$x = "<tr><td>1</td><td>2</td><td><font>3</font></td><td>4</td><tr>";

$x =~ s{<td>(?!<td>)3(?!</td>)</td>}{<td>($1)a($2)</td>}; 
print $x;
#output must be: <tr><td>1</td><td>2</td><td><font>a</font></td><td>4</td><tr>