Block 4 - Functional Groups 1 Flashcards
Alkene properties
Double bond - one sigma, one pi Carbons are sp2 hybridised - flat 120° Considered electron rich as it contains 2 electrons in the sigma bond and 2 in the pi bond Unsaturated
Preparation of alkenes
Usually via elimination reactions
- Acid catalysed dehydration of (removal of H2O from) alcohols (reagent: conc H2SO4)
- Base promoted dehydrohalogenation of (removal of HX from) alkyl halides (reagent: KOH or NaOH in ethanol)
Saytzeff rule
The major product is the most substituted alkene (more Cs); the alkene with the least no of Hs directly attached to the Cs of the C=C
C=C acts as a ….
Nucleophile, as the double bond is electron rich
Alkenes: types of addition reactions
Hydrogenation
Reactions initiated by addition of an electrophile E+
- H+ as an electrophile
- Halogenation
Alkenes: hydrogenation
Reagent: H2/catalyst (Pt or Pd)
Sometimes called a reduction
Occurs with syn stereochemistry - both Hs add to the same side of the molecule, i.e. always cis
- H atoms absorbed onto catalyst surface
Alkenes: H+ as an electrophile
Overall, addition of HZ (Z = halogen, OH, OR) via a carbocation intermediate
Markovnikov’s rule
The more substituted product is formed
Addition of an asymmetrical reagent to an asymmetrical alkene gives the major product of the compound where the electropositive part of the reagent (usually H+) has bonded to the carbon of the C=C that is directly bonded to the greater no of H atoms
1° 2° and 3° carbocation intermediates
3° more stable than 2° more stable than 1°
More stable –> more likely to form –> major product
Halogenation - steps
- Halogen acts as an electrophile. C=C is e- rich, so pushes e- in Br2 to one end –> induced dipole in Br2
- Halide ion acts as a nucleophile
Occurs with anti stereochemistry, i.e. always trans
Halogenation: presence of other nucleophiles
Presence of other nucleophiles can compete and give diff products
How are alkenes often detected in the lab
Discharge of Br2 colour (orange to colourless)
Preparation of alkynes
Di-dehydrohalogenation of dihaloalkanes
Br2 addition to alkene
Always adds trans to an alkene
Why doesn’t benzene undergo reactions typical of alkenes
Due to resonance
Aromatic rings are more stable than normal C=C bonds
Resonance energy of benzene
Conjugated double bonds present gives it extra stability, referred to as ‘resonance energy’
How to tell if cyclic hydrocarbons are aromatic
They contain (4N + 2)pi electrons, where N is the number of rings
Aniline
Benzene ring monosubstituted with NH2
Nitrobenzene
Benzene ring monosubstituted with NO2
Phenol
Benzene ring monosubstituted with OH
Toulene
Benzene ring monosubstituted with CH3
Disubstituted benzene ring positions
Ortho (1)
Meta (2)
Para (3)
> Disubstituted benzene rings - numbering
Use lowest possible sum of numbers for substituents
Alkynes
Triple bond - one sigma, two pi Carbons are sp hybridised - 180° Unsaturated Generally nucleophiles Generally undergo addition reactions
Alkyne: Hydrogenation - reagent
To form alkane: H2/Pt or Ht/Pd
To form Z alkene (cis): Lindlar catalyst/H2 [Pd/Pb(OAC)2]
To form E alkene (trans):
- Li/liq NH3
- H2O
Alkyne: Electrophilic addition of HX and X2
Markovnikov’s rule followed for HX addition
Reaction can be stopped after addition of one mole equivalent of reagent
Anti-stereochemistry of addition is observed
Alkyne: Hydration
Addition of only one mole equivalent of water
Products are ketones (except for ethyne)
Reagent: aq H2SO4 / HgSO4
Tautomeric equilibrium
Species involved are tautomers
Enol (unstable) and keto (more stable)
Formation of alkynide anions from terminal alkynes
The H on a terminal alkyne is weakly acidic and can be removed with a strong base (Na+NH2-)
Forms C- (nucleophile)
Aromatic compound reactions
Have extra stability of ‘resonance energy’ which prevents them from doing addition reaction chemistry
Undergo electrophilic aromatic substitution
Wheland intermediates
Resonance stabilised cations
Positive charges can only be ortho or para to the incoming electrophile group
Benzene mechanism steps
Substitution: addition –> elimination
Electrophile attack - slow step
Proton loss - fast step
How are strong electrophiles generated
Often formed by catalytic action Halogenation Nitration Friedel-Crafts acylation Friedel-Crafts alkylation
Generation of electrophiles - halogenation
Catalyst: Fe used to activate the halogen and generate a very reactive electrophile
X-X + FeX3 –> X+ + FeX4-
Where X+ is the very reactive electrophile
Generation of electrophiles - Nitration
HNO3 + H2SO4 –> NO2+ + HSO4- + H2O
Where NO2+ is very reactive electrophile
Nitro group: NO2
Which reactions can be introduced directly onto aromatic ring using electrophilic aromatic substitution
Br2, NO2, R (short; CH3, CH2CH3, (CH3)2CH2)
Generation of electrophiles - Friedel-Crafts acylation
Adding C=O to ring
Catalyst: AlX3 where X is a halogen
Forms R-C=O: very reactive electrophile, and then reacts with ring to replace a H
Generation of electrophiles - Friedel-Crafts alkylation
Adding R to ring
RX + AlX3 (catalyst)
Only works for small alkanes
R = CH3, CH3CH2, (CH3)2CH
Aromatic ring - reaction with Br2
Reaction only with Br2 adds 2 Br atoms trans to each other
Reaction with Br2 and FeBr3 (catalyst) substitutes an H on the ring with a Br atom
Diazonium ion
Benzene monosubstituted with N2+
Benzene ring to phenol
Ring substituent changes from:
H — HNO3/H2SO4 —> NO2 — Fe/H+ —> NH2 — HNO2 / 0°C —> N2+ — H3O+ —> OH
Benzonitrile
Benzene monosubstituted with nitrile group (CN)
Benzene ring to benzonitrile
Ring substituent changes from:
H — HNO3/H2SO4 —> NO2 — Fe/H+ —> NH2 — HNO2 / 0°C —> N2+ — CuCN —> CN
Substitution of 2nd substituent onto disubstituted benzene ring
All positions around ring are no longer equivalent
Substitution can occur ortho, meta, or para to G
G controls position of incoming electrophile
Substitution of 2nd substituent onto disubstituted benzene ring - need to consider…
- Where will substitution occur? Ortho, meta, para
- Will the reaction occur more or less rapidly than for the same electrophile with benzene? Is G activating / deactivating?
Directing and activating power of substituents - categories
Ortho-para directors:
- Strongly activating (-OH, -OR, -NH2, -NR2)
- Weakly activating (-CH3 alkyl)
- Deactivating (-X (F, Cl, Br, I))
Meta directors:
- Strongly deactivating (-NO2)
- Moderately deactivating (-H(or R)-C=O, OH(or OR)-C=O, CN)
Ortho-para directors
Electron Donating Groups (EDG)
O, N, and halogens have unshared electron pair(s) which can be donated into Ar ring (by resonance)
Alkyl groups can donate electrons into ring (induction)
Meta directors
Electron Withdrawing Groups (EWG)
All groups have a multiple bond to atom that is bonded to aromatic ring sp2 C
All groups have electropositive end of a polar bond attached to aromatic ring carbon
Electrophilic attack when an ortho-para director is attached, e.g. phenol with E+
Ortho substitution: 4 resonance contributors
Meta substitutution: 3 resonance contributors; no charge de-localised by oxygen –> less favourable
Para substitution: 4 resonance contributors
Electrophilic attack when a meta director is attached, e.g. nitrobenzene with E+
Ortho substitutuion: 3 resonance contributors, but only 2 reasonable (+ve charges repel –> unfavourable)
Meta substitution: 3 resonance contributors, all reasonable –> more likely to occur
Para substitution: 3 resonance contributors, but only 2 reasonable
Hence, meta wins by default - NO2 m-directing and de-activating
Alkyl halides
Haloalkanes
Contain a halogen attached to an sp3 hybridised (alkyl) C
Classified as 1°, 2° and 3°
Alcohol to alkyl halide - reagent(s)
SOCl2 preferred for 1° and 2° halides
HCl preferred for 3° halides
Alkyl halide reactions - nucleophile or electrophile
One can replace the halogen of an alkyl halide (electrophile) with an appropriate nucleophile
Alkyl halide reactions - nucleophiles
Cl-, Br-, I-
— increasing ease of substitution (faster reaction) –>
Weak bases –> less reactive –> excellent leaving groups
Alkyl halide - types of substitution
SN1 (substitution nucleophilic) unimolecular mechanism
SN2 bimolecular mechanism
The more substituted the alkyl halide…
The more substituted the carbocation generated
Alkyl halide: SN1 - rate
Rate ∝ [alkyl halide]
Not dependent on strength of nucleophile, but strength/basicity of it may affect course of reaction, e.g. favouring elimination
Alkyl halide - when is SN1 favoured
When intermediate carbocation, from breaking C-X bond, is relatively stable
3° > 2°»_space; 1°
Some benzylic halides
Alkyl halide: SN1 mechanism
Involves substitution by a nucleophile, with only one species involved in rate determining step (when the leaving group departs)
Alkyl halide: SN1 and SN2 - results in…
SN1 results in loss of stereochemistry
SN2 results in inversion of configuration
Alkyl halide: SN1 - R and S enantiomers
R-enantiomer –> R and S (racemate)
S-enantiomer –> R and S (racemate)
Therefore, either enantiomer gives a racemic mixture
Because H2O can add from above (50%) or from below (50%) where the intermediate is achiral
Alkyl halide to alcohol - reagent
H2O or hydroxide (OH-)
Alkyl halide: SN2 - rate
Rate ∝ [alkyl halide][Nu-]
Alkyl halide: SN2 - mechanism
Involves a transition state
Concentrated and synchronous
Substitution by a nucleophile, with 2 species involved in rate determining step
Alkyl halide - when is SN2 favoured
1° > 2° > 3°
From a 1° to a 2° to a 3° alkyl halide, the transition state becomes more crowded –> raises energy of transition state –> raises Ea for reaction –> less likely reaction will happen
Alkyl halide: SN2 - chiral non-racemic 2° alkyl halide
When a chiral non-racemic 2° alkyl halide reacts via an SN2 pathway, a chiral non-racemic (optically active) product results from inversion of configuration
Produces one product
Alkyl halide: SN2 - nucleophile direction
Nucleophile must come in from opposite side of X
Alkyl halide: When looking at stereochemistry, must think about which 3 things?
- What’s happening with starting material? Already a racemic mixture?
- What’s happening with product? Chiral or achiral?
- What’s happening with the mechanism?
Alkyl halide: True or false? If mechanism is SN1, you ALWAYS get a racemic mixture
False
To get a racemic mixture, must have a chiral C - may not have chiral C
Alkyl halide: True or false? If mechanism is SN1, you NEVER get a single enantiomer
True
SN1 means must go through carbocation intermediate and will get ‘scrambling’ of stereochemical information
Alkyl halide: True or false? If mechanism is SN2, you NEVER get a racemic mixture
False
If start with racemic mixture, produces racemic mixture
Is starting material chiral?
Alkyl halide: True or false? If mechanism is SN2, you ALWAYS get a single enantiomer
False
Depends on whether starting compound is a racemic mixture
Depends on whether product is chiral
Alkyl halide: E1 and SN1
E1 and SN1 can compete, leading to product mixtures
Both proceed via a carbocation intermediate
Alkyl halide: E1 rate
rate ∝ [alkyl halide]
Alkyl halide: E1 favoured for…
3° > 2°»_space; 1°
Alkyl halide: when is E favoured over SN1 reactions
Stronger bases, higher temperatures and a non-nucleophilic solvent favours E over SN1
Alkyl halide: E2 bimolecular - rate
Rate ∝ [alkyl halide][Nu-]
where Nu- is the base because instead of attacking the slightly positive C like in SN2, it takes a H instead
Alkyl halide: what does E2 require (reagent)
Strong base RO- or HO-
(CH3)3CO- also used because it’s too bulky for SN2
Alkyl halide: E2 favoured for…
3° > 2°»_space; 1°
However, can be observed for 1° if product extends conjugation
Alkyl halide: E1 and E2 - more than one product?
Sayzeff’s rule applies when more than one alkene can be formed
Alkyl halide: Temperature
Higher temperatures favour elimination
Alkyl halide: sp2 carbons
A halogen bonded to a sp2 carbon (e.g. aryl halide and vinyl halide) can’t undergo SN (substitution)
Vinyl halide reactions
Can undergo elimination reactions with strong bases to form an alkyne
Can’t undergo nucleophilic substitution
Grignard reagents
Alkyl, aryl and vinyl halides form Grignard reagents on treatment with Mg in dry diethyl ether (unreactive) as solvent
Magnesium is electropositive and so the attached C in Grignard reagent can be regarded as a carbanion (R-) –> acts as a carbon nucleophile (base)
