If it's anything like using the 50 euro bill in Spain, it's hard to use them in everyday transactions as usually places don't have enough change (or want to loose that change) for 50 euros if you order a coffee for example.
It's more likely a concern about a counterfeit note, although I've never had that problem with a €50.
And a policy of "no €50s" is simpler and clearer than a policy of "€50s accepted only if we have at least 2 €20s in the till" which means customers won't know if they can pay until they reach the till.
The reasons a small business might not keep a large float of €20s in their till is probably obvious!
That problems happen if you try to use the 100EUR one and obove.