IOXITALAMIC ACID

Chemical Properties

White Solid

Originator

Oxilan,Cook Imaging Corporation

Uses

A substituted 2,4,6-triiodobenzoic acid, an excellent contrast media for ventriculography, radiculography, lumbar myelography and x-rays of the cardiovascular system.

Definition

ChEBI: An organoiodine compound that is 2,4,6-triiodobenzoic acid substituted by an acetylamino group at position 3 and a (2-hydroxyethyl)carbamoyl group at position 5. It is used as a contrast medium.

Manufacturing Process

3-Methoxycarboxyl-5-nitrobenzoic acid (25 g) was hydrogenated in methanol (500 ml) using palladium oxide on charcoal (2.5 g 10%) at atmospheric pressure. When the exothermic reaction was completed the catalyst was fluttered off. After cooling the solution at -20°C for 2.5 h, 12.7 g of 3-amino- 5-methoxycarbonylbenzoic acid was isolated. An additional 6.5 g of it was isolated by concentrating the mother liquor.
The 3-amino-5-methoxycarbonylbenzoic acid (12.0 g) was suspended in water (280 ml), dissolved by addition of concentrated hydrochloric acid (7.1 ml) and glacial acetic acid (28.5 ml). At 60°-70°C NaICl2 solution (73 ml, 58.7 g ICl/100 ml) was added dropwise while stirring in the course of about 3 h. The reaction mixture was heated at 80°-90°C for additional 3 h while stirring.
After cooling to room temperature the mother liquor was decanted and the residue dissolved as ammonium salt in water (80 ml). The ammonium salt was precipitated by adding ammonium chloride (2.4 g) and cooling to 0°C. The ammonium salt was filtered off and dissolved in water (140 ml), charcoaled twice at 80°C and the acid was precipitated at room temperature by addition of hydrochloric acid and was filtered off. The crude product was dissolved in ethyl acetate (100 ml) and the solution was washed 3 times with hydrochloric acid (2 N). By evaporating the solvent, 19 g of 3-amino-5- methoxycarbonyl-2,4,6-triiodobenzoic acid was isolated. Melting point 170°- 176°C.
A mixture of 3-amino-5-methoxycarbonyl-2,4,6-triiodobenzoic acid (198 g) and thionyl chloride (400 ml) was heated while stirring at 70°C for 16 h. The solid material dissolved slowly. Thionyl chloride was evaporated in vacuo, the residue dissolved in chloroform (1000 ml), the solution washed with water (80 ml each), twice with saturated sodium bicarbonate, then 5 times with 2 N sodium hydroxide solution and finally with water to neutral. The solution was dried with CaCl2 filtered and evaporated to dryness. The 3-amino-5- methoxycarbonyl-2,4,6-triiodobenzoyl chloride was dried at 50°C in vacuo. Yield: 203.0 g. Melting point 55°-60°C.
To the 3-amino-5-methoxycarbonyl-2,4,6-triiodobenzoyl chloride (53.0 g) was added acetic anhydride (106 ml). After stirring at room temperature for 20 min then insoluble material was filtered off (3-4 g). To the filtrate was added concentrated sulfuric acid (0.3 ml) whereby a yellowish product started to precipitate. The temperature reached about 50°C. The 3-acetamido-5- methoxycarbonyl-2,4,6-triiodobenzoyl chloride was isolated after storing in refrigerator overnight. Yield: 39.0 g. Melting point 210°-215°C.
The 3-acetamido-5-methoxycarbonyl-2,4,6-triiodobenzoyl chloride was dissolved in a mixture of dioxan and dimethylformamide. In the course of 2 h this solution was added dropwise to a solution of ethanolamine and triethylamine in dioxan. The stirring was continued. A sticky precipitate was filtered off. The filtrate was evaporated to dryness in vacuo. The residue was triturated with aqueous sodium bicarbonate, filtered off and mixed with first fraction. The combined solids were then suspended in aqueous sodium bicarbonate filtered off washed with water and dried in vacuo to give methyl 5-acetamido-2,4,6-triiodo-(N-β-hydroxyethyl)-isophthalamate.
The methyl 5-acetamido-2,4,6-triiodo-(N-β-hydroxyethyl)-isophthalamate was mixed with fresh distilled ethanolamine and stirred. The excess ethanolamine was removed in vacuo at 50°-60°C. The residue was dissolved in water, and charcoaled at pH 5.5. The crude product was precipitated with hydrochloric acid (pH 0.5) and filtered after stirring at 0°C. 5-Acetamido-2,4,6-triiodo-(N- β-hydroxyethyl)isophthalamic acid was suspended in ethanol and dissolved by addition of concentrated ammonia. The ammonium salt started to precipitate in the course and was isolated after stirring. The salt was dissolved in water, filtered and the acid was precipitated with hydrochloric acid (pH 0.5). After stirring the product was filtered off and dried in vacuo.

Therapeutic Function

Diagnostic aid