The UN special envoy for Syria, Staffan de Mistura, has said panic is spreading among the 3 million citizens of Idlib province as he suggested the Assad government and its allies had set 10 September as the date for a full-scale bombardment of the last large rebel enclave.

De Mistura pleaded with the Russian and Turkish presidents to “look each other in the eyes” and find a solution that avoids a humanitarian tragedy in the region.

Civilians in Syria's last rebel stronghold brace for final battle Read more

Vladimir Putin and Recep Tayyip Erdoğan, who have backed the Syrian government and rebels respectively, are due to meet in Tehran on Friday to discuss Idlib. De Mistura suggested that if their discussions fail, it is likely that as many as 800,000 citizens will try to flee the province, including over the border to Turkey.

The northern province and surrounding areas are the last major swathe of territory held by insurgents fighting the Syrian president, Bashar al-Assad, who has been backed by both Russian and Iranian forces in Syria’s seven-year-old civil war. It is held by a complex array of rebels and jihadists, many of whom have been blacklisted as “terrorists” by world powers. Syrian government forces are massing around the north-western province in preparation for the assault.

Marine Gen Joseph Dunford, the chairman of the US joint chiefs of staff, warned on Tuesday that a major Syrian military assault on the rebel-held enclave would lead to a “humanitarian catastrophe” and instead recommended more narrowly tailored operations against militants. “We don’t see any way that significant military operations are going to be beneficial to the people of Syria,” Dunford told reporters during a trip to Athens.

“If major military operations take place we can expect humanitarian catastrophe and I think we would all want to see that be avoided.”

De Mistura repeated his personal offer to go to Idlib to find a formula that avoids further conflict but admitted the airstrikes already launched in Idlib on Tuesday could be a sign that the talks between Russia and Turkey on how to defuse the crisis were not going well.

Turkey has warned against an assault, and has assembled observation posts around the region. Iran insisted it would push the militants out of Idlib, but the Iranian foreign minister, Mohammad Javad Zarif, claimed this could be achieved with minimum human cost. “We will try to prevent any damage to the Syrian people and complete the process of clearing extremists,” Zarif said, according to the state news agency IRNA.

De Mistura also said he believed both sides in the conflict might have access to chlorine-based weapons, describing them as in the grey zone between conventional and chemical weapons.

The White House warned on Tuesday that the US and its allies would respond “swiftly and appropriately” if Assad used chemical weapons again.

De Mistura’s warning came after he set out a proposed timetable for diplomatic talks on a new constitution for Syria in an attempt to revitalise the moribund diplomatic process.

De Mistura said he was asking Turkey, Russia and Iran to meet on 10 and 11 September, followed three days later by a meeting with France, the UK, US, Saudi Arabia, Jordan, Germany and Egypt.

He said the planned meetings represented “a moment of truth” in finding out whether the parties wanted a credible political settlement to end the seven-year civil war. He said this was vital for the millions of Syrian refugees waiting to decide whether to return home.

De Mistura’s aim is to report on the peace process to a US-chaired meeting of the UN security council on 20 September, probably at the time of the UN general assembly.

Late on Monday, the US president, Donald Trump, warned the Syrian president and his allies not to “recklessly attack” Idlib province, warning that hundreds of thousands of people could be killed.

“The Russians and Iranians would be making a grave humanitarian mistake to take part in this potential human tragedy. Hundreds of thousands of people could be killed. Don’t let that happen!” Trump tweeted.

The Kremlin spokesman, Dmitry Peskov, said: “Just to speak out with some warnings, without taking into account the very dangerous, negative potential for the whole situation in Syria, is probably not a full, comprehensive approach.”

The presence of militants in Idlib was undermining the Syrian peace process and making the region a base for attacks on Russian forces in Syria, he added.

The Syrian government feels no external political pressure to rewrite its constitution to give a role to a militarily defeated opposition that it regards as illegitimate. This will make De Mistura’s objective more difficult.

The plan for a constitutional committee was first advanced by the Russians at the beginning of the year. Since then discussions about the size and composition of the committee, including the role of the Kurds or opposition groups, have become deadlocked.

• The map of Syria in this article was updated on 6 September 2018.