Diethylene Glycol → 2,2,6,6-Tetramethyl-1-(2',4',6'-triisopropyl-3,6-dimethoxybiphenyl-2-yl)phosphinane

HRID 874032Notes

Reaction equation

HRID 874032 reaction equation
[CH3:1][C:2]1([CH3:36])[CH2:7][C:6](=O)[CH2:5][C:4]([CH3:10])([CH3:9])[P:3]1[C:11]1[C:16]([O:17][CH3:18])=[CH:15][CH:14]=[C:13]([O:19][CH3:20])[C:12]=1[C:21]1[C:26]([CH:27]([CH3:29])[CH3:28])=[CH:25][C:24]([CH:30]([CH3:32])[CH3:31])=[CH:23][C:22]=1[CH:33]([CH3:35])[CH3:34].C(O)COCCO.O.NN.[OH-].[K+]>>[CH3:36][C:2]1([CH3:1])[CH2:7][CH2:6][CH2:5][C:4]([CH3:9])([CH3:10])[P:3]1[C:11]1[C:16]([O:17][CH3:18])=[CH:15][CH:14]=[C:13]([O:19][CH3:20])[C:12]=1[C:21]1[C:26]([CH:27]([CH3:28])[CH3:29])=[CH:25][C:24]([CH:30]([CH3:32])[CH3:31])=[CH:23][C:22]=1[CH:33]([CH3:35])[CH3:34]

Participants

5

Reactant 4

HCID 8117Diethylene GlycolHCID 14797Potassium HydroxideHCID 24654Hydrazine hydrate (1:1)HCID 666623182,2,6,6-Tetramethyl-1-(2',4',6'-triisopropyl-3,6-dimethoxybiphenyl-2-yl)phosphinan-4-one

Product 1

HCID 666676232,2,6,6-Tetramethyl-1-(2',4',6'-triisopropyl-3,6-dimethoxybiphenyl-2-yl)phosphinaneYield 27%

Conditions

Temperature
210 °C

Procedure

A round bottom flask was charged with 2,2,6,6-tetramethyl-1-(2′,4′,6′-triisopropyl-3,6-dimethoxybiphenyl-2-yl)phosphinan-4-one (1.03 g, 2.02 mmol, 1.0 equiv) and purged with nitrogen for 15 minutes. Then nitrogen-sparged diethylene glycol (10.6 mL, 111 mmol, 55 equiv) was added and the flask was equipped with a Claisen adapter and a Dean-Stark trap. The flask was charged with hydrazine hydrate (0.892 mL, 10.1 mmol, 5 equiv, 55 wt % hydrazine) and potassium hydroxide (918 mg, 10.1 mmol, 5 equiv). The mixture was immersed in an oil bath at 170° C. The temperature of the bath was gradually increased to 210° C. over 1 hour and kept at that temperature for 7 hours. The reaction mixture was cooled to room temperature under a positive pressure of nitrogen. Reaction material that had condensed on the Claisen adapter was washed down into the reaction flask with ethyl acetate (5 mL). The phases were partitioned, and the organic layer was collected. The aqueous layer was washed with ethyl acetate (2×20 mL). The combined organic fractions were washed once with aqueous saturated sodium chloride, dried over sodium sulfate, filtered, and concentrated on a rotary evaporator. Purification of the crude material by silica gel column chromatography on an Isco CombiFlash system (40-g column; gradient: 2 column volumes heptane, ramp up to 85:15 heptane:ethyl acetate over 8 column volumes, hold at 85:15 for 4 column volumes) afforded the title compound as a white solid (266 mg, >99 area % by HPLC, 27% yield). 1H NMR (400 MHz, CDCl3) δ ppm 6.95 (s, 2H), 6.85 (d, J=8.8 Hz, 1H), 6.79 (d, J=8.8 Hz, 1H), 3.82 (s, 3H), 3.56 (s, 3H), 2.95 (hept, J=6.9 Hz, 1H), 2.49 (hept, J=6.7 Hz, 2H), 2.10-1.89 (m, 2H), 1.71-1.51 (m, 2H), 1.45-1.26 (m, 8H), 1.21 (d, J=6.8 Hz, 6H), 1.14 (s, 3H), 1.08 (s, 3H), 0.93 (d, J=6.7 Hz, 6H), 0.80 (d, J=8.6 Hz, 6H). 13C NMR (100 MHz, CDCl3) δ ppm 154.3, 151.9 (d, J=11 Hz), 146.3, 145.5 (d, J=2 Hz), 140.1 (d, J=42 Hz), 132.5 (d, J=9 Hz), 127.7 (d, J=46 Hz), 119.7, 110.6, 107.1, 54.3 (d, J=62 Hz), 40.8 (d, J=4 Hz), 34.0 (d, J=5 Hz), 33.4, 30.7, 30.3 (d, J=24 Hz), 30.1 (d, J=3 Hz), 25.5, 24.2 (d, J=13 Hz), 20.8. 31P NMR (CDCl3, 202 MHz) δ ppm −6.0 (br s). HRMS (TOF-ESI+) calcd for [M, C32H49O2P]+ 496.3470, found 496.3465.

Workup

  1. custompurged with nitrogen for 15 minutes
  2. additionwas added
  3. customthe flask was equipped with a Claisen adapter
  4. customThe mixture was immersed in an oil bath at 170° C
  5. temperatureThe reaction mixture was cooled to room temperature under a positive pressure of nitrogen
  6. customReaction material that
  7. customcondensed on the Claisen adapter
  8. washwas washed down into the reaction flask with ethyl acetate (5 mL)
  9. customThe phases were partitioned
  10. customthe organic layer was collected
  11. washThe aqueous layer was washed with ethyl acetate (2×20 mL)
  12. washThe combined organic fractions were washed once with aqueous saturated sodium chloride
  13. dry with materialdried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated on a rotary evaporator
  16. customPurification of the crude material by silica gel column chromatography on an Isco CombiFlash system (40-g column

Sources & evidence

ORD record
ord-95765f02b1bc443ba5aa7ec18c573251
Source dataset
uspto-grants-2015_03
Patent number
US08975443B2

Reaction notes

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