Does an organic reaction occur? Which atoms are involved in a reaction? What are the products of an organic reaction? An understanding of these concepts will help you predict how organic reactions occur. (Reference: P. Scudder, J. Chem. Educ. 1997, 74, 777)
1. Check: Lewis structure rules of reactants, products, and intermediates; formal charge, charge balance, etc.
2. Coulomb’s law – a positive charge/ion (cation) is attracted to a negative charge/ion (anion). Like charges do not attract, attack, or react with each other. Dications or dianions are not common (see formal charge).
3. Structural features (functional groups) give you information about how organic compounds react.
a. Identify the most reactive nucleophile (electron source) and electrophile (electron sink) to predict the most probable reaction partners. Rank the relative reactivity of the common electron sources and sinks (best to worst) by type and within each type.
Table 1. Nucleophile (Electron Sources) and Electrophile (Electron Sinks) Classification
| Nucleophile Type | Example | Electrophile Type | Example | |
| Organometallics (see carbanions) | alkyl lithium (CH3-) |
Best |
Electron deficient species | carbocations, CH3+, BF3 |
| Group I hydrides (H:–) | NaH | Acids | HCl | |
| Complex metal hydrides | NaBH4 | Single bonds between heteroatoms | C-O (C is the E+) | |
| Active metals | Li metal | Leaving groups on sp3 carbons | CH3I (I is the leaving group) | |
| Lone pair nucleophiles, bases (see pKa table) | ROH, RNH2, OH- | Carboxyl derivatives (sp2-bound L) | acyl halides, anhydrides, esters | |
| Allylic sources | enolates, enamines | Heteroatom-carbon multiple bonds | aldehydes, ketones, nitriles, CO2 | |
| Simple pi bonds | alkenes, alkynes, dienes | Conjugate acceptors | enones, acrylates | |
| Aromatic rings | benzene |
Worst |
redox-active metals | CrO3 |
b. Draw a “curved arrow” from the nucleophile to the electrophile using a known bond breaking/making process.
Table 2. Bond Breaking and Making Processes
| Bond Breaking/Making Process | Example |
| Polar: most organic reactions are polar reactions | |
| 1. Proton transfer | acid-base reactionalkene + HBr |
| 2. Ionization of a leaving group | 1st step of SN1 or E1 |
| 3. Nucleophilic attack on: | |
| a. electron deficient species | Cl– + carbocation |
| b. C bonded to leaving group | SN2 substitution of alkyl halide |
| c. H bonded to b C (C adjacent to a leaving group) to form a p bond | Elimination reaction of alkyl halide |
| d. a polarized multiple bond, e.g., C=O | Grignard reagent + aldehyde |
| 4. 1,2 rearrangement of a carbocation | 2o C+ to 3o C+ |
| Radical: | Alkene polymerization |
| 5. Initiation – non-radical forming radicals. Usually light is required for this step to occur. | |
| 6. Propagation – a radical reacts with a non-radical to produce a new radical and new non-radical. | |
| 7. Termination – two radicals react to form a non-radical. | |
| 8. Pericyclic: Concerted 6 electron pericyclic | Diels-Alder reaction |
A reaction mechanism shows the sequence of elementary steps by which reactants form products. In other words, a reaction mechanism shows the order in which bonds break and form in a reaction. Organic chemists and o-chem students like using curved arrows to show bonds breaking and forming to describe a mechanism. Beginning organic chemistry students often get carried away using curved arrows. If you can describe an elementary step with one of the bond breaking/making processes in Table 2, you’ll be able to describe a mechanism and predict or explain an organic reaction.
c. FOUR types of polar organic reactions: acid-base, addition, substitution, elimination.
4. Chemical reaction concepts: A reaction occurs when reactants collide with sufficient energy for bonds to break and form. Most reactions are exothermic.
a. The “right” atoms in each reactant have to collide together. Alignment and access (steric effect of size and crowdedness) of reactant atoms can limit some reaction paths, such as SN2.
b. Thermodynamics: High energy species, such as free radicals, are unstable and reactive; low energy species, such as alkanes, are stable and unreactive.
c. Thermodynamics: Strong bonds don’t react (see Teflon with strong C-F bonds); weak bonds do react (see weak N-O bonds in TNT). Bond dissociation energies can be used to estimate DHrxn (“bonds broken minus bonds made”) and give relative stabilities of reactants and products.
d. Thermodynamics: The stability of intermediates, such as 1o, 2o, 3o carbocation, anions, radicals, can be used to choose between reasonable alternatives, e.g., Markovnikov’s rule.
e. Kinetics – rate – which process occurs fastest? The fastest reactions produce the major product. E.g., proton transfer is very fast – often the first step in a reaction mechanism. But with weak organic acids and bases, proton transfer is slow enough to allow nucleophilic attack. Refer to elemental mechanistic processes.
f. Many organic reactions are equilibrium (reversible) reactions. E.g., organic acid-base (proton transfer) reactions are equilibrium reactions and tend to form the weaker acid/base. See pKa tables.
5. Medium (solvent) pH – acidic media contain powerful electrophiles and weak nucleophiles; basic media contain powerful nucleophiles and weak electrophiles.
Adapted from P. Scudder, J. Chem. Educ. 1997, 74, 777.