Phenothiazine → HCID 12799390, compound

HRID 1764216Notes

Reaction equation

HRID 1764216 reaction equation
P(Cl)(Cl)(Cl)=O.[CH:6]1[C:19]2[NH:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[S:11][C:10]=2[CH:9]=[CH:8][CH:7]=1.[NH:20]1[CH2:24][CH2:23][CH2:22][C:21]1=O.[OH-].[Na+]>ClCCCl>[N:20]1[CH2:24][CH2:23][CH2:22][C:21]=1[N:20]1[CH2:24][CH2:23][CH:22]=[C:21]1[N:18]1[C:19]2[CH:6]=[CH:7][CH:8]=[CH:9][C:10]=2[S:11][C:12]2[C:17]1=[CH:16][CH:15]=[CH:14][CH:13]=2

Participants

6

Reactant 4

HCID 7108PhenothiazineHCID 120252-PyrrolidoneHCID 14798Sodium HydroxideHCID 24813Phosphorus oxychloride

Product 1

HCID 12799390HCID 12799390, compoundYield 17%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Procedure

Phosphorus oxychloride (38.3 g., 0.25 mole) in 50 ml. of 1,2-dichloroethane is added in one portion to a stirred mixture of phenothiazine (49.8 g., 0.25 mole) and 2-pyrrolidinone (42.6 g., 0.5 mole) in 250 ml. of 1,2-dichloroethane. The mixture is stirred for 4 hr. at room temperature, permitted to stand for a period of 15 hr. and then poured into a mixture of 200 ml. of 5N sodium hydroxide and 100 g. of crushed ice. The 1,2-dichloroethane layer is separated and the aqueous layer extracted with 100 ml. of additional 1,2-dichloroethane. The combined 1,2-dichloroethane fractions are sequentially extracted with 300 ml. of 1.5N hydrochloric acid and 200 ml. of water. The combined acid-water extracts are washed with ether, made basic with 5N sodium hydroxide and extracted repeatedly with chloroform. After drying over magnesium sulfate, the chloroform solution is concentrated and the residual material thus obtained stirred with 200 ml. of acetone to remove the acetone soluble 10-[2-(1-pyrrolinyl)]phenothiazine by-product and filtered. The filter cake is washed with additional acetone and dried providing 14.1 g. (17% yield) of 10-[1-(1-PYRROLIN-2-YL)-2-PYRROLIN-2-YL]PHENOTHIAZINE as the free base, m.p. 199°-201° C. The bis-pyrrolinyl phenothiazine free base suspended in 60 ml. of absolute ethanol, acidified with an equivalent of ethanolic hydrogen chloride, treated with decolorizing charcoal, filtered, and diluted with 200-250 ml. of anhydrous ether providing the hydrochloride salt. Crystallization of the hydrochloride salt from absolute ethanol-anhydrous ether affords analytically pure 10-[1-(1-PYRROLIN-2-YL)-2-PYRROLIN-2-YL PHENOTHIAZINE[HYDROCHLORIDE solvated with 1/5 mole of ethanol as an off white solid, m.p. 237°-239° C. (corr.).

Workup

  1. customat room temperature
  2. waitto stand for a period of 15 hr
  3. additionand then poured into a mixture of 200 ml
  4. customThe 1,2-dichloroethane layer is separated
  5. extractionthe aqueous layer extracted with 100 ml
  6. extractionThe combined 1,2-dichloroethane fractions are sequentially extracted with 300 ml
  7. washThe combined acid-water extracts are washed with ether
  8. extractionextracted repeatedly with chloroform
  9. dry with materialAfter drying over magnesium sulfate
  10. concentrationthe chloroform solution is concentrated
  11. customthe residual material thus obtained
  12. stirringstirred with 200 ml
  13. customof acetone to remove the acetone soluble 10-[2-(1-pyrrolinyl)]phenothiazine by-product
  14. filtrationfiltered
  15. washThe filter cake is washed with additional acetone
  16. customdried
  17. customproviding 14.1 g

Sources & evidence

ORD record
ord-384c703f8e9744e399285c6209f71373
Source dataset
uspto-grants-1978_09
Patent number
US04115571

Reaction notes

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