Synthesis and charge-transfer complexation studies on bis(aminomethyl) m -terphenyl based bis-oxycyclophanes with intra-annular amide functionality

Bis(aminomethyl) m -terphenyl based bis-oxy cyclophanes with amide group as intra-annular functionality were synthesized and characterized from spectral and analytical data. All the cyclophanes form 1:1 charge-transfer (CT) complex with TCNQ.


Introduction
Synthesis of architecturally novel supramolecules in the context of designing simple models for studying supramolecular interactions stimulates the synthetic chemist to modify the molecular structures.6][7] Manganese-oxo complexes of porphyrin ligands 8,9 are reactive intermediates in O-atom transfer process.Cyclophanes containing both ether and amide functionality at the intra-annular ring system show selectivity in the complexation of metal ions. 10The biphenyl 11 based cyclic amides have been reported for anion complexation. 12Supramolecular amides were used as molecular receptors 13 and in molecular recognition 14,15 of biologically interacting substrates including anti-HIV active macrocyclic amides. 168][19][20] The most important aspect of supramolecular chemistry is the host-guest complexation.2][23] Hence it is of interest to synthesize bis-oxy cyclophane diamides 1-5 and study their CT complexation properties with 7,7,8,8tetracyanoquinodimethane (TCNQ), tetracyanoethylene (TCNE) and paraquat (PQT).

Results and Discussion
Seven different bis-oxy cyclophane amides 1-5 shown in Figure 1 were synthesized from a novel bis(aminomethyl) m-terphenyl 22. Reaction of 1.0 equiv. of bis(bromomethyl) m-terphenyl 21 24 with 2.2 equiv. of hexamine 25 in chloroform at reflux resulted in the formation of hexammonium salt.Hydrolysis of hexammonium salt with hydrochloric acid in EtOH-H2O mixture at reflux afforded diamine 22 in about 90% yield (Scheme 1).The structure of diamine 22 was confirmed from the spectral data.The 1 H NMR spectrum of diamine 22 displayed the N-methylene protons as a singlet at δ 3.93.The rest of the aromatic protons appeared in the region δ 7.26-7.79.
In order to test the synthetic utility of diamine 22 for the synthesis of bis-oxy cyclophane diamide, 1.0 equiv of diamine 22 was coupled with 1.1 equiv of diacid chloride 16, 16a, 16b, 17, 18, 19 and 20 in the presence of triethylamine in dry DCM at room temperature under high dilution conditions.The reaction afforded the bis-oxy cyclophane diamides 1, 1a, 1b, 2, 3, 4 and 5 in 35, 40, 52, 42, 43, 30 and 40% yields respectively, after purification by column chromatography (Scheme 1).The 1 H NMR spectrum of cyclophane amide 1a displayed a doublet for the N-methylene protons at δ 4.51, a singlet for O-methylene protons at δ 5.13 and NH protons as a triplet at δ 9.03.The rest of the aromatic protons appeared between δ 7.22 and 7.73.In the 13 C NMR spectrum of cyclophane amide 1a, the N-methylene carbon appeared at δ 42.2, O-methylene carbons at δ 69.6 and carbonyl carbons at δ 166.7.The FT-IR spectrum showed the carbonyl stretching frequency at 1639 cm -1 for the cyclophane amide 1a.Similarly the structure of the cyclophane amides 1, 1b, 2, 3, 4 and 5 has been confirmed from the spectral and analytical data.

Conclusions
In summary we have synthesized various cyclophane amides which show strong CT interactions selectively with TCNQ rather than TCNE and PQT.The biological activity and detailed charge transfer complexation studies of other similar cyclophane amides are under investigation.

Experimental Section
General.Melting points were determined by using a Toshniwal melting point apparatus by open capillary tube method and are uncorrected.The UV visible spectra were recorded on Shimadzu 2550 spectrophotometer.The IR spectra were performed on a PerkinElmer series 2000 FT-IR spectrophotometer. 1 H NMR and 13 C NMR spectra were recorded on a Bruker Advance 400 NMR spectrophotometer with TMS as internal standard.Mass spectra were determined by ESI-MS using PerkinElmer Sciex, API 3000 spectrophotometer.Elemental analyses were performed on a Perkin-Elmer 240B elemental analyser.

General procedure for the synthesis of bis-oxy cyclophane amides (1-5)
A solution of diamine 22 (1.4 mmol) in dry dichloromethane (200 mL) and a solution of the corresponding diacid chloride 16, 16a, 16b, 17, 18, 19 and 20 (1.54 mmol) in dichloromethane (200 mL) were simultaneously added dropwise to a well stirred solution of triethylamine (3.1 mmol) in dry dichloromethane (400 mL) for 8 h.After the addition was complete the reaction mixture was stirred for another 24 h.The solvent was removed at reduced pressure and the residue obtained was then dissolved in chloroform (300 mL), washed with water (2 x 200 mL) to remove triethylammonium chloride and then dried over anhydrous sodium sulphate.Removal of the chloroform under reduced pressure gave the corresponding cyclophane amide as a crude material, which was purified by column chromatography (SiO2 CT complexation studies of cyclophane amides 1, 1a, 1b, 2, 3, 4 and 5 with TCNQ.A solution of TCNQ (4.9 x 10 -6 M) in CH3CN at various dilutions (1 mL, 2 mL, 3 mL, 4 mL, 5 mL and 6 mL) were prepared and added to the solution of the cyclophane amide 1, 1a, 1b, 2, 3, 4 and