Four-time European champions Ajax were the most high-profile casualty on Wednesday evening as they were condemned to the Europa League by a 5-2 aggregate defeat by Rostov.
The Eredvisie runners-up, who last lifted the trophy in 1994, travelled to Russia level at 1-1 but fell behind to an opener from Iran international Sardar Azmoun.
Aleksandr Yerokhin's goal helped Rostov take control before Christian Noboa and Dmitry Poloz put Dmitri Kirichenko's team out of sight.
There was still time for Ajax captain Davy Klaassen to pull one back from the penalty spot after Fedor Kudryashov was dismissed for bringing down substitute Kasper Dolberg but the hosts were convincing winners.