SUPPORTING INFORMATION A Sustainable Approach to Waste-Minimized Sonogashira Cross-Coupling Reaction Based on Recoverable/Reusable heterogeneous Catalytic/Base System and Acetonitrile Azeotrope Vadym Kozell, [a] Michael McLaughlin, [a] Giacomo Strappaveccia, [a] Stefano Santoro, [a] Lucia Anna Bivona, [b],[c] Carmela Aprile, [c] Michelangelo Gruttadauria, [b] Luigi Vaccaro* [a] [a] Vadym Kozel, Michael McLaughlin, Dr. Giacomo Strappaveccia, Prof. Dr. L. Vaccaro CEMIN - Dipartimento di Chimica, Biologia e Biotecnologie, Università di Perugia Via Elce di Sotto, 8; Perugia, Italia. E-mail: luigi.vaccaro@unipg.it [b] Dr. Lucia Bivona, Prof. Dr. Michelangelo Gruttadauria Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF) Sez. di Chimica, Università di Palermo, Viale delle Scienze s/n, Ed. 17, 90128 Palermo, Italy. [c] Dr. Lucia Bivona, Prof. Dr. Carmela Aprile Laboratory of Applied Material Chemistry (CMA), University of Namur, 61 rue de Bruxelles, 5000 Namur, Belgium. Table of contents General information Typical procedures E-factor calculations Representative characterization data for catalyst 1 Characterization data S2 S2 S4 - S5 S6 - S7 S8 - S20 S1
General information Unless otherwise stated, all solvents and reagents were used as obtained from Sigma-Aldrich Co. without further purification. GC-EIMS analyses were carried out by using a Hewlett-Packard HP 6890N Network GC system/5975 Mass Selective Detector equipped with an electron impact ionizer at 70 ev. NMR spectra were recorded on a Bruker DRX-ADVANCE 400 MHz ( 1 H at 400 MHz, 13 C at 100.6 MHz and 19 F at 376.4 MHz) in CDCl 3 using TMS as the internal standard. Elemental Analyses were conducted on a Fisons EA1108CHN. Melting points are not corrected and they were measured on a Büchi 510. An Inductive Coupled Plasma-Optical Emission Spectrometer (ICP-OES 710 Agilent Technology) was used to determine the amount of leached palladium into the reaction products. Typical procedure for the Sonogashira reaction in CH 3 CN/H 2 O azeotrope using homogeneous base (N-methylpiperazine) 1. The reaction was performed in a screw-capped vial with a magnetic stirrer. Catalyst (1) (10% wt. of Pd) (4 mg, 0.4 mmol%), CH 3 CN/H 2 O azeotrope (0.94 ml, 84/16 wt%), 1-methylpiperazine (2) (114 mg, 1.13 mmol, 99% purity), aryl iodide (0.94 mmol), alkyne (1.41 mmol) were consequently added and the resulting mixture was purged with N 2 gas for 5 minutes under stirring. The resulting mixture was left under stirring at 90 C. 2. After reaction completion, the reaction mixture was centrifuged for 10 min (5000 rpm) and the liquid was separated by decantation. 1 ml of acetonitrile/water azeotrope was added and the mixture was stirred for 5 min, centrifuged for 10 min (5000 rpm) and the liquid was separated by decantation. Ethyl acetate (5mL) was added and the organic layer was washed with water (3 x 1.5 ml), dried over anhydrous Na 2 SO 4 and the solvent was removed under vacuum to yield the product. 3. The catalyst was dried under nitrogen at 50 C and reused for the next catalytic cycle where reactants, reaction medium and 1-methylpiperazine were added. Typical procedure for the Sonogashira reaction in CH 3 CN/H 2 O azeotrope using heterogeneous base (PS-piperazine, 8) 1. The reaction was performed in a screw-capped vial with a magnetic stirrer. Catalyst (1) (10% wt. of Pd) (4 mg, 0.4 mmol%), CH 3 CN/H 2 O azeotrope (0.94 ml, 84/16 wt%), PS-piperazine (8) (335 mg, 1.13 mmol, 3.37 mmol/g), aryl iodide (0.94 mmol), alkyne (1.41 mmol,) were consequently added and the resulting mixture was purged with N 2 gas for 5 minutes under stirring. The resulting mixture was left under stirring at 90 C. 2. After reaction completion, 1 ml of acetonitrile/water azeotrope was added and the reaction mixture was stirred for 5 min, centrifuged for 2 min (5000 rpm) and the liquid was separated by decantation. Than 1 ml more of acetonitrile water azeotrope was added to the catalyst-base mixture and stirred for 2 min, centrifuged for 2 min (5000 rpm) and the liquid was separated by decantation. Resulting liquid phases were combined and the solvent was removed under vacuum to yield the product. 3. 1-Methylpiperazine (143 mg, 1.41 mmol, 99% purity) in 1 ml of acetonitrile/water azeotrope was added to the catalyst-base mixture, stirred and after 1h centrifuged for 2 min (5000 rpm) and the liquid phase was separated by decantation. Then 1 ml more of acetonitrile water azeotrope was added to the catalyst-base mixture was stirred for 2 min, centrifuged for 2 min (5000 rpm) and the liquid was separated by decantation. The catalyst-base mixture was dried under vacuum at 50 C and reused for the next catalytic cycle where just reactants and reaction medium were added. Hg-Poisoning test The reaction was performed in a screw-capped vial with a magnetic stirrer. Catalyst (1) (10% wt. of Pd) (4 mg, 0.4 mmol%), CH 3 CN/H 2 O azeotrope (0.94 ml, 84/16 wt%), PS-piperazine (8) (335 mg, 1.13 S2
mmol, 3.37 mmol/g), 4 -iodoacetophenone (231 mg, 0.94 mmol), phenylacetylene (144 mg, 1.41 mmol,) were consequently added and the resulting mixture was purged with N 2 gas for 5 minutes under stirring. The resulting mixture was left under stirring at 90 C until 60% conversion was reached. Then, 100 equivalents (relative to Pd) of Hg(0) were added and the reaction was kept under stirring at 90 C for additional 25 hours. After this time the reaction reached 62% conversion. Hot-filtration test The reaction was performed in a screw-capped vial with a magnetic stirrer. Catalyst (1) (10% wt. of Pd) (4 mg, 0.4 mmol%), CH 3 CN/H 2 O azeotrope (0.94 ml, 84/16 wt%), PS-piperazine (8) (335 mg, 1.13 mmol, 3.37 mmol/g), 4 -iodoacetophenone (231 mg, 0.94 mmol), phenylacetylene (144 mg, 1.41 mmol,) were consequently added and the resulting mixture was purged with N 2 gas for 5 minutes under stirring. The resulting mixture was left under stirring at 90 C until 60% conversion was reached. Then, the reaction mixture was filtered through a pre-heated sintered glass filter with the aid of Celite. Fresh PSpiperazine (8) (335 mg, 1.13 mmol) was added and the reaction was kept under stirring at 90 C for additional 25 hours. After this time the reaction reached 75% conversion. S3
E-Factor calculations Calculations has been aimed at the comparison of the two procedures based on the use of homogeneous or heterogeneous base 7a: Homogeneous: (769 mg {reaction solvent} + 114 mg {2} + 196 mg {5a} + 147 mg {6a} + 818 mg {azeotrope for washing} + 4485 mg {EtOAc} + 4500 mg {H 2 O} + 1500 mg {Na 2 SO 4 } - 137 mg {product})/137 mg = 90 (without considering chromatographic purification) Heterogeneous: (196 mg {5a} + 245 mg {6a} + 143 mg {2 used for regeneration of 8} + 120 mg {5% of azeotrope not recovered by distillation} + 1636 mg {azeotrope for washing} - 129 mg {product})/129 mg = 17 (without considering chromatographic purification) 7b: Homogeneous: (769 mg {reaction solvent} + 114 mg {2} + 236 mg {5b} + 147 mg {6a} + 818 mg {azeotrope for washing} + 4485 mg {EtOAc} + 4500 mg {H 2 O} + 1500 mg {Na 2 SO 4 } - 208 mg {product})/208 mg = 59 7c: Homogeneous: (769 mg {reaction solvent} + 114 mg {2} + 254 mg {5c} + 147 mg {6a} + 818 mg {azeotrope for washing} + 4485 mg {EtOAc} + 4500 mg {H 2 O} + 1500 mg {Na 2 SO 4 } - 218 mg {product})/218 mg = 57 Heterogeneous: (254 mg {5c} + 147 mg {6a} + 143 mg {2 used for regeneration of 8} + 120 mg {5% of azeotrope not recovered by distillation} + 1636 mg {azeotrope for washing} - 207 mg {product})/207 mg = 10 7d: Homogeneous: (769 mg {reaction solvent} + 114 mg {2} + 236 mg {5d} + 147 mg {6a} + 818 mg {azeotrope for washing} + 4485 mg {EtOAc} + 4500 mg {H 2 O} + 1500 mg {Na 2 SO 4 } - 199 mg {product})/199 mg = 62 Heterogeneous: (236 mg {5d} + 147 mg {6a} + 143 mg {2 used for regeneration of 8} + 120 mg {5% of azeotrope not recovered by distillation} + 1636 mg {azeotrope for washing} - 197 mg {product})/197 mg = 11 7e: Homogeneous: (769 mg {reaction solvent} + 114 mg {2} + 207 mg {5e} + 147 mg {6a} + 818 mg {azeotrope for washing} + 4485 mg {EtOAc} + 4500 mg {H 2 O} + 1500 mg {Na 2 SO 4 } - 155 mg {product})/155 mg = 80 (without considering chromatographic purification) Heterogeneous: (207 mg {5e} + 245 mg {6a} + 143 mg {2 used for regeneration of 8} + 120 mg {5% of azeotrope not recovered by distillation} + 1636 mg {azeotrope for washing} - 112 mg {product})/112 mg = 20 (without considering chromatographic purification) 7f: Homogeneous: (769 mg {reaction solvent} + 114 mg {2} + 222 mg {5f} + 147 mg {6a} + 818 mg {azeotrope for washing} + 4485 mg {EtOAc} + 4500 mg {H 2 O} + 1500 mg {Na 2 SO 4 } - 147 mg {product})/147 mg = 84 (without considering chromatographic purification) 7g: Homogeneous: (769 mg {reaction solvent} + 114 mg {2} + 209 mg {5g} + 147 mg {6a} + 818 mg {azeotrope for washing} + 4485 mg {EtOAc} + 4500 mg {H 2 O} + 1500 mg {Na 2 SO 4 } - 117 mg {product})/117 mg = 106 (without considering chromatographic purification) 7h: S4
Homogeneous: (769 mg {reaction solvent} + 114 mg {2} + 201 mg {5h} + 147 mg {6a} + 818 mg {azeotrope for washing} + 4485 mg {EtOAc} + 4500 mg {H 2 O} + 1500 mg {Na 2 SO 4 } - 130 mg {product})/130 mg = 95 (without considering chromatographic purification) 7i: Homogeneous: (769 mg {reaction solvent} + 114 mg {2} + 236 mg {5i} + 247 mg {6b} + 818 mg {azeotrope for washing} + 4485 mg {EtOAc} + 4500 mg {H 2 O} + 1500 mg {Na 2 SO 4 } - 246 mg {product})/246 mg = 50 Heterogeneous: (239 mg {5i} + 247 mg {6b} + 143 mg {2 used for regeneration of 8} + 120 mg {5% of azeotrope not recovered by distillation} + 1636 mg {azeotrope for washing} - 249 mg {product})/249 mg = 9 7j: Homogeneous: (769 mg {reaction solvent} + 114 mg {2} + 236 mg {5d} + 247 mg {6b} + 818 mg {azeotrope for washing} + 4485 mg {EtOAc} + 4500 mg {H 2 O} + 1500 mg {Na 2 SO 4 } - 241 mg {product})/241 mg = 52 Heterogeneous: (236 mg {5d} + 247 mg {6b} + 143 mg {2 used for regeneration of 8} + 120 mg {5% of azeotrope not recovered by distillation} + 1636 mg {azeotrope for washing} - 255 mg {product})/255 mg = 8 7k: Homogeneous: (769 mg {reaction solvent} + 114 mg {2} + 236 mg {5i} + 247 mg {6c} + 818 mg {azeotrope for washing} + 4485 mg {EtOAc} + 4500 mg {H 2 O} + 1500 mg {Na 2 SO 4 } - 249 mg {product})/249 mg = 50 7l: Heterogeneous: (236 mg {5i} + 147 mg {6a} + 143 mg {2 used for regeneration of 8} + 120 mg {5% of azeotrope not recovered by distillation} + 1636 mg {azeotrope for washing} - 191 mg {product})/191 mg = 11 S5
Figure S1. Solid state 13 C CP MAS NMR spectrum of material 1. Figure S2. TEM images (a and b) of material 1. Pd nanoparticles are not clearly visible in the images due to the low content of Pd(0) in the material with the formation of small nanoparticles with a narrow particles size distribution. S6
Figure S3. XPS spectrum Pd core 3d of material 1. The core-level spectrum was referred to the C 1s carbon peak at 284.6 ev. Pd3d 5/2 Pd3d 3/2 Intensity (a. u.) 332 334 336 338 340 342 344 346 Binding Energy (ev) Pd 3d Entry Material 5/2 ev Pd 3d 5/2 ev Pd(0) [Pd 2+ Pd/C ] [Pd 0] [%] 1 1 337.0 335.4 15 0.02 S7
Characterization Data Chem.Name 1,2-diphenylethyne (7a) List.Ref Green Chem., 2015, 17, 1071 1076 Homogeneous base: CH 3 CN/H 2 O azeotrope (0.94 ml, 84/16 wt%), 1-methylpiperazine (2) (114 mg, 1.13 mmol, 99% purity), iodobenzene (5a) (196 mg, 0.94 mmol, 98% purity), phenylacetylene (6a) (147 mg, 1.41 mmol, 98% purity). The crude oil was purified by column chromatography on silica gel (petroleum ether as eluent) to obtain the pure product (7a) as a white solid (137 mg, 82% yield). Heterogeneous base: CH 3 CN/H 2 O azeotrope (0.94 ml, 84/16 wt%), PS-piperazine (8) (335 mg, 1.13 mmol, 3.37 mmol/g), iodobenzene (5a) (196 mg, 0.94 mmol, 98% purity), phenylacetylene (6a) (245 mg, 2.35 mmol, 98% purity). The crude oil was purified by column chromatography on silica gel (petroleum ether as eluent) to obtain the pure product (7a) as a white solid (129 mg, 77% yield). Mult J value/hz Mol Formula C 14 H 10 m.p. 61-63 C Elemental Analysis: C:94.34, H:5.66; found: C:94.24, H:5.60 1 H NMR 400 MHz δ value: No. H CDCl 3 7.34-7.36 6 m 7.53-7.55 4 m 13 C NMR (100.6 Hz, CDCl 3 ) δ: 89.37, 123.28, 128.25, 128.34, 131.61 GC-EIMS (m/z, %): 179 (M + +1, 16), 178 (M +, 100), 177 (12), 176 (21), 152 (13), 151 (7), 150 (5), 126(4). S8
Chem.Name 1-nitro-3-(phenylethynyl)benzene (7b) List.Ref J. Organomet. Chem., 2005, 690, 2956 2966 CH 3 CN/H 2 O azeotrope (0.94 ml, 84/16 wt%), 1-methylpiperazine (2) (114 mg, 1.13 mmol, 99% purity), 1-iodo-3-nitrobenzene (5b) (236 mg, 0.94 mmol, 99% purity), phenylacetylene (6a) (147 mg, 1.41 mmol, 98% purity). The product (7b) was obtained as a pale yellow solid (208 mg, 95% yield). value/hz Mol Formula C 14 H 9 NO 2 m.p. 66-68 C Elemental Analysis: C:75.33, H:4.06, N:6.27; found: C:75.22, H:4.89, N:6.19 1 H NMR 400 MHz δ value: No. H Mult J CDCl 3 7.39 3 m 7.52-7.56 3 m 7.83 1 d 7.6 8.18 1 d 8.4 8.38 1 s 13 C NMR (100.6 Hz, CDCl 3 ) δ: 86.9, 91.9, 122.2, 122.9, 125.1, 126.4, 128.5, 129.1, 129.4, 131.8, 137.2, 148.1. GC-EIMS (m/z, %): 224 (M + +1, 15), 223 (M +, 100), 177 (36), 176 (64), 151 (22), 150 (15). S9
Chem.Name Methyl 4-(phenylethynyl)benzoate (7c) List.Ref Angew. Chem. Int. Ed. 2010, 49, 4067 4070 Homogeneous base: CH 3 CN/H 2 O azeotrope (0.94 ml, 84/16 wt%), 1-methylpiperazine (2) (114 mg, 1.13 mmol, 99% purity), methyl 4-iodobenzoate (5c) (254 mg, 0.94 mmol, 97% purity), phenylacetylene (6a) (147 mg, 1.41 mmol, 98% purity). The product (7c) was obtained as a pale yellow solid (218 mg, 98% yield). Heterogeneous base: CH 3 CN/H 2 O azeotrope (0.94 ml, 84/16 wt%), PS-piperazine (8) (335 mg, 1.13 mmol, 3.37 mmol/g), methyl 4-iodobenzoate (5c) (254 mg, 0.94 mmol, 97% purity), phenylacetylene (6a) (147 mg, 1.41 mmol, 98% purity). The product (7c) was obtained as a pale yellow solid (207 mg, 93% yield). Mult J value/hz Mol Formula C 16 H 12 O 2 m.p. 120-121 C Elemental Analysis: C:81.34, H:5.12; found: C:81.90, H:5.22 1 H NMR 400 MHz δ value: No. H CDCl 3 3.93 3 s 7.36 3 br 7.55 2 d 3.5 7.59 2 d 8.2 8.02 2 d 8.2 13 C NMR (100.6 Hz, CDCl 3 ) δ: 52.33, 88.77, 92.50, 122.86, 128.15, 128.56, 128.88, 129.65, 131.63, 131.87, 166.67 GC-EIMS (m/z, %): 237 (M + +1, 17), 236 (M +, 93), 206 (16), 205 (100), 177 (25), 176 (48), 151 (18), 150 (13), 88 (12). S10
Chem.Name 1-(4-(phenylethynyl)phenyl)ethanone (7d) List.Ref Green Chem., 2015, 17, 1071 1076 Homogeneous base: CH 3 CN/H 2 O azeotrope (0.94 ml, 84/16 wt%), 1-methylpiperazine (2) (114 mg, 1.13 mmol, 99% purity), 4-iodoacetophenone (5d) (236 mg, 0.94 mmol, 98% purity), phenylacetylene (6a) (147 mg, 1.41 mmol, 98% purity). The product (7d) was obtained as a pale yellow solid (199 mg, 96% yield). Heterogeneous base: CH 3 CN/H 2 O azeotrope (0.94 ml, 84/16 wt%), PS-piperazine (8) (335 mg, 1.13 mmol, 3.37 mmol/g), 4-iodoacetophenone (5d) (236 mg, 0.94 mmol, 98% purity), phenylacetylene (6a) (147 mg, 1.41 mmol, 98% purity). The product (7d) was obtained as a pale yellow solid (197 mg, 95% yield). Mult J value/hz Mol Formula C 16 H 12 O m.p. 98 C Elemental Analysis: C:87.25, H:5.49; found: C:87.00, H:5.40 1 H NMR 400 MHz δ value: No. H CDCl 3 2.63 3 s 7.37-7.38 3 m 7.55-7.57 2 m 7.61 2 d 8.3 7.94 2 d 8.3 13 C NMR (100.6 Hz, CDCl 3 ) δ: 26.6, 88.6, 92.7, 122.6, 128.2, 128.3, 128.4, 128.8, 131.69, 131.73, 136.2, 197.3. GC-EIMS (m/z, %): 221 (M + +1, 11), 220 (M +, 64), 206 (18), 205 (100), 177 (23), 176 (49), 151 (16), 150 (13). S11
Chem.Name 1-methyl-4-(phenylethynyl)benzene (7e) List.Ref Green Chem., 2015, 17, 1071 1076 Homogeneous base: CH 3 CN/H 2 O azeotrope (0.94 ml, 84/16 wt%), 1-methylpiperazine (2) (114 mg, 1.13 mmol, 99% purity), 4-iodotoluene (5e) (207 mg, 0.94 mmol, 99% purity), phenylacetylene (6a) (147 mg, 1.41 mmol, 98% purity). The crude oil was purified by column chromatography on silica gel (petroleum ether as eluent) to obtain the pure product (7e) as a white solid (155 mg, 80% yield) Heterogeneous base: CH 3 CN/H 2 O azeotrope (0.94 ml, 84/16 wt%), PS-piperazine (8) (335 mg, 1.13 mmol, 3.37 mmol/g), 4- iodotoluene (5e) (207 mg, 0.94 mmol, 99% purity), phenylacetylene (6a) (245 mg, 2.35 mmol, 98% purity). The crude oil was purified by column chromatography on silica gel (petroleum ether as eluent) to obtain the pure product (7e) as a white solid (112 mg, 62% yield) Mult J value/hz Mol Formula C 15 H 12 m.p. 67-70 C Elemental Analysis: C: 93.71, H: 6.29; found: C: 93.63, H: 6.19. 1 H NMR 400 MHz δ value: No. H CDCl 3 2.37 3 s 7.16 2 d 7.8 7.33-7.36 3 m 7.43 2 d 7.9 7.52-7.54 2 m 13 C NMR (100.6 Hz, CDCl 3 ) δ: 21.5, 88.7, 89.6, 120.2, 123.5, 128.1, 128.3, 129.1, 131.5, 131.6, 138.4. GC-EIMS (m/z, %): 193 (M + +1, 16)192 (M +, 100), 191 (47), 190 (12), 189 (23), 165 (15). S12
Chem.Name 1-methoxy-3-(phenylethynyl)benzene (7f) List.Ref J. Org. Chem., 2016, 81, 5244 5249 CH 3 CN/H 2 O azeotrope (0.94 ml, 84/16 wt%), 1-methylpiperazine (2) (114 mg, 1.13 mmol, 99% purity), 3-iodoanisole (5f) (222 mg, 0.94 mmol, 99% purity), phenylacetylene (6a) (147 mg, 1.41 mmol, 98% purity). The crude oil was purified by column chromatography on silica gel (petroleum ether as eluent) to obtain the pure product (7f) as a white solid (147 mg, 75% yield) Mult J value/hz Mol Formula C 15 H 12 O m.p. 74 C Elemental Analysis: C: 86.51, H: 5.81; found: C: 86.93, H: 6.01. 1 H NMR 400 MHz δ value: No. H CDCl 3 3.83 3 s 6.9 1 d 8.0 Hz 7.07 1 br 7.14 1 d 7.5 Hz 7.24-7.28 1 m 7.34-7.36 3 m 7.53-7.55 2 m 13 C NMR (100.6 Hz, CDCl 3 ) δ: 55.4, 89.3, 89.4, 115.1, 116.4, 123.3, 124.3, 128.46, 128.49, 129.6, 131.8, 159.5. GC-EIMS (m/z, %): 209 (M + +1, 16), 208 (M +, 100), 178 (28), 165 (25), 164 (11), 163 (10). S13
Chem.Name 1-methyl-2-(phenylethynyl)benzene (7g) List.Ref J. Organomet. Chem., 2005, 690, 2956 2966 CH 3 CN/H 2 O azeotrope (0.94 ml, 84/16 wt%), 1-methylpiperazine (2) (114 mg, 1.13 mmol, 99% purity), 2-iodotoluene (5g) (209 mg, 0.94 mmol, 98% purity), phenylacetylene (6a) (147 mg, 1.41 mmol, 98% purity). The crude oil was purified by column chromatography on silica gel (petroleum ether as eluent) to obtain the pure product (7g) as a colorless oil (117 mg, 65% yield). Mult J value/hz Mol Formula C 15 H 12 m.p. oil Elemental Analysis: C: 93.71, H: 6.29; found: C: 93.65, H: 6.21. 1 H NMR 400 MHz δ value: No. H CDCl 3 2.55 3 s 7.17-7.26 3 m 7.36-7.37 3 m 7.52-7.57 3 m 13 C NMR (100.6 Hz, CDCl 3 ) δ: 20.88, 88.49, 93.49, 123.18, 123.72, 125.72, 128.30, 128.44, 128.49, 129.60, 131.65, 131.98, 140.32 GC-EIMS (m/z, %): 193 (M + +1, 15), 192 (M +, 100), 191 (95), 190 (19), 189 (35), 165 (28). S14
Chem.Name 2-(phenylethynyl)thiophene (7h) List.Ref Green Chem., 2015, 17, 1071 1076 CH 3 CN/H 2 O azeotrope (0.94 ml, 84/16 wt%), 1-methylpiperazine (2) (114 mg, 1.13 mmol, 99% purity), 2-iodothiophene (5h) (201 mg, 0.94 mmol, 98% purity), phenylacetylene (6a) (147 mg, 1.41 mmol, 98% purity). The crude oil was purified by column chromatography on silica gel (petroleum ether as eluent) to obtain the pure product (7h) as a white solid (130 mg, 75% yield). Mol Formula C 12 H 8 S m.p. 50-52 C Elemental Analysis: C: 78.22, H: 4.38, S: 17:40; found: C: 78.19, H: 4.30, S: 17.38. 1 H NMR 400 MHz δ value: No. H Mult J value/hz CDCl 3 7.00-7.02 1 m 7.29-7.30 2 m 7.34-7.35 3 m 7.51-7.53 2 m 13 C NMR (100.6 Hz, CDCl 3 ) δ: 82.6, 93.0, 122.9, 123.3, 127.1, 127.2, 128.36, 128.41, 129.2, 131.4, 131.9, 132.5. GC-EIMS (m/z, %): 185 (M + +1, 15)184 (M +, 100), 183 (8), 152 (17), 139 (17), 126 (6). S15
Chem.Name 1-((4-nitrophenyl)ethynyl)-2-(trifluoromethyl)benzene (7i) List.Ref Chem. Eur. J., 2008, 14, 6994 6999 Homogeneous base: CH 3 CN/H 2 O azeotrope (0.94 ml, 84/16 wt%), 1-methylpiperazine (2) (114 mg, 1.13 mmol, 99% purity), 1-iodo-4-nitrobenzene (5i) (236 mg, 0.94 mmol, 98% purity), 2-ethynyl-α,α,α-trifluorotoluene (6b) (247 mg, 1.41 mmol, 97% purity). The product (7i) was obtained as a pale yellow solid (246 mg, 90% yield). Heterogeneous base: CH 3 CN/H 2 O azeotrope (0.94 ml, 84/16 wt%), PS-piperazine (8) (335 mg, 1.13 mmol, 3.37 mmol/g), 1- iodo-4-nitrobenzene (5i) (239 mg, 0.94 mmol, 98% purity), 2-ethynyl-α,α,α-trifluorotoluene (6b) (247 mg, 1.41 mmol, 97% purity). The product (7i) was obtained as a pale yellow solid (249 mg, 91% yield). J value/hz Mol Formula C 15 H 8 F 3 NO 2 m.p. 95 C Elemental Analysis: C: 61.86, H: 2.77, N: 4.81; found: C: 61.76, H: 2.70, N: 4.79. 1 H NMR 400 MHz δ value: No. H Mult CDCl 3 7.47-7.51 1 m 7.54-7.58 1 m 7.66-7.73 4 m 8.23 2 d 8.5 13 C NMR (100.6 Hz, CDCl 3 ) δ: 90.6, 93.0, 120.7, 123.5 (q, J F-C =273.5 Hz), 123.8, 126.3, 129.4, 129.9, 131.9, 132.3, 132.8, 134.4, 147.7. 19 F NMR (376.4 Hz, CDCl 3 ) δ: -62.6 GC-EIMS (m/z, %): 292 (M + +1, 16), 291 (M +, 100), 261 (22), 245 (19), 243 (11), 233 (30), 232 (30), 225 (39), 214 (13). S16
Chem.Name 1-(4-((2-(trifluoromethyl)phenyl)ethynyl)phenyl)ethanone (7j) List.Ref Chem. Eur. J., 2008, 14, 6994 6999 Homogeneous base: CH 3 CN/H 2 O azeotrope (0.94 ml, 84/16 wt%), 1-methylpiperazine (2) (114 mg, 1.13 mmol, 99% purity), 4-iodoacetophenone (5d) (236 mg, 0.94 mmol, 98% purity), 2-ethynyl-α,α,α-trifluorotoluene (6b) (247 mg, 1.41 mmol, 97% purity). The product (7j) was obtained as a pale yellow solid (241 mg, 89% yield). Heterogeneous base: CH 3 CN/H 2 O azeotrope (0.94 ml, 84/16 wt%), PS-piperazine (8) (335 mg, 1.13 mmol, 3.37 mmol/g), 4- iodoacetophenone (5d) (236 mg, 0.94 mmol, 98% purity), 2-ethynyl-α,α,α-trifluorotoluene (6b) (247 mg, 1.41 mmol, 97% purity). The product (7j) was obtained as a pale yellow solid (255 mg, 94% yield). Mult J value/hz Mol Formula C 17 H 11 F 3 O m.p. 80-83 C Elemental Analysis: C: 70.83, H: 3.85; found: C: 70.79, H: 3.80. 1 H NMR 400 MHz δ value: No. H CDCl 3 2.62 3 s 7.46-7.48 1 m 7.53-7.57 1 m 7.63 2 d 8.1 7.68-7.72 2 m 7.96 2 d 8.1 13 C NMR (100.6 Hz, CDCl 3 ) δ: 26.7, 88.4, 93.9, 120.9, 123.6 (q, J F-C =273.3 Hz), 126.0, 127.5, 128.3, 128.5, 131.5, 131.8, 132.3, 133.9, 136.6, 197.3. 19 F NMR (376.4 Hz, CDCl 3 ) δ: -62.7. GC-EIMS (m/z, %): 289 (M + +1, 9), 288 (M +, 48), 274 (18), 273 (100), 245 (30), 243 (7), 225 (26), 219 (6), 214 (6). S17
Chem.Name 1-nitro-4-((4-(trifluoromethyl)phenyl)ethynyl)benzene (7k) List.Ref RSC Adv., 2014, 4, 32643 32646 CH 3 CN/H 2 O azeotrope (0.94 ml, 84/16 wt%), 1-methylpiperazine (2) (114 mg, 1.13 mmol, 99% purity), 1-iodo-4-nitrobenzene (5i) (236 mg, 0.94 mmol, 98% purity), 4-ethynyl-α,α,α-trifluorotoluene (6c) (247 mg, 1.41 mmol, 97% purity). The product (7k) was obtained as a pale yellow solid (249 mg, 91% yield). Mol Formula C 15 H 8 F 3 NO 2 m.p. 110 C Elemental Analysis: C: 61.86, H: 2.77, N: 4.81; found: C: 61.80, H: 2.77, N: 4.85. 1 H NMR 400 MHz δ value: No. H Mult J value/hz CDCl 3 7.66-7.71 6 m 8.25 2 d 8.4 13 C NMR (100.6 Hz, CDCl 3 ) δ: 89.5, 92.8, 123.7, 123.7 (q, J F-C =270.9), 125.4, 125.9, 129.4, 130.7 (q, J F- C=32.8), 132.1, 132.5, 147.3. 19 F NMR (376.4 Hz, CDCl 3 ) δ: -59.6. GC-EIMS (m/z, %): 292 (M + +1, 17), 291 (M +, 100), 272 (11), 261 (43), 245 (12), 233 (37), 232 (13), 225 (34), 176 (39), 175 (12). S18
Chem.Name 1-nitro-4-(phenylethynyl)benzene (7l) List.Ref Green Chem., 2015, 17, 1071 1076 CH 3 CN/H 2 O azeotrope (0.94 ml, 84/16 wt%), PS-piperazine (8) (335 mg, 1.13 mmol, 3.37 mmol/g), 1- iodo-4-nitrobenzene (5i) (236 mg, 0.94 mmol, 98% purity), phenylacetylene (6a) (147 mg, 1.41 mmol, 98% purity). The product (7l) was obtained as a pale yellow solid (191 mg, 91% yield). J value/hz Mol Formula C 14 H 9 NO 2 m.p. 116-118 C Elemental Analysis: C:75.33, H:4.06, N:6.27; found: C:75.10, H:4.99, N:6.20. 1 H NMR 400 MHz δ value: No. H Mult CDCl 3 7.39-7.41 3 m 7.55-7.58 2 m 7.67 2 d 8.7 8.23 2 d 8.7 13 C NMR (100.6 Hz, CDCl 3 ) δ: 87.6, 94.7, 122.1, 123.6, 128.6, 129.3, 130.3, 131.9, 132.3, 147.0. GC-EIMS (m/z, %): 224 (M + +1, 15), 223 (M +, 100), 193 (37), 177 (18), 176 (58), 165 (32), 151 (20), 150 (16). S19
Chem.Name PS-Piperazine (8) Merrifield resin (4g, 200-400 mesh, 3.5-4.5 mmol/g Cl loading, 1% cross-linked with divinylbenzene) was reacted with an excess of piperazine (10 g, 0.115 mol, 99% purity) in toluene (40 ml) at 60 C for 72 hours. The resin was washed with a 0.5M of piperazine in toluene, then toluene, water and acetone to remove the excess of amine and finally dried under vacuum. The amine loading (3.37 mmol/g) was determined by elemental analysis. S20