It happened that usually connections to all of the ports in the range are opened by the firewall. And the firewall has an idle timeout setting.
If these connections are not used for the duration of the connection idle timeout on the firewall or the timeout is to short, then the firewall drops the connection.
When the P4210 or P42101 subsequently tries to save the Sales Order sending traffic across these connections, the firewall does not allow the traffic, because the connection has been dropped and there it is: ASYNCHRONOUS BUSINESS FUNCTION ERROR while trying to save your Sales Order.
And this can be a real headache ...
For more about this error and what needs to be checked please see: Async BSFN Failed And Need Roll Back (Doc ID 2423818.1)