Synlett 2016; 27(02): 249-253
DOI: 10.1055/s-0035-1560702
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of New Arylmethylene Derivatives of Resorcinarene via the Catalyzed Mannich Reaction

Barbara Gawdzik
a  Institute of Chemistry, The Jan Kochanowski University, Świętokrzyska 15G, 25020 Kielce, Poland   Email: mariusz.urbaniak@ujk.edu.pl
,
Alicja Wzorek
a  Institute of Chemistry, The Jan Kochanowski University, Świętokrzyska 15G, 25020 Kielce, Poland   Email: mariusz.urbaniak@ujk.edu.pl
,
Łukasz Lechowicz
b  Institute of Biology, The Jan Kochanowski University, Świętokrzyska 15G, 25020 Kielce, Poland
,
Mariusz Urbaniak*
a  Institute of Chemistry, The Jan Kochanowski University, Świętokrzyska 15G, 25020 Kielce, Poland   Email: mariusz.urbaniak@ujk.edu.pl
› Author Affiliations
Further Information

Publication History

Received: 25 June 2015

Accepted after revision: 03 September 2015

Publication Date:
29 October 2015 (eFirst)

Abstract

The C-arylation of Mannich base is used to obtain a series of new arylmethylene resorcinarene derivatives. Initially, aminomethyl derivative as the intermediate is formed in the Mannich reaction of resorcinarene with iminodiacetic acid. Next, activated aromatic rings act as a nucleophile in the reaction with this Mannich base and the arylmethylene derivatives of resorcinarene are prepared. The mixture of isomeric products is obtained for monosubstituted phenyl rings. Reaction with a suitably substituted phenyl ring gives one main product in good yields.

Supporting Information

 
  • References and Notes

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  • 14 Typical Procedure for the Preparation of Resorcinarene Derivatives 2–8: A mixture of resorcinarene (0.5 g, 0.7 mmol, 1 equiv) and the appropriate aromatic compound (10–60 equiv) in MeCN (10 mL) was stirred and heated until completely dissolved. Then an aqueous solution of formaldehyde (37%, 0.53 mL, 7 mmol) and iminodiacetic acid (0.05 g, 10%) were added, and the reaction mixture was refluxed for 18 h at 85 °C. The reaction mixture was evaporated to dryness, CHCl3 (100 mL) was added and the mixture was washed with H2O (3 × 100 mL). The CHCl3 solution was evaporated and the residues were separated by chromatography. Tetra(methylene 2-phenol) Resorcinarene (2a): The synthesis of derivatives 2a required a 60-fold molar excess of the phenol (4 g), HPLC purification to yield a white solid (0.16 g, 20% yield); mp 200–203 °C. 1H NMR [600 MHz, (CD3)2SO]: δ = 9.94 (s, 4 H, ArOH), 8.69 (s, 8 H, ArOH), 7.40 (s, 4 H, ArH), 6.96 (t, J = 7.4 Hz, 4 H, ArH), 6.77–6.81 (m, 8 H, ArH), 6.65 (t, J = 7.2 Hz, 4 H, ArH), 4.40 (t, J = 7.5 Hz, 4 H, ArCHRAr), 3.76 (s, 8 H, ArCH 2Ar), 2.16 [t, J = 6.6 Hz, 8 H, CHCH 2CH(Me)2], 1.35–1.43 [m, 4 H, CH2CH(Me)2], 0.93 [d, J = 6.2 Hz, 24 H, CH(Me)2]. 13C NMR [150 MHz, (CD3)2SO]: δ = 23.27, 24.46, 26.52, 32.52, 42.71, 114.61, 114.86, 119.82, 122.98, 125.46, 126.92, 127.38, 129.66, 149.79, 154.57. HRMS (ESI): m/z [M+ + Na+] calcd for C72H80O12Na: 1159.55472; found: 1159.55554. Tri(methylene 4-aniline) Mono(methylene 2-aniline) Resorcinarene (3b): The synthesis of derivatives 3b required a 24-fold molar excess of the N,N-dimethylaniline (2.2 mL), the crude product was purified by column chromatography to yield a white solid (0.35 g, 40% yield); Rf 0.44 (EtOAc–hexane, 1:1); mp 182–185 °C. 1H NMR [600 MHz, (CD3)2SO]: δ = 11.09 (s, 2 H, ArOH), 8.69 (s, 2 H, ArOH), 8.51 (s, 4 H, ArOH), 7.54 (d, J = 7.3 Hz, 1 H, ArH), 7.31–7.35 (m, 3 H, ArH), 7.27 (s, 2 H, ArH), 7.21 (t J = 7.3 Hz, 1 H, ArH), 7.11 (t, J = 7.3 Hz, 1 H, ArH), 6.96 (d J = 8.4 Hz, 4 H, ArH), 6.89 (d J = 8.1 Hz, 2 H, ArH), 6.59 (d J = 7.7 Hz, 6 H, ArH), 4.39 (t, J = 7.0 Hz, 2 H, ArCHRAr), 4.36 (t, J = 7.0 Hz, 2 H, ArCHRAr), 3.86 (s, 2 H, ArCH 2Ar), 3.84 (s, 2 H, ArCH 2Ar), 3.72 (s, 4 H, ArCH 2Ar), 2.81 (s, 12 H, N(Me)2], 2.78 (s, 6 H, N(Me)2], 2.73 [s, 6 H, N(Me)2], 2.17–2.26 [m, 4 H, CHCH 2CH(Me)2], 1.96–2.08 [m, 4 H, CHCH 2CH(Me)2], 1.31–1.42 [m, 4 H, CH2CH(Me)2], 0.92 (d J = 6.2 Hz, 24 H, CH(Me)2]. 13C NMR [150 MHz, (CD3)2SO]: δ = 23.09, 23.18, 23.45, 23.48, 26.45, 26.51, 28.66, 28.84, 32.44, 32.50, 41.05, 42.78, 45.94, 113.16, 113.18, 115.73, 115.82, 115.88, 121.94, 124.82, 124.87, 125.63, 125.66, 129.04, 129.25, 129.80, 149.07, 149.11, 149.35, 149.40, 149.52, 149.82, 150.13. HRMS (ESI): m/z [M+ + Na] calcd for C80H100O8N4Na: 1267.74385; found: 1267.74523. Tetramethylene 2-Ethoxy(4-methoxyphenyl) Resorcinarene (8): The synthesis of derivatives 8 required a 12-fold molar excess of the 2-(4-methoxyphenyl)ethanol (1.1 mL), the crude product was purified by column chromatography to yield a white solid (0.69 g, 72% yield); Rf 0.6 (EtOAc–hexane, 1:3); mp 170–172 °C. 1H NMR (500 MHz, CDCl3): δ = 8.54 (s, 8 H, ArOH), 7.11 (d, J = 8.2 Hz, 8 H, ArH), 7.10 (s, 4 H, ArH), 6.86 (d, J = 8.8 Hz, 8 H, ArH), 4.81 (s, 8 H, ArCH 2O), 4.36 (t, J = 8.2 Hz, 4 H, ArCHRAr), 3.79 (s, 12 H, OMe), 3.72 (t, J = 6.9 Hz, 8 H, OCH 2CH2Ar), 2.86 (t, J = 6.9 Hz, 8 H, OCH2CH 2Ar), 2.04 [t, J = 7.5 Hz, 8 H, CH 2CH(Me)2], 1.41–1.51 [m, 4 H, CH2CH(Me)2], 0.98 [d, J = 6.9 Hz, 24 H, CH2CH(Me)2] 13C NMR: δ = 22.82, 26.03, 30.52, 35.08, 42.71, 55.21, 68.24, 72.25, 109.11, 114.03, 122.73, 124.03, 129.74, 130.05, 149.67, 158.28. HRMS (ESI): m/z [M+ + Na] calcd for C84H104O16Na: 1391.72217; found: 1391.72274.
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