Chinese Chemical Letters  2016, Vol. 27 Issue (9): 1551-1553   PDF    
One-pot synthesis of [1+1] and 62-membered [2+2] Schiff base macrocycles
Fang-Fang Wanga, Ya-Xin Denga, Huang Chaoa, Qi-Long Zhangb, Bi-Xue Zhua     
a Key Laboratory of Macrocyclic and Supramolecular Chemistry, Guizhou University, Guiyang 550025, China ;
b Department of Chemistry, Guizhou Medical College, Guiyang 550004, China
Abstract: New [1+1] and 62-membered [2+2] Schiff base macrocycles containing a 2, 6-diamidopyridine subunit have been synthesized by condensation reaction of the precursors pyridine-2, 6-dicarboxamide and 1, 10-bis(20-formylphenyloxy)decane in the presence of phosphoric acid via a one-pot process. The cyclocondensed products were effectively isolated by gel column chromatography and characterized by 1H NMR, FTIR, mass spectrometry and X-ray analysis. The two macrocycles have a twisted structure, and not an open ‘circular’ conformation in the solid state.
Key words: Macrocycles     Schiff base     One-pot synthesis     Crystal structure    
1. Introduction

In the last few decades, much effort has been dedicated to the design of macrocyclic receptors possessing specific structural features because of their importance in the fields of supramolecular and coordination chemistry [1-5]. One representative group of macrocycles comprise Schiff base macrocyclic compounds, which are synthesized by the reaction of dicarbonyl compounds with diamines via a well-understood mechanism [6, 7]. Such a macrocyclic system can be functionalized by inserting appropriate groups into the aliphatic and/or aromatic chains of the formyl, keto, or amine precursors [8-10]. In our previous work, we showed that a new category of macrocyclic Schiff bases can be synthesized employing a metal template procedure [11, 12]. We also noted that a representative Schiff base macrocycle, containing a 2, 6-diamidopyridine subunit, could have an important role to play in the molecular recognition of organic molecules and inorganic anions [13-19]. Here, we report the synthesis and characterization of two Schiff base macrocycles containing a 2, 6-diamidopyridine subunit from the condensation of the diamine and dialdehyde precursors shown in Scheme 1.

Scheme. 1. Synthesis of the two Schiff-base macrocycles 1 and 2.

2. Experimental

Synthesis of the Schiff-base macrocycle 1 and 2: Precursor pyridine-2, 6-dicarboxamide was prepared from the reaction of commercial pyridine-2, 6-dicarbonyl dichloride with 2-nitrobenzenamine according to a literature procedure for similar structures [20]. Precursor 1, 10-bis(2'-formylphenyloxy)decane was also synthesized ina mannersimilartoan existingprocedure[21]. Schiffbase macrocycles 1 and 2 were synthesized by the Schiff base condensation of pyridine-2, 6-dicarboxamide with 1, 10-bis(2'-formylpheny-loxy)decane in the presence of phosphoric acid via a one-pot process. Namely, pyridine-2, 6-dicarboxamide (0.348 g, 1 mmol) and 1, 10-bis(2'-formylphenyloxy)decane (0.382 g, 1 mmol) were dissolved in methanol (50 mL) withstirring. Phosphoric acidinmethanol(10 mL) was added to the mixture (2 equiv. conc. H3PO4 in the solution). This gradually formed a milky solution that was stirred overnight at room temperature. The resultant viscous precipitates were collected by filtration, washed with methanol (3× 5 mL) and hot acetone (3 × 5 mL), and dried under vacuum. The crude product was purified by silica gel column chromatography (CH2Cl2/CH3COOC2H5, v/v=10:1) to afford isolated [1+1] and [2+2] cyclo-condensed products 1 and 2, in 43.6% and 10.3% yields, respectively. Furthermore, solid 1 was dissolved in a mixed solution of dichloromethane/ethyl acetate (5:1 v/v), while 2 was dissolved in a mixed solution of dichloromethane/ THF (1:1 v/v), at room temperature. After slow evaporation of the solutions, yellow block-shaped single crystals of 1 and 2 suitable for X-ray analysis were obtained.

[1+1]Macrocycle 1: Yellow solid (43.6%), mp >300 ℃. 1H NMR (CDCl3, 600 MHz): δ 11.15 (s, 2H), 8.84 (s, 2H), 8.55 (t, 2H, J=10.8 Hz), 8.42 (d, 2H, J=11.4 Hz), 8.13 (t, 1H, J=11.4 Hz), 7.97-8.11 (m, 2H), 7.26 (s, 2H), 6.95-7.04 (m, 6H), 6.57 (d, 2H, J=12.6 Hz), 6.24 (t, 2H, J=10.8 Hz), 3.94 (t, 4H, J=9.6 Hz), 1.38-1.73 (m, 16H); FABMS: m/z calcd. for C43H43N5O4Na 716.2, found: 716.2; IR (KBr) νmax 1686 (νC=O), 1616 (νC=N), 1587, 1524(νC=C); Anal. calcd. for C43H43N5O4: C 74.41, H 6.27, N 10.10; Found: C 74.44, H 6.25, N 10.09.

[2+2]Macrocycle 2: Yellow solid (10.3%), mp >300 ℃. 1H NMR(CDCl3, 600 MHz): δ 11.12 (s, 4H), 8.75 (s, 4H), 8.67 (t, 4H, J=11.4 Hz), 8.45 (d, 4H, J=11.4 Hz), 8.026-8.049 (m, 6H), 7.26 (s, 4H), 7.05 (s, 4H), 6.935-6.97 (m, 8H), 6.63 (d, 4H, J=12.6 Hz), 6.13 (t, 4H, J=11.4 Hz), 3.93 (t, 8H, J=10.8 Hz), 1.16-1.87 (m, 12H), 1.332 (m, 24H); FABMS: m/z calcd. for C86H86N10O8Na 1410.4, found: 1410.4; IR (KBr) νmax 1684 (νC=O), 1618 (νC=N), 1587, 1523(νC=C); Anal. calcd. for C86H86N10O8: C 74.40, H 6.26, N 10.13; Found: C 74.44, H 6.25, N 10.09.

3. Results and discussion 3.1. The choice of acid used to promote the reaction

We were keen to explore how the selectivity of this reaction was affected by the choice of acid used to promote it. Herein, pyridine-2, 6-dicarboxamide was treated with 10-bis (2'-formylphenyloxy) decane in methanol under acidic conditions. The choice of acid used to promote these reactions (HCl, CH3CO2H, CF3CO2H, H3PO4, or H2SO4) played a critical role in defining the product distribution. The experimental results indicated that hydrochloric, acetic, and trifluoroacetic acid led to the formation of oligomers with high molecular weights as the major products, while phosphoric acid and/or sulfuric acid led to the formation of [1+1] and [2+2] macrocycles, 1 and 2, respectively. In contrast, the use of phosphoric acids produced 1 and 2, nearly free of other by-products. According to the references [15-18], we speculated the phosphate possessing templating effect would result in the formation of macrocycles 1 and/or 2, based on the hydrogen-bonding between the tetrahedral anions with each of the two amide NH protons situated on ‘arms’ of the same pyridine ring.

3.2. Characterization of macrocyclic compounds 1 and 2

The two macrocycles were characterized by elemental analysis, 1H NMR, MS and FT-IR spectra. In the 1H NMR spectra of the [1+1] and [2+2] macrocycles, recorded in CDCl3 solution, CONH protons were observed at δ 11.15 and δ 11.12, Schiff base CH=N protons observed at δ 8.84 and δ 8.75, respectively, and each of these signals was observed as a singlet, suggesting the formation of macrocyclic compounds with an n:n stoichiometry [22]. As expected, the O-methylene protons appeared as triplets at around δ 3.94 and δ 3.93, while protons in the flexible methylene chain appearedasa multipletinthe region δ1.38-1.73and δ1.16-1.33in 1 and 2, respectively (Supporting information). The FAB mass spectrum of macrocycle 1 showed the parent ion peak at m/z 716.2 [M+Na]+, confirming the [1+1] nature of the Schiff base compound. The mass spectrum of macrocycle 2 showed a peak at m/z 1410.4 [M+Na]+, attributed to the [2+2] macrocycle (Supporting information). In the IR spectra of the two Schiff-base macrocycles, the C=O stretching frequencies are evident at 1686 and 1684 cm-1, and the corresponding C=N stretching frequencies at 1686 and 1684 cm-1, respectively. Crystallographic data for the structural analysis of 1 and 2 have been deposited at the Cambridge Crystallographic Data Centre (CCDC) as 1433716 and 1433715.

3.3. Crystal structures of the compounds 1 and 2

The macrocyclic structures of 1 and 2 were obtained by single crystal X-ray analysis. Their X-ray structures are shown in Fig. 1. Each of the two compounds had a macrocyclic structure. Crystallographic data are shown in Table S1 (Supporting information), and hydrogen bonding geometries are given in Table S2 (Supporting information).

Figure 1. ORTEP drawings of 1 and 2 with thermal ellipsoids at 20% probability. Some hydrogen atoms have been omitted for clarity. Symmetry code: a 2 -x, 1 -y, 1 -z.

According to X-ray analysis the [1+1] macrocycle 1 (Fig. 1a) had a twisted conformation in the solid state. This three-dimensional structure was stabilized by two pairs of intermolecular hydrogen bonds; each of the two amide NH protons situated on an 'arm' of the same pyridine ring formed two bridged N-H…N hydrogen bonds linking the pyridine nitrogen (N1) atom and Schiff base nitrogen atoms (N4 and N5). The bis(2-aminophenyl)pyridine-2, 6-dicarboxamide fragment was twisted, and the dihedral angles between the central pyridine ring and the two adjacent benzene rings were 153.34° and 153.14°. Intermolecular π-π stacking between the pairs of benzene rings may have assisted in stabilizing the ‘figure-eight’ conformation [23], with the centroid-centroid distance between the one pair of benzene rings being 3.787 Å (Fig. 1a).

Compound 2 (Fig. 1b) was a large 62-membered [2+2] macrocycle. Two bis(2-aminophenyl)pyridine-2, 6-dicarboxamide subunits were linked via double-stranded alkoxy chains forming a twisted macrocyclic structure. Each of the two bis(2-aminophe nyl)pyridine-2, 6-dicarboxamide fragments had a twisted confor mation, in which the two benzene rings linked to the central pyridine ring were twisted with respect to the pyridine plane at dihedral angles of 144.67° and 157.33°. The torsion angles of C5-C8-N2-C7 and C1-C43-N1-C41 were 164.65° and 172.26°, respec tively. The three-dimensional structure was stabilized by two pairs of intermolecular bridging hydrogen bonds between the amide protons(N1Hor N2H)and Schiffbase nitrogenatoms(N3 or N4), as well as the central pyridine nitrogen atom (N5) (Fig. 1b).

4. Conclusion

The new [1+1] and 62-membered [2+2] Schiff base macrocycles containing a 2, 6-diamidopyridine subunit have been obtained via a one-pot synthesis in the presence of phosphoric acid. The two macrocycles had a twisted structure, instead of an open 'circular' conformation in the solid state. The molecular recognition behaviours of both these macrocycles towards guest molecules (or anions) are now under investigation in our laboratory.


This work was supported by the National Natural Science Foundation of China (No. 21061003), and the 'Chun-Hui' Fund of Chinese Ministry of Education (No. Z2012054).

Appendix A. Supplementary data

Supplementary data associated with this article can be found, in the online version, at

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