37441-29-5

Basic information

• Product Name: 5-Amino-2,4,6- triiodisophthaloyl acid dichloride
• Synonyms: 5-amino-2,4,6-triodoisophthalolylchloride;5-amino-2,4,6- triiodisophthaloyl acid dichloride;5-AMINO-2,4,6-TRIIODO-ISOPHTALOYL DICHLORIDE;5-AMINO-2,4,6-TRIIODOISOPHTHALOYL DICHLORIDE;5-Amino-2,4,6-Triiodoiso Phthaloyl Chloride;5-Amino-2,4,6-triiodisophthaloyl dichloride;5-Amino-2,4,6-Triiodo-1,3-Benzenedicarboxylic Acid Dichloride;5-Amino-2,4,6-triiodoisophthaloydichloride
• CAS NO: 37441-29-5
• Molecular Formula: C₈H₂Cl₂I₃NO₂
• Molecular Weight: 595.73
• EINECS: 417-220-1
• Product Categories: Intermediate of Ioversol
• Mol File: 37441-29-5.mol
• Article Data: 32

Chemical Properties

• Melting Point: 231°C(lit.)
• Boiling Point: 566.853 °C at 760 mmHg
• Flash Point: 296.622 °C
• Appearance: /
• Density: 2.827 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.795
• Storage Temp.: Refrigerator, under inert atmosphere
• Solubility: Acetone (Slightly), Methanol (Very Slightly)
• PKA: -3.45±0.10(Predicted)
• CAS DataBase Reference: 5-Amino-2,4,6- triiodisophthaloyl acid dichloride(CAS DataBase Reference)
• NIST Chemistry Reference: 5-Amino-2,4,6- triiodisophthaloyl acid dichloride(37441-29-5)
• EPA Substance Registry System: 5-Amino-2,4,6- triiodisophthaloyl acid dichloride(37441-29-5)

Safety Data

• Hazard Codes: Xi,N
• Statements: 43-51/53
• Safety Statements: 22-36/37-61
• RIDADR: 3077
• HazardClass: 9
• PackingGroup: III
• Hazardous Substances Data: 37441-29-5(Hazardous Substances Data)

Usage

Chemical Properties

Yellow Solid

Uses

5-Amino-2,4,6- triiodisophthaloyl acid dichloride is used in the preparation of trimeric X-ray contrast agents.

Flammability and Explosibility

Notclassified

InChI:InChI=1/C8H2Cl2I3NO2/c9-7(15)1-3(11)2(8(10)16)5(13)6(14)4(1)12/h14H2

Synthetic route

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%

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

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%

5-sulfinylamino-2,4,6-triiodoisophthalic acid chloride → 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5)

Conditions	Yield
With water In acetone for 26h;	85.5%

5-aminoisophthalic acid (99-31-0) → 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 73 percent / ICl; KCl / H2O / 24 h / 55 °C 2: 89.3 percent / SOCl2 / 6 h / Heating View Scheme
Multi-step reaction with 2 steps 1: 74 percent / aq. potassium iododichloride / H2O / 18 h / 55 - 60 °C 2: 92 percent / thionyl chloride View Scheme

5-nitrobenzene-1,3-dicarboxylic acid (618-88-2) → 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: Iodine monochloride / 5 h / 70 °C / Inert atmosphere 2.1: phosphorus pentachloride / 0.67 h / 30 °C 2.2: 0.17 h View Scheme

5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) + Acetoxyacetyl chloride (13831-31-7) → 2-((3,5-bis (chlorocarbonyl)-2,4,6-triiodophenyl)amino)-2-oxoethyl acetate (78314-12-2)

Conditions	Yield
In water	99%
In N,N-dimethyl acetamide at 20℃; for 15h; Cooling;	92%
In tetrahydrofuran; n-heptane at 20℃; Product distribution / selectivity; Heating / reflux;	35%

acetyl chloride (75-36-5) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → 5-acetamido-2,4,6-triiodoisophthaloyl dichloride (31122-75-5)

Conditions	Yield
In water	99%
In ISOPROPYLAMIDE at 0℃; for 12h;	81%
In N,N-dimethyl acetamide at 0 - 20℃; for 4h;	50%
In N,N-dimethyl acetamide at 20℃; Inert atmosphere; Cooling with ice;

acetic anhydride (108-24-7) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → 5-acetamido-2,4,6-triiodoisophthaloyl dichloride (31122-75-5)

Conditions	Yield
sulfuric acid In acetonitrile Product distribution / selectivity;	97%
sulfuric acid for 1h; Product distribution / selectivity;	76%

TFA-Gly (383-70-0) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → 2,4,6-triiodo-5-[2-(2,2,2-trifluoroacetylamino)-acetylamino]-isophthalic acid dichloride (752253-20-6)

Conditions	Yield
Stage #1: TFA-Gly With thionyl chloride In ISOPROPYLAMIDE at 0℃; for 1h; Stage #2: 5-amino-2,4,6-triiodoisophthalic acid dichloride In ISOPROPYLAMIDE at 0 - 20℃; for 96h;	97%

glycinium trifluoroacetate (677-30-5) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → 2,4,6-triiodo-5-[2-(2,2,2-trifluoroacetylamino)-acetylamino]-isophthalic acid dichloride (752253-20-6)

Conditions	Yield
Stage #1: glycinium trifluoroacetate With thionyl chloride In ISOPROPYLAMIDE at 0℃; for 1h; Stage #2: 5-amino-2,4,6-triiodoisophthalic acid dichloride In ISOPROPYLAMIDE at 0 - 20℃; for 96h;	97%

5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → 5-acetamido-2,4,6-triiodoisophthaloyl dichloride (31122-75-5)

Conditions	Yield
With thionyl chloride In acetic acid	93.4%
With sulfuric acid; acetic anhydride
With thionyl chloride In acetic acid

Methoxyacetyl chloride (38870-89-2) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → 5-Methoxyacetamido-2,4,6-triiodoisophthaloyl chloride (76350-03-3)

Conditions	Yield
In 1,4-dioxane at 80 - 90℃;	93%
In N,N-dimethyl acetamide at 10 - 20℃; for 24h;	90.2%
In N,N-dimethyl acetamide at 20℃; for 20h; Cooling with ice;	86%

(S)-2-acetoxypropanoyl chloride (36394-75-9) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → S-(-)-5-[[2-(acetyloxy)-1-oxopropyl]amino]-2,4,6-triiodo-1,3-benzenedicarboxylic acid dichloride (60166-91-8)

Conditions	Yield
In N,N-dimethyl acetamide at 0 - 20℃; Inert atmosphere;	92.3%
In N,N-dimethyl acetamide at 0 - 20℃; for 38h; Inert atmosphere;	91.4%
Stage #1: (S)-2-acetoxypropanoyl chloride In N,N-dimethyl acetamide at -2 - 0℃; for 1h; Stage #2: 5-amino-2,4,6-triiodoisophthalic acid dichloride; metanol at 12℃; for 6h; Stage #3: With 2-ethoxy-ethanol more than 3 stages;	90%
Stage #1: (S)-2-acetoxypropanoyl chloride In N,N-dimethyl acetamide at -2 - 0℃; for 1h; Stage #2: 5-amino-2,4,6-triiodoisophthalic acid dichloride; metanol In N,N-dimethyl acetamide at 12℃; for 6h; Stage #3: With 2-ethoxy-ethanol more than 3 stages;	89%
With N,N-dimethylacetamide hydrochloride In ISOPROPYLAMIDE at 10 - 25℃;

2-acetoxypropionyl chloride (38939-83-2) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → L-5-(2-acetoxy-propionylamino)-2,4,6-triiodo-isophthalic acid dichloride

Conditions	Yield
Zinc chloride In dichloromethane	90.6%
In ISOPROPYLAMIDE; water; acetone

2-methoxyacetic acid (625-45-6) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → 5-Methoxyacetamido-2,4,6-triiodoisophthaloyl chloride (76350-03-3)

Conditions	Yield
Stage #1: 2-methoxyacetic acid With bis(trichloromethyl) carbonate In dichloromethane for 3h; Reflux; Stage #2: 5-amino-2,4,6-triiodoisophthalic acid dichloride In dichloromethane; N,N-dimethyl acetamide; water for 5.5h;	90%
With thionyl chloride In water; N,N-dimethyl-formamide

5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) + malonoyl dichloride (1663-67-8) → 5,5′-[malonylbis(azanediyl)]bis(2,4,6-triiodoisophthaloyl dichloride) (79944-44-8)

Conditions	Yield
In tetrahydrofuran at 20 - 50℃; Inert atmosphere;	89.4%
In tetrahydrofuran for 6h; Heating;	83%
In 1,4-dioxane	81%

[(4-aminophenyl)ethoxycarbonylmethylamino]acetic acid ethyl ester (112335-76-9) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → C36H40I3N5O10 (915228-76-1)

Conditions	Yield
With triethylamine In N,N-dimethyl acetamide at 20℃; for 24h;	85%

tetrahydrofuran-2-carbonyl chloride (52449-98-6) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → N-[3,5-Bis(chlorocarbonyl)-2,4,6-triiodo-phenyl]tetrahydro-2-furancarboxamide (153714-17-1)

Conditions	Yield
In tetrahydrofuran; n-heptane for 6.5h; Heating;	81%
In tetrahydrofuran

ethylenediamine (107-15-3) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → 5-amino-N,N'-bis-(2-aminoethyl)-2,4,6-triiodoisophthalamide (869339-38-8)

Conditions	Yield
Stage #1: ethylenediamine; 5-amino-2,4,6-triiodoisophthalic acid dichloride In tetrahydrofuran at 20℃; for 15h; Stage #2: With lithium hydroxide In ethanol; water pH=8.0;	77%

1-amino-2-propene (107-11-9) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → 5-amino-3-allylcarbamoyl-2,4,6-triiodobenzoyl chloride (1071506-72-3)

Conditions	Yield
In N,N-dimethyl-formamide at 20℃; for 12h; Solvent; Cooling with ice;	63%
In tetrahydrofuran at 0℃; for 10h;	60%

N-methyl-N-allylamine (627-37-2) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → 3-(allyl-methyl-carbamoyl)-5-amino-2,4,6-triiodo-benzoyl chloride (946506-01-0)

Conditions	Yield
In tetrahydrofuran at 50℃; for 18h;	59%
In tetrahydrofuran at 50℃;

3-Amino-1,2-propanediol (616-30-8, 13552-31-3) + serinol (534-03-2) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → 5-amino-N1-(1,3-dihydroxypropan-2-yl)-N3-(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (1096689-22-3)

Conditions	Yield
Stage #1: 3-Amino-1,2-propanediol; 5-amino-2,4,6-triiodoisophthalic acid dichloride With triethylamine In N,N-dimethyl acetamide at -24 - 2℃; for 24h; Stage #2: serinol In N,N-dimethyl acetamide at 0 - 40℃; for 44h;	57%
Stage #1: 3-Amino-1,2-propanediol; 5-amino-2,4,6-triiodoisophthalic acid dichloride With triethylamine In ISOPROPYLAMIDE at -24 - 2℃; Stage #2: serinol In ISOPROPYLAMIDE at 0 - 40℃;
With triethylamine In water; 2,4-dichlorophenoxyacetic acid dimethylamine

phosgene (75-44-5) + ethylenediamine (107-15-3) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → 2,4,6-triiodo-5-[2-(2,2,2-trifluoroacetylamino)-acetylamino]-isophthalic acid dichloride

Conditions	Yield
Stage #1: phosgene; 5-amino-2,4,6-triiodoisophthalic acid dichloride In 1,4-dioxane; toluene at 60℃; for 24h; Stage #2: ethylenediamine In tetrahydrofuran at 20℃; for 25h; Stage #3: With lithium hydroxide In water pH=8.0;	53%
Stage #1: phosgene; 5-amino-2,4,6-triiodoisophthalic acid dichloride In 1,4-dioxane; toluene at 60℃; for 24h; Stage #2: ethylenediamine In tetrahydrofuran at 20℃; for 25h; Stage #3: With lithium hydroxide In water pH=8.0;	53%

5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) + methylamine (74-89-5) → 5-amino-2,4,6-triiodo-3-N-methylaminocarbonylbenzoic acid chloride (51935-29-6)

Conditions	Yield
With triethylamine In tetrahydrofuran at 0 - 20℃; for 48h;	52%

serinol (534-03-2) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → S-N,N'-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-5-amino-2,4,6-triiodo-1,3-benzenedicarboxamide (60166-98-5)

Conditions	Yield
for 0.5h; Milling;	47%
In N,N-dimethyl acetamide for 16h; Ambient temperature;

3-Amino-1,2-propanediol (616-30-8, 13552-31-3) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide (76801-93-9)

Conditions	Yield
In N,N-dimethyl acetamide for 16h; Ambient temperature;
With triethylamine In N,N-dimethyl acetamide at 50℃; for 3.5h; Cooling with ice;

morpholine (110-91-8) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → [3-amino-2,4,6-triiodo-5-(morpholine-4-carbonyl)-phenyl]-morpholin-4-yl-methanone (956914-71-9)

Conditions	Yield
In tetrahydrofuran at 20℃;

N-methyl-N-allylamine (627-37-2) + 5-amino-2,4,6-triiodoisophthalic acid dichloride (37441-29-5) → N,N'-diallyl-5-amino-2,4,6-triiodo-N,N'-dimethyl-isophthalamide (946506-02-1)

Conditions	Yield
In tetrahydrofuran at 20℃;

Upstream product

• 35453-19-1 2,4,6-triiodo-5-aminoisophthalic acid 
• 618-88-2 5-nitrobenzene-1,3-dicarboxylic acid 
• 37091-73-9 2-chloro-1,3-dimethylimidazolinium chloride 
• 99-31-0 5-aminoisophthalic acid 

Downstream Products

• 60166-98-5 S-N,N'-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-5-amino-2,4,6-triiodo-1,3-benzenedicarboxamide 
• 79944-44-8 5,5′-[malonylbis(azanediyl)]bis(2,4,6-triiodoisophthaloyl dichloride) 
• 956914-71-9 [3-amino-2,4,6-triiodo-5-(morpholine-4-carbonyl)-phenyl]-morpholin-4-yl-methanone 
• 946506-02-1 N,N'-diallyl-5-amino-2,4,6-triiodo-N,N'-dimethyl-isophthalamide 
• 869339-38-8 5-amino-N,N'-bis-(2-aminoethyl)-2,4,6-triiodoisophthalamide 
• 31122-75-5 5-acetamido-2,4,6-triiodoisophthaloyl dichloride 
• 78314-12-2 2-((3,5-bis (chlorocarbonyl)-2,4,6-triiodophenyl)amino)-2-oxoethyl acetate 
• 76350-03-3 5-Methoxyacetamido-2,4,6-triiodoisophthaloyl chloride 
• 946506-01-0 3-(allyl-methyl-carbamoyl)-5-amino-2,4,6-triiodo-benzoyl chloride 
• 946506-13-4 3-amino-5-diallylcarbamoyl-2,4,6-triiodo-benzoyl chloride 
• 956914-83-3 N,N,N',N'-tetraallyl-5-amino-2,4,6-triiodo-isophthalamide 
• 752253-20-6 2,4,6-triiodo-5-[2-(2,2,2-trifluoroacetylamino)-acetylamino]-isophthalic acid dichloride 
• 76801-93-9 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide 
• 77868-40-7 N₁,N₃-bis(2,3-dihydroxypropyl)-5-(2-hydroxyacetamido)-2,4,6-triiodobenzene-1,3-dicarboxamide 

Relevant articles and documents

Optimisation of the preparation and isolation of 5-amino-2,4,6-triiodoisophthalic acid dichloride

A scaleable process for the chlorination of 5-amino-2,4,6-triiodoisophthalic acid to the corresponding acid chloride, a building block for the synthesis of iodinated X-ray contrast agents, has been developed. Two dimeric byproducts have been isolated and assigned structures consistent with an amide and an anhydride. Hydrolysis of the N-sulfinyl intermediate and simultaneous crystallisation of the phthalic acid chloride have been optimised by applying fractional factorial design.

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