Synthesis and Applications of THF

Tetrahydrofuran(THF)is a nonplanar compound existing in various conformations. It is also known as oxolane and is present in numerous natural products as a substructure of biological importance. It is a versatile solvent, used in organic synthesis  and the preparation of varnishes.

Physical Properties 

Tetrahydrofuran is a colorless, volatile, flammable, pleasant-smelling liquid with low viscosity and a bp of 64°C. It is one of  the most polar cyclic ethers. THF should not be distilled to dryness because it leaves a residue of high explosive  peroxides. The 1 H NMR spectrum in CCl4  showed two peaks at δ 3.61 ppm for C2 –H and C5 –H, while a peak at δ 1.79 ppm is  designated for C3 –H and C4 –H protons. The 13C NMR showed two peaks at δ 68.60 ppm for C2  and C5 , while a peak at δ 26.20 ppm was assigned for C3 and C4.

Synthesis 

Commercially, Gilbert and Howk in 1956 prepared THF by catalytic hydrogenation of maleic anhydride in the  presence of Ni catalyst at 180–300°C and 150 kg/cm2  pressure. Du Pont later synthesized THF by the catalytic hydrogenation of parent furan.

Presently, THF is manufactured by acid (H3 PO4  or H2 SO4 )-catalyzed dehydration of 1,4-butanediol.

 A convenient high-yielding general synthesis of optically active THF has been developed through ring expansion of 2-substituted and 2,2-disubstituted oxetanes with dimethylsulfoxonium methylide.

Applications 

THF is used as a solvent in organic synthesis and chromatographic analysis, and is an intermediate of nylon-6,6.  It is also used as an intermediate for synthetic pesticides, e.g., fenbutatin. It is directly used for synthetic fibers,  synthetic resins, synthetic rubber, as well as a solvent for many polymeric materials. It is widely used as surface  coatings, anticorrosion coatings, and printing inks. In the pharmaceutical industry, THF is used for the synthesis of  carbetapentane, rifamycin, progesterone, and some hormone drugs.