CH167

rules for drawing organic molecules (skeletal)

• represent carbon chains as zig-zag line

• do not show C or H labels in C-H bonds

• label all other atoms (functional groups, including H)

• draw benzene as Kemble structure as it is easier for mechanisms

epoxide functional group

hemiacetal functional group

acetal functional group

hemiaminal

imine functional group

nitro group

sulfonic acid

acetone

diethyl ether

tetrahydrofuran (THF)

N,N-dimethylformamide (DMF)

dimethylsulfoxide (DMSO)

what is the order of priority of functional groups (starting with highest priority first)

1. carboxylic acid

2. ester

3. amide

4. nitrile

5. aldehyde

6. ketone

7. alcohol

8. amine

9. alkene

10. alkyne

11. alkane

12. ether

13. halogenalkane

14. nitro

structural isomer definition

identical formulae but different connectivity of the atoms

double bond equivalents definition

the degree of unsaturation in a molecule based on its molecular formula

equation to work out double bond equivalents

DBE = C + N/2 - H/2 - X/2 + 1

• X = any halogen

conformational isomers definition

structures that can be converted by rotation around a single bond

what conformational isomer of ethane is most stable and why

staggered conformation is more stable sue to electrons repelling

what is a mesomeric effect

used to describe electrons withdrawing/donation properties of substituents based on relevant resonance structures

what is negative mesomeric effect and draw example

when the substituent is an electron-withdrawing group

what is positive mesomeric effect and draw example

when the substituent is an electron donating group

what is the inductive effect

shifting of electrons in a sigma bond due to difference in electronegativity of nearby atoms, resulting in bond polarisation

what is a polar molecule

a molecule that has an overall molecular dipole as a result of polarised bonds within their structure

what is the difference in range between mesomeric and inductive effect

mesomeric can be very long range but inductive effect is only significant over a short range

how do you stabilise carbocations

carbocations with adjacent pi-bond or atom with lone pari can be stabilised through resonance (mesomeric)

more hyperconjugation = more stable

what stabilises/destabilises carbocations vs carbanions

Carbocations	Carbanions
Stabilised by delocalisation into adjacent pi-systems	Stabilised by delocalisation into adjacent pi-systems
Stabilised by adjacent atoms bearing lone pairs	Destabilised by adjacent atoms bearing lone pairs
Stabilised by inductively donating groups	Destabilised by inductively donating groups
Destabilised by inductively withdrawing groups	Stabilised by inductively withdrawing groups
Occupy a vacant p-orbital (high energy unfilled)	Can occupy a p-orbital (if in conjugation with pi-system). Otherwise, stabilised by increased 's' character in orbital

what is pK_a

a measure of the ability of an acidic compound to give up a proton

strong acid = low pK_a

what does the difference in pK_a tell you

the log of the equilibrium constant

factors that affect pK_a

• intrinsic stability of the conjugate base

• strength of HA bond

• how well cations and anions are solvated

how can you stabilise an anion

• electronegativity of atom bearing negative charge

  • negative charge better stabilised on a more electronegative element

• hybridisation of atom bearing the negative charge

  • Better stabilised in an orbital with more s character

• size of atom bearing negative charge

  • better stabilised on larger atom

• delocalisation of negative charge (mesomeric effect)

  • more delocalisation = better stabilised

• inductively electron-withdrawing

  • inductively electron-withdrawing groups stabilise negative charge

what is pK_a^H

pK_a of corresponding conjugate acid

lower pK_a^H = weaker base

factors affecting pK_a^H

• availability of lone pair

  • increasing s-character of lone pair = held tighter to nucleus so less available = weaker base

• stability of cationic ammonium

  • more resonance forms = more stable = more basic

what is a chiral object

objects that cannot be superimposed onto their mirror image

what is an achiral object

object that can be superimposed onto their mirror image (contains an internal mirror plane)

what are enantiomers

non-superimposable mirror images, that rotate plane polarised light in equal and opposite directions

how to convert between enantiomers

invert all stereocentres

racemic mixture definition

an equimolar mixture of two enantiomers

how to assign absolute configuration

1. prioritise 4 substituents based on atomic number

2. arrange molecule such that lowest priority is pointing away

3. if the other substituents priorities are clockwise then it is R configuration and anticlockwise = S

how to interchange between R and S configuration

either:

1. draw mirror image

or

2. swap any two substituents

how to work out how many stereoisomers a molecule will have depending on number of stereogenic centres

number of stereoisomers = 2^N

• N = number of stereogenic centres

diastereoisomers definition

stereoisomers that are not enantiomers:

• non-superimposable, non-mirror images

• different chemical and physical properties

how to convert between diastereoisomers

invert at lease one, but not all stereo centres

mess compounds definition

a compound that contains two or more stereocentres but is superimposable on its mirror image

• contain internal mirror plane

• identical substituents on each stereo centre must be identical

• achiral

conformation definition

any one of the infinite number of possible spatial arrangements of atoms in a molecule

how to convert between conformations

rotation about sigma bonds

configuration definition

spatial arrangement of atoms in a molecule

• finite number of possible configurations

• can only be converted by breaking bond s

what are achiral diastereoisomers

trans/cis alkenes ar enon-superimposable non-mirror images and are diastereoisomers even if they don’t contain stereocentres

what is a cis alkene

Z alkene

what defines whether geometric isomers can be cis or trans

1. restricted rotation

2. atoms bearing substituents have at least one substituent the same

what does the Hammond Postulate state

the transition state will be most similar in structure to the species it is closest to in energy

how to predict a reaction mechanism

1. electrons start somewhere electron-rich (nucleophile)

   • order of choice

     • negative charge

     • lone pair

     • multiple bond

     • weak single bond

2. electrons move somewhere electron-poor (electrophile)

   • order of choice

     • positively charges carbon or hydrogen

     • an atom directly attached to a positively charged heteroatom

     • partial positive charge on a carbon or hydrogen

3. electrons end up somewhere goof

   • either:

     • quenched by C+ and H+ by a new bond being formed to C or H

     • by breaking pi bond to a heteroatom, leave it with a single bond

     • by breaking sigma bond to a heteroatom, disconnecting it from the molecule

4. charges must be balanced

5. may have to reapply rules 1-3 again

nucleophile definition

a reagent that forms a bond to its reaction partner by donating both bonding electrons

electrophile definition

a reagent that forms a bond to its reaction partner by accepting both bonding electrons

bronsted base definition

a reagent that forms a bond to a proton by donating both bonding electrons

bronsted acid definition

a reagent that donates a proton to form a new bond

what is the priority of where electrons start

1. anion

2. lone pair

3. multiple bond

4. weak single bond

how to choose between electrons starting from reactive sites at the same level

1. electronegativity

   • less electronegative = more reactive as they need to give away a pair of electrons

2. mesomeric effects (resonance)

   • resonance stabilises anion or lone pair = less nucleophilic

3. steric effects

   • less hindered = most nucleophilic

order of priority of where electrons move to

1. electron deficiency

   • more electron deficient = more electrophilic

2. steric effects

   • least sterically hindered = more favoured site of reaction

regioselectivity definition

the preference of chemical bonding or breaking in one direction over all other possible directions

what does an S_N2 reaction mean

S = substitution

N = nucleophilic

2 = bimolecular rate determining step

what are the factors affecting S_N2 reactions

1. reactivity of nucleophile

2. leaving group ability of X

3. substitution at the electrophilic carbon

4. nature of the solvent

what affects the reactivity of the nucleophile

less electronegative elements are more nucleophilic

steric hinderance reduces nucleophilicity

higher pK_a^H = better nucleophile

what factors affect leaving group ability

• strength of C-X bond

• stability of the leaving group anion

• strong acids readily dissociate to form stabilised anions

how do you know anion stability

check pK_a

• lower pK_a = more stable anion

what happens to rate of reaction as degree of substitution increases

more substitution = slower rate of reaction so tertiary substituted atoms are probably S_N1 because its so slow

what type of solvent favours S_N2

polar aprotic solvents (e.g. DMF and acetone)

what is the Walden Inversion

when electrophile of S_N2 reaction is chiral, reaction occurs with inversion of stereochemical configuration at C

draw a generic mechanism for S_N1 reaction

what factors affect S_N1 reactions

1. leaving group ability of X

2. substitution at the electrophilic carbon

3. nature of the solvent

how does leaving group ability affect S_N1 reactions

rate of reaction increases if leaving group ability increases

how does increasing number of substituents change reaction rate of S_N1 reactions and why

rate of reaction increases

• substituents stabilise cationic intermediate through hyperconjugation

how does increasing mesomerically donating groups affect rate of reaction

increasing rate of reaction as charge is allowed to spread out

what type of solvent favour S_N1 mechanism

polar protic solvents due to stabilisation of both ion pairs in intermediate

draw generic E2 mechanism

what two orbital interactions occur in E2 mechanism

2 electrons form base donate into σ*_C-H breaking C-H bond

2 electrons form σ_C-H donate into empty σ*_C-X and forming C=C bond

what favours E2 over SN2

more basic nucleophiles/bases

more sterically hindered nucleophiles/bases

higher reaction temperatures

what is the effect of temperature on elimination vs substitution reactions

in elimination, number of molecules increase so products are more disordered than reactants

• elimination reactions involve positive change in entropy

• become favourable at higher temperature

• often performed above room temp

draw generic E1 mechanism

what is E1 favoured by over S_N1

• higher reaction temperatures

• weak, non-nucleophilic bases

draw a table summary for substitution reactions vs elimination reactions for different substrates (methyl, unhindered primary, hindered primary, secondary and tertiary) and different nucleophiles (poor nu, weakly basic nu, strong unhindered nu, strong hindered nu)

draw MO diagram for C=O

what reactants are needed to go from a 1^o alcohol to a carboxylic

CrO₃, H₃O⁺ in acetone

how to go from a 1^o alcohol down to an aldehyde, without going down to a carboxylic acid

use pyridinium chlorochromate (PCC) in anhydrous conditions

how to oxidise from 2^o alcohol to ketone

use CrO₃ and H₃O⁺

what is the general reaction mechanism for the addition of nucleophiles to aldehyde/ketone

what is the Burgi-Dunite angle

angle of attack

how does reactivity change for aldehydes and ketones

• increased hyperconjugation/resonance = increased stability

  • inductive effect due to O being more electronegative than C

mechanism to form C-C bond on aldehyde/ketones using cyanide and acid

mechanism to remove cyanide using base to a ketone/aldehyde

how do sterics affect K

• planar molecules cause less crowding so larger K

• larger substituents are felt more so lower K

mechanism for addition of organolithiums to aldehydes/ketones

reaction to form Grignard reagent

mechanism of Grignard reagent to aldehyde/ketones

mechanism for nucleophilic addition of water to aldehyde/ketone (uncatalysed)

acid catalysis of protonation of carbonyl

base catalysis of nucleophilic addition of aldehyde/ketone

mechanism for acid catalysed acetal/ketal formation from aldehyde/ketone

PADPEAD

what are acetals used for

protect C=O bond from nucleophilic attack

reaction to form aldimine