| Identification | Back Directory | [Name]
sodium 3-(acetylamino)-2,4,6-triiodo-5-[(methylamino)carbonyl]benzoate | [CAS]
1225-20-3 | [Synonyms]
D03603
Conray-400
Angio-Conray
Mediocontrix
Angio-Contrix
Conray 400 (tn)
SODIUMIOTHALAMATE
Iothalamate sodium
Iothalamic acid sodium
Iothalamate sodium (usp)
Sodium Iotalamate Injection
iothalamic acid sodium salt
Sodium Iotalamate USP/EP/BP
Sodium Iothalamate Labeled d3
Sodium iotalamate injection (jp15)
Sodium 3-acetamido-2,4,6-triiodo-5-(methylcarbamoyl)benzoate
sodium 3-(acetylamino)-2,4,6-triiodo-5-[(methylamino)carbonyl]benzoate
Benzoic acid, 3-(acetylamino)-2,4,6-triiodo- 5-[(methylamino)carbonyl]-, monosodium salt | [EINECS(EC#)]
214-955-8 | [Molecular Formula]
C11H8I3N2NaO4 | [MDL Number]
MFCD01717604 | [MOL File]
1225-20-3.mol | [Molecular Weight]
635.895 |
| Hazard Information | Back Directory | [Originator]
Angio-Conray,Mallinckrodt Inc.,USA | [Uses]
Diagnostic aid (radiopaque medium). | [Manufacturing Process]
Normal aqueous sodium hydroxide (0.02 eq) was added at room temperature
with rapid swirling to a solution of 5-nitroisophthalic acid, dimethyl ester, (4.8
g, 0.02 mole) in acetone-methanol (100 ml each). The clear solution
immediately assumed a deep red-purple color which gradually lightened to a
brown color over a 25-minute period. On standing overnight the solution
lightened in color to a pale pink.
The solvent was evaporated, and the residue extracted with warm water (50
ml). The residue of unsaponified diester (0.23 g), 4.2%; m.p. 115°-117°C
was filtered off, and the filtrate was acidified toprecipitate the crude
monomethyl ester of 5-nitroisoftalic acid. Yield 3.4 g (75%). M.p. 170.5°-
175.5°C.
The preparation was repeated on a larger scale with certain variations.
Methanolic potassium hydroxide was substituted for the aqueous sodium
hydroxide, and acetone was used as the solvent for the 5-nitroisophthalic
acid, dimethyl ester. Yield, 78%. M.P. 175°-179°C (corrected).
Crude 5-nitroisophthalic acid, monomethyl ester (46.3 g, 0.21 mole) was
dissolved in 35% aqueous methylamine solution (500 ml). On standing, the
orange solution became blood red. The reaction mixture was evaporated
overnight on the steam bath, the cool residue was treated with 50 ml of water
and the solution was acidified with hydrochloric acid. A yellow precipitate of
crude N-methyl-5-nitroisophthalamic acid was separated and dried (yield 41.5
g). This acid was redissolved in dilute ammonia solution and the resulting
solution (pH 5.2) was treated with charcoal. Acidification of the treated
solution yield a pale yellow product of neutral equivalent 213. A small portion
(10 g) was recrystaliized from 1:1 water-ethanol (300 ml) to yield orange Nmethyl-5-nitroisophthalamic acid. M.p. 251°-252.5°C.
Crude N-methyl-5-nitrosophthalamic acid (11.2 g, 0.05 mole) was reduced
with hydrogen in a low pressure hydrogenator. The solvent was anhydrous
methanol (250 ml) and the catalyst was 5% palladium on charcoal slurried in
10 ml of water. After the theoretical quantity of hydrogen for reduction of the
nitro group had been absorbed the solution was filtered to remove the catalyst
and the solvent was evaporated under reduced pressure, leaving a white
residue of crude 5-amino-N-methylisophthaIamic acid. M.p. 227°-230°C
(corrected).
The crude 5-amino-N-methylisophthalamic acid was dissolved in hydrochloric
acid (100 ml concentrated acid and 100 ml of water) and this solution was
diluted to 1 liter with water. Iodine monochloride (27.4 g of 95% ICI, 0.16
mole) in concentrated hydrochloric acid (30 ml) was added in one portion to
the stirred solution maintained at 54°C. The solution was heated on a steam
bath. After 2 hours the solution was diluted to 1.5 liters and after 3 hours
titration of an aliquot indicated that 50% of the iodine monochloride had been
consumed. Precipitation of a solid began after 33/4 hours of reaction (75°C).
Intermittent heating and stirring was continued for 4 days, 10 g of 95% iodine
monochloride was added during the third day. After 4 days, titration of an
aliquot indicated that 96% of the theoretical quantity of iodine monochloride
had been consumed. The precipitated solid was filtered off, washed with water
and dried at 75°C under reduced pressure. Yield of 5-amino-2,4,6-triiodo-N-methylisophthalamic acid 20.6 g. M.p. 266-268°C (dec.)
1.95 molar KICl2 a solution (1144 ml, 2.22 moles) was added during 0.5 hour
to a stirred suspension of 5-amino-N-methylisophthalamic acid (196 g, 1.01
moles) in 2.5 liters of water. After three hours of additional stirring, a solution
of sodium hydroxide (88 g, 2.2 moles of NaOH in 200 ml of water) was
added. Then, additional 1.95 molar KICl2 solution (522 ml, 1.01 mole) was
added during 0.5 hour. The reaction mixture was stirred overnight after which
the crude product was collected and purified by conversion first to the
ammonium salt, then to the free acid. Yield of 5-amino-2,4,6-triiodo-Nmethylisophthalamic acid, 310 g (53.6%).
Acetyl chloride (17 ml, 0.24 mole) was added in portions during 10 minutes to
a stirred slurry of 5-amino-2,4,6-triiodo-N-methylisophthalamic acid (57.2 g,
0.1 mole) in dimethylacetamide (120 ml). Solution occurred in 0.5-1 hour and
after a total of 1.5 hours 20 ml of water was added and the reaction mixture
was evaporated to a thick slurry. The product was purified by twice dissolving
it as a sodium salt and precipitating the free acid by the addition of mineral
acid. The resulting nearly colorless 5-acetamido-2,4,6-triiodo-Nmethylisophthalamic acid decomposed at about 285°C but did not melt below
300°C. Yield, 47 g (76.5%).
5-Acetamido-2,4,6-triiodo-N-methylisophthalamic acid was slurried in water
and dissolved by the addition of an equivalent quantity of sodium hydroxide.
The solution was evaporated to dryness to yield the sodium salt of 5-
acetamido-2,4,6-triiodo-N-methylisophthalamic acid. Its solubility in water at
25°C is approximately 85 g per 100 ml of solution. The acute intravenous
LD50 of this salt in male albino mice is approximately 19.2 g/kg. | [Brand name]
Conray (Mallinckrodt). | [Therapeutic Function]
Diagnostic aid |
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