failed to send email with the following error:421 4.3.2 System not accepting network messages

432 messages are catchalls, somewhat like 421.

To debug this depends on if you have logs for the machine raising the 432 return code.

If you do, then it's easy to debug. Just review your logs for the answer.

If you're sending mail, then you'll have to debug the path between your sending IP + the system returning the 432. First debugging question in this case is if the 432 is returned all the time, for all sending IPs or only some of the time or for only some sending IPs.

First provide a copy of a full email being send (envelop), which will include the sender + recipient. This is a good starting point.

check if isp was on blacklist

Do you have something between Exchange and the internet that is scanning the SMTP traffic? If so then that is the cause of the problems. Ideally firewalls etc shouldn't be scanning SMTP traffic, they rarely make a good job of it.

Where are you seeing the error? On your Web Application? If so, use Telnet to test Email relay via your exchange server. Following article is for Exchange 2019 but is valid for all Versions. If it fails, you will need to setup an relay receive connector.

https://docs.microsoft.com/en-us/exchange/mail-flow/test-smtp-with-telnet?view=exchserver-2019