1,3-Butanediol

1,3-Butanediol

Skeletal formula of 1,3-butanediol
Ball and stick model of 1,3-butanediol (S) Spacefill model of 1,3-butanediol (S)
Names
Preferred IUPAC name Butane-1,3-diol
Other names 1,3-butylene glycol, butane-1,3-diol, or 1,3-dihydroxybutane
Identifiers
CAS Number	107-88-0  Y 6290-03-5 (R) Y 24621-61-2 (S) Y
3D model (JSmol)	Interactive image
Beilstein Reference	1731276 1718944 (R) 1718943 (S)
ChEBI	CHEBI:52683  N
ChEMBL	ChEMBL1231503  N
ChemSpider	7608  Y 553103 (R) Y 394191 (S) Y
DrugBank	DB02202  N
ECHA InfoCard	100.003.209
EC Number	203-529-7
E number	E1502 (additional chemicals)
Gmelin Reference	2409 2493173 (R) 1994384 (S)
KEGG	D10695  N
MeSH	1,3-Butylene+glycol
PubChem CID	7896 637497  (R) 446973  (S)
RTECS number	EK0440000
UNII	3XUS85K0RA  Y
CompTox Dashboard (EPA)	DTXSID8026773
InChI InChI=1S/C4H10O2/c1-4(6)2-3-5/h4-6H,2-3H2,1H3 N Key: PUPZLCDOIYMWBV-UHFFFAOYSA-N N
SMILES CC(O)CCO
Properties
Chemical formula	C4H10O2
Molar mass	90.122 g·mol−1
Appearance	Colourless liquid
Density	1.0053 g cm−3
Melting point	−50 °C (−58 °F; 223 K)
Boiling point	204 to 210 °C; 399 to 410 °F; 477 to 483 K
Solubility in water	1 kg dm−3
log P	−0.74
Vapor pressure	8 Pa (at 20 °C)
Refractive index (nD)	1.44
Thermochemistry
Std molar entropy (S⦵298)	227.2 J K−1 mol−1
Std enthalpy of formation (ΔfH⦵298)	−501 kJ mol−1
Std enthalpy of combustion (ΔcH⦵298)	−2.5022 MJ mol−1
Hazards
GHS labelling:
Pictograms
Signal word	Warning
Hazard statements	H319, H413
Precautionary statements	P305+P351+P338
NFPA 704 (fire diamond)	1 1 0
Flash point	108 °C (226 °F; 381 K)
Autoignition temperature	394 °C (741 °F; 667 K)
Related compounds
Related butanediol	1,2-Butanediol 1,4-Butanediol 2,3-Butanediol
Related compounds	2-Methylpentane
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). N  verify  (what is  YN ?) Infobox references

1,3-Butanediol is an organic compound with the formula CH₃CH(OH)CH₂CH₂OH, not to be confused with 1,4 Butanediol. With two alcohol functional groups, the molecule is classified as a diol. The compound without the R (or D) designation is racemic, which is what has been used in most studies before 2023. The compound is a colorless, bittersweet, water-soluble liquid. It is one of four common structural isomers of butanediol. ^{[1] [2] [3]} It is used in grape flavoring, ^[4] and as a precursor to some antibiotics. ^[5]

Production and uses

Hydrogenation of 3-hydroxybutanal gives 1,3-butanediol: ^[6]

CH₃CH(OH)CH₂CHO + H₂ → CH₃CH(OH)CH₂CH₂OH

Dehydration of 1,3-butanediol gives 1,3-butadiene:

CH₃CH(OH)CH₂CH₂OH → CH₂=CH-CH=CH₂ + 2 H₂O

Pharmacology

1,3-Butanediol has sedative, hypotensive and hypoglycaemic action comparable to ethanol, with the (R), also known as (D), enantiomer being more active. ^{[7] [8]} Fatty acid esters of 1,3-butanediol such as the acetoacetate, lactate or hexanoate have been researched for inducing ketogenesis. ^{[9] [10] [11] [12] [13] [14] [15]} Recent research highlights the stereospecific metabolism of (R)-1,3-butanediol, emphasizing its efficient conversion to β-hydroxybutyrate via alcohol dehydrogenase. This process involves zinc coordination and maintains cellular redox balance. Notably, (R)-1,3-butanediol induces mild euphoric effects through ketone body signaling pathways, distinct from the GABAergic mechanisms associated with ethanol. ^[16]

Occurrence

1,3-Butanediol has been detected in green bell peppers, orange bell peppers, pepper ( Capsicum annuum ), red bell peppers, and yellow bell peppers. ^[17] 1,3 Butanediol, | quote = Also referred to as 1,3-Butylene glycol, maintains FDA GRAS status as a flavor molecule. ^[18]

Biochemistry

The metabolism of (R)-1,3-butanediol is compartmentalized within hepatic cells, occurring in both cytosolic and mitochondrial domains. Enzymatic studies have quantified the distribution of alcohol dehydrogenase isoforms involved in its conversion to β-hydroxybutyrate, underscoring the molecule's potential in therapeutic ketone body production. ^[16]

References

1. Gräfje H, Körnig W, Weitz HM, Reiß W, Steffan G, Diehl, et al. (2000). "Butanediols, Butenediol, and Butynediol". Ullmann's Encyclopedia of Industrial Chemistry . Weinheim: Wiley-VCH. doi:10.1002/14356007.a04_455. ISBN   9783527306732.
2. "1,3 Butylene Glycol". Parchem Fine & Specialty Chemicals.
3. Dymsza HA (November 1975). "Nutritional application and implication of 1,3-butanediol". Federation Proceedings. 34 (12): 2167–2170. PMID   1102338.
4. Dymsza HA. Nutritional application and implication of 1,3-butanediol. Fed Proc. 1975 Nov;34(12):2167-70 PMID   1102338
5. Guo X, Gao Y, Liu F, Tao Y, Jin H, Wang J, et al. (June 2023). "A short-chain carbonyl reductase mutant is an efficient catalyst in the production of (R)-1,3-butanediol". Microbial Biotechnology. 16 (6): 1333–1343. doi:10.1111/1751-7915.14249. PMC   10221522 . PMID   36946330.
6. Kohlpaintner C, Schulte M, Falbe J, Lappe P, Weber J (2008). "Aldehydes, Aliphatic". Ullmann's Encyclopedia of Industrial Chemistry . Weinheim: Wiley-VCH. doi:10.1002/14356007.a01_321.pub2. ISBN   978-3527306732.
7. Frye GD, Chapin RE, Vogel RA, Mailman RB, Kilts CD, Mueller RA, et al. (February 1981). "Effects of acute and chronic 1,3-butanediol treatment on central nervous system function: a comparison with ethanol". The Journal of Pharmacology and Experimental Therapeutics. 216 (2): 306–314. doi:10.1016/S0022-3565(25)32419-5. PMID   7193248.
8. Lowder J, Fallah S, Venditti C, Musa-Veloso K, Kotlov V (2023). "An open-label, acute clinical trial in adults to assess ketone levels, gastrointestinal tolerability, and sleepiness following consumption of (R)-1,3-butanediol (Avela™)". Frontiers in Physiology. 14: 1195702. doi: 10.3389/fphys.2023.1195702 . PMC   10338333 . PMID   37457035.
9. Hashim SA, VanItallie TB (September 2014). "Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester". Journal of Lipid Research. 55 (9): 1818–1826. doi: 10.1194/jlr.R046599 . PMC   4617348 . PMID   24598140.
10. Place DE, Kanneganti TD (March 2019). "Fueling Ketone Metabolism Quenches Salt-Induced Hypertension". Trends in Endocrinology and Metabolism. 30 (3): 145–147. doi:10.1016/j.tem.2019.01.004. PMID   30670332.
11. Evans M, McClure TS, Koutnik AP, Egan B (December 2022). "Exogenous Ketone Supplements in Athletic Contexts: Past, Present, and Future". Sports Medicine. 52 (Suppl 1): 25–67. doi:10.1007/s40279-022-01756-2. PMC   9734240 . PMID   36214993.
12. Mah E, Blonquist TM, Kaden VN, Beckman D, Boileau AC, Anthony JC, et al. (2023). "A randomized, open-label, parallel pilot study investigating metabolic product kinetics of the novel ketone ester, bis-hexanoyl (R)-1,3-butanediol, over one week of ingestion in healthy adults". Frontiers in Physiology. 14: 1196535. doi: 10.3389/fphys.2023.1196535 . PMC   10324611 . PMID   37427402.
13. Stubbs BJ, et al. A randomized, open-label, cross-over pilot study investigating metabolic product kinetics of the palatable novel ketone ester, bis-octanoyl (R)-1,3-butanediol, and bis-hexanoyl (R)-1,3-butanediol ingestion in healthy adults. Toxicology Research and Application 2023; doi : 10.1177/23978473231197835
14. Deemer SE, Roberts BM, Smith DL, Plaisance EP, Philp A (July 2024). "Exogenous ketone esters as a potential therapeutic for treatment of sarcopenic obesity". American Journal of Physiology. Cell Physiology. 327 (1): C140 –C150. doi:10.1152/ajpcell.00471.2023. PMID   38766768.
15. Ottosen RN, et al. Preparation and Preclinical Characterization of a Simple Ester for Dual Exogenous Supply of Lactate and Beta-hydroxybutyrate. Journal of Agricultural and Food Chemistry 2024; 72(36):19883–19890. doi : 10.1021/acs.jafc.4c04849
16. Ryan P (April 27, 2025). "R-1,3-Butanediol – Structure, Metabolism, and Biological Roles". SSRN Electronic Journal.
17. "Metabocard for 1,3-Butanediol". Human Metabolome Database. HMDB0031320. Retrieved 2022-05-12.
18. "FDA GRAS for 1,3 Butanediol for flavoring CFR - Code of Federal Regulations Title 21". www.accessdata.fda.gov. Archived from the original on September 15, 2003. Retrieved 2022-05-12.