C. Duangkamol et al.
Table 3 Comparison of the reported methods for the synthesis of N,N0-dicyclohexylcarbodiimide (3l) under different conditions
Entry
Conditions
X
Time/h
Yield/% [References]
1
2
3
4
5
6
7
8
(EtO)3SiH, iron catalyst, THF, 60 °C
S
24
7
95 [17]
N-Methyl-2-pyridinecarbamoyl chloride, DMAP, Et3N, THF
p-(HO(Ph)IOS(=O)2)C6H4Me, Et3N, AcOEt, 0 °C
Phosphorous pentoxide, pyridine, reflux
S
84 [19]
S
8
67 [15]
O
O
O
S
2.25
2
76 [10]
o-Iodoxybenzoic acid, Et3N, CH2Cl2, 0 °C-RT
4-BrC6H4SO2Cl, K2CO3, BnN(CH3)3Cl, CHCl3, reflux
I2, Et3N, AcOEt, 0 °C
45 [47]
NA
NA
1
50 [6]
0 [14]
Ph3P, I2, Et3N, CH2Cl2, sonication, RT
S,O
78, 81 [this work]
Acknowledgments Financial support from the Thailand Research
Fund through the Royal Golden Jubilee Ph.D. Program (Grant No.
PHD/0086/2557) to C.D. is gratefully acknowledged.
low-cost and easy to handle reagents with simple experi-
mental setup.
Experimental
References
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All compounds were used as received from the suppliers.
Ultrasonic bath equipped with thermostat with operating at
37 kHz [Elmasonic S 30(H), Germany] was used for all
ultrasonic-assisted synthesis. The reaction was monitored
by thin-layer chromatography carried out on silica gel
plates (60F254, MERCK, Germany) and visualized under
UV light (245 nm). Column chromatography was per-
formed over silica gel 60 (70–230 mesh, MERCK,
Germany). Melting points were determined using SANYO,
Gallenkamp apparatus at a heating rate of 10 °C/min. NMR
measurements were conducted on a Bruker AVANCETM
1
(400 MHz for H NMR) using chloroform-d (CDCl3) as
the solvent and tetramethylsilane (TMS) as an internal
standard.
General procedure for the synthesis of carbodiimide
To a solution of 0.0844 g iodine (0.33 mmol) and
0.0872 g triphenylphosphine (0.33 mmol) in 2 cm3 CH2-
Cl2 was added
a
solution of thiourea or urea
(0.275 mmol) and 0.0701 g triethylamine (0.69 mmol) in
2 cm3 CH2Cl2 under sonication. The reaction mixture was
further sonicated until completion of the reaction as
indicated by TLC. The crude mixture was concentrated
under reduced pressure then purified by column chro-
matography using hexane to give the carbodiimide (see
supporting information for characterization data of all
products).
27. Yu RT, Rovis T (2008) J Am Chem Soc 130:3262
123