Sn1, Sn2, E1, E2 Mechanism Explained in SMILES.

In Organic Chemistry, we enter mechanisms through substitution and elimination reactions. Which you should remember from organic chemistry but good to review on your own.

• Sn1, Sn2 — Substitution nucleophile and the amount of steps. 2 is one step. 1 is 2 step.
• E1, E2 — Elimination Reactions to the first and the amount of steps. 2 is one step. 1 is 2 step.

Let’s take four examples of each mechanism and write the SMILES from the source which I found to be the best drawings for me to explain them:

Sn2

Lets begin by writing the SMILES of (R)-2-bromobutane with sodium cyanide in DMF.

solvent = 'CN(C)C=O'
r_two_bromobutane = 'C[C@@H](Br)CC'
reactant = '[Na]C#N'

Sn2 happens in one step and so can start off with the leaving group, LG - Bromine, and the nucleophile, Nu, cyanide group in a solvent of DMF. I wrote the nucleophile in it’s ionized form to kind of get the reaction going.

#                   LG      Nu         Solvent
reaction = 'C[C@@H](Br)CC.[C-]#N.[Na+].CN(C)C=O'

The next step would be to actually push the arrows and this took me a bit to kind of decipher where we basically have our carbon in question placed with a * and the nucleophile and leaving group marked with a v to stand for virtual bond. I decided to use virtual bonds because it’s not really a real bond it’s the process of breaking and forming at the same time.

#              *     v        v    
first_step = 'CC(CC)(~Br)([H])~C#N.[Na+].CN(C)C=O'

You can place the image in ChemDraw if you like. The final product after this formation is then:

final_product = 'CC([H])(C#N)CC'

putting it all together

Putting it all together we get something like:

1. C[C@@H](Br)CC.[C-]#N.[Na+].CN(C)C=O
2. CC(CC)(~Br)([H])~C#N.[Na+].CN(C)C=O
3. CC([H])(C#N)CC.[Br-].[Na+].CN(C)C=O

Whew not too bad but was a little complex with generating the complex for the mechanism. Let’s try the Sn1 which has more steps.

Sn1

Let’s get our reaction going:

reaction = 'C[C@@H](O)CC.[H]Cl'

The first step is the generation of the LG where the oxygen of the (R)-2-butanol is converted into a electrophilic water leaving group from the hydrochloric acid and formation of the chloride ion.

complex_formation = 'CC([OH2+])CC.[Cl-]'

Now the substitution will occur in two steps where the leaving group will leave and then the attack of the nucleophile:

first_step = 'C[CH+]CC.O.[Cl-]'
second_step = 'CC(Cl)CC.O'

Which is actually pretty easy to do as compared to the Sn2 because we don’t have a complex formation with virtual bonds. We also lose some stereochemistry, when the charge forms the molecule can lose it’s orientation.

E2

Elimination and let’s only do it for formations of alkenes. So let’s eliminate (R)-2-bromobutane with a bulky base in which the reaction will have a one step process.

reaction = 'C[C@H](CC)Br.CC(NC(C)C)C'

So the first step is the attack of the basic nitrogen from disopropylamine onto the Beta hydrogen from the adjacent carbon to the halide carbon.

first_step = 'CC(~C([H]~N(C(C)C)C(C)C)C)~Br'

Which looks something like this:

In which there are virtual bonds placed across the major bonds that will be forming. The nitrogen comes to the hydrogen and then formation of the alkene but it’s still not an official bond order and the bromine leaving group. It then forms our final product:

final_product = 'C/C=C/C'

This should be getting pretty easy for you to do by now and let’s wrap it up with one more elimination.

E1

Where again we take our (R)-2-butanol and dehydrate it with sulfuric acid. in two steps so let’s setup our reaction.

reaction = 'C[C@H](CC)O.O=S(O)(O)=O'

The first step is the generation of the leaving group where one hydrogen from the sulfuric acid is placed on the alcohol.

first_step = 'CC([OH2+])CC.O=S([O-])(O)=O'

The leaving group then leaves to form the carbocation, here is the step where the elimination occurs and the alkene bond is going to form between the carbocation and the beta carbon.

second_step = 'C[CH+]~C[H]~O([H])[H]'

Now we have a pretty good idea of what is going with the virtual bonds and then to our final product.

final_product = 'C/C=C/C'

Alright well that seems to be kind of cool as a concept and perhaps we can do a formal standard of organic chemistry mechanisms stored in SMILES strings so we have a good set. Maybe something I can work on in my spare time in between molecules or if others want to draw mechanisms.