If Perl were to guess that "#" indicates a comment, it'll introduce a paradox. Consider

s{foo}{
  bar
  #}xe
}
[download]

If Perl stops at the second "}", then the replacement expression is not code and "#" are not comments and Perl should have stopped at the first "}".

If Perl stops at the first "}", then the replacement expression is code ("e") and "#" are comments ("x") and Perl should have stopped at the second "}".

Perl needs to find the end of the operator to find the "e" and "x" flags. To find the end of the operator, Perl initially treats the expression as a replacement string. When the "e" flag is found is the replacement string is reparsed as code. Only then does "x" have any meaning.

Perl 6 fixes this by placing the flags before the replacement expression.