Overview:
We will see that the point of this step is to actually just extend the carbon chain by one. This problem seems like it could have easily been circumvented, but remember that the carbon alpha to the amine was donated by the formaldehyde from the Mannich reaction. There is no way to add two carbons in this way, and so we are left with the somewhat roundabout way of extending the carbon chain.
One thing to note first of all is the solvent, DMF. DMF (if you are not familiar) is a very useful solvent. Like DMSO, it dissolves a very wide range of compounds and is quite polar (you can view the resonance structures on the wiki page). However, because of its high polarity, it has a very high boiling point (153 ºC). Solvents with BP's this high are very difficult to remove completely from you compound, and so you must always be careful when using DMF, that you can remove it from your reaction. For example, don't use DMF for a solvent if your final compound is a liquid/oil. Chances are you are going to have a hard time separating the two if you don't have a good distillation column (actually our lab doesn't even have a distillation column, not sure if most labs nowadays do). So, why is DMF used then!? Two reasons. First, DMF is a polar aprotic solvent. You may remember from Organic I, that these types of solvent are polar, but have no hydrogens available for hydrogen bonding. What these solvents effectively do for SN2 reactions is to stabilize the nucleophile and the leaving group. This brings down the activation energy of the reaction and dramatically (and I mean dramatically) increase the rate. One example I found briefly online showed that performing an SN2 in methanol vs DMSO, took 20h for ~70%, or 20 minutes for ~90% conversion, respectively. That is a huugee difference!
The second important part of the DMF, is that it is a high boiling point solvent, and so it allows an increase in the temperature up to 150 ºC, which should help drive the reaction forward. Other factors driving the reaction forward include the excess amount of sodium cyanide, as well as the leaving group. The tetraalkyl ammonium group is positively charge, and as it coverts to a neutral species in the transition state, it becomes actually not such a great nucleophile (tertiary amines are significantly worse nucleophiles than primary amines). I could go on and on and on about SN2 reactions, and maybe I will make a post about them in the future. In the meantime, if you are still curious about all the possibilities I recommend 2 sources. This page, and "Modern Physical Organic Chemistry" by Anslyn and Dougherty (Chapter 11).
Workup:
For this reaction, simply mixing the two compounds (In a fume hood because of the sodium cyanide!) and heating for 1 h completes the reaction. As I said before, DMF is a great solvent for SN2 reactions. However, removing the DMF can usually be problematic. However, in this case, isolation was actually very easy. Diluting the solution of DMF (70 mL) into 350 mL of water precipitated out the product (again, our product is pretty non-polar, and DMF dissolves just about everything). Isolating the solid on a vacuum funnel and washing with water should remove all the DMF. Further purity of the sample was obtained by recrystallizing from ethanol.
Here is one thing that I would like to say that I believe is so so so often left out of descriptions, and can actually be very tricky in the laboratory. How do you pick a solvent to recrystallize from? All the advice I have recieved, is just "try a lot of different solvents". Not the best advice... So here is where I would like to give some insight into the choice of ethanol. Ethanol is usually a great choice for recrystalliztion of aromatic compounds. It's a trend I have noticed through some of my literature searching, as well as brief experience. If you come across an aromatic compound, chances are you can recrystallize it from ethanol or often isopropyl alcohol too. Ethanol is a polar solvent and usually aromatics are not that polar. Thus, by heating, the aromatics will usually dissolve (as ethanol can be heated up to ~70 ºC). Also of importance in this reaction was the fact that it was performed under nitrogen atmosphere. But why? Well, water getting into the reaction can be bad because it can destroy some of the sodium cyanide. The pka of the cyanide ion is 9.1, meaning that if you put the sodium cyanide into a water solution at pH 7, actually most of the sodium cyanide (about 99%) would turn to hydrogen cyanide (the poisonous gas you are scared about) and so it is important to keep the sodium cyanide in its ionic form for the sake of the reaction, and for yourself.
Lastly, how does one deal with the aqueous waste leftover? After all, there are likely still cyanide ions leftover in the water solution. As with many things, there are lots of ways, but most commonly you will see some sort of oxidant used. This can be KMnO4, hydrogen peroxide, bleach (sodium hypochlorite). By making sure that the solution stays basic (around pH 9-10) ensures a quick reaction. Using ~100mM hydrogen peroxide at pH 10, the reaction was essentially complete in 9 minutes (Link).
Looking Ahead:
Anyways, there is always so much to talk about and I really end up writing much more than I ever though I would. At this point we are still attempting to create a ring (specifically this ring is known as ring V) of the strychnine molecule. Our next step will be to reduce the cyanide group into a primary amine. To do this, we will need a strong reducing agent (LiAlH4).
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