Ch. 7 - Substitution ReactionsWorksheetSee all chapters
All Chapters
Ch. 1 - A Review of General Chemistry
Ch. 2 - Molecular Representations
Ch. 3 - Acids and Bases
Ch. 4 - Alkanes and Cycloalkanes
Ch. 5 - Chirality
Ch. 6 - Thermodynamics and Kinetics
Ch. 7 - Substitution Reactions
Ch. 8 - Elimination Reactions
Ch. 9 - Alkenes and Alkynes
Ch. 10 - Addition Reactions
Ch. 11 - Radical Reactions
Ch. 12 - Alcohols, Ethers, Epoxides and Thiols
Ch. 13 - Alcohols and Carbonyl Compounds
Ch. 14 - Synthetic Techniques
Ch. 15 - Analytical Techniques: IR, NMR, Mass Spect
Ch. 16 - Conjugated Systems
Ch. 17 - Aromaticity
Ch. 18 - Reactions of Aromatics: EAS and Beyond
Ch. 19 - Aldehydes and Ketones: Nucleophilic Addition
Ch. 20 - Carboxylic Acid Derivatives: NAS
Ch. 21 - Enolate Chemistry: Reactions at the Alpha-Carbon
Ch. 22 - Condensation Chemistry
Ch. 23 - Amines
Ch. 24 - Carbohydrates
Ch. 25 - Phenols
Ch. 26 - Amino Acids, Peptides, and Proteins
Johnny Betancourt

The SN2 reaction is a bimolecular nucleophilic substitution reaction that occurs in one step. The nucleophile performs a backside attack on the carbon to which the leaving group is attached. If the carbon is asymmetric, inversion of stereochemistry is observed. 

Mechanism

The SN­­2 mechanism proceeds through a concerted mechanism. All that means is that it proceeds in one step and there’s no intermediate. As the nucleophile (Nu–) performs a “backside attack,” the leaving group (LG) dissociates. In other words, the nucleophile makes a bond and breaks the bond of the leaving group to the carbon holding it. 

SN2 generic mechanismSN2 generic mechanism
 In this generic reaction, the nucleophile is attacking the carbon holding the leaving group, which causes the nucleophile to dissociate. Notice that the net charge of the reaction stays the same. There’s no intermediate in this reaction; it goes straight from reagents to products.

SN2 transition stateSN2 transition state

As the nucleophile forms a bond to the carbon, the leaving group’s bond is broken. This is called the transition state, and it’s indicated from the double dagger (­≠) that’s generally placed at the top right of the box it’s included in. Notice that both the nucleophile and leaving group have partial negative charges. That makes sense because the nucleophile is donating an electron while the leaving group is accepting an electron. 

Now that we know what’s happening in the reaction, let’s look at the reaction-coordinate diagram:

SN2 reaction coordinate diagramSN2 reaction coordinate diagram

In this diagram, there are really only three parts: the reagents, the transition state, and the products. The transition state is the point in the reaction with the highest energy level, and the difference in energy between the reagents and transition state is called the activation energy (often abbreviated as Ea). Remember that the rate-determining step is the step that has the highest activation energy in the reaction.

Nucleophile

The nucleophile in SN2 reactions is generally anionic. Sometimes the negative charges aren’t shown explicitly because a cationic metal is used to stabilize the negative. A great example of this is NaCN. CN is negatively charged, and Na is positively charged. It’s an ionic bond that readily dissociates in the presence of a good electrophile or leaving group. Group 1 atoms like Na, Li, and K are a dead giveaway! 

Leaving groups

Atoms or molecules that can easily hold a negative charge are generally good leaving groups. What’s a good way to know if a molecule can be a good leaving group? Check its conjugate acid’s pKa! 

Bromide leaving groupBromide leaving group

When a leaving group dissociates from the substrate, it gains an electron. If it can hold the resulting negative charge “comfortably,” it’s a good leaving group. The bromine in the reaction above is a good leaving group because the pKa of its conjugate acid HBr is -9, which means it can hold a negative charge well.

Not all leaving groups are created equal! Even if you’ve got a bromine like in the example above, its degree greatly influences reactivity toward SN2 reactions.

Degree affects reactivity toward SN2Degree affects reactivity toward SN2

Methyl (0º) leaving groups are very reactive toward SN2 reactions, and tertiary (3º) are not reactive toward them at all. Secondary leaving groups risk competing with E2 reactions. Try to imagine a nucleophile trying to overcome the sterics of even three methyl groups, let alone three phenyl groups. It’s almost impossible for it to squeeze through; SN1 reactions are much more likely to happen in that case. 


Steric hindranceSteric hindrance

See how hard it is for the nucleophile to bypass all the R-groups to get to the carbon holding the tertiary halogen (X)? A tertiary halide with just methyl groups is the best-case scenario, and that’s already enough to stop an SN2 from occurring. 

Let’s look at this oversimplified coordinate diagram of a theoretical tertiary SN2 reaction relative to secondary, primary, and methyl reactions. 

Theoretical tertiary SN2 reaction coordinate diagramTheoretical tertiary SN2 reaction coordinate diagram

The activation energy is so ridiculously high that it’s just not going to happen. Other reactions that have lower activation energies will happen instead. 

Solvent

SN2 reactions function best in polar aprotic reactions. Basically that means polar solvents that don’t have any acidic protons. Acetone, DMSO, and dimethyl chloride are commonly used polar aprotic solvents. 

Reaction rate

The reaction rate of SN2 reactions depends on the concentrations of both the nucleophile and the leaving group. That’s why it’s called a bimolecular nucleophilic substitution reaction. Here’s the rate law:

SN2 rate lawSN2 rate law

So, what happens to the rate if we double the concentration of the nucleophile? The leaving group? Both?

  • Nucleophile = rate doubles
  • Leaving group = rate doubles
  • Both = rate quadruples

Examples

Let’s go ahead and react an achiral, secondary alkyl halide with NaCN. 

Sodium-cyanide-and-isopropyl-bromideSodium cyanide and isopropyl bromide

All that happens is that the –CN attacks the secondary carbon bonded to the Br, and the formation of that bond causes the C-Br bond to break. The NaBr salt that forms is an inorganic product, and it can generally be ignored.

Now, wait a minute. See how I specified that the alkyl halide above was achiral? What happens when the leaving group is at a chiral center like in the following example?

Hydroxide and 2-iodobutaneHydroxide and 2-iodobutane

In this case, the mechanism looks the same, but there’s one key difference. The iodine was on a wedged bond, but the resulting alcohol is on a dashed bond. That’s inversion of stereochemistry! In the very first paragraph, I said that the nucleophile performs a “backside attack,” and this is the result. Remember that the iodine is facing toward us, so that means the hydroxide attacked from the back and forms a bond on dash. 

P.S. In case you’re wondering how we know if an anion will work as a nucleophile vs base, check out the Big Daddy Flowchart! It’ll also help you determine if a mechanism will be SN1, SN2, E1, or E2. 




Johnny Betancourt

Johnny got his start tutoring Organic in 2006 when he was a Teaching Assistant. He graduated in Chemistry from FIU and finished up his UF Doctor of Pharmacy last year. He now enjoys helping thousands of students crush mechanisms, while moonlighting as a clinical pharmacist on weekends.


Additional Problems
Construct a mechanism for the following reaction. Include the transition state in your reaction mechanism.
Draw the transition state for the reaction between (S)-1-iodo-3-methylpentane and NaSCH3
Identify the correct potential energy diagram for a tertiary alkyl chloride (3°RCl) versus primary alkyl chloride (1°RX) undergoing an SN2 reaction. Provide rationale to support your choices. 
Draw the major product(s) for the following reaction in the box provided. Indicate stereochemistry where appropriate. When a racemic mixture is formed, you must draw both enantiomers and write RACEMIC. The mechanism of each reaction (SN2, E2, SN1, or E1) is written below the reaction arrow. Therefore draw your product accordingly.
The reaction below exhibits a second-order rate reaction:  Show the mechanism for the reaction above.
The reaction below exhibits a second-order rate reaction: What happens to the rate if the concentration of 1-iodopropane is doubled and the concentration of sodium hydroxide is tripled?   
Draw the product for each of the following SN2 reactions: (S)-2-Chloropentane and NaCN
Provide a full arrow pushing mechanism showing all steps and the transition state formed for the following reaction. 
Draw the mechanism for each of the following reactions: 
Draw the product of the reaction between (R)-3-bromohexane and NaSH in DMSO.
Which compound would react fastest by an S N2 mechanism?
Which rate law best depicts an S N2 type mechanism? (Note: [E] is the electrophile concentration and [N] is the nucleophile concentration). A)  R=k[N] B)  R=k[E] C)  R=k[N][E] D)  R=k[N][E]2
Rank the following alkyl halides in order of increasing SN 2 reactivity. (1 – least reactive, 3 – most reactive).
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 all answers in skeletal form.
In July 1917 British soldiers on the Western front in Ypres were attacked by the German army using mustard gas, the chemical structure of which is shown below. Use curved arrows to show mechanism and draw the product of the intramolecular nucleophilic substitution reaction that this compound undergoes in the box provided.
Consider the following reaction: This reaction has been determined to be second order. What is the rate equation for this reaction?
Which alkyl halide would you expect to react more rapidly by an S N2 mechanism? Explain your answer.  
Which alkyl halide would you expect to react more rapidly by an S N2 mechanism? Explain your answer.  
Which alkyl halide would you expect to react more rapidly by an S N2 mechanism? Explain your answer.  
Which SN2 reaction of each pair would you expect to take place more rapidly in a protic solvent?  
For the following haloalkanes, rank them from 1-4 with respect to reactivity in an SN2 reaction, with a 1 under the LEAST REACTIVE HALOALKANE, and a 4 under the MOST REACTIVE HALOALKANE.
Complete the energy diagram below for an SN2 reaction. Draw the curved line ONLY, do not indicate any other details.
Show how you might use a nucleophilic substitution reaction of 1-bromopropane to synthesize each of the following compounds. (You may use any other compounds that are necessary.)  
Stereochemical inversion; Draw the product for each of the following SN2 reactions:   a. (S)-2-chloropentane and NaSH b. (R)-3-iodohexane and NaCl c. (R)-2-bromohexane and NaOH
In the reaction below, the configuration of the starting material is S and the configuration of the product is also S. Is this consistent with the SN2 mechanism? Explain your reasoning.
Using line-angle ONLY, draw the MAJOR product expected from the following reaction. Be sure to show stereochemistry if appropriate. If no reaction occurs write NR.
Consider the following SN2 reaction below and answer the following questions:  a. Draw the mechanism b. What is the rate equation? c. What would happen to the rate if the solvent changed from DMSO to ethanol? d. Draw the energy diagram.  e. Draw the transition state of the reaction.    
Using line-angle ONLY, draw the MAJOR product expected from the following reaction. Be sure to show stereochemistry if appropriate. If no reaction occurs write NR.
Circle the least reactive substrate in an SN2 reaction:
How many atoms and electrons are directly involved in the bond-making and bond-breaking for an SN2 substitution reaction?  (A) two atoms, two electrons  (B) three atoms, two electrons  (C) four atoms, two electrons  (D) two atoms, four electrons  (E) three atoms, four electrons
Consider the following SN2 reaction given below. A) Write a mechanism for the reaction. Use curved arrows to show the movement of electrons. You must include the transition state.       B) Identify the following:   substrate:   leaving group:   nucleophile:   spectator ion:   solvent:
A bimolecular nuclephilic substitution (SN2) is a) a two-step process in which a bond is broken, then a new bond is formed, and there is inversion of configuration.  b) a two-step process in which a bond is broken, then a new bond is formed, and there is retention of configuration. c) a one-step process with inversion of configuration. d) a one-step process with retention of configuration.
Which is the order from fastest to slowest for the rates of the SN2 reactions of these alkyl bromides with CH3S—  / DMSO?
Devise a synthetic pathway to form the following product.  (S) – 2 – chlorohexane to (S) – 2 hexanenitrile  
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.
In the SN2 reaction, the "2" stands for a) two reactants in the reaction b) two steps in the reaction c) two intermediates in the reaction d) bimolecular kinetics for the reaction
Provide the final reaction product or "no reaction" if you believe it is the case. Please provide the R/S stereochemistry for each chiral center in the product provided (if any), also indicate if the compound is not optical active.
Provide the major product for the following compound. 
1-Chloro-4-fluorobutane is reacted with one equivalent of sodium iodide in acetone. During the reaction a precipitate forms. What is the precipitate?  a) FCH2CH2CH2CH2l b) ClCH2CH2CH2CH2l c) NaCl d) NaF
For the following pairs of reactions, mark an “X” in the box on the right indicating which will go faster. The compound on top of the arrow is the solvent.
The rate law for the following reaction is   
 Provide the major product for the following reaction. 
Consider the following reaction: (a) Draw the curved arrows showing a mechanism for this process.
Consider the following reaction: (b) Identify the two characteristic arrow-pushing patterns that are required for this mechanism.
Consider the following reaction: (i) Is the reaction first order or second order?  
Consider the following reaction: (k) Will the rate be affected by an increase in temperature?  
Assuming no other changes, what effect on the rate would result from simultaneously doubling the concentrations of both butyl bromide and OH - ion? CH3CH2CH2CH2Br  +  OH -   →   CH3CH2CH2CH2OH  +  Br - No effect It would double the rate. It would triple the rate. It would quadruple (4x) the rate. It would sextuple (6x) the rate.
Draw a three-dimensional representation for the transition state structure in the S N2 reaction of N=C:- (cyanide anion) with bromoethane, showing all nonbonding electron pairs and full or partial charges.  
Predict the product:  
Provide the major product for the following compound.
Provide the major product for the following compound.
When ethyl bromide reacts with potassium cyanide in methanol, the major product is CH3CH2CN. Some CH3CH2NC is formed as well, however. Write Lewis structures for the cyanide ion and for both products and provide a mechanistic explanation of the course of the reaction.  
Draw the transition state. Be sure to include relative lengths of bonds breaking and/or forming, hybridization of the α‐ carbon, and partial charges.
Give structures for the products of each of the following reactions:  
The derivative shown undergoes an SN2 substitution reaction with NaCN. Draw the resulting organic product. Assign the R or S configuration to the starting reactant (starting derivative) and the product. Briefly comment on the result. 
A pentacoordinate carbon is a transition state in the _____ mechanism. a) SN1 b) SN2 c) E1 d) E2
Competition experiments are those in which two reactants at the same concentration (or one reactant with two reactive sites) compete for a reagent. Predict the major product resulting from each of the following competition experiments:  
Competition experiments are those in which two reactants at the same concentration (or one reactant with two reactive sites) compete for a reagent. Predict the major product resulting from each of the following competition experiments:  
Features of SN2 Reactions
For each of the following pairs of molecules, CIRCLE the molecule that will undergo an SN2 reaction faster. 
Which of the following compounds will undergo an S N2 reaction most readily? a) (CH3)2CHCH2CH2CH2I b) (CH3)3CCl c) (CH3)2CHCH2CH2CH2Cl d) (CH3)2CHI e) (CH3)3CCH2I
Which of the following reacts the slowest with sodium cyanide, NaCN?
Predict the product(s) for the following reaction.
Predict the product(s) for the following reaction.
Construct a mechanism for the SN2 product formed when methyl bromide is reacted with tert-BuOK. Construct a reaction coordinate diagram for the reaction above. Label the axes, starting material(s), intermediate(s), transition state(s), and product(s).
Which of the following molecules is expected to selectively NOT participate in Sn2 reactions?
Which of the following would be most likely to undergo substitution via the SN2 mechanism?
What is the stereoelectronic requirement of the incoming nucleophile of an Sn2 reaction?
Write the rate equation (rate law) of this substitution.
Add curved arrows to the reactant side of the following SN2 reaction.
This molecule will undergo a bimolecular nucleophilic substitution reaction with hydroxide ion. Draw the major organic product of that reaction, including correct stereochemistry using wedges and dashes
Rank the relative rates of the following alkyl halides in an SN2 reaction. (Drag the structure to the appropriate box, fastest on the top to slowest on the bottom.) 
Draw the product you expect from the reaction of (R)-2-bromooctane with CN. Use the wedge/hash bond tools to indicate stereochemistry. Include H atoms at chiral centers only.
Draw the structure of the major organic product you would expect from the reaction of 1-bromopropane with NaNH2. You do not have to explicitly draw H atoms. Draw only the product derived from 1 -bromopropane. Do not draw other organic by-products.
For the following reaction, choose the most likely reaction pathway and draw the organic product Remember to include formal charges. 
Click the draw structure button to activate the drawing utilityDraw the product formed from the following reaction
Draw the product you expect from the reaction of (S)-3-iodohexane with -CN. Be sure to show stereochemistry.
For the following SN2 reaction, draw the organic and inorganic products of the reaction, and identify the nucleophile, substrate, and leaving group. Include wedge/dash bonds and H on a stereocenter.  
Name the organic product of the following nucleophilic substitution reaction. OH- + CH3CH2Cl → ___________ + Cl- 
Predict the product for the following SN2 reaction. 
Draw the major organic substitution product(s) of the reaction. Indicate the stereochemistry at every stereocenter with a single bold (up), hashed (down), or wavy (a mixture of up and down: either) bond. 
Draw the organic product of the reaction.
Draw the major organic product(s) of the following reaction.  
1-bromopropane with sodium methoxide under SN2/E2 conditions a. substitution product b. elimination product c. both substitution and elimination products d. no products
When (S)-1-bromo-1-phenylethane undergoes an SN2 reaction with CH3O- Na+, the product is the compound shown below. What is/are the configuration(s) of the product(s) obtained from this reaction?a. a mixture of the enantiomers, with slightly more R than S.b. S onlyc. R onlyd. a mixture of the enantiomers, with slightly more S than R.e. equal mixture of R and S. 
Which of the following statements is not true regarding SN2 reactions? a. Aprotic solvents are good choices for SN1 reactions. b. The mechanism has only one step. c. The stereochemical outcome is inversion at the carbon bearing the leaving group. d. A carbocation intermediate is formed. 
Which of the following alkyl halides will unlikely react with a SN2 reaction mechanism?a. Ib. IVc. IId. III 
Identify the alkyl halide that reacts the fastest in an SN2 reaction. a. 1-chloropropane b. 1-iodopropane c. 1-fluoropropane d. 1-bromopropane