(2R)-1,1,1-trifluoropropan-2-ol
[CAS# 17628-73-8]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyrimidine compound >> Alcohol
• Name: (2R)-1,1,1-trifluoropropan-2-ol
• Synonyms: (R)-1,1,1-Trifluoropropan-2-ol
• Molecular Formula: C₃H₅F₃O
• Molecular Weight: 114.07
• CAS Registry Number: 17628-73-8
• EC Number: 803-296-7
• SMILES: C[C@H](C(F)(F)F)O

Properties

• Density: 1.2±0.1 g/mL, Calc.^*
• Index of Refraction: 1.312, Calc.^*
• Boiling Point: 67.0±35.0 ºC (760 mmHg), Calc.^*
• Flash Point: 38.8±17.0 ºC, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software

Safety Data

• Hazard Symbols: GHS02;GHS07 Danger
• 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
Specific target organ toxicity - single exposure	STOT SE	3	H335
Skin irritation	Skin Irrit.	2	H315
Flammable liquids	Flam. Liq.	2	H225
Eye irritation	Eye Irrit.	2	H319
Eye irritation	Eye Irrit.	2A	H319

Discovory and Applicatios

In the ever-evolving landscape of chemical science, fluorinated compounds have carved a unique niche due to their exceptional properties. Among these, (2R)-1,1,1-trifluoropropan-2-ol, a chiral fluoroalcohol with the molecular formula C3H5F3O, stands out as a compound of significant interest. Known for its specific stereochemistry—denoted by the (R) configuration—this substance has garnered attention for its versatility in synthetic chemistry, pharmaceutical research, and material science. Its discovery and subsequent applications highlight the ingenuity of modern organic chemistry and its pursuit of novel molecular tools.

The origins of (2R)-1,1,1-trifluoropropan-2-ol can be traced to broader efforts to synthesize fluorinated alcohols, which gained momentum in the mid-20th century as fluorine chemistry advanced. Fluorinated compounds, prized for their stability and unique reactivity due to the electronegative trifluoromethyl (CF3) group, became targets for exploration. While the racemic form, 1,1,1-trifluoro-2-propanol, was known earlier, the isolation of its enantiomerically pure (R)-form emerged from advancements in asymmetric synthesis. Techniques leveraging chiral auxiliaries or catalysts enabled chemists to selectively produce (2R)-1,1,1-trifluoropropan-2-ol, with its stereochemistry confirmed through spectroscopic methods like NMR and optical rotation measurements (specific rotation [α]22/D +8.3°, c = 1% in chloroform).

The synthesis of this compound typically involves the reduction of trifluoroacetone or related precursors using stereoselective reagents. For instance, employing a chiral sulfinamide auxiliary or enzymatic methods has proven effective in achieving high enantiomeric purity, a critical factor for its applications. The compound’s discovery was not a singular event but a culmination of iterative refinements in fluorination techniques and chiral resolution strategies, reflecting the collaborative progress of organic chemists worldwide.

The applications of (2R)-1,1,1-trifluoropropan-2-ol are as diverse as they are impactful. In organic synthesis, it serves as a valuable building block and solvent. The presence of the trifluoromethyl group enhances its acidity (pKa ~12.4, more acidic than typical alcohols), making it a potent hydrogen-bond donor. This property is exploited in reactions like the Baeyer-Villiger oxidation, where it boosts the reactivity of peroxides, and in Lewis-acid-catalyzed epoxide ring-opening reactions. Its chirality further enables the synthesis of enantiopure intermediates, crucial for producing stereospecific pharmaceuticals where molecular handedness dictates biological activity.

In pharmaceutical research, (2R)-1,1,1-trifluoropropan-2-ol has been instrumental in crafting fluorinated amino acids and peptides. The trifluoromethyl group imparts metabolic stability and lipophilicity to drug candidates, enhancing their bioavailability. For example, it has been used to synthesize derivatives like 1,1,1-trifluoropropan-2-yl esters, which are explored as potential therapeutic agents. Its role extends to studying protein folding and enzyme interactions, where its fluorinated nature provides insights via NMR spectroscopy, a technique sensitive to fluorine’s nuclear properties.

Beyond synthesis and drug development, this compound finds use in material science. Its polarity and hydrogen-bonding capacity make it a candidate solvent for dissolving polar polymers like polyamides and polyesters, aiding in the development of advanced materials. While its industrial production remains limited due to cost and scale, its niche applications underscore its value in high-precision fields.

Looking forward, (2R)-1,1,1-trifluoropropan-2-ol exemplifies the promise of fluorinated chiral molecules. Ongoing research aims to streamline its synthesis and expand its utility, potentially unlocking new frontiers in catalysis and green chemistry. As a testament to human curiosity and innovation, this compound bridges fundamental discovery with practical application, enriching our chemical toolkit.

References

Begue, J. P., Bonnet-Delpon, D., and Crousse, B., 2004. Fluorinated alcohols as solvents in catalysis. Synlett, 2004(1), pp. 18-29.
DOI: 10.1055/s-2003-44973

Kitazume, T. and Yamazaki, T., 1998. Enzymatic synthesis of optically active fluorinated compounds. Journal of Fluorine Chemistry, 89(1), pp. 73-77.
DOI: 10.1016/S0022-1139(98)00084-8

Prakash, G. K. S., Mandal, M., and Olah, G. A., 2001. Asymmetric synthesis of trifluoromethylated allylic alcohols. Organic Letters, 3(18), pp. 2847-2850.
DOI: 10.1021/ol016398v