Three-Steps Synthesis of Tryptamine Derivatives from Indole-3-Carboxaldehyde
Keywords:
tryptamine , aliphatic amine , Ni(OAc)2·4H2O , NaBH4, reduction reactionAbstract
Background and Objectives : The conventional approach to synthesizing tryptamine derivatives typically involves reducing 3-(2-nitrovinyl)indoles using LiAlH4 as a reducing reagent in a dry THF solvent. However, the method often leads to partial dehalogenation of the 3-(2-nitrovinyl)indole bearing halogen atom on the indole ring, resulting in a mixture of tryptamine and halotryptamine products. Furthermore, limitations of this method include harsh reaction conditions, sensitivity to air and moisture, and the requirement for an expensive reducing agent LiAlH4. In this study, a three-step synthesis of tryptamine derivatives from commercially available indole-3-carboxaldehyde was developed utilizing the Henry reaction and reduction of the resulting vinyl nitro moiety to ethyl amine, employing a combination of NaBH4 and Ni(OAc)2×4H2O as the reducing agent.
Methodology : To study the synthesis of tryptamine derivatives via a three-step process from commercially available indole-3-carboxaldehyde involves the Henry reaction and reduction of the resulting vinyl nitro group to ethyl amine, using NaBH4 and Ni(OAc)2∙4H2O as the reducing agent. The synthesis of tryptamine derivatives using various starting materials of 3-(2-nitrovinyl)indole was demonstrated.
Main Results : Initially, 3-(2-nitrovinyl)indole derivatives were synthesized in good to excellent yields from indole-3-carboxaldehyde via Henry reaction. The resulting 3-(2-nitrovinyl)indole derivatives were then reduced using NaBH4, leading to the formation of 3-(2-nitroethyl)indoles. In the final steps, the conversion 3-(2-nitroethyl)indoles to the desired tryptamine derivative was accomplished by employing a combination of NaBH4 (4 equiv) as a reducing agent and Ni(OAc)2∙4H2O (1 equiv) as a catalyst in a mixed solvent of acetonitrile and water (60:1) at room temperature for 20 minutes.
Conclusions : Tryptamine derivatives, including halogenated tryptamines, were synthesized in moderate to good yield via a three-step process from commercially available indole-3-carbladehydes. The key approach involves the use of a combination between NaBH4 and Ni(OAc)2∙4H2O for reducing 3-(2-nitroethyl)indoles to tryptamine derivatives.
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