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Topic: Methylation of primary amines  (Read 10352 times)

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Offline java

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Methylation of primary amines
« on: December 21, 2006, 03:24:16 PM »
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 ..java


*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.




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Offline java

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Re: Methylation of primary amines
« Reply #1 on: December 22, 2006, 12:57:30 AM »
it seems that the answer was there in the first article where they methylated an  2-aminoethanol with a 93% yield....I guess it goes to show one must study and read the references carefully. however one can now methylate an amine in the presence of an OH with the knowledge that the OH will not be affected in this neat  methylating reaction using no solvents...file this one....java
It's better to die on your feet, than live on your knees.Emiliano Zapata..."Prefiero morir de pie que vivir siempre arrodillado."

Offline java

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Re: Methylation of primary amines
« Reply #2 on: January 03, 2007, 05:19:51 PM »
Quote
General Procedure for the Methylation of
Primary or Secondary Amines
A flask was charged with primary amine (10 mmol), paraformaldehyde
(4a, 20 mmol) and oxalic acid dihydrate (5a, 0.1 mol) and briefly flushed
with nitrogen. In the case of secondary amines, 10 mmol of 4a and
50 mmol of 5a were used. For amines with multiple amino functions,
10 mmol of 4a and 50 mmol of 5a were applied per methyl group to be
introduced. The vessel was closed and heated to 100 C for 1 h, and to
120 C for 10 min. The reaction mixture was cooled to room temperature.
The white, crystalline mass obtained was crushed, and calcium oxide
(0.1 mol) suspended in 50 ml of ethanol was added. The mixture was stirred
vigorously for 30 min, solids were removed by filtration, and the solvent was
removed in vacuo to produce the pure amine.

...source,

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)


My question is since a metal container is out of the question how could one do it? I was  thinking of using  in a glass round bottom flask with a column and a ballon  at thhe top  to control the pressure inside as the closed system refluxes for one hour so that the flask won't break....any suggestions or would this work? , P1V1 /T1 at work so since the temp will increase the volume will increase with the pressure hence the temp will be able to be attained ..java
It's better to die on your feet, than live on your knees.Emiliano Zapata..."Prefiero morir de pie que vivir siempre arrodillado."

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