CHAPTER 23: ENOLS ENOLATES KETO-ENOL TAUTOMERISM · 20 (water solvent) >50 1 Carey, F.A., ......
Transcript of CHAPTER 23: ENOLS ENOLATES KETO-ENOL TAUTOMERISM · 20 (water solvent) >50 1 Carey, F.A., ......
Page 1
CHAPTER 23: ENOLS + ENOLATES
KETO-ENOL TAUTOMERISM
TAUTOMERISM
ACIDIC MECHANISM
BASIC MECHANISM
Page 2
EQUILIBRIUM CONSTANTS
K 1 1 × 10–5 8 × 10–8 1.7 × 10–8
K 1 0.23 (water solvent) 29 (CCl4 solvent) 20 (water solvent) >50
1 Carey, F.A., Sundberg, R.J., Advanced Organic Chemistry, 4th ed., Kluwer Academic/Plenum Publishing, 2000, pp. 429.
RC
O
CR
OH K= [enol] [keto]
H3CC
O
H H2CC
OH
H H3CC
CH3
O
CH3C
H2C
OH
Page 3
1H NMR spectra can be used to generate K’s:
Problem: Below are various tautomers of Vitamin C (ascorbic acid). Choose the major form at equilibrium.
BIOCHEMISTRY APPLICATION
Glucose Phosphoenol pyruvate (PEP)
Last step of Glycolysis
Page 4
ALPHA RACEMIZATION
WHY THIS OCCURS IN BASE
WHY THIS OCCURS IN ACID
APPLICATION
Odilute HCl (aq)
dilute KOH (aq)or
[α] = +x˚
[α] = 0˚
N
O
O
NHO
O N
O
O
NHO
O
Thalidomide
Helps morning sickness Serious birth defects
(These racemize in the body.)
Page 7
REACTIONS AT THE ALPHA CARBON
ALPHA HALOGENATION
REACTION + MECHANISM
X = Cl, Br, I
HALOFORM REACTION
Note: Purification of water using chlorine sometimes creates CHCl3 (carcinogen) from reaction of organic impurities that contain methyl ketones.2
2 Solomons, G., Fryhle, C.B., Organic Chemistry, 8th ed., Wiley, 2004, pp. 778.
Iodoform Test for Methyl Ketones (Left = Negative, Right = Positive)
Page 8
EXAMPLES
ALPHA ALKYLATION
REACTION + MECHANISM
Oa. 1 equiv. LDA
b. CH3X
Oa. 1 equiv. LDA
b. I
Page 9
APPLICATION
MALONIC ESTER SYNTHESIS
THE PROCESS
STEPS A+B (ALKYLATION)
Tamoxifen (anticancer drug, has been successful against breast cancers)
O
OCH3
O
OCH3 ON(CH3)2
Malonic ester
Page 11
BIOCHEMISTRY APPLICATIONS
Step 3 of the citric acid cycle:
Pentose Phosphate Pathway3:
Synthesis of 5-Carbon Carbohydrates (like what is used in DNA + RNA) from 6-Carbon Glucose
ACETOACETIC ESTER SYNTHESIS
THE PROCESS
EXAMPLE
3 McMurry, J., Begley, T., The Organic Chemistry of Biological Pathways, 2nd edition, 2016, pp. 228.
–O2C CO2–
OH
CO2–
NAD+ –O2C CO2–
O
CO2–
O
O
OO O
O
O=
OOH
POHOHO
OH
Glucose-6-phosphate
O
O
POHOHO
OH
NADP+ H2OOH
O
POHOHO
OH
OOH
O
POHO
O OH
O
NADP+
Acetoacetic ester