A to Z Directory – Virginia Commonwealth University
Chapter 19 – Amines
• Nomenclature
o Classification of amines
▪ Amines are classified as 1°, 2°, or 3° based on how many R groups are attached to the nitrogen
[pic]
▪ When there are four R groups attached to a nitrogen, it is called a quaternary ammonium salt.
o Common names
▪ Say the alkyl groups attached and then say “amine”
[pic]
o IUPAC names
▪ Find the longest carbon chain with the nitrogen attached.
[pic]
▪ Name that as the parent, remove the –e, and replace it with amine
• Heptane → 3-heptanamine
▪ Whatever else is on the nitrogen is named as a substituent, with N as the locant.
N-methyl-3-heptanamine
▪ If the amine is not the high-priority group, then the nitrogen is named as an amino substituent.
[pic]
5-amino-N-methyl-2-heptanol
• Structure of amines
o Trigonal pyramidal
o Chirality
▪ Amines can be chiral, but the lone pair flips from side to side of the nitrogen, changing them from R to S.
▪ There are two times when chirality is locked.
• Quaternary ammonium salts
• Sometimes sterics can prevent the lone pair from flipping.
• Physical properties
o Strongly polar
o Can hydrogen-bond if they are 1° or 2°
▪ Remember that the hydrogen bonding of nitrogen is not as strong as that with oxygen, so boiling points will be lower than similarly sized alcohols.
o Small amines will be water-soluble. Larger ones will not.
• Basicity of amines
o The pKb of ammonia is 4.74.
o Amines are slightly stronger bases because the alkyl groups are electron donating groups, as we have seen in previous chapters.
▪ Amines have pKb’s around 3-4.
▪ Aniline has a pKb around 10 because the lone pair is conjugated with the aromatic system.
[pic]
▪ Pyridine also has a pKb around 10, because the lone pair is less available in the sp2 orbital than it would be in a sp3 orbital.
▪ Pyrrole is even less basic, with a pKb around 16, because its lone pair is involved in aromaticity.
o EDGs will increase basicity, while EWGs will decrease basicity.
o My weird way of thinking about basicity:
▪ The lone pair of a base is like teeth that want to bite a proton.
▪ The bigger the teeth, the stronger the base.
▪ EDGs make the teeth bigger, EWGs suck the teeth back into the gums.
▪ When the teeth are involved with aromaticity, that’s like they’re already chewing something, so they’re not available to bite a proton.
• This is why pyrrole has a pKb around 15.
▪ When the teeth are in sp2 orbitals, they are held closer in to the mouth, and aren’t as available.
• This is why pyridine has a pKb of 8.75
• Amine salts and extraction
o By protonating an amine, you make it more water-soluble.
o Mr. Baker likes to ask questions about what would be left in the organic or aqueous layer after adding either an acid or base.
▪ If on a test or quiz he doesn’t specifically say that you drain off the aqueous phase, make sure to ask.
▪ Below, you are not draining in between.
[pic]
o Here’s an example with draining in between. Remember that he can change up when you drain, which would change the answer.
[pic]
• Phase transfer catalysts
o Large 4° ammonium salts are somewhat soluble in both organic and aqueous phases. As such, they can move ionic reagents into the organic phase so that they can react.
o Crown ethers also make good phase transfer catalysts.
• Substitution of aniline
o In chapter 17 we said that NH2 was a strong ortho-, para-director, but is it?
[pic]
▪ All the electrophilic aromatic substitution conditions were acidic, so the nitrogen would become positive, and thus now a meta-director.
[pic]
• You need to protect the –NH2, often by acylating it.
[pic]
▪ That said, when aniline is not protonated, it is a strong ortho-, para-directing activator.
• In fact, it’s so active that you can halogenate without the metal Lewis-acid catalyst.
[pic]
• Alkylation of amines by alkyl halides
o Just SN2 followed by deprotonation.
[pic]
o The problem with this reaction is that it’s difficult to control how many alkyl groups add.
▪ This works if you want a 4° ammonium salt.
▪ This also works if you add excess ammonia, so that you get one addition.
• Acylation of amines by acid chlorides
o This is a nucleophilic substitution at the carbonyl
[pic]
o The acid chloride is more reactive than ketones and aldehydes, and amines are not nucleophilic enough to add to the amide formed in the substitution.
o Acylating aniline is a way to maintain the ortho-, para-directingness of the –NH2 and the acyl group is easily removed by acid hydrolysis.
[pic]
• Formation of sulfonamides
o Just like Acylation, but with sulfonyl chlorides
▪ Is it me, or did all the colors make this one exciting?
[pic]
• Hofmann Elimination
o An E2-like reaction where 4° nitrogen is the leaving group, and you get the less-substituted alkene.
▪ First, excess of an alkyl halide (usually CH3X) is added to give quaternary ammonium salt.
[pic]
▪ Then, a strong base abstracts a proton to give a carbanion intermediate.
[pic]
• This carbanion intermediate explains why you get the anti-Zaitsev product with Hoffman elimination.
▪ Elimination occurs to expel the amine, giving an alkene product.
[pic]
o Sometimes Ag2O (aq) is the base used.
▪ It generates O2-, to a small extent.
• This is the conjugate base of hydroxide. Yikes!
▪ But remember that because it’s aqueous, it just deprotonates the water, forming hydroxide.
• You cannot have a base stronger than hydroxide in an aqueous environment.
o For those of you going on to take inorganic, you’ll see that this is called “solvent leveling.”
• Diazonium salts
o Formation
▪ Reaction of HNO2 (nitrous acid) with 1° alkyl amines
• Often formed in situ with NaNO2 with HCl
[pic]
▪ Reaction of HNO2 with aryl amines
[pic]
• The last step of the N2 gas falling off doesn’t happen because the aryl cation would be unstable.
o Reactions of aryl diazonium salts
▪ You don’t need to know any mechanisms here.
[pic]
o Now we can do even more synthesis!
[pic]
• Step 1:
[pic]
• Step 2:
[pic]
• Step 3:
[pic]
• Step 4:
[pic]
• Step 5:
[pic]
• Step 6:
[pic]
• Step 7:
[pic]
• Step 8:
[pic]
• Synthesis of amines by acylation-reduction
o Just what it sounds like
o Acylate
o LiAlH4 completely chops off the oxygen of an amide instead of reducing the carbonyl to an alcohol
• Gabriel synthesis – always makes 1° amines
o Phthalimide is deprotonated by a strong base
▪ The pKa is 8.3.
[pic]
o The anion is a good nucleophile (but weak base) which performs an SN2 on a suitable alkyl halide or tosylate.
[pic]
o Hydrolysis gives you the amine
[pic]
• Reduction of azides and nitriles
o Once an azide has been used as a nucleophile in an SN2 reaction, it can be reduced to the amine by either LiAlH4 or catalytic hydrogenation.
[pic]
Nitriles are also reduced to the amine by the same conditions.
[pic]
▪ Be sure not to lose a carbon here.
• Reduction of nitro groups to NH2
o LiAlH4
o Catalytic hydrogenation
o Fe, Zn, or Sn in acid
• Removing the oxygen from amides to form amines
[pic]
• Hoffman rearrangement
o 1° amide + bromine or chlorine in base → amine where the whole carbonyl is gone.
[pic]
o You are not responsible for the mechanism.
................
................
In order to avoid copyright disputes, this page is only a partial summary.
To fulfill the demand for quickly locating and searching documents.
It is intelligent file search solution for home and business.
Related download
- the alkane a homologous series
- organic chemistry
- summary of alcohol syntheses ch
- lecture 1 key concepts in stereoselective synthesis
- nomenclature of organic compounds
- a to z directory virginia commonwealth university
- unit 3 organic chemistry
- type content here font arial size 12
- chemical nomenclature
- chapter 13 introduction to organic chemistry and