In the vast field of organic synthetic chemistry, diethylaminosulfur trifluoride (DAST) is a legend in the world of fluorinating reagents. Since its initial report by Middleton in the 1970s, this seemingly ordinary yellowish-brown liquid has become one of the most indispensable nucleophilic fluorinating reagents in the laboratory. From anticancer drugs to pesticide molecules, from glycochemistry to materials science, DAST continues to drive the forefront of fluorine-containing compound synthesis with its unique reactivity and broad substrate applicability.
Molecular Profile
Chemical Formula: C₄H₁₀F₃NS
Molecular Weight: 161.19 g/mol
CAS Number: 38078-09-0
Structural Characteristics: Et₂N-SF₃ (diethylamino group attached to sulfur trifluoride group)
Physical State: Yellowish-brown liquid with a characteristic odor
DAST is a nucleophilic fluorinating agent. Its core mechanism of action lies in the synergistic effect of the electrophilicity of the sulfur atom and the nucleophilicity of the fluoride ion:
Mechanism Pathway of Alcohol Fluorination
When DAST reacts with an alcohol, the following key steps occur:
Nucleophilic Attack: The oxygen atom of the alcohol’s hydroxyl group attacks the sulfur atom, forming an intermediate.
Leaving Group Activation: The diethylamino group, as an excellent leaving group, is eliminated.
Fluoride Ion Transfer: The fluoride ion transfers from the sulfur center to the carbon atom, completing SN2 or SN1 substitution.
For primary alcohols, the reaction is usually started at -78°C to control exothermic reactions, followed by natural warming to room temperature; secondary alcohols require heating or reflux to promote complete reaction.
A Key Role in Cyanide-Free Reactions
In 2024, Hee Nam Lim’s team at Yeungnam University in South Korea reported in *Chemical Communications* the innovative application of DAST in the synthesis of cyanide-free thiocyanates and cyanamides. This reaction utilizes DAST as a nucleophilic fluorine donor to induce the cleavage of deacetylated C-C bonds, achieving the conversion from thiols and amines to the corresponding cyanides, avoiding the high toxicity issues of traditional cyaniding reagents.
Competition and Complementarity of Novel Fluoridating Reagents
Despite the widespread application of DAST, its safety concerns have spurred the development of a series of improved reagents:
Deoxofluor (BAST): Bis(2-methoxyethyl)aminosulfur trifluoride, with better thermal stability, decomposing slowly upon heating rather than exploding.
XtalFluor series: Crystalline solids, easy to handle and weigh.
FLUOLEAD®: 4-tert-butyl-2,6-dimethylphenylsulfur trifluoride, a safer alternative.
However, DAST still dominates in laboratory-scale synthesis due to its cost-effectiveness and extensive literature support.
From a laboratory gem in the 1970s to a staple of synthetic chemistry in the 21st century, the evolution of DAST is a microcosm of the development of fluorine chemistry. Despite the emergence of numerous new fluorinating agents, DAST continues to play an irreplaceable role in drug discovery, pesticide development, and materials science due to its mature reaction system, broad substrate applicability, and high atom economy.
With the application of safe technologies such as continuous flow chemistry and its expanded functionality in new fields such as amide synthesis, this “old reagent” is experiencing a resurgence. For organic synthetic chemists, mastering the art of using DAST is undoubtedly a golden key to unlocking the door to fluorine chemistry.
Post time: Feb-26-2026
