Chapters 20 and 24 Flashcards
Describe how primary amines are named
Root name is based on the longest chain with the NH2
Number so the amine has the lowest possible number
Add -amine suffix
Describe how secondary amines are named differently than primary amines
The other alkyl group is treated as a substituent, with an N locant and is listed before numerical locant
N-propylamine
Describe how tertiary amines are named differently than primary amines
The other alkyl groups are treated as substituents with N as the locant and are listed before numerical locants
N-ethyl-N-methylpropanamine
What is the structure of aniline?
Benzenamine, phenylamine, amino benzene
NH2 directly attached to benzene ring
What is the structure of p-toluidine?
4-methylbenzylamine
NH2 and CH3 on benzene ring, directly across from each other
What is the structure of imidazole?
Five carbon ring, NH on top peak, N on bottom, double bonds on sides
What is the structure of pyrrole?
Five carbon ring, NH on top peak, double bonds on sides
How is amine basicity connected to the charge on nitrogen?
Increases with higher negative charge
conjugate base is always more basic
How is amine basicity connected to conjugation?
Conjugated amines are worse bases
Resonance in conjugate base to distribute the negative charge from donating
How is amine basicity connected to inductive effects?
Inductive effects decrease basicity
Remove electron density from conjugate base, stabilizing it
How is amine basicity connected to pi-donating or pi-accepting?
Basicity decreases when acting as a pi-donor
Significant resonance form where lone pairs on nitrogen form new pi-bond with carbon
Basicity is decreased when attached to pi-acceptor or meta director (as in inductive effects)
How is amine basicity connected to hybridization?
Lone pairs on SP hybridized nitrogens are the least basic, those on SP3 are the most basic
How does amine basicity compare to amide basicity?
Amides are far less basic
Lots of resonance stabilization in conjugate base
How do you make amines from ammonia? How do you control the substitution?
RX + NH3 → RNH2
Add excess RX for increased substitution
How do you make amines from NaN3? What are the two things it can react with initially? What is the intermediate? What are the four things it can then react with?
RX (or acid chloride) + NaN3 → RN3 + Na/EtOH (or LiAlH4 or H2/Ni or NaBH4) → RNH2
How can you convert a nitro group to an amine? What two things can it react with?
RNO2 + LiAlH4 (or H2/Ni) → RNH2
How can you convert an amide to an amine? Give the two methods and all possible reactants. (ignore named reactions)
Amide + LiAlH4 (or H2/Ni) → RNH2
Replaces the =O with hydrogens
OR
Amide + Very Strong Acid/Base → R2NH
Describe the two-step process of the first stage of Gabriel synthesis
Phthalimide + KOH + RX → Phtalimide with R instead of H, called an N-substituted phthalimide
Describe the two options for the second stage of Gabriel synthesis
N-sutstituted phalimide + NH2NH2 and EtOH/heat → RNH2
N-substituted phalimide + (1)H+/H2O/heat + (2)OH- → RNH2
How can you create amines from nitriles (CN)? What are the two options for reactants?
RX + NaCN → RCN + (1) LiAlH4/ether (or H2/Ni) + (2) H2O → primary amine
How can you create amines from aldehydes and ketones?
Add NH3 (1), RNH2 (2) or R2NH (3*) and source of H (such as NaBH4)
Replaces the =O with hydrogen and the reactant
Describe the Hoffman Rearrangement
Amide + (1) Br2/NaOH + (2) H2O → RNH2
R is from the other group attached to =O (Nh2 is the other one)
Remove =O and single bond other groups to each other
Describe the Curtius Rearrangement
Acid Chloride + (1) NaN3 + (2) heat + (3) H2O → RNH2
Amine + Formaldehyde → ? + (1)H+ (2)NaBH3CN → ?
Imine, RN(H)CH3 (replace an H with CH3)
Amine + HCl → ?
R3NH+ and Cl-
Primary or Secondary Amine + RX → ?
Add R, create + charge
Diisopropyl amine + n-BuLi → ?
LDA
R2NH + Acid Chloride or Ester or Acetic Anhydride or Carboxylic Acid → ?
R’C(=O)NR2
R2NH (2*) + NaNO2 (and acid) → ?
R2N-N=O
RNH2 (1*) + NaNO2 (and acid) → ?
RNN
What can RNN react with to produce alcohols, halogens (Cl, Br, I, F), and nitriles?
H2O for alcohols
CuCl, CuBr, Ki, HBF4/heat
CuCN
R2NH + ClSO2Ar → ? + (1)acid/base + (2)base/acid → ?
Sulfonamide R2NSO2Ar
Original R2NH
What are the four parts of an amino acid?
Amino group, hydrogen, R side chain, carboxylic acid group
Describe the structure of a peptide bond, its formation, and its destruction
also called amide bond, formed between carboxylic acid and amino group
during formation, water is lost and an amide functional group is formed
can be broken back down to amino acids by acid and water
Describe “zwitterions” in relation to amino acids
At physiological (near neutral) pH, the amine group will tend to bind a protein, becoming negatively charged and the acid group will tend to donate its proton, becoming negatively charged This produces a “zwitterion” where the amino group resembles NH3+ and the carboxylic acid group resembles COO_
How do you determine R/S chirality? (rectus and sinister)
Identify the chiral carbon
Rank substituents by atomic number
Lowest in the back, trace highest 3
Clockwise is R, counterclockwise is S
How do you determine L/D chirality? (laevus and dexter)
Place amino acid in Fischer projection with carbonyl at the top and R at the bottom
If the amine is to the left and the H is to the right, it is L
If the amine is to the right and the H is to the left, it is D
How can you convert a 3D configuration to a Fisher configuration?
The easiest way is guess and check
Place the R on the bottom and the carboxyl on top, and guess for amine vs H
Check to see if it has the correct R/S designation
If so, it’s correct, you can see what side the amine is on
If not, it’s incorrect, group swap amine and hydrogen
Which amino acids are L (opposed to D) and which amino acids are S (opposed to R)?
All amino acids are L
All amino acids except for cystine have an S configuration
**All L amino acids are S except for cystine, which is R
Describe neutral amino acids
In the zwitterion form, both the amine and the carboxylic acid are neutralized, so the amino acid is neutral unless there is an extra acid or base
Amino acids with an amide on the side chain are not basic
Tryptophan is neutral due to two rings
Neutral amino acids can be either polar or nonpolar
Describe how to determine the polarity of neutral amino acids
more alkyl groups is less polar
What are the acidic amino acids? How can you tell?
Aspartate and Glutamate
R side chains contain carboxylic acids that are acidic enough to lose their protons
What are the basic amino acids? How can you tell?
Arginine, Lysine, and Histidine
Side chains contain amine’s whose pKa’s are high enough that they tend to bind protons
How can you make amino acids with a modified form of gabriel synthesis? You will start with potassium phthalimide and diethyl bromomalonate.
→ N-substituted phthalimide + base → Negatively Charged + 1. RBr + 2. NaOH/H2O/heat + 3. Acid/Heat → Amino Acid
How can you make amino acids using Strecker synthesis?
Aldehyde + Ammonia + HCN + (2)H2O → AA
Describe how to add and remove a Z protecting group
Benzyl chloroformate
Produces a Benzyloxycarbonyl or “Z” protecting group (base catalyst)
Can be removed by strong acids or hydrogenolysis with H2/Pd
Describe how to add and remove a Boc protecting group
Di-tert-butyl dicarbonate (Boc2O)
Produces a “Boc” protecting group (base catalyst)
Can be removed by an acid like HCl or CF3CO2H (trifluoroacetic acid)
Describe how to synthesize peptides using SOCl2
Take an amino acid and add a protecting group, then add PCl5 or SOCl2
Add another protected amino acid, producing a protected dipeptide
Remove the protecting group by “deprotection” to produce the dipeptide
Describe how to synthesize peptides using (1)Et3N (2)ClCO2Et
Take an amino acid and add a protecting group, then add 1)Et3N (2)ClCO2Et
Add another amino acid, producing a protected dipeptide (and CO2/EtOH)
Remove the protecting group by “deprotection” to produce the dipeptide
What is the structure for alanine (Ala,A)?
methyl R group
What is the structure for glycine (Gly,G)?
hydrogen R group
What is the structure for phenylalanine (phe,F)?
CH2-Benzene ring R group
What is the structure for histidine (his, H)?
CH2-ring
5-member ring has N on the other bottom corner, double bonds up the sides, and NH on the peak
What is the structure for lysine (lys,K)?
CH2-CH2-CH2-CH2-Amine R group
What is the structure for serine (ser, S)?
CH2-OH R group
What is the structure for cysteine (cys, c)?
CH2-SH R group
What is the structure for aspartic acid (asp, D)?
CH2-carboxylic acid R group
What is the structure for glutamic acid (glu, E)?
CH2-CH2-Carboxylic acid R group
What is the structure for tyrosine (tyr, Y)?
CH2-Ph-OH R group
What is the structure for valine (val, V)?
isopropyl R group
