Organic Chemistry Flashcards
What makes a good nucleophile?
- nucleophilicity increased as basicity increases (high pKa)
- negatively CHARGED species more nucleophilic than corresponding neutral species
- nucleophilicity increases down a periodic table
What makes a good leaving group?
Good leaving groups have stable anions.
Which solvents promote SN2 reactions?
Polar aprotic (can’t donate H bonds) solvents (e.g. DMSO, DMF) solvate cations better than anions. Anion/nucleophile is able to get to substrate, increasing reaction rate.
Which solvents hinder SN2 reactions?
Polar protic solvents can donate H bonds and solvate nucleophile, lowering reaction rate.
Which solvents promote SN1 reactions?
Polar solvents stabilise the intermediate (solvate both positive and negative charge) so charge separation increases, as rate depends on stability of transition state 1.
Note: protic solvent don’t promote SN1 but holds back SN2 so SN1 is more likely.
Which conformation of cyclohexane is more favourable? Chair or boat?
Chair is lower in energy. There is no angle strain in chair or boat but in boat there is torsional strain and steric strain.
Note: the difference is not enough to knock one out of existence, though most of the time it is in chair structure.
Axial and equatorial hydrogens
Axial H points up when C is up and down when C is down. Equatorial H points out at angles (alternate between angled up and down).
Note: bulky substituents prefer equatorial positions.
What is the kinetic product?
The product associated with the lowest energy barrier to its formation (rate of product formation).
What is the thermodynamic product?
The most stable product with the lowest energy (the relative stability of the products).
Conditions for SN1
- good leaving group
- substrate: stable carbocation intermediate (tertiary, allylic halides, benzylic halides)
- solvent: polar solvents stabilise intermediate
Note: proceeds with racemisation of stereochemistry
Conditions for SN2
- good nucleophiles
- substrate: steric hindrance disfavours SN2
- solvent: polar aprotic solvents stabilise cations
Note: proceeds with inversion of stereochemistry
Conditions for E2
- nucleophile: strong base, bulky so approaches H
- proton abstracted needs to be antiperiplanar to leaving group
Note: endothermic reaction (requires energy to break bonds)
Reaction is stereospecific - can only give E (opposite sides)
Conditions for E1
- can be H+ catalysed dehydration
- goes through cationic intermediate (E1 not proposed in base)
Note: endothermic reaction
Reaction can be stereospecific - gives E to minimise clash
Regioselective (one of two regions reacts) - choice in which H is lost
E1cB
- goes through anionic intermediate (never proposed in acid) e.g. use NaOH
- intermediate is conjugate base of starting material
- usually bad leaving group
Professor Hammond’s Postulate
The structure of transition state (TS) resembles structure of nearest stable species (in energy).
- TS for endothermic reaction will resemble products (late transition state)
- TS for exothermic reaction will resemble starting materials (early transition state)
The Diels Alder reaction (pericycling) involves:
Diene
- conjugated and s-cis conformation
Dienophile
- needs to have electron withdrawing group
Predict stereochemistry products (cycloadduct) of Diels Alder reactions
Dienophile - Z (same side) gives cis product (same) - E gives trans product Diene - E,E diene/Z,Z diene gives syn product - E, Z diene gives anti product Note: If cycloadduct is chiral, it's formed as a racemate. Reaction is also insensitive to solvent, as mechanism involves no polar reagents or intermediates.
Requirements for a system to be aromatic
- cyclic
- fully conjugated
- planar
- has (4n + 2) pi electrons
Conditions for electrophilic aromatic substitution
- powerful electrophiles required
- Lewis acid catalyst needed for benzenes to react with Br2 (FeBr3) and Cl2 (FeCl3)
- for nitration use conc HNO3/conc H2SO4 to generate nitronium ion NO2+
- for sulfonation use conc H2SO4 to generate SO3H+
- for de-sulfonation use dilute aqueous H2SO4 at high temperatures
Ortho, meta, para directing for activating and deactivating groups
- activating (OH, NH2, CH3, OCH3, NHCOCH3) - o/p directing
- deactivating (NO2, CHO, COOH, CN, SO3H, NMe3+) - m directing
- deactivating (Cl, Br, I) - o/p directing (intermediates formed can be stabilised by any of these substituents)
Imines and enamines. Electrophile or nucleophile?
Imines are electrophiles and enamines are nucleophiles.
Enols and enolates are electrophiles or nucleophiles?
Enols and enolates react as carbon-centred nucleophiles (through alpha carbon), like enamines.
Reagents/conditions for radical reactions: halogenation and dehalogenation
Halogenation
- thermolysis or photolysis of compounds containign weak bonds e.g. peroxide (o-o), Br2
Dehalogenation
- AIBN, Bu3SNH
Pericyclic reaction: electrocyclic
One sigma bond formed or one sigma bond broken.
Pericyclic reaction: sigmatropic rearrangement
After reaction, same amount of sigma and pi bonds as before reaction.
Reagents/conditions for SEAr: halogenation
Br2, FeBr3 (catalyst)
Reagents/conditions for SEAr: nitration
- conc. HNO3, conc. H2SO4
- Results in NO2
Reagents/conditions for SEAr: sulfonation
- 99% H2SO4
- Results in SO3H
Reagents/conditions for SEAr: de-sulfonation
dilute aq. H2SO4, 160 degrees C
Reagents/conditions for Friedel-Crafts alkylation and acylation
Alkylation
- AlCl3 and alkyl halide
Acylation
- AlCl3 and acyl halide
Reagents/conditions for oxidation
KMnO4, H2O, 95 degrees C
Reagents/conditions for reduction
H2, Pd/C
Reagents/conditions for synthesis of anilines
From NO2 to NH2
- H2, Pd/C
- OR Sn, HCl (to get NH3Cl) then NaOH, H2O
Reagents/conditions for formation of diazonium salts
From NH2 to N2+
- NaNO2, H2SO4, 0-5 degrees C
Reagents/conditions for formation of imine and enamine
Imine
- ketone + primary amine, PhSO3H catalyst
Enamine
- ketone + secondary amine, PhSO3H catalyst
Reagents/conditions for formation of acetal
2 alcohol and PhSO3H catalyst
