N-Methylsuccinimide
| Names | |
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| IUPAC name
1-Methylpyrrolidine-2,5-dione
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| Systematic IUPAC name
1-Methyl-2,5-pyrrolidinedione | |
Other names
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| Identifiers | |
3D model (JSmol)
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| Abbreviations | MSI |
| 110486 | |
| ChEMBL | |
| ChemSpider | |
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PubChem CID
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| UNII | |
CompTox Dashboard (EPA)
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| Properties | |
| C5H7NO2 | |
| Molar mass | 113.116 g·mol−1 |
| Appearance | White to off-white crystalline powder |
| Density | 1.127 g/mL |
| Melting point | 66 to 69 °C (151 to 156 °F; 339 to 342 K) (also reported as 68–71 °C and 66–67 °C) |
| Boiling point | 235 °C (455 °F; 508 K) (also reported as 234–235 °C) |
| Soluble in water | |
| Vapor pressure | 0.0±0.5 mmHg at 25 °C (Predicted) |
| Hazards | |
| Occupational safety and health (OHS/OSH): | |
Main hazards
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Irritant |
| GHS labelling: | |
| Warning | |
| H315, H319, H335 | |
| P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, P501 | |
| Flash point | 142.1(Predicted) |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references
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N-Methylsuccinimide (also known as 1-methyl-2,5-pyrrolidinedione, abbreviated MSI) is an organic compound chemically related to succinimide. It is primarily characterized as a major metabolic product of the industrial solvent N-methyl-2-pyrrolidone (NMP) in mammals, including humans and rats.
Industrial production and use
One patent describes the reaction of aqueous ammonia and succinate with a methylating agent at temperatures ranging from 100 °C to 400 °C. The resulting N-methylsuccinimide can subsequently be purified and hydrogenated to form NMP.[1] It can also be produced by the reaction of diammonium succinate with methanol or by the reaction of succinic anhydride with methylamine.[2]
In the microelectronics industry, the oxidative degradation of NMP during fabrication processes results in the formation of N-methylsuccinimide.[3] Consequently, it is found in waste NMP mixed liquors. Patents describe methods for purifying waste NMP by removing impurities such as N-methylsuccinimide and gamma-butyrolactone (GBL) using alkali treatment to recover high-purity NMP.[4]
Toxicokinetics
In toxicology and occupational health, N-methylsuccinimide is identified as a metabolite of NMP. Upon exposure to NMP, the compound undergoes a metabolic pathway in which it is first hydroxylated to form 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP). This intermediate is further oxidized to N-methylsuccinimide (MSI), which is subsequently metabolized to 2-hydroxy-N-methylsuccinimide (2-HMSI).[5]
Experimental studies on male volunteers exposed to NMP vapors indicated that MSI levels in plasma and urine are correlated with exposure concentrations. However, 2-HMSI is often preferred as a biomarker due to its accumulation and delayed excretion profile. In human toxicokinetic studies, the renal clearance of MSI was calculated to be approximately 0.12 L/h, with a total clearance of 8.5 L/h. The apparent volume of distribution for MSI was found to be approximately 120 liters.[5]
Research using rat whole embryo culture systems found that the toxic effects of NMP exposure are due to NMP itself rather than its known metabolic products.[6]
Analysis and detection
Methods using gas chromatography (GC), sometimes coupled with mass spectrometry (GC-MS), have been used to analyze MSI in plasma and urine samples.[5]
Solid-phase extraction (SPE) combined with gas chromatography and a flame thermionic detector (GC/FTD) has been developed for the determination of NMP and its metabolites, including MSI, in urine.[7]
Studies evaluating biomarkers have employed mass spectrometry to analyze plasma and urine concentrations of MSI and related metabolites.[8]
References
- ^ EP1572644A1, Werpy, Todd A.; Jr, John G. Frye & White, James F. et al., "Process for producing N-methyl succinimide", issued 14 September 2005
- ^ "Process for microwave assisted synthesis of N-methyl pyrrolidone". Google Patents. 2014-09-04. Retrieved 2026-01-05.
- ^ Lennon, Gavin; Willox, Shannon; Ramdas, Ragini; Funston, Scott J.; Klun, Matthew; Pieh, Robert; Fairlie, Stewart; Dobbin, Sara; Cobice, Diego F. (2020). "Assessing the Oxidative Degradation of N-Methylpyrrolidone (NMP) in Microelectronic Fabrication Processes by Using a Multiplatform Analytical Approach". Journal of Analytical Methods in Chemistry. 2020 (1) 8265054. doi:10.1155/2020/8265054. ISSN 2090-8873. PMC 7073504. PMID 32190404.
- ^ CN113727969B, 沈成元, "Method for purifying waste N-methyl-2-pyrrolidone mixed liquor", issued 4 March 2025
- ^ a b c Jönsson, B. A. G.; Åkesson, B. (1 May 2003). "Human experimental exposure to N-methyl-2-pyrrolidone (NMP): toxicokinetics of NMP, 5-hydroxy-N-methyl-2-pyrrolidone, N-methylsuccinimide and 2-hydroxy-N-methylsuccinimide (2-HMSI), and biological monitoring using 2-HMSI as a biomarker". International Archives of Occupational and Environmental Health. 76 (4): 267–274. Bibcode:2003IAOEH..76..267J. doi:10.1007/s00420-003-0438-5. ISSN 1432-1246. PMID 12684812.
- ^ Poet, Torka S.; Kirman, Chris R.; Bader, Michael; van Thriel, Christoph; Gargas, Michael L.; Hinderliter, Paul M. (13 February 2010). "Quantitative Risk Analysis for N-Methyl Pyrrolidone Using Physiologically Based Pharmacokinetic and Benchmark Dose Modeling". Toxicological Sciences. 113 (2): 468–482. doi:10.1093/toxsci/kfp264. ISSN 1096-6080. PMID 19875680.
- ^ Kubota, Ryuichi; Endo, Yoko; Takeuchi, Akito; Inoue, Yoshinori; Ogata, Hiroko; Ogawa, Masanori; Nakagawa, Tomoo; Onda, Nobuhiko; Endo, Ginji (1 July 2007). "SPE–GC/FTD determination of N-methyl-2-pyrrolidone and its metabolites in urine". Journal of Chromatography B. 854 (1): 204–210. doi:10.1016/j.jchromb.2007.04.022. ISSN 1570-0232. PMID 17485256.
- ^ Åkesson, Bengt; Carnerup, Martin A.; Jönsson, Bo AG (2004). "Evaluation of exposure biomarkers from percutaneous absorption of N-methyl-2-pyrrolidone". Scandinavian Journal of Work, Environment & Health. 30 (4): 306–312. doi:10.5271/sjweh.799. ISSN 0355-3140. PMID 15458014.