96-83-3

Basic information

• Product Name: Iopanoic acid
• Synonyms: 3-amino-alpha-ethyl-2,4,6-triiodo-benzenepropanoicaci;3-amino-alpha-ethyl-2,4,6-triiodobenzenepropanoicacid;3-amino-alpha-ethyl-2,4,6-triiodo-hydrocinnamicaci;3-Amino-ethyl-2,4,6-triiodobenaenepropanoicacid;3-Amino-ethyl-2,4,6-triiodohydrocinnamicacid;beta-(3-amino-2,4,6-triiodophenyl)-alpha-ethylpropionicacid;bilijodon;choladine
• CAS NO: 96-83-3
• Molecular Formula: C₁₁H₁₂I₃NO₂
• Molecular Weight: 570.93
• EINECS: 202-539-9
• Product Categories: PREVACID
• Mol File: 96-83-3.mol
• Article Data: 0

Chemical Properties

• Melting Point: 153 °C
• Boiling Point: 529.058 °C at 760 mmHg
• Flash Point: 273.765 °C
• Appearance: /
• Density: 2.2567 (estimate)
• Vapor Pressure: 5.06E-12mmHg at 25°C
• Refractive Index: 1.732
• Storage Temp.: 2-8°C
• Solubility: DMSO, Methanol
• PKA: 4.8(at 25℃)
• Water Solubility: 348.3mg/L(37 oC)
• Merck: 14,5058
• CAS DataBase Reference: Iopanoic acid(CAS DataBase Reference)
• NIST Chemistry Reference: Iopanoic acid(96-83-3)
• EPA Substance Registry System: Iopanoic acid(96-83-3)

Safety Data

• Statements: 20/21/22
• Safety Statements: 22-26-36/37/39
• WGK Germany: 1
• RTECS: NW5075000
• Hazardous Substances Data: 96-83-3(Hazardous Substances Data)

Usage

Chemical Properties

Light Brown Solid

Originator

Telepaque,Winthrop,US,1952

Uses

Iodopanoic Acid is an iodine-containing radiocontrast medium used in cholecystography. Iodopanoic Acid is a potent inhibitor of thyroid hormone release from thyroid gland.

Manufacturing Process

(A) Preparation of α-Ethyl-m-Nitrocinnamic Acid: This acid is prepared from 100 g of m-nitrobenzaldehyde, 210 g of butyric anhydride and 73 g of sodium butyrate. The crude α-ethyl-m-nitrocinnamicacid is crystallized from ethanol giving about 105 g, MP 140° to 142°C. From the filtrates there may be isolated a small amount of a stereoisomer, which when pure melts at 105° to 106°C.(B) Preparation of m-Amino-α-Ethylhydrocinnamic Acid: A mixture of 50 g of α-ethyl-m-nitrocinnamic acid, 9.1 g of sodium hydroxide, 600 cc of water and 5 teaspoons of Raney nickel catalyst is shaken at 32°C in an atmosphere ofhydrogen at an initial pressure of 450 psi until the calculated amount of hydrogen is absorbed. The filtered solution is acidified with hydrochloric acid, made basic with ammonium hydroxide and again acidified with acetic acid. Upon concentration of this solution, an oil separates which crystallizes upon standing, giving about 20 g, MP 60° to 68°C. Complete evaporation of the filtrate and extraction of the residue of inorganic salts with ether gives about 20 g of additional material, MP 54° to 59°C. Recrystallization of the combined product from benzene petroleum ether gives about 35 g of m-amino-α- ethylhydrocinnamic acid, MP 67° to 70°C.(C) Preparation of β-(3-Amino-2,4,6-Triiodophenyll-α-Ethylpropionic Acid: A solution of 5.0 g of m-amino-α-ethylhydrocinnamic acid in 100 cc of water containing 5 cc of concentrated hydrochloric acid is added over a period of ? hour to a stirred solution of 3.2 cc of iodine monochloride in 25 cc of water and 25 cc of concentrated hydrochloric acid heated to 60°C. After addition is complete, the heating is continued for one hour longer at 60° to 70°C. A black oil separates which gradually solidifies.The mixture is then cooled and sodium bisulfite added to decolorize. Recrystallization of the product from methanol gives about 8 g, MP 147° to 150°C. The β-(3-amino-2,4,6-triiodophenyl)-α-ethylpropionic acid may be purified further by precipitation of the morpholine salt from ether solution and regeneration of the free amino acid by treatment of a methanol solution of the morpholine salt with sulfur dioxide. The pure amino acid has the MP 155° to 156.5°C.

Therapeutic Function

Diagnostic aid (radiopaque medium)

InChI:InChI=1/C11H12I3NO2/c1-2-5(11(16)17)3-6-7(12)4-8(13)10(15)9(6)14/h4-5H,2-3,15H2,1H3,(H,16,17)

Synthetic route

2-(3-amino-benzyl)-butyric acid (16623-25-9) → iopanoic acid (96-83-3)

Conditions	Yield
With hydrogenchloride; Iodine monochloride

2-(3-Nitro-benzyliden)-buttersaeure (5253-02-1) → iopanoic acid (96-83-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: Raney nickel; sodium hydroxide; diethyl ether / Hydrogenation 2: iodine monochloride; aqueous hydrochloric acid View Scheme

dehydroepiandrosterone (53-43-0) + iopanoic acid (96-83-3) → dehydroepiandrosterone iopanoate (83172-20-7)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane Ambient temperature;	98%

iopanoic acid (96-83-3) + chloroacetyl chloride (79-04-9) → 3-<(chloroacetyl)amino>-α-ethyl-2,4,6-triiodobenzenepropanoic acid (80980-80-9)

Conditions	Yield
With ISOPROPYLAMIDE for 0.5h; Ambient temperature;	95%
With hydrogenchloride; sodium hydroxide In water; 2,4-dichlorophenoxyacetic acid dimethylamine	95.3%

cholesterol (57-88-5) + iopanoic acid (96-83-3) → cholesteryl iopanoate (83172-18-3)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane Ambient temperature;	95%
With sodium hydride; 1,1'-carbonyldiimidazole 1) THF, reflux, 10 min; 2) THF, room temperature, 1 h; Yield given. Multistep reaction;

Pregnenolone (145-13-1) + iopanoic acid (96-83-3) → pregnenolone iopanoate (83172-19-4)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane Ambient temperature;	93%

1,3-dihydroxyacetone dimer (62147-49-3) + iopanoic acid (96-83-3) → 1,3-dihydroxypropan-2-one 1,3-diiopanoate (103959-66-6)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane for 66h;	85%

ethanol (64-17-5) + iopanoic acid (96-83-3) → (+/-)-iopanoic acid ethyl ester (100850-30-4)

Conditions	Yield
With thionyl chloride for 3h; Heating;	82.4%

oxalyl dichloride (79-37-8) + 6-<(chloroacetyl)amino>hexanoic acid (61435-75-4) + iopanoic acid (96-83-3) → 3-<<6-<(chloroacetyl)amino>-1-oxohexyl>amino>-α-ethyl-2,4,6-triiodobenzenepropanoic acid (160982-41-2)

Conditions	Yield
With pyridine; hydrogenchloride In tetrahydrofuran; dichloromethane; water; N,N-dimethyl-formamide; acetonitrile	79%

iopanoic acid (96-83-3) + 1-palmitoyl-3-O-trityl-rac-glycerol (69256-58-2) → 1-palmitoyl-2-iopanoyl-3-O-trityl-rac-glycerol

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane Ambient temperature;	60%

2-Oleoylglycerol (3443-84-3, 13822-11-2, 116435-34-8) + iopanoic acid (96-83-3) → 2-oleoylglycerol 1,3-bis

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane for 72h; Ambient temperature;	53%

rac-1-monopalmitoylglycerol (305847-08-9) + iopanoic acid (96-83-3) → 1-palmitoyl-3-iopanoyl-rac-glycerol

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane	49%

iopanoic acid (96-83-3) + glyceryl 1,3-diiopanoate (103980-81-0) → glyceryl 1,2,3-triiopanoate (103959-76-8)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane Ambient temperature;	34%

4-morpholinecarboxaldehyde (4394-85-8) + iopanoic acid (96-83-3) → 2-(2,4,6-triiodo-3-morpholin-4-ylmethyleneamino-benzyl)-butyric acid (101286-38-8)

Conditions	Yield
With trichlorophosphate

iopanoic acid (96-83-3) → ω-(2,4,6-triiodophenyl)-α-ethyl-propionic acid (51374-95-9)

Conditions	Yield
With sulfuric acid; copper; sodium nitrite 1) glac. AcOH, 12 deg C, 45 min, 2) glac. AcOH, MeOH, 20 deg C, 30 min.; Yield given. Multistep reaction;

6-<(chloroacetyl)amino>hexanoic acid (61435-75-4) + iopanoic acid (96-83-3) → 3-<<6-<(chloroacetyl)amino>-1-oxohexyl>amino>-α-ethyl-2,4,6-triiodobenzenepropanoic acid (160982-41-2)

Conditions	Yield
With pyridine; oxalyl dichloride 1.) DMF, CH2Cl2, 5 deg C, 1 h, 2.) THF, CH3CN, 5 deg C, then 40 deg C, 2 h, 3.) THF, reflux, 3 h; Yield given. Multistep reaction;

iopanoic acid (96-83-3) → 3-<<6-<<<2-<(2-aminoethyl)amino>ethyl>amino>acetylamino>-1-oxoethyl>amino>-α-ethyl-2,4,6-triiodobenzenepropanoic acid (160982-42-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) oxalyl dichloride, 2.) pyridine / 1.) DMF, CH2Cl2, 5 deg C, 1 h, 2.) THF, CH3CN, 5 deg C, then 40 deg C, 2 h, 3.) THF, reflux, 3 h 2: 48 percent / 6 h / 50 °C View Scheme

iopanoic acid (96-83-3) → α-ethyl-2,4,6-triiodo-3-<<1-oxo-6-<<(1,4,7,10-tetraazacyclododec-1-yl)acetyl>amino>hexyl>amino>benzenepropanoic acid (175732-28-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) oxalyl dichloride, 2.) pyridine / 1.) DMF, CH2Cl2, 5 deg C, 1 h, 2.) THF, CH3CN, 5 deg C, then 40 deg C, 2 h, 3.) THF, reflux, 3 h 2: 59 percent / dimethylacetamide / 0.5 h / 70 °C View Scheme

iopanoic acid (96-83-3) → 3-<<<2-<(2-aminoethyl)amino>ethyl>amino>acetylamino>-α-ethyl-2,4,6-triiodobenzenepropanoic acid

Conditions	Yield
Multi-step reaction with 2 steps 1: 95 percent / dimethylacetamide / 0.5 h / Ambient temperature 2: 57 percent / 2.) conc. HCl / 3 h / 50 °C View Scheme

iopanoic acid (96-83-3) → 10-<2-<<3-(2-carboxybutyl)-2,4,6-triiodophenyl>amino>-2-oxoethyl>-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid

Conditions	Yield
Multi-step reaction with 3 steps 1: 95 percent / dimethylacetamide / 0.5 h / Ambient temperature 2: 60 percent / 1.) dimethylacetamide, 2.) HCl / 1.5 h / 60 °C 3: 13 percent / 2N NaOH / H2O / 20 h / 50 °C / pH = 10 View Scheme

iopanoic acid (96-83-3) → 3-<<<<2-<<2-ethyl>(carboxymethyl)amino>ethyl>(carboxymethyl)amino>acetyl>amino>-α-ethyl-2,4,6-triiodobenzenepropanoic acid

Conditions	Yield
Multi-step reaction with 3 steps 1: 95 percent / dimethylacetamide / 0.5 h / Ambient temperature 2: 57 percent / 2.) conc. HCl / 3 h / 50 °C 3: 33 percent / 10N NaOH / H2O / 20 h / Ambient temperature; pH = 10 View Scheme

iopanoic acid (96-83-3) → α-ethyl-2,4,6-triiodo-3-<<(1,4,7,10-tetraazacyclododec-1-yl)acetyl>amino>benzenepropanoic acid trishydrochloride

Conditions	Yield
Multi-step reaction with 2 steps 1: 95 percent / dimethylacetamide / 0.5 h / Ambient temperature 2: 60 percent / 1.) dimethylacetamide, 2.) HCl / 1.5 h / 60 °C View Scheme

iopanoic acid (96-83-3) → 10-<2-<<6-<<3-(2-carboxybutyl)-2,4,6-triiodophenyl>amino>-6-oxohexyl>amino>-2-oxoethyl>-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) oxalyl dichloride, 2.) pyridine / 1.) DMF, CH2Cl2, 5 deg C, 1 h, 2.) THF, CH3CN, 5 deg C, then 40 deg C, 2 h, 3.) THF, reflux, 3 h 2: 59 percent / dimethylacetamide / 0.5 h / 70 °C 3: 48 percent / 10N NaOH / H2O; ethanol / 18 h / Ambient temperature; pH = 9 View Scheme

iopanoic acid (96-83-3) → 18-<<3-(2-carboxybutyl)-2,4,6-triiodophenyl>amino>-3,6,9-tris(carboxymethyl)-11,18-dioxo-3,6,9,12-tetraazaoctadecanoic acid

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) oxalyl dichloride, 2.) pyridine / 1.) DMF, CH2Cl2, 5 deg C, 1 h, 2.) THF, CH3CN, 5 deg C, then 40 deg C, 2 h, 3.) THF, reflux, 3 h 2: 48 percent / 6 h / 50 °C 3: 41 percent / 10N NaOH / H2O / 3 h / 50 °C / pH = 10 View Scheme

iopanoic acid (96-83-3) → 1-palmitoyl-2-iopanoyl-rac-glycerol

Conditions	Yield
Multi-step reaction with 2 steps 1: 60 percent / 4-(dimethylamino)pyridine, dicyclohexylcarbodiimide / CH2Cl2 / Ambient temperature 2: 97 percent / 10 percent H3BO3/ silica gel / petroleum ether; diethyl ether View Scheme

iopanoic acid (96-83-3) → pregnenolone<ω-(2,4,6-triiodophenyl)-α-ethyl>-propionate

Conditions	Yield
Multi-step reaction with 2 steps 1: 1) NaNO2, conc. H2SO4, 2) Cu powder / 1) glac. AcOH, 12 deg C, 45 min, 2) glac. AcOH, MeOH, 20 deg C, 30 min. 2: 79 percent / dicyclohexylcarbodiimide, 4-dimethylaminopyridine / CH2Cl2 / 24 h / Ambient temperature View Scheme

iopanoic acid (96-83-3) → cholesteryl<ω-(2,4,6-triiodophenyl)-α-ethyl>-propionate

Conditions	Yield
Multi-step reaction with 2 steps 1: 1) NaNO2, conc. H2SO4, 2) Cu powder / 1) glac. AcOH, 12 deg C, 45 min, 2) glac. AcOH, MeOH, 20 deg C, 30 min. 2: 75 percent / dicyclohexylcarbodiimide, 4-dimethylaminopyridine / CH2Cl2 / 24 h / Ambient temperature View Scheme

iopanoic acid (96-83-3) → glyceryl 1,3-diiopanoate (103980-81-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / 4-dimethylaminopyridine (DMAP), 1,3-dicyclohexylcarbodiimide (DCC) / CH2Cl2 / 66 h 2: 75 percent / NaBH4 / tetrahydrofuran; benzene; H2O / 0.5 h / 5 °C View Scheme

iopanoic acid (96-83-3) → 2-palmitoylglycerol 1,3-diiopanoate (103959-73-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: 85 percent / 4-dimethylaminopyridine (DMAP), 1,3-dicyclohexylcarbodiimide (DCC) / CH2Cl2 / 66 h 2: 75 percent / NaBH4 / tetrahydrofuran; benzene; H2O / 0.5 h / 5 °C 3: 75 percent / 4-dimethylaminopyridine (DMAP), 1,3-dicyclohexylcarbodiimide (DCC) / CH2Cl2 / 66 h View Scheme

iopanoic acid (96-83-3) → glyceryl 1,2,3-triiopanoate (103959-76-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 85 percent / 4-dimethylaminopyridine (DMAP), 1,3-dicyclohexylcarbodiimide (DCC) / CH2Cl2 / 66 h 2: 75 percent / NaBH4 / tetrahydrofuran; benzene; H2O / 0.5 h / 5 °C 3: 34 percent / 4-dimethylaminopyridine (DMAP), 1,3-dicyclohexylcarbodiimide (DCC) / CH2Cl2 / Ambient temperature View Scheme

Upstream product

• 5253-02-1 2-(3-Nitro-benzyliden)-buttersaeure 
• 16623-25-9 2-(3-amino-benzyl)-butyric acid 

Downstream Products

• 101286-38-8 2-(2,4,6-triiodo-3-morpholin-4-ylmethyleneamino-benzyl)-butyric acid 
• 100850-30-4 (+/-)-iopanoic acid ethyl ester 
• 83172-20-7 dehydroepiandrosterone iopanoate 
• 83172-19-4 pregnenolone iopanoate 
• 103959-76-8 glyceryl 1,2,3-triiopanoate 
• 51374-95-9 ω-(2,4,6-triiodophenyl)-α-ethyl-propionic acid 
• 160982-41-2 3-<<6-<(chloroacetyl)amino>-1-oxohexyl>amino>-α-ethyl-2,4,6-triiodobenzenepropanoic acid 
• 80980-80-9 3-<(chloroacetyl)amino>-α-ethyl-2,4,6-triiodobenzenepropanoic acid 
• 51374-99-3 2-(3-acetamido-2,4,6-triiodobenzyl)butanoic acid 
• 83172-18-3 cholesteryl iopanoate 
• 103959-66-6 1,3-dihydroxypropan-2-one 1,3-diiopanoate 
• 103959-73-5 2-palmitoylglycerol 1,3-diiopanoate 
• 103980-81-0 glyceryl 1,3-diiopanoate 
• 175732-28-2 α-ethyl-2,4,6-triiodo-3-<<1-oxo-6-<<(1,4,7,10-tetraazacyclododec-1-yl)acetyl>amino>hexyl>amino>benzenepropanoic acid