It has happened before:
The original eastern I-86, which was created when the ill-fated I-84 to Providence was being proposed, ran from East Hartford to Sturbridge. Once it was determined that I-84 would never reach Providence, I-86 was decommissioned as a result, and I-84 now occupies the East Hartford-Sturbridge route, with the immediate branch to the east becoming I-384.
(Of course, I-86 would reappear a decade later, as a new route connecting Erie to Binghamton, with several disconnected segments along the way.)
Does that really count, though? I-86 remained an Interstate, it just got a different number. There have been other instances of that around the country over the years, perhaps most obviously with the replacement of suffixed route numbers. In other words, the
number "I-86" was decommissioned, but the Interstate designation applicable to that road was not. I thought the OP was inquiring about the total downgrading of an Interstate highway to a different class of road–to use that example, perhaps if the old I-84 had been designated CT-84 instead of I-384.
To answer the original question, I could perhaps foresee a scenario in which a
portion of a 2di might be decommissioned as an Interstate, most likely if the route is relocated to a new alignment and the state doesn't think it's necessary to keep the old one as an Interstate. (Hypothetically, I-93 through Franconia Notch could be the sort of segment where that sort of thing could be worthwhile if we assume, for discussion purposes, that there were a viable alternative alignment that would allow for compliance with Interstate standards, recognizing of course that if such an option existed it probably would have been done in the first place.) But it seems unlikely that a
full 2di would be decommissioned unless federal highway funding laws change big time.