Trifluoromethylethyne
[CAS# 661-54-1]

Identification

• Classification: Chemical reagent >> Organic reagent >> Alkyne
• Name: Trifluoromethylethyne
• Synonyms: 3,3,3-Trifluoropropyne
• Molecular Formula: C₃HF₃
• Molecular Weight: 94.04
• CAS Registry Number: 661-54-1
• EC Number: 211-548-7
• SMILES: C#CC(F)(F)F

Properties

• Solubility: Slightly soluble (4.1 g/L) (25 ºC), Calc.^*
• Density: 1.202±0.06 g/cm³ (20 ºC 760 Torr), Calc.^*
• Boiling point: -48-47 ºC (705 Torr)^**
• Flash point: -94.5±13.9 ºC, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2016 ACD/Labs)^**Finnegan, Wm. G.; Journal of Organic Chemistry 1963, V28, P1139-40.

Safety Data

• Hazard Symbols: GHS04;GHS07 Warning
• Hazard Statements: H221-H280-H315-H319-H335-H380
• Precautionary Statements: P261-P264-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P321-P332+P313-P337+P313-P362+P364-P377-P381-P403-P403+P233-P405-P410+P403-P501
• Transport Information: UN 3161 2.1

Discovory and Applicatios

Trifluoromethylethyne, also known as 3,3,3-trifluoropropyne and chemically represented by the formula CF₃C≡CH, is a fluorinated alkyne compound with distinct structural and chemical characteristics. It is a colorless and flammable gas at room temperature, with a sharp, ethereal odor. The molecule consists of a terminal alkyne group bonded to a trifluoromethyl substituent, an arrangement that significantly influences its chemical reactivity. The discovery and study of trifluoromethylethyne trace back to investigations in organofluorine chemistry during the mid-20th century.

The earliest documented synthesis of trifluoromethylethyne was achieved in the early 1960s. Researchers obtained this compound through dehydrohalogenation reactions involving halogenated trifluorinated ethane derivatives. For example, 1,1,1-trifluoro-2-chloro-2-bromoethane was treated with strong bases such as potassium tert-butoxide to eliminate hydrogen halides, yielding the desired alkyne. The compound's synthesis was performed under strictly controlled conditions due to its volatility and flammability. The generation of the compound in a relatively pure form required careful low-temperature distillation under an inert gas atmosphere. These early studies contributed to a growing understanding of how the trifluoromethyl group influences the acidity and stability of acetylenic compounds.

Trifluoromethylethyne is notable for its significantly acidic terminal hydrogen. The electron-withdrawing nature of the trifluoromethyl group lowers the pK_a of the alkyne, making it more acidic than unsubstituted acetylenes. This property allows for the facile formation of metal acetylides when reacted with strong bases or metal alkoxides. These metal derivatives have proven useful as intermediates in various carbon-carbon bond-forming reactions.

Applications of trifluoromethylethyne are primarily found in organic synthesis. One well-established use is in palladium-catalyzed cross-coupling reactions, particularly the Sonogashira coupling. In this transformation, trifluoromethylethyne serves as the alkyne partner and reacts with aryl or vinyl halides to produce substituted acetylenes bearing the trifluoromethyl group. These products are valuable in medicinal and agrochemical research due to the desirable properties imparted by the CF₃ group, such as increased lipophilicity and metabolic stability.

Another important application is in cycloaddition chemistry. Trifluoromethylethyne participates in \[3+2] cycloadditions with azides, leading to the formation of 1,2,3-triazoles bearing a trifluoromethyl group. These fluorinated triazoles are of interest for the development of bioactive molecules, given their potential for improved pharmacokinetic profiles. Additionally, reactions with nitrile oxides have produced isoxazole derivatives, further expanding the utility of trifluoromethylethyne in heterocyclic synthesis.

The compound also undergoes electrophilic addition reactions under appropriate conditions, although the CF₃ group can reduce the electron density on the triple bond, making such reactions less favorable than with other alkynes. Nonetheless, the reactivity remains sufficient for strategic chemical transformations under optimized conditions.

Despite its promising synthetic utility, trifluoromethylethyne has not seen extensive industrial application. This is largely due to the hazards associated with its handling, including flammability and potential for spontaneous polymerization. In laboratory-scale synthesis, it remains an important intermediate for constructing fluorinated molecular frameworks and introducing the trifluoromethyl functionality in a linear fashion.

Through its unique electronic properties and demonstrated reactivity in carbon-carbon and carbon-heteroatom bond formation, trifluoromethylethyne continues to serve as a useful compound in the synthesis of fluorinated materials, contributing to advancements in pharmaceuticals, agrochemicals, and materials science.

References

1963. Ein Fundamentalproblem der Strukturchemie Untersuchungen �ber die Additivit�t der Atomabst�nde, Fortschritte der Chemischen Forschung (1)
DOI: 10.1007/bfb0051918

2006. Synthesis of heterocycles with polyfluoroalkyl substituents from unsaturated compounds containing polyfluoroalkyl groups. (Review), Chemistry of Heterocyclic Compounds (42)
DOI: 10.1007/s10593-006-0087-1

2009. New Preparation and Synthetic Reactions of 3,3,3-Trifluoropropynyllithium, -Borate and -Stannane: Facile Synthesis of Trifluoromethylated Allenes, Arylacetylenes and Enynes, Future Medicinal Chemistry (4)
DOI: 10.4155/fmc.09.69