35453-19-1

Basic information

• Product Name: 5-Amino-2,4,6-triiodoisophthalic acid
• Synonyms: ATIPA;5-AMINO-2,4,6-IODOISOPHTHALIC ACID;5-AMINO-2,4,6-TRIIODOBENZENE-1,3-DICARBOXYLIC ACID;5-AMINO-2,4,6-TRIIODOISOPHTHALIC ACID;5-Amino-2,4,6-Triod-Isophthalic Acid;Aminoiodoisophthalicacid;5-Amino-2,4,6-triiodoisophtalic acid;5-AMINO-2,4,6-TRIIODOISOPHTHALIC ACID, 9 5%
• CAS NO: 35453-19-1
• Molecular Formula: C₈H₄I₃NO₄
• Molecular Weight: 558.84
• EINECS: 252-575-4
• Product Categories: Organic acids;(intermediate of iohexol);Aromatic Amino Acids;Peptide Synthesis;Unnatural Amino Acid Derivatives;Amines;Aromatics;Sulfur & Selenium Compounds;Intermediate of Ioversol;Pyrimidines
• Mol File: 35453-19-1.mol
• Article Data: 11

Chemical Properties

• Melting Point: 265-270 °C(lit.)
• Boiling Point: 539.4 °C at 760 mmHg
• Flash Point: 280 °C
• Appearance: slightly yellow powder
• Density: 3.053 g/cm³
• Vapor Pressure: 1.83E-12mmHg at 25°C
• Refractive Index: 1.869
• Storage Temp.: Refrigerator
• Solubility: DMSO, Methanol
• PKA: 0.83±0.10(Predicted)
• CAS DataBase Reference: 5-Amino-2,4,6-triiodoisophthalic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 5-Amino-2,4,6-triiodoisophthalic acid(35453-19-1)
• EPA Substance Registry System: 5-Amino-2,4,6-triiodoisophthalic acid(35453-19-1)

Safety Data

• Hazard Codes: Xn
• Statements: 42/43
• Safety Statements: 26-36/37/39
• WGK Germany: 3
• Hazardous Substances Data: 35453-19-1(Hazardous Substances Data)

Usage

Chemical Properties

Beige Solid

Uses

Different sources of media describe the Uses of 35453-19-1 differently. You can refer to the following data:
1. Intermediate for nonionic iodinated X-ray contrast agents.
2. 5-Amino-2,4,6-triiodoisophthalic Acid (Iohexol EP Impurity K) is an intermediate for nonionic iodinated X-ray contrast agents.

InChI:InChI=1/C8H4I3NO4/c9-3-1(7(13)14)4(10)6(12)5(11)2(3)8(15)16/h12H2,(H,13,14)(H,15,16)

Synthetic route

5-aminoisophthalic acid (99-31-0) → 2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1)

Conditions	Yield
With potassium iodate; sulfuric acid; potassium iodide In water at 30 - 75℃; for 5h; pH=< 0.5; Reagent/catalyst; Temperature; pH-value;	95.3%
With sulfuric acid; iodine; iodic acid In water at 72℃; for 6.2h; pH=1; Product distribution / selectivity;	82.6%
With K(1+)*Cl2I(1-) In water at 60 - 90℃; for 25h;	75%

5-amino-1,3-benzenedicarboxylic acid sodium salt → 2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1)

Conditions	Yield
With sulfuric acid; iodine; Iodine monochloride; sodium hydrogensulfite In hydrogenchloride; water
With sulfuric acid; iodine; Iodine monochloride; sodium hydrogensulfite In hydrogenchloride; water

sodium metabisulfite + 5-aminoisophthalic acid (99-31-0) → 2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1)

Conditions	Yield
With Iodine monochloride In water

5-nitrobenzene-1,3-dicarboxylic acid (618-88-2) → 2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1)

Conditions	Yield
With Iodine monochloride at 70℃; for 5h; Inert atmosphere;

2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) → 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5)

Conditions	Yield
With pyridine; thionyl chloride In 1,2-dichloro-ethane at 70 - 85℃; for 8.5h;	100%
With pyridine; thionyl chloride In 1,2-dichloro-ethane at 70 - 85℃; for 7.5 - 8h;	100%
With pyridine; thionyl chloride In 1,2-dichloro-ethane at 70 - 85℃; for 7.5 - 8h;	100%

diazomethane (186581-53-3, 908094-01-9) + 2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) → dimethyl 5-amino-2,4,6-triiodo-1,3-benzenedicarboxylate (154921-11-6)

Conditions	Yield
In methanol; diethyl ether 1.) O deg C, 2 h, 2.) r.t., overnight;	98%

2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) + acetic anhydride (108-24-7) → 5-acetylamino-2,4,6-triiodo-isophthalic acid (90947-02-7)

Conditions	Yield
sulfuric acid In acetonitrile Product distribution / selectivity;	97%
sulfuric acid for 0.5h; Product distribution / selectivity;	83%

methane (34557-54-5) + 2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) → 5-amino-2,4,6-triiodoisodecanoyl chloride

Conditions	Yield
With hydrogenchloride; oxygen; triphenylphosphine at 100℃; for 10h; Temperature;	97%

2-(2-propyl)-1,3-dioxane-5-carboxylic acid (116193-72-7) + 2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) → C16H16I3NO7

Conditions	Yield
Stage #1: 2-(2-propyl)-1,3-dioxane-5-carboxylic acid With N,N-dimethyl acetamide; bis(trichloromethyl) carbonate In dichloromethane at 0℃; for 0.5h; Stage #2: 2,4,6-triiodo-5-aminoisophthalic acid In dichloromethane at 0 - 50℃; for 16h;	95.7%

2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) + 2-chloro-1,3-dimethylimidazolinium chloride (37091-73-9) → 5-amino-2,4,6-triodoisophthaloyl dichloride + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5)

Conditions	Yield
In hexane; toluene	A 95% B n/a

methanol (67-56-1) + 2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) → dimethyl 5-amino-2,4,6-triiodo-1,3-benzenedicarboxylate (154921-11-6)

Conditions	Yield
With sulfuric acid for 4h; Reagent/catalyst; Reflux; Large scale;	95%

acrylic acid anhydride (2051-76-5) + 2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) → 2,4,6-triiodo-5-(prop-2-enamido)benzene-1,3-dicarboxylic acid (783279-02-7)

Conditions	Yield
With sulfuric acid In acetonitrile at 80℃;	95%

2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) + glycinium trifluoroacetate (677-30-5) → 2,4,6-triiodo-5-{methyl-[2-(2,2,2-trifluoroacetyl-amino)-acetyl]-amino}isophthalic acid dichloride

Conditions	Yield
Stage #1: glycinium trifluoroacetate With thionyl chloride In ISOPROPYLAMIDE at 0℃; for 1h; Stage #2: 2,4,6-triiodo-5-aminoisophthalic acid In ISOPROPYLAMIDE at 0 - 20℃; for 96h;	94%

2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) + 2-chloro-1,3-dimethylimidazolinium chloride (37091-73-9) → 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5)

Conditions	Yield
	93%

formaldehyd (50-00-0) + 2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) → 2,4,6-triiodo-5-(methylamino)isophthalic acid (40976-89-4)

Conditions	Yield
With sulfuric acid at 5 - 55℃; for 3.25h;	91.6%
With sulfuric acid In methanol at 45 - 50℃; for 3h; Concentration;	83.7%
With sulfuric acid In water at 40 - 50℃; for 2h;
Stage #1: 2,4,6-triiodo-5-aminoisophthalic acid With sulfuric acid at 50℃; Stage #2: formaldehyd at 40 - 50℃; for 2h;

2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) + (S)-2-acetoxypropanoyl chloride (36394-75-9) → (S)-5-(2-acetoxypropanamido)-2,4,6-triiodoisophthalic acid

Conditions	Yield
In ISOPROPYLAMIDE at 20 - 50℃; for 22h;	81%
In N,N-dimethyl acetamide at 20 - 50℃; for 22h; Time; Temperature;	81%

2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) → 5-amino-2,4-diiodo-1,3-phthalic acid

Conditions	Yield
With sodium tetrahydroborate; palladium 10% on activated carbon; sodium hydroxide In water at 1 - 25℃; for 5h; Reagent/catalyst;	81%

1,4-bis(2-methyl-1H-imidazol-1-yl)butane (52550-63-7) + 2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) + cobalt(II) diacetate tetrahydrate (6147-53-1) → [Co(1,4-bis(2-methyl-imidazol-1-yl)butane)(5-amino-2,4,6-triiodoisophthalate)]

Conditions	Yield
In water; N,N-dimethyl-formamide at 80℃; for 72h; Autoclave;	80.56%

1,4-bis(2-methyl-1H-imidazol-1-yl)butane (52550-63-7) + 2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) + cobalt(II) diacetate tetrahydrate (6147-53-1) → [Co(1,4-bis(2-methyl-imidazol-1-yl)butane)(5-aminoisophthalate)]

Conditions	Yield
In water; N,N-dimethyl-formamide at 150℃; for 72h; Autoclave;	79.6%

zinc(II) nitrate hexahydrate + 1,3-di(4-pyridyl)propane (17252-51-6) + 2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) + water (7732-18-5) → [Zn8(5-amino-2,4,6-triiodoisophthalate)8(1,3-di(4-pyridyl)propane)8]*4H2O

Conditions	Yield
In ethanol; water; N,N-dimethyl-formamide Zn compd. (0.0277 mmol), H2atip (0.0179 mmol), dpp (0.05 mmol) in DMF/EtOH/H2O=5/2/1, mixt. stirred at room temp. for 10 min; filtered, crystd. on storage for 3 d at 90°C, elem. anal.;	75%

1,3,5-benzene tris(carbonyl chloride) (4422-95-1) + 2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) → C33H12I9N3O15

Conditions	Yield
With dmap In N,N-dimethyl acetamide at 25℃; for 12h; Inert atmosphere;	71%

1,4-bis(2-methyl-1H-imidazol-1-yl)butane (52550-63-7) + 2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) + cobalt(II) diacetate tetrahydrate (6147-53-1) → [Co(1,4-bis(2-methyl-imidazol-1-yl)butane)(5-amino-2,4,6-triiodoisophthalate)]·2H2O

Conditions	Yield
In water; N,N-dimethyl-formamide at 130℃; for 72h; Autoclave;	70.21%

1,4-bis(2-methyl-1H-imidazol-1-yl)butane (52550-63-7) + 2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) + water (7732-18-5) + zinc(II) acetate dihydrate (5970-45-6) → {[Zn(1,4-bis(2-methyl-imidazol-1-yl)butane)(5-amino-2,4,6-triiodoisophthalate)]·2water}n

Conditions	Yield
In ethanol at 150℃; for 36h; High pressure;	70.2%

2,4,6-triaminopyrimidine (1004-38-2) + 2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) → C4H7N5*C8H4I3NO4

Conditions	Yield
In ethanol; water for 0.5h;	70%

1,1'-(1,4-butanediyl)bis(imidazole) (69506-86-1) + aqueous cadmium chloride + 2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) → C8H2I3NO4(2-)*Cd(2+)*C10H14N4

Conditions	Yield
Stage #1: 2,4,6-triiodo-5-aminoisophthalic acid With sodium hydroxide In water at 20℃; Stage #2: 1,1'-(1,4-butanediyl)bis(imidazole); aqueous cadmium chloride In water at 20℃;	70%

2,2'-biimidazole (492-98-8) + aqueous cadmium chloride + 2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) → C8H2I3NO4(2-)*Cd(2+)*2H2O*C6H6N4

Conditions	Yield
Stage #1: 2,4,6-triiodo-5-aminoisophthalic acid With sodium hydroxide In water at 20℃; Stage #2: 2,2'-biimidazole; aqueous cadmium chloride In methanol; water at 20℃;	68%

[2,2]bipyridinyl (366-18-7) + aqueous cadmium chloride + 2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) → [Cd(5-amino-2,4,6-triiodoisophthalato)(2,2'-bipyridine)(H2O)]*3H2O

Conditions	Yield
With NaOH In water addn. of aq. soln. of CdCl2*2.5H2O to mixt. of 5-amino-2,4,6-triiodoisophthalic acid in H2O and NaOH whilst stirring at molar ratio NH2C6I3(COOH)2:NaOH=1:2, addn. of soln. of 2,2'-bipy in water; crystn., filtration; elem. anal.;	67%

4,4'-bipyridine (553-26-4) + zinc(II) nitrate hexahydrate + 2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) + water (7732-18-5) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → [Zn2(5-amino-2,4,6-triiodoisophthalate)2(4,4'-bipyridine)2]*2DMF*3H2O

Conditions	Yield
In ethanol; water; N,N-dimethyl-formamide Zn compd. (0.0277 mmol), H2atip (0.0179 mmol), 4,4'-bpy (0.064 mmol) in DMF/EtOH/H2O=5/2/1, mixt. stirred at room temp. for 10 min; filtered, crystd. on storage for 1 wk at room temp., elem. anal.;	65%

4,4'-bis-(1H-imidazol-1-yl)biphenyl (855766-92-6) + cobalt(II) nitrate hexahydrate + 2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) → Co(2+)*C18H14N4*2C8H3I3NO4(1-)*2H2O

Conditions	Yield
With sodium hydroxide In ethanol; water; N,N-dimethyl-formamide at 134.84℃; for 72h; pH=6; Autoclave;	63%

2,2'-biimidazole (492-98-8) + zinc(II) nitrate hexahydrate + 2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) → C8H2I3NO4(2-)*Zn(2+)*C6H6N4*3H2O

Conditions	Yield
Stage #1: 2,4,6-triiodo-5-aminoisophthalic acid With sodium hydroxide In water at 20℃; Stage #2: 2,2'-biimidazole; zinc(II) nitrate hexahydrate In methanol; water at 20℃;	62%

aqueous cadmium chloride + 2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) + water (7732-18-5) + 1,4-bis(1,2,4-triazol-1-yl)butane (345952-55-8) → [Cd(5-amino-2,4,6-triiodo-2,4,6-triiodoisophthalate)(1,4-bis(1,2,4-triazsol-1-yl)butane)(H2O)2]*3H2O

Conditions	Yield
With NaOH In water NaOH and isophthalic acid deriv. dissolved in water, then aq. CdCl2*2.5H2O added while stirring, bis(triazolyl)butane in water added; filtered; elem. anal.;	61%

methanol (67-56-1) + [2,2]bipyridinyl (366-18-7) + copper(II) nitrate trihydrate + 2,4,6-triiodo-5-aminoisophthalic acid (35453-19-1) → [Cu(5-amino-2,4,6-triiodoisophthalato)(2,2'-bipyridine)]*3H2O*CH3OH

Conditions	Yield
With NaOH In methanol; water addn. of aq. soln. of Cu(NO3)2*3H2O to mixt. of 5-amino-2,4,6-triiodoisophthalic acid in H2O and NaOH whilst stirring at molar ratio NH2C6I3(COOH)2:NaOH=1:2, addn. of soln. of 2,2'-bipy in MeOH; crystn., filtration; elem. anal.;	61%

Upstream product

• 99-31-0 5-aminoisophthalic acid 
• 618-88-2 5-nitrobenzene-1,3-dicarboxylic acid 

Downstream Products

• 40976-89-4 2,4,6-triiodo-5-(methylamino)isophthalic acid 
• 154921-11-6 dimethyl 5-amino-2,4,6-triiodo-1,3-benzenedicarboxylate 
• 136949-58-1 iobitridol 
• 76350-18-0 2,4,6-triiodo-5-(methylamino)isophthaloyl dichloride 
• 869339-38-8 5-amino-N,N'-bis-(2-aminoethyl)-2,4,6-triiodoisophthalamide 
• 60166-93-0 Iopamidol 
• 60166-91-8 S-(-)-5-[[2-(acetyloxy)-1-oxopropyl]amino]-2,4,6-triiodo-1,3-benzenedicarboxylic acid dichloride 
• 1288844-65-4 [Zn(5-amino-2,4,6-triiodoisophthalic acid(-2H))(2,2'-dipyridylamine)](n) 

Relevant articles and documents

Method for preparing 5 -amino -2, 4 and 6 -iodoisophthalate

The invention relates to a method for preparing 5 - amino -2, 4 and 6 - triiodoisophthalic acid, in particular to an iodine simple substance. The iodate is reacted with 5 - aminoisophthalic acid or a salt thereof in a mixed solution. The reaction product can be used in the synthesis X-ray imaging diagnosis technology intermediate of contrast medium. The preparation method is convenient and simple in process operation, excellent in yield, safe, environment-friendly and green, and can be used for large-scale industrial production.

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