Synlett 2015; 26(14): 1977-1980
DOI: 10.1055/s-0034-1378790
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Novel C-Pivot Lariat 18-Crown-6 Ethers and Their Efficient Purification

Susovan Jana
Department of Chemistry, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431, USA   Email: slepore@fau.edu
,
Vallabh Suresh
Department of Chemistry, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431, USA   Email: slepore@fau.edu
,
Salvatore D. Lepore*
Department of Chemistry, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431, USA   Email: slepore@fau.edu
› Author Affiliations
Further Information

Publication History

Received: 20 April 2015

Accepted after revision: 12 June 2015

Publication Date:
29 July 2015 (online)


Abstract

The syntheses of various lariat ethers including several not previously reported and their efficient purification are presented. The synthesis route brings together reactions from a variety of previous works leading to a robust and generalized approach to these C-pivot lariats. The main steps are condensation of functionalized diols with pentaethylene glycol ditosylate in the presence of potassium as a templating cation. Purification of the final products was achieved without chromatography by extracting from an aqueous potassium hydroxide solution.

Supporting Information

 
  • References and Notes

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  • 19 General Procedure for the Synthesis of Benzyl-Protected 18-C-6 Lariat Ethers 1c–7c To a solution of benzylated diol 1b–7b (25 mmol) in THF (240 mL) was added KOt-Bu (100 mmol) at r.t. After the mixture was allowed to react 1 h under a nitrogen atmosphere, a solution of pentaethylene glycol ditosylate (27.5 mmol) in THF (48 mL) was added over a period of 1 h with stirring. The mixture was stirred for an additional 1 h at r.t., refluxed for 24 h, and cooled to r.t. The volatile solvents were removed by distillation under reduced pressure. The crude solids were dissolved in H2O, and the resulting solution was extracted with CH2Cl2 (5 × 20 mL). The combined organic layer was dried over anhydrous Na2SO4. After filtration and evaporation, the crude product (approx. 3.5 g) was directly used for the debenzylation in the next step.
  • 20 General Procedure for the Synthesis of 18-C-6 Lariat Ethers 1d–7d To a dry round-bottom flask was added 10% (w/w) of 5% Pd/C and anhydrous EtOH (200 mL) was added to the reaction flask. The solution was degassed by bubbling the H2 gas through it twice. Benzylated lariat ethers 1c7c (approx. 3.5 g) dissolved in anhydrous EtOH (20 mL) was added into the reaction flask. The solution was degassed twice. The reaction mixture was stirred for 48 h under 1.013 bar of hydrogen. TLC with alumina plates using 4% 2-PrOH–CH2Cl2 as the eluent indicated the formation of product (Rf = 0.15). The product mixture was filtered and concentrated. The crude reaction mixture was then stirred into KOH aq (1 M, 50 mL) for 5 min. After this time, the impurities were removed by extraction using EtOAc until TLC showed the absence of any impurity (usually three extractions). The H2O layer was then extracted with CH2Cl2 (3 × 20 mL, monitored by alumina TLC; 4% 2-PrOH–CH2Cl2 eluent). The organic layer was collected, the solvent was removed in vacuo, and the resulting material was passed through a small plug of neutral alumina (10% MeOH–EtOAc as eluent) to furnish noncomplexed lariat products. 2-Hydroxymethyl-18-C-6 (1d) 2a–g Obtained in 65% yield (1.74 g) as a colorless viscous oil. 1H NMR (400 MHz, CDCl3): δ = 2.93 (s, 1 H, OH), 3.46–3.82 (m, 25 H, 12 × CH2 and 1 × CH). 13C NMR (100 MHz, CDCl3): δ = 63.0 (CH2OH), 69.6 (CH2O), 70.6 (CH2O), 70.7 (CH2O), 70.75 (2 × CH2O), 70.8 (CH2O), 70.83 (CH2O), 71.0 (CH2O), 71.03 (CH2O), 71.2 (CH2O), 71.8 (CH2O), 79.4 (CH). ESI-HRMS: m/z [M + H] calcd for C13H26O7: 295.1757; found: 295.1751. 2-[Hydroxy-(ethoxymethyl)]-18-C-6 (2d) Obtained in 60% yield (1.66 g) as a colorless viscous oil. 1H NMR (400 MHz, CDCl3): δ = 2.84 (s, 1 H, OH), 3.50–3.84 (m, 29 H, 14 × CH2 and 1 × CH). 13C NMR (100 MHz, CDCl3): δ = 61.8 (CH2OH), 69.8 (CH2O), 70.7 (CH2O), 70.73 (CH2O), 70.77 (CH2O), 70.8 (CH2O), 70.83 (CH2O), 70.9 (CH2O), 70.95 (CH2O), 71.0 (CH2O), 71.1 (CH2O), 71.13 (CH2O), 71.4 (CH2O), 72.7 (CH2O), 78.3 (CH). ESI-HRMS: m/z [M + H] calcd for C15H30O8: 339.2019; found: 339.2017. 2-[Hydroxy-(ethoxy)-(ethoxymethyl)]-18-C-6 (3d) Obtained in 55% yield (1.56 g) as a colorless viscous oil. 1H NMR (400 MHz, CDCl3): δ = 2.76 (s, 1 H, OH), 3.47–3.81 (m, 33 H, 16 × CH2 and 1 × CH). 13C NMR (100 MHz, CDCl3): δ = 61.8 (CH2OH), 69.9 (CH2O), 70.4 (CH2O), 70.6 (CH2O), 70.7 (2 x CH2O), 70.73 (CH2O), 70.76 (CH2O), 70.8 (CH2O), 70.9 (2 × CH2O), 70.93 (CH2O), 71.0 (CH2O), 71.4 (CH2O), 71.5 (CH2O), 72.6 (CH2O), 78.3 (CH). ESI-HRMS: m/z [M + H] calcd for C17H34O9: 383.2281; found: 383.2276. 2-Hydroxyethyl-18-C-6 (4d) Obtained in 50% yield (1.35 g) as a colorless viscous oil. 1H NMR (400 MHz, CDCl3): δ = 1.65–1.85 (m, 2 H, CH2), 3.01 (s, 1 H, OH), 3.58–3.75 (m, 22 H, 11 × CH2), 3.75–3.90 (m, 3 H, 1 × CH2 and 1 × CH). 13C NMR (100 MHz, CDCl3): δ = 34.8 (CH2), 60.1 (CH2OH), 69.4 (CH2O), 70.6 (CH2O), 70.7 (CH2O), 70.77 (CH2O), 70.8 (CH2O), 70.86 (CH2O), 70.9 (CH2O), 71.0 (CH2O), 71.05 (CH2O), 71.7 (CH2O), 74.5 (CH2O), 77.7 (CH). ESI-HRMS: m/z [M + H] calcd for C14H28O7: 309.1913; found: 309.1908. 2-Hydroxypropyl-18-C-6 (5d) 2h Obtained in 48% yield (1.31 g) as a colorless viscous oil. 1H NMR (400 MHz, CDCl3): δ = 1.51–1.68 (m, 4 H, 2 × CH2), 2.30 (s, 1 H, OH), 3.50–3.76 (m, 24 H, 12 × CH2), 3.83–3.88 (m, 1 H, 1 × CH). 13C NMR (100 MHz, CDCl3): δ = 28.5 (CH2), 28.9 (CH2), 62.8 (CH2OH), 69.6 (CH2O), 70.6 (CH2O), 70.68 (CH2O), 70.7 (CH2O), 70.9 (2 x CH2O), 70.91 (CH2O), 70.92 (CH2O), 70.94 (CH2O), 71.0 (CH2O), 74.2 (CH2O), 79.0 (CH). ESI-HRMS: m/z [M + H] calcd for C15H30O7: 323.2070; found: 323.2064. 2-Hydroxybutyl-18-C-6 (6d) Obtained in 45% yield (1.24 g) as a colorless viscous oil. 1H NMR (400 MHz, CDCl3): δ = 1.26–1.62 (m, 6 H, 3 × CH2), 2.48 (s, 1 H, OH), 3.62–3.74 (m, 24 H, 12 × CH2), 3.80–3.85 (m, 1 H, 1 × CH). 13C NMR (100 MHz, CDCl3): δ = 21.9 (CH2), 31.5 (CH2), 32.9 (CH2), 62.7 (CH2OH), 69.5 (CH2O), 70.67 (4 × CH2O), 70.7 (CH2O), 70.8 (CH2O), 70.9 (CH2O), 71.0 (CH2O), 71.1 (CH2O), 74.3 (CH2O), 79.3 (CH). ESI-HRMS: m/z [M + H] calcd for C16H32O7: 337.2226; found: 337.2221. 1,2-Dihydroxymethyl-18-C-6 (7d) 2l Obtained in 55% yield (1.24 g) as a colorless viscous oil. 1H NMR (400 MHz, CDCl3): δ = 2.60 (s, 1 H, OH), 3.44 (s, 1 H, OH), 3.59–3.84 (m, 26 H, 12 × CH2 and 2 × CH). 13C NMR (100 MHz, CDCl3): δ = 61.8 (2 × CH2OH), 70.2 (2 × CH2O), 70.3 (2 × CH2O), 70.5 (2 × CH2O), 70.9 (2 × CH2O), 70.91 (2 × CH2O), 80.7 (2 × CH). ESI-HRMS: [M + H] calcd for C14H28O8: 325.1862; found: 325.1857.