ethoxymethanedithioic acid

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

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

Procedure: 1.00 g (3.9 mmol) of 2-(bromomethyl)pyridine hydrobromide and 0.36 g (3.9 mmol) of O-ethyldithiocarbonic acid, potassium salt were combined in a 50 ml round bottom flask with 20 ml of 100% ethanol. The reaction vessel was sealed with a rubber septum and oxygen was removed by several freeze-pump-thaw cycles. The reaction mixture was then warmed to room temperature and allowed to stir under positive nitrogen pressure. A white precipitate was observed after the first few minutes of the reaction. The reaction was allowed to stir for an additional 20 hours. 20 mL of 0.5M aqueous sodium hydroxide was then added causing the reaction mixture to become homogenous and take on a red color. Extraction with hexane after addition of an additional 20 ml of the sodium hydroxide solution yielded a fluorescent yellow-green solution. Hexane was removed and the residue was passed over a silica column (ethyl acetate as the elluent). The final product appears as a yellow-green liquid and fluoresces blue when exposed to long wavelength ultra-violet light. Yield=0.342 g (39%). 1H NMR (CDCl3) δ=1.212 (t, 3H), δ=4.353 (s, 2H), δ=4.47 (q, 2H), δ=7.002 (t, 1 H), δ=7.234 (d, 1H), δ=7.466 (t, 1H), δ=8.377 (d, 1H). 13C NMR (CDCl3) δ=13.929, δ=42.135, δ=70.358, δ=122.494 (CH), δ=123.424 (CH), δ=136.777 (CH), δ=149.660 (CH), δ=156.152 (C), δ=213.730 (C═S). was removed by several freeze-pump-thaw cycles after the first few minutes of the reaction to stir for an additional 20 hours Extraction with hexane after addition of an additional 20 ml of the sodium hydroxide solution yielded a fluorescent yellow-green solution Hexane was removed

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

Procedure: Alternately, combine methyl 2-methoxy-5-aminobenzoate (1.0 g, 5.6 mmol) and 12 M aqueous hydrochloric acid solution (1.2 g and cool in an ice bath. Add a solution of sodium nitrite (0.37 g, 5.3 mmol) in water (3 mL). After 1.5 hours, add ethyl xanthic acid, sodium salt (0.76 g, 6.3 mmol) and sodium carbonate (0.67 g, 6.3 mmol). After 2 hours, evaporate in vacuo and add sodium sulfide (0.69 g, 2.7 mmol) and a 1 M aqueous sodium hydroxide solution (10 mL). After 4 hours, add dimethylsulfate and heat to reflux. After 24 hours, cool to ambient temperature, acidify with 12 M hydrochloric acid solution and extract with ethyl acetate. Separate the organic layer, extract with brine, dry over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with ethyl acetate/hexane 2/1 to give methyl 2-methoxy-5-methylthiobenzoate. Elemental Analysis calculated for C9H12O3S: C, 54.53; H, 5.08. Found: C, 54.64; H, 4.95. cool in an ice bath After 2 hours evaporate in vacuo After 4 hours heat to reflux After 24 hours extract with ethyl acetate Separate the organic layer extract with brine dry over Na2SO4 filter evaporate in vacuo to give a residue

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: 2-mercapto-5-trifluoromethylaniline hydrochloride (22.79 gm, 0.01 mol) was heated to reflux in 200 ml 95% ethanol by volume with 20 ml of 22% (by weight) aqueous potassium hydroxide and 16.0 gm (0.1 mol) of O-ethylxanthic acid, potassium salt. When hydrogen sulfide evolution had ceased, the solution was filtered, cooled and acidified with HCl. The initial precipitate was collected by filtration and discarded. The filtrate was allowed to stand to precipitate 13.79 gm (59% of theory) of desired product, with a melting point of 221°-222° C. The resulting 2-mercapto-5-trifluoromethylbenzothiazole (11.75 gm, 0.05 mol) was slurried in 50 ml of 95% ethanol, treated with 7.1 gm of triethylamine, and then refluxed 1 hour with 7.1 gm (0.05 mol) of iodomethane. The mixture was filtered hot, cooled, concentrated, and treated with water to precipitate 11.54 gm (93% of theoretical) of 2-methylthio-5-trifluoromethylbenzothiazole (melting point of 66° -69° C.). This compound (11.0 gm, 0.044 mol) was then heated to 130°-156° C. with 8.22 gm (0.044 mol) of methyl-p-toluenesulfonate for 5 minutes. After cooling, the resulting solid was washed and triturated with acetone to yield 15.05 gm (78% of theory) of 3-methyl-2-methylthio-5-trifluoromethyl-benzothiazolium p-toluenesulfonate with a melting point of 189°-191° C. This quaternary salt (4.35 gm, 0.01 mol) was dissolved with 1.91 gm (0.01 mol) of rhodanine-3-acetic acid in 20 ml of methanol. After 2.02 gm (0.02 mol) of triethylamine was added thereto, the mixture was stirred at room temperature for 4.5 hours before isolating the precipitated dye by filtration. After washing the filtered solid with methanol, 2.74 gm (54% of theoretical) of this dye was obtained. the solution was filtered cooled The initial precipitate was collected by filtration to precipitate 13.79 gm (59% of theory) of desired product The mixture was filtered hot cooled concentrated treated with water to precipitate 11.54 gm (93% of theoretical) of 2-methylthio-5-trifluoromethylbenzothiazole (melting point of 66° -69° C.) After cooling the resulting solid was washed triturated with acetone

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

Procedure: 2-mercapto-5-trifluoromethylaniline hydrochloride (22.79 gm, 0.01 mol) was heated to reflux in 200 ml 95% ethanol by volume with 20 ml of 22% (by weight) aqueous potassium hydroxide and 16.0 gm (0.1 mol) of O-ethylxanthic acid, potassium salt. When hydrogen sulfide evolution had ceased, the solution was filtered, cooled and acidified with HCl. The initial precipitate was collected by filtration and discarded. The filtrate was allowed to stand to precipitate 13.79 gm (59% of theory) of desired product, with a melting point of 221°-222° C. The resulting 2-mercapto-5-trifluoromethylbenzothiazole (11.75 gm, 0.05 mol) was slurried in 50 ml of 95% ethanol, treated with 7.1 gm of triethylamine, and then refluxed 1 hour with 7.1 gm (0.05 mol) of iodomethane. The mixture was filtered hot, cooled, concentrated, and treated with water to precipitate 11.54 gm (93% of theoretical) of 2-methylthio-5-trifluoromethylbenzothiazole (melting point of 66° -69° C.). This compound (11.0 gm, 0.044 mol) was then heated to 130°-156° C. with 8.22 gm (0.044 mol) of methyl-p-toluenesulfonate for 5 minutes. After cooling, the resulting solid was washed and triturated with acetone to yield 15.05 gm (78% of theory) of 3-methyl-2-methylthio-5-trifluoromethyl-benzothiazolium p-toluenesulfonate with a melting point of 189°-191° C. This quaternary salt (4.35 gm, 0.01 mol) was dissolved with 1.91 gm (0.01 mol) of rhodanine-3-acetic acid in 20 ml of methanol. After 2.02 gm (0.02 mol) of triethylamine was added thereto, the mixture was stirred at room temperature for 4.5 hours before isolating the precipitated dye by filtration. After washing the filtered solid with methanol, 2.74 gm (54% of theoretical) of this dye was obtained. the solution was filtered cooled The initial precipitate was collected by filtration to precipitate 13.79 gm (59% of theory) of desired product The mixture was filtered hot cooled concentrated treated with water to precipitate 11.54 gm (93% of theoretical) of 2-methylthio-5-trifluoromethylbenzothiazole (melting point of 66° -69° C.) After cooling the resulting solid was washed triturated with acetone

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

Procedure: 5-Chloromethyl-8-methyl-2-oxo-4H-m-dioxino-[4,5-c]pyridine is converted to the corresponding ethyl xanthogenate and reduced in accordance with the procedure of Example 19, Step B, to give 5-mercaptomethyl-8-methyl-2-oxo-4H-m-dioxino[4,5-c]pyridine.

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

Procedure: 2-Methyl-3-ethoxycarbonyloxy-4-ethoxycarbonyloxymethyl-5-chloromethylpyridine is converted to the corresponding ethyl xanthogenate and reduced in accordance with the procedure of Example 19 Step B to give 2-methyl-3-ethoxycarbonyloxy-4-ethoxycarbonyloxymethyl-5-mercaptomethylpyridine.

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

Procedure: 2-Methyl-3-ethoxycarbonyloxy-4-ethoxycarbonyloxymethyl-5-chloromethylpyridine is converted to the corresponding ethyl xanthogenate and reduced in accordance with the procedure of Example 19 Step B to give 2-methyl-3-ethoxycarbonyloxy-4-ethoxycarbonyloxymethyl-5-mercaptomethylpyridine.

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Bromo-5-trifluoromethyl-phenylamine (4.0 mL, 28.3 mmoles) was dissolved into concentrated HCl (70 mL). This solution was chilled to 0° C. and to it was slowly added a solution of sodium nitrite (2.5 g, 36.2 mmoles) in 50 mL of water. After completion of the addition enough ethanol (90%) was added (25 mL) to affect nearly complete dissolution of the resultant mixture. The mixture was stirred at 0° C. for an additional 20 minutes. After this period the heterogeneous mixture was quickly transferred (cold) to an addition funnel. The diazonium mixture was added to a solution of O-ethylxanthic acid, potassium salt (5.7 g, 35.6 mmoles) in 50 mL of water at 60° C. The mixture was next heated to 90° C. and was stirred at this temperature for 2 hours. After this period the mixture was allowed to cool to ambient temperature, and the crude xanthate (a red liquid) was removed from the bottom of the aqueous mixture via pipette. The crude product taken up in 100 mL of diethyl ether and was washed with water (2×25 mL) and brine (20 mL). The ether layer was evaporated in vacuo to yield crude xanthate. The crude product was purified using flash silica chromatography (0-1% EtOAc/Hexane) to yield 4.7 g (51% yield) of dithiocarbonic acid S-(3-bromo-5-trifluoromethyl-phenyl) ester O-ethyl ester as a red liquid. 1H-NMR (CDCl3): δ 7.83 (d, J=5.8 Hz, 2H), 7.71 (s, 1H), 4.63 (q, J=7.1 Hz, 2H), 1.36 (t, J=7.1 Hz, 3H). After this period the heterogeneous mixture was quickly transferred The mixture was next heated to 90° C. was stirred at this temperature for 2 hours After this period the mixture was allowed to cool to ambient temperature the crude xanthate (a red liquid) was removed from the bottom of the aqueous mixture via pipette was washed with water (2×25 mL) and brine (20 mL) The ether layer was evaporated in vacuo to yield crude xanthate The crude product was purified

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

Procedure: Alternately, combine methyl 2-methoxy-5-aminobenzoate (1.0 g, 5.6 mmol) and 12 M aqueous hydrochloric acid solution (1.2 g and cool in an ice bath. Add a solution of sodium nitrite (0.37-g, 5.3 mmol) in water (3 mL). After 1.5 hours, add ethyl xanthic acid, sodium salt (0.76 g, 6.3 mmol) and sodium carbonate (0.67 g, 6.3 mmol). After 2 hours, evaporate in vacuo and add sodium sulfide (0.69 g, 2.7 mmol) and a 1 M aqueous sodium hydroxide solution (10 mL). After 4 hours, add dimethylsulfate and heat to reflux. After 24 hours, cool to ambient temperature, acidify with 12 M hydrochloric acid solution and extract with ethyl acetate. Separate the organic layer, extract with brine, dry over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with ethyl acetate/hexane 2/1 to give methyl 2-methoxy-5-methylthiobenzoate. Elemental Analysis calculated for C9H12O3S: C, 54.53; H, 5.08. Found: C, 54.64; H, 4.95. cool in an ice bath After 2 hours evaporate in vacuo After 4 hours heat to reflux After 24 hours extract with ethyl acetate Separate the organic layer extract with brine dry over Na2SO4 filter evaporate in vacuo to give a residue