SN1 SN2 Substitution
which reaction is 2-bromobutane?
- Sn1 and sn2 with heat -but faster than 2-chlorobutane due to Br- being both a better nucleophile since it has a weaker conjugate base and a better leaving group since it relieves congestion upon substitution -consists of an electronegative substituent, making it a good leaving group capable of undergoing SN1. -On the other hand, the steric accessibility of the carbon bearing halogen allows for a backside attack. -secondary halide
which reaction is 1-bromobutane?
- Sn2 -occurred faster due to the fact that bromine is a better leaving group since it is large and thus forms a weaker bond with carbon
which reaction is benzyl chloride?
- both Sn1 and Sn1 -undergoes SN2 as it is a primary halide and thus has less steric strain in the transition state of the mechanism. The carbon also has p character that will overlap with the benzene ring to make it more stable. Benzyl chloride can also undergo SN1 due to the resonance effects of the carbocation, which delocalize the positive charge to form a positive carbocation, even though it is primary
Side products from synthesis of n-butyl bromide?
- di-n-butyl ether ( alcohol attacking butyloxnium ion during an SN2 reaction between two 1-butanol molecules - gaseous 1- butene ( butyloxonium ion is attacked by water, bimolecular elimination reaction)
How should the solvent for SN2 be like?
- polar aprotic ( have hydrogens somewhere but lack OH and NH bonds) -acetone or DMSO - this helps stabilize the charge without decreasing the reactivity of the nucleophile -does not have acidic hydrogen nor exhibits hydrogen bonding, but still stabilizes ions - clustering of protic solvent molecules supresses nucleophilicty of anion, suppressing rate of reaction= no bueno
Side products from formation of t-butyl chloride?
- regeneration of starting material which leads to low yield. This occurs if water attacks the carbocation. - low yield can also be due to low extraction fidelity, insufficeint reflux time, insufficient heat
carbocation formation in SN1
After the formation of the carbocation, the nucleophile can then attack from either side of the empty p orbital and thus result in the formation of a racemic mixture.
SN2 reaction coordinate
As you can see there is no carbocation formed, so there is only one hump.
Reaction coordinate for SN1
As you can see, there is carbocation character as the transition state is closer to the reactants than the products
examples of good nucleophiles
Br-, OH-, RO-, CN-, N3-
silver nitrate- AgNO3 solvent
-Its in ethanol- powerful ionizing solvent- polar protic. -nitrate ion is poor nucleophile - silver ion will assist ionization of alkyl halide- form silver halide precipitate - SN1
which reaction is bromocyclohexane?
-SN2 -SN1 in the presence of heat (by lowering the activation energy barrier). Though the bromine is initially equatorial, it becomes axial with a chair flip thereby readily allowing a backside attack via a nucleophile.
which reaction is t-butyl chloride?
-Sn1 -a tertiary halide, it is expected that it would undergo the SN1 reaction as it forms a tertiary carbocation that is stabilized due to resonance, hyperconjugation, and inductive effects from the methyl groups
which reaction is 1-chlorobutane?
-Sn2 -primary halide, and are thus far too unstable to form a carbocation in an SN1 mechanism.
which reaction is bromobenzene?
-does not undergo SN1 or SN2 -The SN2 reaction cannot occur since the nucleophile cannot attack from the backside due to the presence of the benzene ring. The SN1 reaction would also not occur since a benzene cation would be too unstable and can also not undergo resonance because the orbitals are not aligned
What are the four main characteristics a substitution reaction is dependent on?
1. Nucleophilie 2. Leaving group 3. Substituents 4.Solvent
What should a good nucleophile do?
1. should be electron dense, NOT electronegative ( so it can readily donate its electrons 2. Should be poorly solvated- to increase availability of electrons 3. should be polarizable 4. should form strong bonds with carbon ( so it can easily displace the carbon) - all these are more important for SN2 because that involves the nucleophile in the rate determining step.
What should a good leaving group be?
1. should electronegative ( like Cl-) and be well solvated 2. polarizable- high dielectric constants help sta and able to form weak bonds with carbon ( so it can easily break off) 3. should be large ( again, so it can easily leave) Br is a better leaving group than Cl because it is larger- it has a greater atomic radius so the bond length is weaker 4. leaving group ability to leave is estimated by comparing the pKa of the conjugate acid ( base with hydrogen added). More negative pka ( weak base)= better leaving group. - acidic leaving groups are preferred since they can easily dissociate from conjugate base
What competes with Sn2?
Elimination. We use a poor nucleophile because we dont want an E2 reaction to occur which would happen if we have a very strong base. A base can extract a hydrogen and lead to elimination. Whats a good nucleophile but not a good base? sulfur.
What is nucleophilic strength?
It is the measure of how fast a lewis base displaces a leaving group from a substrate. So the more basic it is, the more reactive the nucleophile.
examples of fair nucleophiles
NH3-, Cl-. F-, RCO2-
What is a nucleophile?
Nucleophiles are Lewis bases that have an unshared electron pair they can use to form a covalent bond between an electrophile
explain reaction mechanism of t-butyl chloride
The reaction starts off with hydrochloric acid dissociating and thereby protonating the water, turning it into an acid catalyst. The lone pairs on the oxygen atom in t-butyl alcohol then abstract a proton from the hydronium ion, thus forming a better leaving group. The water molecule then dissociates from the alkyloxonium ion in the rate-determining step to form a tertiary carbocation, which can undergo an attack from either the chloride nucleophile to develop the product or a water molecule to regenerate the t-butyl alcohol. Once two layers were formed, extraction was used with water and sodium bicarbonate to isolate t-butyl-chloride.
How should the SN1 substituents be like?
They should be electron donating to stabilize the carbocation through inductive and or resonance effects and or hyperconjugation
How should the substituents for SN2 be like?
They should just be small to reduce steric congestion. Since the transition state for SN1 is trigonal bipyramidal, there should be less strain so less substitution.
SN2 reactivity
Typically uses primary sp3 carbon and methyl so there is less steric congestion to allow for a backside attack. No carbocation is formed so inductive effects dont matter.
SN1 Reactivity
Typically uses secondary or tertiary sp3 carbons so that the carbocation is stabilized. It has nothing to do with sterics because there is no backside attack.
which reaction is 2-Chlorobutane?
both Sn1 and Sn2 with heat -consists of an electronegative substituent, making it a good leaving group capable of undergoing SN1. -On the other hand, the steric accessibility of the carbon bearing halogen allows for a backside attack. -secondary halide, possess conditions that favor both mechanistic pathways
why did we use a heat reflux?
due to the stereochemistry of the transition state imposed by the attack from Br-, heat is needed to drive the reaction forward. -reflux was set to trap the gaseous HBr emitted
SN2 rate law
rate law for SN2 mechanisms is k[ROH][X], the reaction is dependent on the concentration of the nucleophile in addition to the substrate
How should the solvent for SN1 be like?
should be polar protic ( large dipole, electronegative difference, and typically OH or NH bonds- hydrogen bonds) -ammonia, ethanol, t-butanol, methanol, acetic acid, water - electrons from hydrogen bond stabilizes the transition state and positive charge in carbocation -able to undergo hydrogen bonding, contains an acidic hydrogen, is able to stabilize ions.
why is excess sulfuric acid used?
to shift the equilibrium and thus speed the reaction by producing higher concentration of HBr. -Sulfuric acid protonates the hydroxyl group of n-butyl alchol, making it a better leaving group because a water is a better leaving group than OH-. -sulfuric acid also protonates the water, which deactivates it as a nucleophile and prevents the conversion of the alkyl halide back into an alcohol.
Which layer was our desired product formed?
upper organic layer, it also had: RBr, RCH=CH2, ROH, and H+. Best way to get rid of all this extra product is to add acid because it protonates which makes them charged and brings to aqueous layer. We still have H+, which we get rid of by adding bicarbonate- forms CO2. -lower aqueous layer had: sulfuric acid, NaHSO4, HBr, NaBr, some ROH
examples of weak nucleophiles
water, ROH- (CH3CH2OH)
NaI solvent
- I- is an excellent nucleophile -acetone- polar aprotic -NaI is soluble in acetone but precipitate forms when bromide or chloride ions are produced in the reaction since they are insoluble in acetone -SN2
which reaction is bromocyclopentane?
- Sn1 and Sn2 ring becomes staggered which relieves strain and lowers the activation energy of the transitional state. The structure of bromocyclopentane goes from a tetrahedral to trigonal planar in SN1 and a tetrahedral to trigonal bipyramidal in SN2, thus lowering the energy of the transition state and carbocation.
examples of very good nucleophiles
I-, HS-, RO-, CN-, N3-
Purpose of H2SO4
Ionic compounds dissolve in concentrated H2SO4. Concentrated H2SO4 protonates all organic compounds containing heteroatoms or a double bond. Alkyl halides are not protonated
Which mechanism does the synthesis of n-butyl bromide use?
SN2 reaction
where did we get HBr from?
Since its expensive, we had to generate it ourselves by using excess sulfuric acid and sodium bromide. The excess sulfuric acid serves to shift the equilibrium to the right, thus generating a higher concentration of hydrobromic acid. We dont use HCl because Cl will attack too- sulfate wont.
sn1 rate law
Since the rate of the equation is equal to k[ROH], the concentration of the nucleophile will have no effect on the rate of the reaction
what reaction mechanism does the synthesis of t-butyl chloride use?
Sn1 because formation of a stable carbocation after the dissociation of tert-butyloxonium ion is tetrasubstituted- which allows for indcutive effects and hyperconjugated affects from the three methyl groups.
Explain reaction mechanism for n-Butyl bromide
The excess sulfuric acid serves to shift the equilibrium to the right, thus generating a higher concentration of hydrobromic acid. The acid catalyst is then used to protonate the hydroxyl group of the n-butyl alcohol, consequentially making it a better leaving group. The acid catalyst also prevents the conversion of the alkyl halide back into an alcohol by protonating the water molecules and deactivating them as a potential nucleophile in the reaction. Finally, the Br- nucleophile attacks the alyloxonium ion and the water molecule is cleaved at the same time
What is the extraction scheme?
The first extraction served to remove the di-n-butyl byproduct using sulfuric acid. A water wash extraction was also used to remove some of the 1-butanol. Throughout the extraction, the product mainly stayed in the organic layer, which is ultimately washed with water and saturated NaHCO3 to remove traces of acid.
