Amines Flashcards
What are five aspects of amine chemistry on Test 8?
- Nomenclature
- Structure and physical properties
- Preparation
- Reactions
- Diazonium salts (preparation, reactions)
What are three general “forms” of amines?
- alkyl amines
- aryl amines
- heterocyclic amines
What are four “classes” of amines?
- primary
- secondary
- tertiary
- quaternary salts
How do you name a primary amine? (two methods)
- named as alkyl amines
2. named by dropping e ending and adding amine to hydrocarbon name
How do you name a secondary or tertiary amine?
named as N-substituted derivatives of primary amine (ex. N,N-dimethyl-1-propanamine)
How do you name a quaternary salt?
named as substituted ammonium ions (ex. isopropylamine -> isopropylammonium bromide)
How do you name an aryl or heterocyclic amine?
Special, common names
Draw the structure for aniline
Benzene with NH2 substituted
Draw the structure for sulfanilic acid
Benzene with NH2 and SO3H para substituted
Draw the structure for anthranilic acid
Benzene with NH2 and COOH ortho substituted
Draw the sturcture for p-toluidine
Benzene with CH3 and NH2 para substituted
Draw the structure for anisidine
Benzene with NH2 and OCH3 para substituted
Draw the structure for phenetidine
Benzene with NH2 and OCH2CH3 ortho substituted
What are four aromatic heterocyclic amines?
- pyridine
- pyrrole
- imidazole
- indole
What are two not-aromatic heterocyclic amines?
- piperidine
2. pyrrolidine
Draw the sturcture for pyridine
Benzene with sp2 nitrogen (no H) substituted for one of the carbons
Draw the structure for pyrrole
Five-membered ring containing one sp3 nitrogen; double bond alternating between carbons (lone pair on nitrogen continues conjugation)
Draw the structure for imidazole
Five-membered ring containing two nitrogen at 1,3 position; nitrogen at 3 position is sp2 hybridized (it doesn’t have an H)
Draw the structure for indole
Two ring systems [6-member and 5-member sharing 2 carbons]: a benzene ring with an “N-C=C” attached to carbons in 1 and two position. Essentially benzene + pyrrole.
Draw the structure for piperidine
Cyclohexane with sp3 nitrogen (has an H) substituted for one of the carbons.
Draw the structure for pyrrolidine
Cyclopentane with sp3 nitrogen (has an H) substituted for one of the carbons.
What structural feature is responsible for amine boiling point trends?
Polarity of bonds with N
What is the boiling point trend for primary, secondary and tertiary amines?
primary > secondary > tertiary (more Hs = more hydrogen bonding)
Amines have comparable boiling points to what other functional groups?
Aldehydes and ketones.
What is the solubility trend for amines? (2 components)
- Amines with less than 6 carbons tend to be soluble in H2O
2. amine salts are water soluble
The lone pair on nitrogen in an amine gives it what important chemical property?
Base/nucleophile
What are three factors affecting the basicity of an amine?
- resonance
- electron donating/withdrawing groups
- orbitals
How does resonance affect the basicity of an amine?
Resonance stabilization will stabilize the lone pair and make amine less basic.
How does electron donating/withdrawing groups affect the basicity of an amine?
Electron donating groups will make nitrogen more electron rich and make it less stable (a stronger base).
Electron withdrawing groups will make nitrogen less electron rich and make more stable (a weaker base).
How do orbitals affect the basicity of an amine?
More s-character in the hybridization (i.e. Sp2 > Sp3) will make lone pair more stable (less basic).
How is the acidity of ammonium salts related to the basicity of amines?
An amine that is a stronger base has an ammonium salt (conjugate acid) that is a weaker acid.
What are four important nitrogen-containing functional groups?
- Amines
- Amides
- Imines
- Enamines
What is an amine?
A substituted ammonia derivative
What is an amide?
A carboxylic acid derivative with an amine nitrogen adjacent to the carbonyl carbon.
What is an imine?
Nitrogen-containing analogue of ketones (C=O is replaced with C=N-)
What is an enamine?
A nitrogen-containing analogue of enols (amine nitrogen bonded to an sp2 carbon)
What are two special types of imines?
- Oxime
2. Hydrazone
What is an oxime?
An imine where the group single-bonded to N is hydroxyl.
What is a hydrazone?
An imine where the group single-bonded to N is an amine nitrogen.
What are the reactants for alkylation of amines?
Ammonia (or primary, secondary amine) with an alkyl halide.
Why is alkylation of amines not a good method to make amines?
Multiple alkylations will result in quaternary salt.
How can the issue with alkylation of amines be minimized?
Use a very high concentration of NH3 so that it reduces the likelihood multiple substitutions.
What are four ways to prepare an amine?
- Gabriel synthesis
- Reduction of Nitrogen containing compounds
- Reductive amination
- Hofmann rearrangement
What class of amines can be made from gabriel synthesis?
Primary amines
What class of amines can be made from reduction of nitrogen containing compounds?
- aromatic nitro groups: primary
- Nitrile: primary
- Azide: primary
- Amides: primary, secondary and tertiary (corresponding to amide used)
What class of amines can be made from reductive amination? (3 starting compounds)
- ammonia: primary
- Imine: secondary
- Enamine: tertiary
What class of amines can be made from Hofmann rearrangement?
Primary amines
What are the reagents used in Gabriel synthesis?
1) Alkyl halide + Phthalimide
2) hydrazine
Predict the product in a Gabriel synthesis
Primary amine with the same alkyl group as alkyl halide.
Draw the structure for Phthalimide
Benzene with two acyl carbons sharing a common nitrogen
Draw the structure for Hydrazine
H2N-NH2
What are four nitrogen containing compounds that can be reduced to form amines, and what are their structures?
- aromatic nitro groups: ph-NO2
- Nitriles: -CtriplebondN
- Azides: -N=N+=N-
- Amides: -CONR2
What reagents will reduce an aromatic nitro group? (2 options)
- Metal catalyst (Sn), Hcl
2. Pd-C/H2
What reagents will reduce a nitrile to an amine? (2 options)
- LiAlH4
2. Pd-C/H2
What reagents will reduce an azide to an amine? (2 options)
- LiAlH4
2. Pd-C/H2
What reagents will reduce an amide to an amine?
LiAlH4
Describe the process of reductive amination
Primary or secondary amine is added to an aldehyde or ketone to form an imine or an enamine; product is reduced with NaCNBH3 to form secondary or tertiary amine.
Predict the product of an aldehyde/ketone with a primary amine
Imine: replace =O with =N-R where the alkyl group comes from primary amine.
Predict the product of an aldehyde/ketone with a secondary amine
Enamine: replace =O with -N(R2) where alkyl groups come from secondary amine; remove a hydrogen from an alpha carbon to form a double bond. (Remember, the amine nitrogen is on an Sp2 carbon; analogue to enol)
Predict the product of an imine in water.
Hydrolyze imine to aldehyde/ketone and primary amine.
Predict the product of an enamine in water.
Hydrolyze enamine to aldehyde/ketone and secondary amine.
What reagents can be used to reduce an imine or an enamine to a secondary/tertiary amine? (2 options)
- Sodium cyanoborohydride (NaCNBH3)
2. NaBH(OAc)3
Describe the Hofmann rearrangement process
A primary amide is treated with NaOH and Br2 to form a primary amine.
Predict the product for a Hofmann rearrangement reaction
Remove the C=O from primary amide (the hydrocarbon chain decreases by 1 carbon in product)
What are two important reactions of amines?
- Hofmann elimination (of ammonium salts) to form an alkene
2. Formation of diazonium salts
Describe the Hofmann elimination process to form an alkene from an amine (two steps)
- Amine is converted to a quaternary salt by exhaustive alkylation (treatment with CH3I)
- Quaternary salt is heated with Ag2O; amine nitrogen leaves and an alpha hydrogen is removed to form the least stable (less substituted) alkene.
Why does the Hofmann elimination process form the least stable alkene?
The transition state has carbanion-like character; increased branching will add electron density (hyperconjugation) and increase instability.
