Another reaction commonly covered in the first weeks of organic chemistry is the SN1 reaction. The SN1 reaction introduces you to repetitive concepts and rules you will encounter all semester, this time focusing on carbocation formation and reactivity. In this article, we will review the important topics of an SN1 reaction. Sign up with StudyOrgo today to get detailed reaction mechanisms and explanations to prepare you to ace your next exam!
Alkyl halides as SN1 substrates
One of the most reactive molecules involving substitution reactions via SN1 are 2° and 3° alkyl halides. However, there are a number of considerations to keep in mind to determine if this mechanism of substitution describes your reaction. First, let’s look at a simple SN1 reaction; a sec-butyl halide (a 2° methyl-ethyl carbon center).
Carbocation formation and stability: Let’s break down the reaction name more simply. The term SN1 reaction gives you 3 pieces of information, first the ‘S’ indicating ‘substitution’, the ‘N’ denoting the reaction involves a nucleophile and ‘1’ describing the process as unimolecular – meaning only the formation of the reactive substrate intermediate determines the rate of reaction. This process is referred to as the rate determining step of the reaction, and can be thought of as the ‘bottleneck’ in the reaction. The leaving group will break the bond to carbon and take the electrons for the bond with it forming a carbocation intermediate. Halogens are good leaving groups because of the inductive effects (or electron withdrawing potential) of the halogen atom and is the characteristic of good leaving groups. Carbocation formation is the first, and rate determining step, in the reaction.
Product formation and racemization: Once the leaving group bond is broken, stability of the carbocation is the factor that determines if this mechanism occurs. The more substituted the carbon center, i.e. 2° and 3°, the more stabilized the carbocation becomes as the positive charge becomes delocalized to the other carbons. Following formation of the carbocation, it will then react with the nucleophile. Since the carbocation assumes a planar shape, attack by the nucleophile can occur from either side of the plane. This leads to formation of a mixture of enantiomers, referred to as a racemic mixture. This is in contrast to SN2 which will only produce the inverted stereoisomer of the reactant.
Carbocation Rearrangement: As mentioned before, stability of the carbocation is the key step in determining rate and completion of SN1 reactions. In some instances, the leaving group is bonded to a carbon center than neighbors a more substituted carbon center. Let’s consider the reaction below, chloride leaves 2-chloro-3-methylpropane to form a 2° carbocation. The neighboring carbon center is 3°, and would make a more stable carbocation. In this instance, the neighboring hydrogen will shift to the 2° carbocation to form a new 3° carbocation, which is much more stable in a process referred to as a 1,2-hydride shift. Attack of the methanol hydroxyl group on the carbocation followed by proton abstraction by chloride leads to formation of the 3-methoxy-3-methylpropane product.
The start of first semester organic chemistry can be an information overload. For the first few classes, you will review general chemistry concepts and then… the reactions start coming! One of the first reactions that will be covered is the SN2 reaction, mainly because it is relatively straight forward and a good tutorial for how to describe reaction mechanisms. In this article, we will review the important topics of an SN2 reaction. Sign up with StudyOrgo today to get detailed reaction mechanisms and explanations to stay on top of your class!
Alkyl halides as SN2 substrates
One of the most reactive molecules involving substitution reactions are alkyl halides. However, there are a number of considerations to keep in mind to determine if the SN2 mechanism describes your reaction. First, let’s look at a simple SN2 reaction; methyl chloride and NaOH to form methanol and NaCl.
Let’s break down the reaction mechanism into the basic elements. An SN2 reaction gives you 3 pieces of information, first the ‘S’ indicating ‘substitution’, the ‘N’ denoting the reaction involves a nucleophile and ‘2’ describing the process as bimolecular – meaning both the substrate and the nucleophile determine the rate of the reaction. The hydroxide will attack the carbon center and form a new bond with carbon (which makes it the nucleophile) and the chlorine atom will leave the carbon center with the electrons from the C-Cl bond (which makes it the leaving group).
Inductive effects of leaving groups: Chloride is a good leaving group because of the inductive effects (or electron withdrawing potential) of the halogen atom. This is the characteristic of good leaving groups. The electronegativity of chlorine makes the carbon center slightly electrophilic, meaning it has a partial positive charge, which is strongly attracted to electron-rich nucleophiles.
Strong bases as a nucleophile: In order to form a new bond with carbon, a good nucleophile has to be electron rich. The strong basic properties of NaOH make the charge on oxygen negative, and thus a good nucleophile. Likewise, the poor basic properties of Cl anion make it an excellent leaving group. Below is a chart to help illustrate the contrasting properties of nucleophiles and leaving groups.
Inversion of stereochemistry due to geometry of attack: Once the nucleophile attacks the carbon center, a partial formation of C-O bond and breaking of C-Cl bond occurs in a concerted (or instantaneous) fashion, depicted below. Because the angle of attack for the nucleophile has to be opposite of the leaving group, the OH adds to the opposite side of the carbon center, causing an inversion of stereochemistry. This is an important clue in determining if reactions occur using the SN2 mechanism.