But in general, if there’s interruption on the communication line between W5100 and remote device, W5100 re-sends request within time defined in Retry Time register. Note that interruption may work in both directions: W5100 sends request, remote device does not receive it, then W5100 re-sends request. Or W5100 sends request, remote device receives it, then sends response, and W5100 does not receive the response.
But anyway 2.5 seconds is relatively long interval of time for modern networking.
You should explain your problem in more detail, what you do and what exactly you get (in your application and as seen by the W5100 LEDs).
But right now you can make small test - if it is possible - move remote server as close to the W5100 device as possible (the best using single hub between W5100 and device) to see if timing (2.5s) is the same, and effect of your actions is the same.
PS. Is WO2015107570 your work?