Which one of the following reactions will not lead to the desired ether formation in major proportion?
(iso- Bu ⇒ isobutyl, sec -Bu ⇒ sec-butyl, nPr ⇒ n-propyl, ᵗ Bu ⇒ tert-butyl, Et ⇒ ethyl)

Solution

Chemistry ma’am · 3 steps

In Williamson synthesis, look at the halide, not the alkoxide: only a methyl or primary halide gives ether.

1. The rule. Williamson synthesis is an S_N2 attack by the alkoxide on the carbon carrying the halogen. An alkoxide is also a strong base, so if that carbon is crowded, it pulls off a β-hydrogen instead and you get an alkene by E2.

   Option	Alkoxide (nucleophile and base)	Alkyl halide	Major product
   (a)	phenoxide	n-PrBr, primary	ether by S_N2
   (b)	isobutoxide	sec-BuBr, secondary	butenes by E2
   (c)	cyclohexoxide	CH₃Br, methyl	ether by S_N2
   (d)	tert-butoxide	EtBr, primary	ether by S_N2

2. Why (b) fails. The bromine in sec-butyl bromide sits on a secondary carbon, which hinders backside attack. The strong base isobutoxide removes a β-hydrogen instead, so but-1-ene and but-2-ene form, not the ether.
3. So. Reaction (b) does not give the desired ether in major proportion. A better route to sec-Bu–O–iso-Bu is sec-butoxide with isobutyl bromide, a primary halide.

The idea to keep. For Williamson synthesis, put the bulky group on the alkoxide and keep the halide methyl or primary. Secondary and tertiary halides with alkoxides give mainly alkenes.

Answer from the NTA final answer key. Solution by PrepWiser.