Exam 4 Flashcards
Formic Acid
Acetic Acid
Propionic Acid
Butyric Acid
Valeric Acid
Benzoic Acid
Acrylic Acid
Oxalic Acid
Malonic Acid
Succinic Acid
Maleic Acid
Phthalic Acid
Carboxylic Acid
Common Nomenclature
Name substituents with alpha, beta, gamma, delta, etc.
Carboxylic Acid
IUPAC Nomenclature
Highest Priority:
suffix = -oic acid
branch = -carboxylic acid
Carboxylate Salt
Nomenclature
- List complexed salt first
- Replate -ic acid with -oate
Acidity of Carboxylic Acids
EWG’s on α-C increase acidity of molecule,
but drops off quickly with distance
Acid-Base Extraction
Add sodium hydroxide to create the carboxylate salt that stays in the aqueous layer, while the other organic molecules are removed in the ether layer, and recreate the carboxylic acid solid by adding hydorchloric acid.
Mass Spectrometry
McLafferty Rearrangment
Peak around 60 m/c that’d indicitive of a carboxylic acid
Primary Alcohol
to
Carboxylic Acid
Reagants:
Warm, conc. Na2Cr2O7 / H2SO4
Aldehyde
to
Carboxylic Acid
Reagants:
Br2 / H2O or Ag(NH3)2OH
Alkene
to
Carboxylic Acid
Reagents:
Warm, conc. KMnO4
Alkyne
to
Carboxylic Acid
Reagents:
1) O3, 2) H2O
Alkyl Bromide
to
Carboxylic Acid
Reagents:
1) Mg°, 2) CO2, 3) HCl
Carbons with a +3 Oxidation
to
Carboxylic Acid
Reagents:
H3O+ / Δ
Methyl Benzene
to
Carboxylic Acid
Reagents:
Warm, conc. Na2Cr2O7 / H2SO4
Fischer Esterification
Reagents:
Carboxlyic acid + primary alcohol
0.1 eq. p-TsOH
**Not highly favored, 60:40, but more favored when the carboxylic acid and alcohol are on the same molecule **
Indirect Esterification
Reagents:
Carboxylic acid
1) SOCl2, 2) Primary Alcohol
Diazomethane Esterification
Reagents:
Carboxylic Acid
1) CH2N2 (diazomethane)
**Advantages: high yield, clean reaction: Disadvantages: limited to methyl esters, limited to small scale**
Direct Amidation
Reagents:
Carboxylic Acid
1) Primary amine / Δ / H2O (steam)
**Acid/base reaction competes**
Indirect Amidation
Reagents:
1) Carboxylic acid + SOCl2
2) Secondary amine
Reducation of Carboxylic Acids
Reagents:
1) LAH (strong reducing agent)
2) HCl(aq)
Partial Reduction of Carboxylic Acids
Reagents:
Carboxylic Acid → Aldehyde
1) CH2N2, 2) DIBAL-H, 3)H3O+
or
1) SOCl2, 2)LiAl(t-Butyl oxide)3H
Selective Reduction of Carboxylic Acids
Reagents:
Oxo Carboxylic Acid → Hydroxy Ketone
1) BH3•THF, 2) HCl
Alkylation of Carboxylic Acids
Reagents:
Carboxylic acid → Ketone
1) 2 eq. CH3Li, 2) H3O+
or
1) SOCl2, 2) (CH3)2CuLi
Ester
to
Carboxylic Acid
Reagents:
1) NaOH / H2O / HOEt, 2) HCl
What is a derivative of a carboxylic acid?
Functional groups that have a carbon in a +3 oxidation state
(A carbon with three bonds to a non-carbon atom, ex: O, N, X)
Reactivity of Carboxylic Acid Derivatives
Acid Chloride
Nomeclature
Replace -ic acid with -yl chloride
Anhydride
Nomeclature
Replace -acid with -anhydride
Unsymmetrical andyrhides: name each carboxylic acid equivalent in alphabetical order, then add -anhydride to the end
Anhydride
to
Carboxylic Acid w/Ester
Reagents:
ROH
Esters
Nomenclature
Add alkyl group as branch name to beginning of the name, then replace -ic acid with -ate
Cyclic Ester (Lactones)
Nomenclature
IUPAC: Add lactone to the end of the carboxylic acid name
Common: Remove hydroxy, then replace -ic acid with -o lactone
Amide
Nomenclature
Replace -oic acid / -ic acid with -amide and indicate branches off of the N with N/N’-
Cyclic Amide (Lactams)
Nomenclature
IUPAC: Add lactam to the end of the carboxylic acid name
Common: Remove amino and replace -ic acid with -olactam
What are significant structural features of amines?
1) Roational barrier between O=C-N bond: caused by the significant double bond character from -O-C=N+ resonance structure.
2) The oxygen is more acidic than the nitrogen, so the oxygen will be protonated first.
3) The hydrogen on the nitrogen is most acidic, so the nitrogen will be deprotonated first.
Nitrile
Nomenclature
IUPAC: Add nitrile to base alkane name
Common: Replace -ic acid with -o nitrile
Primary Amide
to
Nitrile
Reagents:
P(O)Cl3 or P2O5
Nomenclature for Groups Off a Ring
Nucleophilic Acyl Substitution
with
Strong Electrophile + Weak Nucleophile
Strong E+: acid chlorides, anhydrides
Weak Nu-H: H2O, ROH, RNH2
Nucleophilic Acyl Substitution
with
Weak Electrophile + Strong Nucleophile
Weak E+: Ester, amide
Strong Nu-: -OH, -OR, -NR2
Nucleophilic Acyl Substitution
with
Weak Electrophile activated by H+ + Weak Nucleophile
Weak E+: Acid chlorides, anhydrides
H+: p-TsOH
Weak Nu-H: H2O, ROH, HNR2
What is suprising about the bp trends of the carboxylic acid derivates?
1) Nitriles and primary alcohols have similar bp (nitriles slightly higher than alcohols) even though nitriles cannot hydrogen bond.
2) Tertiary amides being higher than alcohols, nitrils, and acids even though they cannot hydrogen bond. Shows significance of its resonance structure with a significant dipole moment over the O=C-N bonds
Why are thioester more reactive than esters?
They have poor pi bond overlap because of the longer C-S bond length
Carboxylic Acid
Reduced to
Primary Alcohol
Reagents:
1) LAH, 2) H3O+ or 1) BH3, 2) H3O+
Ester
Reduced to
Primary Alcohol
Reagents:
1) LAH, 2) H3O+
Ester
Reduced to
Aldehyde
Reagents:
1) DIBAL-H, 2) H3O+
Acid Chloride
Reduced to
Aldehyde
Reagents:
LiAl(t-Butyl oxide)3H
(mild hydride donor)
Amide
Reduced to
Amine
Reagents:
1) LAH, 2) H2O
Nitrile
Reduced to
Primary Amine
Reagents:
1) LAH, 2) H2O or H2/Pd
Nitrile
Reduced to
Ketone
Reagents:
1) CH3MgBr, 2) H3O+
Ester
Reduced to
Tertiary Alcohol
Reagents:
1) 2 eq. RMgBr, 2) H3O+
What is a carbonic acid derivative?
Any carbon center with a +4 oxidation center
Carbonic Acid
Carbonate
Nomenclature
List the R groups in alphabetical order, followed by carbonate
Carbamate / Urethane
Nomeclature
List the alkyl group attached to the oxygen, then name the nitrogen branches with the prefix N-
IUPAC: End name with carbamate
Common: End name with urethane
Urea
Nomeclature
Name the alkyl groups off the nitrogens with the prefixes N, N’- giving the most substituted nitrogen N
End the name with urea
Carbonic Acid Derivatives
Starting Materials
Method of Carbomate and Carbamate Synthesis
via Phosgene / Triphosgene
Isocyanate Synthesis
Carbamate Synthesis
Via Isocyanate
Urea Synthesis
Via Isocyanate
α - Substitution
C center with +2 oxidation state tautomerizes to enol, which acts as a nucleophile to add an electrophile to the α-carbon
Acid-Catalyzed Enol Formation
Base-Catalyzed Enol Formation
Enol Derivative
Reactivities
Acidity of Alcohol
16
Acidity of Ketones
19
Acidity of Esters
24
**Oxygen acts as an EDG, so it makes the α-hydrogen less acidic**
Acidity of Amines
38
**LDA is an amine, which is why it’s such a good base**
Acidity of Ethyl Acetoacetate
11
**More acidic than esters because of the second carbonyl = 3 resonance structures**
Acidity of Diethyl Malonate
13
**Less acidic than ethyl acetoacetate because of both oxygens, but more acidic than esters because of 3 resonance structures**
Acidic Halogenation of Carbonyls
(α-Substitution)
Acidic conditions favor monohalogenation because first Br makes the enol less nucleophillic (more acidic) than the unsubstituted enol
**Excess reagents will polyhalogenate**
Basic Halogenation of Carbonyls
(α-Substitution)
Basic conditions favor polyhalogenation because the monosubstituted enol is more acidic than the unsubstituted enol
Haloform Reaction
**Iodoform commonly used as a methyl ketone test**
Brominating Carboxylic Acid
Reagents:
1) PBr3 / Br2, 2) H2O / Δ
**PBr3 turns the -OH into a -Br**
Direct Alkylation of Enolate Ions
Reagents:
Ketone
1) LDA, 2) R-X
**E2 and aldol condensation compete with this reaction**
Stork Enamine Alkylation
Reagents:
Aldehyde or Ketone
1) HNR2, 2) R’-X, 3) H3O+
Alkylation of β-dicarbonyl compounds
Reagents:
Acetoacetic ester or Malonate ester
1) NaOEt, 2) R-X, 3) H3O+ / Δ
**Loss of CO2 indicated by [1,3] dicarbonyls after initiation acid hydrolysis**
Acid Hydrolysis
Reagents:
H3O+ / Δ
Aldol Condensation Reaction
Reagents:
2 Aldehydes or 1 Aldehyde + 1 Ketone
NaOH / H2O / HOR
**Product typically dehydrates under basic and acidic conditions**
Claisen Ester Reaction
Reagents:
2 Esters
1) NaOEt, 2) H3O+
**Remember to neutralize basic conditions with Step 2 in mechanism!**
Dehydration of Aldol in Basic Conditions
Dehydration of Aldol in Acidic Conditions
Well Designed Aldol Condensation
Nucleophile with one α-C group
Electrophile with no α-C group
Cyclic Aldol Condensation Reaction
**Wants to form most stable ring (6 carbons)!!**
Dieckmann Ester Condensation
(Cyclic Claisen Reactions)
What is a Michael Addition Reaction?
Adding a nucleophile to a carbonyl in the [1,4] position
**Thermodynamic product, so heat required**
What reagents favor [1,2] addition?
Strong Nucleophiles:
Grignard (RMgBr)
Organolithium (RLi)
Acetylide Ion (R-C≡C- +Na)
What reagents favor a Michael [1,4] addition?
Michael Donor: mild to moderate nucleophile
Michael Acceptor: Double bond with an EWG in conjugation
Robinson Annulation
(Michael Reaction + Cyclic Aldol Reaction)
D-(+)-glucose
D-galactose
D-fructose
D-(-)-ribose
What are epimers?
A type of diasteromer that has only a one chiral center difference between the two structures
Ex: D-(+)-allose is the C2 epimer of D-(+)-altrose
What are anomers?
α anomer = CH2OH and OH groups are trans to each other
β anomer = CH2OH and OH groups are cis to each other
How do you convert a Fischer projection to a Haworth projection?
Hemiacetal
to
Acetal
Reagents:
cat. pTsOH / ROH
What is a glycoside?
It’s a sugar with an aglycone unit attached at the end of the chain
Ex: OR, NR2,OROH, etc. replacing hemiacetal -OH group
Enediol Rearrangment
Creates two possible sugars:
1) Switch the chirality of the first row
2) Replace the first row with a carbonyl group
Complete Oxidation of Sugars
Reagents:
HNO3
**Strong oxidizer**
Partial Oxidation of Sugars
Reagents:
Br2 / H2O or Ag(NH3)2OH
**Mild oxidizer**
Reducing Sugars
A sugar that contains an aldehyde that can react with Ag+/Cu+ to create Ag/Cu metal
Replace acetal -OH groups with -OR groups
Reagents:
Excess RI / Ag2O
Replace acetal -OH groups with -OAc groups
Reagents:
Ac2O / pyridine
Reducing Sugars
Reagents:
NaBH4
**Mild hydride donor**
Phenyl Osazone
Reagents:
3 eq. PhNHNH2 / HA / A-
Ruff Degradation
Reagents:
1) Br2 / H2O, 2) Fe2(SO4)3 / H2O2
Fischer-Killiani Chain Lengthening
Reagents:
1) NaCN / H2O, 2) H2 / Pd / BaSO4, 3) H3O+
**Produces epimers / 2 products**
