Methyl 4-iodo-3-methylbenzoate

Uses

METHYL 4-IODO-3-METHYLBENZOATE is used in the synthesis of novel colchicine-derived nitrate esters

Uses

Methyl 4-iodo-3-methylbenzoate is used in the synthesis of novel colchicine-derived nitrate esters as immunosuppressant agents.

Synthesis

(a) 3-Methyl-4-iodobenzoic acid: 20 g (0.132 mol) of 3-methyl-4-aminobenzoic acid 175 ml of sulfuric acid (20%) was introduced into a three-necked flask. A solution of 11.9 g (0.172 mol) of sodium nitrite in 50 ml of water was added dropwise at -10C and the mixture was stirred for 2 hours. The solution was added dropwise to 35 g (0.211 mol) of potassium iodide 35.2 g (0.185 mol) of copper iodide and 175 ml of sulfuric acid (20%) by means of an ampoule frozen at -5C. The mixture was stirred for eight hours, the reaction medium was filtered, the solid obtained was dissolved in ethyl acetate, washed with water, then with sodium sulfite solution, dried with magnesium sulfate and evaporated. 24.4 g (70%) of 3-methyl-4-iodobenzoic acid with a melting point of 205-10 C was collected.

(b) Methyl 4-iodo-3-methylbenzoate: 24.4 g (0.093 mol) of 3-methyl-4-iodobenzoic acid 250 ml of methanol was introduced into a flask and 2.5 ml of concentrated sulfuric acid was added dropwise. The mixture was refluxed for twelve hours, the reaction medium was evaporated, the residue was dissolved in ethyl acetate and water, the organic phase was decanted, dried over magnesium sulfate and evaporated. The residue was ground in methanol, filtered, and 21.9 g (85%) of the expected methyl 4-iodo-3-methylbenzoate with a melting point of 58-9 C was collected.