Spain has said it would not veto an attempt by an independent Scotland to join the EU, in a boost to Nicola Sturgeon’s campaign for a second independence referendum and the clearest sign yet that Brexit has softened Madrid’s longstanding opposition.

Alfonso Dastis, the Spanish foreign minister, made it clear that the government would not block an independent Scotland’s EU hopes, although he stressed that Madrid would not welcome the disintegration of the UK.

He also said Edinburgh would have to apply for membership, a process fraught with uncertainty that is likely to take several years. But asked directly whether Spain would veto an independent Scotland joining the EU, Dastis said: “No, we wouldn’t.”

Madrid is keen not to fuel Catalonia’s desire for independence. “We don’t want it [Scottish independence] to happen,” he said. “But if it happens legally and constitutionally, we would not block it. We don’t encourage the breakup of any member states, because we think the future goes in a different direction.”

The change in tone could prove a significant boon to Scotland’s first minister, who has repeatedly demanded the right from Westminster to hold a second independence referendum before Brexit. Scotland voted overwhelmingly to remain in the EU during the referendum last year, but it has been believed Spain would block it from rejoining if independent from the UK.

The softening stance this weekend reflects the new approach being taken by Dastis, a career diplomat, who was promoted to foreign minister last November after the centre-right prime minister, Mariano Rajoy, formed a government following 300 days of political paralysis in 2016.

In the run-up to Scotland’s 2014 independence referendum, Rajoy said Scottish independence would be a catastrophe that would risk Europe’s disintegration, but the political calculus in Madrid and Brussels has shifted since Britain voted to leave the EU.

EU leaders are more sympathetic to Scotland, where 62% voted to remain in the EU, while insisting that Scots cannot inherit Britain’s EU membership.

The European commission spelled out earlier this month that an independent Scotland would have to apply to join the bloc, a point reinforced by Dastis. “They would have to join the line of candidates at some point and would have to start negotiations,” he said.

Scotland would have no chance of winning the perks enjoyed by the UK, such as the rebate on EU payments. Current EU law also requires new joiners to sign up to the euro, an issue that would pose fundamental problems for Scotland’s trade with the rest of the UK.

Experts have suggested negotiations could take three to four years, but the timing is uncertain. EU diplomats are reluctant to get into the details of a hypothetical event, especially when the bloc’s energies are being absorbed by Brexit.

Recent polls have cast doubt on the Scottish appetite to abandon the UK for a closer relationship with Europe. A study by the NatCen social research organisation found that Scots wanted similar controls on immigration to people from other parts of the UK.

The Spanish minister was speaking to the Guardian and other European newspapers in the week that Britain’s most senior diplomat in Brussels handed in a letter from Theresa May formally announcing the intention to leave the EU.

Describing the prime minister’s letter as “constructive and respectful”, Dastis disagreed with suggestions that the UK was attempting to use security as a bargaining chip. “I didn’t take it as a threat,” he said. “Security cooperation is good not only for the EU, but also the UK. The fact the UK is leaving raises a challenge, but we [the EU] have to develop security cooperation.”

The Brexit minister, David Davis, hit the phones on Wednesday afternoon, seeking to reassure diplomats across Europe that Britain was not using security as a bargaining chip.

Dastis emphasised his agreement with the EU’s chief Brexit negotiator, Michel Barnier, who insists the UK must agree the divorce settlement before embarking on trade talks. This sequence is likely to be agreed without dispute when the EU’s 27 prime ministers and presidents meet to finalise its negotiating principles on 29 April.

In a separate interview with El País, Dastis said Spain preferred a soft Brexit, although he doubted it would be possible. “Spain is closer to soft Brexit. We regret the UK is leaving. We want a balanced, reasonable agreement. But if they’re leaving the single market and the customs union, it’s difficult to think of a soft Brexit. Spain would like a close relation, as similar as possible to the one we have now.”

In a clear diplomatic victory for Spain, the draft guidelines, which were circulated to national capitals on Friday, come down in favour of Madrid in the centuries-old dispute with Britain over Gibraltar. The text gives Spain an effective right to exclude Gibraltar from any transitional single market access arrangement or future trade deal with the UK if it is not satisfied with the status of the territory.

Spain also has a strong interest in settling the status of EU nationals, a key plank of the divorce agreement. More than 300,000 Britons have settled in Spain and their right to healthcare, employment and social security will be shaped by the Brexit deal. Dastis thought it possible to reach a settlement in a few months.

Leaders on both sides of the Channel have talked up the importance of an early agreement on citizens’ rights, but the issue is laced with complexity. An early political statement aimed at reassuring citizens is possible, but the reality of settling knotty questions of health, employment and social security rights could take longer. “Nothing is agreed until everything is agreed,” states the EU draft text.

Spain and Britain have already clashed since article 50 was triggered earlier this week over the future of Gibraltar. The UK has said it will stand up for the island’s interests after the territory accused Spain of using Brexit to forward its territorial aims. The UK foreign secretary, Boris Johnson, insisted on Friday that Britain remained “implacable and rock-like” in its support.