Physical Organic Chemistry and Conformational analysis Flashcards
How are the starting materials, transition state, intermediate, product and competing pathways shown on a potential energy diagram?
Starting materials shown as potential well at the beginnibg
Transition states as peaks
Intermediate as troph in the middle
Products as troph at the bottom
Competing pathways shown on the same diagram with different energy levels
What are two useful tools in understanding the mechanism of a reaction?
The stereochemistry - inversion of stereochemistry / loss of stereochemistry
Structures of bi products
What is isotopic labelling?
a technique where a specific element in a compound is replaced with a less abundant isotope and the distribution of labelled and unlabelled compounds is investigated and the position of the labelling
e.g - The C-D bond is harder to break than the C-H bond so which bond is broken in the rds can be investigated in kinetics
How can intermediates be observed?
NMR
IR
UV
GC, HPLC
MS
EPR
How can short lived intermediates be observed?
Trap them
We can porve that benzyne is formed in the reaction PhCl +NH2 by trapping it in a diels alder reaction with another cyclic aromatic compound such as furan
We can spin trap by converting a shirt lived radical intermediate into a stable radical (e.g nitroxide radical) that can be analysed by EPR
How quickly does excitation, ligand loss, solvent coordination, molecular rearrangements and bond formation happen?
Excitation: 10-15 - 10-12 s
Ligand: 10-10 s
Solvent coordination: 10-10 - 10-9 s
Molecular rearrangements: 10-9 - 10-7 s
Bond formation: 10-8 - 10-6 s
What are the steps in a chair flip?
Which direction does the equilibrium of the chair flip lie?
The equilibrium lies towards the substituent in the equatorial position.
K is larger in the equatorial conformer
K = [Equatorial conformer] / [Axial conformer]
When the substituent is very large K is larger
How do 1,3-diaxial interactions affect the equilibrium constant?
How does adding a substituent to a ring affect the equilibrium constant?
Cis - substituents on same side of the ring - ring inversion is the same energy - no affect on K
Trans - substituents on opposite sides of the ring - the axial conformer is higher energy so the equikibrium lies towards the equatorial version
How can we control the chair flip equilibrium
Use locking groups to force the chair into one conformation
tBu group has very high steric strain to the equilibrium lies so far towards the equatorial conformer that it almost always is in that position
What are the trans and cis conformations of decalins?
What are the trans and cis versions of cholesterol?
What is the ring inversion of a cis decalin?
What is the ring flip for a trans decalin?
There is no ring inversion for the trans decalin
The 6 memberred ring is npt big enough to ring flip a trans decalin
Both joining positions between rings would have to be acial
What is the structure of decalins?
Two isomeric forms of a decalin - trans fused or cis fused
In the cis decalkin the bridgehead hydrogen atoms are on the same face of the rings
In the trans decalin bridgehead hydrogens are on opposite faces of the rings
Both isomeric forms can be represented using chair cyclohexyl-like conformations
Flips and rotations do not interconvert cis and trans - the configurations are fixed
How does nucleophilic substituion occur on the a cyclohexane ring?
What are the ring opening and closing reactions of cyclohexyl eqpoxides?
How do cis and trans cyclic epoxides form?
What are the ring flips for C6H10O, C7H12, C6H10?
How do nucleophiles attack cyclohexyl carbonyls?
How does the type of hydride affect the product in the reductionof cyclohexyl carbonyl?
How does cyclohexene react with bromine?
How does cyclohexene react with N-bromosuccinimide and water?
How are systems with multiple rings named?
How does NaBH4 react with Bicyclo[2.2.1]heptane and bicyclo[3.2.0]hept-2-ene?
What can the Arhenius and Eyring equation be used to find?
Arhenius: k = A . e^-Ea/RT
lnk = lnA - Ea/RT
Eyring equation: k = kBT/h e^ -ΔG†/RT
= kBT/h e^ - ΔH†/RT e^ ΔS†/ R
lnk/T = - ΔH†/RT + lnkB/h + ΔS†/ R
Plotting lnk vs 1/T gives ΔH† and ΔS† graphically
What does activation entropy tell us about mechanisms?
Activation entropy is +ve for dissociative reactions and -ve for associative reactions
Dissociative reactions have transition states in the rate determining step that are more disordered than the starting materials
What does activation enthalpy tell us about mechanisms?
If no bonds are broken or formed in the rate determinin step activation enthalpy is < 100 kJ mol-1
If more bonds are broken than formed the activation enthalpy is > 100 kJ mol-1
What are the limitations of activation parameters?
Only works well in the gas phase - solvation often changes enthalpy-entropy balance - data can still be used for solid/liquid reactions but caution should be used
Only provide information about r.d.s
Only provide information about the trabnsition state but in ,any cases the TS represents a high energy inetermediate/product so it could be acceptable to consider intermediates/products as models of TS
What are extrathermodynamic effects?
Small changes that happen to a process due to a small effect
i.e - changes to activation parameters or rate of a reaction due to different substituents
What are linear free energy relationships?
Plot of ΔG for one reaction vs ΔG for another - gives straight line
Allows you to predict one ΔG without doing the reaction
Deviations from linearity can be due to different mechanisms or steric effects
What is the Hammett equation?
ΔG is not practical to useso we use base 10 logs of equilibrium or rate constants
For irreversible reactions the eyring equation states that ΔG† is proportional to log(k)
For reversible reactions ΔG = -RTlnK
This gives the Hammett equation from rearranging linear free energy relationships:
log(kx/kH) = ρ x σ - for irreversible reactions
log(Kx/KH) = ρ x σ - for reversible reactions
What reference points are used to calibrate the Hammett equation?
The value of ρ was assigned to ρ = 1 for ionisation of substituted benzoic acids
σ = 0 when substituent = H - this is for any reaction
How can σ be calculated for a benzoic acid with pKa of 4.2?
log(Kx/KH) = logKx - logKH = -pKx + pKH = -pKx + 4.2 = σρ = 1xσ
Therefore pKH - pKx = σ . pKH
σ = 4.2 - pKx
What is σ?
σ is a quantitative measure of an electronic effect of a substituent (of an aromatic group)
σ > 0 = electron withdrawing group
σ < 0 = electron donating group
How can ρ be measured?
Plot of log(kx/kH) vs σ gives a straight line with gradient ρ
What is ρ?
ρ represents the sensitivity of the reaction to the electronic effect of substituents
ρ > 0 = the reaction is facilitated by electron withdrawing groups - -ve charge is formed in the rds and +ve charge is reduced
ρ < 0 = reaction facilitated by electron donating groups
- +ve charge formed in the rds and -ve charge reduced
What affects the magnitude of ρ?
If the charge can be directly conjugated to the ring the magnitude of ρ is larger (>2 ish)
If the charge is on the ring there is a very large ρ value
If charge is one atom from the ring ρ ~ 1
If the cgarge is two away from the ring ρ ~ 0
How does σ change with the position of the substituent
For meta substituents σm is used
For para substituents σp is used
There are no σ parameters for ortho substituents because ortho substituents have both steric and electronic effect
The Hammett equation cannot decouple the effects and therefore can only deal woth 1 effect
Can the Hammett equation deal with two electronic effects?
Some substituents have two electronic effects such as p-OMe (-I effect pulling electron density away from reactuoin centre and +M effect pushing electron density towards the reaction centre)
The Hammett equation breaks down in these situations
However in the meta position a negative charge on the reaction centre cannot be delocalised onto the substituent so effectively only the -I affects the reaction centre
Hammett equation works well mwhen charge from reaction centre does not mesomerically delocalise onto the substituent
What happens when charge from the reaction centre is delocalised onto the substituent purely througn a mesomeric effect?
The delocalisation of charge from the reaction centre to a substituent through resonance is called direct conjugation
This is different to the electronic effects of a substituent
New set of parameters defined:
σ+ for direct conjugation with a +ve charge and σ- for direct conjugation with a -ve charge
These can be used on the same graphnas σm and σp
How should the σ parameters be used?
if the charge cannot conjugate to the ring σm and σp are used
If the +ve charge is conjugated to the ring use σm for meta substituents, σ+ for +M substituents in the para position and σp for other substituents in the para position - the x axis is labelled σ+
If the -ve charge is conjugated to the ring use σm for meta substituents, σ- for +M substituents in the para position and σp for other substituents in the para position - the x axis is labelled σ-
How can mesomeric and inductive effects be separated?
Inductive effects are sometimes given the parameters: σ* and σ0
When separating the effects σI is used for inductive effects and σR is used for mesomeric effects
log(kx/kH) = (ρI x σI) + (ρR x σR)
How else can the Hammett equation be modified?
log(kX/kH) = (ρI x σI) + (ρR x σR) + (δ x Es)
(δ x Es) is used for steric terms
How are multiple substituents taken account of by the Hammett equation?
Provided there is no interaction between the two substituents such as steric effects, the effects of the two substituents can be added together
log(kX/kH) = ρ x Σσ
How can we explain non-linear Hammett plots?
Non linear Hammett plots can show two gradient lines with two different ρ values
This is often seen in reaction that can proceed by two meachnisms such as SN1 and SN2
The SN1 mechanism produces a carbocation and is stabalised by electron donating groups so ρ should be -ve
The SN2 mechanism goes through a transition state snd is stabalised by electron withdrawing groups so ρ should be more positive
Howdl we determine what is happening when we have two competeing pathways and when we have consecutive reactions?
When there are two competing reaction if the graph is concave downwards the reaction mechanism changes as you change substituent - overall rate determined by teh rate of fastest pathway
When there are consecutive reactions theoverall rate is determined by the slowest pathway - if the graph is concave upwards the rate determining step changes as you change substituent
Why do we study solvent effects?
The solvent can change the mechanism - when reacting an α, unsaturated carboyl to an organolithium a non polar solvent can cause 1,2 addition whereas a polar solvent can cause 1,4 additon
Can change rate of reaction - when charged species produced polar solvents increase rate
Solvents can participate in the reaction - polar solvents can add nucleophlically to electrophilic reactants
What do polar solvents stabalise best?
Ions > charged-dispersed species > neutral species
Reactions are accelerated by polar solvents if the transition states are better solvated that the starting materials
What is the kinetic isotope effect?
The strength of chemical bonds - vibrational energy
E = h x ν
How do you calculate the ratio of vibrational energies of hydrogen and deuterium?
ν = sq root (force constant (f) / reduced mass (μ)
μ = (mX x mH)/(mX + mH)
mH << mX
μ = (mX x mH)/(mX) = mH
EH/ED = hνH/hνD = sq root μD/μH = sq root mD/mH
How do the C-H and C-D bonds differ?
Energy to break the C-H bond is less than C-D bond
C-D bond stronger
The bonds are chemically equivalent but deuterated compounds should react slower when the X-H bond is being broken in the rate determining step
How do we calculate the kinetic isotope effect?
KIE = kH/kD
Max kH/kD = ca. 8-9 if the bond is exactly half broken in the transition state
What is the primary kinetic isotope effect?
When X-H bond is broken in the rate determining step
For primary effects kH/kD is always > 2
What is the secondary isotope effect?
When X-H is not broken in the rate determining step
kH/kD is < 2
α effect: when teh H is attached to the α C - kH/kD = 0.8-1.4
β effect: when the H is attached to the β C
Normal effect: kH/kD > 1
Inverse: kH/kD < 1
What is the origin of the secondary isotope effect
In an sp3 hybridised C the bond angle is 109.5° and the vibrational frequency of the C-H bond is 1350 cm-1
In a sp2 hybridised system teh angle is 120° and the vibrational frequency is 800 cm-1
When do reactions usually have normal and inverse secondary kinetic isotope effects?
Usually normal on sp3-sp2 hybridisation change and inverse for sp2-sp3 change
