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Electronic Supplementary Material (ESI) for RSC Advances. This journal is The Royal Society of Chemistry 215 Aqueous MW eco-friendly protocol for amino group protection. M. ardi, a. errera Cano, b P. Costanzo, c M. liverio, c G. Sindona a and A. Procopio c a Dipartimento di Chimica, Università della Calabria Cubo 12C, 8736-Arcavacata di Rende (CS), Italia. E- mail: monica.nardi@unical.it. Fax: +3998449233; Tel: +3998449285 b IFIQC, Departamento de Química rgánica, Facultad de Ciencias Químicas, Universidad acional de Córdoba, Ciudad Universitaria, Córdoba 5, Argentina. c Dipartimento di Scienze della Salute, Università Magna Graecia, Viale Europa, 88-Germaneto (CZ), Italia. General methods and experimental procedures. 2 1, 13 C and MS spectra of compounds... 7

General: All chemicals and solvents were purchased from common commercial sources and were used as received without any further purification. All reactions were monitored by TLC on silica Merck F254 percolated aluminum plates and were developed by spraying with ninhydrin solution when possible or with a GC-MS Shimadzu workstation, constituted by a GC 21 (provided of a 3 m- QUADREX 7 5MS capillary column, operating in splitless mode, 1 ml min 1 flow of e as carrier gas) and a 21 quadrupole mass-detector. All reactions were carried out in the a Syntos 3 Microwave oven (Anton-Paar) with rotor 4 24MG5. Proton nuclear magnetic resonance ( 1 - MR) spectra were recorded on a Brücker spectrometer at 3 Mz. Chemical shifts are reported in δ units with TMS as reference (δ.). All coupling constants (J) are reported in ertz. Multiplicity is indicated by one or more of the following: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet). Carbon nuclear magnetic resonance ( 13 C-MR) spectra were recorded on a Brücker at 3 Mz. Chemical shifts are reported in δ units relative to CDCl 3 (δ 77.). Melting points were obtained on a Kofler apparatus. General Procedure to determine the substrate scope To a stirred solution of tosyl chloride, fmoc chloride, boc anidride and acetyl chloride (2.2 mmol), in 2 (3 ml) was added the -nucleophile (2. mmol) and conducted in MW. The reaction mixture until TLC indicated consumption of the starting material. The reaction mixture presents a organic precipitate. The same, repeatedly washed with water is subsequently dried. -Benzyl-p-toluenesulfonamide (1a): yellow solid obtained in 9 % yield (mp 115.1-115.9 C); 1 -MR (3 Mz, CDCl 3 ): = 7.76 (d, 2, J = 8.24, C ar ), 7.24-7.32 (m, 4, C ar ), 7.17 7.21, (m, 2, C ar ), 4.76 ( t, 1,, J = 6.15), 4.11 (d, 2, C 2, J = 6.22), 2.44 (s, 3, C 3 ). 13 C-MR (75 Mz, CDCl 3 ): 21.85, 47.59, 114.34, 127.52, 128.2, 129.1, 136.7, 137.26, 136.64, 143.84. -(9-Fluorenylmethoxycarbonyl) benzylamine (1b): Colorless solid obtained in 98 % yield. 1 -MR (3 Mz, CDCl 3 ): = 7.58-7.79 (m, 4, C ar ), 7.25-7.46 (m, 5, C ar ), 4.51 (dd, 2, C 2 ), 4.21-4.39 (m, 2, C 2 ). 13 C-MR (75 Mz, CDCl 3 ): 46.2, 47.32, 66.71, 79.74, 125., 127.5, 127.39, 127.55, 127.69, 127.27, 128.73, 141.33, 142.42, 143.93, 156.43. -(tert-butoxycarbonyl) benzylamine (1c): white solid obtained in 98% yield (mp 55-57 C); 1 -MR (3 Mz, CDCl 3 ): = 7.25-7.35 (m, 5, Car), 4.31 (d, J= 5.49, 2), 1.46 (s, 9) 13 C-MR (75 Mz, CDCl 3 ): 46.2, 47.32, 66.71, 79.74, 125., 127.5, 127.39, 127.55, 127.69, 127.27, 128.73, 141.33, 142.42, 143.93, 156.43. -benzylacetamide (1d): yellow flake solid obtained in 98% yield (mp -62 C). Spectroscopic data compared to those of the pure product.

-phenyl-p-toluenesulfonamide (2a): white solid obtained in 98 % yield (mp 11.5-12.2 C);. 1 -MR (3 Mz, CDCl 3 ): 7.67 (d, J= 7.5 z, 2, Car), 7.8-7.32 (m, 5, -Ar), 7.11 (d, J= 7.5 z, 2, Car), 2.38 (s, 3, C 3 ), 1.74, (s, 1, ). 13 C-MR (75 Mz, CDCl 3 ): 21.5, 111.1, 121.1, 125.7, 126., 129.5,136.7, 143.1. 149.6. -(9-fluorenylmethoxycarbonyl) aniline (2b): Brown solid obtained in 92 % yield; 1 - MR (3 Mz, CDCl 3 ) 7.79 (d, 2, Car, J=7.4 z), 7.63 (d, 2, Car, J=7. z), 7.43-7.5 (m, 8, Car), 6.63 (br s, 1), 4.56 (d, 2, J=6.4 z), 4.28 (t, 1, J=6.4 z). 13 C-MR (75 Mz, CDCl 3 ) : 47.1, 66.8, 118.81, 12., 123.6, 124.9, 127.1, 127.8, 129.1, 137.7, 141.4,143.8, 153.4. -(tert-butoxycarbonyl) aniline (2c): White solid obtained in 94 % yield (mp 133-137 C); 1 -MR (3 Mz, CDCl 3 ) 1 -MR (3 Mz, CDCl 3 ): 7.38-7.25 ( m, 4 ), 1.52 (s, 9), 7.25 (tt, 1, Ar, J= 7.27; J= 1.38), 6.49 (s, 1, ), 13 C-MR (75 Mz, CDCl 3 ): 28.69, 8.83, 118.89, 123.38, 129.31, 138.69, 153.99. -Acetyl aniline (2d): White solid obtained in 98 % yield (114-116 C). Spectroscopic data compared to those of the pure product. -toluidine p-toluenesulfonamide (3a): Coloress oil obtained in 98 % yield. Spectroscopic data compared to those of the pure product. -(9-Fluorenylmethoxycarbonyl)-toluidine (3b): colorless solid obtained in 9 % yield (mp 195-197 ºC). 1 -MR (3 Mz, CDCl 3 ) δ= 7.79-7.77 (m, 2, C ar ), 7.63-7.61 (m, 2, C ar ), 7.44-7.26 (m, 6, C ar ), 7.11-7.9 (m, 2, C ar ), 7.8-6.9 (m, 4, C ar ), 4.53 (m, 2), 4.27 (br, 1, ), 2.3 (s, 3), 13 C-MR (75 Mz, CDCl 3 ) δ = 2.76, 47.17, 66.74, 12.3, 127.11, 127.16, 129.55, 141.86, 143.8. -(tert-butoxycarbonyl)-toluidine (3c): brow solid obtained in 98 % yield (mp 34 36 ºC); 1 -MR (3 Mz, CDCl 3 ): = 7.22-7.26 (m, 2, C ar ), 7.8 (d, J= 8.25, 2, C ar ), 6.56 (s, 1, ), 2.29 (s, 3), 1.5 (s, 9); 13 C-MR (75 Mz, CDCl 3 ): 28.69, 8.64, 119.3, 129.78, 132.87, 136.6, 153.23 -Acetyl-toluidine (3d): off white to brown flake solid obtained in 97 % yield (mp 34 36 ºC). -(p-nitro-aniline) p-toluenesulfonamide (4a): yellow flake solid obtained in 85 % yield (mp 19-191 C). Spectroscopic data compared to those of the pure product. -(9-fluorenylmethoxycarbonyl) p-nitro-aniline (4b): yellow solid obtained in 8 % yield. C; 1 -MR (3 Mz, CDCl 3 ): = 8.14-8.17 (m, 2, Car), 7.19-7.79 (m, 1, Car), 4.53 4.63 (m, 1, C), 4.26 (t, 2, C 2, J = 6.5). 13 C-MR (75 Mz, CDCl 3 ): 46.2, 47.32, 66.71, 79.74, 125., 127.5, 127.39, 127.55, 127.69, 127.27, 128.73,

141.33, 142.42, 143.93, 156.43. -( tert-butoxycarbonyl) p-nitro-aniline (4c) yellow flake oil obtained in 98 % yield. Spectroscopic data compared to those of the pure product. -p-nitro-aniline acetamide (4d): Solid, yellow obtained in 96% yield (mp 214-216 C). Spectroscopic data compared to those of the pure product. -p-nitro-aniline-p-toluenesulfonamide (5a) white solid obtained in 98% yield (mp 181-183 C). Spectroscopic data compared to those reported in the literature. 2 -(9-fluorenylmethoxycarbonyl) p-methoxybenzylamine (5b): yellow solid obtained in 95 % yield (mp ). 1 MR (3 Mz, CDCl 3 ) : 7.77 (d, 2, J=7. z), 7.59 (d, 2, J=5.8 z), 7.51-7.19 (m, 6), 6.87 (d, 2, J=6.9 z), 4.45 (d, 2, J=5.5 z), 4.45-4.22 (m, 5 ) 3.8 (s, 3). 13 C-MR (75 Mz, CDCl 3 ) : 44.6, 47.3, 55.3, 66.6, 114.1, 12., 125., 127., 127.7, 128.9, 13.5, 141.3, 143.9, 156.3, 159.1 -(tert-butoxycarbonyl) p-methoxybenzylamine (5c): colourless oil 98. 1 -MR (3 Mz, CDCl 3 ) = 7.26-7.19 (m, 2, Car), 6.87-6.84 (m, 2, Car), 4.25-4.23 (m, 2, C 2 ), 3.79 (s, 3), 1.47 (s, 9), 13 C-MR (75 Mz, CDCl 3 ): 28.76, 44.52, 55.64, 79.74, 114.34, 129.19, 131.36, 156.18, 159.25. p-methoxybenzyl acetamide (5d): yellow oil obtained in 97 % yield. Spectroscopic data compared to those of the pure product. -ctyl p-toluenesulfonamide (6a): yellow oil obtained in 83 % yield. 1 -MR (3 Mz, CDCl 3 ) = 7.73 (d, J= 7.4 z, 2, Car), 7.31 (d, J= 7.4 z, 2, Car), 3.17-3.15 (m, 2, C 2 ), 2.4 (s, 3, C 3 ), 1.56-1.53 (m, 2, C 2 ), 1.37-1.2 (m, 1, 5 C 2 ),.9-1. (m, 3, C 3 ),. 13 C-MR (75 Mz, CDCl 3 ): 14.38, 22.83, 24.53, 43.53, 27.11, 29.48, 29.61, 31.23, 41.5, 127.28, 128.97, 136.37, 141.74. -(9-fluorenylmethoxycarbonyl) ctylamine (6b): Pale yellow solid obtained in 95% yield (mp 91-93ºC). 1 -MR (3 Mz, CDCl 3 ): = 7.8-7.19 (m, 8, C ar ), 4.5-4.32 (m, 2, C 2 ), 4.32-4.2 (m, 1, C), 3.19 (dd, 2, C 2, J = 12.9, J = 6.66), 1.58 1.4 (m, 2, C 2 ), 1.38-1.5- (m, 1, 5 C 2 ),.9-.7 (m, 3, C 3 ). 13 C-MR (75 Mz, CDCl 3 ): 14.42, 22.97, 44.52, 27.7, 29.54, 29.57, 32.12, 41.44, 47.65, 66.8, 12.28, 125.36, 127.34, 127.97, 141.66, 144.37, 156.75. -(tert-butoxycarbonyl) ctylamine (6c): Colourless oil obtained in 91% yield. Spectroscopic data compared to those reported in the literature. 21 -ctyl acetamide (6d): Colorless oil obtained in 97% yield. Spectroscopic data compared to those of the pure product.

p-toluenesulfonamide phenylalanine (7a): White solid obtained in 98 % yield (mp 165-166 C). Spectroscopic data compared to those of the pure product. -(9-fluorenylmethoxycarbonyl)-phenylalanine (7b): white solid obtained in 92 % yield (mp 18-187 C). Spectroscopic data compared to those of the pure product. -(tert-butoxycarbonyl)-phenylalanine (7c): white solid obtained in 94 % yield (mp 85-87 C). Spectroscopic data compared to those of the pure product. -Acetil-phenylalanine (7d): white solid obtained in 97 % yield (mp 171-173 C). Spectroscopic data compared to those of the pure product. p-toluenesulfonamide phenylalanine methyl ester (8a): white solid obtained in 94% yield. 1 -MR (CDCl 3, 3 Mz) 7.63 (d, J=8.25 z, 2), 7.28-7.2 (M, 5), 7.5 (dd, J=5.42, 2.2 z, 2), 5.8 (d, 1,, J = 9.6), 4.2 (dt, J= 9.6, J = 5.9, z, 2), 3.48 (s, 3, C 3 ), 3.2 (d, 2, J = 5.9), 2.4 (s, 3, C 3 ); 13 C-MR (CDCl 3, 75 Mz) 21.84, 39.7, 52.68, 56.93, 127.5, 127.57, 128.9, 129.72, 129.92, 135.25, 136.94, 143.92, 171.56. -(9-fluorenylmethoxycarbonyl)-phenylalanine methyl ester (8b): white solid obtained in 92% yield. 1 -MR (CDCl 3, 3 Mz) d 7.76 (d, J=7.5 z, 2), 7.56 (t, J=6.7 z, 2), 7.4 (td, J=7.5,.6 z, 2), 7.33 7.27 (m, 5), 7.8 (d, J=6.5 z, 2), 5.26 (d, J=8.1 z, 1), 4.67 (m, 1), 4.44 (dd, J=1.6, 7.1 z, 1), 4.34 (dd, J=1.6, 6.9 z, 1), 4.2 (t, J=7. z, 1), 3.73 (s, 3), 3.11 (m, 2); 13 C-MR (CDCl 3, 75 Mz) 38.4, 47.3, 52.6, 54.9, 67.1, 12.2, 125.3, 127.3, 127.4, 127.9, 128.8, 129.5, 135.9, 141.5, 144., 155.7, 172.1. -(tert-butoxycarbonyl)-phenylalanine methyl ester (8 c): white solid obtained in 96% yield. (mp 36-4 C). Spectroscopic data compared to those of the pure product. -Acetil-phenylalanine methyl esther (8d): colorless oil obtained in 95% yield. Spectroscopic data compared to those of the pure product. p-toluenesulfonamide alanine (9a): white solid obtained in 96% (mp 132-137 C). Spectroscopic data compared to those of the pure product. -(9-fluorenylmethoxycarbonyl)-alanine (9b): white solid obtained in 96% (mp 147-153 C). Spectroscopic data compared to those of the pure product. -(tert-butoxycarbonyl)- alanine (9c): white solid obtained in 96% (mp 79-83 C). Spectroscopic data compared to those of the pure product. -Acetil-alanine (9d): white solid obtained in 96 % yield. (mp 126-128 C). Spectroscopic data compared to those of the pure product.

p-toluenesulfonamide alanine methyl ester (1a): white solid obtained in 98% yield (mp 11-13 C). Spectroscopic data compared to those reported in the literature. 22 -(9-fluorenylmethoxycarbonyl)-alanine methyl ester (1b): white solid obtained in 92% yield (mp 11 112 C). Spectroscopic data compared to those of the pure product. -(tert-butoxycarbonyl)-alanine methyl ester (1c): colorless oil obtained in 93% yield. Spectroscopic data compared to those reported in the literature. 23 -Acetil-alanine methyl ester (1 d): colorless oil obtained in 97% yield. Spectroscopic data compared to those of the pure product. p-toluenesulfonamide isoleucine (11a): white solid obtained in 86% yield (mp 14-145 C). Spectroscopic data compared to those of the pure product. -(9-fluorenylmethoxycarbonyl)-isoleucine (11b): white solid obtained in 8% yield (mp 145-147 C). Spectroscopic data compared to those of the pure product. -(tert-butoxycarbonyl)-isoleucine (11c) white solid obtained in 85% yield (mp 66-69 C). Spectroscopic data compared to those of the pure product. -Acetil-isoleucine (11d) white solid obtained in 87% yield (mp 132-147 C). Spectroscopic data compared to those of the pure product. p-toluenesulfonamide isoleucine methyl ester (12a): white solid obtained in 98% yield (mp 84 86 C). Spectroscopic data compared to those reported in the literature. 24 -(9-fluorenylmethoxycarbonyl) isoleucine methyl ester (12b): white solid obtained in 93% yield (mp 14-143 C). Spectroscopic data compared to those of the pure product. -(tert-butoxycarbonyl)-isoleucine methyl ester (12c): white solid obtained in 97% yield (mp 68-72ºC). Spectroscopic data compared to those of the pure product. -Acetil-isoleucine methyl ester (12d): colorless oil obtained in 95% yield. Spectroscopic data compared to those of the pure product.

1, and 13 C spectra of compounds 1a S AME : nat36 EXP : 1 PRC : 1 Integral 7.7716 7.7442 7.321 7.318 7.2916 7.2894 7.2824 1.8563 7.2784 7.2757 7.2717 7.21 6.769 7.2577 7.2412 7.281 7.1992 7.1925 7.183 7.1763 /4 4.7623 4.7429.9443 4.1241 4.134 2.3 2.4366 2.978 /2 -. 8.5 8. 7.5 7. 6.5 6. 5.5 5. 4.5 4. 3.5 3. 2.5 2. 1.5 1..5. AME : nat36c13 EXP : 1 PRC : 1 143.8426 137.2596 136.6436 13.698 129.125 128.234 127.5231 77.7829 77.3 76.9371 47.5987 21.8459 17 1 15 14 13 12 11 9 8 7 5 4 3 2 1

1b AME : nat57 EXP : 1 PRC : 1 Integral 13. 4.419 7.7973 7.7731 7.752 7.9 7.5847 7.4643 7.4394 7.4152 7.411 7.3715 7.3466 7.3432 7.3183 7.355 7.2813 7.2558 4.5667 4.5412 4.4772 4.4544 4.3985 4.3797 4.3339 4.384 4.2835 4.2532 4.2317 4.212 9.5 9. 8.5 8. 7.5 7. 6.5 6. 5.5 5. 4.5 4. 3.5 3. 2.5 2. 1.5 1..5. -.5-1. AME : nat57c13 EXP : 1 PRC : 1 156.4286 143.9338 142.4259 141.3318 128.7267 128.267 127.6878 127.5591 127.3936 127.534 125.767 125.37 66.7125 47.3221 46.296 1 15 14 13 12 11 9 8 7 5 4 3 2 1

1c AME : nat44 EXP : 1 PRC : 1 /2 Integral 5. 2.68 9.221 7.352 7.3465 7.3282 7.3227 7.353 7.2852 7.2632 7.2564 4.3195 4.312 1.4 -. 7.5 7. 6.5 6. 5.5 5. 4.5 4. 3.5 3. 2.5 2. 1.5 1..5. AME : nat44c13 EXP : 1 PRC : 1 156.2271 139.264 128.9298 127.7989 127.6518 77.7829 77.3 76.9371 45.427 28.7415 1 15 14 13 12 11 9 8 7 5 4 3 2 1-1

2b 153.7355 153.6711 144.817 141.74 138.44 129.3895 128.127 127.4587 127.4127 125.275 125.315 12.3792 77.7829 77.3 76.9371 67.1453 47.4791 AME : nat58c13 EXP : 1 PRC : 1 1 14 12 8 4 2

2c AME : nat29 EXP : 1 PRC : 1 /2 Integral 4.15.9478 9.5843 7.3686 7.3414 7.394 7.2851 7.259 7.2566 7.57 7.526 7.478 7.341 7.284 7.254 7.87 7.47 7.1 6.485 1.5191 -. 8.5 8. 7.5 7. 6.5 6. 5.5 5. 4.5 4. 3.5 3. 2.5 2. 1.5 1..5. AME : nat29c13 EXP : 1 PRC : 1 138.6847 129.3159 123.3765 118.8898 8.8354 77.7829 77.3 76.9371 28.6956 1 15 14 13 12 11 9 8 7 5 4 3 2 1-1

3b AME : nat28 EXP : 2 PRC : 1 Integral 7.7954 7.774 7.6334 7.612 7.442 7.4158 2.361 7.3913 7.3492 2.968 7.3259 7.33 6.889 7.2685 2.78 7.2654 7.1169 7.9 /2 4.542 4.52 4.2987 4.2767 4.2541 1.9994 1.37 2.352 3.511 1.7373 -. 8.5 8. 7.5 7. 6.5 6. 5.5 5. 4.5 4. 3.5 3. 2.5 2. 1.5 1..5. -.5-1. -1.5 AME : nat28c13 EXP : 1 PRC : 1 143.851 141.3594 129.5542 127.7613 127.1178 124.9847 12.291 77.44 77.374 76.6145 66.74 47.175 2.73 -. 15 14 13 12 11 9 8 7 5 4 3 2 1-1 -2

3c AME : : EXP : WISPC1D PRC : AT3 /4 Integral 1.95 1.88 3.5 9.2274 7.259 7.2477 7.222 7.987 7.712 6.488 2.294 1.611 1.517 1.4857 7.5 7. 6.5 6. 5.5 5. 4.5 4. 3.5 3. 2.5 2. 1.5 1..5. AME : nat3c13 EXP : 3 PRC : 1 153.2343 136.641 132.873 129.783 119.38 8.645 77.7858 77.3 76.9342 28.6934 21.437 15 14 13 12 11 9 8 7 5 4 3 2 1

4b 2 AME : nat55c13 EXP : 1 PRC : 1 153.275 143.747 141.7372 128.277 127.5415 125.54 125.774 12.4712 118.1451 77.7829 77.3 76.9371 67.5867 47.2953 17 1 15 14 13 12 11 9 8 7 5 4 3 2 1

5c 3 C AME : nat31 EXP : 1 PRC : 1 /4 Integral 2.117 1.9386 1.9372 2.9999 8.9969 7.2633 7.2221 7.1935 6.8748 6.8681 6.8458 4.2542 4.2359 3.7976 1.4582 -. 7. 6.5 6. 5.5 5. 4.5 4. 3.5 3. 2.5 2. 1.5 1..5. AME : nat31c13 EXP : 1 PRC : 1 159.252 156.1811 131.357 129.1964 114.3295 79.7413 77.7829 77.3 76.9371 55.6435 28.7599 17 1 15 14 13 12 11 9 8 7 5 4 3 2 1

6b

6c AME : nat45 EXP : 1 PRC : 1 /2 Integral 2..147 22.795 2.9553 7.2664 4.5211 3.982 3.763 1.7846 1.5152 1.4311 1.3817 1.2614.8863.8429 7.5 7. 6.5 6. 5.5 5. 4.5 4. 3.5 3. 2.5 2. 1.5 1..5. -.5 AME : nat45c13 EXP : 2 PRC : 1 156.319 77.7829 77.3 76.9371 4.9697 32.166 3.3965 29.569 29.5322 28.7415 27.732 27.1234 22.9492 14.383 1 15 14 13 12 11 9 8 7 5 4 3 2 1

C 3 S 8a AME : nat38 EXP : 1 PRC : 1 Integral 7.262 7.2612 7.251 7.2488 7.2339 2.1 7.2272 7.2224 7.799 5.1369 7.667 7.553 2.1647 7.486 1.256 5.982 5.68 1.775 4.2356 4.2157 4.249 4.1958 4.185 4.1653 3.745 3.4851 2.83 3.376 3.18 3.254 2.48 1.6328 8. 7.5 7. 6.5 6. 5.5 5. 4.5 4. 3.5 3. 2.5 2. 1.5 1..5. AME : nat38c13 EXP : 1 PRC : 1 171.5629 143.9254 136.9378 135.2553 129.9227 129.725 128.922 127.569 127.547 77.7829 77.3 76.9371 56.937 52.683 39.79 21.8459 18 1 14 12 8 4 2-2