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Let's revisit the definition of basic terms in IBDP organic chemistry!
Basic terms
- Nucleophile: electron-rich chemical species that forms bonds by donating an electron pair
- Electrophile: electron-deficient chemical species that forms bonds by accepting an electron pair
- Nucleophilic substitution: chemical reactions in which an electron-rich chemical species (nucleophile) replaces a functional group within another electron-deficient molecule (electrophile)
General reaction
Nuc: + R-LG → R-Nuc +LG:
- The electron pair (:) from the nucleophile (Nuc) attacks the substrate (R-LG) forming a new bond
- the leaving group (LG) departs with an electron pair, giving the main product (R-Nuc)
- The nucleophile may be electrically neutral or negatively charged
- the substrate is typically neutral or positively charged
- E.g. hydrolysis of an alkyl bromide
SN1/SN2 reactions
- Two main mechanisms(SN1/SN2) at work in a nucleophilic substitution, both competing with each other
- S stands for chemical substitution, N stands for nucleophilic and the number represents the kinetic order of the reaction
SN1 Mechanism
- First order, two-step reaction
- (1) the removal of the leaving group creates a positively charged carbon(electrophile)
- (2) nucleophile approaches to the carbocation and bond by donating the electrons
- usually happen when the carbocation is not easily accessible (surrounded with bulky group)
- in above example, nucleophile = Cl ion, tertiary carbon ---> SN1
SN2 Mechanism
- Second order, simultaneous reaction
- the removal of the leaving group and approaching of nucelophile take place at the same time
- usually occur where the central carbon atom is easily accessible to the nucleophile (no bulky group surrounding the carbocation)
- in above example, nucleophile = ammonia with lone pair electrons, primary carbon ---> favors SN2
Predicting order of nucleophilic substitution
(1) Electrophile
- leaving group is attached to methyl/primary carbon ---> favors SN2 (less substituted C)
- leaving group is attached to tertiary/allylic/bezylic carbon ---> favors SN1 (more substituted C/ bulky group attached)
(2) Nucleophile
- more negatively charged nucleophile ---> SN2
- weak nucleophile like H2O, alcohol ---> SN1
Factors affecting reactivity
- Reactivity: Acid chlorides > acid anhydrides > esters > amides
- The more stable the leaving group, the easier it leaves
- The greater the electrophilic strength, the more reactive the acid derivative
Leaving group
- the more stable the ions formed as leaving group, the faster the nucleophilic substitution
- More electronegative atoms can stabilise a charge better as they tend to draw electrons towards themselves (i.e. Cl > O > N > C)
- A -ve charge can be stabilised or destabilised by the inductive effects of neighboring groups.
- A -ve charge can be stabilised by resonance effects
Summary
- Nucleophilic substitution reactions are possible with carboxylic acid derivatives
- Reactivity: Acid chlorides > acid anhydrides > esters > amides
- Reactivity depends on (1) the stability of the leaving group (2) electrophilic strength of the carbonyl group
- IMPOSSIBLE to make a reactive acid derivative from a less reactive one
- Primary alkyl halides ---> SN2 mechanism
- Tertiary Alkyl Halides ---> SN1 mechanism
- Secondary Alkyl halides ---> SN1 or SN2 mechanisms
- if the alkyl groups are both small ---> SN2
- if the alkyl groups are both large ---> SN1
This is the end of this topic.