Molecules 2018, 23, 1891
10 of 14
3
.5. Procedure for the Formation of Methyl (2R)-2-(furan-2- ylmethylene) amino)-3-((3-morpholino-4-
oxocyclopent-2-en-1-yl)thio]propanoate (1D)
Morpholine (2.2 mmol) was added to a stirred solution of furfural (1 mmol) in ChCl–urea eutectic
◦
mixture (1 mL). The resulting mixture was stirred at 60 C for 5 min. After this time, cysteine
methyl ester hydrochloride (1 mmol) was added to the reaction mixture and stirred for further 4 h to
obtain 4-(methyl-L-cysteinate)-2-morpholino cyclopent-2-enone 1C [14]. In order to obtain the imine
derivative of 1C, 1 mmol of furfural was added to the reaction mixture described above and maintained
under stirring for 5 min and monitored by GC/MS analysis. The reaction was quenched with water
and extracted with AcOEt (3
evaporation under reduced pressure to remove the solvent to give the corresponding product 1D in
×
2 mL). The organic phases were dried over Na SO , followed by
2 4
7
5% yield.
1
H-NMR (300 MHz, CDCl ): 2.47 (dd, 1H, J = 8.4 Hz, J = 4.5 Hz, COCHN=), 2.56 (m, 1H, SCH ), 2.85 (m,
3
2
1
H, SCH ), 3.13–3.16 (m, 4H, morpholine), 3.44 (dd, 1H, J = 8.1 Hz, J = 3.3 Hz, COCH ), 3.50 (dd, 1H,
2
2
J = 5.1 Hz, J = 3.0 Hz, COCH ), 3.03 (s, 3H, CH ), 3.63 (t, 1H, SCH), 3.71–3.82 (m, 4H, morpholine),
2
3
6
.23 (d, J = 3.0 Hz, 1H, COC=CH), 6.27 (dd, J = 3.0 Hz, J = 2.1 Hz, 1H, OCH=CH), 6.31 (d, J = 2.1 Hz,
13
1H, OC=CH) 6.38 (d, J = 3.0 Hz, 1H, OCH=C), 7.33 (s, 1H, CH=N); C-NMR (75 MHz, CDCl ) 29.7,
3
3
0.4, 44.2, 47.3, 53.1, 66.5, 78.6, 108.9, 110.0, 129.2, 141.8, 142.4, 151.6, 152.9, 174.9, 201.8. MS(EI): m/z
+
.
(%) = 378 (4) [M] , 319 (3), 277 (2), 245 (3), 212 (18), 180 (100), 166 (47), 146 (4), 138 (13), 120 (16),
+
+
111 (17), 93 (13), 44(8). HRMS (ESI) for ([C H N O S] + H) 378.1249, found 379.1328 [M + H] ,
18
22
2
5
+
4
01.1143 [M + Na] .
3
.6. Recycling of Deep Eutectic Solvent
The recycling of DES was examined in the reaction of furfural and morpholine in the ChCl–urea
mixture under optimized conditions. After the reaction was completed, AcOEt (3 mL) was added
to the reaction mixture, and stirred for 5 min. The stirring was stopped to allow phase separation,
and the upper organic layer was removed. This extractive procedure was repeated two more times
and the combined organic extracts were washed with water (3
×
5 mL), dried (Na SO ), filtered,
2 4
and evaporated under reduced pressure to afford the crude reaction product. The residual volatile
organic solvent present in the DES phase was removed under vacuum evaporation. Then, the next
reaction cycle was performed with the DES, adding fresh furfural and morpholine. This reaction
mixture was again subjected to the above-described procedure, and further reaction cycles were
repeated using the recycled DES phase.
4
. Conclusions
In conclusion, we have described an effective and rapid method for the synthesis of
bifunctionalized cyclopentenones in an eco-friendly and biodegradable DES based on the ChCl–urea
mixture. The advantages of this method are operational simplicity, green medium, DES recoverability,
short reaction time, high yields and no chromatographic purification procedures. The recyclability of
the DES (up to four reaction runs) and its synergistic effect on the reaction outcome have also been
demonstrated. Furthermore, the DES can be used as a low-cost, safe and efficient solvent with feasible
large-scale preparation.
To the best of our knowledge, this is the first report on the synthesis of trans-4,5-diaminocyclopent-
2
-enones derivatives and 2,4-diaminocyclopent-2-enones in DESs.
Moreover, this synthetic strategy can be utilized for the construction of many other novel
cyclopentenone derivative compounds of pharmaceutical importance.
Supplementary Materials: The HR-MS, GC/MS, 1H- and 13C-NMR spectra of new synthesized compounds are
available online.