Hydrogen Sulfide → N-Butyl-10-[(2RS)-1-(N-ethyl-N-methylamino)-2-propyl]-2-phenothiazinecarbothioamide

HRID 704192Notes

Reaction equation

HRID 704192 reaction equation
[CH2:1]([N:3]([CH2:5][CH:6]([N:8]1[C:21]2[CH:20]=[C:19]([C:22](=[S:24])[NH2:23])[CH:18]=[CH:17][C:16]=2[S:15][C:14]2[C:9]1=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH3:7])[CH3:4])[CH3:2].[CH2:25](N)[CH2:26][CH2:27][CH3:28].S>C(O)C>[CH2:25]([NH:23][C:22]([C:19]1[CH:18]=[CH:17][C:16]2[S:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[N:8]([CH:6]([CH3:7])[CH2:5][N:3]([CH2:1][CH3:2])[CH3:4])[C:21]=2[CH:20]=1)=[S:24])[CH2:26][CH2:27][CH3:28]

Participants

5

Reactant 3

HCID 402Hydrogen SulfideHCID 8007ButylamineHCID 1453655410-[(2RS)-1-(N-ethyl-N-methylamino)-2-propyl]-2-phenothiazinecarbothioamide

Product 1

HCID 14536555N-Butyl-10-[(2RS)-1-(N-ethyl-N-methylamino)-2-propyl]-2-phenothiazinecarbothioamide

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 10-[(2RS)-1-(N-ethyl-N-methylamino)-2-propyl]-2-phenothiazinecarbothioamide (2.1 g) and butylamine (8.5 cc) in absolute ethanol (30 cc) is saturated with hydrogen sulphide and heated for 16 hours to a temperature in the region of 100° C. After cooling, the orange solution obtained is concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. The residual brown oil is purified by chromatography on a column (height: 4 cm; diameter: 3 cm) of silica gel (0.2-0.063 mm), eluting successively with methylene chloride (2 liters) and with a mixture (90:10 by volume) (1 liter) of methylene chloride and methanol and collecting 60-cc fractions. Fractions 36 to 39 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. The residual orange oil (1.8 g) is again purified by chromatography on a column (height: 25 cm; diameter: 4 cm) of silica gel (0.04-0.063 mm) under a slight excess pressure of nitrogen (40 kPa), eluting with mixture (75:25 by volume) (1 liter) of ethyl acetate and cyclohexane and collecting 60-cc fractions. Fractions 5 to 12 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. N-Butyl-10-[(2RS)-1-(N-ethyl-N-methylamino)-2-propyl]-2-phenothiazinecarbothioamide (1.25 g) is thereby obtained in the form of a yellow oil. This product is dissolved in isopropyl ether (100 cc) and treated, dropwise and with stirring, with a 0.28N solution (10.9 cc) of hydrochloric acid in isopropyl ether. After 1 hour's stirring at a temperature in the region of 5° C, the precipitate formed is drained, washed with isopropyl ether (3×10 cc) and dried under reduced pressure (5 mm Hg; 0.68 kPa) at 40° C. N-Butyl-10-[(2RS)-1-(N-methyl-N-ethylamino)-2-propyl]-2-phenothiazinecarbothioamide hydrochloride (1.1 g) is thereby obtained in the form of a yellow solid, m.p. 102° C. (melts forming a paste).

Workup

  1. temperatureAfter cooling
  2. customthe orange solution obtained
  3. concentrationis concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C
  4. customThe residual brown oil is purified by chromatography on a column (height: 4 cm; diameter: 3 cm) of silica gel (0.2-0.063 mm)
  5. washeluting successively with methylene chloride (2 liters) and with a mixture (90:10 by volume) (1 liter) of methylene chloride and methanol
  6. customcollecting 60-cc fractions
  7. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C
  8. customThe residual orange oil (1.8 g) is again purified by chromatography on a column (height: 25 cm; diameter: 4 cm) of silica gel (0.04-0.063 mm) under a slight excess pressure of nitrogen (40 kPa)
  9. washeluting with mixture (75:25 by volume) (1 liter) of ethyl acetate and cyclohexane
  10. customcollecting 60-cc fractions
  11. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C

Sources & evidence

ORD record
ord-e866030f658c49d8b513656d8693beeb
Source dataset
uspto-grants-1991_01
Patent number
US04985419

Reaction notes

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