Download chem 464l survival guide

CHEM 464 SURIVIVAL GUIDE
Abrol Section
(Expanded from Dr. Fischhaber’s and Dr. Crowhurst’s guides)
A. Organic Chemistry
** Also: review pg 11 – 19 and 216 – 217 of the textbook (6th Ed.), and nucleophilic substitution rxns **
Some key terms:
•
nucleophile – an electron-rich group which is either negatively charged or contains unshared electron pairs
that easily form covalent bonds with electron-deficient centers (electrophiles)
•
electrophile – an electron-deficient group which is either positively charged, contains an unfilled valence
electron shell, or is adjacent to an electronegative atom and has a strong tendency to accept electrons from a
nucleophile
•
covalent bond – a chemical bond involving the sharing of electron pairs
•
hydrogen bond – a weak electrostatic attraction between one electronegative atom (oxygen, nitrogen, etc.)
and a hydrogen atom covalently linked to a second electronegative atom
•
lone pair – pair of electrons residing on one atom and not shared by other atoms; unshared electron pair
•
leaving group – an atom or a group of atoms that is displaced as a stable species during a substitution or
displacement reaction. What molecular properties make good leaving groups?
i. Amines - are nucleophilic in the “free base” form (on the right side in the examples below).
Primary amines are
the most nucleophilic, secondary less nucleophilic, and tertiary amines are generally too sterically hindered to
carry out nucleophilic attack. The pKa of a typical ammonium is pH 9-10. Most of the molecules in a solution of
amines are therefore protonated (i.e “ammonium salts”) if the sample is at biological pH (~7.0). N-H bonds are
highly polar and nitrogen lone pairs readily form hydrogen bonds.
A.
Example 1: Ethylamine Hydrochloride, a primary amine, both basic AND nucleophilic.
NH3
B.
NH2
+ Cl
+ H
+ Cl
Example 2: Tris Hydrochloride, a tertiary amine: basic but NOT nucleophilic.
H
HO
OH
N
OH
HO
+ Cl
N
+ H
+ Cl
OH
OH
Trishydroxymethylaminomethane Hydrochloride (a.k.a. “Tris HCl”) shown in both the protonated
ammonium form (left) and deprotonated amino form (right). Tris is a useful buffer in biochemistry
laboratories because its pKa (~8.1) is close to biological pH. It is a tertiary amine, however, which means
that it is not nucleophilic because the nitrogen lone pair (right structure) is too sterically hindered to
attack an electrophile.
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As an exercise: what product would you obtain if each of these compounds was incubated with methyl
bromide in solution at pH 2.0? What would you get if each were incubated with methyl bromide at pH
11.0? Draw an arrow-pushing mechanism to show any reactions that give products.
Carbonyls - have an electrophilic “pecking order”. Here is the order from most electrophilic (left) to least
electrophilic (right):
C.
ii.
O
O
O
O
O
O
O
O
N
Cl
Acyl
chloride
H
O
Anhydride
Hydrolyze readily in water
Aldehyde
Ketone
(Aldehydes and ketones
don’t hydrolyze – they
have no leaving group)
O
OH
Ester
Carboxylic
acid *
Amide
Hydrolyze slowly in acid
(Min-Hrs)
(Days-Weeks)
*The carboxylic acid technically does hydrolyze, but the product is the exact same molecule as the starting
material, so you wouldn’t be able to “see” it hydrolyze unless you labeled it somehow, for instance, by making
the oxygen atoms 18O and hydrolyzing it in regular water containing 16O.
A.
As an exercise, draw all the resonance structures for an ester. Which resonance structure most clearly
illustrates the electrophilic character of an ester? Now draw all the resonance forms for a ketone. Which
resonance form(s) illustrate why the ester is less electrophilic than a ketone (i.e. the ones not common to
both structures).
B.
Is it more appropriate to think of a carbonyl carbon as an “electron-rich” carbon or an “electron poor”
carbon? Explain your answer.
C.
Consider the resonance forms of an amide, below. Why is the amide nitrogen not very nucleophilic?
..
..
O
O
N
D.
N
Would the molecule above be a good at forming hydrogen bonds in aqueous solution? Does this enable
its water solubility?
iii. Hydroxyl Groups (OH) and Sulfhydryl groups (SH) - are a little bit acidic, especially the sulfhydryl group.
The pKa of a hydroxyl is usually similar to water (~pH 16) while a suflhydryl group has an average pKa of about 8.
Both groups generally impart water solubility to biomolecules because the O-H and S-H bonds are both very
polar (electron density of the bond clusters around the electronegative oxygen and sulfur atoms, respectively).
Both functional groups form hydrogen bonds readily via the hydrogen atoms (the hydrogen bond donor) and the
oxygen or sulfur lone pairs (the hydrogen bond acceptors). Additionally, sulfhydryl (a.k.a. “thiol”) groups can
perform some types of nucleophilic reactions in biochemistry as well as reduction-oxidation (redox) reactions.
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A.
Is a protonated hydroxyl (ROH) a good leaving group or a good nucleophile? Is a deprotonated hydroxyl
(RO–) a good leaving group or a good nucleophile? Explain your answers.
B.
As an exercise, write an equilibrium expression for β−mercaptoethanol (shown below) as it is
deprotonated to the alkoxide-thiolate form (the fully deprotonated form). It is a two-step equilibration
because the pKa of the thiol and hydroxyl groups are very different from each other.
O
HO
S
SH
pH < ?
C.
? < pH
? < pH < ?
As an exercise draw a picture of what β−mercaptoethanol would look like when hydrogen bonded to
water molecules in aqueous solution.
O
H
H
S
iv. Chirality, leaving groups and substitution – Use your organic chemistry textbook to help you review:
•
•
•
chiral centers: be able to recognize, assign R vs S
nucleophilic substitution: know SN1 versus SN2, be able to recognize which is the nucleophile and which
is the electrophile, understand what is a good versus a bad leaving group, etc.
pKa: understand how pKas work, and how it affects the reactivities of molecules
v. Nomenclature - Just as though you were in a foreign language class, a firm understanding of the functional
group terminology from your pre-requisite organic chemistry classes is KEY to being able to follow your
instructor during lectures in CHEM 464 and to understand what you read in the textbook. Draw generic
structures (like those shown for the carbonyls above) for each of the following functional groups. Practice
imagining the functional groups in your head (in their appropriate states of protonation) as you say their names,
much like you will need to be able to quickly recall the functional group structures as your instructor says them
while lecturing. ** you should also be familiar with their reactivities (i.e. which part of the molecule is
nucleophilic or electrophilic, etc.) **
• methyl
• sulfhydryl / thiol
• ethyl
• thiolate
• isopropyl
• disulfide
• hydroxyl / alcohol
• thioester
• phenyl
• sulfate
• phenol / phenolate
• Imine
• enol / enolate
• N-substituted imine
• carboxylate
• pyridine / pyridinium
• carbonyl – aldehyde
• guanidinium / guanidine
• carbonyl – ketone
• imidazole
• ester
• phosphate
• anhydride
• phosphoryl
• amine / amino / ammonium
• phosphoanhydride
• amide / amido
• acyl phosphate (mixed anhydride)
Page 3 of 10
Additional functional groups of interest:
CH3
Isopropyl
R
H
O
Sulfate
R
S
CH3
O
-
O
-
O
Thiolate
R
-
R
P
S
O
-
O
Pyridine
N
-
Phosphate
Page 4 of 10
B. Physical Chemistry
Local geometries around atoms in molecules based on VSEPR (Valence Shell Electron Pair Repulsion) Theory:
Example
Orbital
Hybridizations
sp
sp2
sp3
sp3d
sp3d2
Electronegativities of some Elements in the periodic table:
Page 5 of 10
Resonance structures guided by electronegativities:
Example 1: Carbonyl group
Example 2: Carboxylate group
Page 6 of 10
Example 3: Amide bond
Page 7 of 10
Hydrogen bonding interactions in Chemistry and Biology:
Example 1: Water-Water interactions
Example 2: Water-Amide interactions
Page 8 of 10
Oxidation States in organic molecules guided by relative electronegativities:
Page 9 of 10
Le Chatelier’s Principle:
Let us take an exothermic chemical reaction shown below at equilibrium:
A(g) + 2B(g) ⇌ C(g) + D(g) + Heat
Le Chatelier’s principle states that if the equilibrium of this reaction system is changed by any means, the equilibrium will shift in a
direction that will resist the change.
Three types of changes are easy to understand:
1.
Change in concentration
a. If the concentration of B is decreased, the equilibrium will shift to the left to create more B molecules.
b. If the concentration of C is decreased, the equilibrium will shift to the right to create more C molecules.
2.
Change in pressure (3 gas reactant molecules are being converted to 2 gas product molecules reducing pressure)
a. If the pressure is decreased, the equilibrium will shift to the left to increase the pressure.
b. If the pressure is increased, the equilibrium will shift to the right to decrease the pressure.
3.
Change in temperature
a. If the temperature is increased, the equilibrium will shift to the left to consume heat and lower the temperature.
b. If the temperature is decreased, the equilibrium will shift to the right to produce heat and increase temperature.
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