All three remaining British teams crashed out of the Europa League as Liverpool and Manchester City failed to overturn first-leg deficits and Rangers were beaten by PSV Eindhoven.
Liverpool were trailing Braga 1-0 from the first leg of their last-16 tie and, although Andy Carroll started his first game for the club, the Reds struggled to produce clear-cut chances and were held to a 0-0 draw.
Liverpool, who have qualified for Europe every year since 1999, will have to finish fifth or above in the Premier League if they are to be involved next season.
Mario Balotelli was sent off as Manchester City failed to overturn a 2-0 first leg deficit against Dynamo Kiev, with a 1-0 win on the night not enough to prevent them crashing out of the Europa League.
Balotelli was issued a straight red card for a crashing 36th-minute challenge on Goran Popov, but City gave themselves hope three minutes later when Aleksandar Kolarov hit a low free-kick under Oleksandr Shovkovskiy.
The Ukrainians defended deep in the second half and restricted City to few chances, threatening to make the game safe themselves when Denis Garmash had a header cleared off the line but holding on for their last eight place.
Rangers - having secured a 0-0 draw in the Netherlands in the first leg - were defeated 1-0 at home by PSV Eindhoven. Jeremain Lens scored in the 13th minute and it proved enough to send the Eredivisie side through as the hosts struggled to provide a response.
Santi Cazorla and Giuseppe Rossi teamed up brilliantly to help Villarreal ease into the quarter-finals with a 2-1 victory over Bayer Leverkusen at El Madrigal.
Holding a slender lead following their 3-2 win in Germany last week, the Spanish side made sure of their progression thanks to Cazorla's first-half goal and Rossi's strike after the break against a spirited Leverkusen side who clawed one back through Gonzalo Rodriguez's late own goal.
Porto's pursuit of the treble continued as they progressed with a 2-1 home win over CSKA Moscow.
Having taken a one-goal lead back to Portugal with an impressive win a week ago, Andres Villas Boas' men got off to the perfect start when Hulk gave them a first-minute lead. Things improved 23 minutes later when Fredy Guarin put them 3-0 up overall and, despite Zoran Tosic pulling one back for Moscow, Porto's pursuit of the league, cup and European trophies remains intact.
Spartak Moscow hammered Ajax 3-0 at the Luzhniki Stadium to wrap up a 4-0 aggregate win with a free-kick from Brazilian Alex adding to first-half strikes from Dmitri Kombarov and Welliton.
Spartak, who had suffered an embarrassing 4-0 loss at Rostov in their Russian League opener on Monday night, dominated although Christian Eriksson hit the bar for Ajax and was also denied by Spartak goalkeeper Andriy Dikan.
Reigning Russian champions Zenit St Petersburg staged an heroic comeback bid at home to FC Twente, but their 2-0 win on the night was not enough and they slid to a 3-2 aggregate defeat.
Roman Shirokov and Alexander Kerzhakov gave Zenit hope with first-half strikes but Twente defended well and ought to have put the game out of Zenit's reach when Oguchi Onyewu missed a fine chance late on.
Benfica nudged through 3-2 on aggregate after a 1-1 draw with Paris St Germain in the French capital. Nicolas Gaitan opened the scoring for Benfica on 27 and Mathieu Bodmer's 35th-minute equaliser was not enough.