dormouse (Member)
04-19-00 14:04
No 122765
      Viability of Delepine Rxn  Bookmark   

Author  Topic:   Viability of Delepine Rxn 
Junior Member   posted 10-30-98 12:53 PM          
Here is my translation of Mr. Delepine's article on the combination of primary, secondary and tertiary halogens with hexamine. With longer chain secondary halogens (iodobutane) the salt with hexamine isn't formed. But, as luck (or fate) would have it a salt does form with the secondary iodopropane. The only things is that Delepine doesn't give a yield for this, he only says that it does work, but that the rxn takes longer with some side products. This doesn't prove that this reaction is viable for bromo/iodo safrole but I think that it justifies serious experimental dreaming
Action of some non-cyclique halogen derivatives on Hexametyhlene-Tetramine
by M.Delepine and M.Jaffeyx
Bull. Soc. Chim. (4), p.108, 1921

Translated by Icculus

We have prepared a very large number of combinations of HMTA with halogen compounds, non-cyclique or cyclique, but the halogen function is always primary. We know that these combinations must be considered like
quaternary salts of ammonia C6H12N4-RX, the group RX(=R'CH2X) attached to the base, which acts like a tertiary amine.
Our foremost goal was to react the four isomers of iodobutane with HMTA to judge their different reactivities. Two are primary: CH3CH2CH2CH2I and (CH3)2CH2CH2I; one secondary: CH3CHICH2CH3 and the last tertiary: (CH3)3CI. The differences in reactivities of these compounds are
attributable solely to the structure of these isomers. Here are the results of our observations.

Iodo-n-butylate: C6H12N4-C4H9I
This iodobutylate was prepared without difficulty by the method indicated by us(1). One heats to reflux in a double boiler 1mol of HMTA dissolved in 12-15 times its weight in chloroform with 1 mol of the iodo-n-butane. The quaternary salt precipitates at the end and is a sign
of its production. Collect after the temperture progresses; we verified that 12 hours is sufficient; it is necessary to distill some of the chloroform towards the end of the reaction to finish with a suitable
speed; after 12 hours the yield is 90-92% of theory and is good enough that one need not be preoccupied with perfection by
concentrating the
mother liquors.
The combination of the idoine with the base takes place equally well in the cold. It also takes place in cold alcohol; after 45 days, 7.5 grams of base in 50ml of alcohol with 6.5 grams of the iodine formed 7.5 grams of crystals as opposed to the 8.1 grams theorized. It takes place the same in cold water, on the condition of shaking time to time; if one heats it you only obtain a gummy mass that can't be crystallized.
The noral iodobutylate of HMTA is a substance well crystallized in thin white leaves(in needles when done in the cold), here are the characteristics for this combination: flavor is bitter, moderate
colubility in water (5%), less in alcohol (0.5%) and less still in chloroform (0.08% and ether. Melting is observed ~140 C., but with yellowing and decomposition, this is only an indication. M.Deroux found a temperature much higher (198 C). The transformation to butylamine by decomposition with HCL in alchol is an easy test.

Bromo-butylate: C6H12N4-C4H9Br
This subsatnce is obtained by replacing the iodine with bromine. It precipitates in colorless flakes, has a bitter flavor and melts at 95 C with decomposition. It combines with bromine.

Iodo-i-butane: C6H12N4-C6H9I
The rections is much slower and less complete than with the normal iodine compound. Theyield after 15 hours was only 27% and it is likely that longer heating wouldn't increase it, also the chloroform solution was yellow. Besides, the salt isn't pure; the bitter taste is clearly
accompanied with an acidic flavor. The quaternary salts of HMTA are neutral. like HMTA itself, while the salts of HMTA are acidic. We were able to measure the acidity of the ppt. and found that it contained 15%
of the iodine salt of HMTA.

Action of Secondary and Tertiary Iodo-Butylates: CH3CHICH2CH3 and (CH3)3CI
These iodines give only slowly a white salt, with a distince acidic taste, not bitter, when they are heated with HMTA in chloroform. The salt is composed almost exclusively of the iodohydrate of the base.
These results show the large differences in the ability to join HMTA with halogen butanes. We wanted to see if these conclusions were generalisable.

Other Primary Iodines
Among the other primary iodines we took two compunds different enough: iodo-propane normal and iodo-(octyle). The first formed excellent yields (80% after five hours, crystals melt @138 C with decomposition. The
second reacted much slower; it formed a sour substance, slightly acidic, containig more idoine than expectd (40.7% instead of 33.4%), consistent with M. Deroux who obtained 44.3%
In other words the combination is more difficult when the molecular weight is increased.

Secondary and tertiary Derivatives
We addressed the iodo-isopropyl (CH3CHICH3) and the iodo capryle (C6H11CHICH3), the isomer of the octyle normal.
The iodo isopropyl reacted, but more difficultly than the normal, and gave the combination C6H12N4-C3H7I; the reaction is visibly accompanied by the formation of secondary products that strongly color the solution after several hours.
The iodine of capryle formed only a small quantity of the idodhydrate of HMTA after many hours.

Tertiary Iodine of C8
We examined the methyl-3-iodo-3-heptane: CH3CH2CI(CH3)C4H9. It formed paridly a large portion of the iodohydrate of HMTA.

To sum up, aside from the iodo-isopropyl, the secondary and tertiary halogens don't form salts with HMTA.

1. M. Delepine, Bull. Soc. Chim (3), p.353, 1895

Junior Member   posted 11-06-98 01:21 PM          
So I guess nobody cares one way or the other.
Well, I guess I was the same way. I thought that this rxn wouldn't work at all for iodo/bromosafrole. Then I read a very old french article that seems to say it will work.
Rhodium and I agree that the way to go would be to use a phase transfer catalyst to chlorinate safrole (since brominating with a PTC aparently yields only tar). Then refluxing with acetone and Na/KI to get the iodocmpd.

Then dissolve an equal molar amt. of hexamine in chlorform or ethanol, add the same molar amt of iodosafrole. One can then let it sit for awhile, or reflux it till crystals form.

Member   posted 11-06-98 10:30 PM          
This reaction I have a bit of interest in, but it's important to remember the differences in reactivity between compounds which have aryl and alkyl substituents.
I guess I'm just a bit suspicious util someone suggests a mechanism for the reaction. Thanks for the translation.


drone 342
Member   posted 11-07-98 12:16 PM          
Thr subject of the Delapine and the use of alpha-substituted alkyl halides has already been discussed months ago. Looking around enoug, you'll find ref's-a-plenty detailing just what you're looking for, including a lot of details regarding conditions, etc. A lot of work went into by YoursTruly, as well as others, but I'm reluctant to put much more effort into it.
The problem with the addition of HX on safrole using a PTC is that if you use a PTC, you're opening yourself up to destroying that methylenedioxy ring. I wasn't aware that chlorosafrole had been made this way, but maybe (doubtful.)

-drone #342

Junior Member   posted 11-09-98 09:12 AM          
I don't know where I was when that was discussed. It seems that question was never answered. I was just trying to show that secondary hexamine salts had been formed. It seems noone else had ever found any. Possibly because it only seems to work with shorter carbon chains, and therefore not many scientists have found use of this reaction.
I think Ritter said that chlorosafrole could be made with a PTC. He said that the PTC with Br/I destroyed the methylenedioxy bridge.

Whatever happened to Ritter's Delpeine synth in TSII?

drone 342
Member   posted 11-09-98 04:03 PM          
It *WAS* discussed, and I think I might have even been the one to provide the example of a secondary alkyl halide being used that way. I'll dig through my ref's, but I *KNOW* there are examples in the literature (an overview done by some Yugoslavians a few years back comes to mind as a good starting point for this stuff.)

-drone #342

Junior Member   posted 11-09-98 09:15 PM          
I know it was discussed, cause me used the search engine and pulled up the thread.
A long time ago, I guess this stuff is from April if not earlier, you had been looking for refs. (or people's experiences) on rxns of secondary alkyl halides with hexamine, forming the salt between the two, etc. I recently found one, and thought I would post it for all to see.

You said that you had posted some examples of secondary halides. Are you speaking of the benzedrine refs. that you mentioned in the old posts? I never saw any literature, maybe I missed it.

I think you may be refering to an article from JACs by Galat and the Hexamine review by Balzaivic or somebody?

In the Galat article they form (I think) phenyletylamine. Now, I thought the halogen was on the secondary carbon, but since they don't say it could be either.

In the other one the only secondary halides are next to carboxylic acids I believe. I haven't seen it in months, this is just from memory.

Or maybe, you are talking about some other completely different article.

I know this isn't "serious" chemistry, I was just trying to find evidence one way or the other, for once and all, that this reaction could work. I guess the real proof will come when I finally dream about it!