P-Toluenesulfonamide → HCID 20437341, compound

HRID 1980168Notes

Reaction equation

HRID 1980168 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([NH2:11])(=[O:10])=[O:9])=[CH:6][CH:7]=1.[H-].[Na+].[CH2:14]([NH:30][C:31]1[CH:39]=[CH:38][C:34]([C:35](O)=[O:36])=[CH:33][CH:32]=1)[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29].S(Cl)(Cl)=O>C(COC)OC.C(Cl)Cl.CC(N(C)C)=O.O>[CH2:14]([NH:30][C:31]1[CH:32]=[CH:33][C:34]([C:35]([NH:11][S:8]([C:5]2[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=2)(=[O:10])=[O:9])=[O:36])=[CH:38][CH:39]=1)[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]

Participants

9

Reactant 4

HCID 6269P-ToluenesulfonamideHCID 24386Thionyl ChlorideHCID 24758Sodium hydrideHCID 472634-(Hexadecylamino)benzoic acid

Product 1

HCID 20437341HCID 20437341, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolventHCID 31374DimethylacetamideSolvent2×

Procedure

A solution of 34.25 g. of p-toluenesulfonamide in 250 ml. of dry dimethylacetamide is added dropwise over 30 minutes to a stirred and cooled (water bath) suspension of 5.5 g. of sodium hydride in 100 ml. of dry dimethylacetamide. Stirring is continued at room temperature for 3 hours until foaming subsides. In the meantime, a mixture of 36.2 g. of p-hexadecylaminobenzoic acid in 1200 ml. of methylene chloride, 300 ml. of dimethoxyethane, and 40 ml. of thionyl chloride is refluxed for 1 hour and 15 minutes. The solution is evaporated to an oil which is co-evaporated twice with added dioxane to remove excess thionyl chloride. To the resulting oily residue of p-hexadecylaminobenzoyl chloride is added, in one portion, the previously prepared mixture of sodium p-toluenesulfonamide in dimethylacetamide. The mixture is stirred for 30 minutes, without cooling, and is filtered through a bed of diatomaceous earth. The filtrate is poured into 2 l. of water and the resulting suspension is coagulated by the addition of 250 ml. of saturated sodium chloride solution. The gummy solid is decanted and the product is dissolved in 700 ml. of methylene chloride. The mixture is filtered through diatomaceous earth and brine is added to break the emulsion. The layers are separated and the organic phase is dried over anhydrous sodium sulfate and filtered. The filtrate is concentrated on the steam bath to approx. 300 ml. and is filtered through 300 g. of hydrous magnesium silicate using 3 l. of methylene chloride as elutant. The first approx. 600 ml. of filtrate is discarded and the remainder is evaporated to a tan, pasty solid. The solid is crystallized from 75 ml. of 2:1 toluene:hexane solution to give a colorless solid containing a less polar by-product. The mixture is crystallized from absolute ethanol in which the by-product separates out first. The mixture is filtered and the filtrate is concentrated to dryness and the residue is crystallized again from ethanol. This process is repeated until all of the by-product is removed. The product fractions were combined and crystallized twice from 2:1 toluene:hexane to give 8.3 g. of the title compound as colorless crystals, melting point 123°-124° C.

Workup

  1. temperaturecooled
  2. stirringStirring
  3. additionIn the meantime, a mixture of 36.2 g
  4. customThe solution is evaporated to an oil which
  5. customto remove excess thionyl chloride
  6. additionTo the resulting oily residue of p-hexadecylaminobenzoyl chloride is added, in one portion
  7. additionthe previously prepared mixture of sodium p-toluenesulfonamide in dimethylacetamide
  8. stirringThe mixture is stirred for 30 minutes
  9. temperaturewithout cooling
  10. filtrationis filtered through a bed of diatomaceous earth
  11. additionThe filtrate is poured into 2 l
  12. additionof water and the resulting suspension is coagulated by the addition of 250 ml
  13. customThe gummy solid is decanted
  14. dissolutionthe product is dissolved in 700 ml
  15. filtrationThe mixture is filtered through diatomaceous earth and brine
  16. additionis added
  17. customThe layers are separated
  18. dry with materialthe organic phase is dried over anhydrous sodium sulfate
  19. filtrationfiltered
  20. concentrationThe filtrate is concentrated on the steam bath to approx. 300 ml
  21. filtrationand is filtered through 300 g
  22. customthe remainder is evaporated to a tan, pasty solid
  23. customThe solid is crystallized from 75 ml
  24. customof 2:1 toluene:hexane solution to give a colorless solid
  25. additioncontaining a less polar by-product
  26. customThe mixture is crystallized from absolute ethanol in which the by-product
  27. filtrationThe mixture is filtered
  28. concentrationthe filtrate is concentrated to dryness
  29. customthe residue is crystallized again from ethanol
  30. customis removed
  31. customcrystallized twice from 2:1 toluene
  32. customhexane to give 8.3 g

Sources & evidence

ORD record
ord-d990cf1f59dc46a5910356d92a05290e
Source dataset
uspto-grants-1984_11
Patent number
US04485105

Reaction notes

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