s/
   &
   (?!
      (?:
         # (?: x[\da-f]+ | \d+ )
      |
         [a-z]+
      )
      ;
   )
/&/xi

##</code><code>##

local our %known = map { $_ => 1 } qw(
   eacute
   Eacute
   ecirc
   Ecirc
   ...
);

s/
   &
   (?!
      (?:
         \# (?: x[\da-f]+ | \d+ )
      |
         ([a-z]+) (?(?{ !$known{$1} }) (?!) )
      )
      ;
   )
/&amp;/xi

##</code><code>##

use Regexp::List qw( );

my @known = qw(
   eacute
   Eacute
   ecirc
   Ecirc
   ...
);

my $known = Regexp::List->new()->list2re(@known);

s/
   &
   (?!
      (?:
         \# (?: x[\da-f]+ | \d+ )
      |
         $known
      )
      ;
   )
/&amp;/xi