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The synthesis of Pseudopelletierine starts from glutardialdehyde, which reacts with methylamine and acetonedicarboxylic acid in a two-fold Mannich reaction.

This is the reaction:

enter image description here

I need to write the mechanism for this reaction. It needs to be under basic conditions also.

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MY ANSWER SO FAR:

There will be a Mannich reaction followed by a second intramolecular Mannich reaction in order to form a ring by joining al three reagents together. Finally there will be a decarboxylation to remove the carboxylic acid groups.

This is the mechanism I have done:

enter image description here

enter image description here

Is this right? Any help would be appreciated.

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    $\begingroup$ I was going to post essentially the same answer as @jerepierre but he beat me to it. Don't forget that you have a N-Me group missing in the structures in the second row from the end. You can also compare your mechanism with this $\endgroup$
    – K_P
    Nov 7 '14 at 20:06
  • $\begingroup$ Thanks for telling me about the missing N-Me group. That link you gave me is an acid catalysed reaction and the problem i am having is that mine is base catalysed. $\endgroup$
    – user5181
    Nov 7 '14 at 20:32
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You are very close. The only issue I see is that the Mannich reaction takes place between an enol(ate) and an imine (iminium). Your mechanism goes to the hemiaminal, and then the enolate must displace a hydroxide leaving group. Essentially that's an SN2 with a hydroxide as a leaving group, which does not occur. Instead, from the hemiaminal, the nitrogen kicks out the hydroxide to form an iminium, which is a much more reactive electrophile. The enolate attacks readily. Repeat that process, decarboxylate & tautomerize twice, and you're there.

enter image description here

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  • $\begingroup$ on the second reaction arrow, where it says "H+ transfer", how would you draw curly arrows to show that? Is one of the H's from the N+ being put onto the O-? Also where would I then be using the Na2HPO4 in my reaction for the synthesis of Pseudopelletierine? $\endgroup$
    – user5181
    Nov 7 '14 at 20:22
  • $\begingroup$ @user5181 It sort of depends on your instructor. The most correct way would be for the anionic oxygen to take a proton from HPO4- and for hydroxide to take a proton from the cationic nitrogen in two steps. I'm a lazy guy, so I usually draw what you suggest, with the anionic oxygen deprotonating the cationic nitrogen in a single step. Some instructors don't like that, so I tend to not draw that on this site. Since the proton transfer steps are fast and we don't always know the exact species taking or giving the proton (or the order, like in this case), some people just write "H+ transfer". $\endgroup$
    – jerepierre
    Nov 7 '14 at 21:37
  • $\begingroup$ @user5181 The mixture of Na2HPO4 with hydroxide gives a phosphate buffer that you can use to shuttle protons around. HPO4- will be the strongest acid and PO4(2-) will be the strongest base in the reaction mixture, so those species can play the acid and base roles in your mechanism. $\endgroup$
    – jerepierre
    Nov 7 '14 at 21:50
  • $\begingroup$ so can i actually draw a mechanism for the Na2HPO4 acting as the buffer or is it just not included in the mechanism. Also can i just check, can the H+ transfer still occur in basic conditions? I'm just worried as there isn't supposed to be any H+ in the reaction. $\endgroup$
    – user5181
    Nov 8 '14 at 0:39
  • $\begingroup$ @user5181 yes, proton transfer still occurs under basic conditions. There just can't be any free protons or strong acids generated. $\endgroup$
    – jerepierre
    Nov 9 '14 at 14:41

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