451 4.4.0 primary target ip address responded with 421 4.2.1 unable to connect

MS exchange q Viewer gives this below message
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SoulwinnerIT ManagerAsked:
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Belal KhalladSR ConsultantCommented:
The possible causes for the “451 4.4.0 Primary target ip address responded with: "421 4.2.1 Unable to connect." are:

 

1. Your hub transport server or edge server are unable to resolve the external domain names. It can be caused by the incorrect DNS sever settings.

2. Your firewall or ISP block the outbound traffics on port 25.

3. The IP address of your hub transport server or edge server are blocked by the target domain or other issues on the target domain.

The FQDN on the Receive Connector doesn't matter, that is inbound email only. It is only the FQDN on the send connector that is an issue. Ideally the FQDN on the send connector should match the PTR your ISP has set on your external IP address
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MAS (MVE)EE Solution GuideCommented:
Please mention the version of Exchange.
Please make sure your DNS working properly.
Please configure external for external lookup.
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SoulwinnerIT ManagerAuthor Commented:
@mas, exchange on Prem 2010 , we have O365 federation service
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Scott CSenior Systems EnginerCommented:
What SP / RU level are you at?  You can find this by running the following Exchange PS command.

Get-Command exsetup | foreach {$_.FileVersionInfo}

Assuming this was a working environment, what, if anything, has changed?  New ISP, new SmartHost, network equipment...etc..
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Todd NelsonSystems EngineerCommented:
This may or may not be related but review the article and check the NIC settings on the Exchange server...

https://oddytee.wordpress.com/2016/08/16/exchange-server-message-queue-error-451-4-4-0-dns-query-failed/
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SoulwinnerIT ManagerAuthor Commented:
the problem was with the SMTP port 25 on the firewall. Now its sorted
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Todd NelsonSystems EngineerCommented:
Belal should be award the points.
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MAS (MVE)EE Solution GuideCommented:
Agree with Todd,
Belal cleary explained about the port 25 block to check in post
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SoulwinnerIT ManagerAuthor Commented:
sorry guys :) thanks for your feedback
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