H -imidazole

: Imidazolines are a valuable class of organic compounds, namely ligands of imidazoline receptors, chiral ligands for metal catalysis, synthetic intermediates. The title compound has been prepared through a modiﬁed procedure, employing N -benzylethylenediamine and thiophene-2-carbaldehyde under the action of N -bromosuccinimide (NBS) in dichloromethane (DCM) in a good 78% yield.


Results
The reaction of thiophene-2-carbaldehyde (1) with N-benzylethylenediamine (2) was carried out in DCM at 0 • C for 30 min and resulted in the in situ formation of aminal 3. Subsequent addition of NBS and overnight stirring at rt furnished the target molecule 4 in 78% yield (Scheme 1). The structure determination of the title compound 4 was achieved with 1 H and 13 C NMR spectroscopy, IR spectroscopy and mass spectrometry (for details, see Supplementary Materials). The brutto formula was devised with the help of high-resolution mass spectrometry.

Discussion.
Comparing the above procedure to Fujioka's original work, the following differences were noted: Firstly, the use of nitrogen atmosphere does not grant any benefits and the reaction can be performed in a closed vessel without nitrogen; secondly, and more importantly, the use of more concentrated solutions are crucial for the effective reaction. Thus, carrying out the reaction in 0.32 M DCM solution instead of 0.1 M gives the product 4 with 78% yield, comparing to 65% under greater dilution. It is worth noting that the procedure also works excellently for p-methoxybenzaldehyde and p-nitrobenzaldehyde, giving the corresponding imidazolines.

General
Starting reagents were purchased from commercial sources and were used without any additional purification. 1 H and 13 C NMR spectra were acquired on a Jeol JNM-ECA 600 spectrometer (JEOL Ltd., Tokyo, Japan, with operating frequencies of 600 and 150 MHz, respectively) at room temperature and referenced to the residual signals of the solvent. The solvent used for NMR was CDCl3. Chemical shifts are reported in parts per million (δ/ppm). Coupling constants (J) are reported in Hertz (Hz). The peak patterns are indicated as follows: s, singlet; t, triplet; m, multiplet. Infrared spectra were measured on an Infralum FT-801 FT/IR instrument. The wavelengths are reported in reciprocal centimeters (ν max/cm −1 ). Mass spectra were recorded with LCMS-8040 Triple quadrupole liquid chromatograph mass spectrometer from Shimadzu (Shimadzu corp., Japan, ESI) and Kratos MS-30 mass-spectrometer (Shimadzu division, Japan, EI, 70 eV). HRMS spectra were recorded on a Bruker MicrOTOF-Q II (Bruker corp., Bremen, Germany). Elemental analysis was performed with a Euro Vector EA-3000 elemental analyzer (EuroVector S.p.A., Milan, Italy). The reaction progress was monitored by TLC and the spots were visualized under UV light (254 or 365 nm). Column chromatography was performed using silica gel (60-75 mesh). Melting points were determined on an SMP-10 apparatus and were uncorrected. Solvents were distilled and dried according to standard procedures.

Discussion
Comparing the above procedure to Fujioka's original work, the following differences were noted: Firstly, the use of nitrogen atmosphere does not grant any benefits and the reaction can be performed in a closed vessel without nitrogen; secondly, and more importantly, the use of more concentrated solutions are crucial for the effective reaction. Thus, carrying out the reaction in 0.32 M DCM solution instead of 0.1 M gives the product 4 with 78% yield, comparing to 65% under greater dilution. It is worth noting that the procedure also works excellently for p-methoxybenzaldehyde and p-nitrobenzaldehyde, giving the corresponding imidazolines.

General
Starting reagents were purchased from commercial sources and were used without any additional purification. 1 H and 13 C NMR spectra were acquired on a Jeol JNM-ECA 600 spectrometer (JEOL Ltd., Tokyo, Japan, with operating frequencies of 600 and 150 MHz, respectively) at room temperature and referenced to the residual signals of the solvent. The solvent used for NMR was CDCl 3 . Chemical shifts are reported in parts per million (δ/ppm). Coupling constants (J) are reported in Hertz (Hz). The peak patterns are indicated as follows: s, singlet; t, triplet; m, multiplet. Infrared spectra were measured on an Infralum FT-801 FT/IR instrument. The wavelengths are reported in reciprocal centimeters (ν max/cm −1 ). Mass spectra were recorded with LCMS-8040 Triple quadrupole liquid chromatograph mass spectrometer from Shimadzu (Shimadzu corp., Japan, ESI) and Kratos MS-30 mass-spectrometer (Shimadzu division, Japan, EI, 70 eV). HRMS spectra were recorded on a Bruker MicrOTOF-Q II (Bruker corp., Bremen, Germany). Elemental analysis was performed with a Euro Vector EA-3000 elemental analyzer (EuroVector S.p.A., Milan, Italy). The reaction progress was monitored by TLC and the spots were visualized under UV light (254 or 365 nm). Column chromatography was performed using silica gel (60-75 mesh). Melting points were determined on an SMP-10 apparatus and were uncorrected. Solvents were distilled and dried according to standard procedures.

Conflicts of Interest:
The authors declare no conflict of interest.