How can we tell which mechanism to use? This question will get more complicated unfortunately, but for now we can use the following factors to answer this question.
Concept: How do we predict if the mechanism is SN1 or SN2?4m
Now I've taught you two different mechanisms that we can use to perform a substitution. And it's already hard enough that you have to memorize all these different facts about the rate and about what's favored and what's not favored. But one of the even more confusing parts can just be figuring out when do I use SN2 and when do I use SN1.
So what I want to do is I want to put together a little list of rules, a little list of basically, comparisons so that we can figure out when do we use one mechanism and when do we use another. Just as a heads up, this is actually going to get more complicated later on once you start talking about elimination. But for right now, since we're just in substitution, we can simplify it down to just two variables.
And you're probably going to guess what they are. Let's just go ahead and get started. It's just going to be – we're going to look at nucleophile strength and we're going to look at leaving group substitution. This has to do with the things that I keep saying are different between SN2 and SN1.
So actually, why don't you guys help me fill these in. The first thing we look at is nucleophile strength. What type of nucleophile is favored for an SN1 reaction? Do you guys remember? We said weak. Because remember that weak means that it's not going to start the reaction, it's going to wait for the carbocation to form. So that means what kind of nucleophile's favored for SN2? Strong. Strong is favored because we want it to do a back side attack. Is that cool so far?
What's the other thing? Well, we look at leaving group substitution. Leaving group substitution says that which type of degree – remember alkyl halides are measured in degrees. Which degree is the most favored for SN1? Remember that it goes in order of the best carbocations. Remember carbocations, they're the most stable when they have the most R groups around them. That's just a rule that I told you to memorize that I'll explain more later. That just means that tertiary is going to be more stable than secondary, more stable than primary and that's it. And then methyl is the worst.
So then alternatively for SN2, which one is the most favored? And it turns out it's the opposite trend. For SN2, methyl is the most favored, then primary, then secondary, then tertiary. In fact, just so you guys know, for SN1, primary and methyl don't even happen because they're so bad at making carbocations. For SN2 tertiary doesn't even happen because it's so bad it has a terrible back side.
So I'm just going to put here bad carbocation for this one. And I'm going to put here bad back side. If you understand the mechanisms, this should be too confusing of what I'm saying. That basically the best carbocation is going to be tertiary. The best back side is going to be methyl.
Now for these next questions. I'm going to basically pile everything together. I'm not going to tell you what the mechanisms are. You have to go ahead and determine first of all what the mechanism is using these rules and then you have to draw the final product based on everything I've taught you about these mechanisms. I know that sounds challenging, but I believe in you guys. I think you can at least get close.
So go ahead and try to draw the mechanisms and the products of the following reaction.
When given a substitution reaction, use the following two factors to determine the mechanism:
Nucleophile Strength: SN1 = WEAK SN2 = STRONG
Leaving Group Substitution: SN1 = 3° > 2° SN2 = 0° > 1° > 2°
Problem: Predict the product of the reaction4m
Problem: Predict the product of the reaction6m
The observed relative reactivities of primary, secondary, and tertiary alcohols with a hydrogen halide are 3o > 2o > 7o. If secondary alcohols were to undergo an SN2 reaction rather than an SN1 reaction with a hydrogen halide, what would be the relative reactivities of the three classes of alcohols?
For each reaction, give the expected substitution product, and predict whether the mechanism will be predominantly first order (SN1) or second order (SN2).
(a) 2-chloro-2-methylbutane + CH3COOH
(b) isobutyl bromide + sodium methoxide
(c) 1-iodo-1-methylcyclohexane + ethanol
(d) cyclohexyl bromide + methanol
(e) cyclohexyl bromide + sodium ethoxide
Draw the configuration(s) of the substitution product(s) that will be formed from the reactions of the following compounds with the indicated nucleophile:
Draw the products obtained from each of the following reactions and show their configurations
a. under conditions that favor an SN2 reaction.
b. under conditions that favor an SN1 reaction.
The following reaction sequence gives rise to two isomeric products A and B. Write the structures of A and B and propose a detailed mechanism for their formation.
b. Which one of compounds A and B will be favored under kinetic or thermodynamic control. Explain your answer with one sentence for each compound.
Each reaction shown below is a nucleophilic substitution reaction. Compare the mechanisms of the two reactions. Label each mechanism as Sn1 or Sn2.
Predict the organic product of the following reaction. When appropriate, be sure to indicate stereochemistry. If more than one product is formed be sure to indicate the major product. Draw your answer in skeletal form. You will be graded on the product your draw from the reaction no other information is needed for this question.
Put a circle around the statements that relate to an SN 2 mechanism and put a square around the ones that talk about SN1.
CH3X > 1˚ > 2˚ No rearrangements
Rearranged products Rate = k [alkyl halide] [Nuc]
Polar protic solvent Racemization
Inversion at chiral carbon Rate = k [alkyl halide]
3˚ > 2˚ Polar aprotic solvent
Strong nucleophile Weak nucleophile (may also be solvent)
The following reaction will not occur. Explain why the reaction will fail.
In contrast to SN2 reactions, SN1 reactions show relatively little nucleophile selectivity. That is, when more than one nucleophile is present in the reaction medium, SN1 reactions show only a slight tendency to discriminate between weak nucleophiles and strong nucleophiles, whereas SN2 reactions show a marked tendency to discriminate. (b) Show how your answer accounts for the following:
In contrast to SN2 reactions, SN1 reactions show relatively little nucleophile selectivity. That is, when more than one nucleophile is present in the reaction medium, SN1 reactions show only a slight tendency to discriminate between weak nucleophiles and strong nucleophiles, whereas SN2 reactions show a marked tendency to discriminate. (a) Provide an explanation for this behavior.
When the alkyl bromides (listed here) were subjected to hydrolysis in a mixture of ethanol and water (80% EtOH/20% H2O) at 55°C, the rates of the reaction showed the following order:
(CH3)3CBr ˃ CH3Br ˃ CH3CH2Br ˃ (CH3)2CHBr
Provide an explanation for this order of reactivity.
1-Bromobicyclo[2.2.1]heptane is extremely unreactive in either SN2 or SN1 reactions. Provide explanations for this behavior.
Consider the reaction of I - with CH3CH2Cl.(a) Would you expect the reaction to be SN1 or SN2? The rate constant for the reaction at 60°C is 5 x 10 -5 L mol-1 s-1.
Which of these structures best depicts the transition state for the reactions of CH 3I with CH3OK in CH3OH?
What is the stereochemistry of the nitrile produced in the reaction shown?
Does the following chart depict and S N1 or SN2 type mechanism?
What is (are) the organic product(s) of the following reaction?
Predict the major organic substitution product for the following reaction:
Which of the following is NOT a possible step in a substitution reaction?
Which one of the following correctly describes the reaction below?
Identify the substitution product(s) in the following reaction.
d) a mixture of A and B
Determine the product(s) for the following reaction
d) a mixture of A and B
Compare the following reactions and decide which reaction in each group would occur faster. Write your answer and concisely defend your choice.
For the following reaction
a) Label the nucleophile, electrophile, and leaving group.
b) Identify if it follows SN1 or SN2 mechanism.
c) Provide a detailed curved arrow mechanism
For each of the following pairs of SN2 reactions, tick the box that corresponds to the SLOWEST reaction of the two:
Give the rate equation for the reaction occuring between NaCN and CH 3CH2Cl. Write your answer in the box below.
For a unimolecular nucleophilic substitution (________) reactions, bond breaking and bond formation occur _______, ________ is/are involved in the transition state of the rate-determinining step. However, for biomolecular nucleophilic substitution (_______) reactions, bond breaking and bond formation occur _______. A bimolecular reaction is one in which _______ is/are involved in the transition state of the rate determining step.
Consider the following reaction. Assuming no other changes, what would happen to the rate of the reaction if the concetration of the nucleophile was doubled and if the concentration of the alkyl halide was tripled?
a. There would be no effect
b. The rate would double
c. The rate would triple
d. The rate would increase 6-fold
e. The rate would increase 9-fold
The SN2 reaction is a one-step bimolecular substitution that occurs between a nucleophile and a molecule with a methyl, primary, or secondary leaving group. The SN1 reaction is a two-step unimolecular substitution between a molecule with a secondary or tertiary leaving group.
The SN2 reaction
The SN1 reaction
Has no intermediate
Has an intermediate
Prefers leaving groups that are not sterically hindered
Prefers leaving groups that are sterically hindered
Reaction rate depends on the concentrations of both the nucleophile and the substrate
Reaction rate depends solely on the concentration of the substrate
Prefers polar aprotic solvents
Prefers polar protic solvents
Produces a racemic mixture
The SN2 reaction prefers leaving groups that aren’t sterically hindered because the substitution occurs through a nucleophilic backside attack; more R-groups means more steric hindrance.
The SN1 reaction prefers leaving groups with more R-groups attached because the rate-determining factor is the carbocation produced by leaving-group dissociation; R-groups stabilize carbocations through hyperconjugation.
To illustrate the mechanisms, let’s use an achiral alkyl halide as our substrate and hydroxide as our nucleophile.
SN2 transition state
In an SN2 reaction, the nucleophile does a “backside attack” on the leaving group’s carbon, inverting chirality if present. SN2 reactions only have one transition state, and it has partial bonds between the nucleophile and carbon and between the carbon and leaving group. The nucleophile and carbon both have partial negative charges.
SN1 transition states
In an SN2 reaction, the leaving group dissociates first, and the nucleophile results the resulting electrophile (the carbocation). SN1 reactions have two different transition states. The first one shows the dissociation of the leaving group with a partial negative on the leaving group and partial positive on the carbon. The second shows the bonding of the nucleophile to the carbon with a partial negative on the nucleophile and a partial positive on the carbon.
SN2 energy diagram
SN2 reaction diagrams have one single peak because there is only one transition state. The more sterically hindered the leaving group, the greater the energy requirement is to reach the transition state.
SN1 energy diagram
SN1 reactions have two transition states and an intermediate between them. Transition state 1 (TS1) is higher energy than TS2 because it leads to the formation of the carbocation. Carbocation formation is the rate-determining step. The less stable the carbocation, the higher in energy both TS1 and the intermediate are.
P.S. Check out my video on how to determine if a mechanism will proceed through SN2, SN1, E2, or E1 using the BIG DADDY FLOWCHART.
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