Whatyou%should%remember%from%the% lastlecture% 232 Daily Summaries3.… ·...
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What you should remember from the last lecture Aldehyde and Ketone Chemistry: Electrophilic at the carbonyl carbon, basic on oxygen Hydride reducing agents LiAlH 4 , NaBH 4 Nucleophiles add to the carbonyl carbon Carbanions: Grignards, alkyl lithiums, others Amines: FormaDon of imines and enamines Alcohols: FormaDon of acetals, hemiacetals
Transcript of Whatyou%should%remember%from%the% lastlecture% 232 Daily Summaries3.… ·...
What you should remember from the last lecture
Aldehyde and Ketone Chemistry: Electrophilic at the carbonyl carbon, basic on oxygen Hydride reducing agents LiAlH4, NaBH4 Nucleophiles add to the carbonyl carbon Carbanions: Grignards, alkyl lithiums, others Amines: FormaDon of imines and enamines Alcohols: FormaDon of acetals, hemiacetals
What you should do before the next lecture
Review Chapter 19. Review Chapter 20, secDons 20.7 and 20.13. Read Chapter 22. The first several secDons are ‘general interest’ reading.
InteresDng esters and amides
NH
HN
NH
O
O
O
O
Nylon 6-‐6
HN
O
NH
O
O
HN NH
O
Kevlar
HN
O
HN
O O
HN
HN
ONomex
H2NNH
OCH3
O
CO2HO
Aspartame
H2NNH
HN
NH
HN CO2H
O
O
O
O
SCH3Met-‐enkephalin
InteresDng esters and amides
O
O
O O
O
HO OH
OHO
N
O
OCH3
OH
OHN
S
CO2H
HN
O
O
Penicillin G
N
S
O
CO2H
HN
O
NH2
Cefradine
Erythromycin
InteresDng lactones and lactams
Some ‘issues’
The quesDon of the nucleophilic (or basic) oxygen in an ester or acid – what is acceptable?
O
O
O
O
O
OH
H
HH H
O
O
H
HO
OH
HO
OH
H
O
O
H
δ
δ
What you should remember from the last lecture Carboxylic Acid DerivaDves, including acid chlorides, anhydrides, esters, amides, and nitriles. Recognize that these same kinds of derivaDves can be made from many other acids, including sulfur-‐based acids (sulfates, sulfonates), and phosphoric acids (phosphates).
What you should remember from the last lecture
The reac5vity of different carboxylic acid derivaDves toward nucleophilic acyl subsDtuDon: Acid chlorides (most reacDve), Anhydrides, Esters, Amides (least reacDve) Fisher Esterifica5on – Acid catalyzed condensaDon of an acid and an alcohol to form an ester.
What you should remember from the last lecture
• Nucleophilic Acyl Subs5tu5on. This process adds an acyl group (RC=O) to a nucleophile.
• Ester forma5on from alcohols and acids is reversible under acidic condiDon. Base hydrolysis is saponifica5on.
• Forma5on of Acid Chlorides. ReacDon of an acid with thionyl chloride (SOCl2) produces an acid chloride.
• Forma5on of esters and amides from acid chlorides, and forma5on of amides with diimides.
What you should do before the next lecture
Read Chapter 23 through secDon 23.8
ClarificaDon from the last lecture
N
C
N
Cy
Cy
R OH
O
R
O
O
H
CN
NCy
Cy
R
O
O
H
CN
NCy
Cy
R
O
OC
NH
NCy
Cy
NH2
CH3
R OC
NH
NCy
Cy
ONHCH3
R
O
NH
CH3C
NH
HNCy
Cy
O
Dicyclohexylurea (DCU)
Some ‘issues’
The quesDon of the mechanism of amide formaDon using carbodiimides (like DCC)….
O
O
HDCC
O
O
C
N
NH
R
R
O
O O?
NH
O
R
H2N RH2N R
Design an experiment that will disBnguish between these two pathways.
Pudng it into pracDce….
O
OHHO
cat. H2SO4
O
O
O
OH
DCC, CH3NH2
HO
O
OH
SOCl2O
O
O
O
Cl
O
Cl
O
O
NH
CH3
What you should remember from the last lecture Reac5ons of Acids, Esters, and Amides: Fisher Esterifica5on – Acid catalyzed condensaDon of an acid and an alcohol. Saponifica5on – Hydrolysis of esters under basic condiDons. Hydrolysis of amides, esters, and nitriles under acidic and under basic condiDons. Transesterifica5on and ester-‐amide exchange
Pudng it into pracDce….
NH
H O
KOH, H2O
Reflux
NH2
HO
O K
HCl, H2O
NH3
HO
OH
CO2HHO2C1. SOCl2
2.
OH
O
OO
O
Pudng it into pracDce….
O
O
HHN
O
NH
O
H2N CO2CH3
DCC
NH
OHN
O
NH
O
CO2CH3
O OH
AcO
OAc
OAc
AcO CH3OH, Na2CO3O OH
HO
OH
OH
HO O
CH3 O CH3
+ 4
AcO R
O
CH3 O R
Pudng it into pracDce….
H2N CO2Et H3N CO2EtCl
Amino acid esters are rarely stored as the free amines, but instead as the amine hydrochloride salt. Why?
Pudng it into pracDce….
Fisher EsterificaDon of the hydroxy acid below could result in cyclizaDon or in polymerizaDon. What condiDons would favor each pathway?
HO CO2H
cat. TsOH
OO
O
O
O
O
O
O
OR
CyclizaDon: Low concentraBon (to slow down bimolecular reacBons). PolymerizaDon: High concentraBon.
O
N
NN
N
NH2
O
OHO
HH
HH
OP
O
O
PO
OHOH
O P
O
O
NH
O
NH
OH
O
SS
O
Acetyl-‐CoA (Acetyl-‐SCoA)
Where would you rank a thioester?
Cl O O NH
O O O O O
S
O
Cl O O NH
O O O O O
S
O
Acetyl-‐CoA (Acetyl-‐SCoA)
Acetyl Choline (a neurotransmieer)
Some reacDons of Acetyl-‐CoA
Oxaloacetate Citrate (+ HS-‐CoA)
O
SCoA
CO2
CO2
OCO2HO
CO2
CO2
Citrate synthaseKey step in the Tricarboxylic acid cycle (aka the Krebs cycle) that is fundamental to aerobic metabolism.
O
SCoA
HON
Choline synthase (an acetyl transferase)
ON
O
What you should remember from the last lecture Enols and Enolates. FormaDon, mechanism, acid strengths. pKa (for a ketone) is ~ 20. Halogena5on of enols and enolates. MonohalogenaDon occurs under acid (enol) condiDons, but polyhalogenaDon tends to occur under basic (enolate) condiDons. Enolates are ambident nucleophiles, but are typically more nucleophilic at carbon than at oxygen, even if the oxygen has more negaDve charge in the hybrid.
What you should remember from the last lecture Forma5on of Enols and Enolates by deprotona5on of carbonyl compounds. Thermodynamic (more highly subsDtuted) enolates: Favored by strong bases (NaOEt), proDc solvents (EtOH), and warm temperatures (25 ˚C) KineDc (less subsDtuted) enolates: Favored by strong, hindered bases (LDA), aproDc solvents (THF) and low temperatures (-‐78 ˚C)
What you should remember from the last lecture
Thermodynamic and Kine5c Enolates. Moderate base/proDc solvents/warm temperatures favor the thermodynamic enolate. Strong base (LDA), aproDc solvent (THF), and low temperatures favor the kineDc enolate. Alkyla5on of enolates with alkyl halides C-‐alkylaDon rather than O-‐alkylaDon.
Acetoace5c Ester Syntheses Equivalent to alkylaDon of acetone. Uses very mild condiDons.
Pudng it into pracDce…. O
1. LDA, THF, -78 ˚C
2.
Br
O
OHOAc, Br2
O
Br
Na2CO3
DMF
O
O
CO2EtNaOEt
Br
O
CO2Et1. NaOH
2. HCl, H2O
O
Pudng it into pracDce….
O
CO2Et
O O
OEtis 2. HCl, H2O
O O
OH1. NaOH, H2O
O O
O
H
is
OH
O
Pudng it into pracDce….
EtO2C CO2Et 1. NaOEt, EtOH
CH2Br
O2N
2.
EtO2C CO2Et
O2N 1. NaOH, H2O2. HCl, H2O
O2N
O
O
O
OH
H
O2N
HO
OH
O2N
O
OH
Pudng it into pracDce….
CO2HH
O
1. CH3MgBr 2. HCl, H2O
CH3 OHH
EtO2C CO2Et 2 NaOEt
BrBr
1. NaOH
2. HCl, H2O
CO2Et
O1. NaOEt, n-C4H9Br
2. NaOH, H2O3. HCl, H2O
Pudng it into pracDce….
CO2Et
O1. NaOEt, EtOH
2.
Br
O
O
CO2Et
O
O
O1. NaOH, H2O2. HCl, H2O
O
O
OH
O
O
O
OH
O
- CO2
Pudng it into pracDce….
O
How could this compound be made?
from O
Br
from
CH2
O
Br
Br
O
Br
CO2Et
from
Br
Br
CO2Et
O
O
CO2EtNaOEt
BrBr
O
CO2Et
Br
NaOEt CO2Et
O
PracDce! How could this be made?
O
NH2from
EtO OEt
O O 1. NaOEt
2.Br
EtO OEt
O O
1. NaOEt2. EtBr
EtO OEt
O O
2. HCl, H2O
1. NaOH, H2O
OH
O
1. SOCl22. NH3
Pudng it into pracDce….
O
1. NaOEt, EtOH
2. Et-Br
O
O
NH
cat. TsOH
N
O
2. Et-Br
1. LDA, THF, -78˚
O
O
2. Et-Br
1. NaOEt, EtOH
Something to think about….
N 1. PhCH2Br
2. H3O ?
What you should remember from the last lecture Malonic Ester and Acetoace5c Ester Syntheses
Equivalent to alkylaDon of aceDc acid and to alkylaDon of acetone, respecDvely. Uses very mild condiDons.
Exam 3 is Wednesday Every exam is cumula5ve. This exam will cover material through the end of Chapter 23.
Something to think about….
N 1. PhCH2Br
2. H3O ?
NN
Ph
1. PhCH2Br
O
Ph
2. H3O
Pudng it into pracDce….
EtO2C CO2EtBr
O
NaOEt
O
CO2Et
CO2Et
EtO2C CO2Et
O
NaOEt
O
Br CO2Et
CO2Et
O
Br
NaOEt
O
Br
O
YES
Ugh….
E1CB
Will this work?
Pudng it into pracDce…. O
Br Br
CH3O OCH3CH3OH, TsOH
O
CO2Et
CO2Et
H3O
CH3O OCH3 CO2
CO2
NaOH
EtO2C CO2Et
NaOEt
CH3O OCH3 CO2Et
CO2Et
O
CO2H
H3O
PracDce! O
Cl
AlCl3O
MgBr
OH
OH
OSOCl2
BrMg
O
O
CH3OH, cat. TsOH
What’s the product, and how?
CH3O OH
O
O
O
H
OCH3
H
O
O
H H
OCH3
O
HOO
CH3
H
H
OCH3
O
HOO
CH3
O
HOO
CH3
H
OCH3
H
O
HOO
CH3
H O
O
OCH3
H
H
H
OCH3
O
O
OCH3
H
Why do diet sodas go bad?
H2NNH
OCH3
O
CO2HO
S S
Aspartame
Solvent: Water with Phosphoric Acid……
Acid-‐catalyzed hydrolysis of the methyl ester!
H2NNH
OCH3
O
CO2HO
H3O H2NNH
OH
O
CO2HO
Synthesis pracDce
Target: Requirements: any inorganic reagents, ethyl acetoacetate, any organic reagents of 4 C’s or less.
DCC
Immediately the problem is simplified to the quesDon of how do you make this acid and this amine.
O
OH HN
N
O
Synthesis pracDce
OH
OBr 1. Mg
2. CO23. HCl, H2O
NH
NaBH4
EtNO
EtNH2, cat TsOH
CO2Et
O
1. NaOH, H2O
2. HCl, H2OCO2Et
O
BrBr
2 NaOEt
What you should remember from the last lecture Malonic Ester and Acetoace5c Ester Syntheses
Equivalent to alkylaDon of aceDc acid and to alkylaDon of acetone, respecDvely. Uses very mild condiDons.
Changes to the Grading Scale
The cutoffs for A’s and B’s remains the same. The cutoff for earning a C has been changed to 55% (from 60%), and for passing it is now set at 40% (from 50%).
