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. 2002 Jul 31;7(7):511–516. doi: 10.3390/70700511

Synthetic Studies on Optically Active Schiff-base Ligands Derived from Condensation of 2-Hydroxyacetophenone and Chiral Diamines

Wen Tao Gao 1,2, Zhuo Zheng 1,*
PMCID: PMC6146446

Abstract

Three optically active Schiff-base ligands have been prepared by condensation of 2-hydroxyacetophenone with (1R,2R)-(-)-1,2-diaminocyclohexane, (1S,2S)-(-)- 1,2-diphenylethylenediamine or  R-(+)-2,2’-diamino-1,1’-binaphthalene, respectively. The products have been characterized by their IR, 1H- and 13C-NMR spectra.

Keywords: Schiff-base, ligands, 2-hydroxyacetophenone, chiral diamines

Introduction

Schiff-base ligands derived from salicylaldehyde and chiral amines have been widely applied in enantioselective cyclopropanation of styrenes [1], asymmetric aziridination of olefins [2], enantioselective epoxidation [2,3], enantioselective ring opening of epoxides [3,4], borohydride reduction of aromatic ketones [4], asymmetric oxidation of methyl phenyl sulfide [5], enantioselective oxidation of silyl enol [6] and trimethylsilylcyanation of benzaldehydes [4,7]. In particular the Merck company has successfully developed a process for the industrial manufacture of antibacterial drug Cilastatin using chiral copper (II) Schiff-base complexes derived from salicylaldehyde and chiral amine [8]. However, so far there have been few reports about the synthesis and application of Schiff-base ligands derived from 2-hydroxyacetophenone and chiral amines. In order to investigate the electronic, steric and geometric effect of a methyl group on an imine carbon on asymmetric catalytic reactions, 2-hydroxyacetophenone (1) was chosen to synthesize Schiff-base ligands 2, 3, 4 by the condensation with chiral diamines such as 1,2-diaminocyclohexane, 1,2-diphenylethylenediamine and 2,2’-diamino-1,1’-binaphthalene (Scheme 1).

Scheme 1.

Scheme 1

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Results and discussion

The Schiff-base ligand 2 was easily prepared in 70.5% yield by refluxing two equivalents of 2-hydroxyacetophenone (1) with (1R,2R)-(-)-1,2-diaminocyclohexane in anhydrous ethanol. Complete condensation of all primary amino groups is confirmed by the lack of N-H stretching bands in the 3150-3450cm-1 IR region and the presence of strong C=N stretching bonds. The 1H-, 13C-NMR, and infrared data for 2 are completely consistent with the formulation indicated in Scheme 1. After we failed to synthesize the Schiff-base ligands of 2-hydroxyacetophenone and chiral 1,2-diphenylethylenediamine and 2,2’-diamino-1,1’-binaphthalene using the method described above, we tried replacing the solvent anhydrous ethanol with butanol to increase the reaction temperature and adding 4-methylbenzenesulfonic acid as catalyst, but the expected products were still not obtained. Compounds 3 and 4 were finally obtained in 69.6% and 25.1% yield, respectively, by using activated alkaline aluminum oxide as dehydrating agent and anhydrous toluene as solvent.

Experimental

General

Melting points were determined on a YAZAWA instrument and are uncorrected. Infrared spectra were recorded as KBr pellets on a PERKIN-ELMER 683. NMR spectra were recorded on a BRUKER BRX 400 spectrometer and chemical shifts are expressed in ppm using TMS as internal standard. Elemental analysis was performed on a PE-2400 elemental analyzer.

Synthesis of N,N’-(1R,2R)-(-)-1,2-cyclohexylenebis(2-hydroxyacetophenonylideneimine) (2).

To a solution of (1R,2R)-(-)-1,2-diaminocyclohexane(140mg, 1.23mmol) in absolute ethanol (1mL) was added 2-hydroxyacetophenone 1 (334mg, 2.46mmol). The resulting mixture was then refluxed for 36 h. After cooling to room temperature, water (5mL) was added and the mixture stirred for 30 min, the yellow precipitate formed was filtered, washed with water and dried. Recrystallization from absolute ethanol afforded yellow needles (303mg, 70.5%); mp: 144-145°C; [α]D24=-788.12° (c =1.1×10-3 in CH2Cl2); IR (neat) cm-1: 3060 (OH), 1618 (C=N); 1H-NMR(CDCl3): 16.40 (s, 2H, OH), 7.37-6.67 (m, 8H, Ar-H), 3.86 (dd, 2H, CH), 3.05 (s, 6H, CH3), 1.92-1.46 (m, 8H, CH2CH2); 13C-NMR (CDCl3) (see Figure 1 for numbering system): 170.72 (C7), 163.54 (C2), 132.24 (C4), 128.27 (C6), 119.11(C1), 118.36 (C5), 117.00 (C3), 62.84 (C9), 32.23 (C10), 24.06 (C11), 14.25 (C8); Anal.: Calcd. for C22H26N2O2: C, 75.40; H, 7.48; N, 7.99; Found: C, 75.25; H, 7.26; N, 7.85.

Fig.1.

Fig.1

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NMR numbering of ligand 2 

Synthesis of (1S,2S)-(-)- 1,2-diphenylethylenebis(2-hydroxyacetophenonylideneimine) (3).

To a solution of (1S,2S)-(-)-1,2-diphenylethylenediamine (212mg, 1.00mmol) in absolute toluene (3mL) was added 2-hydroxyacetophenone 1 (272mg, 2.00mmol) and activated alkaline aluminum oxide (100mg, 0.98mmol). The resulting mixture was refluxed with stirring for 24 h. After the aluminum oxide was filtered off, the solvent was evaporated in vacuo to gave a yellow solid. Chromatography on silica (elution with 10% EtOAc/petroleum ether) afforded bright yellow crystals (312mg, 69.6%), mp: 173-175°C; [α]D19=-138.03°(c=1 in CHCl3); IR (neat) cm-1: 3062 (OH), 1618(C=N); 1H-NMR(CDCl3): 16.06 (s, 2H, OH), 7.39-6.68 (m, 18H, Ar-H); 5.26 (s, 2H, CH), 2.26 (s, 6H, CH3); 13C-NMR (CDCl3) (see Figure 2): 172.35 (C7), 162.79 (C2), 139.16 (C10), 132.38 (C4), 128.33 (C6), 127.97 (C11,12), 127.48 (C13), 119.58 (C1), 118.18 (C5), 117.41 (C3), 71.01 (C9), 15.16 (C8); Anal.: Calcd. for C30H28N2O2: C, 80.33; H, 6.29; N, 6.25; Found: C, 80.12; H, 6.26; N, 6.10.

Fig.2.

Fig.2

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NMR numbering of ligand 3 

Synthesis of R-(+)-1,1’-binaphthalene-2,2’-diaminobis(2-hydroxyacetophenonylideneimine) (4).

To a solution of R-(+)-2,2’-diamino-1,1’-binaphthalene (284mg, 1.00mmol) in absolute toluene (3mL) was added 2-hydroxyacetophenone 1 (272mg, 2.00mmol) and activated alkaline aluminum oxide (125mg, 1.23mmol). The resulting mixture was refluxed with stirring for 72 h. After the aluminum oxide was filtered off, the solvent was evaporated in vacuo to gave a yellow solid. Chromatography on silica (10% EtOAc/petroleum ether) afforded bright yellow needles (118mg, 25.1%), mp: 262-264°; [α]D18=15.87°(c=0.232 in CHCl3); IR (neat) cm-1: 3065 (OH), 1618 (C=N); 1H-NMR (CDCl3): 15.58 (s, 2H, OH), 7.89-6.67 (m, 20H, Ar-H), 2.17 (s, 6H, CH3); 13C-NMR (CDCl3)(Figure 3): 170.65 (C7), 161.40 (C2), 143.27 (C9), 133.07 (C11), 132.63 (C16), 131.29 (C4), 128.86 (C6), 128.50 (C10), 128.23 (C17), 126.70 (C15), 125.60 (C12), 125.50 (C13), 125.21 (C14), 121.50 (C5), 119.66 (C1), 117.99 (C18), 117.69 (C3), 18.05 (C8); Anal.: Calcd. for C36H28N2O2: C, 83.05; H, 5.42; N, 5.38; Found: C, 83.01; H, 5.11; N, 5.13.

Fig.3.

Fig.3

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NMR numbering of ligand 4 

Acknowledgements

We are grateful for the financial support provided by the National Natural Science Foundation of China (No.29933050).

Footnotes

Sample Availability: Samples of the ligands 2 and 3 are available from the MDPI.

References and Notes

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