Bromo-Fed, Possible Solutions to Grignard's RXN

[ADDkid]

Swig had mention that the OH on fed could easily turn into Bromo-fed, and then the rxn could proceed using Grignard reaction to make meth.  Rhodium corrected me by stating that this would not work because of the active hydrogens on the amino group.  However, I came up with a possible way to solve the active hydrogen problem.  One could use 3 eqi. of Grignard, and when the reaction is over the hydrogens would be replaced when water is added. Also people don't seem to like this rxn in this forum, becasue it reacts with any moisture in the air.  The solution is Nitrogen, you are saying now, "where the fuck am I going to get nitrogen", well you don't have to.  Can you get helium.  If not try to find any inert gas. ADDkid

[Rhodium]

One could use 3 eqi. of Grignard

Of what?

The reaction won't start when the active hydrogen is on the same molecule as the halogen you want to turn into a RMgX species.

[ADDkid]

How do you know that?

[Rhodium]

Because that would be equivalent to the reaction being 'wet' (water also has active hydrogens) and if you have a wet reaction setup grignard reactions fail to initiate.

Ultrasound might be a way of counteracting this phenomenon though:

https://www.thevespiary.org/rhodium/Rhodium/chemistry/grignard.wet.html

[lugh]

Simply by running these words through a search engine, active, hydrogen, halogen, reaction, grignard, molecule, and mechanism
this web page written by Dr Gray was found:

http://www.sbuniv.edu/~ggray.wh.bol/CHE3314/cp17outl.html

6. Limitations to utilizing Grignard reagents in synthesis:
 
a. Any compound with hydrogens attached to an electronegative element (i.e., O, N, S or terminal alkyne) will donate the hydrogen to the Grignard reagent and decompose it.

b. Water, O2, CO2, etc., must be removed since they react with the Grignard reagent.

c. Compounds containing a halogen and a second, reactive group cannot be used to make Grignard reagents (e.g., Cl-CH2CH2-OH).

d. Aryl magnesium halides (i.e., Grignard reagents made with halogens attached to aromatic rings) cannot be made with aromatic rings that contain any of the following structures on the ring:

 
1) Acid.
2) -OH
3) -NH2
4) SO3H
5) Ester group
6) Nitrile group
7) Nitro group
-S-H group.

e. The carbonyl compounds with which the Grignard reagents are to be reacted also may not have any of the groups listed above (in addition to the carbonyl) at the time of reaction.

f. The only groups an aromatic ring may contain (in addition to the halogen) and still be used to make a Grignard reagent are...
 
1) -R groups
2) -Ar groups
3) -OR (ether) groups

You really need to start researching your ideas much more thoroughly before posting them, instead of typing every idea that comes to mind    This is elementary organic chemistry, which can be learned by making the required effort  

[ADDkid]

Well, according to my mentor, this reaction can work with about 75% yield,  I am leaning towards him since he is a doctor of chem.  "You must ask yourself if the reaction is limited, or if you are limited".
Some of the biggest finding in this field have been the result of trying to do things that the books or internet say can't happend.  For example look at the history of Victor Auguste.  His boss said that the idea of the grignard was no big deal, and that it would not amount to anything.  As we all know he was rewarded with noble prize.  Don't belive everything you read, do your own research. ADDkid.
Wouldn't the Mg first react with the Br, then rip of the H from the amino group, which would react and from amino-MgBr.

P.S.  All those things that you just mention above, say "on the aromtic ring, the Halogen and the amino group is not on the aromtic ring.  Also I do think that Active Hydrogen is not like water, Last time I check the pH of that H on the amino group is a lot higher then the H of water.

[Rhodium]

Could you please ask your mentor for a literature example of a secondary halo-amine undergoing a grignard reaction? It would be really interesting if you could dig up some evidence that it really could be done, as everything I've read says otherwise.

[WizardX]

Could you please ask your mentor for a literature example of a secondary halo-amine undergoing a grignard reaction? It would be really interesting if you could dig up some evidence that it really could be done, as everything I've read says otherwise.

Yes, I second that! I won't post anything until ADDKid posts some evidences. I think your fishing for information ADDKid?

[ADDkid]

Look, I would not ask a question like that because that would be dumb, it would be obvious why I would ask that question, and my Schooling is more important then any drug.
The question that I asked was just about the active hydrogens interfering with grignard, he responded with an ester and proceeded to show me that it could be done with the above information that I have already stated. Rhodium please respond to the other comments that I made, you made no attempt to prove me other wise. ADDkid

Rhodium, with respect I disgree with you about the rxn never starting with the amino group. You are forgetting about lewis acids, and lewis base.  The MgO coat will get reduced by the Iodine to leave Mg.  The Mg is a lewis base and would react with the strongest lewis acid.  In this case assuming that everything is dry will react with the group that is the strongest lewis acid, either NH or -Br.  I not sure what the pH value of is , but if I had to guess I would say -Br.  either way as long as the rxn is keep dry both fuctional groups will form grignard reagent.  It might help to reflux for a long time, lets say 3x as long.  When water is added then the amino goup will get H that was lost. Forming methamphetime. As long as the group is not chiral then you should not have a problem.  The chiral part might be why they do not suggest doing this with fuctional goup.  When they write rxn for books, they always pick the best way for the reaction. This might not be the best way, but hell aren't we Clandestine Chemist?  ADDkid
P.S. Wizard I don't fish for anything, If I have a question I will ask it.

[ADDkid]

Lugh: recives a : (Good Read) for his incorrect information, and not sticking to thte subject, when all the stuff that he as stated stricly states "On the aromatic compound"
ADDkid:  Recives no credit for his creativty on the subject, and contribution on the subject.

Allow the bees to judge for themselves, recently I have been receiving many email from this site and my personal websites, that show much respect for my ideas. Thanks for the support. ADDkid

[Rhodium]

Some of the biggest finding in this field have been the result of trying to do things that the books or internet say can't happend.  For example look at the history of Victor Auguste.  His boss said that the idea of the grignard was no big deal, and that it would not amount to anything. 

And some of the biggest failures are the result of people not learning from other people's failures. Innovation isn't about repeating experiments which didn't work the last time someone tried it out, it is to charter unknown territories where hidden treasures are believed to be found.

We say that we do not believe this reaction can take place, until you show us any proof that it will. You can either dig up a literature reference or perform the experiment yourself and then report back to us. But until you have done either, your postings here are nothing more than a cry for someone to try out your unlikely ideas for you, which will not happen anyway, so you are only wasting our time.

As we all know he was rewarded with noble prize.

It's very ignoble to spell the Nobel prize that way.

All those things that you just mention above, say "on the aromtic ring, the Halogen and the amino group is not on the aromtic ring.

Incorrect, as #6c contradicts your proposed synthesis. The example shows an alcohol, but amines are almost as reactive.

Also I do think that Active Hydrogen is not like water, Last time I check the pH of that H on the amino group is a lot higher then the H of water.

Definitely, the pKa of water is ~15 and that of amines is ~30-35. These values pale in comparison to grignard reagents, which usually approaches a pKa of ~50!

The point here being that I believe it is impossible to form a base with pKa ~50 in the presence of a pKa ~30 amine, so that the RMgX won't form in the first place, and thus cannot quench intramolecularly to give methamphetamine from bromoephedrine.

I would not ask a question like that because that would be dumb, it would be obvious why I would ask that question

Is it an obviously drug-related question to ask your respected mentor if he can present a grignard reaction of a molecule containing both a secondary amine and a halogen? I wouldn't say so.

The question that I asked was just about the active hydrogens interfering with grignard, he responded with an ester and proceeded to show me that it could be done with the above information that I have already stated.

What ester, and with which pKa?

The Mg is a lewis base

No.

http://dbhs.wvusd.k12.ca.us/AcidBase/Intro-to-Lewis-AcidBase.html

and would react with the strongest lewis acid.  In this case assuming that everything is dry will react with the group that is the strongest base, either NH or -Br. 

No, Grignard reagent formation is not about simple acid/base chemistry. The reaction RX + Mg -> RMgX is radical in nature, but the precise mechanism has not yet been elucidated. DOI:

10.1333/s00897030725a

[Nicodem]

Rhodium, I think you are wasting your time trying to explain ADDkid the Gringnard reaction. Since he is such a master of pKa's and acid-base chemistry I will try to use as much of his discourse as possible.

ADDkid, you have to use a free-base of your bromo-amphetamine for the Gringard rxn. You can’t dispute this, right?
Well this free-base isn’t particularly stable as it rearrange into an appropriate aziridine hydrobromide,.especially if the conditions are basic (you know, the Gringard reagents are VERY basic). The hydrobromide salt that would not precipitate from ether-solvent would react with Mg as the ammonium ions have as slightly acidic character (pk~10) and you would get some H₂, MgBr₂ and the aziridine. Now, before you say that the aziridine might be reduced by Mg, consider that the product (of such a non-existent) rxn would be 1-pheny-1-methylamino-propane (not amphetamine). Additionally, even if you can do miracles and start a Gringard rxn with an unprotected amine the so formed Gringard would react with the aziridine giving you a lot of great tar product, but luckily that can not happen as the rxn would never start.

Look, its nice you have ideas but it would not hurt you if you would do a literature search. I know this can be very boring, libraries are such boring places (I don’t enjoy them neither), but they are the best places to learn old things in order to realize your new ideas.
For example, you could go in the library and do a search on a potential Zn/AcOH reductions of benzylhalogenides, rationalize on why it would/wouldn’t work on your “bromo-fed” and post your thought with all the nice ref’s.

[ADDkid]

Today at school I asked two Doctors, and one grad student,  and this is the results, however I do not have proof, and I am currectly looking for the information to support myself.

The reason why "they" say you can't use grignard when using fuctional groups is because you will have a problem adding a new carbon bond to the compound, but guess what we are not talking about a new carbon bond are we.  We are talking about reduceing the compound, and this is what exactly happends.  I don't not know the exact yields of the compound to be created as side products and I doubt that I would be able to find a book that would give those yields.  Rhodium I am not crying for anything, Swig is in the making of trying to do this procedure. I was just mentioning this because I wanted to make a contribution to the war against drugs. ADDkid.

[WizardX]

OK! Enough talk. ADDKid do an experiment. Make the chloro or bromo halo-ephedrine (anhydrous) and then add acid washed and dried Mg, one crystal of iodine and gently reflux to initiate the reaction, all in a super dry ether. Quench with water.

Post your results please.