06-06-04 23:09
No 511825
As in most reactions , save the reduction with sodium borohydride and Iodine, reducing the COOH in the Phenylalanine the precaution of protecting the amine group comes into play. In methylating the amine with iodomethane , my question is then....Will the methylating of the amine affect the COOH and is this the best way to do this and what solvent and conditions would apply? I have checked the search sources and Rhodium for the answer but not yet found it.....
Note There are many ways to reduce the the COOH and with the amine group methylated, as it works as a protection against side reactions, the routes increase and the need for the lithiums and hydrides and Boron become less needed. ....java
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(Chief Bee)
06-07-04 00:38
No 511844
In methylating the amine with iodomethane , my question is then....Will the methylating of the amine affect the COOH and is this the best way to do this and what solvent and conditions would apply?
Carboxylic acids are only methylated with alkyl halides under basic conditions, i.e. when it is in the form of a carboxylate salt.
The problem isn't really the presence of a carboxylic acid function, but rather that you will mainly end up with N,N-dimethyl-phenylalanine and its methiodide (i.e. the quaternary ammonium iodide) if you react phenylalanine with MeI just like that.
There are many ways to reduce the the COOH and with the amine group methylated, as it works as a protection against side reactions, the routes increase
Really? I don't know any reductions which significantly differentiates between primary and secondary amines when it comes to side-reactions.
The Hive - Clandestine Chemists Without Borders
(Hive Bee)
06-07-04 19:48
No 512010
Rhodium ...After reading ../rhodium /ampheta
As to the reactions that are parallel to the reduction of the COOH once the amine group has been methylated , as with the method stated above, how about the Phosphorous /Iodine environment in the reduction of the OH in ephedrine, Pseudoephedrine? I also didn't imply that the reaction differentiated between on or the other, that you read into the question.....java
Addendum; I especially liked the one with formaldehyde, I wonder if the amino acid will be soluble in this solvent to form the formaldehyde imine in a reflux? then hydrogenate with Pt. to reduce to the desired methylated amine.
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(Chief Bee)
06-07-04 21:21
No 512030
The article is directed to the treatment of amphetamines so would this also work for phenylalanine?
Yes, that is likely. As long as the conditions are mild and you don't reduce the acid to the aldehyde in the process (something which might happen if you perform a reductive alkylation with Al-Hg/HCHO for example). Aminoaldehydes polymerizes.
As to the reactions that are parallel to the reduction of the COOH once the amine group has been methylated, as with the method stated above, how about the Phosphorous /Iodine environment in the reduction of the OH in ephedrine, Pseudoephedrine?
Post 499398 (Rhodium: "Aren't carboxylic acids rather inert to HI?", Stimulants)
I also didn't imply that the reaction differentiated between on or the other, that you read into the question...
Huh? Then what did you infer with the following statement? "There are many ways to reduce the the COOH and with the amine group methylated, as it works as a protection against side reactions, the routes increase" There are no less side-reactions when reducing N-Methyl-phenylalanine compared to plain phenylalanine - there is still a N-H function present.
The Hive - Clandestine Chemists Without Borders
(Hive Bee)
06-07-04 22:43
No 512048
Rhodium...Well that is good news, I plan to hydrogenate using Pt , the environment should be mild enough to avoid the conversion to aminoaldehyde mentioned. Will the N,methylated phenylalanine have an easier time being reduced to an alcohol or a CH3 ? Or the established methods sodium borohydride, lithium, and the others still work the same ? Also if I chose to go to the aldehyde then OH will I have a problem with polymerization as mentioned in your reply? As to my statement of less side reactions....I stand corrected ........java
We're all in this world together,
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(Chief Bee)
06-08-04 00:06
No 512069
(Rated as: excellent)
Will the N,methylated phenylalanine have an easier time being reduced to an alcohol or a CH3? Or the established methods sodium borohydride, lithium, and the others still work the same?
Should be pretty much the same. You cannot reduce the COOH to CH3 with anything less than triethylborohydride, everything else will give the alcohol. You must probably also protect the nitrogen somehow (acetylation perhaps?) before halogenating the primary alcohol, or it may polymerize (the formed alkyl halide alkylating the nitrogen of another molecule).
I believe that you will get higher yields in the end if you first reduce phenylalanine to amphetamine, and first afterwards methylate your product to meth.
Also if I chose to go to the aldehyde then OH will I have a problem with polymerization as mentioned in your reply?
Exactly. Amines and aldehydes in the same pot (or in the same molecule) will invariably form imines and depending on structure, they may continue to react from there.
The Hive - Clandestine Chemists Without Borders
(Chief Bee)
06-09-04 03:07
No 512264
(Rated as: good read)
Here is a prep of N-methyl-phenylalanine, N-methyl-alanine and other N-methylated amino acids. As the intermediate product is the N-Benzyl-N-methyl-amino acid, you have your protecting group attached which you can use to prevent side-reactions on the nitrogen. When you have reduced the carboxylic acid to a methyl group via the intermediate halide you can then remove the benzyl group with Zinc/Ammonium Formate as described in Post 512088 (Rhodium: "Zinc/Formate: CTH Debenzylation (N-/O-/S-)", Novel Discourse)
Die Synthese optisch aktiver N-Monomethyl-Aminosäuren
P. Quitt, J. Hellerbach und K. Vogler
Helv. Chim. Acta 46, 327-333 (1963) (../rhodium/pdf /n-methyl-ami
Abstract
A synthesis of optically active N-monomethylated amino acids (V) is described. It involves a three-step process, starting from optically active amino acids (I) which are converted into their benzyl derivatives (III), subsequently methylated (IV) and finally hydrogenolyzed. The reaction sequence proceeds without racemization.
The Hive - Clandestine Chemists Without Borders
(Hive Bee)
08-08-04 23:08
No 524302
This is a post that compliments this inquiry....thanks to Rhodium bringing it to my
attention......java
Post 524301 (Rhodium: "NaBH(OAc)3 Reductive Alkylation of Amino Acids", Novel Discourse)
Just hold on to the thread...that keeps us going
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