A new "coalition for the national interest" is needed to make the case for the UK staying in the European Union, Nick Clegg will say, as he acknowledges that a referendum on links with Brussels is inevitable.
The Deputy Prime Minister appealed to business leaders and charities to speak out in favour of the EU before it is too late and Britain finds it has "stumbled out of the EU" - a move which would be "economic suicide".
Mr Clegg will issue the call to arms because he believes next year's European elections are set to be a proxy for the question of whether the UK should sever its ties with the EU.
The Deputy Prime Minister has written to more than 100 organisations including business and trade groups and charities, pleading with them to speak out in support of the EU.
Mr Clegg will attack David Cameron's pledge for a referendum on membership of the EU by the end of 2017 as a policy fix designed to hold the Conservative Party together over Europe until the next general election, but following a rebel attempt to tear up the Prime Minister's timetable it was "not even clear they'll make it that long".
In a speech at the London headquarters of Swiss technology firm Buhler Group, he will admit that pro-Europeans have been too quiet but "we cannot afford that silence any more" because "we are no longer asking if Britain will have a referendum on continued membership; we are asking when Britain will have a referendum on continued membership".
He will say: "My great fear, in all of this, is that pro-Europeans are being too slow to wake up to the danger ahead.
"The day I dread - the day I hope never comes - is a time when it is all too late: Britain has stumbled out of the EU, and we look back to these days and say we should have done more.
"It will not be enough to speak up on the eve of a referendum. We need to start challenging some of the ludicrous myth-making by the isolationists now."
While Mr Cameron had promised to renegotiate links with Brussels and put it to a public vote by the end of 2017 if he is in power after the next election, Mr Clegg said that timetable was "chosen for internal party management" and it would be better for a referendum to be in response to the next change to EU rules.
But he added that a referendum would take place: "We all agree that it will happen at some point or another."
Mr Clegg will acknowledge: "Next May the Euro-elections are bound to become a proxy for the bigger questions of 'in versus out' - a debate that will play out in the 2015 general election, too."
He will say that "you cannot overstate the damage" that leaving the EU would do to British livelihoods and predicts that having to negotiate individual trade treaties would take a decade.
"We simply will not be taken seriously by the Americans, the Chinese, the Indians, all the big superpowers, if we're isolated and irrelevant in our own backyard," he will say.
In his message to business leaders he will say: "I am asking you to be part of a coalition for the national interest - standing up for Britain remaining in Europe; for a Britain that is richer, safer, greener and stronger in the world."
Mr Clegg will accept that reform of the EU is needed, but claim that no repatriation of powers that Mr Cameron can win will placate Tory eurosceptics.
"Of course a future British government will be able to cobble together a package of reforms with Germany and other member states with like-minded views on European competitiveness and so on," he will say.
"But the question is not can a reform package be negotiated. The question is will it ever be acceptable to the large swathes in the Conservative party who want to be semi-detached from the EU or out of it altogether?"
It emerged at the weekend that Tory legislation to enshrine the 2017 vote deadline in law is set to be hijacked by rebels, led by Adam Afriyie, who will push for a vote in 2014.
Mr Clegg will highlight his coalition partner Mr Cameron's difficulties, saying: "The promise of unilateral repatriation was made at a time when the Conservative party needed to find a way to plaster over their internal division on Europe.
"They needed a position that, in the lead up to the election, all sides can get behind - a policy fix. Although, judging from this weekend, it's not even clear they'll make it that long.
"It's a short-sighted political calculation that could jeopardise the long-term national interest. It is playing with fire and, if we go down this track, it is Britain that will get burned."
In another dividing line with his Tory colleagues he will issue a strong defence of the European Convention of Human Rights as a "huge success for European co-operation".
Home Secretary Theresa May has indicated that the possibility of the UK leaving the convention could not be ruled out following a string of clashes with Strasbourg judges over human rights laws.