“ 451 4.7.0 Timeout”
To better undestand where it was problem we enabled verbose logging on each Exchange server Hub Transport that faced problems to send intrasite and externally emails:
There was “ 451 4.7.0 Timeout” as you can see.
Then we executed ping command with a particular parameter to understand if there was some packed dropped during connection:
And ping computer_name or IP_address -f -l 1472 was unsuccessfully. (http://support2.microsoft. com/kb/159211/en-us )
So, following this article, we understood that it was a networking problem and we opened a major case to MPLS provider and we solved after their intervention.
[update 2016.06.07]
Here they are articles about MTU and ping parameter and how to enable verbose logging on exchange server about send/receive connectors
How to Troubleshoot Black Hole Router Issues
SMTP Routing in Exchange 2010 (Part 4)