Optimisation of the Preparation and Isolation of 5-Amino-2,4,6-triiodoisophthalic Acid Dichloride

Gijsen, H.J.M.; Bakel, H.C.C.K. van; Zwaan, W.; Hulshof, L.A.

doi:10.1021/op980055+

Cited by 8 publications

(3 citation statements)

References 9 publications

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“…Acyl/sulfonyl halides can react with alcoholic solvents to form the corresponding nongenotoxic esters. However, most esterification reactions involving acyl/sulfonyl halides are typically catalyzed by a base (e.g., pyridine, N-methylmorpholine, tertiary amines, quaternary ammonium salts) to remove evolved HCl from the reaction mixture, 44 and in the absence of a catalyst the reaction rate is much lower. Bentley et al 45 evaluated the S N 2 mechanism for alcoholysis, aminolysis, and hydrolysis of acyl chlorides.…”

Section: Discussionmentioning

confidence: 99%

Do Carboxylic/Sulfonic Acid Halides Really Present a Mutagenic and Carcinogenic Risk as Impurities in Final Drug Products?

Amberg

Harvey

Czich

et al. 2015

Org. Process Res. Dev.

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There is substantial mutagenicity data on acyl/sulfonyl halides available in the public domain and these data are the basis for many in silico models of mutagenicity (e.g. DEREK Nexus and Leadscope). A review of these data indicates that the perceived mutagenic potential of this class of compounds is based on a number of non-reproducible positive findings in the bacterial mutagenicity assay and positive bacterial mutagenicity data on a series of compounds where formation of reactive halodimethylsulfides (HDMS) in DMSO may have compromised the interpretation of the Ames data (HDMS are typically mutagenic). The only genuine mutagenic, genotoxic and carcinogenic compound within the 50+ acyl/sulfonyl halides described herein, was dimethylcarbamic chloride, which is appropriately considered to be a potential human carcinogen. Some in silico systems, such as Derek Nexus, contain rules which detail that the activity of this class should be considered a false positive flag for mutagenicity and ideally any in silico structure activity rules for mutagenicity in other systems should be likewise addressed. The data presented here supports the view that these alerts should currently be interpreted as a false positive flag for mutagenicity and the entire class viewed as low concern from a mutagenicity perspective. The formation of these reactive halodimethylsulfides is an example of the classical Pummerer rearrangement.The chemical reactivity of this class of compounds also supports the contention that they are of limited concern from a mutagenic and carcinogenic impurity risk perspective when used in the synthesis of drug products. They can be expected to rapidly purge from any reaction sequence with generic predicted purge factors in the range 1x10 3 -3x10 5 /stage and hence should be effectively eliminated at the stage of introduction.We would therefore recommend avoiding DMSO as solvent for mutagenicity tests with acyl/sulfonyl halides due to the potential for false positive results arising from DMSO reaction products, which are not relevant in aqueous, physiological conditions. Furthermore, as indicated by the Ames test data for mesyl chloride/2-fluorobenzoyl chloride, even non-DMSO organic solvents may not be appropriate for certain members of this class (acyl/sulfonyl halides), suggesting that they may not be amenable to adequate testing in the Ames assay.

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Section: Discussionmentioning

confidence: 99%

Do Carboxylic/Sulfonic Acid Halides Really Present a Mutagenic and Carcinogenic Risk as Impurities in Final Drug Products?

Amberg

Harvey

Czich

et al. 2015

Org. Process Res. Dev.

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“…5-Amino-2,4,6-triiodoisophthalic moiety is ap recursor of the synthesis of aw ide range of contrast agents of water-soluble, nonionic iodinated X-ray contrast agents for imaging soft tissues, such as Iopamidol, Iohexol, Ioversol [1][2][3]. The synthesis of these agents produces intermediate triiodinated compounds in waste water from production plants [4].…”

Section: Discussionmentioning

confidence: 99%

Crystal structure of tetrapyridyl(5-amino-2,4,6-triiodoisophthalato-κO)- copper(II) monohydrate, Cu(C5H5N)4(C8H2I3NO4) ·H2O

Zhao¹,

Tang²

2009

Zeitschrift Für Kristallographie - New Crystal Structures

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“…5-Amino-2,4,6-triiodoisophthalic moiety is a precursor of the synthesis of a wide range of contrast agents of water-soluble, nonionic iodinated X-ray contrast agents for imaging soft tissues, such as Iopamidol, Iohexol, Ioversol [1][2][3]. The synthesis of these agents produces intermediate triiodinated compounds in waste water from production plants [4].…”

Section: Discussionmentioning

confidence: 99%

Crystal structure of tetrapyridyl(5-amino-2,4,6-triiodoisophthalato-k0)-copper(II)monohydrate,Cu(C5H5N)4(C8H2I3NO4)*H2O

Zhang¹,

Zhao²,

Tang³

2009

Zeitschrift Für Kristallographie - New Crystal Structures

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Source of materialReagents and solvents used had commercially available quality. To a stirring solution of 5-amino-2,4,6-triiodoisophthalic acid (558 mg, 1 mmol) in hot MeOH (20 ml), Cu(N0 3 )2 · 3H 2 0 (242 mg, 1 mmol) was added dropwise, followed by a solution of sodium azide (65 mg, 1 mmol). A blue crystalline product was formed rapidly. The precipitate was filtered off, washed with MeOH and dried in vacuo. The product was dissolved in pyridine that was allowed to evaporate at room temperature. After several weeks royal purple crystals appeared. Experimental detailsHydrogen atoms were positioned geometrically and refined using a riding model, with d(C-H) = 0.85 -0.97 Â and ÍWH) = 1.2

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Optimisation of the Preparation and Isolation of 5-Amino-2,4,6-triiodoisophthalic Acid Dichloride

Cited by 8 publications

References 9 publications

Do Carboxylic/Sulfonic Acid Halides Really Present a Mutagenic and Carcinogenic Risk as Impurities in Final Drug Products?

Do Carboxylic/Sulfonic Acid Halides Really Present a Mutagenic and Carcinogenic Risk as Impurities in Final Drug Products?

Crystal structure of tetrapyridyl(5-amino-2,4,6-triiodoisophthalato-κO)- copper(II) monohydrate, Cu(C5H5N)4(C8H2I3NO4) ·H2O

Crystal structure of tetrapyridyl(5-amino-2,4,6-triiodoisophthalato-k0)-copper(II)monohydrate,Cu(C5H5N)4(C8H2I3NO4)*H2O

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