Macmillan Learning In each reaction box, place the best reagent and conditions from the list. 1. H 2. 3. Answer Bank Zn(Hg), HCl NH
CH
NH
Br
, FeBr
NaCN NaBH
, CH
CH
OH H
, Pt NaNH
H
SO
CH
CN PBr
, pyridine CH
MgBr Mg, Et
O CN
The correct reagents for the three-step synthesis are:
- NaBH₄, CH₃CH₂OH
- PBr₃, pyridine
- NaCN
Explanation
This synthesis transforms benzaldehyde into phenylacetonitrile in three steps. The overall process involves reducing the aldehyde, converting the resulting functional group into a good leaving group, and finally, adding the nitrile group through a substitution reaction.
Step 1: Reduction of the Aldehyde
The initial reactant is benzaldehyde, which contains a carbonyl group (C=O). The target product has a methylene group (CH₂) attached to the benzene ring. The first step is to reduce the aldehyde to a primary alcohol, benzyl alcohol. Sodium borohydride (NaBH₄) in an alcohol solvent like ethanol (CH₃CH₂OH) is an excellent choice for this transformation. It selectively reduces aldehydes and ketones to alcohols without affecting the aromatic ring. The hydride ion (H⁻) from NaBH₄ attacks the partially positive carbonyl carbon, and a subsequent workup protonates the oxygen, yielding benzyl alcohol (PhCH₂OH).
Step 2: Conversion to an Alkyl Halide
The hydroxyl group (-OH) of benzyl alcohol is a poor leaving group. To facilitate the next substitution step, it must be converted into a better one, such as a halide. Phosphorus tribromide (PBr₃) is a standard reagent used to convert primary and secondary alcohols into alkyl bromides. The reaction proceeds by converting the -OH group into a good leaving group, which is then displaced by a bromide ion. Pyridine is often added as a weak base to neutralize the HBr byproduct that forms during the reaction, preventing side reactions. This step produces benzyl bromide (PhCH₂Br).
Step 3: Nucleophilic Substitution to Form the Nitrile
The final step is to introduce the nitrile (-CN) group and extend the carbon chain by one carbon. Sodium cyanide (NaCN) is a source of the cyanide ion (CN⁻), which is a strong nucleophile. Benzyl bromide is a primary benzylic halide, making it highly reactive in SN2 reactions. The cyanide nucleophile attacks the carbon bearing the bromine atom, displacing the bromide ion and forming the final product, phenylacetonitrile (PhCH₂CN).
