Water excellent solvent for the synthesis of bifunctionalized cyclopentenones

Transcription

1 Electronic upplementary Material (EI) for Green Chemistry. This journal is The Royal ociety of Chemistry 207 Water excellent solvent for the synthesis of bifunctionalized cyclopentenones M. ardi,* a,b P. Costanzo, c A. De ino, a M. L. Di Gioia, d F. livito, c G. indona a and A. Procopio c a Dipartimento di Chimica, Università della Calabria, Cubo 2C, Arcavacata di Rende (C), Italy, Tel.: Fax: monica.nardi@unical.it b Dipartimento di Agraria, Università Telematica an Raffaele, Roma, Via di Val Cannuta, 247, 0066, Italia. c Dipartimento di cienze della alute, Università Magna Graecia, Viale Europa, 8800-Germaneto (CZ), Italia. d Dipartimento di Farmacia e cienze della alute e della utrizione, Edificio Polifunzionale, Università della Calabria, Arcavacata di Rende, Cosenza.

2 IDICE Pag. Experimental ection 3 General MW-assisted protocol for synthesis of trans- 4,5 diaminocyclopent-2- enones (a-0a). pectroscopic data (a-0a). 3 General protocol for the synthesis of 2,4 diaminocyclopent-2-enones (b-3b) and (c-j). pectroscopic data (b-3b) and (c-j). 4 H MR spectrum (b) C MR spectrum (b) 7 H MR spectrum (j) 8 3 C MR spectrum (j) 9 HRM (EI) spectrum (3a, 4a, 6a) 0 HRM (EI) spectrum (c, e, f, g, j) 2

3 Experimental section 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 60 F 254 pre-coated aluminum plates Proton nuclear magnetic resonance ( H MR) spectra were recorded on a Brüker spectrometer at 300 MHz. Chemical shifts are reported in δ units (ppm) with TM as reference (δ 0.00). All coupling constants (J) are reported in Hertz. Multiplicity is indicated by one or more of the following: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet). Carbon nuclear magnetic resonance ( 3 C MR) spectra were recorded on a Brüker at 75 MHz. Chemical shifts are reported in δ units (ppm) relative to CDCl 3 (δ 77.0). MW-assisted reactions were performed on a ynthos 3000 instrument from Anton Paar, equipped with a 4 24MG5 Rotor and an IR probe used for external temperature control. LC-M analysis were carried using an Agilent 6540 UHD Accurate Q-TF LC M (Agilent, anta Clara, CA) fitted with a electrospray ionisation source (Dual AJ EI) operating in positive ion mode. Chromatographic separation was achieved using a C8 RP analytical column (Poroshell 20, B-C8, mm, 2.7 μm) at 30 C with a elution gradient from 5% to 95% of B over 3 min, A being H 2 (0.% FA) and B CH 3 C (0.% FA). Flow rate was 0.4 ml/min. General MW-assisted protocol for synthesis of trans- 4,5 diaminocyclopent-2-enones (a- 0a). To a water solution (3 ml) of furfural ( mmol) in a 3 ml glass vial, the amine (2.2 mmol) was added. The mixture was reacted for 5 min in a ynthos 3000 microwave instrument, fixed on the temperature value of 60 C (IR Limit). The reaction was monitored by TLC and GC/M analysis. Diethyl ether was added after the completion of reaction and the products were isolated after evaporation of the solvent to yield compounds a-0a in % yields. trans-4,5-dimorpholinocyclopent-2-en--one (a): pectral data were in accordance with the literature. 9a trans-4,5-bis(phenylamino)cyclopent-2-en--one (2a): pectral data were in accordance with the literature. 9a 3

4 trans-4,5-bis(methyl(phenyl)amino)cyclopent-2-en--one (3a): pectral data were in accordance with the literature. 9a HRM (EI) for ([C 9 H 20 2 ] + H) , found [M+H] +. trans-4,5-di(pyrrolidin--yl)cyclopent-2-en--one (4a): pectral data were in accordance with the literature. 8f HRM (EI) for ([C 3 H 20 2 ] + H) , found [M+H] +, [M+a] +. trans-4,5-di(piperidin--yl)cyclopent-2-en--one (5a): pectral data were in accordance with the literature. 9a trans-4,5-bis(dibenzylamino)cyclopent-2-en--one (6a): pectral data were in accordance with the literature. 9a HRM (EI) for ([C 33 H 32 2 ] + H) , found , [M+H] +, , [M+a] +. trans-4,5-di(isoindolin-2-yl)cyclopent-2-en--one (7a): pectral data were in accordance with the literature. 9a trans-4,5-bis(3,4-dihydroquinolin-(2h)-yl)cyclopent-2-en--one (8a): pectral data were in accordance with the literature. 9a trans-4,5-bis(diisobutylamino)cyclopent-2-enone (9a): pectral data were in accordance with the literature. trans-4,5-bis(diallylamino)cyclopent-2-enone (0a): pectral data were in accordance with the literature. 9a General protocol for the synthesis of 2,4 diaminocyclopent-2-enones (b-3b) and (c-j). To a water solution (3 ml) of furfural ( mmol) in a 3 ml glass vial, the amine (2.2 mmol) was added. The mixture was reacted for 5 min in a ynthos 3000 microwave instrument, fixed on the temperature value of 60 C (IR Limit). In order to obtain the 2,4 bisubstituted cyclopentenones b-3b the reaction mixture, after MW irradiation, was kept at room temperature for further 4 hour. After completion, diethyl ether was added (3 2 ml) and the organic phase was dried over a 2 4 and filtered. The products were isolated after evaporation of the diethyl ether to afford compounds b-3b in 85-9 % yields. 4

5 Instead, for the synthesis of compounds c-j, after MW irradiation, the addition of various nucleophiles ( mmol) was necessary. Also in this case the mixture was maintained at room temperature for further 4 hours. The reaction was monitored by TLC and GC/M analysis. After completion, water was removed under reduced pressure and the resulting crude product was purified by flash chromatography (CH 2 Cl 2 /MeH 9.5:0.5). The products c-j were obtained in % yields. 2,4-dimorpholinocyclopent-2-enone (b): H MR (300 MHz, CDCl 3 ) 6.24 (d, J = 2.9 Hz, H, CC=CH), 3.78 (t, J = 4.7 Hz, 4H, morpholine), 3.73 (t, J = 4.7 Hz, 4H, morpholine), (m, H, CCH 2 CH), (m, 4H, morpholine), (m, 4H, morpholine), (m, H, CCH 2 ), (m, H, CCH 2 ); 3 C MR (75 MHz, CDCl 3 ) 38., 48., 50.0, 60.3, 66.6, 67., 29.5, 5.7, ,4-bis(phenylamino)cyclopent-2-enone (2b): pectral data were in accordance with the literature. 0a 2,4-bis(methyl(phenyl)amino)cyclopent-2-enone (3b): pectral data were in accordance with the literature. 0a 4-(ethylthio)-2-morpholinocyclopent-2-enone (c): pectral data were in accordance with the literature. 0a HRM (EI) for ([C H 7 2 ] + H) , found [M+H] +. 4-(cyclohexylthio)-2-morpholinocyclopent-2-enone (e): pectral data were in accordance with the literature. 0a HRM (EI) for ([C 5 H 23 2 ] + H) , found [M+H] +. 4-(phenylthio)-2-morpholinocyclopent-2-enone (f): pectral data were in accordance with the literature. 0a HRM (EI) for ([C 5 H 7 2 ] + H) , found [M+H] +. 4-(benzylthio)-2-morpholinocyclopent-2-enone (g): pectral data were in accordance with the literature. 0a HRM (EI) for ([C 6 H 9 2 ] + H) , found [M+H] (methyl-l-cysteinate)-2-morpholino cyclopent-2-enone (j): H MR (300 MHz, CDCl 3 ) 6.23 (d, J = 3.0 Hz, H, CC=CH), 4.02 (dt, J = 9.3 Hz, J = 5.5 Hz, H, CCHH 2 ), (m, 4H, morpholine), (m, H, CH), 3.03 (s, 3H, CH 3 ), 2.79 (t, 2H, J = 9.3 Hz, CCH 2 ), (m, 4H, morpholine), (m, H, CH 2 ), (m, H, CH 2 ); 3 C MR (75 MHz, CDCl 3 ) 37.9, 43.9, 44.2, 48.0, 49.0, 49.9, 66.9, 0.0, 52.9, 74.8, HRM (EI) for ([C 3 H ] + H) , found [M+H] +. 5

6 H-MR Compound b 3 C-MR Compound b 6

7 H-MR Compound j H 2 Me 7

8 3 C-MR Compound j H 2 Me 8

9 HRM (EI) Ph Compound 3a Ph Cpd : C9 H20 2 FAL 5, ,574 Abund 008 Formula C9 H20 2 Tgt 292,576 (ppm) -0,64 MFG Formula C9 H20 2 C9 H20 2 Cpd : C9 H ,644 5, ,574 9

10 M pectrum Peak List z Abund Formula 293, , ,47 C9H ,57 C9H , ,6 C9H202 Compound 4a Cpd : C3 H20 2 FAL, ,576 Abund Formula C3 H20 2 Tgt 220,576 (ppm) 0,4 MFG Formula C3 H20 2 C3 H20 2 Cpd : C3 H ,649, ,576 M pectrum Peak List z Abund Formula 22, , , , , , ,06 C3H ,73 C3H ,66 C3H ,89 C3H202 33,93 C3H ,8 C3H202 (M+a)+ (M+a)+ Compound 6a Cpd : C33 H32 2 FAL Abund Formula Tgt (ppm) MFG Formula 8, , C33 H ,255 8,29 C33 H32 2 Bn 2 Bn 2 C33 H32 2 Cpd : C33 H ,2583 8, , x ([C33H322]+H) ([C33H322]+a) Counts vs. -to-charge () 0

11 M pectrum Peak List 473, , , ,2627 z Abund Formula 20558,72 C33H ,94 C33H ,57 C33H ,4 C33H322 (M+a)+ (M+a)+ Compound c Cpd : C H72 FAL 3, ,0978 Abund Formula C H72 Tgt 227,098 (ppm) -,2 MFG Formula C H72 C H72 Cpd : C H72 228,048 4, ,0978 M pectrum Peak List z Abund Formula 228, ,48 230,09 23, 66983,06 C5 H ,63 C5 H ,65 C5 H ,93 C5 H232 Compound e Cpd : C5 H232 FAL 4,938 28,449 Abund 0020 Formula C5 H232 Tgt 28,449 (ppm) -,04 MFG Formula C5 H232 C5 H232 Cpd : C5 H ,523 4,938 28,449

12 M pectrum Peak List z Abund Formula 282, , , , ,6 C5 H ,74 C5 H ,94 C5 H232 49,4 C5 H232 Compound f Cpd : C5 H72 FAL Abund Formula Tgt (ppm) MFG Formula 6, , C5 H72 275,098,04 C5 H72 C5 H72 Cpd : C5 H72 276,05 6, ,0977 M pectrum Peak List 276,05 277,2 278,04 279,09 Compound g z Abund Formula 990,05 C5 H ,74 C5 H ,45 C5 H72 049,4 C5 H72 Cpd : C6H92 FAL Abund Formula Tgt (ppm) MFG Formula 6, , C6H92 289,36,35 C6H92 C6H92 Cpd :C6H92 290,22 6, ,3 2

13 M pectrum Peak List 290,22 29,28 292, ,83 z Abund Formula 9890,05 C6H ,25 C6H ,8 C6H92 988,98 C6H92 Compound j H 2 Cpd : C3 H FAL Me Abund Formula Tgt (ppm) MFG Formula 2, ,4 03 C3 H ,44 -,04 C3 H C3 H Cpd : C3 H ,24 2, ,4 M pectrum Peak List 30,24 302, ,94 304,82 z Abund Formula 030,6 C3H ,74 C3H ,96 C3H ,4 C3H2024 3