*note* I am not trying to claim any credit for this method at all. All of it was gathered from the internet; I am just trying to put it into a format that's simpler to follow.

If this all makes sense and people find it useful I'll post the rest in the same format (hexamine route to methylamine, then gassing to mdma)

If I've made any mistakes or if there is a simpler way to do any of this I'd appreciate having them pointed out, and I will update this post with corrections.


---All starting materials besides the acetone are ACS reagent grade, acetone is kleen-strip brand)---

edit: Water is always DI water, NOT tap water

---Any evolved fumes are removed with a water aspirator---



1. Add 19 mL GAA and 10.4 mL 47.6% Hydrobromic acid to flask

2. Add 10 mL conc H2SO4 dropwise, allow to cool

3. Add 14.6 mL sassafrass oil, swirl gently

4. Cool flask in ice bath for 24 hrs

5. Decant into another flask, carefully leaving solids behind

6. Disolve solids in water, add to seperatory funnel, extract  with DCM, combine organic layer with liquid decanted in step 5

7. Pour organic layer+decanted layer from 6 into sep. funnel, wash with 2x volumes of water,

8. drain off organic layer, discard water layer

9. Pour organic layer back into clean sep. funnel

10. Add equal volume of water, slowly add baking soda until fizzing stops.

11. Repeat steps 8+9

12. Wash with water, repeat steps 8+9

13. Wash with brine

14. Vacuum distil off DCM

15. ------weigh bromosafrole------

(For each g of bromosafrole use 10 ml acetone and .65g NaI)

16. Combine acetone, NaI, and bromosafrole

17. Stir gently for 30 minutes

18. Repeat steps 5,6,7,8,9,12,13, and 14

19. ------weigh iodosafrole------

Reading through some old info by strike on lyceum he describes using H2SO4 to dehydrate 48% HBr so it will successfully brominate the safrole without needing 66 % HBr sol'n (which would be difficult for me to get).

The science looks right to me, but I could be wrong.

Maybe some of the H2SO4 stuff came from making the HBr in situ with a bromide salt?

Nah, you're misreading his post.

It's possible that strike was wrong, but his post is pretty clear- I'm not misreading it

Next: Will H2SO4 work to dehydrate an alkene so as to allow bromination to dominate? If this does work it would allow people to use regular 48% aq HBr, for which there are tons of sources and tons of recipes for (see below for recipes). Let's gloss over the theory of this mechanism first.

We know that using ~50% HBr will promote acid catalyzed hydration of the beta carbon of safrole, right? Right. But H2SO4 in sufficient quantity is a dehydrator of alcohols. If one has an alcohol and would like to make an alkene out of it they would zap it excess H2SO4 and the alcohol would go bye-bye. The same principal is promoted here. If 48% HBr is used, the water of that reaction is dominant and will keep popping into the beta carbon spot that should rightly belong to the Br. With a sufficient quantity of H2SO4 present, that H2SO4 will keep stripping out that OH group as fast as it forms. Sure, another OH will more than likely take its place, but sonner or later a Br will pop in. The H2SO4 will keep recycling that beta position millions of times a minute until a bromine, which is resistant to H2SO4 attack slides in. Eventuallly, the reaction equilibrium swings toward dominant bromination.

Some of you may ask why the sulfuric acid would not compete with HBr because both attack the double bond of an alkene (safrole) in the same manner. You know what? Strike doesn't know why either! Yet it may very well work and this is not merely conjecture on Strike's part. Eleusis made reference to Vogel using this strategy for halogenating alkenes. Strike has the most modern version of Vogel's masterpiece book: "Practical Organic Chemistry" (3rd ed., 1966). There is no mention of the direct halogenation of alkenes. Mr. Vogel seems to prefer getting his species brominated by going through an alcohol intermediate. Yeah so what? Well, take a look at this recipe from pages 277-278:

"III,35. Sec-Butyl Bromide (HBr-H2SO4 Method)

To 250g. of 48 per cent. hydrobromic acid contained in a 500ml. round-bottomed flask add 75g. (41 ml.) of concentrated sulphuric acid in portions with shaking (1); some hydrogen bromide may be evolved. Add 88g. (110ml.) of sec-butyl alcohol, followed by 60g. (32.5ml.) of concentrated sulphuric acid in several portions with shaking, and finally a few chips of broken glass. Attach a reflux condensor to the flask and reflux the mixture gently on a wire gauze for 2-3 hours; during this period the formation of sec-butyl bromide is almost complete and a layer separates above the acid. If the preparation is carried out in the open laboratory, fit an absorption device (compare Fig. II,13,8 and Fig.III,28,1) to the top of the condenser i order to absorb any hydrogen bromide and sulfur dioxide which may have evolved. Allow the contents of the flask to cool, remove the condensor and set it for downward distillation; connect the condenser to the flask by means of a wide (7-8mm. diameter bent glass tube. Distil the mixture until no more oily drops of sec-butyl bromide to pass over (30-40 minutes). Transfer the distillate to a separatory funnel and remove the halide which forms the lower layer. Wash it successively with water, an equal volume of concentrated hydrochloric acid (2), water, 5 per cent. sodium bicarbonate or sodium carbonate solution, and water. Separate the water as completely as possible and dry with 2-3g. of anhydrous calcium chloride or anhydrous magnesium sulphate; the desiccant should be left in contact with the bromide for at least 30 minutes and shaken occasionally. Filter the dried product through a small funnel supporting a fluted filter paper or small cotton wool plug into a 200ml. distilling flask, add a few chips of porous porcelain and distill either from an air bath (Fig.II,5,3) or on an asbestos-centered wire gauze. Collect the protion boiling at 100-103�. The yield is 155g.

Notes. (1) the acid mixture may be prepared (compare Section II,49,1) by placing 120g. (37.5ml) of bromine and 130g. of crushed ice in a 500ml. flask , cooling the latter in ice, and passing sulphur dioxide (from a siphon of the liquified gas) into the bromine layer at such a rate that the gas is completely absorbed. The flask is shaken occasionally, and the flow of gas is stopped immediatley the red colour due to free bromine has disappeared; the mixture will then have a yellow colour. The resulting mixture is equivalent to 250g. of 48 per cent. hydrobromic acid to which 75g. of concentrated sulphuric acid have been added; it need not be distilled for preparation of sec-butyl bromide.

Owing to the comparatively negligible difference in the cost of bromine and the equivalent quantity of constant boiling point hydrobromic acid, there is little to be gained--apart from the instructional value-- in preparing the hydrobromic acid from bromine in the preparation of alkyl bromides.

CAUTION. Bromine must be handled with great care and in the fume cupboard. The liquid produces painful burns amd the vapour is unpleasant. Bromine burns shouls be treated immediately with a liberal quantity of glycerine. If the vapour is inhaled, relief may be obtained by soaking a handkerchief in alcohol and holding it near the nose.

(2) The crude bromide contains a little unchanged alcohol and is said to contain some n-butyl ether (b.p. 141�). The former is removed by washing the concentrated hydrochloric acid and this purification process is satisfactory for most purposes. Both the alcohol and the ether are removed by washing with 11-12ml. of concentrated sulphuric acid; the butyl bromide is not affected by this reagent."

Can you see what happened in the recipe? Vogel took a species (sec-butyl alcohol) that had an OH already at a secondary 'beta' carbon and stripped it with H2SO4 so as to allow bromination to occur. That one could start this recipe with an alkene (not an alcohol) should make no difference. The HBr would promote OH addition which would, in essence, be the same damn starting material as in the above recipe. And, just like in the above recipe, the H2SO4 would keep stripping off that OH to favor dominant bromination.

Yes, folks! Happy days with 48% aq. HBr are here again!

I was talking to %1 who posted above me. He thought you posted about forming the HBr in situ from sulphuric acid and NaBr which does work as the sulphuric acid is converted to sodium bisulphate which doesn't cleave ethers and will precipitate out. That works to get to bromosafrole, what you posted will not. He misread your post