31127-80-7

Basic information

• Product Name: 5-(Acetamido)-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide
• Synonyms: 5-Acetamino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide;5-Acetamino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-;Iohexol Related Compound A (100 mg) (5-(acetylamino)-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide);5-AcetaMido-N1,N3-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalaMide;Iohexol Related CoMpound A;5-(acetaMido)-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzendicarboxaMide;1,3-BenzenedicarboxaMide,5-(acetylaMino)-N1,N3-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-;Iodixanol Impurity B
• CAS NO: 31127-80-7
• Molecular Formula: C₁₆H₂₀I₃N₃O₇
• Molecular Weight: 747.06
• EINECS: 445-830-8
• Product Categories: Intermediate of Iodixanol;Amines;Aromatics
• Mol File: 31127-80-7.mol
• Article Data: 22

Chemical Properties

• Melting Point: 274-276°C
• Boiling Point: 746.085 °C at 760 mmHg
• Flash Point: 405.018 °C
• Appearance: white to off-white solid
• Density: 2.29 g/cm³
• Storage Temp.: Refrigerator
• Solubility: DMSO (Sparingly, Heated), Methanol (Slightly, Heated)
• PKA: 11.45±0.46(Predicted)
• Stability: Hygroscopic
• CAS DataBase Reference: 5-(Acetamido)-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide(CAS DataBase Reference)
• NIST Chemistry Reference: 5-(Acetamido)-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide(31127-80-7)
• EPA Substance Registry System: 5-(Acetamido)-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide(31127-80-7)

Safety Data

• Hazardous Substances Data: 31127-80-7(Hazardous Substances Data)

Usage

Chemical Properties

Whitye To Off-White Solid

Uses

5-(Acetamido)-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide can be used as an intermediate used in the synthesis of imaging agents such as Iohexol (I729500).

Synthetic route

5-acetamido-2,4,6-triiodo-1,3-phthalamide + epichlorohydrin (106-89-8) → N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide (31127-80-7)

Conditions	Yield
Stage #1: 5-acetamido-2,4,6-triiodo-1,3-phthalamide; epichlorohydrin With 1-hexyl-3-methylimidazolium hexafluorophosphate at 80℃; for 3h; Stage #2: With water at 30℃; for 5h; Reagent/catalyst; Temperature;	97%

5-acetamido-2,4,6-triiodoisophthaloyl dichloride (31122-75-5) + 5-(acetylamino)-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide sodium salt + 3-Amino-1,2-propanediol (616-30-8, 13552-31-3) → N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide (31127-80-7)

Conditions	Yield
With hydrogenchloride In methanol; water; 2,4-dichlorophenoxyacetic acid dimethylamine	92%

iohexol (66108-95-0) + 3-monochloro-1,2-propanediol (96-24-2) → N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide (31127-80-7)

Conditions	Yield
With lithium hydroxide In methanol	92%

5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9) + acetic anhydride (108-24-7) → N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide (31127-80-7) + 3-(3-acetamido-5-((2,2-dimethyl-1,3-dioxolan-4-yl)methylcarbamoyl)-2,4,6-triiodobenzamido)-propane-1,2-diyl diacetate + 5-acetamido-N,N′-bis-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl-2,4,6-triiodoisophthaldiamide + 3-acetamido-N-(2,3-dihydroxypropyl)-5-(5-hydroxymethyl-2,2-dimethyloxazolidine-3-carbonyl)-2,4,6-triiodobenzamide + 3-acetamido-N-(2,3-dihydroxypropyl)-5-(5-hydroxymethyl-2,2-dimethyloxazolidine-3-carbonyl)-2,4,6-triiodobenzamide

Conditions	Yield
Stage #1: 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide; acetic anhydride With toluene-4-sulfonic acid In acetone for 0.25h; Reflux; Stage #2: With sodium hydroxide In water; acetone	A 70% B 32% C 17% D n/a E n/a

5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9) + acetic anhydride (108-24-7) → N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide (31127-80-7) + 3-acetamido-N-(2,3-dihydroxypropyl)-5-(5-hydroxymethyl-2,2-dimethyloxazolidine-3-carbonyl)-2,4,6-triiodobenzamide + 3-acetamido-N-(2,3-dihydroxypropyl)-5-(5-hydroxymethyl-2,2-dimethyloxazolidine-3-carbonyl)-2,4,6-triiodobenzamide

Conditions	Yield
Stage #1: 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide; acetic anhydride With toluene-4-sulfonic acid In acetone for 0.25h; Reflux; Stage #2: With sodium hydroxide In water; acetone Stage #3: With sulfuric acid In water; acetone pH=0;	A 70% B n/a C n/a

5-Amino-N,N'-bis[2,3-dihydroxypropyl]-1,3-benzenedicarboxamide (76820-35-4) → N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide (31127-80-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: Iodine monochloride / 6 h / 50 °C 2: sulfuric acid / water / 50 - 100 °C 3: sodium hydroxide; water / 20 °C / pH 9 - 11 View Scheme

5-nitro-N,N'-bis-(2,3-dihydroxypropyl)isophthalamide (76820-34-3) → N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide (31127-80-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: 5%-palladium/activated carbon; hydrogen / 70 °C / 9000.9 Torr / Autoclave 2: Iodine monochloride / 6 h / 50 °C 3: sulfuric acid / water / 50 - 100 °C 4: sodium hydroxide; water / 20 °C / pH 9 - 11 View Scheme

dimethyl 5-nitroisophthalate (13290-96-5) → N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide (31127-80-7)

Conditions	Yield
Multi-step reaction with 5 steps 1: sodium methylate / methanol / 20 - 50 °C 2: 5%-palladium/activated carbon; hydrogen / 70 °C / 9000.9 Torr / Autoclave 3: Iodine monochloride / 6 h / 50 °C 4: sulfuric acid / water / 50 - 100 °C 5: sodium hydroxide; water / 20 °C / pH 9 - 11 View Scheme

N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide (31127-80-7) + epichlorohydrin (106-89-8) → iohexol (66108-95-0) + iodixanol (92339-11-2)

Conditions	Yield
With hydrogenchloride; boric acid; potassium hydroxide In water pH=10 - 11; Product distribution / selectivity; Industry scale;	A 7.5% B 86.3%
Stage #1: N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide With sodium hydroxide In methanol at 45℃; Stage #2: epichlorohydrin With hydrogenchloride In methanol at 20℃; for 48h; Product distribution / selectivity;	A 7.42% B 52.1%
With hydrogenchloride; sodium hydroxide In water at 20℃; for 48h; pH=12.2 - 12.7;	A 5.1% B 43.5%

1-azido-2,3-epoxypropane (80044-09-3) + N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide (31127-80-7) → C19H25I3N6O8 (1309926-44-0)

Conditions	Yield
With boric acid; sodium hydroxide In methanol; water at 40℃; for 6h;	70%

N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide (31127-80-7) + epichlorohydrin (106-89-8) → iodixanol (92339-11-2)

Conditions	Yield
With hydrogenchloride; sodium hydroxide In 2-methoxy-ethanol; water at 20℃; for 192h; Product distribution / selectivity;	69.1%
Stage #1: N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide With sodium hydroxide In 1-methoxy-2-propanol; water at 15 - 55℃; Stage #2: epichlorohydrin With hydrogenchloride In 1-methoxy-2-propanol at 15℃; Product distribution / selectivity;	59.4%
Stage #1: N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide With sodium hydroxide In methanol at 45℃; Stage #2: epichlorohydrin With hydrogenchloride In methanol at 10℃; for 48h;	46.8%

3-chloro-2-hydroxy-1-propyl acetate (24573-30-6) + N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide (31127-80-7) → 3-(N-(2,5-bis((2,3-dihydroxypropyl)carbamoyl)-2,4,6-triiodophenyl)acetamido)--2-hydrooxypropylacetate

Conditions	Yield
With sodium methylate In N,N-dimethyl acetamide at 20℃; for 18h; pH=11.5 - 12; pH-value; Reagent/catalyst; Solvent; Temperature;	63%

N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide (31127-80-7) + tert-butyl N-(2-oxiranylmethyl)carbamate (148982-76-7, 149057-20-5, 115198-80-6) → 5-[Acetyl-(3-amino-2-hydroxy-propyl)-amino]-N,N'-bis-(2,3-dihydroxy-propyl)-2,4,6-triiodo-isophthalamide (1150307-23-5)

Conditions	Yield
Stage #1: N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide With potassium hydroxide In water; tert-butyl alcohol at 40℃; Stage #2: With boric acid In water; tert-butyl alcohol Stage #3: tert-butyl N-(2-oxiranylmethyl)carbamate With hydrogenchloride; potassium hydroxide more than 3 stages;	19%
With hydrogenchloride; potassium hydroxide; boric acid In water; tert-butyl alcohol	19%

2-chloromethyl-2-methyloxiran (598-09-4) + N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide (31127-80-7) → 5,5'-(2-hydroxy-2-methylpropane-1,3-diyl)bis(acetylazanediyl)bis(N1,N3-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide) (1186057-94-2)

Conditions	Yield
Stage #1: 2-chloromethyl-2-methyloxiran; N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide With boric acid; potassium hydroxide In methanol; water at 20℃; pH=12.6 - 13; Stage #2: With hydrogenchloride In methanol; water pH=4;	3%

1-chloro-3-methoxypropan-2-ol (4151-97-7) + N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide (31127-80-7) → N,N'-bis(2,3-dihydroxypropyl)-5-[N-(2-hydroxy-3-methoxypropyl)acetamido]-2,4,6-triiodoisophthalamide + 5-[Acetyl-(2-hydroxy-3-methoxy-propyl)-amino]-N,N'-bis-(2,3-dihydroxy-propyl)-N-(2-hydroxy-3-methoxy-propyl)-2,4,6-triiodo-isophthalamide + 5-[Acetyl-(2-hydroxy-3-methoxy-propyl)-amino]-N-(2,3-dihydroxy-propyl)-N'-[3-hydroxy-2-(2-hydroxy-3-methoxy-propoxy)-propyl]-2,4,6-triiodo-isophthalamide + 5-[Acetyl-(2-hydroxy-3-methoxy-propyl)-amino]-N-(2,3-dihydroxy-propyl)-N'-[2-hydroxy-3-(2-hydroxy-3-methoxy-propoxy)-propyl]-2,4,6-triiodo-isophthalamide

Conditions	Yield
With sodium hydroxide; calcium chloride multistep reaction; cationic influence on the N/O alkylation selectivity; various metals chloride; var. concentr., var. reaction times and temperatures;	A 83.85 % Chromat. B n/a C n/a D n/a

N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide (31127-80-7) + 5--N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (171897-76-0) → 5,5'-(N-acetyl-2-hydroxypropane-1,3-diyldiamino)bis

Conditions	Yield
In water for 48h; Ambient temperature; pH=12.0;

N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide (31127-80-7) + 3-monochloro-1,2-propanediol (96-24-2) + butan-1-ol (71-36-3) → iohexol (66108-95-0)

Conditions	Yield
With sodium hydroxide; Ca(OH)2 In water
With sodium hydroxide; Ca(OH)2 In water

N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide (31127-80-7) → iohexol (66108-95-0)

N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide (31127-80-7) + oxiranyl-methanol (556-52-5) → iohexol (66108-95-0)

Conditions	Yield
With potassium hydroxide In methanol; dimethyl sulfoxide; isopropyl alcohol
Stage #1: N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide With boric acid; potassium hydroxide In water at 10℃; for 48h; pH=12.4; Stage #2: oxiranyl-methanol In water at 10℃; for 24h; pH=12.6-13; Time; pH-value;

N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide (31127-80-7) + 3-monochloro-1,2-propanediol (96-24-2) → iohexol (66108-95-0)

Conditions	Yield
With sodium methylate In propylene glycol
Stage #1: N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide With sodium hydroxide In methanol; 1-methoxy-2-propanol at 25 - 45℃; Stage #2: 3-monochloro-1,2-propanediol In methanol; 1-methoxy-2-propanol at 25℃; for 25.5h; Product distribution / selectivity;
Stage #1: N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide With sodium hydroxide In 1-methoxy-2-propanol; water at 25 - 45℃; Stage #2: 3-monochloro-1,2-propanediol In 1-methoxy-2-propanol; water at 35℃; for 27h; Product distribution / selectivity;

N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide (31127-80-7) → C29 (70894-76-7)

Conditions	Yield
In methanol; chloroform
	3.8 g (45%)

1,3-diiodo-2-(iodomethyl)propane (66587-78-8) + N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide (31127-80-7) → tris(N-acetyl-N-(3,5-bis(2',3'-dihydroxypropylaminocarbonyl)-2,4,6-triiodophenyl)aminomethyl)methane

Conditions	Yield
Stage #1: 1,3-diiodo-2-(iodomethyl)propane; N,N'-bis(2,3-dihydroxypropyl)-5-acetamido-2,4,6-triiodoisophthalamide With potassium hydroxide; boric acid In methanol; water at 10 - 40℃; for 48h; Stage #2: In methanol; water pH=3.5;

Upstream product

• 76801-93-9 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide 
• 108-24-7 acetic anhydride 
• 64-19-7 acetic acid 
• 106-89-8 epichlorohydrin 
• 13290-96-5 dimethyl 5-nitroisophthalate 
• 76820-34-3 5-nitro-N,N'-bis-(2,3-dihydroxypropyl)isophthalamide 
• 76820-35-4 5-Amino-N,N'-bis[2,3-dihydroxypropyl]-1,3-benzenedicarboxamide 
• 174416-65-0 C₂₄H₂₈I₃N₃O₁₁ 
• 31122-75-5 5-acetamido-2,4,6-triiodoisophthaloyl dichloride 
• 616-30-8 3-Amino-1,2-propanediol 
• 37441-29-5 5-amino-2,4,6-triiodoisophthalic acid dichloride 
• 66108-95-0 iohexol 
• 96-24-2 3-monochloro-1,2-propanediol 

Downstream Products

• 66108-95-0 iohexol 
• 70894-76-7 C₂₉ 
• 92339-11-2 iodixanol 
• 89797-00-2 N,N'-bis(2,3-dihydroxypropyl)-5-[N-(2-hydroxy-3-methoxypropyl)acetamido]-2,4,6-triiodoisophthalamide 
• 1309926-46-2 C₃₄H₆₇I₃N₄O₈Si₅ 
• 1309926-45-1 C₃₄H₆₅I₃N₆O₈Si₅ 
• 1150307-18-8 C₃₂H₃₈I₆N₆O₁₄ 
• 1309926-44-0 C₁₉H₂₅I₃N₆O₈ 
• 1186057-94-2 5,5'-(2-hydroxy-2-methylpropane-1,3-diyl)bis(acetylazanediyl)bis(N₁,N₃-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide) 
• 1150307-23-5 5-[Acetyl-(3-amino-2-hydroxy-propyl)-amino]-N,N'-bis-(2,3-dihydroxy-propyl)-2,4,6-triiodo-isophthalamide 
• 1048964-64-2 N,N,N'-tris-(3-{acetyl-[3,5-bis-(2 3-dihydroxy-propyl-carbamoyl)-2,4,6-triiodo-phenyl]-amino}-2-hydroxy-propyl)-dicarbonimidic diamide 
• 171897-74-8 5,5'-(N-acetyl-2-hydroxypropane-1,3-diyldiamino)bis 

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The invention discloses a preparation method of an iodixanol hydrolysate. The preparation method comprises the following steps: in ionic liquid, condensing and hydrolyzing 5-acetamido-2,4,6-triiodo-1,3-benzenedicarboxamide and epoxy chloropropane under the action of a solid base catalyst to obtain the product 5-(acetamido)-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide, wherein the solid base catalyst takes a metal oxide as a first active component, takes one or more of corresponding metal hydroxide, carbonate and bicarbonate as a second active component, and takes strongly basic anion exchange resin as a carrier. The catalyst is simple in preparation process, good in activity, long in service cycle, high in product yield, good in purity and free of trace impurities limited by drugs. Equipment is not corroded in the production process, product post-treatment is convenient, the production cost is low, and the method is economical, practical, green and environmentally friendly.

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