(2S)-1,1,1-Trifluoropropan-2-ol
[CAS# 3539-97-7]

Identification

• Classification: Organic raw materials >> Alcohols, phenols, phenolic compounds and derivatives
• Name: (2S)-1,1,1-Trifluoropropan-2-ol
• Synonyms: (S)-(-)-1,1,1-Trifluoro-2-propanol
• Molecular Formula: C₃H₅F₃O
• Molecular Weight: 114.07
• CAS Registry Number: 3539-97-7
• EC Number: 690-088-2
• SMILES: C[C@@H](C(F)(F)F)O

Properties

• Solubility: Soluble (76 g/L) (25 ºC), Calc.^*
• Density: 1.235±0.06 g/cm³ (20 ºC 760 Torr), Calc.^*
• Boiling point: 67.0±35.0 ºC (760 Torr), Calc.^*
• Flash point: 38.8±17.0 ºC, Calc.^*
• Index of refraction: 1.312 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2013 ACD/Labs)

Safety Data

• Hazard Symbols: GHS02;GHS07 DangerGHS02
• Hazard Statements: H225-H315-H319-H335
• Precautionary Statements: P210-P233-P240-P241-P242-P243-P261-P264-P264+P265-P271-P280-P302+P352-P303+P361+P353-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P370+P378-P403+P233-P403+P235-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Flammable liquids	Flam. Liq.	2	H225
Eye irritation	Eye Irrit.	2A	H319
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335

Discovory and Applicatios

(2S)-1,1,1-Trifluoropropan-2-ol is a chiral fluorinated alcohol that has been studied for its applications in asymmetric synthesis and pharmaceutical intermediate development. The compound contains a trifluoromethyl group at the terminal carbon, a secondary alcohol at the 2-position, and exhibits (2S) stereochemistry, making it optically active. The trifluoromethyl group is strongly electron-withdrawing, which influences both the acidity of adjacent protons and the reactivity of the hydroxyl group, while the chiral center allows for enantioselective transformations. Its discovery is associated with efforts in organofluorine chemistry during the late 20th century, when chemists were increasingly exploring the synthesis of small fluorinated chiral molecules for use as building blocks in pharmaceuticals and agrochemicals.

The primary application of (2S)-1,1,1-trifluoropropan-2-ol is as an intermediate in the preparation of enantiomerically pure fluorinated compounds. Its secondary alcohol functionality can undergo esterification, etherification, and oxidation reactions, while the trifluoromethyl group modifies the electronic environment and increases metabolic stability in downstream products. In medicinal chemistry, derivatives of this compound are valuable for the synthesis of fluorinated drugs and drug candidates, as the trifluoromethyl group can enhance lipophilicity, improve bioavailability, and slow metabolic degradation. The presence of a chiral center allows for the generation of enantiomerically enriched products, which is critical in the development of active pharmaceutical ingredients with high specificity and reduced side effects.

In asymmetric synthesis, (2S)-1,1,1-trifluoropropan-2-ol is employed as a chiral building block for constructing more complex molecules. The combination of the hydroxyl group and the trifluoromethyl substituent enables stereoselective reactions such as nucleophilic additions, reductions, and substitutions. This makes it a versatile intermediate for preparing chiral fluorinated alcohols, ethers, and other functionalized scaffolds. The ability to introduce both a trifluoromethyl group and a stereocenter in a single building block streamlines synthetic routes, which is advantageous in both laboratory and industrial settings.

The compound has also been explored in agrochemical synthesis, where fluorinated chiral intermediates are used to develop herbicides and fungicides with improved efficacy and environmental stability. The trifluoromethyl group increases the chemical robustness of these compounds, while the chiral center can influence biological activity and selectivity toward target organisms.

The discovery and application of (2S)-1,1,1-trifluoropropan-2-ol illustrate the broader significance of chiral fluorinated building blocks in modern chemistry. Its structural features provide both reactivity and stereochemical control, making it a valuable tool for the synthesis of enantiomerically enriched pharmaceuticals, agrochemicals, and specialty chemicals. The compound exemplifies how the incorporation of trifluoromethyl groups and stereocenters into small molecules can expand the possibilities of synthetic design and improve the performance of downstream products.

References

2017. Characterization of two carbonyl reductases from Ogataea polymorpha NBRC 0799. Applied Microbiology and Biotechnology, 101(24).
DOI: 10.1007/s00253-017-8668-8

2012. Process Research and Development for Heterocyclic p38 MAP Kinase Inhibitors. Synlett, 2012(13).
DOI: 10.1055/s-0031-1290425