Prodine Analogue Idea - Need Advice

[Bwiti]

Are you familiar with

Patent US2765315

?

  To Make N,N',N"-trimethyltrimethylenetriamine
In a typical preparation of this reactant, 76 parts by weight of 37% formaldehyde solution is slowly added to 83 parts by weight of aqueous 40% methylamine solution with stirring and cooling, the temperature of the reaction mixture being kept below 10*C. Solid caustic soda is then added in increments until two liquid phases form and separate. The upper layer is taken. The lower layer is extracted with benzene and the extracts are added to the upper layer. The resulting solution is dried over anhydrous potassium carbonate and distilled. At 65* - 75*C./35mm., there is obtained a fraction of practically pure N,N',N"-trimethyltrimethylenetriamine in an amount of at least 36 parts by weight..
-----------------------------------------
  My question is, what if diethylamine is used in place of the methylamine above?? What compound would result? Could a secondary amine work instead of the methylamine? What would the name of this precursor be? As far as this goes, I'm ignorant.

  Alright, lets say that the precursor made from diethylamine/formaldehyde is reacted with a-methylstyrene, phosphoric acid, acetic or propionic acid, blah, blah.. Is it likely that the product would be active?
 
  Are secondary amines a no-no? What amines can be used? Any help and insights would be much appreciated!!!!!!!!!! Peace!!!!!!!!

[Pimpo]

N,N',N"-trimethyltrimethylenetriamine looks like this:

      CH3
      |  
      N---CH2
     /     \
  H2C       N---CH3
     \     /
      N---CH2
      |
      CH3

Each nitrogen is bridged by two methylene groups leaving room for only one alkyl group. Therefore only primary amines will form trialkyltrimethylentriamines.

[Bwiti]

Cool, thanks for clearing that up for me! Hmmmm.. In my dreams, maybe propylamine could be used. Better yet, I could use benzylamine because it's heavier, thus less stinky to work with. Thanks again!

[josef_k]

If you would use propylamine or benzylamine you would get an inactive product (or atleast very weak). But if you on the other hand used phenethylamine you would get a product thats more potent than the one with methylamine.

[Bwiti]

Shit! Thanks for the heads-up on the amine usage. I suppose the product from butylamine would be weak or inactive also? I can't get my hands on phenethylamine, so I'm bummed-out. Can ammonia be used - triammoniumtrimethylenetriamine? Do you know of any other amines that can be used? Any references? Any help would be much appreciated!

[Bwiti]

Alright, Rhodium said that with ammonia/formaldehyde, I'd probably end-up with hexamethylenetetramine, and I don't know if that would be of any use.
  Are you folks starting to get the idea that I dislike making methylamine?
  What if hydroxylamine was used? Also, what about phenylpropanolamine(PPA)?

[Bwiti]

Can't remember if I asked this before, but can isobutylene be used in place of a-methylstyrene to obtain an active product? I've used the search engine, but can't find an answer so far.. Having trouble getting ahold of a-methylstyrene.. Besides a-ethylstyrene, what else could be used?

[Pimpo]

a-methylstyrene "supplies" the aromatic ring to the molecule, so only styrene-derivatives will do (or maybe other arylalkenes). Don't want to be rude, but I think you don't understand how the molecule is furnished. I'll illustrate which part of the "prodine"-molecule comes from which precursor (Please correct me if I'm wrong).

         
         O
         ?
  Ph   O-C-CH2-CH3
    \ /
     C
    / \
 H2C   CH2
   |   |
 H2C   CH2
    \ /
     N
     |
     CH3 

black - a-methylstyrene
red - propionic acid
blue - N,N',N"-trimethyltrimethylenetriamine

[Bwiti]

Cool, so maybe 4-methoxystyrene will work.. What do you think about the use of hydroxylamine in place of methylamine?

[Rhodium]

I don't think that the resulting product is active, if the hydroxylamine even would survive the reaction conditions.

It is much more interesting to answer questions you might have if you state precise goals at the beginning, instead of you wildly changing directive all the time, in which case one may start to doubt if the time one has taken to find the answers for you will ever come to use or not... It has taken me well over an hour of research to answer your Prodine-related questions you've had lately.

[Bwiti]

Thanks for all your help.

[SPISSHAK]

I have the papers on clarke eschewieler cyclicicyzations and other  pertinent reactions simliar to this so you can understand the mechamisms.
let me know, I thought I already sent this to you.
in the case of say for example, alpha-methyl-styrene, reaction with, trimethyl,triazine, aka. trimethyl trimethylene,triamine, and propionic acid.
the mechanism is a an aminomethylation of the alkene followed by formation of the tertiary carbonioum ion (the pre cyclization intermediate) which is then saturated by the carboxylic acid, this explains why this procedure works like a dream, and without any hitches the mechanism is beautiful..
Email me you know who I i am.

 and to clarify, I have studied the mechanism in concert with others well educated in chemistry and we can conclude that methyl phenyl tetrahydropyridine is not a by-product of this reation by mechanistic studies.
Believe me I would not lie about this.
the key is to exclude water completely!!! Since tertiary alcohols are the easieast to dehydrate and in this reaction scheme water is needed to cause this hydrolysis, it is imperative to exclude water.
Hence the use of amino methylation reageants as trimethyl triazine as oppopsed to it's cousin, the amino formaldimine




 in the prescence of H2O?
BTW those heavier amines give way lower yields due to thier solubilty in the reation matrix.
I.E. phenyl-ethylamine.
for example.