Study On The Synthesis Of 2-Thiophene-2-yl-ethylamine

2-Thiophene-2-yl-ethylamine was synthesized from thiophene via two different routes. Vilsmeier-Haauc reaction of thiophene with DMF and POCl₃ gave thiophene-2-carbaldehyde in 83% yield. Knoevenagel condensation of thiophene-2-carbaldehyde with nitromethane gave 2-(2-nitrovinyl)thiophene in 61% yield. Reduction of 2-(2-nitrovinyl)thiophene with lithium aluminum hydride gave 2-thiophene-2-yl-ethylamine in 67% yield. Knoevenagel-Doeber condensation of thiophene-2-carbaldehyde with malonic acid gave the intermediate 3-thiophene-2-yl-acrylic acid in 87% yield. Reaction of 3-thiophene-2-yl-acrylic acid with SOCl₂ and NH3 followed by double bond reduction gave 3-thiophene-2-yl-propionamide in 89% overall yield. 2-Thiophene-2-yl-ethylamine was then obtained in 64% yield from 3-thiophene-2-yl-propionamide via Hofmann rearrangement.Different reducing agents, such as hydrazine, NaBH₄/BiCl_s were tried to reduce the double bond of 3-thiophene-2-yl-acrylamide. It was found that 3-thiophene-2-yl-acrylami-de can be reduced to 3-thiophene-2-yl-propionamide in 91% yield with NaBH₄/BiCl₃.The catalyst BiCl₃ was recoved and recycled in the reaction for 4 times without decreasion of the yield of 3-thiophene-2-yl-propionamide. The experiments show that the four-step route starting from thiophene-2-carbaldehyde and the malonic acid via Knoevenagel-Doebner condensation, amidation, reduction of double bond with NaBH₄/BiCl₃ and Hofmann rearrangement, has several advantages, such as higher overall yield, no use of dangerous raw material or reagent and recycling of the catalyst BiCl₃ without poisoning.