Week 7-12 Structure and Reactivity ILOs

Only relevant ones

Explain the existence of isomers in internal alkenes, in terms of orbital overlap in pi systems

Multiple structural isomers exist in alkenes because the pi (double) bond can be between different carbons.

Use the Cahn-Ingold-Prelog priority rules to assign the absolute stereochemistry (E/Z) of alkenes and analogous systems (e.g. oximes, imines)

1. Higher atomic number has higher priority

2. If equal priority, tiebreak by listing the next attached atoms in atomic order

3. Multiple bonds: list element twice

note: basically highest atomic weight/ total atomic number wins but this is not technically correct

Explain the origin of molecular chirality

Molecular chirality occurs when a carbon center bonded to 4 different atoms or groups of atoms are nonsuperposable on their mirror images: cannot align perfectly with their mirror image through rotation or translation and the two molecules are enantiomers.

Use the Cahn-Ingold-Prelog priority rules to assign the absolute stereochemistry (R/S) of stereogenic centres

1. Highest atomic number has highest priority

Assign numbers 1-4. Rotate molecule so that 4th priority is facing back (into the page). If 1→2→3 is clockwise, R, if anticlockwise, S

Explain how optical activity is measured using a polarimeter

1. light emitted through a light source, e.g. sodium lamp

2. unpolarized light passed through a linear polarizer to get linearly polarized light beam

3. polarized light passed through polarimeter tube containing the molecule under investigation (usually solution)

4. light hits a rotatable linear analyser to measure the angle of optical rotation

Calculate the specific rotation of a compound using polarimetry data

1. obtain observed rotation (alpha)

2. measure path length (l) of sample cell in dm

3. determine the concentration of the sample in g mL^-1

4. use the formula angle of rotation (alpha) depending on wavelength and temperature = angle of rotation/(path length dm x concentration g mL-1)

Determine the enantiomeric composition of a sample of a chiral compound, and describe this using appropriate stereochemical terminology

Pass through polarimeter and calculate angle of rotation. Refer to data tables to assign which enantiomer it is, R (clockwise) or S (anti clockwise). If the angle of rotation is 0 but you know it is nonsuperposable on its mirror image, it is a racemic mixture with an equal 1:1 ratio of each enantiomer.

Identify and draw diastereomers of a given molecular structure

Diastereomers - stereoisomers (same structural formula but different arrangement in space) that are not enantiomers/not mirror images

Calculate the maximum number of possible stereoisomers of a given compound

2^n where n is the number of chiral centres in the molecule

Identify meso compounds

Optically inactive member of a set of stereoisomers - achiral molecule with multiple chiral centres, usually symmetrical.

Explain the principles of resolving chiral compounds using enantiopure derivatising agents or chiral stationary phase chromatography

Resolution - mix the racemic compound and a single enantiomer of a resolving agent (enantiopure deriving agents) to give seperable diastereomer products

Chromatography - use a chiral stationary phase and one enantiomer will elute before the other

Use cis/trans and fac/mer nomenclature to describe the geometries of square planar and octahedral transition metal complexes

mer isomers follow a meridian - in a line/plane (mer=meridian)

fac isomers have 3 identical ligands in a corner (fac=face)

cis isomers if 2 identical ligands next to each other

trans isomers if 2 identical ligands, one above and one below in a straight line

Convert molecular structures from skeletal formulae to sawhorse and Newman projections with the aid of molecular models,

Describe the conformations of simple molecules in terms of dihedral angles, the terms 'staggered' and 'eclipsed', and using the Klyne-Prelog system,

Dihedral angle: angle between front substituent and back substituent

Staggered: Front substituents are equally between back substituents when looking from the front

Eclipsed: Front substituents are directly in front of back substituents

Understand the origins of torsional and steric strain,

Torsional strain - occurs when molecules are in eclipsed conformations due to electron-electron repulsion between eclipsing substituents

Steric strain - occurs when substituents are close together (within their van der waals radii) and there is electron-electron repulsion between the groups

Predict the relative energies of the conformations of small molecules on the basis of torsional and steric strain,

Torsional and steric strain increase the energies of conformations.

Construct and interpret torsional energy profiles for small molecules

Shows the energy of a molecule as a function of rotation around a bond (see image: torsional energy profile for ethane)

Rationalise the geometries of cycloalkanes (C3-C6) on the basis of angle and torsional strain

Angle strain: increase in energy of a molecule due to bond angle values deviating from ideal, hybridised bond angles. For example, sp³ hybridised angle is 109.5 but is 60 in cyclopropane so cyclopropane has angle strain

Use the terms axial and equatorial to describe the positions of substituents on cyclohexane rings,

Axial - substituents are above and below the plane of carbon atoms

Equatorial - substituents are in the planes of the carbon atoms

Evaluate the relative energies of substituted cyclohexane chair conformers and isomers and predict which is more stable on the basis of A-values and steric arguments.

Substituted cyclohexane chair conformers usually have substituents in the equatorial position as this reduces steric strain that would occur with Hs in the axial positiion

Use the Brønsted-Lowry definition of acids and bases to classify molecules as potentially acidic or basic, on the basis of their structure and bonding,

BL acid - proton (H+) donator

BL base - proton (H+) acceptor

Write equations defining pH, pKa, pKb and pKaH,

pH = -log[H⁺]

pKa = -log[Ka] where Ka is the acid dissociation constant

pKb = -log[Kb] where Kb is the base dissociation constant

pkaH = -log[KaH] where KaH is the acid dissociation constant of the conjugate acid of a base (reverse reaction for Kb)

State approximate pKa and pKaH values for common functional groups,

carboxylic acid pKa ~ 5

alcohol pKa 16-18

amine pKa 38-40

phenol pKa ~ 10

water pKa ~ 14-15

Calculate equilibrium constants for acid-base reactions using pKa and pKaH values,

Ka = 10^-pKa

KaH = 10^-pKaH

Explain periodic trends in acidity and basicity,

Across a period - acidity increases and basicity decreases due to increase in electronegativity and effective nuclear charge (Z_eff) so it is easier for atom to donate protons.

Down a group - acidity decreases and basicity increases as increasing atomic size means Z_eff decreases, harder to release a proton and easier to accept a proton

Explain how inductive (+I, −I) effects stabilise charged species,

Inductive - through sigma framework as some atoms more electronegative, leading to polarized bond and redistribution of electron density

-I occurs when electron withdrawing groups pull electron density away from adjacent atoms, increasing the positive charge on those atoms (e.g. halogens)

+I occurs when electron donating groups push electron density towards adjacent atoms, reducing positive charge (e.g. methyl groups)

Define and explanation hyperconjugation as part of inductive stabilisation

Hyperconjugation - delocalisation of electrons from a sigma bond (usually C-H or C-C) to an adjacent empty or partially filled p orbital or pi system when a filled orbital overlaps with empty p or pi system, usually stabilising carbocations and alkenes.

Explain how resonance/mesomeric (+M, −M) effects stabilise charged species,

Resonance/mesomeric - through pi framework of the molecule through delocalisation and spreading the charge across multiple atoms

+M electron donating groups, stabilise cations

-M electron withdrawing groups, stabilise anions

Rationalise and predict the relative acidity or basicity of molecules on the basis of inductive and resonance (mesomeric) effects.

Strong acids have weak conjugate bases and strong bases have weak conjugate acids.

Inductive effects - electron withdrawing or donating groups caused by difference in electronegativity, can stabilise conjugate bases, leading to stronger acids. E.g. halogen is electron withdrawing group and increases acidity because pulls e.d. away from oxygen atom in water and stabilising hydroxide ion

Resonance effects - delocalisation of electron pairs through resonance stabilise charges on conjugate base, making it more stable and more likely to donate a proton, making stronger acid. Resonance of double bond can stabilise hydronium ion, making it a stronger acid than water.

Identify nucleophiles and electrophiles in polar reactions, and the frontier orbitals (HOMO and LUMO) of these species,

Nucleophiles - high electron density, attracted to regions of positive charge or cations. Usually donate electrons

Electrophiles - electron deficient, attracted to regions of high electron density or anions. Usually accept electrons

Create and interpret reaction coordinate diagrams for simple reactions

Energy on y axis, reaction coordinate/progress on x axis

Identify and define transition states and intermediates, and indicate these on a reaction coordinate diagram,

Transition states - maximums on reaction coordinate diagrams. Barriers between reaction intermediates with bonds partially broken or formed with a very short lifetime.

Reaction intermediates - minima on reaction coordinate diagrams. Stable species with finite lifetimes that form during a chemical reaction and are later used so do not appear in overall reaction equation

Draw and justify the reaction mechanism for the electrophilic addition of alkenes (exemplified by, but not limited to, the reaction of HBr with an unsymmetrical alkene),

Heterolytic bond fission in H-Br with Br getting both electrons. Pi electrons bond to H+ from H-Br to form a carbocation. Br- acts as nucleophile and forms bond with the positive C in the carbocation to form a bromoalkane

Explain the (Markovnikov) selectivity observed in electrophilic addition reactions of alkenes,

H added to site where H most present because this mechanism forms greater substituted carbocations which are more stable due to hyperconjugation and inductive effects from alkyl groups. Primary carbenium ions are less stable as not stabilised by resonance or hyperconjugation. This causes the energy on the reaction coordinate diagram to increase, as well as the energy of the transition state before the carbenium ion intermediate (same factors that destablise carbenium ion apply to transition state - build up of positive charge in same place).

Predict the stereochemical outcome of electrophilic addition reactions of alkenes

If a stereogenic center is formed in the reaction, the products will be racemic as the carbenium ion is sp² hybridised and planar, equal probability of attack on either side of the planar carbenium ion

Draw and justify reaction mechanisms for nucleophilic addition to carbonyl compounds, as exemplified by cyanohydrin formation and nucleophilic attack by borohydride and organometallic species such as organolithiums and Grignard reagents,

Cyanohydrins - alcohol bonded to CN on same group as OH

Nucleophilic attack to carbonyl compounds (mainly aldehydes or ketones) proceeds by:

1. Nucleophile HOMO (lone pair on C in -CN) begins to interact with carbonyl LUMO which is the pi* orbital

2. Filling the pi* orbital causes the pi bond to break (BO is now 0)

3. Electrons from the pi bond end up as a negative charge on the more electronegative atom - which is O

in forming cyanohydrins and nucleophilic attack by borohydride:

4. protonation of - charge on O by bonding with H+ molecule

in nucleophilic attack by borohydride:

Instead of breaking B-H bond in BH4- to form H- (which is non-nucleophilic as small and charge dense), B-H bond is transferred to the carbonyl compound with the H effectively taking electrons with it

in nucleophilic attack by organometals or grignard reagents (R-MgX where X halide):

Bond between the metal and carbon is polarised towards carbon, interacts with the carbonyl LUMO, bond forms between carbon from metal-carbon bond and carbon in carbonyl compound

Identify prochiral carbonyl compounds and explain the stereochemical implications of nucleophilic addition to these systems,

Prochiral carbonyl compounds - achiral carbonyl compounds that can be converted to chiral carbonyl compounds with changing only one atom.

Carbonyl carbon atom is sp² hybridised and planar so nucleophile can attack from top or bottom side, forming a racemic mixture.

Draw and justify reaction mechanisms for nucleophilic substitution at acyl carbons (exemplified by the synthesis of esters from acid chlorides or anhydrides).

Nucleophilic substitution at acyl carbons with alcohol to form esters occur with the nucleophile being the OR- (where R is an alkyl group) and attacking the acyl carbon centre LUMO (pi*) which breaks the pi bond and forces the electron density towards the O to form a tetrahedral intermediate. Instead of protonating the O- in addition reactions, the C=O bond reforms with O- donating electron density to the C centre to form an ester. This occurs in the presence of a base.

Draw and justify the mechanisms for bimolecular (SN2) and unimolecular (SN1) nucleophilic substitution at tetrahedral carbon atoms,

Explain reactivity trends in SN1 and SN2 reactions as a function of leaving group ability,

More stable the anion, the better the leaving group (lower pKaH = better leaving group) As you go down group 7 with group 7 elements as leaving groups, rate of reaction increases as anions get bigger so the - charge is stabilised. Conjugate bases of strong acids make good leaving groups.

Explain reactivity trends in SN1 and SN2 reactions as a function of nucleophile (effects of charge, resonance stabilisation, periodic trends),

• negatively charged better nucleophiles because electrostatic attraction stronger, usually higher electron density to donate

• higher pKaH (more basic) of nucleophile is more reactive, faster rate of reaction

• resonance stabilised nucelophiles are less good nucleophiles, harder to donate an electron pair if shared about molecule

• as we go down a group, tends to get more nucleophilic (e.g. S compounds better nucleophile than O compounds because larger molecule, less electronegative, hold electrons less well)

Suggest appropriate electrophiles for synthetically useful SN2 reactions, including the activation of alcohols by conversion to their sulfonate esters,

Alcohols converted to sulfonate esters which can undergo SN2 (OH on alcohol bad leaving group with high pKaH, replace the H on OH with something else) through treatement with base, reacting with sulfonyl chloride where chloride leaves the molecule and sulfonate ion bonds to the O of the OH group. Toluenesulfonyl chloride and methanesulfonyl chloride usually used. Sulfonate ion now is a better leaving group so can undergo SN2 reactions.

Predict the operative mechanism for a given nucleophilic substitution reaction (excepting reactions of secondary electrophiles),

Tertiary compounds react by SN1, primary by SN2 due to increased stability of the tertiary carbocation during SN1 mechanisms. This stability is because of inductive effects as alkyl groups have high electron density and are electron donating sigma bonds, pushing electron density towards the positively charged C, reducing the positive charge. Stability also because of hyperconjugation: donation of electron density from adjacent C-H sigma bonds in to the empty p orbital of the carbocation (as is sp² hybridised)

Use the results of polarimetry experiments to infer the operative mechanism in a given nucleophilic substitution reaction,

SN1 produces racemic mixtures (no optical activity) whereas SN2 reactions always result in complete inversion of configuration, same angle but opposite to starting compound when polarimetry performed.

Explain the reaction kinetics for SN1 and SN2 reactions with reference to reaction coordinate diagrams.

SN1 is unimolecular, 2 steps:

1. Leaving group departs (RDS) forming a carbocation intermediate

2. Nucleophile attacks the carbocation, forming the product

SN1 mechanism has 2 transition states (maximums) and 1 intermediate (minimum - the carbocation).

SN2 is bimolecular, 1 step

1. Nucleophile attacks substrate simultaneously as the leaving group departs.

No intermediates, only 1 transition state where the carbon centre is partially bonded to both the nucleophile and the leaving group.