Organic Synthesis Unit 2

Bond Fission

Alkanes are not particularly reactive due to the non-polar nature of their bonds. They can, however, react with halogens in the presence of sunlight or UV light where halogenoalkanes are produced along with steamy fumes of the corresponding hydrogen halide. In this reaction an atom of hydrogen has been replaced with an atom of a halogen, and is an example of a substitution reaction.

This substitution reaction is thought to occur by a chain reaction which has 3 main steps: Propagation, Initiation and Termination.

Bond breaking CH4 + Cl2  CH3Cl + HCl This reaction will not take place in the dark, it requires UV light to provide energy to break the Cl-Cl bond. This splits the chlorine molecules into chlorine atoms. Cl-Cl  Cl● + Cl● (the dot represents an unpaired electron). This type of bond breaking is known as homolytic fission and usually occurs when the bond is non-polar or very slightly polar.

In homolytic bond fission one electron from the bond goes to one atom while the other electron goes to the other atom. Atoms with unpaired electrons are known as radicals which are incredibly unstable and are therefore incredibly reactive. The initiation step in a chain reaction produces radicals.

Heterolytic bond fission If a bond were to split unevenly, ions are formed. The atom that got both electrons would be –ve, the other +ve. This is called heterolytic bond fission and will be favoured when the bond is polar. Reactions proceeding via heterolytic bond fission tend to produce far fewer products and are therefore better suited for synthesis.

Electrophiles and nucleophiles

In reactions involving heterolytic bond fission, attacking groups are classified as “nucleophiles” or “electrophiles”. Electrophiles are chemical species that are electron deficient and are therefore “electron loving” species. Electrophiles are molecules or positively charged ions which are capable of accepting an electron pair. They will seek out electron rich sites in organic molecules. Examples include NO2+ and SO3H+

Nucleophiles are chemical species that are rich in electrons and are “electron donating” species. Nucleophiles are molecules or negatively charged ions which have at least one lone pair of electrons that they can donate and form dative bonds. They will seek out electron-deficient sites in organic molecules. Examples include H2O, NH3 and halide ions.

Curly arrow notation Double headed curly arrows are used to indicate the movement of electron pairs in a reaction. The tail of the arrow shows where the electrons originate from and the head shows where they end up. An arrow starting at the middle of a covalent bond indicates that heterolytic bond fission is occurring. When an arrow is drawn with the head pointing to the space between two atoms, this indicates that a covalent bond will be formed between these two atoms.

A single headed curly arrow indicates the movement of a single electron. These are useful in discussions about radical chemistry mechanisms.

Haloalkanes

Haloalkanes can be regarded as substituted alkanes where one or more of the hydrogen atoms have ben replaced with a halogen atom. In naming haloalkanes the halogen atoms are treated as branches and naming is done in the same way as for branched alkanes.

Name this haloalkane 2-bromo-2-chloro-1,1,1-trifluoroethane Remember, branches are named in alphabetical order.

MONOHALOALKANES Have three different structural types which are primary, secondary and tertiary. These are determined by the number of alkyl groups (R) attached to the carbon atom directly attached to the halogen atom (X).

Primary

Secondary

Tertiary

Due to the polar nature of the Carbon-Halogen bond, haloalkanes are susceptible to nucleophilic attack. The presence of the slight positive charge on the carbon atom makes haloalkanes susceptible to nucleophilic attack.

The nucleophile donates a pair of electrons forming a bond with the carbon atom of the C-X bond. The halogen is “thrown out” and substituted by the nucleophile. The mechanism for this will be covered later.

Nucleophilic substitutions of monohaloalkanes

Making alcohols Reactions of monohaloalkanes with alkalis produce alcohols. A solution of aqueous KOH or NaOH is used.

Making Ethers Reactions with alcoholic potassium alkoxides (Potassium methoxide in methanol CH3OK) produces ethers.

Making Nitriles Reactions of ethanolic potassium cyanide or sodium cyanide (KCN or NaCN in ethanol) produces nitriles.

Making carboxylic acids The end nitrile contains one more carbon than the original haloalkane. This is very useful in synthetic organic chemistry as a way of increasing the chain length of an organic compound. The nitrile can be converted into the corresponding carboxylic acid through acid hydrolysis.

Elimination to form alkenes Monohaloalkanes can undergo elimination reactions to form alkenes. This is achieved by heating the monohaloalkane under reflux with ethanolic potassium or sodium hydroxide.

In this reaction a hydrogen halide is removed from the original monohaloalkane and for some it can result in two different alkenes being produced. This is due to the availability of more than one H atom that can be removed in the formation of the hydrogen halide. For example, 2-chlorobutane can result in but-1-ene and but-2-ene, of which but-2-ene is the major product.

Just because I knew adam or aimee would ask… Zaitsev's rule "The alkene formed in greatest amount is the one that corresponds to removal of the hydrogen from the β-carbon having the fewest hydrogen substituents."  For example, when 2-iodobutane is treated with alcoholic KOH, but-2-ene is the major product and but-1- ene is the minor product.

Don’t learn the previous slide!!!