Chapter 19 Flashcards
Nitrogens that are a part of a ring are called _______, that are an important group of biologically active amines (drugs)
alkaloids
Amines are classified by counting how many _______ groups are attached to the N
alkyl
1) NH3 =
2) R-NH2 =
3) R2-NH =
4) R3-N =
5) R4-N+ =
1) ammonia
2) 1° amine
3) 2° amine
4) 3° amine
5) ammonium salt
Common nomenclature of amines:
name the groups attached to N as _______ followed by the suffix _______
substituents
amine
IUPAC: in amines with more complicated structures, where the NH2 group is a substituent it is called _______
amino
- When there is a functional group with a higher root priority
IUPAC: 2° and 3° amine substituents are named by classifying the N atom as an alkylamino group. The _______ or _______ complicated alkyl group is taken to be the parent molecule (root)
largest
more
- use when other functional group is present on root with higher priority
IUPAC: In aromatic amines, the amino group is bonded to a benzene ring. The parent compound is called _______
aniline
IUPAC: When naming a heterocylic amine, the N is assigned position number _____
1
ex) in pyridine
IUPAC: simple amines are named like alcohols but with _______ ending
amine
- for 1° amines with only C on root
IUPAC: the substituents (not main chain) of more complicated amines are given the number for their location of _____
N
- ex) N,2-dimethylcyclopentamine
- use when only C’s are present on root
Nitrogen is Sp3 hybridized with a lone pair of electrons resulting in an angle _______ than 109.5
less
Nitrogen may have 3 different groups and a lone pair, but enantiomers cannot be isolated because they _______ rapidly. This is known as _______
interconvert
nitrogen inversion
What are the 3 scenarios when chiral amines can be resolved into enantiomers?
1) when on a chiral carbon
2) when quaternary ammonium salt with asymmetric nitrogens
3) when nitrogen is a part of a restricted ring (3C & 4C) thats not meso
N-H bond is _______ polar than O-H bond
less
1° and 2° amines are hydrogen bond _____ and _____. They have weaker hydrogen bonds and _______ boiling points than the corresponding alcohols
donor
acceptor
lower
3° amines are hydrogen bond _______ only, which = ________ boiling points than primary and secondary amines
acceptor
lower
All amines form hydrogen bonds with hydroxylic solvents, such as water and alcohol. Therefore, amines tend to be _______ in alcohols and water. Amines also have the characteristic odor of rotting fish
soluble
An amine is a _______ (_______) because its lone-pair of nonbonding electrons can form a bond with an electrophile
nucleophile
Lewis base
An amine can also act as a _______ by accepting a proton from a proton acid
bronsted lowry base
Amines are strongly _______ and can abstract a proton from water. The equilibrium constant for this reaction is called the base dissociation constant (_____), which is used to measure the strength of the amine
basic
Kb
Strong bases = _______ pKb and _______ pKa values
small
large
- mainly use pKa so universal
What are the 3 things that affect amine basicity?
1) Resonance
2) substitution by alkyl groups
3) hybridization
- this is the order to determine
Rank NH3, 1°, 2°, 3° amine basicity based on substitution by alkyl group (EDG) and solvation effect
NH3 < 1° = 3° < 2°
- EDG’s stabilize positive charge
- 3° R blocks solvent that would stabilize + charge
Resonance = _______ basic
less
- breaking aromaticity is worse than breaking conjugation
Hybridization: electrons are held more tightly by orbitals with more _______ character making them a weaker base
S
- Sp3 better base than Sp2 and Sp
Because -NH2 is a strong activator and op-director, reaction with Br2, NaHCO3 will result in _________ substitutions
multiple
- EAS
Protonation of the amine under acidic conditions converts the group into a strong _______ (_____)
strong deactivator (R-NH3+)
- Can lead to formation of TNT
EAS of pyridine:
1) strongly _______ toward electrophilic attack
2) substitutes in the _______ in a manner analogous to the m-substitution
1) deactivated
- no Friedel-crafts
2) 3-position
- ex. SO3H to aniline is added at 3 position
NAS of pyridine:
pyridine is deactivated toward EAS attack, but it is ______ toward Nucleophilic aromatic substitution
activated
In NAS of pyridine, nucelophile will replace a good leaving group in the _____ or _____ position
2-
4-
Ammonia and alkyl amines are good nucleophiles, but these reactions don’t stop cleanly after a single addition.
1) with excess amine, you get ______
2) with excess alkyl halide you get _______
1) 1° amine
2) 4° amine (ammonium salt)
Both 1° and 2° amines will undergo acylation reactions to form _______
amide
- proceeds by nucleophilic acyl substitution mechanism
Amides are _______ basic and _______ nucleophilic than amines because of resonance structures
less
less
- allows it to be a good protecting group
Amides can be used as protecting groups to prevent _______ and allow _______
polysubstitutions
friedel-crafts reactions (to para position)
Under acidic conditions, what are the reagents for hydrolysis to remove the amide-protecting group?
H3O+
Under basic conditions, what are the reagents for hydrolysis to remove the amide-protecting group?
NaOH, H2O
Hoffman elimination converts an amine to alkene by _____ elimination
E2
Because -NH2 and -NHR are poor leaving groups, they need to be converted into better leaving groups via _______
exhaustive methylation
- creates ammonium salt, which is a good leaving group
- Always use CH3I in hoffman elimination
What reagents are needed to create the base -OH for Hoffman elimination?
Ag2O, H2O, Δ
Hoffman elimination gives the _______ substituted double bond and eliminates the _______ H with respect the the LG Nitrogen
less
anti
What are the reagents needed for cope oxidation?
any peroxy-acid + heat
- ex H2O2 or mCPBA
Cope oxidation:
2° amines oxidize to _______
hydroxylamine (–NOH)
Cope oxidation:
3° amines oxidize into _______ often in good yields
amine oxide (R3N+–O-)
The N-oxide can undergo _______ to form alkenes in a reaction analogous to the Hoffman elimination
elimination
- syn elimination and intramolecular
Arene diazonium salts are useful synthetic intermediates. _____ is readily replaced by different nucleophiles
N2+
Reaction of amines with nitrous acid:
1) _______
2) _______ the nitro group
3) Generation of _______ salt
4) _______ replacement
1) nitration
2) reduce
3) Diazonium
4) nucleophile (can vary)
What reagents are needed to go from amine group to diazonium group?
NaNO2, H2SO4
The _______ reaction uses reagents such as:
1) Ar-Cl
2) Ar-Br
3) Ar-CN
Sandmeyer (Cu)
For all diazonium salt reactions check quizlet
https://quizlet.com/1025427418/reactions-of-amines-with-nitrous-acid-diagram/?i=1ha23w&x=1jqt
_______ is the most general synthesis for amines, capable of adding a 1° or 2° alkyl group to an amine
reductive amination
What are the 2 steps for reductive amination?
1) form imine or oxime
- imine for 2° product and oxime for 1° product
2) reduce the amine
- have to start with aldehyde or ketone
What reagents are used to reduce an imine or oxime to 1° or 2° amine in reductive amination?
Reducing reagents:
H2/Ni
LiAlH4, H2O
NaBH(OAc)3
How many steps are in the reduction amination for 3° amine product?
1 step
- For the formation of 3° amines, condensation of a ketone or aldehyde
What are usually the reagents for reduction amination for a 3° amine product starting from a ketone or aldehyde?
any 2° amine
NaBH(OAc)3
CH3COOH
In acylation-reduction, the added alkyl group is always _____ because the C bonded to the N is derived from the carbonyl group of the amide which is reduced to a _______ group
1°
CH2 (methylene)
What are the steps, with reagents, to acylation reduction?
1) acylation
- needs pyridine or NaOH in addition to the acid chloride because it will neutralize the acid
2) reduction
- always use LiAlH4
Ammonia and 1° amines are very reactive and can lead to over alkylation, to avoid this problem, use the reagent _______ to make 1° amines
pthalimide
- Gabriel synthesis
- forms 1° amines
When using gabriel reagent, _______ is used to activate it, and _______ is used to unmask the reagent
-OH
2 eq NH2NH2, Δ
Two good nucleophiles for introducing a N atom are the _______ and _______ ion
azide (-N3) and cyanide (-CN) ion
addition of an azide introduces a _______ group after reduction, while addition of a Cyanide ion introduces a _______ group after reduction
NH2
CH2NH2
- cyanide ion is good for adding amine and one carbon
To reduce nitro to amine use:
1) H2/ Pd
or
2) clemmenson
- 1) (Fe or Sn or Zn), H3O+
2) NaOH
