Organic Chemistry: Sn2 and Sn1 Reactions

Mnemonic to remember that carbocation formation is associated with Sn1 reaction?

"One" rhymes with "Ion" Sn1 results in a carbocatION

When are proton transfers necessary during a substitution reaction? (Sn1)?

1) At the beginning so as to provide a stable leaving group or 2) At the end given that there is a neutral nucleophile and the product needs to transfer a proton to have a net neutral charge

Why do methyl and primary substrates tend to undergo Sn2 reactions?

1) Litle to no steric hinderance, thus, nucleophile is free to attack backside of substrate molecule. 2) Methyl and primary carbocations aren't stable enough to be created

What 4 factors determine whether Sn1 or Sn2 reactions occur?

1) Substrate (primary, secondary, tertiary) 2) Leaving Group 3) Nucleophile 4) Solvent

What type of substrates react the most slowly with respect to steric hindrance?

3º groups react the most slowly since they have more groups which can cause inhibition in bumping

What is a hydride shift?

A Hydride shift occurs when a hydride ion (a hydrogen with 2 electrons) transfers to form another bond with another carbon in order to produce a more stable carbocation. ex: a hydride shifting to form a tertiary carbocation instead of a secondary carbocation

A transition state represents what in an energy diagram?

A peak

What analogy can be used to figure out if a Sn2 reaction will take place with a given nucleophile?

A poor nucleophile is like mother teresa and is nice and will therefore wait for the leaving group to depart first (Sn1) whereas a good (strong) nucleophile will butt in rudely and force the leaving group to depart (Sn2).

If a leaving group for a reaction is not very suitable, (the leaving group isn't stable) then what can occur in order for a more suitable leaving group to arise?

A proton can be donated in order to allow for a more stable leaving group so form.

If the nucleophile does not have a negative charge, what must occur after the nucleophilic attack?

A proton transfer at the end of the rxn to remove the positive charge once the nucleophile has attached to the substrate

If an Sn1 reaction is taking place and the substrate is an Alcohol (ROH) what must occur before the leaving group can leave?

A proton transfer in order to produce a more stable leaving group or convert it into OTs or OMe

If an Sn2 reaction takes place with a chiral alpha carbon, what configuration does the product typically result in?

An inverted configuration i.e. R goes to S or S goes to R

Why do Sn2 reactions require polar aprotic?

Because the aprotic solvent won't interact with the nucleophiles charge. Protic solvents interact via charge and interact with nucleophile thus decreasing its effect.

Sn1 reactions can react with which solvent type?

Both but they prefer polar protic

How can we determine whether a reaction is Sn2 or Sn1 based off of kinetics? (rate of the reaction)

By altering the concentration of reactants we can determine the mechanism. Sn1 reactions are first order and only depend on the concentration of the substrate whereas Sn2 reaction rates can be affected by the substrate OR nucleophile concentration.

In order for an Sn2 reaction to induce a stereochemical change, what must the substrate be?

Chiral, otherwise it will have no effect

What does stereospecific mean?

Configuration of the products depends on the configuration of the starting reactants.

What is DMF?

Dimethylformamide

What is DMSO?

Dimethylsulfoxide

What are electrophiles?

Groups with positive or partially positive charges

In order for a Sn1 reaction to be effective, the leaving group must be what?

Highly stable (weak base)

Under what circumstances if Fluorine a weak nucleophile?

In polar protic solvents

Which anion is the best leaving group and which is the worst? i.e. which is the least electronegative (most stable) and which is the most electronegative (least stable)?

Iodide is the best leaving group while fluoride is the worst.

A weak nucleophile favors which substitution reaction?

It disfavors Sn2 allowing Sn1 to occur

In order for an electrophile to act as a substrate in a substitution reaction, what must it contain?

It must contain a leaving group

How does the size of an atom affect its strength as a nucleophile?

Larger atoms can more easily disperse a charge and are stronger nucleophiles

What two systems should we recognize when looking for resonance stabilized carbocations?

Leaving Groups in either Benzylic or Allylic positions

What is the relationship between number of alkyl groups and the rate of both the Sn1 reaction and Sn2 reaction?

Methyl and Primary substituted molecules react the quickest for Sn2 reactions but the opposite is true for Sn1 reactions

What are protic solvents?

Molecules containing a hydrogen bonded to an electronegative atom

What type of nucleophiles require a proton transfer at the end of a substitution reaction?

Neutral Nucleophiles require a proton transfer so the product does not have a charge

Are non polar solvents good for performing Sn1 or Sn2 reactions?

No because the reactants are charged. i.e. polar

Can enantiomers be separated?

No, they have same chemical reactivity

What is a methyl shift?

Occurs when a methyl groups shifts in order to form a more stable carbocation.

When do rearrangements occur in a Substitution reaction?

Once the leaving group has left a rearrangement will typically take place. The nucleophile may attack quicker than the rearrangement in which case there will be a mixture of products however the rearrangement is typically faster.

Sn2 reactions only happen on what type of hybridized carbons?

Only on sp3 hybridized carbons. I.e. a bromine attached vinylicly to an alkene will not undergo Sn2

What class of solvents are DMF, HMPA and DMSO?

Polar Aprotic

Sn2 reactions require which type of solvent?

Polar aprotic

What type of solutions do Sn2 reactions occur the best in?

Polar aprotic solution i.e. any polar solvent without a proton available to donate, not an acid.

What are polar aprotic solvents?

Polar molecules in which there is no hydrogen attached to an electronegative atom.

What type of solvents do Sn1 reactions occur the best in?

Polar protic solutions i.e. solutions with a polar and acidic solvent (one with a hydrogen available for bonding) Any polar solvent with protons bonded to oxygen, nitrogen and fluorine.

In Sn2 reactions, which type of carbocation reacts the quickest and which the slowest?

Primary and secondary carbocation react quicker than tertiary carbocations due to steric hinderance

If the nucleophile is neutral, what step is required for Sn1 and Sn2?

Proton transfer at end of mechanism

What additional steps can occur between both Sn1 and Sn2?

Proton transfers occur between both but Sn1 can also have a carbocation rearrangement

What is the rate expression for Sn1 reactions?

R = k [Substrate]

What is the rate expression for Sn2 reactions?

R = k [substrate] [nucleophile] increasing concentration increases collision frequency.

What are Solvolysis reactions?

Reactions in which the solvent functions as the nucleophile

The strength of the nucleophile only affects which type of substitution reaction?

SN2 since it has both a nucleophile and electrophile in the rate determining step.

What type of substrates favor either Sn1 or Sn2?

Secondary, Allylic and Benzylic substrates

What mechanism is favored by polar protic solvents and why?

Sn1 mechanisms because polar protic solvents help to stabilize both the cation and anion

Which type of reaction results in a racemic mixture?

Sn1 reactions because the carbocation formed is sp2 hybridized making it flat, thus allowing the nucleophile to attack from either side.

A strong nucleophile will favor which substitution reaction?

Sn2

Which Sn reactions results in an inversion of configuration?

Sn2

What mechanism do Polar Aprotic solvents favor and why?

Sn2 because they increase the effectiveness of the nucleophile in attacking the electrophile by stabilizing the cation attached to the nucleophile. The anion cannot interact with the Polar Aprotic solvent due to steric hinderance and is therefore left to interact with the substrate.

Which type of reaction results in an inversion of configuration?

Sn2 reactions because the nucleophile attacks from the opposite side of the leaving group as it departs from the substrate.

What are polar protic solvents?

Solvents that have at least one hydrogen connected to an electronegative element. The solvent is also polar. Ex: Water, methanol, acetic acid

What are nucleophiles?

Species with either negative charges or nonbonding pairs of electrons that are available to form a bond. The nucleus is positive thus nucleophiles are attracted to the nucleus

What is steric hindrance?

Steric hindrance refers to when large groups on one of the reacting molecules inhibits that molecule from bumping into others to cause a chemical reaction.

Good leaving groups are the conjugate bases of what?

Strong Acids

What is a Sn2 reaction?

Substitution reaction. It is a nucleophilic reaction (thats what the N stands for). and it is bimolecular (indicated by the 2). The bimolecular aspect refers to the fact tat there are 2 things bumping into one another during the rate determining step of the mechanism.

How does steric hinderance affect the rate of Sn2 reactions?

Tertiary and Secondary alkyl halides react slower than primary ones due to hinderance. Even if the beta carbons have more alkyl groups, they can affect the rate.

What does stereospecific mean in a reaction?

That the configuration of the product is dependent on the configuration of the starting material

What is the effect of tight ion pairing?

The LG slightly hinders front side attack which is why inversion is slightly favored in Sn1

What part of the substrate does the nucleophile attack in Sn2 reactions?

The back, the side away from the leaving group.

What is the alpha position of an Alkyl Halide?

The carbon directly bonded to the halogen

What are the Beta positions of an Alkyl Halide?

The carbons bonded to the alpha carbon

What is tight ion pairing?

The close association of the LG with the carbocation in Sn1.

During Sn1 reactions, what happens to the geometry of the carbocation when the leaving group exits the carbon in the first step?

The leaving group causes the geometry to be trigonal planar

In a Sn1 reaction, why is a trigonal planar geometry for the carbocation significant with respect to the nucleophile colliding with it?

The nucleophile can collide on either side of the carbocation since it is planar.

What happens to the configuration of molecules in a Sn1 reaction?

The product that forms will either have the same configuration or an inverted configuration resulting in a racemic mixture usually although there is a SLIGHT preference for the inverted configuration

With respect to an energy diagram, which step is the rate determining step?

The rate that has the highest peak for the transition state indicating that it requires the most energy.

The lower the pKa of an acid.....

The stronger the acid

What happens to the configuration of the substrate in an Sn2 reaction?

The substrate undergoes an "inversion of configuration where the stereo center changes. Ex: Changing from (R) to (S)

The stronger the acid...

The weaker (more stable) the conjugate base

How do we determine the strength or weakness of a nucleophile?

There are three main factors: 1. Charge. HO:- > H2O: 2. Electronegativity. H3N: > H2O: 3. Bulk (steric hindrance): CH3O:- > (CH3)3CO:-

Why does the nucleophile attack from the rear of the substrate in a Sn2 reaction?

There is more overlap between the HOMO of the nucleophile and the LUMO of the substrate

What are Sn1 reactions?

They are unimolecular nucleophilic reactions. There is only one molecule during the rate determining step.

How do alkyl groups stabilize carbocations?

They donate their electron density to the un-hybridized p orbital on the positively charged carbon, therefore stabilizing it. Hyperconjugation

Why do tertiary substrates tend to undergo Sn1 reactions?

They have a lot of steric hinderance thus they only really undergo Sn1 reactions.

What type of Sn reaction do secondary substrates undergo?

They undergo Sn2 reactions if they have good nucleophiles in aprotic solvents, They undergo Sn1 reactions with poor nucleophiles in protic solvents.

What must be used to transform a Hydroxyl into a good leaving group?

TsCl and Pyridine

What type of substrate does not Favor Sn1 or Sn2?

Vinylic and aryl substrates. i.e. when the leaving group is in a vinyl position (directly attached to one of the carbons in a double bond)

What are some examples of polar protic solvents?

Water, alcohols (methanol, ethanol), carboxylic acids (acetic acid)

In what rare circumstance will a Leaving Group leave at the same time a carbocation Rearrangement occurs?

When the Leaving groups departure would result in a very unstable carbocation, thus a simultaneous rearrangement is necessary

During Sn2 reactions an inversion of configuration generally occurs when what is true?

When the alpha carbon (carbon bonded to halogen) is a chiral center

What are some common polar aprotic solvents?

acetone, DMSO, DME, and DMF

What is HMPA?

hexamethylphosphoramide

In general, if an acids pKa is negative, then it is a good candidate to be the?

leaving group

Do we ever get a 50/50 mixture of enantiomers in an Sn1?

not perfectly, Inversion is slightly favored