Synthese von neuen (Phenylalkyl)aminen zur Untersuchung von Struktur–Aktivitätsbeziehungen. Mitteilung 2

Synthesis of Novel (Phenylalkyl)amines for the Investigation of Structure–Activity Relationships. Part 2¹). 4‐Thio‐Substituted 2‐(2,5‐Dimethoxyphenyl)ethyl]amines (=2,5‐Dimethoxybenzeneethanamines) The 4‐substituted 2‐(2,5‐dimethoxyphenyl)ethyl]amines (=2,5‐dimethoxybenzeneethanamines) and its α‐methyl analogs are known to act as potent 5‐HT_2A/C ligands, which have, depending on their 4‐substituent, agonistic or antagonistic character. Generally, compounds with a small lipophilic substituent typically are agonists and those with a larger lipophilic substituent predominantly antagonists or at least partial agonists. Since little is known about the transition and more information is needed about the structural requirements of the 4‐substituent to control the functional activity, 12 novel 4‐thio‐substituted 2‐(2,5‐dimethoxyphenyl)ethyl]amines were synthesized and spectroscopically characterized. Thus 2,5‐dimethoxybenzenethiol ( 7 ) was converted to the thioether derivatives 8a – l with several alkyl, fluoroalkyl, alkenyl, and benzyl halides. Subsequent Vilsmeier‐formylation afforded the benzaldehydes 9a – l , condensation with MeNO₂ the nitroethenyl derivatives 10a – l , and reduction with AlH₃ the desired (2‐phenylethyl)amines 11a – l .