Understanding SN1 and SN2 Reactions PDF

Substitution Reactions Leaving Groups A leaving group is a group that is replaced in a substitution reaction. The typical good leaving groups are: Halides (Cl, Br, I) They get better as they get big...

Substitution Reactions Leaving Groups A leaving group is a group that is replaced in a substitution reaction. The typical good leaving groups are: Halides (Cl, Br, I) They get better as they get bigger because the longer bond dissociates more easily and they're more stable after the fact. SN2 Reaction Definition “Substitution Nucleophilic 2” Characteristics Bimolecular: 2 reactant molecules are involved in the slow step of the reaction. Second-order: 2 molecules are involved in the slow step. Nucleophile: Electron-rich, such as cyanide (CN-). Backside attack: The nucleophile attacks the carbon from the opposite side of the leaving group, resulting in Walden inversion. https://www.turbolearn.ai/content/03936758-3e9b-46c6-a582-5130aa8a9d0e 9/2/24, 12 30 AM Page 1 of 16 :  Inversion: The configuration of the chiral center is inverted. Single step reaction: Everything happens in a concerted fashion. Rate Law Reactant Concentration Effect on Rate Electrophile Doubles the rate if concentration is doubled Nucleophile Doubles the rate if concentration is doubled Solvent Reduces the rate by a factor of 4 if volume is doubled SN1 Reaction Definition “Substitution Nucleophilic 1” Characteristics Unimolecular: Only 1 reactant molecule is involved in the slow step of the reaction. First-order: Only 1 molecule is involved in the slow step. No strong nucleophile: The leaving group leaves to form a carbocation, which is the slow step. Multi-step reaction: Typically involves multiple steps. https://www.turbolearn.ai/content/03936758-3e9b-46c6-a582-5130aa8a9d0e 9/2/24, 12 30 AM Page 2 of 16 :  Rate Law Reactant Concentration Effect on Rate Electrophile (Alkyl Halide) Rate is proportional to concentration Formation of Carbocation The leaving group leaves to form a carbocation, which is the slow step. This process is often facilitated by heat. Attack by Nucleophile The nucleophile (water in this case) attacks the carbocation to form a product. Deprotonation The product forms a strong acid, which gets deprotonated by the solvent (water). Chiral Center A chiral center is formed, and the reaction results in a mixture of enantiomers, known as a racemic mixture.## SN1 and SN2 Reactions: Key Differences Formation of Chiral Centers In SN1 reactions, if a nuclear f adds to form a chiral center, racemization occurs. https://www.turbolearn.ai/content/03936758-3e9b-46c6-a582-5130aa8a9d0e 9/2/24, 12 30 AM Page 3 of 16 :  In SN2 reactions, if a nuclear f adds to form a chiral center, inversion occurs. Solvolysis Reactions “A solvolysis reaction is an SN1 reaction where the solvent is the nucleophile.” Nucleophiles Strong nucleophiles are required for SN2 reactions. Typically have a negative charge. Follow the trend: stronger as you go up and left in the periodic table. Exceptions: nitrogen and phosphorus can be moderately strong nucleophiles even without a negative charge. Weak nucleophiles are acceptable for SN1 reactions. Water is an example of a weak nucleophile. Electrophiles In SN2 reactions, the electrophile should have small atoms bonded to the carbon with the leaving group to facilitate backside attack. Methyl halides are ideal electrophiles. Primary halides react relatively quickly. https://www.turbolearn.ai/content/03936758-3e9b-46c6-a582-5130aa8a9d0e 9/2/24, 12 30 AM Page 4 of 16 :  Secondary halides react slowly, and tertiary halides do not react via SN2. In SN1 reactions, the electrophile should form a stable carbocation. Tertiary carbocations are more stable than secondary carbocations. Primary and methyl carbocations are not stable unless stabilized by resonance. Solvents Solvent Type SN1 SN2 Protic (e.g., water, alcohols, Required Not preferred (except for large carboxylic acids) nucleophiles) Aprotic (e.g., acetone, DMSO, THF) Not Preferred (especially for small suitable nucleophiles) Leaving Groups A good leaving group is necessary for both SN1 and SN2 reactions. The trend for leaving groups is: iodide > bromide > chloride. Rearrangements Rearrangements occur through carbocation intermediates. https://www.turbolearn.ai/content/03936758-3e9b-46c6-a582-5130aa8a9d0e 9/2/24, 12 30 AM Page 5 of 16 :  Which reaction goes through carbocation intermediates? SN1.## SN1 and SN2 Reactions SN1 Reactions SN1 reactions do not involve a carbocation intermediate, whereas SN2 reactions do. In SN1 reactions, there is no inversion of configuration due to the lack of carbocation intermediate, resulting in racemization. SN1 reactions typically use polar protic solvents, which can be memorized: Water Alcohols Carboxylic acids Ethers (including THF) SN2 Reactions SN2 reactions involve a carbocation intermediate, resulting in inversion of configuration. SN2 reactions use polar aprotic solvents, which should be memorized: DMSO Acetone DMF https://www.turbolearn.ai/content/03936758-3e9b-46c6-a582-5130aa8a9d0e 9/2/24, 12 30 AM Page 6 of 16 :  Acetonitrile Ethers (including THF) SP2 Hybridized Carbons SP2 hybridized carbons are not primary, secondary, or tertiary carbons. SN1 and SN2 reactions do not react when the leaving group is on an SP2 hybridized atom. The pi electrons in SP2 hybridized carbons repel nucleophiles, making them unreactive. Elimination Reactions: E2 and E1 E2 Reactions E2 reactions are concerted mechanisms, involving a single step. E2 reactions are second-order or bimolecular. E2 reactions require a strong base, typically with a negative charge on oxygen (e.g., NaOH, NaOCH3, NaOCH2CH3). The reaction involves deprotonation and formation of an alkene in a single step. E1 Reactions E1 reactions are not concerted mechanisms, involving multiple steps. https://www.turbolearn.ai/content/03936758-3e9b-46c6-a582-5130aa8a9d0e 9/2/24, 12 30 AM Page 7 of 16 :  E1 reactions are first-order or unimolecular. E1 reactions require a weak base, typically an alcohol or water. The reaction involves two steps: formation of a carbocation and deprotonation to form an alkene. Comparison of E2 and E1 Reactions Base Rate-Determining Reaction Mechanism Order Strength Step E2 Concerted 2nd Strong Deprotonation and alkene order formation E1 Step-wise 1st Weak Formation of carbocation order Key Concepts “Base: A species that can donate an electron pair. Nucleophile: A species that can donate an electron pair to form a new bond.” Polar Protic and Aprotic Solvents Polar protic solvents: capable of donating a proton (H+), stabilizing carbocations. Polar aprotic solvents: incapable of donating a proton (H+), used in SN2 reactions. Leaving Groups and Carbocations https://www.turbolearn.ai/content/03936758-3e9b-46c6-a582-5130aa8a9d0e 9/2/24, 12 30 AM Page 8 of 16 :  A leaving group is a species that leaves a molecule, typically taking a pair of electrons with it. Carbocations are electron-deficient species that can react with nucleophiles. Trends in E1 and SN1 Reactions Tertiary alkyl halides are more reactive than secondary or primary alkyl halides in E1 and SN1 reactions. Polar protic solvents are required to stabilize the carbocation intermediate. Good leaving groups are necessary for both E1 and SN1 reactions.## E2 Elimination Substituted Alkyl Halides In E2 elimination, the more substituted alkyl halide leads to a more substituted alkene. This is opposite to the trend observed in SN2 reactions. Carbocation Formation E2 elimination does not involve carbocation formation. Primary halides can undergo E2 elimination, but methyl halides cannot. Solvents Strong bases are typically negatively charged. https://www.turbolearn.ai/content/03936758-3e9b-46c6-a582-5130aa8a9d0e 9/2/24, 12 30 AM Page 9 of 16 :  Polar aprotic solvents facilitate E2 reactions, but protic solvents can also be used. Protic solvents are more commonly used for E2 reactions. Solvent Characteristics Polar aprotic Facilitates E2 reactions Protic Can be used for E2 reactions, more commonly used Stereochemical Requirements The hydrogen and leaving group must be antiperiplanar (coplanar) for E2 elimination to occur. Antiperiplanar means they are in the same plane, but 180° apart. “"Anti" means against, and "peri" means plane.” E2 Reaction The reaction involves deprotonation, formation of the alkene, and removal of the leaving group simultaneously. Zaitsev's Rule Zaitsev's rule states that the more substituted alkene is preferred. This rule is based on the idea that the more substituted alkene is https://www.turbolearn.ai/content/03936758-3e9b-46c6-a582-5130aa8a9d0e 9/2/24, 12 30 AM Page 10 of 16 :  more stable. Exceptions to Zaitsev's Rule In some cases, the more substituted alkene is not possible due to stereochemical constraints. This can occur in cyclohexane rings with an equatorial leaving group. Cyclohexane Rings In cyclohexane rings, the hydrogens on adjacent carbons cannot point exactly 180° away from the leaving group when it is equatorial. This means that the more substituted alkene may not be possible, and the less substituted alkene may be formed instead. Leaving Group Position Hydrogen Position Equatorial Not antiperiplanar Axial Antiperiplanar Multiple Possible Products In some cases, multiple alkenes can form from a single reactant. The specific product formed depends on the stereochemical constraints. https://www.turbolearn.ai/content/03936758-3e9b-46c6-a582-5130aa8a9d0e 9/2/24, 12 30 AM Page 11 of 16 :  Reactant Possible Products Alkyl halide 2-3 alkenes (including stereoisomers) Cyclohexane ring 1-2 alkenes (depending on leaving group position) Bulky Bases Bulky bases, such as t-butoxide, can be used to facilitate E2 elimination. These bases are typically larger and more sterically hindered, which can influence the reaction outcome.## E2 Reaction with Bulky Bases Bulky Base: A base that is large in size, making it difficult to approach the hydrogens on a primary carbon. When working with bulky bases and tertiary halides, the E2 reaction will form the less substituted alkene. However, this is not a general rule and only applies to tertiary halides. Important Exception: If you see a bulky base, do not always follow Zaitsev's rule. Instead, form the less substituted alkene, but only if you have a tertiary halide. Substitution Elimination Map Use the substitution elimination map to determine the reaction pathway based on the type of nucleophile or base. https://www.turbolearn.ai/content/03936758-3e9b-46c6-a582-5130aa8a9d0e 9/2/24, 12 30 AM Page 12 of 16 :  Weak Nucleophile/Weak Base: No negative charge. Examples include alcohols and water. Strong Nucleophile/Strong Base: Has a negative charge. Examples include hydroxide, methoxide, and ethoxide. Nucleophile/Base Characteristics Reaction Pathway Weak No negative charge SN1 and E1 (mixture of products) Strong Negative charge SN2 or E2 (depending on solvent and halide) Examples Example 1: Weak Nucleophile/Weak Base Nucleophile/Base: Alkyl halide (no negative charge) Reaction Pathway: SN1 and E1 (mixture of products) Result: Mixture of substitution and elimination products Example 2: Strong Nucleophile/Strong Base Nucleophile/Base: Sodium methoxide (negative charge) Reaction Pathway: SN2 (methyl and primary halides) or E2 (if protic solvent) Result: Substitution product (SN2) or elimination product (E2) Factors Affecting Reaction Pathway https://www.turbolearn.ai/content/03936758-3e9b-46c6-a582-5130aa8a9d0e 9/2/24, 12 30 AM Page 13 of 16 :  Solvent: Polar protic solvents favor SN1 and E1, while polar aprotic solvents favor SN2 and E2. Halide: Methyl and primary halides favor SN2, while tertiary halides favor E2. Nucleophile/Base: Weak nucleophiles/weak bases favor SN1 and E1, while strong nucleophiles/strong bases favor SN2 or E2. Mister Zaitsev's Rule Mister Zaitsev's Rule: In an E2 reaction, the most substituted alkene is formed. Exception: When working with bulky bases and tertiary halides, form the less substituted alkene. If the halide is secondary, you may get a mixture of products.## Exceptions to Zaitsev's Rule Bulky Base A bulky base is not present in this reaction. Only an ethoxide ion (not a t- butoxide ion) is involved. Absence of Anticoplanar Hydrogen The carbon atom has two hydrogens, one of which can be oriented anticoplanar to the leaving group (bromine) due to free rotation around the single bond. Predicting Products Major product: predicted by Zaitsev's rule https://www.turbolearn.ai/content/03936758-3e9b-46c6-a582-5130aa8a9d0e 9/2/24, 12 30 AM Page 14 of 16 :  Minor product: anti-Zaitsev or Hoffman product (present in smaller amount) In this case, there are only two possible products, as the methyl groups are identical. Strong or Weak Base? The ethoxide ion has a negative charge, making it a strong base and a strong nucleophile. The solvent is protic, which favors an E2 reaction over an SN2 reaction. Solvent and Reaction Type Solvent Type Reaction Type Protic E2 Aprotic SN2 Note: Although aprotic solvents would result in a faster E2 reaction, protic solvents are commonly used for E2 reactions. Stereochemical Requirement The reaction requires an anticoplanar arrangement of the leaving group (bromine) and the hydrogen being removed. Due to the presence of a phenyl group, the reaction can only https://www.turbolearn.ai/content/03936758-3e9b-46c6-a582-5130aa8a9d0e 9/2/24, 12 30 AM Page 15 of 16 :  form one stereoisomer, either cis or trans. Determining Stereochemistry “"If the reaction can happen in the conformation you're in, great, then you know who's gonna end up trans. If it can't form in this conformation, then they can't end up trans."” In this case, the hydrogen and bromine are not anticoplanar, so the reaction cannot occur in the current conformation, and the cis stereoisomer is formed by default. https://www.turbolearn.ai/content/03936758-3e9b-46c6-a582-5130aa8a9d0e 9/2/24, 12 30 AM Page 16 of 16 :