1,3-dichloro-2-isothiocyanatobenzene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 0.5 g of 3,4-diamino-2,5-dimethylthiophene dihydrochloride, 30 ml of anhydrous THF and 0.49 g of triethylamine was stirred at room temperature for 30 minutes and then admixed with 0.569 g of 2,6-dichlorophenyl isothiocyanate. After the mixture had been heated to 40° C. for 30 minutes, it was stirred at room temperature for approx. 18 hours, the solvent was distilled off, the residue admixed with water and the precipitate filtered off and purified by column chromatography on silica gel using a mixture consisting of equal parts by volume of toluene and ethyl acetate. After the solvent had been distilled off, a foamy, amorphous product of m.p. 143–148° C. was obtained which, after melting, solidified again with a new m.p. of >300° C. After the mixture had been heated to 40° C. for 30 minutes it was stirred at room temperature for approx. 18 hours the solvent was distilled off the residue admixed with water and the precipitate filtered off purified by column chromatography on silica gel using a mixture After the solvent had been distilled off a foamy, amorphous product of m.p. 143–148° C. was obtained which

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1.87 g of 3,4-diaminothiophene dihydrochloride, 60 ml of anhydrous THF and 2.58 g of N-ethyl-N,N-diisopropylamine was stirred at room temperature for 30 minutes and then admixed with 2.04 g of 2,6-dichlorophenyl isothiocyanate. After the mixture had been heated to 40° C. for 10 minutes, it was stirred at room temperature for approx. 18 hours, and the solvent was distilled off, and the residue admixed with water and extracted repeatedly with ethyl acetate. After the combined organic phases had been treated with activated carbon, they were dried over sodium sulfate and the solvent was again distilled off. A crystalline solid was obtained and, after stirring with a little ethyl acetate, was filtered off. M.p. 165° C. After the mixture had been heated to 40° C. for 10 minutes it was stirred at room temperature for approx. 18 hours the solvent was distilled off the residue admixed with water and extracted repeatedly with ethyl acetate After the combined organic phases had been treated with activated carbon, they were dried over sodium sulfate the solvent was again distilled off A crystalline solid was obtained was filtered off

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-Cyclohexyl-1,1-dimethyl-2-hydroxyethanamine was prepared in a manner analogous to Method B4a. A solution of 2,6-dichlorophenyl isothiocyanate (1.2 g, 6.0 mmol) and N-cyclohexyl-1,1-dimethyl-2-hydroxyethanamine (1.0 g, 6.0 mmol) in CH2Cl2 (10 mL) was stirred for 20 h at room temp. The resulting mixture was concentrated under reduced pressure, then treated with a 33% HCl solution (15 mL). The resulting mixture was heated at the reflux temp. for 1 h, cooled to room temp. and neutralized with a 45% NaOH solution. The resulting slurry was filtered, and the resulting solids were washed with water (20 mL), then recrystallized (EtOH) to yield 2-(2,6-dichlorophenylimino)-3-cyclohexyl-4,4-dimethyl-1,3-thiazolidine (0.70 g, 33%/o): mp 134° C. When appropriate, the product was converted into the HCl salt by dissolving the free base (5 mmol) in Et2O (50 mL) and treating this solution with a 2N ethereal HCl solution until no more solid precipitated. The resulting slurry was filtered and the resulting solids were washed with Et2O (25 mL) followed by EtOAc (25 mL). The resulting mixture was concentrated under reduced pressure treated with a 33% HCl solution (15 mL) The resulting mixture was heated at the reflux temp cooled to room temp. The resulting slurry was filtered the resulting solids were washed with water (20 mL) recrystallized (EtOH)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-Cyclohexyl-1,1-dimethyl-2-hydroxyethanamine was prepared in a manner analogous to Method B4a. A solution of 2,6-dichlorophenyl isothiocyanate (1.2 g, 6.0 mmol) and N-cyclohexyl-1,1-dimethyl-2-hydroxyethanamine (1.0 g, 6.0 mmol) in CH2Cl2 (10 mL) was stirred for 20 h at room temp. The resulting mixture was concentrated under reduced pressure, then treated with a 33% HCl solution (15 mL). The resulting mixture was heated at the reflux temp. for 1 h, cooled to room temp. and neutralized with a 45% NaOH solution. The resulting slurry was filtered, and the resulting solids were washed with water (20 mL), then recrystallized (EtOH) to yield 2-(2,6-dichlorophenylimino)-3-cyclohexyl-4,4-dimethyl-1,3-thiazolidine (0.70 g, 33%/o): mp 134° C. When appropriate, the product was converted into the HCl salt by dissolving the free base (5 mmol) in Et2O (50 mL) and treating this solution with a 2N ethereal HCl solution until no more solid precipitated. The resulting slurry was filtered and the resulting solids were washed with Et2O (25 mL) followed by EtOAc (25 mL). The resulting mixture was concentrated under reduced pressure treated with a 33% HCl solution (15 mL) The resulting mixture was heated at the reflux temp cooled to room temp. The resulting slurry was filtered the resulting solids were washed with water (20 mL) recrystallized (EtOH)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2,6-dichlorophenyl isothiocyanate (500 mg) and THF (5 ml) was added dropwise under argon within 20 minutes to a solution of ethylenediamine (3.68 g) and abs. THF (4 ml). After stirring for a further 30 min, the mixture was added to water, acidified with 10% HCl and extracted three times with ethyl acetate. The aqueous phase was made basic using saturated potassium carbonate solution, and extracted three times with ethyl acetate. The combined organic phases were dried over magnesium sulfate, the solvent was removed under reduced pressure and the residue was co-evaporated twice with toluene. After drying in high vacuum, the desired product was obtained as a white solid (532 mg). extracted three times with ethyl acetate extracted three times with ethyl acetate The combined organic phases were dried over magnesium sulfate the solvent was removed under reduced pressure After drying in high vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2,6-dichlorophenyl isothiocyanate (500 mg) and THF (5 ml) was added dropwise under argon within 20 minutes to a solution of ethylenediamine (3.68 g) and abs. THF (4 ml). After stirring for a further 30 min, the mixture was added to water, acidified with 10% HCl and extracted three times with ethyl acetate. The aqueous phase was made basic using saturated potassium carbonate solution, and extracted three times with ethyl acetate. The combined organic phases were dried over magnesium sulfate, the solvent was removed under reduced pressure and the residue was co-evaporated twice with toluene. After drying in high vacuum, the desired product was obtained as a white solid (532 mg). extracted three times with ethyl acetate extracted three times with ethyl acetate The combined organic phases were dried over magnesium sulfate the solvent was removed under reduced pressure After drying in high vacuum