Williamson Ether Synthesis

* Produces unsymmetrical ethers through a nucleophilic substitution reaction (a nucleophile is a species that donates an electron pair to a positively charged species called an electrophile) * Involves an SN2 reaction of an alkoxide ion (which is the conjugate base of an acid – one less hydrogen - and is therefore an organic group bonded to a negatively changed oxygen atom) such as a sodium alkoxide and a primary alkyl halide (chemical compounds derived from alkanes containing one or more halogens – alkanes have only hydrogen and carbon atoms with single bonds and no cyclic structures) * An SN2 reaction is also known as a bimolecular nucleophilic substitution and it is where a lone electron pair from an nucleophile bonds to an electron deficient electrophilic center, causing a group called the “leaving group” to be expelled from the electrophile * The following reaction is the general form of a Williamson Ether Synthesis reaction

Alkoxide Alkyl Ether Leaving ion halide group

* The alkoxide ion reacts with the substrate (chemical species being observed, reacts with a reagent) which must have a good leaving group * Typically these substrates are alkyl halides, alkyl sulfonates, and dialkyl sulfates * Results in the formation of an ether with a leaving group as the other product of the reaction * The following reaction is a specific example of a Williamson Ether Synthesis used to produce an ether

CH3CH2CH2OH + NaH CH3CH2CH2O

R–O- is prepared from 1º, 2º, 3º, or any other alcohol as follows:

R–O–H R–O- M+
Where M is added and can be Na, K, etc.

R'–X can be 1º which yields best results, 2º which yields worse results, but not 3º as there will be no reaction. X can be Cl, Br, I, etc.

H3C–OH + PBr3 H3C–Br

+ H3C–Br

Structure
- Ethers are organic compounds that contain an ether group – an oxygen atom bonded to two alkyl (functional group which consists of single-bonded carbon and hydrogen atoms) or aryl (refers to any functional group derived from an aromatic ring) groups
- Aromaticity criteria are that the molecule must be cyclic, every atom in the ring must have a p-orbital that overlaps with the p-orbitals on either side, must be planar, and must contain an odd number of pairs of pi electrons (pi bonds are ones where two lobes of one orbital overlap two lobes of another)
- Structurally, ethers can be pure aliphatic (acyclic – open chain compound), pure aromatic, or mixed
- Have a general formula of R–O–R' (where R is a placeholder for radicals)
- R and R' can be the same (symmetrical ether), different (unsymmetrical ether), or connected (cyclic ether)

Chemical and Physical Properties
- Chemically, ethers are comparatively unreactive as the linkage is stable in the presence of most oxidizing agents, reducing agents, dilute acids, and alkali’s (basic ionic salt)
- Unlike alcohols, do not have hydroxyl groups – without the polarized O−H bond these molecules cannot form hydrogen bonds with each other
- Lack of hydrogen bonding results in a relatively low boiling point in comparison to analogous alcohols (alcohols with the same radicals) with similar molecular weights
- The boiling point of ethers increases with increasing carbon chain lengths – Van der Waals dispersion forces are proportional to surface area, therefore as the length of the chain is increased the surface area is as well, thus increasing the ability of individual molecules to attract one another and it takes more energy – a higher boiling point – to send the molecules out into the atmosphere as gases
- The difference in the boiling point of an ether and its isometric alcohol becomes smaller as the carbon lengths become longer as the Van der Waals forces of the prolonged carbon chain prevails over the hydrogen bonds
- Although ethers themselves do not contain hydrogen bonds, they have nonbonding electron pairs on their oxygen atoms that allow them to hydrogen bond with other molecules that have O-H (hydroxyl) or N-H (amino) bonds (such as alcohols and amines)
- This hydrogen bonding ability makes ethers good solvents for many organic and inorganic compounds
- Ethers are slightly polar, more polar than alkenes but less polar than alcohols, esters or amides of similar structure – the bond angle in the functional group of C-O-C is approximately 109.5º and the C-O dipoles don’t cancel one another out
- Cyclic ethers are miscible in water due to the exposed oxygen atom with nonbonding electron pairs that allows for hydrogen bonding with water – cyclic ethers are polar and are therefore miscible in a polar solvent such as water, as opposed to aliphatic ethers which are acyclic and are not miscible in water