Going on the assumption that your pattern is correct, 
s/
   &
   (?!
      (?:
         # (?: x[\da-f]+ | \d+ )
      |
         [a-z]+
      )
      ;
   )
/&/xi

[download]

I factored out the "#" and removed extraneous captures and groupings, but the key is (?!)

Update: And if you wanted to only accept known entities, 

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

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

[download]

or 

use Regexp::List qw( );

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

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

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

[download]

Update: Escaped "#" as per reply.

In reply to Re: Matching ampersands that are NOT part of an HTML entity? by ikegami
in thread Matching ampersands that are NOT part of an HTML entity? by Anonymous Monk

Title:
Use:  <p> text here (a paragraph) </p>
and:  <code> code here </code>
to format your post, it's "PerlMonks-approved HTML":


  • Posts are HTML formatted. Put <p> </p> tags around your paragraphs. Put <code> </code> tags around your code and data!
  • Titles consisting of a single word are discouraged, and in most cases are disallowed outright.
  • Read Where should I post X? if you're not absolutely sure you're posting in the right place.
  • Please read these before you post! —
  • Posts may use any of the Perl Monks Approved HTML tags:
    a, abbr, b, big, blockquote, br, caption, center, col, colgroup, dd, del, details, div, dl, dt, em, font, h1, h2, h3, h4, h5, h6, hr, i, ins, li, ol, p, pre, readmore, small, span, spoiler, strike, strong, sub, summary, sup, table, tbody, td, tfoot, th, thead, tr, tt, u, ul, wbr
  • You may need to use entities for some characters, as follows. (Exception: Within code tags, you can put the characters literally.)
            For:     Use:
    & &amp;
    < &lt;
    > &gt;
    [ &#91;
    ] &#93;
  • Link using PerlMonks shortcuts! What shortcuts can I use for linking?
  • See Writeup Formatting Tips and other pages linked from there for more info.