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Synlett 2006(10): 1564-1568  
DOI: 10.1055/s-2006-941587
LETTER
© Georg Thieme Verlag Stuttgart · New York

Dimethylaminomethylphosphonic Acid Derivatives-Promoted CuI-Catalyzed Synthesis of Aryl Ethers

Ying Jina, Jinyong Liua, Yingwu Yina, Hua Fu*a, Yuyang Jianga,b, Yufen Zhaoa
a Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. of China
Fax: +86(10)62781695; e-Mail: fuhua@mail.tsinghua.edu.cn;
b Key Laboratory of Chemical Biology, Guangdong Province, College of Shenzhen, Tsinghua University, Shenzhen 518057, P. R. of China
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Publication History

Received 23 March 2006
Publication Date:
12 June 2006 (online)

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Abstract

An inexpensive and efficient catalyst system for synthesis of aryl ethers has been developed by using 20 mol% CuI as the catalyst, 30 mol% dimethylaminomethylphosphonic acid derivatives as the new ligands, K2CO3 as the base and toluene as the ­solvent. This is the first example using aminophosphonates as the ligands for Ullmann ether coupling reaction.

Key words

Ullmann reaction - aryl ether - copper-catalyzed - di­methylaminomethylphosphonic acid derivative

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7

Synthesis of Diisopropyl Dimethylaminomethyl-phosphonate (L ¹ ).
The mixed solution of diisopropyl phosphite (22 mmol, 3.7 g), dimethylamine hydrochloride (22 mmol, 1.79 g) and Et3N (22 mmol, 3.2 mL) in EtOH (30 mL) was added dropwise to 37% aq formaldehyde (1.8 mL), and the resulting solution was refluxed for 8 h. The 31P NMR spectroscopy showed that the starting material diisopropyl phosphite was almost quantitatively transferred into ligand L ¹ (δ = 26.9 ppm). The solvent was removed by rotary evaporation, the residue was isolated by silica gel column chromatography using CHCl3-MeOH (10:1) as eluent, and the pure L ¹ was obtained as a colorless liquid. Yield 4.50 g, 92%. 31P NMR (121.5 MHz, CDCl3): δ = 26.9 ppm. 1H NMR (300 MHz, CDCl3): δ = 4.78-4.71 (m, 2 H), 2.75 (d, J = 20.4 Hz, 2 H), 1.33 (s, 6 H), 2.41-2.38 (m, 12 H). 13C NMR (75 MHz, CDCl3): δ = 70.2, 56.9, 47.4, 24.0. ESI-HRMS: m/z calcd for C9H23NO3P [M + H]+: 224.1416; found: 224.1411.
Synthesis of Ethyl Dimethylaminomethylphosphonate (L ² ).
The mixed solution of diethyl phosphite (22 mmol, 3.0 g), dimethylamine hydrochloride (22 mmol, 1.79 g) in EtOH (30 mL) was added dropwise to 37% aq formaldehyde (1.8 mL), and the resulting solution was refluxed for 6 h. The solvent was removed by rotary evaporation, the residue was dissolved in 5 mL of H2O and 10 mL of EtOH. Then, LiOH (22 mmol, 0.53 g) was added, and the solution was stirred at 60 °C for 3 h. The solution was extracted with CH2Cl2, the aqueous phase was acidified with 3 M HCl to pH 3, and evaporated to dryness to provide a solid mixture. MeOH was added to the remaining solid, and the insoluble solid was filtrated. The filtrate was concentrated and dried over P2O5 in vacuo, and the desired product ethyl dimethylamino-methylphosphonate hydrochloride salt (L ² ) was obtained in the form of a white solid. Yield 3.81 g, 85%. 31P NMR (121.5 MHz, CDCl3): δ = 6.8 ppm. 1H NMR (300 MHz, CDCl3): δ = 8.98 (s, 1 H), 3.71-3.61 (m, 2 H), 2.80 (d, J = 20.4 Hz, 2 H), 2.59 (s, 6 H), 0.95 (t, J = 7.0 Hz, 3 H). 13C NMR (75 MHz, CDCl3): δ = 60.5, 55.2, 55.3, 45.3, 16.7. ESI-HRMS: m/z calcd for C5H15NO3P [M + H]+: 168.0790; found: 168.0783.
Synthesis of Dimethylaminomethylphosphonic Acid (L ³ ).
This compound was synthesized according to the known method.2 Dimethylamine hydrochloride (50 mmol, 4.2 g), H3PO4 (50 mmol, 4.1 g) and 20 mL of HCl (6.5 M in H2O) were added to a round-bottom flask fitted with a reflux condenser, and the solution was heated for 5 min. Then, 52 mmol (3.87 mL) of formaldehyde (36% aq solution) was added, and the solution was refluxed for 90 min. After removal of H2O in vacuo, the residue was heated in 60 mL of EtOH to lead to the formation of a white solid. This solid was collected after filtration, and dried in vacuo to obtain dimethylaminomethyl phosphonic acid hydrochloride salt (L ³ , 8.42 g, 96%). 31P NMR (121.5 MHz, DMSO-d 6,): δ = 9.3 ppm. 1H NMR (300 MHz, DMSO-d 6): δ = 5.86 (s, 2 H), 3.30 (d, J = 12.7 Hz, 2 H), 2.83 (s, 6 H). 13C NMR (75 MHz, DMSO-d 6): δ = 54.7, 52.8, 44.8. ESI-HRMS: m/z calcd for C3H11NO3P [M + H]+: 140.0477; found: 140.0481.

8

Characterization data of two representative compounds are shown as follows:
4-Nitrophenyl Phenyl Ether (3j) 9
Yellow solid; mp 58-60 °C (Lit.7 60 °C). 1H NMR (300 MHz, CDCl3): δ = 8.17 (d, J = 9.27 Hz, 2 H), 7.42 (t, J = 7.89 Hz, 2 H), 7.25 (t, J = 7.56 Hz, 1 H), 7.08 (d, J = 7.82 Hz, 2 H), 7.00 (d, J = 8.85 Hz, 2 H). 13C NMR (75 MHz, CDCl3): δ = 163.5, 154.8, 142.7, 130.4, 126.0, 125.5, 120.6, 117.2. HRMS (EI): m/z calcd for C12H9NO3 [M+]: 215.0582; found: 215.0574.
Bis(4-methoxyphenenyl)ether (3m) 5b
White solid; mp 101-103 °C (Lit.5b 102-103 °C). 1H NMR (300 MHz, CDCl3): δ = 6.92 (d, J = 9.27 Hz, 4 H), 6.85 (d, J = 9.27 Hz, 4 H), 3.79 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 155.4, 151.7, 119.6, 114.8, 55.8. HRMS (EI): m/z calcd for C14H14O3 [M+]: 230.0943; found: 230.0949.