We are going to prepare anthranilic acid using the Hoffman rearrangement of thalamide using

sodium hypochlorite bleach.

There are a few published procedures but they are not always consistently repeatable.

This method is the one we've tweaked and used consistently.

First dissolve 18 grams of sodium hydroxide in 80 ml of cold water and with a few ice

cubes added to make up to 100 ml.

Stir and then chill.

The solution weighed out 30 grams of thalamide.

Take the chilled sodium hydroxide solution.

We've put a thermometer in here so you can see the temperature changes that will occur.

Be sure to use a beaker large enough to hold 500 to 600 ml of liquid.

With stirring and the temperature at around 10 degrees C, add the thalamide powder to

the sodium hydroxide.

This will dissolve over a few minutes and add an extra 50 ml of water if you need to

in order to.

Obtain a clear solution.

The temperature will rise slightly to around 20 degrees.

Take the resulting solution and chill back down to 10 degrees over about 20 minutes.

We've now created a solution of sodium thalamide.

This will hydrolyze so we need to use it quickly.

Add to this a chilled solution of sodium hypochlorite bleach.

We are using an 8.25% concentration.

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Use 190 mils, giving us the molar equivalent to, the thalamide.

Stir this for 15 minutes, and you will notice a, slow temperature, increase up to between 35 and 40 degrees, C.

This is the formation of the isocyanate intermediate, you may, see that the liquid is a very faint yellow color.

Heat to 75 degrees C.

Then allow the solution to cool and chill down, the, temperature increase makes, sure that all the unstable isocyanate rearranges, to form our anthranilic acid product in the form of, sodium anthranilate.

Take 40 milliliters of the chilled product and reserve separately.

This is in case we accidentally neutralize too far in, the next step.

The pH of the solution, is at this stage.

Strongly, alkaline.

We now need to get it to exactly neutral, by, carefully adding concentrated hydrochloric acid.

As you add the acid you'll see CO2 given off, and a precipitate forming, and re-dissolving, stir the solution well.

You'll see the color change to a yellow-orange, around, 20 to 30 mils of acid, is required for complete, neutralization.

But.

Be very careful, and try not to overshoot.

We're nearly there.

And now slightly over, so add in the reserved 40 milliliters, and add acid drop-wise testing carefully, until the solution is, neutral at pH 7.

The neutralized solution, is a yellow color.

Perhaps very slightly alkaline, but close enough.

Now we add a weak acid, glacial acetic acid, to, the solution in order to precipitate the anthranilic acid.

Add, the acid very slowly, and stir vigorously as the mixture, may foam.

I've transferred the solution to a larger beaker, to avoid any risk of this.

Keep adding and stirring and anthranilic acid will precipitate.

This, takes around 30 mils of acid to complete.

The residual solution, is now a dark brown color.

Vacuum filter the product, and keep it on the pump.

For at least 30 minutes to get as much water, out as possible.

Don't get too excited, because the precipitate is very light.

Unfortunately a large volume has a small weight.

After washing, the solution is ready to use.

We'll continue with 100 ml of cold water, re-filtering and then, drying in a warm oven to constant weight.

Here's our, crude product.

We obtain 12.4 grams of anthranilic acid.

This is a, 44%, yield from the starting material.

Which is not, great.

But the product is fairly clean and pure.

We'll, continue to refine the process, as we have obtained up, to 60% in the past.

But it's not clear exactly, where the change will be.

The challenge lies. The product can also be re-crystallized from boiling water. Make sure the water is over 95 degrees C as this makes a big difference to the solubility. You obtain crystals, which are a slightly darker color, which look like this, when dried.

Anthranilic acid is a versatile and fun starting point to benzene, anti-inflammatory drugs, dyes, and quinazolinone heterocycles.