Bachelor of Science in Electrical and Electronics Engineering, Lecture notes of Electrical and Electronics Engineering

Download Bachelor of Science in Electrical and Electronics Engineering and more Lecture notes Electrical and Electronics Engineering in PDF only on Docsity! 1 Supplementary Information Amidation of phenol derivatives: a direct synthesis of paracetamol (acetaminophen) from hydroquinone Roxan Joncour, a Nicolas Duguet, a Estelle Métay, a Amadéo Ferreira b and Marc Lemaire* a a Laboratoire de CAtalyse SYnthèse et ENvironnement (CASYEN), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), CNRS, UMR-5246, Université Claude Bernard Lyon 1, 43 boulevard du 11 novembre 1918, Bât. Curien/CPE, 69622, Villeurbanne, France. E-mail: marc.lemaire.chimie@univ-lyon1.fr; Fax: +33-472-43-14-08; Tel: +33-472-43-14-07. b Minakem SAS, 145 chemin des Lilas, 59310 Beuvry-la-Forêt, France. Table of contents 1. Calculation of theoretical atom-economies and E factors ............................................. 2 2. General information ......................................................................................................... 4 3. HPLC method for the amidation of hydroquinone ....................................................... 4 4. General procedures ........................................................................................................... 5 5. Characterization data of the products ............................................................................ 7 6. 1 H and 13 C spectra ............................................................................................................. 8 Electronic Supplementary Material (ESI) for Green Chemistry. This journal is © The Royal Society of Chemistry 2014 2 1. Calculation of theoretical atom-economies and E factors Theoretical atom-economies (AE) and E factors were calculated for the production of paracetamol (M = 151.16 g.mol -1 ) in accordance with Trost’s definition 1 of atom-economy and with Sheldon’s definition 2 of E factor. These indicators were calculated using the following relations: Four different routes were evaluated for the industrial production (or considered as such) of paracetamol from benzene (Scheme A). - Route 1: Nitration of chlorobenzene. - Route 2: Nitration of phenol. - Route 3: Reduction of nitrobenzene. - Route 4: Acetamidation of hydroquinone (this work). Scheme A. Routes for paracetamol synthesis 1 a) B. M. Trost, Science, 1991, 254, 1471-1477. b) B. M. Trost, Angew. Chem. Int. Ed. Engl. 1995, 34, 259–281. c) C.-L. Li and B. M. Trost, PNAS 2008, 105, 13197-13202. 2 a) R. A. Sheldon, Chem. Ind. 1992, 903-906. b) R. A. Sheldon, C. R. Acad. Sci. Paris, IIc 2000, Chemistry 3, 541- 551. 5 Table C. Retention and detection wavelength of measured compounds Compound Retention time Detection wavelength p-Aminophenol 2.6-2.7 min 254 nm Hydroquinone 7.0-7.5 min 290 nm Paracetamol 12.0-12.7 min 290 nm The yields of hydroquinone, para-aminophenol and paracetamol were calculated from calibration curves. Figure B. Example of a HPLC chromatogram of a crude mixture. 4. General procedures a. General procedure for scope and optimization (procedure a) A phenol derivative (40 mmol, 1 equiv), ammonium acetate (6.3 g, 80 mmol, 2 equiv) and acetic acid (11.5 mL, 200 mmol, 5 equiv) were successively added in a 30-mL steel reactor equipped with an inner glass tube and an inner temperature sensor. The reactor was purged with argon and heated to 160 °C (graphite bath) before stirring. The temperature was then increased to 220 °C and the mixture was stirred at this temperature for 15 hours. For optimization reactions, the mixture was diluted with methanol and water, poured into a 250-mL volumetric flask and completed to 250 mL with water and methanol. The reaction was finally analysed by HPLC. For the scope, the mixture was diluted with water (75 mL) and neutralized with sodium carbonate (Na2CO3, 22 g) and extracted three times with ethyl acetate (EtOAc, 3  75 mL). The organic layers were combined and the solvent was removed under reduce pressure (60 °C, 8 mbar). The crude product was purified by column chromatography (cyclohexane / EtOAc). 6 b. Medium-scale preparation of paracetamol (procedure b) Hydroquinone (44.0 g, 0.4 mol, 1 equiv), ammonium acetate (63.0 g, 0.8 mol, 2 equiv) and acetic acid (114 mL, 2 mol, 5 equiv) were added in a 300-mL Parr Instrument reactor equipped with a temperature sensor and a mechanical stirrer. The autoclave was purged with argon and heated to 160 °C (heating mantle) before stirring. The temperature was further increased to 230 °C and the mixture was stirred at this temperature for 15 hours. The reactor was cooled down to room temperature and the homogeneous mixture was transferred to a 250-mL flask (a sample was taken at that stage in order to run HPLC analyses). A distillation set-up was then installed and acetic acid was evaporated under reduced pressure. A total amount of 98 mL was recovered which corresponds to a 85% recovery. The reaction mixture was cooled down to room temperature and the precipitate was filtered, washed twice with water (2  20 mL) and dried to give paracetamol (53.0 g, 88%) as a white solid. HPLC analysis revealed a 99% purity. 7 5. Characterization data of the products N-(4-Hydroxy-phenyl)-acetamide [103-90-2]. The title compound was prepared from hydroquinone (44.0 g, 0.4 mol) following the procedure b to give paracetamol (53.0 g, 88% yield) as a white solid. M.p. 170 °C; 1 H NMR (300 MHz, CD3OD): δ 2.08 (s, 3H), 6.72 (d, 2H, J = 8.7), 7.30 (d, 2H, J = 8.7); 13 C NMR (75 MHz, CD3OD): δ 23.5 (CH3), 116.2 (2 CH Ar ), 123.4 (2 CH Ar ), 131.5 (Cq Ar ), 155.3 (Cq Ar ), 171.4 (Cq C=O ); IR (ATR)  max: 3322, 3160, 1651; MS (ESI + ): 110.1 ([HO-C6H4-NH3] + , 9), 152.1 ([M+H] + , 100). N-(3-Hydroxy-phenyl)-acetamide [621-42-1]. The title compound was prepared from resorcinol (4.40 g, 40 mmol) following the procedure a. The crude product was purified by column chromatography (cyclohexane / EtOAc 90 : 10) to give N-(3-hydroxy-phenyl)-acetamide (3.01 g, 50% yield) as a white solid. M.p. 148 °C; 1 H NMR (300 MHz, CD3OD): δ 2.09 (s, 3H), 6.53 (ddd, 1H, J = 8.1, 2.4, 0.9), 6.91 (ddd, 1H, J = 8.1, 2.1, 0.9), 7.08 (t, 1H, J = 8.1), 7.17 (t, 1H, J = 2.1); 13 C NMR (75 MHz, CD3OD): δ 23.8 (CH3), 108.4 (CH Ar ), 112.1 (CH Ar ), 112.3 (CH Ar ), 130.5 (CH Ar ), 140.9 (Cq Ar ), 158.8 (Cq Ar ), 171.6 (Cq C=O ); IR (ATR)  max: 3322, 3058, 1604; MS (ESI + ): 110.1 ([HO-C6H4-NH3] + , 18), 152.1 ([M+H] + , 100), 174.1 ([M+Na] + , 28). N-(2-Hydroxy-phenyl)-acetamide [614-80-2]. The title compound was prepared from catechol (4.40 g, 40 mmol) following the procedure a. The crude product was purified by column chromatography (cyclohexane / EtOAc 60 : 40) to give N-(2-hydroxy-phenyl)-acetamide (0.52 g, 9% yield) as a grey solid. M.p. 207 °C; 1 H NMR (300 MHz, CD3OD): δ 2.17 (s, 3H), 6.80 (td, 1H, J = 7.7, 1.5), 6.85 (dd, 1H, J = 7.8, 1.5), 6.99 (td, 1H, J = 7.8, 1.5); 13 C NMR (75 MHz, d6-DMSO): δ 23.6 (CH3), 116.0 (CH Ar ), 119.0 (CH Ar ), 122.4 (CH Ar ), 124.7 (CH Ar ), 126.4 (Cq Ar ), 147.9 (Cq Ar ), 169.0 (Cq C=O ); IR (ATR)  max: 3400, 3031, 1656; MS (ESI + ): 110.1 ([HO-C6H4-NH3] + , 25), 152.0 ([M+H] + , 100), 174.0 ([M+Na] + , 19). N-Naphthalen-1-yl-acetamide [575-36-0]. The title compound was prepared from 1-naphthol (5.77 g, 40 mmol) following the procedure a. The crude product was purified by column chromatography (cyclohexane / EtOAc 95 : 5) to give N-naphthalen-1-yl-acetamide (2.70 g, 36% yield) as an orange solid. M.p. 160 °C; 1 H NMR (300 MHz, d6-DMSO): δ 2.20 (s, 3H), 7.48 (t, 1H, J = 7.8), 7.52-7.56 (m, 2H), 7.71 (d, 1H, J = 7.5), 7.75 (d, 1H, J = 8.1), 7.92-7.95 (m, 1H), 8.08-8.11 (m, 1H), 9.93 (br s, 1H, NH); 13 C NMR (75 MHz, d6-DMSO): δ 23.5 (CH3), 121.5 (CH Ar ), 122.7 (CH Ar ), 125.0 (CH Ar ), 125.6 (CH Ar ), 125.7 (CH Ar ), 126.0 (CH Ar ), 127.7 (Cq Ar ), 128.1 (CH Ar ), 133.7 (2 Cq Ar ), 168.9 (Cq C=O ); IR (ATR)  max: 3269, 1654, 1540; MS (ESI + ): ([C10H7NH3] + , 37), 186.1 ([M+H] + , 100). N-Naphthalen-2-yl-acetamide [581-97-5]. The title compound was prepared from 2-naphthol (5.77 g, 40 mmol) following the procedure a.The crude product was purified by column chromatography (cyclohexane / EtOAc 95 : 5) to give N-naphthalen-2-yl-acetamide (4.12 g, 56% yield) as a white solid. M.p. 130 °C; 1 H NMR (300 MHz, CD3OD): δ 2.15 (s, 3H), 7.32-7.43 (m, 2H), 7.52 (dd, 1H, J = 8.9, 2.0), 7.71-7.77 (m, 3H), 8.18 (d, 1H, J = 1.8); 13 C NMR (75 MHz, CD3OD): δ 23.9 (CH3), 117.7 (CH Ar ), 121.2 (CH Ar ), 125.9 (CH Ar ), 127.4 (CH Ar ), 128.5 (2 CH Ar ), 129.5 (CH Ar ), 132.0 (Cq Ar ), 135.2 (Cq Ar ), 137.3 (Cq Ar ), 171.8 (Cq C=O ); IR (ATR)  max: 3281, 1685, 1547; MS (ESI + ): 144.2 ([C10H7NH3] + , 34), 186.1 ([M+H] + , 100). 10 N-(2-Hydroxy-phenyl)-acetamide 1H (300 MHz, CD3OD) N-(2-Hydroxy-phenyl)-acetamide 13C (75 MHz, d6-DMSO) 11 N-Naphthalen-1-yl-acetamide 1H (300 MHz, d6-DMSO) N-Naphthalen-1-yl-acetamide 13C (75 MHz, d6-DMSO) 12 N-Naphthalen-2-yl-acetamide 1H (300 MHz, CD3OD) N-Naphthalen-2-yl-acetamide 13C (75 MHz, CD3OD)