Diethylene Glycol → 1',3',5'-Triphenyl-5-(2,2,6,6-tetramethylphosphinan-1-yl)-1'H-1,4'-bipyrazole

HRID 78978Notes

Reaction equation

HRID 78978 reaction equation
[CH3:1][C:2]1([CH3:39])[CH2:7][C:6](=O)[CH2:5][C:4]([CH3:10])([CH3:9])[P:3]1[C:11]1[N:15]([C:16]2[C:17]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[N:18][N:19]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:20]=2[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[N:14]=[CH:13][CH:12]=1.C(O)COCCO.O.NN.[OH-].[K+]>CCCCCCC.C(OCC)(=O)C>[C:27]1([N:19]2[C:20]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)=[C:16]([N:15]3[C:11]([P:3]4[C:2]([CH3:39])([CH3:1])[CH2:7][CH2:6][CH2:5][C:4]4([CH3:10])[CH3:9])=[CH:12][CH:13]=[N:14]3)[C:17]([C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=3)=[N:18]2)[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

7

Reactant 4

HCID 8117Diethylene GlycolHCID 14797Potassium HydroxideHCID 24654Hydrazine hydrate (1:1)HCID 58067276HCID 58067276, compound

Product 1

HCID 666788931',3',5'-Triphenyl-5-(2,2,6,6-tetramethylphosphinan-1-yl)-1'H-1,4'-bipyrazoleYield 68%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 8900HeptaneSolvent

Conditions

Temperature
210 °C

Procedure

A round bottom flask was charged with 2,2,6,6-tetramethyl-1-(1′,3′,5′-triphenyl-1′H-1,4′-bipyrazol-5-yl)phosphinan-4-one (1.25 g, 2.35 mmol, 1.0 equiv) and purged with nitrogen for 15 minutes. Then nitrogen-sparged diethylene glycol (12.3 mL, 129 mmol, 55 equiv) was added and the flask was equipped with a Claisen adapter and a Dean-Stark trap. The mixture was charged with hydrazine hydrate (1.07 mL, 11.7 mmol, 5 equiv, 55 wt % hydrazine) and potassium hydroxide (658 mg, 11.7 mmol, 5 equiv). The mixture was immersed in an oil bath at 125° C. under a nitrogen atmosphere. The temperature of the bath was 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, and then diluted with heptane (10 mL) and ethyl acetate (10 mL). The phases were partitioned, and the aqueous layer was collected. The aqueous layer was then washed with ethyl acetate (2×20 mL), and the combined organic fractions were washed once with aqueous saturated sodium chloride (50 mL), dried over sodium sulfate, filtered, and concentrated on a rotary evaporator. The crude concentrate was dissolved in a minimal amount of hot ethanol, and the solution was allowed to cool, effecting the crystallization of the product as a white solid. (826 mg, 95 area % by HPLC, 68% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.91 (d, J=1.9 Hz, 1H), 7.52-7.42 (m, 4H), 7.38-7.26 (m, 3H), 7.25-7.19 (m, 5H), 7.19-7.11 (m, 3H), 6.61 (d, J=1.8 Hz, 1H), 1.53 (dd, J=14.1, 12.0 Hz, 5H), 1.21 (ddd, J=24.9, 11.7, 5.7 Hz, 2H), 0.85 (dd, J=24.4, 18.8 Hz, 6H), 0.01 (d, J=11.6 Hz, 3H), −0.27 (d, J=11.5 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ ppm 149.3 (d, J=2 Hz), 145.0, 143.2 (d, J=27 Hz), 141.0 (d, J=2 Hz), 139.8, 139.6 (d, J=2 Hz), 131.5, 129.5, 128.5, 128.3, 128.0, 127.9, 127.8, 127.3, 127.2, 125.1, 120.9, 113.0 (d, J=5 Hz), 37.1 (dd, J=8, 2 Hz), 29.9, 29.8, 29.3 (d, J=2 Hz), 29.2 (d, J=2 Hz), 29.1 (d, J=2 Hz), 28.8 (d, J=2 Hz), 28.8 (d, J=8 Hz), 20.2. 31P NMR (CDCl3, 202 MHz) δ ppm −17.0 (s). LRMS (ESI+) found for [M+H, C33H36N4P]+ 519.2.

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 125° C. under a nitrogen atmosphere
  5. temperatureThe reaction mixture was cooled to room temperature under a positive pressure of nitrogen
  6. customThe phases were partitioned
  7. customthe aqueous layer was collected
  8. washThe aqueous layer was then washed with ethyl acetate (2×20 mL)
  9. washthe combined organic fractions were washed once with aqueous saturated sodium chloride (50 mL)
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated on a rotary evaporator
  13. concentrationThe crude concentrate
  14. dissolutionwas dissolved in a minimal amount of hot ethanol
  15. temperatureto cool
  16. customthe crystallization of the product as a white solid

Sources & evidence

ORD record
ord-bdee1c7c6b0240999752b7b37fcb4dd0
Source dataset
uspto-grants-2014_09
Patent number
US08841487B2

Reaction notes

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