Amine and Nitrile Synthesis
SN2 Synthesis
Amines and nitriles can be synthesized from an alkyl halide (or other good leaving group) with the appropriate amine or cyanide nucleophile. The same rules apply as always for an SN2 backside attack. The reaction works best if the backside of the alkyl halide is not crowded or sterically hindered. Methyl and 1° alkyl halides work well, 2° alkyl halides work OK, but 3° alkyl halides do not work well. Any good leaving group on the substrate will work. The leaving group can be tosylates or halides like iodide, bromide, or chloride.
3. Draw the products of the following reactions.
a)
b)
c)
d)
e)
f)
Reduction of nitriles
Nitriles can be reduced to primary amines. Notice that there are three carbon-nitrogen bonds in the nitrile. A good reducing agent like lithium aluminum hydride, LiAlH4 (LAH) can reduce the cyano group to a primary amine making an –NH2 group. The hydrides, H:-, can twice attack the carton atom of the nitrile. Following protonation of the doubly negative nitrogen atom, a primary amine is formed.
4. Draw the products of the following reactions.
a)
b)
Reduction of imines
Much like nitriles, imines (C=N compounds) can be reduced with a good reducing agent like lithium aluminum hydride, LiAlH4 (LAH). The imine is like the nitrile, but it is already half reduced to the final primary amine. Once the hydride has attacked the carbon atom of the imine, H:-, followed by quenching with acid/water, an amine is formed.
It is a good reminder that carbonyl (C=O) compounds can react with amines, lose water, and form imines.
5. Draw the products of the following reactions.
a)
b)
Reduction of amides
Amides can also be reduced to amines. The C=O carbonyl of the amide can be reduced (making fewer carbon-oxygen bonds) to a methylene -CH2- with a strong reducing agent like lithium aluminum hydride, LiAlH4 (LAH) followed by quenching with acid water. Similarly, a hydrogenation using H2 and Ni catalyst can perform this reduction.
6. Draw the products of the following reactions.
a)
b)
Reduction of nitrobenzene
Aniline synthesis to set up the Sandmeyer reaction
We have already learned how to nitrate an aromatic ring with nitric and sulfuric acid. A reduction of a nitro group on an aromatic ring to an amino group with fewer nitrogen-oxygen bonds is accomplished by reducing it with iron filings and hydrochloric acid followed by hydroxide. The meta-directing nitro group is now an o,p-directing amino group. Remember that aminobenzene is commonly called aniline. Memorize this Fe, HCl reagent, but realize that you might encounter other reductions in the future (SnCl2/HCl or H2/Pt).
7. Show the two reaction steps needed to turn propyl benzene into 4-aminopropylbenzene.
Answers
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