Yes I am aware I spelt amination incorrectly, thanks for that.
I have been quite successful in finding information using TFSE, BUT I have never done this and like to be able to picture everything in my mind before starting any project. So with that said I don’t understand part 1, and seeing as with this reaction everything seems to hinge on making sure there is NO H2O in this reaction.
SO are these assumptions correct?
As far as SWIM can see there are 2 different ways of getting the ammonia into the MeOH.
1. Adding ammonia acetate directly to the MeOH, would it be good to let this sit with some MgSO4 for a few hours and then filter before adding the MDP2P then adding the NaBH4 over time done at ~6c…, or-.
2. Dripping NaOH on the ammonia chloride to produce ammonia gas running through a drying tube with CaCL2 into pre dried cold ~ -20c MeOH after adding ~10 molar excess of ammonia gas letting it warm up to ~6c and adding pre chilled MDP2P and adding NaBH4 slowly over 6-7 hours keeping the temp around ~6c, after 7 hours letting the temp rise while stirring for ~20+ hours.
SWIM doesn’t have any silica beads, if the is done via the 2nd mention will water still form during the reaction? If so could some large chunks of MgSO4 be added to the reaction to keep what little water forms under control or will that affect yields also.
Also saw a few posts suggestion slightly acidic reaction improved yields, they had suggested adding ~ml of glacial acidic acid but that has water in it <well SWIM 80% does> Could this be added to the MeOH before it was dried via MgSO4?
This is some of the information I was able to find, have been going over it and have not found good description of this first crucial step.
In the MDMA pot you can throw the ketone in at once, the imine forms nearly directly.
We talk here about MDA, with the NH3/AA methods, and then you must create an excess of NH3gas(a lot) and some NH4+ and acetate- ions(just enough to buffer the pH) in solution, against ketone molecules, so that's why you drip the ketone in the methanolic solution, and keep slowlybubbling in NH3gas, to maintain that excess of NH3gas and NH4+, when ketone reacts with NH3 and NH4+ (this is by the way a much more complicated soup of ions than only NH3 and NH4+, UTFSE.)
The water which will not be instantly removed by the drying agents silicagel + MgSO4, will force the NH3gas to dissolve and dissociate in it, and add extra NH4+ ions to the mix, but also instignate extra OH- ions, that's why you need the acetate- (or carbonate-, or even (from NH4Cl)chloride-) ions to buffer(balance) the fast changing pH back to around 5.
And again, the MDA imine step untill maximal completion costs much more time than the MDMA imine step.
To push the product(imine) forming, you remove the side product water from the reactants solution with silicagel+ MgSO4, and keep it saturated with NH3gas.
The whole problem here is to produce enough imine, and stop it from reversing back to ketone, or proceeding further to the -ol. LT/
AN IMPORTANT THEORETICAL PS (thanks to foxy2 for digging up this formidable website ):
For those who do not exactly understand the underlaying theory, the following MUST-reads (download the MDL-Chime plugin, there's a new one out for Windows SP2 now, it works again, Netscape always worked):
http://www.cem.msu.edu/~reusch/OrgPage/VirtualText/aldket1.htm#rx1b
Nomenclature of Aldehydes and Ketones. Read all s.v.p.
Look at "Formation of Imines and Related Compounds" exerpts:
""The reaction of aldehydes and ketones with ammonia or 1°-amines to give imine derivatives (compounds having a C=N function) plays an important role in the synthesis of amines, as discussed earlier. As for acetal formation, water is eliminated in this reaction, which is also acid-catalyzed and reversible.""
And an interesting remark, this could be a novel Hive method for identification of questionable prepared KETONES:
""With the exception of unsubstituted hydrazones, these derivatives are easily prepared and are often crystalline solids - even when the parent aldehyde or ketone is a liquid. Since melting points can be determined more quickly and precisely than boiling points, derivatives such as these are useful for comparison and identification of carbonyl compounds. If the aromatic ring of phenylhydrazine is substituted with nitro groups at the 2- & 4-positions, the resulting reagent and the hydrazone derivatives it gives are strongly colored, making them easy to identify.""
Look at: ketone + (excess) hydrazine --> hydrazone in the top of the right block.
If we make the MDP2P and P2P and other interesting hydrazone ketone-derivatives, and they have a distinct color, then we have a perfect new ketone identification method found, the Reusch Ident, let's give the Man his well earned reward, what a fine teacher/computer-addept!
Most important remark for this thread discussion:
""The rate at which these imine-like compounds are formed is generally greatest near a pH of 5, and drops at higher and lower pH's. This agrees with a general acid catalysis in which the congugate acid of the carbonyl reactant combines with a free amino group, as shown in the above animation. At high pH there will be a vanishingly low concentration of the carbonyl conjugate acid, and at low pH most of the amine reactant will be tied up as its ammonium conjugate acid.
With the exception of imine formation itself, most of these derivatization reactions do not require active removal of water (not shown as a product in the previous equations). The reactions are reversible, but equilibrium is not established instantaneously and the products often precipitate from solution as they are formed.""
(What a pitty this doesn't work for our ketones, that would make the procedure piss-easy).
Now we take a look at:
""Irreversible Addition Reactions", and see there this interesting tidbit:
""Aminols (Y = NHR) are intermediates in imine formation, and also revert to their carbonyl precursors if dehydration conditions are not employed.""
""It follows then, that if nucleophilic reagents corresponding to H:(-), R:(-) or Ar:(-) add to aldehydes and ketones, the alcohol products of such additions will form irreversibly.""
And this is the description of NaBH4 reactions with ketones, sadly no reaction with imine is included, but a lot of the theory fits imine reduction also:
""Reduction by Complex Metal Hydrides"":
Exerpt:
""Addition of a hydride anion to an aldehyde or ketone would produce an alkoxide anion, which on protonation should yield the corresponding alcohol. Aldehydes would give 1°-alcohols (as shown) and ketones would give 2°-alcohols.
RCH=O + H:(-) RCH2O(-) + H3O(+) RCH2OH
Two practical sources of hydride-like reactivity are the complex metal hydrides lithium aluminum hydride (LiAlH4) and sodium borohydride (NaBH4). These are both white (or near white) solids, which are prepared from lithium or sodium hydrides by reaction with aluminum or boron halides and esters. Lithium aluminum hydride is by far the most reactive of the two compounds, reacting violently with water, alcohols and other acidic groups with the evolution of hydrogen gas.""
""Some examples of aldehyde and ketone reductions, using the reagents described above, are presented in the following diagram. The first three reactions illustrate that all four hydrogens of the complex metal hydrides may function as hydride anion equivalents which bond to the carbonyl carbon atom. In the LiAlH4 reduction, the resulting alkoxide salts are insoluble and need to be hydrolyzed (with care) before the alcohol product can be isolated. In the borohydride reduction the hydroxylic solvent system achieves this hydrolysis automatically. The lithium, sodium, boron and aluminum end up as soluble inorganic salts.""
And that's why flooding with water and distillation of the raw MDMA or MDA or Meth bases will take care of the problem how to get rid of the sodium borate salts left in solution.
""Modification of the Carbonyl Group.
I. Reduction:
The metal hydride reductions and organometallic additions to aldehydes and ketones, described above, both decrease the carbonyl carbon's oxidation state, and may be classified as reductions. As noted, they proceed by attack of a strong nucleophilic species at the electrophilic carbon.""
One for the hydrogenation lovers:
""Other useful reductions of carbonyl compounds, either to alcohols or to hydrocarbons, may take place by different mechanisms. For example, hydrogenation (Pt, Pd, Ni or Ru catalysts), reaction with diborane, and reduction by lithium, sodium or potassium in hydroxylic or amine solvents have all been reported to convert carbonyl compounds into alcohols.
However, the complex metal hydrides are generally preferred for such transformations because they give cleaner products in high yield.
http://www.cem.msu.edu/~reusch/OrgPage/VirtualText/special3.htm#top3
Reducing Agents, Oxidizing Reagents etc.
scroll to: Imine and Hydrazone Anions.
Exerpt:
""Still another way of circumventing some of the undesired aspects of enolate anion chemistry is to replace the oxygen of an aldehyde or ketone substrate with a 1°-amino group, in other words, to convert the carbonyl function to an imine. Imine derivatives are relatively easy to prepare, starting with an aldehyde or ketone and a 1°-amine or hydrazine derivative. The resulting C=N function does not activate alpha-C-H groups as effectively as a carbonyl function, but very strong bases such as LDA, alkyl lithiums and Grignard reagents will convert imines to their enamide conjugate bases quantitatively. This general reaction is shown in the green shaded box below."" See there for the reaction mechanism.
Another need to know fact:
""The C=N function of imines is a poor acceptor of nucleophiles,""
= = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = = =
http://www.cem.msu.edu/~reusch/OrgPage/VirtualText/amine1.htm#amin6
Nomenclature and Structure of Amines.
Click the button near the bottom: "To see an animated mechanism for imine formation". Read the whole page also. At the bottom you also can click for the "Leuckart procedure".
See also: Preparation of 1°-Amines : nr 4, change NaCNBH3 to NaBH4.
Mechanism is nearly the same as for MDA imine forming, forget the H2+Ni 2nd reaction condition:
NH3 + RCH=O -->Addition / Elimination <==>>> RCH=NH (imine) + H2O(^) --> NaBH4 Reduction --> RCH2-NH2.
