When were the four angels placed at the Euphrates River?
"One saying to the sixth angel who had the trumpet, 'Release the four angels who are bound at the great river Euphrates.' And the four angels, who had been prepared for the hour and day and month and year, were released, so that they would kill a third of mankind" (Revelation 9:14).
This refers back to:
"After this I saw four angels standing at the four corners of the earth, holding back the four winds of the earth, so that no wind would blow on the earth or on the sea or on any tree. And I saw another angel ascending from the rising of the sun, having the seal of the living God; and he cried out with a loud voice to the four angels to whom it was granted to harm the earth and the sea, saying, 'Do not harm the earth or the sea or the trees until we have sealed the bond-servants of our God on their foreheads'" (Revelation 7:1-3).
Keep in mind that Revelation is written in symbolic terms. God had planned significant destruction to the Roman Empire that had persecuted the church. That destruction was delayed so that God could arrange for His people's protection. Revelation 9 tells us that even after the damage caused by the releasing of the angels, the wicked did not learn any lessons and did not change.
"The rest of mankind, who were not killed by these plagues, did not repent of the works of their hands, so as not to worship demons, and the idols of gold and of silver and of brass and of stone and of wood, which can neither see nor hear nor walk; and they did not repent of their murders nor of their sorceries nor of their immorality nor of their thefts" (Revelation 9:20-21).