2-(chloromethyl)-1,3,5-trimethylbenzene

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: To 60 ml DMF, was added 11-(piperidin-4-yl)-5H,11H-pyrrolo[2,1-c][1,4]benzoxazepine (5.0 g, 0.0186 mole), 2,4,6-trimethylbenzyl chloride (4.2 g, 0.025 mole), milled K2CO3 (15 g, 0.1 mole) and KI (0.01 g).

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of indole (1.185 g) in dry DMSO (3 ml) is dropped into a suspension of sodium hydride (60% mineral oil suspension; 0.44 g) in dry DMSO (10 ml). After two hours, the resulting solution is added with a solution of 2,4,6-trimethylbenzyl chloride (1.9 g) in dry DMSO (2 ml) heating at 60° C. for 6 h. The reaction mixture is kept at room temperature overnight, then poured into water (250 ml) extracted with ethyl acetate and dried (Na2SO4). The drying agent is filtered off, the solvent is evaporated off under reduced pressure and the resulting residue is purified by column chromatography (silica gel; eluent n-hexane/AcOEt 9/1) to obtain 2.2 g of 1-(2,4,6-trimethylbenzyl)indole. The reaction mixture is kept at room temperature overnight extracted with ethyl acetate dried (Na2SO4) The drying agent is filtered off the solvent is evaporated off under reduced pressure the resulting residue is purified by column chromatography (silica gel; eluent n-hexane/AcOEt 9/1)

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

Procedure: A mixture of 17 gms (0.05 mole) 2-mercaptopyridine N-oxide, sodium salt (40% aqueous solution) and 8.5 gms (0.05 mole) α2 chloroisodurene in 50 ml of ethanol is brought to reflux for 15 minutes. The volatiles are removed and the residue extracted with 150 ml of boiling chloroform, filtered and dried over sodium sulfate. Evaporation and trituration of the residue with a few drops of acetone induce crystallization. A yield of 11.5 gms of 2-(2,4,6-trimethylphenylmethylthio)pyridine N-oxide is obtained. Melting point 137° - 138° C. Structure confirmed by IR and NMR. to reflux for 15 minutes The volatiles are removed the residue extracted with 150 ml of boiling chloroform filtered dried over sodium sulfate Evaporation and trituration of the residue with a few drops of acetone crystallization

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

Procedure: 50 ml of a methanolic solution of 12.3 g (0.22 mole) of potassium hydroxide was added to 50 ml of an ice-cooled methanolic solution of 23.1 g (0.22 mole) of N-carboethoxyhydroxylamine to prepare a solution containing a potassium salt of N-carboethoxyhydroxylamine, and 50 ml of a methanolic solution of 33.7 g (0.2 mole) of 2,4,6-trimethylbenzyl chloride was added to the resulting solution at room temperature. The resulting mixture was heated under refluxing for 1 hour, and the solvent was distilled off. 150 ml of diethyl ether and 50 ml of water were then added to the residue and the organic layer was separated, dried over anhydrous sodium sulfate and concentrated under a reduced pressure. The residue thus obtained was distilled under a reduced pressure to obtain 25.5 g (53.8% yield) of substantially pure N-carboethoxy-O-(2,4,6-trimethylbenzyl)hydroxylamine having a boiling point of 148°-153° C/0.9 mmHg. to prepare a solution was added to the resulting solution at room temperature The resulting mixture was heated under refluxing for 1 hour the solvent was distilled off 150 ml of diethyl ether and 50 ml of water were then added to the residue the organic layer was separated dried over anhydrous sodium sulfate concentrated under a reduced pressure The residue thus obtained was distilled under a reduced pressure

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

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

Procedure: The procedure is as in Example 29 for the preparation of ethyl (4-methylbenzylthio)acetate, starting with 2,4,6-trimethylbenzyl chloride (10.25 g), a 2M ethanolic solution of sodium ethylate (32.5 cc) and ethyl 2-mercaptoacetate (7.1 g) in ethanol (150 cc). Ethyl (2,4,6-trimethylbenzylthio)acetate (11 g) is thereby obtained, and is used in the crude state in the subsequent syntheses.

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

Procedure: The procedure is as in Example 29 for the preparation of ethyl (4-methylbenzylthio)acetate, starting with 2,4,6-trimethylbenzyl chloride (10.25 g), a 2M ethanolic solution of sodium ethylate (32.5 cc) and ethyl 2-mercaptoacetate (7.1 g) in ethanol (150 cc). Ethyl (2,4,6-trimethylbenzylthio)acetate (11 g) is thereby obtained, and is used in the crude state in the subsequent syntheses.

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

Procedure: A mixture of 52.0 g (0.30 mole) of 3-aminobenzenesulfonic acid, 83.0 g (0.61 mole) of sodium acetate trihydrate, 33.7 g (0.20 mole) of 2,4,6-trimethylbenzyl chloride, 225 ml of water and 150 ml of acetonitrile was refluxed for 4 hrs, then acidified by the dropwise addition of 40 ml of conc. HCl over 30 minutes during which time approximately 100 ml of acetonitrile was distilled off. The resulting mixture was vacuum filtered while hot (80° C.) and a grayish-white powder obtained which was then slurried in 300 ml of hot (65° C.) water for 20 minutes and vacuum filtered. The slurrying process was repeated with water and then with 300 ml of boiling methanol for 20 minutes. Vacuum filtration followed by drying in vacuo at about 60° C. afforded 24.85 g (40.7% yield) of purified 3-(((2,4,6-trimethylphenyl)methyl)amino)benzenesulfonic acid as a white powder having a melting point greater than 275° C. was refluxed for 4 hrs was distilled off filtered while hot (80° C.) a grayish-white powder obtained which vacuum filtered Vacuum filtration by drying in vacuo at about 60° C.

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

Procedure: A mixture of 52.0 g (0.30 mole) of 3-aminobenzenesulfonic acid, 83.0 g (0.61 mole) of sodium acetate trihydrate, 33.7 g (0.20 mole) of 2,4,6-trimethylbenzyl chloride, 225 ml of water and 150 ml of acetonitrile was refluxed for 4 hrs, then acidified by the dropwise addition of 40 ml of conc. HCl over 30 minutes during which time approximately 100 ml of acetonitrile was distilled off. The resulting mixture was vacuum filtered while hot (80° C.) and a grayish-white powder obtained which was then slurried in 300 ml of hot (65° C.) water for 20 minutes and vacuum filtered. The slurrying process was repeated with water and then with 300 ml of boiling methanol for 20 minutes. Vacuum filtration followed by drying in vacuo at about 60° C. afforded 24.85 g (40.7% yield) of purified 3-(((2,4,6-trimethylphenyl)methyl)amino)benzenesulfonic acid as a white powder having a melting point greater than 275° C. was refluxed for 4 hrs was distilled off filtered while hot (80° C.) a grayish-white powder obtained which vacuum filtered Vacuum filtration by drying in vacuo at about 60° C.