Synthesis of thiophenophanes with ethyne and ethene spacers

Synthesis of thiophenophanes with ethyne and ethene spacers has been achieved by O -alkylation, Glaser-Eglinton and McMurry coupling techniques.


Introduction
Remarkable advances have been made in the area of cyclophanes having acetylenic linkages in recent decades.The ability of the alkyne unit(s) in generating the cyclophane cavity with shape persistence 1 has often reflected its ability to complex metal ions or organic molecules, 2 or to selfaggregate in some cases. 3,4The advantage of using acetylene linkage is the linearity of the ethynic bond, which turns the molecule more rigid and creates non-collapsible cavity. 5,6Further the molecules will possess molecular co-planarity due to the presence of sp hybridised carbon atoms.The cavity size of a macrocycle can be altered by increasing or decreasing the number of acetylene linkages in the molecule. 7Owing to the well-ordered structures and infinite conjugation of these macrocycles, they possess interesting optical, electronic, and magnetic properties and can be ideal materials in organic light-emitting diodes, (OLEDs), 8 organic fieldeffect transistors (OFETs), 9 nonlinear optics (NLOs) 10 and organic solar cells. 11Cyclophanes with excess non-bonding electrons or dense π-electron clouds could be regarded as electron rich cyclophanes. 12Electron rich cyclophanes like stilbenophanes 13 are important class of supramolecular structures in the cyclophane family since they can undergo functional group transformations and interesting photoisomerization.
2,5-Bis(4-(bromomethyl)phenyl)thiophene 5 on O-alkylation with but-2-yne-1,4-diol 8 in the presence of NaH in refluxing THF afforded the thiophenophane 2 in 57 % yield.The 1 H NMR spectrum of thiophenophane 2 displayed three singlets at δ 4.21, 4.50 and 7.40 for eight, eight and four hydrogens corresponding to the O-methylene hydrogens attached to the phenyl unit and the acetylene unit and the thiophene ring system respectively.The hydrogens in the benzene ring appeared as two doublets at δ 7.69 -7.72 (J = 8.0 Hz) and 7.81 -7.83 (J = 8.0 Hz) integrating for eight hydrogens each.In the 13 C NMR spectrum, thiophenophane 2 showed the O-methylene carbon signals at  58.6 and 65.7 along with seven signals of carbon in the aromatic region.The structure of the thiophenophane 2 was also confirmed from mass and elemental analysis.
In a similar manner, thiophenophanes 3 and 3a were synthesized from the corresponding diol 9 and 9a obtained by the Sonogashira coupling procedure.The structure of the thiophenophanes 3 and 3a was confirmed from 1 H NMR, 13 C NMR, FAB-MS and analytical data.
Treatment of one equivalent of the dialdehyde 10 with twenty equivalents of TiCl4 and forty equivalents of Zn in THF under McMurry coupling conditions afforded the thiophenophane 4 in 68 % yield (Scheme 1).In the 1 H NMR spectrum, thiophenophane 4 displayed a singlet at δ 7.28 for the four thiophene hydrogens, two doublets at δ 7.18 -7.21 (J = 7.5 Hz) and 7.67 -7.70 (J = 7.2 Hz) for the cis olefinic hydrogens integrating for two protons each and two more doublets at δ 7.38 -7.40 (J = 7.2 Hz) and 7.51 -7.54 (J = 7.5 Hz) for the ortho substituted hydrogens integrating for eight hydrogens each.The 13 C NMR of thiophenophane 4 displayed signals for seven carbons, which further confirmed the structure of thiophenophane 4. The structure 4 was also confirmed from mass and elemental analysis.
Thiophenophanes with ethyne and ethene spacers have been synthesized in moderately good yield.

Conclusions
In conclusion, we have successfully synthesized electron rich thiophenophanes with ethyne and ethene spacers.The complexation of thiophenophanes with electron deficient guest molecules is under way.© ARKAT-USA, Inc.

Experimental Section
General.All melting points are uncorrected.The 1 H and 13 C NMR spectra were recorded on Bruker 300 and 400 MHz spectrometers.The chemical shifts are reported in ppm () with TMS as internal standard and coupling constant (J) are expressed in Hz.EI-MS spectra were recorded on JEOL DX-303 mass spectrometer.The FAB-MS spectra were recorded on JEOL SX 102/DA-6000 mass spectrometer using p-nitrobenzyl alcohol (NBA) as matrix.Elemental analyses were performed on a Perkin-Elmer 240B elemental analyzer.Column chromatography was performed on silica gel (ACME, 100 -200 mesh).Routine monitoring of the reaction was made using thin layer chromatography developed on glass plates coated with silica gel-G (ACME) of 25mm thickness and visualized with iodine.

General procedure for O-alkylation using sodium hydride
To a solution of sodium hydride (4 mmol) in dry THF (50 mL), alcohol (4 mmol) was added dropwise and stirred for 0.5 h at room temperature.Then the dibromide 5 (1 mmol) was added slowly to the reaction mixture and was refluxed for 12 h.The reaction mixture was allowed to attain room temperature and then methanol (5 mL) was added to the reaction mixture to quench the excess sodium hydride and the reaction mixture was evaporated to dryness.The residue obtained was extracted with CH2Cl2 (2×100 mL), washed with water (2×100 mL), brine (100 mL) and dried over anhydrous Na2SO4.Evaporation of the organic layer gave a residue, which was purified by column chromatography using suitable eluent as mentioned for each compound to give the corresponding O-alkylated product.