Question

Using your roadmaps as a guide, show how to convert 1-butanol into racemic 4-octanol. You must use 1-butanol as the source of all carbon atoms in the target molecule. Show all reagents and all molecules synthesized along the way.

Short answer

Question: Convert 1-butanol into racemic 4-octanol using a step-by-step reaction pathway. Answer: The following reaction pathway can be followed to convert 1-butanol into racemic 4-octanol: 1. Convert 1-butanol to 1-bromobutane using hydrobromic acid (HBr). 2. Form a Grignard reagent (butylmagnesium bromide) by reacting 1-bromobutane with magnesium in diethyl ether. 3. Elongate the carbon skeleton by reacting the butylmagnesium bromide with ethylene oxide, followed by protonation to form 1-butylhexan-1-ol. 4. Convert 1-butylhexan-1-ol to 1-bromoheptane using HBr. 5. Prepare a sulfonate ester (1-tert-butyldimethylsilyl ether-heptane) by reacting 1-bromoheptane with tert-butyl sulfonyl chloride (TsCl) and pyridine. 6. Form 1-heptene by reacting the sulfonate ester with sodium iodide (NaI) in acetone. 7. Perform oxymercuration on 1-heptene using mercuric acetate (Hg(OAc)2) and water to form a mercurial intermediate. 8. Complete the oxymercuration-demercuration process by reacting the mercurial intermediate with sodium borohydride (NaBH4) to obtain racemic 4-octanol.

Step-by-step solution

Conversion of 1-Butanol to 1-Bromobutane

To convert 1-butanol into 1-bromobutane, we can use a hydrobromic acid (HBr) as the reacting agent: 1-Butanol + HBr → 1-Bromobutane + H2O

Grignard Reagent Formation

To form a Grignard reagent, which will be used in the next step to elongate the carbon skeleton, react 1-bromobutane with magnesium in the presence of diethyl ether as solvent: 1-Bromobutane + Mg → butylmagnesium bromide (Grignard reagent)

Carbon Skeleton Elongation

To elongate the carbon skeleton, react the butylmagnesium bromide with ethylene oxide (oxirane) followed by protonation: Butylmagnesium bromide + Ethylene oxide → 1-butylhexan-1-ol (after protonation)

Conversion of 1-Butylhexan-1-ol to 1-Bromohexane

Similar to Step 1, we will convert the alcohol group in 1-butylhexan-1-ol to a bromide group using HBr: 1-Butylhexan-1-ol + HBr → 1-Bromoheptane + H2O

Formation of Sulfonate Ester

To further convert 1-bromoheptane into an alkene, we need to first prepare a sulfonate ester. Use _tert_-butyl sulfonyl chloride (TsCl) and pyridine as reagents: 1-Bromoheptane + TsCl + Pyridine → 1-tert-butyldimethylsilyl ether-heptane (Sulfonate ester)

Formation of 1-Heptene

To form the alkene, react the sulfonate ester with sodium iodide (NaI) in acetone: 1-Tert-Butyldimethylsilyl ether-heptane + NaI (in acetone) → 1-heptene + tert-butyldimethylsilyl iodide

Oxymercuration of 1-Heptene

To introduce an alcohol group to the middle of the carbon chain, we need to carry out oxymercuration-demercuration (Markovnikov addition). Use mercuric acetate (Hg(OAc)_2) and water for the oxymercuration step: 1-Heptene + Hg(OAc)_2 + H2O → Mercurial intermediate

Demercuration of Mercurial Intermediate

To remove the mercury group and complete the oxymercuration-demercuration process, add sodium borohydride (NaBH4) to the mercurial intermediate: Mercurial intermediate + NaBH4 → Racemic 4-octanol

Key concepts

Grignard Reagent Formation

Grignard reagents are pivotal in synthetic organic chemistry for creating new carbon-carbon bonds. A Grignard reagent is formed when an alkyl halide reacts with magnesium metal in a dry ether solvent. Typically, the reaction vessel is scrupulously dry, since water can react with the Grignard reagent. The general formula for a Grignard reagent is R-Mg-X, where R is the alkyl group and X is a halide.

In our problem, we use 1-bromobutane and magnesium to make butylmagnesium bromide. This reagent is highly reactive due to the presence of the partial negative charge on the carbon atom bonded to the magnesium. The reactivity of Grignard reagents makes them suitable for a variety of reactions including carbon chain elongation, as seen in the given exercise. Such reagents are also used to form alcohols, acids, and other functional groups, making them versatile tools in molecular synthesis.

Carbon Chain Elongation

Carbon chain elongation is a crucial step in synthesizing larger organic molecules from smaller ones. There are various techniques to accomplish this, and one efficient method involves the use of Grignard reagents. When a Grignard reagent comes into contact with a compound containing a good leaving group, like an epoxide, it can open the ring and insert the alkyl chain.

This process is illustrated in the conversion of butylmagnesium bromide to 1-butylhexan-1-ol via reaction with ethylene oxide. The Grignard reagent attacks the less hindered carbon of the epoxide, which leads to ring opening and formation of a new carbon-carbon bond. Following protonation, the resulting molecule has an elongated carbon skeleton. This step-by-step construction allows for the controlled synthesis of complex molecules with precise carbon counts, which is a foundational aspect of organic synthesis.

Oxymercuration-Demercuration

Oxymercuration-demercuration is a two-step pathway commonly used to hydrate alkenes to alcohols. It follows Markovnikov's rule, meaning the resulting alcohol group attaches to the more substituted carbon atom, and it proceeds via an electrophilic addition mechanism. Initially, mercuric acetate and the alkene react in the presence of water, creating a mercurinium ion intermediate.

This intermediate is then attacked by a water molecule, leading to the formation of a mercury-alcohol adduct. Traditionally, this addition is anti-stereoselective, and the reaction proceeds without the risk of rearrangements. The final step involves treatment with sodium borohydride to replace the mercury atom with a hydrogen atom, resulting in the alcohol product. This method is favored over direct hydration because it substantially reduces the potential for by-products such as carbocation rearrangement, which is especially crucial in synthesis aiming to obtain racemic mixtures with high purity.