decarbonylation of aldehydes catal­ysed by commercially available palladium on carbon in a green two-solvent system is reported. Various aromatic, aliphatic and heteroaromatic aldehydes were transformed to the corresponding decarbonylated products in good yields. Pro­duct isolation from the reaction mixture is simple in practice, and the cat­alyst can be reused three times.}, doi = {10.2298/JSC220128024T}, file = {:D\:/OneDrive/Mendeley Desktop/Terzi{'{c}}-Jovanovi{'{c}}, Ajda{v{c}}i{'{c}} - 2022 - Palladium on carbon in PEG-400cyclohexane Recoverable and recyclable catalytic system for efficient d.pdf:pdf;:01_11599_5549.pdf:PDF}, keywords = {defunctionalization, heterogeneous catalysis}, publisher = {National Library of Serbia}, url = {https://www.shd-pub.org.rs/index.php/JSCS/article/view/11599}, }