Triacetin
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| Names | |
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| Systematic IUPAC name
Propane-1,2,3-triyl triacetate | |
Other names
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| Identifiers | |
3D model (JSmol) |
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| ChEBI | |
| ChEMBL | |
| ChemSpider | |
| ECHA InfoCard | 100.002.775 |
| EC Number |
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| E number | E1518 (additional chemicals) |
| KEGG | |
PubChem CID |
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| RTECS number |
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| UNII | |
CompTox Dashboard (EPA) |
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| Properties | |
| C9H14O6 | |
| Molar mass | 218.205 g·mol−1 |
| Appearance | Oily liquid |
| Density | 1.155 g/cm3[2] |
| Melting point | −78 °C (−108 °F; 195 K)[3]: 3–534 |
| Boiling point | 259 °C (498 °F; 532 K)[3]: 3–534 |
| 6.1 g/100 mL[4][page needed] | |
| Solubility in ethanol | Miscible |
| Solubility in benzene | soluble |
| Solubility in diethyl ether | soluble |
| Solubility in acetone | very soluble |
| Vapor pressure |
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Refractive index (nD) |
1.4301 (20 °C (68 °F; 293 K))[3]: 3–534 |
| Viscosity | 23 mPas (20 °C (68 °F; 293 K))[2] |
| Thermochemistry[5][3]: 6–121 | |
Heat capacity (C) |
389 J⋅mol−1·K-1 |
Std molar entropy (S⦵298) |
458.3 kJ⋅mol−1·K-1 |
Std enthalpy of formation (ΔfH⦵298) |
−1330.8 kJ⋅mol−1 |
Std enthalpy of combustion (ΔcH⦵298) |
4211.6 kJ⋅mol−1 |
Enthalpy of vaporization (ΔfHvap) |
85.74 kJ⋅mol−1 |
| Hazards[2] | |
| NFPA 704 (fire diamond) | |
| Flash point | 138 °C (280 °F; 411 K) |
| 430 °C (806 °F; 703 K) | |
| Explosive limits | 7.73%-? |
| Lethal dose or concentration (LD, LC): | |
LD50 (median dose) |
3 g/kg (rat, oral)[2] |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Triacetin, also known as glyceryl triacetate, is the organic compound with the formula C3H5(OCOCH3)3. It is classified as a triglyceride, i.e., the triester of glycerol with acetic acid. It is a colorless, viscous, and odorless liquid with a high boiling point and a low melting point. It has a mild, sweet taste in concentrations lower than 500 ppm, but may appear bitter at higher concentrations.[6] It is one of the glycerine acetate compounds.
Uses
[edit]Triacetin is a common food additive, for instance as a solvent in flavorings, and for its humectant function, with E number E1518 and Australian approval code A1518. It is used as an excipient in pharmaceutical products, where it is used as a humectant, a plasticizer, and as a solvent.[7]
Potential uses
[edit]The plasticizing capabilities of triacetin have been utilized in the synthesis of a biodegradable phospholipid gel system for the dissemination of the cancer drug paclitaxel (PTX).[8] In the study, triacetin was combined with PTX, ethanol, a phospholipid and a medium chain triglyceride to form a gel-drug complex. This complex was then injected directly into the cancer cells of glioma-bearing mice. The gel slowly degraded and facilitated sustained release of PTX into the targeted glioma cells.
Triacetin can also be used as a fuel additive as an antiknock agent for gasoline, and to improve low-temperature viscosity properties of biodiesel.[9]
It has been considered as a possible source of food energy in artificial food regeneration systems on long space missions. It is believed to be safe to get over half of one's dietary energy from triacetin.[10]
Supplement and medical use
[edit]Triacetin is a controlled-release ester prodrug of the short-chain fatty acid acetate (acetic acid) and can be used to deliver acetate in the gut and body.[11][12][13] It is cleaved into glycerol and acetate (three per triacetin molecule) by pancreatic and gastric lipases.[12][13] Triacetin is water-soluble and has been of interest for potential use in parenteral nutrition.[12] It has also been investigated for the potential treatment of irritable bowel syndrome (IBS) and has been marketed for use in dietary supplements use under brand names like REBiome.[14] By delivering acetate, triacetin may increase levels of the major acetate-consuming and butyrate-producing gut bacteria Faecalibacterium prausnitzii.[14][15][16] It is a potential alternative to dietary fiber in increasing beneficial butyrate-producing gut bacteria like F. prausnitzii, which is relevant as fiber is often poorly tolerated in people with IBS due to gas production and bloating.[14]
Synthesis
[edit]Triacetin was first prepared in 1854 by the French chemist Marcellin Berthelot. Triacetin was prepared in the 19th century from glycerol and acetic acid.[17][18]
Its synthesis from acetic anhydride and glycerol is simple and inexpensive:
- 3 (CH3CO)2O + C3H5(OH)3 → C3H5(OCOCH3)3 + 3 CH3CO2H
This synthesis has been conducted with catalytic sodium hydroxide and microwave irradiation to give a 99% yield of triacetin.[19] Synthesis has also been conducted with a cobalt(II) Salen complex catalyst supported by silicon dioxide and heated to 50 °C (122 °F) for 55 minutes to give a 99% yield of triacetin.[20]
Safety
[edit]The US Food and Drug Administration has approved it as generally recognized as safe food additive and included it in the database according to the opinion from the Select Committee On GRAS Substances (SCOGS). Triacetin is included in the SCOGS database since 1975.[21][22]
Triacetin was not toxic to animals in studies of exposure through repeated inhalation over a relatively short period.[23]
See also
[edit]- Acetic acid (acetate)
- Tripropionin
- Tributyrin
References
[edit]- ↑ The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals (11th ed.). Merck. 1989. p. 9405. ISBN 091191028X.
- 1 2 3 4 "Triacetin SDS". fishersci.com. ThermoFisher Scientific. Retrieved 2025-12-05.
- 1 2 3 4 5 Lide D, ed. (2004). CRC Handbook of Chemistry and Physics (85th ed.). Boca Raton, Florida: CRC Press. ISBN 978-0-8493-0485-9.
- ↑ Lide DR, ed. (2009). CRC Handbook of Chemistry and Physics (90th ed.). Boca Raton, Florida: CRC Press. ISBN 978-1-4200-9084-0.
- ↑ Triacetin in Linstrom, Peter J.; Mallard, William G. (eds.); NIST Chemistry WebBook, NIST Standard Reference Database Number 69, National Institute of Standards and Technology, Gaithersburg (MD)
- ↑ Arctander S (1969). Perfume and Flavor Chemicals (II K - Z). Elizabeth, N.J.: Published by the Author. p. 2971. ISBN 978-0-931710-37-7.
- ↑ "Triacetin". drugtopics.modernmedicine.com. Advanstar Communications, Inc. Archived from the original on 2012-02-19. Retrieved 2014-06-20.
- ↑ Chen T, Gong T, Zhao T, Liu X, Fu Y, Zhang Z, et al. (August 2017). "Paclitaxel loaded phospholipid-based gel as a drug delivery system for local treatment of glioma". International Journal of Pharmaceutics. 528 (1–2): 127–132. doi:10.1016/j.ijpharm.2017.06.013. PMID 28596136.
- ↑ Gupta M, Kumar N (2012). "Scope and opportunities of using glycerol as an energy source". Renewable & Sustainable Energy Reviews. 16 (7): 4551–4556. Bibcode:2012RSERv..16.4551G. doi:10.1016/j.rser.2012.04.001.
- ↑ Shapira J, Mandel AD, Quattrone PD, Bell NL (1968). "Current Research On Regenerative Systems" (PDF). Life Sciences in Space Research. 7. Tokyo: Committee On Space Research, Eleventh Annual Meeting: 123–9. PMID 12197534. Retrieved 2024-07-16.
- ↑ Ibeanu GC, Eze DU, Eze A, Atoyebi SO, Akingbade T, Folarin AA, et al. (2026). "Exploring the mechanistic interplay between chronic high sugar consumption, gut microbiota, and Alzheimer's disease: Implications for drug discovery". The Journal of Nutritional Physiology. 6 100019. doi:10.1016/j.jnphys.2026.100019. Retrieved 9 July 2026.
Pharmacological analogs of SCFAs are an emerging therapeutic strategy that seeks to harness SCFA-like benefits for immune modulation and gut barrier maintenance, with the broader goal of influencing the gut–brain axis upstream to potentially delay neurodegenerative processes relevant to AD (Yang et al., 2024). These mimetics are typically designed either to deliver an SCFA payload in a more stable, tolerable form or to reproduce SCFA signaling by activating the same host receptors. A common structural approach uses ester prodrugs that preserve the short-chain carboxylate chemistry but package it for controlled release, such as triacetin (glycerol triacetate; SMILES CC(=O)OCC(COC(=O)C)OC(=O)C (Van den Abbeele et al., 2025; National Center for Biotechnology Information) and tributyrin (glyceryl tributyrate; a glycerol triester of butyric acid CCCC(=O)OCC(COC(=O)CCC)OC(=O)CCC). (Ullah et al., 2025; National Center for Biotechnology Information).
- 1 2 3 Wächtershäuser A, Stein J (August 2000). "Rationale for the luminal provision of butyrate in intestinal diseases". Eur J Nutr. 39 (4): 164–171. doi:10.1007/s003940070020. PMID 11079736.
Another possible source of butyrate are structured lipids, e. g. SCFA-containing triglycerides (SCT). Butyryl triglyceride (tributyrin or glyceryl tributyrate) is a SCT with butyrate esterified at the 1, 2, and 3 positions and a candidate precursor for butyrate that could be administered orally [18]. Like triacetin it is neutral, chemically stable, and rapidly hydrolysed by pancreatic and gastric lipases to glycerol and their respective even-numbered SCFA, butyrate or – in the case of triacetin – acetate. Parenterally administered SCTs are readily hydrolised to glycerol and free fatty acids in the bloodstream [20]. In contrast to tributyrin, triacetin is water-soluble and does not require emulsification, which makes it a very versatile, alternative energy source to be incorporated into parenteral nutrition (TPN) or total enteral nutrition regimens.
- 1 2 Stein J (April 1999). "Chemically defined structured lipids: current status and future directions in gastrointestinal diseases". Int J Colorectal Dis. 14 (2): 79–85. doi:10.1007/s003840050190. PMID 10367252.
Therefore, provision of SCFA-containing triglycerides (e.g., triacetin and tributyrin) may be an excellent alternative source of SCFAs. Short-chain triglycerides (SCTs) such as triacetin (C2:0) and tributyrin (C4:0) are neutral, chemically stable, and rapidly hydrolyzed by pancreatic and gastric lipases to glycerol and their respective evennumbered SCFAs, acetate and butyrate. Parenterally administered SCTs are readily hydrolyzed to glycerol and free fatty acids in the bloodstream. The fact that triacetin, in contrast to tributyrin, is water-soluble and does not require emulsification, as does tributyrin, to be infused makes it a very versatile alternative energy source to be incorporated into total parenteral nutrition (TPN) or total enteral nutrition regimens [5].
- 1 2 3 Van den Abbeele P, Poppe J, Baudot A, Vu LD (September 2025). "Triacetin and a Mushroom Blend Restore Butyrate Production by IBS Microbiomes Ex Vivo, Thus Promoting Barrier Integrity". Int J Mol Sci. 26 (19): 9388. doi:10.3390/ijms26199388. PMC 12524982. PMID 41096656.
- ↑ Martín R, Rios-Covian D, Huillet E, Auger S, Khazaal S, Bermúdez-Humarán LG, et al. (July 2023). "Faecalibacterium: a bacterial genus with promising human health applications". FEMS Microbiol Rev. 47 (4) fuad039. doi:10.1093/femsre/fuad039. PMC 10410495. PMID 37451743.
Cross-feeding occurs when a species metabolizes metabolites produced by another species (D'Souza et al. 2018). SCFAs in particular acetate, are among the most common cross-fed metabolites in the bacterial communities of the human gut (D'Souza et al. 2018). Acetate consumption is the major driver of butyrate production by members of Faecalibacterium genus (process known as acetate-cross feeding) in the healthy human gut (Miquel et al. 2013). [...] Some improve Faecalibacterium abundance, perhaps because traditional probiotics often produce acetate. Acetate promotes the growth of Faecalibacterium via cross-feeding (Ramirez-Farias et al. 2009).
- ↑ Miquel S, Martín R, Bridonneau C, Robert V, Sokol H, Bermúdez-Humarán LG, et al. (2014). "Ecology and metabolism of the beneficial intestinal commensal bacterium Faecalibacterium prausnitzii". Gut Microbes. 5 (2): 146–151. doi:10.4161/gmic.27651. PMC 4063839. PMID 24637606.
F. prausnitzii is an acetate consumer and butyrate producer, and it can also produce carbon dioxide, formate, and D-lactate, although none of the strains isolated to date produce hydrogen.1,53 In batch cultures, most of the carbon in the butyrate produced (around 85%) is derived from external acetate, with only 15% provided directly from glucose.54 [...] This is consistent with a putative symbiotic cooperation or cross feeding between F. prausnitzii and microbes generally recognized as beneficial, such as Bifidobacterium and Lactobacillus spp.45,46 For instance, Bifidobacteria are acetate producers in the gut, and one possible approach to increase the F. prausnitzii population is to feed Bifidobacteria, which then feed F. prausnitzii by producing acetate.
- ↑ Berthelot M (1854). "Sur les combinaisons de le glycérine avec les acides et sur la synthèse des principes immédiats des graisses des animaux" [On the compounds of glycerin with acids and on the synthesis of immediate principles of animal fats]. Annales de Chimie et de Physique. 3rd series (in French). 41: 216–319.
- ↑ "Preparation of glyceryl triacetate". Journal of the Chemical Society, Abstracts. 38: 312. 1880. doi:10.1039/CA8803800307.
- ↑ Rajabi F, Saidi MR (2005). "A Cheap, Simple, and Versatile Method for Acetylation of Alcohols and Phenols and Selective Deprotection of Aromatic Acetates Under Solvent-Free Condition". Synthetic Communications. 35 (3): 483–491. doi:10.1081/SCC-200048988. ISSN 0039-7911. S2CID 96001761.
- ↑ Rajabi F (2009). "A heterogeneous cobalt(II) Salen complex as an efficient and reusable catalyst for acetylation of alcohols and phenols". Tetrahedron Letters. 50 (4): 395–397. doi:10.1016/j.tetlet.2008.11.024.
- ↑ "21 CFR § 184.1901 Listing of Specific Substances Affirmed as GRAS: Triacetin". eCFR.gov. FDA. 21 Feb 1989. Retrieved 25 Apr 2023.
- ↑ "Glycerin and Glycerides". www.fda.gov. U.S. Food and Drug Administration. Archived from the original on 2017-10-31. Retrieved 2014-06-20.
Triacetin and two types of acetooleins have been found to be without toxic effects in long-term feeding tests in rats at levels that were several orders of magnitude greater than those to which consumers are exposed.
- ↑ Fiume MZ (2003). "Final report on the safety assessment of triacetin". International Journal of Toxicology. 22 Suppl 2 (3): 1–10. doi:10.1080/747398359. PMID 14555416.