Synlett 2009(9): 1437-1440  
DOI: 10.1055/s-0029-1217173
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Improving the Efficiency of Forming ‘Unfavorable’ Products: Eight-Residue Macrocycles from Folded Aromatic Oligoamide Precursors

Shuliang Zoua, Youzhou Hea, Yongan Yanga, Yi Zhaoa, Lihua Yuana, Wen Feng*a, Kazuhiro Yamatob, Bing Gong*b
a College of Chemistry, Key Laboratory for Radiation Physics and Technology of Ministry of Education, Institute of Nuclear Science and Technology, Sichuan University, Chengdu, 610064, P. R. of China
Fax: +86(28)85418755; e-Mail: [email protected];
b Department of Chemistry, University at Buffalo, The State University of New York at Buffalo, Buffalo, NY 14260, USA
Fax: +1(716)64568002243; e-Mail: [email protected];
Further Information

Publication History

Received 11 February 2009
Publication Date:
13 May 2009 (online)

Abstract

Oligoamide macrocycles consisting of eight meta-linked benzene residues were synthesized based on the cyclization of aromatic oligoamide precursors having folded backbones rigidified by three-center hydrogen bonds. An alternative route based on the condensation of pentadimeric diamine and trimeric diacid provided the cyclic octamer in 75% yield using EDCI/HOBt as the coupling reagent.

    References and Notes

  • 1 Gloe K. In Macrocyclic Chemistry: Current Trends and Future Perspectives   Springer; Dordrecht: 2005. 
  • 2 McCallien DWJ. Sanders JKM. J. Am. Chem. Soc.  1995,  117:  6611 
  • 3a Knops P. Sendhoff N. Mekelburger HB. Voegtle F. Top. Curr. Chem.  1992,  161:  1 
  • 3b Rossa L. Voegtle F. Top. Curr. Chem.  1983,  113:  1 
  • 4a Bazzicalupi C. Bencini A. Bianchi A. Danesi A. Faggi E. Giorgi C. Santarelli S. Valtancoli B. Coord. Chem. Rev.  2008,  252:  1052 
  • 4b Müller TJJ. Bunz UHF. Functional Organic Materials - Synthesis, Strategies and Applications   Wiley-VCH; Weinheim: 2007.  p.225 
  • 4c Zhang W. Moore JS. Angew. Chem. Int. Ed  2006,  45:  4416 
  • 4d Zhao D. Moore JS. Chem. Commun.  2003,  807 
  • 4e MacLachlan Mark J. Pure Appl. Chem.  2006,  78:  873 
  • 4f Grave C. Schlüter AD. Eur. J. Org. Chem.  2002,  3075 
  • 5a Höger S. Meckenstock A.-D. Chem. Eur. J.  1999,  5:  1686 
  • 5b Martell AE. Perutka J. Kong D. Coord. Chem. Rev.  2001,  216:  55 
  • 6a Shetty AS. Zhang J. Moore JS. J. Am. Chem. Soc.  1996,  118:  1019 
  • 6b Seo SH. Jones TV. Seyler H. Peters JO. Kim TH. Chang JY. Tew GN. J. Am. Chem. Soc.  2006,  128:  9264 
  • 6c Pasini D. Ricci M. Curr. Org. Synth.  2007,  4:  59 
  • 7 Helsel AJ. Brown AL. Yamato K. Feng W. Yuan LH. Clements AJ. Harding SV. Szabo G. Shao ZF. Gong B. J. Am. Chem. Soc.  2008,  130:  15784 
  • 8 Carver FJ. Hunter CA. Shannon RJ. J. Chem. Soc., Chem.Commun.  1994,  1277 
  • 9 Owston PG. Peters R. Ramsammy E. Tasker PA. Trotter J. J. Chem. Soc., Chem. Commun.  1980,  1218 
  • 10 Jiang H. Leger J.-M. Guionneau P. Huc I. Org. Lett.  2004,  6:  2985 
  • 11a Yuan LH. Feng W. Yamato K. Sanford AR. Xu DG. Guo H. Gong B. J. Am. Chem. Soc.  2004,  126:  11120 
  • 11b Sanford AR. Yuan LH. Feng W. Yamato K. Flowers RA. Gong B. Chem. Commun.  2005,  4720 
  • 12a Gong B. Acc. Chem. Res.  2008,  41:  1376 
  • 12b Yuan LH. Zeng HQ. Yamato K. Sanford AR. Feng W. Atreya HS. Sukumaran DK. Szyperski T. Gong B.
    J. Am. Chem. Soc.  2004,  126:  16528 
  • 12c Gong B. Zeng HQ. Zhu J. Yuan LH. Han YH. Cheng SZ. Furukawa M. Parra RD. Kovalevsky AY. Mills JL. Skrzypczak-Jankun E. Martinovic S. Smith RD. Zheng C. Szyperski T. Zeng XC. Proc. Natl. Acad. Sci. U.S.A.  2002,  99:  11583 
  • 12d Zhu J. Parra RD. Zeng H. Skrzypczak-Jankun E. Zeng XC. Gong B. J. Am. Chem. Soc.  2000,  122:  4219 
  • 13 Yuan LH. Sanford AR. Feng W. Zhang AM. Zhu J. Zeng HQ. Yamato K. Li MF. Ferguson JS. Gong B. J. Org. Chem.  2005,  70:  10660 
14

Selected Spectroscopic Data of Compounds 4-8
Compound 4c: ¹H NMR (400 MHz, 95% CDCl3-5% CD3OD): δ = 10.00 (s, 4 H), 9.90 (s, 4 H), 9.40 (s, 2 H), 9.23 (s, 2 H), 9.00 (s, 2 H), 8.70 (s, 2 H), 6.80 (s, 2 H), 6.69 (s, 2 H), 6.50 (s, 4 H), 4.47 (s, 16 H), 3.99-3.43 (m), 3.28 (s, 24 H). MS (MALDI-TOF): m/z calcd for C120H168N8NaO48
[M + Na]: 2512.08; found: 2512.1. ESI-HRMS: m/z [M + Na] calcd for C120H168N8NaO48: 2513.0882; found: 2513.0955.
Compound 6: ¹H NMR (400 MHz, CDCl3): δ = 9.75 (s, 2 H), 9.37 (s, 1 H), 8.88 (s, 2 H), 6.63 (s, 2 H), 6.55 (s, 1 H), 4.40 (t, J = 4.8 Hz, 4 H), 4.25 (t, J = 4.8 Hz, 4 H), 4.00 (t, J = 4.8 Hz, 4 H), 3.94 (t, J = 4.8 Hz, 4 H), 3.92 (s, 6 H), 3.84 (s, 6 H), 3.80 (t, J = 4.8 Hz, 4 H), 3.68 (m, 12 H), 3.58 (m, 12 H), 3.47 (q, 4 H), 3.37 (s, 6 H), 3.32 (s, 6 H). ESI-HRMS: m/z [M + H] calcd for C54H81N2O24: 1141.5179; found: 1141.5125.
Compound 7: ¹H NMR (400 MHz, CDCl3): δ = 9.57 (s, 2 H), 9.21 (s, 1 H), 8.96 (s, 2 H), 6.65 (s, 2 H), 6.41 (s, 1 H), 4.48 (t, J = 4.8 Hz, 4 H), 4.33 (t, J = 4.8 Hz, 4 H), 4.01 (t, J = 4.8 Hz, 4 H), 3.87 (s, 6 H), 3.84 (t, J = 4.8 Hz, 4 H), 3.71 (m, 8 H), 3.63 (m, 8 H), 3.57 (m, 12 H), 3.47 (m, 4 H), 3.37 (s, 6 H), 3.32 (s, 6 H).¹³C NMR (100 MHz, CDCl3): δ = 164.8, 161.2, 160.9, 160.7, 145.6, 138.1, 120.1, 116.1, 111.4, 98.2, 94.4, 71.9, 71.8, 70.6, 70.5, 70.5, 70.4, 70.3, 69.4, 69.2, 69.0, 68.5, 58.9, 58.8, 55.8. ESI-HRMS: m/z [M - H] calcd for C52H75N2O24: 1111.4710; found: 1111.4769.
Compound 8a: ¹H NMR (400 MHz, CDCl3): δ = 9.88 (s, 2 H), 9.65 (s, 2 H), 9.20 (s, 3 H), 8.98 (s, 2 H), 6.63 (s, 2 H), 6.56 (s, 1 H), 6.47 (s, 2 H), 4.49 (t, J = 4.8 Hz, 4 H), 4.36 (t, J = 4.8 Hz, 4 H), 4.07 (s, 6 H), 3.96 (t, J = 4.8 Hz, 4 H), 3.92 (d, 12 H), 3.76 (t, J = 4.8 Hz, 4 H), 3.70 (t, J = 4.8 Hz, 4 H), 3.64 (t, J = 4.8 Hz, 4 H), 3.56 (m, 12 H), 3.46 (m, 12 H), 3.31 (s, 12 H). ¹³C NMR (100 MHz, CDCl3): δ = 161.6, 160.1, 160.0, 153.8, 151.0, 146.3, 137.0, 121.4, 120.6, 117.4, 115.3, 114.6, 97.7, 95.6, 95.2, 71.8, 70.7, 70.6, 70.6, 70.5, 70.4, 70.3, 69.4, 69.1, 69.0, 58.9, 56.7, 56.5, 56.1. ESI-HRMS: m/z [M + H] calcd for C68H93N6O30: 1473.5936; found: 1473.5927.
Compound 8b: prepared from hydrogenation of its dinitro compound 8a in 90% yield. ¹H NMR (400 MHz, DMSO-d 6): δ = 10.07 (s, 2 H), 10.02 (s, 2 H), 9.32 (s, 1 H), 8.91 (s, 2 H), 7.90 (s, 2 H), 7.10 (s, 2 H), 6.96 (s, 1 H), 6.75 (s, 2 H), 4.63 (s, 8 H), 4.03 (s, 6 H), 4.01-3.98 (m, 8 H), 3.91 (s, 6 H), 3.84 (s, 6 H), 3.65 (m, 8 H), 3.60-3.40 (m, 8 H), 3.36 (m, 8 H), 3.23 (s, 6 H), 3.21 (s, 6 H), 3.16-3.10 (m, 8 H).(15) Procedure For MacrocyclizationRoute A A mixture of 7 (23.7 mg, 0.021 mmol), EDCI (10.2 mg, 0.053 mmol), and HOBt (7.3 mg, 0.054 mmol) in CH2Cl2 (10 mL) was stirred at r.t. for 50 min and then 8b (30.0 mg, 0.021 mmol) was added. The mixture was stirred at 28 ˚C overnight. After washing with H2O, the residue was subjected to chromatography (CHCl3-MeOH, 5:1) to afford the product 4c as an off-white solid (37.5 mg, 75%).
Route B
The diacid chloride (0.020 mmol), prepared from diacid 7 and (COCl)2 in CH2Cl2, was added to the diamine 1 (0.020 mmol) in the presence of Et3N in 0.5 h. The mxiture was stirred 6 h. After washing with 10% HCl, the residue was recrystallized several times from acetone to provide 4c in 40% yield.