solo
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Primary Amine Methylation
In the methylation of a primary amine* if there happens to be an OH reactive group in the aromatic amine (primary amino alcohol) will the methylation
with oxalic acid and paraformaldehyde at 100 C or other methods, affect the OH group .................solo
*References
A SOLVENT-FREE AND FORMALIN-FREE ESCHWEILER-CLARKE METHYLATION FOR AMINES
Thomas Rosenau,1 Antje Potthast,1 Ju¨ rgen Ro¨ hrling,1 Andreas Hofinger,1 Herbert Sixta,2 and Paul Kosma1,
SYNTHETIC COMMUNICATIONS, 32(3), 457–465 (2002)
http://mihd.net/2rl6de
Abstract
Primary and secondary amines are N-methylated by a mixture of paraformaldehyde and oxalic acid dihydrate in good to excellent yields. The reaction
proceeds without involvement of organic solvents and toxic formalin. Reaction temperatures of 100 C are required for the decomposition of oxalic acid
into the intermediate formic acid which acts as the actual reductant. The reaction conditions have been optimized, and the mechanism has been
elucidated by means of deuteration experiments.
other references
The Action of Formaldehyde on Amines and Amino Acids'
BYH . T.C LARKEH, . B. GILLESPIAEN D S. 2. WEISSHAUS
Journal of the American Chemical Society 0002-7863, vol: 55 1933 p:4571
http://mihd.net/176lgc
Summary
Simple aliphatic amines are smoothly methylated to the corresponding tertiary amines by warming in formic acid solution with
formaldehyde.Dibenzylamine, under these conditions, is mainly converted into methyldibenzylamine, but at the same time yields some benzaldehyde and a
more volatile base (probably dimethylbenzylamine).
Tetra-alkyl-diaminomethanes,o n warming with formic acid, are converted into equimolar quantities of the corresponding dialkylamine and
methyldialkylamine. Hexamethylenetetramine reacts with warm formic
acid yielding mainly ammonia and trimethylamine, with smaller amounts of mono- and dimethylamines; only three-quarters of the methylene carbon
reappears as methyl in the final mixture.
Only about two-thirds of the anticipated amount of carbon dioxide, calculated on the assumption that the formic acid is the sole hydrogen donor, is
obtained in these reactions; apparently some of the formaldehyde also contributes hydrogen.
Amino acids react with formaldehyde in warm formic or acetic acid with detachment of some of the nitrogen in the form of volatile bases. Dimethyl
derivatives were isolated from the reaction in formic acid with glycine, P-aminopropionic acid, a-aminoisobutyric acid and a-amino-aphenylbutyric
acid. Other amino acids yielded breakdown and condensation of various degrees of complexity. Benzaldehyde was
isolated from a-aminophenylacetic acid, propiophenone from a-amino-aphenylbutyric acid, and a-(4-phenyl-2,3-diketopyrrolidyl)-/3-phenylpropionic acid
from phenylalanine. Mechanisms by which these products may be formed are suggested.
Download both articles here,....
[Edited on 22-12-2006 by solo]
Attachment: methylation of primary amines articles.zip (1.2MB)
This file has been downloaded 795 times
It's better to die on your feet, than live on your knees....Emiliano Zapata.
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XxDaTxX
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"(primary amino alcohol) ... will the methylation affect the OH group"
They got 93% yield of the tertiary amine using 2-aminoethanol without affecting the alcohol, however, I suspect you are not interested in tertiary
product no? ... or perhaps you meant a reactive phenol moiety?
....or PERHAPS we should talk of DCM wax interactions .... hahahhaa
[Edited on 22-12-2006 by XxDaTxX]
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solo
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Thanks for pointing that out as I didn't notice it ............regardless of wheather it's a primary or a secondary amine the reaction of methylation
doesn't seem to effect the OH group.....however one thing was discovered with this neat study , that is methylation without solvents in quantitative
yields without affecting the OH groups...............solo
[Edited on 22-12-2006 by solo]
It's better to die on your feet, than live on your knees....Emiliano Zapata.
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not_important
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I did some digging around when I ran into the oxalic+paraformaldehyde, and someone I know informed me that an associate of theirs had a grad student
try a few other amines (sorry, that is getting to be a bit indirect). Alcohols did dehydrate to some extent if they were prone to that anyway. The
other thing that happened was the formation of a 6-member ring as a side product in a case where there were 3 alkyl carbons between the O of OH and N
of amine; the COH2 ended up bridging the O and N as a methylene.
And, no, I don't know the exact compounds that gave the side reactions. But I was told that the seem to be fairly special case examples.
Another concern might be in cases with a fairly active aromatic ring the formldahyde might react with the ring, likely leading to condensation
products.
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solo
International Hazard
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Nothing like a test to verify the claims of this study since it doesn't take much to find out . however the resutls may be very helpful to some who
find this study helpful in their reactions...................solo
It's better to die on your feet, than live on your knees....Emiliano Zapata.
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