Organic

• Dissociation of an O-H bond results in the formation of an oxygen anion (negative charge) and a proton (positive charge)

  
  

  In water, the proton is bonded to a water molecule, generating H3O+

  
  

  Stabilising the anion (RCO2−)will enhance the acidity(move equilibrium towards the right
• pKa = − log Ka
• IUPAC definition: molecular entity that is an electron-pair acceptor (acid) or donor (base)
• The effect of replacing a carbon fragment by a singly bonded oxygen then a doubly bonded oxygen is large; 3 is much more acidic (equilibrium further to the right). This effect must result from the stabilisation of the anion

  
• Distributing electron density increases stability
• Resonance structures can be interrelated by curved arrows (these show movement of two electrons), a single double headed arrow (not equilibrium arrows) is used to denote this relationship.

  
• Resonance is characteristic of π-systems - double bonds, triple bonds, lone pairs. Charge distribution will depend on other factors, for example, electronegativity.

  Conjugated Double Bonds Adjacent π-systems extends the overall MO
• Butadiene - Compare ethene and butadiene

  Experimental data indicates that indeed the C2-C3 bond is shorter than expected for a C-C single bond

  
• Allyl Cation

  Experimental data indicates that indeed the allyl cation reacts with electron rich species at C1 and C3 but not at C2.

  
• Allyl Anion

  Experimental data indicates that indeed the allyl anion reacts with electron poor species at C1 and C3 but not at C2.

  
• Benzyl Cation

  Experimental data indicates that indeed the benzyl cation is much more stable than an unconjugated cation.

  
• • The carbonyl carbon is electron deficient (somewhat positive) and therefore reacts with electron rich species.


  The carbonyl oxygen is electron rich (somewhat negative) and therefore reacts with electron poor species, e.g. H+, metal cations.

  
• Esters and Amides

  The lone pair can be conjugated (O in esters and N in amides must be sp2 hybridised) and therefore stabilising the carbonyl.

  Notice that the partial positive charge on the carbonyl carbon is shared with the heteroatom. Electron rich species are therefore less likely to react with esters and amides compared with ketones and aldehyde

  Resonance is more effective with N-atom than O-atom; amides are more stable than esters.

  
• Peptide Amide Bond

  Experimental Observations:

  • The peptide bond is polar.
  • The N-C bond is shorter than expected(typically 1.33 A vs 1.47 A in amines).
  • It is planar showing the potential for resonancestabilisation (X-Ray data).
  • Rotation is hindered (therefore slow - see later notes).


  This explains four important properties of amides:

  • They are unreactive compared to other carbonyl groups.
  • They are good at forming hydrogen bonds.
  • They are planar.
  • They display hindered rotation
• Benzene

  Molecular formula: C6H6Physical properties: clear, colourless liquid, b.p. 81 oC, m.p. 5 oC Chemical properties:

  •Difficult to hydrogenate but does react (confirms unsaturation) •Hydrogenation eventually affords cyclohexane

  •Undergoes substitution rather addition reactions (addition reactions expected for unsaturated compounds).
• The Kekulé Proposal

  This proposal....

  1.satisfies the valence requirements of C and H;

  2. makes all C and H-atoms equivalent;

  ...but

  Experimental data indicates that the chemistry of benzene is different from an alkene

  Modern structure determination methods (X-ray or electron diffraction) provide detail of the structure:

  planar; all angles are 120; all C-C distance are 1.394A; all C-H distances are 1.00A
• The Electron Delocalisation Model

  Resonance theory suggests that there are two equally valid distributions of the double bonds; both structures are necessary to give a true description with the real structure being a superposition of both, referred to as a resonance hybrid.

  
• Huckel's rule

  Huckel’s rule can be generalised to the number of electrons for benzene-like behaviour being (4n + 2) π-electrons (where n = 0, 1, 2, 3 etc)

  The Huckel formalism for planar regular conjugated arrays always has one low energy orbital and the others paired in energy as far as possible.

  In this case the scheme generates three bonding MOs and three antibonding MOs. The MO energy increases as the number of nodes increases.With 6 electrons, only the bonding MOs are populated.

  
• Anti-Aromatic Stuctures

  Conjugated cycloalkenes have different numbers of p AO making up their π-array, e.g. cyclobutadiene. Analysis of the MOs can reveal why aromatic stabilisation is absent.

  
• Heteroaromatic Compounds

  To identify compounds of this type, look for full cyclic conjugation, with (4n + 2) electrons in the π-system (Huckel’s rule).

  
• Six-membered heterocyclic ring systems

  Pyridine is relatively unreactive but can function as a weak base.

  Note that protonation does not perturb the π -array since the lone pair which accepts the proton is not part of it (it is "orthogonal" to the π -system).
• Pyridine and the Alkaloids

  Nicotine and Quinine are examples of the alkaloids (basic, nitrogen containing secondary metabolites).

  • Many alkaloids are toxic
  • Some are addictive
  • Some form part of some pharmaceuticals
• Heteroaromatics with Five-membered Rings

  If X = NH: 3 σ bonds formed - 2 to carbon, 1 to H (or other substituent)


  If X = O or S: 2 σ bonds to carbon

   

  
• Acidity/basicity of Pyrrole

  
• Imidazole

  Imidazole is a common heterocycle with two N atoms, and is part of the amino acid histidine.

  One N atom is bonded to 1 H atom & 2 C atoms via sp2 orbitalsTWO electrons in a pz orbital are used to complete the 6 p electrons needed to confer aromatic character.

  The other N atom has its lone pair is in an sp2 orbital.Lone pair can be donated to H+ or any other electron deficient species (hence it’s basic character).

  
• Conformation and Rotation About Single Bonds

  Conformations are defined as the different shapes adopted by molecules, accessible by rotations about single bonds. No bonds are made or broken in conformational changes.

  Energy barrier is called Pitzer strain or torsion energy.This barrier is low in this case (12.5 kJmol-1) and means that torsional rotation is rapid under ambient conditions (> 105 rotations sec-1 at 25 oC).

  
• The Boltzmann Distribution

  
• Longer Chains

  Butane CH3CH2CH2CH3

  Two staggered conformations anti and gauche (Energy difference is 3.76 kJmol-1). This small energy difference dictates that both of these populations will be significantly populated.

  Two eclipsed conformations. Measuring from the most stable anti-conformation, the barriers to rotation via the eclipsed conformations are 14 kJmol-1 and 20 kJmol-1.
• Hexane

  Longer linear chains can be treated as multiple butane fragments.Each dihedral angle is more often anti than gauche (i.e. the anti conformers are more stable than gauche.)Most common conformation has the fully staggered conformation, but statistically 1 or more gauche conformations are often also present.
• Example 2-Fluoroethanol FCH2CH2OHUnlike ethane (anti preferred, energy barrier = 12.5 kJmol-1), 2-fluoroethanol is more stable gauche than anti.

  F-H interaction stabilises gauche conformation. Now gauche is favoured by 2 kJmol-1 over anti.
• Isomerisation about Double Bonds

  C=C Alkenes

  One characteristic of a double bond is that there is hindered rotation, i.e. one geometric isomer cannot convert to another.

  At the transition state the π-bond is completely lost. Hence, the barrier to cis/trans isomerisation is high, ~250 kJmol-1. The rate of cis/trans isomerisation is negligibly slow at room temperature.

  
• Isomerisation about Partial Double Bonds

  Amides

  Degree of double bond character can be measured by increase in barrier to rotation compared to that in a pure single bond.

  A typical single C-N bond has barrier to rotation of ~20 kJmol-1, whereas a C-N double bond (C=N) has barrier of ~250 kJmol-1.

  Barrier for C-N rotation in amide is ~75 kJmol-1.(Extra 55 kJmol-1 is from loss of π-bonding in transition state.)
• Rate of Rotation

  At room temperature, isomers interconvert too quickly to isolate if the barrier for interconversion is < 60 kJmol-1.

  If the barrier is > 100 kJmol-1 separation is possible. Changing temperature changes this rule of thumb.
• geometric isomers= Alkenes with different substituents at both ends of the double bond
• E/Z Isomerism

  The IUPAC system uses E- and Z-prefixes according to the following rules:

  • At each end of the double bond, prioritise the substituents, by atomic number at the first attached atom.
  • If there is no distinction at the first attached atom, move to the second, and keep going until there is a distinction.
  • A doubly bonded atom counts as two single bonds.If the higher priority substituents are on the same sides = Z-configurationIf the higher priority substituents are on the opposite sides = E-configuration
• Isomerism= Same molecular formula - different arrangements of atoms in space
• Constitutional Isomers= Have the same molecular formula - different sequence of atoms or linkages between atoms

  Interconversion possible only by breaking and remaking bonds (i.e. by changing the “connectivity” of the atoms).
• Stereoisomers =Have the same molecular formula, same sequence of atoms or linkages between atoms but different arrangement of atoms in space

  Interconversion by rotating or “bending” bonds (no change in atom connectivity).
• Chirality, Enantiomers, and Diastereoisomers

  An object (including a molecule) is chiral if it has a non-superimposable mirror image.

  For chiral compounds, the non-superimposable mirror images are called enantiomers.

  An object with a superimposable mirror image is achiral. Similarly, an object or molecule which possesses a plane of symmetry is achiral.

  Two stereoisomers that are not mirror images are called diastereoisomers
• Chirality and Plane-polarised Light

  A solution of a chiral molecule rotates the plane of plane-polarised light. This phenomena is termed optical rotation (or optical activity).

  Each enantiomer rotates polarised light by the same amount, but it opposite directions (clockwise or anticlockwise).

  A 1:1 mixture of enantiomers of a compound is called a racemic mixture and has no effect on plane polarised light.