Synthesis of Novel Molecular Clips via Click Chemistry Based on Diethoxy carbonyl Glycoluril

Abstract

A novel class of molecular clips based on diethoxycarbonyl glycoluril was synthesized via click chemistry. Seven different arylacetylenes were used in this research, and all reaction products gave satisfying ^¹H NMR, ^¹³C NMR, HRMS, and IR spectra. The structure and conformation of 7a were further confirmed by single-crystal X-ray diffraction. A primary study on the metal-ion binding ability of 7f showed that its fluorescence was obviously quenched by Fe^³+, Ag⁺, and Cu^²+ among metal ions examined.

clip receptor - diethoxycarbonyl glycoluril - molecular recognition - 1,2,3-triazole - fluorescence

References and Notes

1a Lehn JM. Supramolecular Chemistry   VCH; Weinheim: 1995. 

1b Steed JW. Atwood JL. Supramolecular Chemistry   Wiley; New York: 2000. 

2 Hof F. Craig SL. Nuckolls C. Rebek J. Angew. Chem. Int. Ed.  2002,  41:  1488 

3a Rowan AE. Elemans JAAW. Nolte RJM. Acc. Chem. Res.  1999,  32:  995 

3b Wang ZG. Zhou BH. Chen YF. Yin GD. Li YT. Wu AX. Isaacs L. J. Org. Chem.  2006,  71:  4502 

3c Chen YF. She NF. Meng XG. Yin GD. Wu AX. Isaacs L. Org. Lett.  2007,  9:  1899 

3d Ghosh S. Wu AX. Fettinger JC. Zavalij PY. Isaacs L. J. Org. Chem.  2008,  73:  5915 

3e Yin GD. Wang ZG. Chen YF. Wu AX. Pan YJ. Synlett  2006,  49 

3f She NF. Meng XG. Gao M. Wu AX. Isaacs L. Chem. Commun.  2008,  3133 

4a Lagona J. Mukhopadhyay P. Chakrabarti S. Isaacs L. Angew. Chem. Int. Ed.  2005,  44:  4844 

4b Kim K. Selvapalam N. Ko YH. Park KM. Kim D. Kim J. Chem. Soc. Rev.  2007,  36:  267 

5 Reek JNH. Priem AH. Engelkamp H. Rowan AE. Elemans JAAW. Nolte RJM. J. Am. Chem. Soc.  1997,  119:  9956 

6 Hu SL. She NF. Yin GD. Guo HZ. Wu AX. Yang CL. Tetrahedron Lett.  2007,  48:  1591 

7a Kang J. Kim J. Tetrahedron Lett.  2005,  46:  1759 

7b She NF. Gao M. Cao LP. Yin GD. Wu AX. Synlett  2007,  2533 

8 Tornoe CM. Christensen C. Meldal MJ. J. Org. Chem.  2002,  67:  3057 

9 Rostovtsev VV. Green LG. Fokin VV. Sharpless KB. Angew. Chem. Int. Ed.  2002,  41:  2596 

10a Moses JE. Moorhouse AD. Chem. Soc. Rev.  2007,  36:  1249 

10b Wang Q. Chan TR. Hilgraf R. Fokin VV. Sharpless KB. Finn MG. J. Am. Chem. Soc.  2003,  125:  3192 

10c Tron GC. Pirali T. Billington RA. Canonico PL. Sorba G. Genazzani AA. Med. Res. Rev.  2008,  28:  278 

10d Binder WH. Sachsenhofer R. Macromol. Rapid Commun.  2007,  28:  15 

10e Miljanić O. Dichtel WR. Aprahamian I. Rohde RD. Agnew HD. Heath JR. Stoddart JF. QSAR Comb. Sci.  2007,  26:  1165 

11 Whiting M. Muldoon J. Lin YC. Silverman SM. Lindstrom W. Olson AJ. Kolb HC. Finn MG. Sharpless KB. Elder JH. Fokin VV. Angew. Chem. Int. Ed.  2006,  45:  1435 

12 Maisonneuve S. Fang Q. Xie J. Tetrahedron  2008,  64:  8716 

13 Chang KC. Su IH. Senthilvelan A. Chung W.-S. Org. Lett.  2007,  9:  3363 

14 Ornelas C. Aranzaes JR. Cloutet E. Alves S. Astruc D. Angew. Chem. Int. Ed.  2007,  46:  872 

15 Li Y. Flood AH. Angew. Chem. Int. Ed.  2008,  47:  2649 

16 Juwarker H. Lenhardt JM. Pham DM. Craig SL. Angew. Chem. Int. Ed.  2008,  47:  3740 

17 Pandey PS. Kumar A. Org. Lett.  2008,  10:  165 

18 Burnett CA. Logona J. Wu A. Shaw JA. Coady D. Fettinger JC. Day AI. Isaacs L. Tetrahedron  2003,  59:  1961 

19 Li YT. Yin GD. Guo HZ. Zhou BH. Wu AX. Synthesis  2006,  2897 

20

Compound 5: IR (KBr): 2984, 1721, 1598, 1415, 1358, 1176, 907, 817, 663, 554 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 7.78 (d, J = 8.4 Hz, 4 H), 7.35 (d, J = 8.4 Hz, 4 H), 4.73 (d, J = 14.4 Hz, 4 H), 4.30-4.25 (m, 8 H), 4.04 (t, J = 5.2 Hz, 4 H), 2.90 (t, J = 5.2 Hz, 4 H), 2.48 (s, 6 H), 1.30 (t, J = 7.2 Hz, 6 H). ^¹³C NMR (150 MHz, CDCl₃): δ = 164.8, 158.3, 144.8, 132.5, 129.7, 127.7, 75.8, 67.2, 63.3, 59.7, 49.7, 21.4, 13.6. ESI-MS: m/z = 765.0 [M + H]⁺.

21

Compound 6: IR (KBr): 2989, 2100, 1767, 1709, 1407, 1276, 899, 725 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 4.88 (d, J = 14.0 Hz, 4 H), 4.36 (d, J = 14.0 Hz, 4 H), 4.30 (q, J = 7.2 Hz, 4 H), 3.36 (t, J = 5.6 Hz, 4 H), 2.90 (t, J = 5.6 Hz, 6 H), 1.32 (t, J = 7.2 Hz, 6 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 165.0, 158.4, 76.0, 63.4, 59.9, 50.4, 48.6, 13.8. ESI-MS: m/z = 506.2 [M]⁺.

22 Ciana LD. Haim A. J. Heterocycl. Chem.  1984,  21:  607 

23 Takahashi S. Kuroyama Y. Sonogashira K. Hagihara N. Synthesis  1980,  627 

24 Crisp GT. Jiang YL. Synth. Commun.  1998,  28:  2571 

25 Polin J. Schottenberger H. Org. Synth.  1996,  73:  262 

26

General Procedure for the Synthesis of Compound 7
The azide 6 (0.20 mmol) and arylacetylene (0.40 mmol) were suspended in 1:1 mixture of H₂O and t-BuOH (10 mL). Ascorbate acid (0.020 mmol, 20 µL of freshly prepared 1.0 M solution in H₂O, 10 mol%) was added, followed by copper(II) sulfate pentahydrate (0.010 mmol, 100 µL of 0.10 M solution in H₂O, 5.0 mol%). The heterogeneous mixture was stirred vigorously for 24 h under Ar protection. After total consumption of the starting material (determination by TLC), the solvent was removed in vacuo, and the residue was isolated by column chromatography on SiO₂ to get the pure product 7.
Compound 7a: IR (KBr): 3244, 2985, 1705, 1444, 1282, 1047, 767, 697 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 7.86 (d, J = 7.6 Hz, 4 H), 7.60 (s, 2 H), 7.45 (t, J = 7.6 Hz, 4 H), 7.35 (t, J = 7.6 Hz, 2 H), 4.82 (d, J = 13.6 Hz, 4 H), 4.36 (t, J = 6.0 Hz, 4 H), 4.28 (q, J = 7.2 Hz, 4 H), 4.19 (d, J = 13.6 Hz, 4 H), 2.93 (t, J = 6.0 Hz, 4 H), 1.30 (t, J = 7.2 Hz, 6 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 164.9, 158.6, 147.3, 130.6, 128.9, 128.1, 125.6, 120.3, 76.0, 63.5, 60.0, 50.1, 47.0, 13.8. ESI-HRMS: m/z [M + Na]⁺ calcd for C₃₄H₃₈N₁₂NaO₆: 733.2929; found: 733.2898.
Compound 7b: IR (KBr): 3423, 3137, 2988, 1766, 1730, 1707, 1612, 1411, 1286, 1234, 1045, 907, 718 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 8.68 (d, J = 5.6 Hz, 4 H), 7.88 (s, 2 H), 7.77 (d, J = 5.6 Hz, 4 H), 4.81 (d, J = 13.6 Hz, 4 H), 4.45 (t, J = 5.2 Hz, 4 H), 4.31-4.22 (m, 8 H), 3.03 (t, J = 5.2 Hz, 4 H), 1.31 (t, J = 7.2 Hz, 6 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 164.7, 158.5, 150.3, 144.9, 137.9, 122.0, 119.8, 75.9, 63.6, 59.9, 50.1, 47.6, 13.8. ESI-HRMS: m/z [M+Na]⁺ calcd for C₃₂H₃₆N₁₄NaO₆: 735.2834; found: 735.2814.
Compound 7c: IR (KBr): 3447, 3134, 2939, 2840, 1760, 1718, 1459, 1299, 1248, 1231, 1027, 825, 717 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 7.78 (d, J = 8.4 Hz, 4 H), 7.50 (s, 2 H), 6.97 (d, J = 8.4 Hz, 4 H), 4.82 (d, J = 13.2 Hz, 4 H), 4.33-4.25 (m, 8 H), 4.18 (d, J = 13.2 Hz, 4 H), 3.80 (s, 6 H), 2.88 (t, J = 6.0 Hz, 4 H), 1.30 (t, J = 7.2 Hz, 6 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 164.9, 159.5, 158.5, 147.2, 126.9, 123.3, 119.5, 114.2, 76.0, 63.5, 60.0, 55.2, 50.1, 46.8, 13.8. ESI-HRMS: m/z [M + Na]⁺ calcd for C₃₆H₄₂N₁₂NaO₈: 793.3141; found: 793.3100.
Compound 7d: IR (KBr): 3448, 3367, 2982, 2849, 1720, 1621, 1502, 1416, 1291, 1233, 1029, 906, 837, 715 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 7.61 (d, J = 8.0 Hz, 4 H), 7.48 (s, 2 H), 6.68 (d, J = 8.0 Hz, 4 H), 4.79 (d, J = 13.6 Hz, 4 H), 4.28-4.24 (m, 8 H), 4.12 (d, J = 13.6 Hz, 4 H), 3.90 (br s, 4 H), 2.87 (t, J = 6.0 Hz, 4 H), 1.27 (t, J = 7.2 Hz, 6 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 164.9, 158.5, 147.6, 146.7, 126.7, 120.6, 119.1, 115.1, 76.0, 63.5, 59.9, 50.0, 46.7, 13.8. ESI-HRMS: m/z [M + Na]⁺ calcd for C₃₄H₄₀N₁₄NaO₆: 763.3147; found: 763.3120.
Compound 7e: IR (KBr): 3362, 3150, 2984, 2844, 1726, 1678, 1617, 1414, 1235, 1030, 982, 910, 858, 776, 713 cm^-¹. ^¹H NMR (400 MHz, DMSO-d ₆): δ = 8.50 (s, 2 H), 8.02 (s, 2 H), 7.98 (d, J = 8.0 Hz, 4 H), 7.91 (d, J = 8.0 Hz, 4 H), 7.42 (s, 2 H), 4.78 (d, J = 13.6 Hz, 4 H), 4.50 (t, J = 6.0 Hz, 4 H), 4.29-4.21 (m, 8 H), 3.01 (t, J = 6.0 Hz, 4 H), 1.21 (t, J = 7.2 Hz, 6 H). ^¹³C NMR (100 MHz, DMSO-d ₆): δ = 167.5, 164.9, 158.3, 145.4, 133.4, 133.3, 128.3, 124.8, 122.5, 75.8, 63.5, 59.3, 49.6, 46.9, 13.7. ESI-HRMS: m/z [M + Na]⁺ calcd for C₃₆H₄₀N₁₄NaO₈: 819.3046; found: 819.2999.
Compound 7f: IR (KBr): 3423, 3137, 2988, 1766, 1730, 1707, 1612, 1411, 1286, 1234, 1045, 907, 718 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 8.43 (d, J = 8.0 Hz, 2 H), 7.82 (d, J = 8.0 Hz, 4 H), 7.70 (d, J = 8.0 Hz, 2 H), 7.55-7.47 (m, 8 H), 4.82 (d, J = 13.6 Hz, 4 H), 4.34 (t, J = 6.0 Hz, 4 H), 4.27 (q, J = 7.2 Hz, 4 H), 4.20 (d, J = 13.6 Hz, 4 H), 2.95 (t, J = 6.0 Hz, 4 H), 1.28 (t, J = 7.2 Hz, 6 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 164.8, 158.5, 146.5, 133.7, 130.7, 128.8, 128.3, 127.8, 127.1, 126.7, 126.0, 125.4, 125.3, 122.9, 75.9, 63.5, 60.0, 50.2, 47.1, 13.8. ESI-HRMS: m/z [M + Na]⁺ calcd for C₄₂H₄₂N₁₂NaO₆: 833.3242; found: 833.3220.
Compound 7g: IR (KBr): 3448, 3122, 2982, 1719, 1414, 1232, 1035, 906, 821, 712, 505, 488 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 7.47 (s, 2 H), 4.81-4.78 (m, 8 H), 4.34-4.30 (m, 8 H), 4.27 (q, J = 7.2 Hz, 4 H), 4.20 (d, J = 13.2 Hz, 4 H), 4.10 (s, 10 H), 2.94 (t, J = 5.6 Hz, 4 H), 1.29 (t, J = 7.2 Hz, 6 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 164.9, 158.5, 146.4, 119.5, 76.0, 75.5, 69.6, 68.6, 66.5, 63.5, 60.0, 50.3, 47.1, 13.8. ESI-HRMS: m/z [M + Na]⁺ calcd for C₄₂H₄₆Fe₂N₁₂NaO₆: 949.2273; found:949.2215.

27

Crystal Data for Compound 7a
C₃₄H₃₈N₁₂O₆, MW = 710.78, triclinic, a = 10.0153 (5), b = 12.0495 (6), c = 16.3995 (8) Å, α = 102.658 (0)˚, β = 103.272 (0)˚, γ = 108.398 (0)˚, V = 1734.28 (15) Å^³, T = 294 (2) K, space group Z = 4, m(MoKα) = 0.094 mm^-¹, 15230 reflections measured, 6724 unique (Rint = 0.0981) which were used in all calculations. The final wR ₂ (F ₂) was 0.1531. CCDC 699457 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

28 Callan JF. de Silva AP. Magri DC. Tetrahedron  2005,  61:  8551 

29 Valeur B. Leray I. Coord. Chem. Rev.  2000,  205:  3 

30 Job P. Ann. Chim.  1928,  9:  113