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

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

• 154921-11-6 dimethyl 5-amino-2,4,6-triiodo-1,3-benzenedicarboxylate 
• 37441-29-5 5-amino-2,4,6-triiodoisophthalic acid dichloride 
• 76801-93-9 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide 
• 60166-98-5 S-N,N'-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-5-amino-2,4,6-triiodo-1,3-benzenedicarboxamide 
• 1026150-94-6 2,4,6-Triiodo-5-isocyanato-isophthalic acid dimethyl ester 
• 154921-12-7 dimethyl 2,4,6-triiodo-5-<<(oxiranylmethoxy)carbonyl>amino>-1,3-benzenedicarboxylate 
• 148051-08-5 N,N'-bis[2-(acetyloxy)-1-[(acetyloxy)methyl]ethyl]-5-amino-2,4,6-triiodo-1,3-benzenedicarboxamide 
• 76801-94-0 5-amino-N,N'-bis[2,3-bis(acetyloxy)propyl]2,4,6-triiodo-1,3-benzenedicarboxamide 
• 189242-93-1 Acetic acid 3-acetoxy-2-[3-(2-acetoxy-1-acetoxymethyl-ethylcarbamoyl)-2,4,6-triiodo-5-isocyanato-benzoylamino]-propyl ester 
• 136452-99-8 acetic acid 2-acetoxy-3-[3-(2,3-diacetoxy-propylcarbamoyl)-2,4,6-triiodo-5-isocyanato-benzoylamino]-propyl-1-ester 
• 154921-13-8 <3,5-bis<<<2-(acetyloxy)-1-<(acetyloxy)methyl>ethyl>amino>carbonyl>-2,4,6-triiodophenyl>carbamic acid, oxyranylmethyl ester 
• 154921-15-0 N,N'-bis<2-(acetyloxy)-1-<(acetyloxy)methyl>ethyl>-5-<4-(hydroxymethyl)-2-oxo-3-oxazolidinyl>-1,3-benzenedicarboxamide 
• 136453-00-4 <3,5-bis<<<2,3-bis(acetyloxy)propyl>amino>carbonyl>-2,4,6-triiodophenyl>carbamic acid, oxyranylmethyl ester 
• 136453-01-5 N,N'-bis<2,3-bis(acetyloxy)propyl>-5-<4-(hydroxymethyl)-2-oxo-3-oxazolidinyl>-2,4,6-triiodo-1,3-benzenedicarboxamide 

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.

Method for preparing 5-amino-2,4,6-triiodoisophthalic acid

The invention relates to a method for preparing iodized aniline. The method specifically comprises the steps that an iodized metal salt or hydrogen iodide is taken to react with iodoxylic acid or a salt thereof, and then subjected to an iodine reaction with the compound shown in the formula (I) in a polar solvent under acidic conditions, purification is conducted, and 5-amino-2,4,6-triiodophthalicacid as shown in the formula (II) is obtained. The 5-amino-2,4,6-triiodophthalic acid is an intermediate which can be used for synthesizing an iodic contrast medium widely applied to medical imaging.According to the preparation method, the raw materials are stable, the process is simple, and the yield is very high, large-scale industrial production can be achieved, and industrial application andpopularization are facilitated.

Iopamidol synthesis and preparation of iopamidol synthesis intermediate

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Process for the iodination of aromatic compounds

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Highly-iodinated fullerene as a contrast agent for X-ray imaging

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Preparation of tri-iodo benzene compounds

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PROCESS FOR THE PREPARATION OF A HALOSUBSTITUTED AROMATIC ACID

The present invention refers to a process for the preparation of 5-amino-2,4,6-triiodo-1,3-benzenedicarboxylic acid, comprising the following steps: a) catalytic hydrogenation of 5-nitro-1,3-benzenedicarboxylic acid in neutral or basic environment, which gives an aqueous solution of 5-amino-1,3-benzenedicarboxylic acid sodium salt; b) direct iodination of the 5-amino-1,3-benzenedicarboxylic acid sodium salt solution deriving from step a), without further purification, with a solution of ICl in HCl, being the 5-amino-1,3-benzenedicarboxylic acid sodium salt solution previously added with HCl and H2SO4.

PROCESS FOR THE PREPARATION OF A DICARBOXYLIC ACID DICHLORIDE

The present invention refers to a Process for the preparation of S-(-)-5-[[2-(acetyloxy)-1-oxopropyl]amino]-2,4,6-triiodo-1,3-benzenedicarboxylic acid dichloride of formula (I) comprising the reaction between S-(-)-[2-(acetyloxy)]propionic acid chloride and 5-amino-2,4,6-triiodo-, 1,3-benzenedicarboxylic acid dichloride, in an aprotic dipolar solvent and in presence of a halogenhydric acid.

Heterocyclic Nonionic X-ray Contrast Agents. 3. The Synthesis of 5--2,4,6-triiodo-1,3-benzenedicarboxamide Derivatives

The syntheses of 2,4,6-triiodo-1,3-benzenedicarboxamide analogs, 12c, 12e, and 17c, of interest as X-ray diagnostic agents and in which the 5 position is linked to the N atom of a 4-(hydroxymethyl)-oxazolidin-2-one moiety, are described.The heterocycle was built from suitably protected 5-amino-2,4,6-triiodo-1,3-benzenedicarboxylic acid derivatives by a three-step procedure consisting of (1) phosgene treatment to obtain the corresponding isocyanates, (2) phenylmercuric chloride-catalyzed addition of glycidol (10) resulting in glycidil carbamates, and (3) pyridine-catalyzed intramolecular N-alkylation, followed by deprotection, to obtain the oxazolidin-2-ones.The intramolecular N-alkylation reaction was highly regioselective and was not appreciably accompanied by O-alkylation products under the experimental conditions employed.The two carboxamide nitrogen atoms in the intermediates and end products carry either 2,3-dihydroxypropyl or 1,3-dihydroxypropyl residues.These highly congested benzenoid compounds exhibited interesting NMR spectral features due to atropisomerism arising from hindrance to free rotation about the three single bonds that link the aromatic moiety to the N-containing functionalities.