Nick Clegg has predicted Scotland would become independent "in a heartbeat" if the UK left the European Union.
The Deputy Prime Minister's comments came just hours before the Conservative Culture Secretary Sajid Javid, tipped as a future party leader, said he would not shed a tear if the UK left the EU.
David Cameron has pledged an In/Out referendum on membership in 2017 if the Tories win the General Election.
But Mr Clegg warned that the Mr Cameron and his team run the risk of accidentally sliding out of Europe.
Speaking at the launch of his party's plans to cut the deficit after May's General Election , the Liberal Democrat leader said that businesses were worried about "the real risk that the Conservatives will mismanage their inner demons on Europe, will mismanage the referendum on Europe (and) will see Britain topple out of the EU.
"And as night follows day if the UK pulls out of the European Union, Scotland, in my view, within a heartbeat will pull out of the UK and we will then have lost two unions in one parliament."
He added: "That is not only terrible for our country and the character of our country it is disastrous for business."
First Minister Nicola Sturgeon has called for a 'double lock' that would prevent the UK leaving the EU unless Scotland, Wales and Northern Ireland separately agree.
SNP MSP Christina McKelvie said: "If Nick Clegg truly believes that the UK is a 'family of nations' as we were told during the referendum campaign, he should back the First Minister's common sense plan to ensure Scotland isn't ripped out of the EU against our will."
The row came as Mr Clegg likened the Tories to the US 'Tea Party' and dismissed the party's plans for swingeing public sector spending cuts as "implausible and undeliverable".
Mr Clegg set out Lib Dem proposals for an £8 billion tax hike, targetting wealthy individuals and businesses, in the next parliament.
Both the Tories and the Lib Dems have pledged to clear the deficit by 2017/18, which the independent Office For Budget Responsibility (OBR) estimates will need £30 billion of fiscal "consolidation".
The Tories have said that they will get much of the money from welfare cuts which would affect the working age poor.
The Lib Dems say their plans require £8bn less in social security reductions than the Conservatives.
Mr Clegg was speaking in the Shangri La Hotel on the 52nd floor of the Shard, one of the most expensive buildings in London.
He said his party's "sensible, balanced approach" meant the end of austerity was "in sight".
He also predicted that the Tories would continue cutting public services, for ideological reasons, long after the deficit had been cleared.
He also attacked Labour's plan to clear the deficit more slowly over the course of the next parliament, with corresponding lower spending cuts, as action "on the never-never".
That plan would lead to £70 billion more in borrowing before 2020, Mr Clegg predicted.
Labour Treasury spokesman Chris Leslie said the Lib Dems could not be trusted because the party broke its promise not to raise VAT when it entered coalition with the Tories in 2010.
Mr Cameron claimed the Lib Dem proposals would hit "hard working people" with tax rises.
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