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Organic chemistry is the study of carbon containing compounds. The name
is derived from the belief that only organisms could make organic
compounds. It was later showed that organic compounds can be made from
minerals. The chemistry of organism is now called biochemistry.
- Structure
- Bonding: Where two lines meet or a line ends without a atom
label is a carbon with the appropriate number of hydrogens.
- Covalent: An equal sharing of electrons in a bond.
- Polar Covalent: An unequal sharing of electrons in a
bond towards a more electronegative atom.
- Ionic: Bonding between cations and anions.
- Hydrogen Bonding: Bonding between the elements of two
polar-covalent bonds made up of a heteroatom and hydrogen.
- Conjugation: When p atomic orbital on adjacent (vicinal)
atoms are parallel to each other, we say they are conjugated.
- An isolated Pi system or bond is when only two p orbitals
are conjugated.
- An extended Pi system is when more than two p orbitals are
conjugated.
- There are linear Pi systems.
- An extended Pi system with three p orbitals in a row
is called alllylic.
- Allylic cation
- Allylic radical
- Allylic cation
- Polyenes have alternating double and single bonds.
- There are cyclic Pi systems also called annulenes.
- Aromatic
- Flat cyclic Pi systems that are more stable than
alkenes
- For monocyclic Pi systems, they have 4n + 2 cyclic
Pi electrons (Huckel's rule) that are all paired
and in bonding or non-bonding orbitals.
- There are benzenoid aromatic compounds.
- There non-benzenoid (neutral, anions, cations), and
heterocyclic aromatic compounds where conjugation
requires that atoms that where previously viewed as
tetrahedral be actually trigonal so that their
non-bonding electrons are in a p orbital and are part of
the extended Pi system.
- The Pi character (bond order) and bond lengths of
many aromatic molecules can be estimated by averaging
their resonance structures.
- Anti-Aromatic
- Flat cyclic Pi systems (three, four or five
membered rings) that are less stable than alkenes
- For monocyclic Pi systems, they have 4n cyclic
Pi electrons (Huckel's rule) that are either
unpaired (di-radicals) or in anti-bonding orbitals.
- Nonaromatic
- Cyclic Pi systems that are just alkenes because
they are not flat (not completely conjugated) either
because of sterics or because being flat would make
them less stable anti-aromatic systems.
- Electrons in conjugated p orbitals exhibit wave behavior.
- The Huckel method is a simplified wave or quantum
mechanics used to describe this behavior.
- An n x n matrix where n is the number of p orbitals in the Pi
system is set up.
- The diagonal is the energy of the Pi system with the same
variable, x, representing it.
- In the off diagonal positions a 1 represents conjugation
between adjacent p orbitals.
- A zero represents no adjacency or conjugation.
- The determinant of this adjacency matrix yields the energies
of the Pi system as its roots when set to zero.
- Placing each energy, one at a time, back into the adjacency
matrix and multiplying by a coefficient vector gives an equation that describes the phases of the waves.
- Linear Pi systems behave like plucked strings.
- The lowest energy orbital is called the fundamental
motion and is when electrons move in unison up and down
through the sigma framework plane.
- Higher molecular orbitals have increasing numbers of
nodes splitting the string in ever increasing pieces and are
referred to as harmonics.
- The full range of motion in an orbital is called the
envelop.
- Molecular orbitals (MO) are combinations of atomic orbitals with either color coding or
signs (±) denoting the relative position of electron
density. These signs are not charges but rather phases
of the waves.
- The energy of the orbitals is distributed around
the zero energy level like a latter with upper and lower
bound of ± 2.
- For linear Pi systems with an odd number of p orbitals,
there is a zero energy or non-bonding molecular orbital.
- The molecular orbitals are populated with the number of
Pi electrons in the system to determine the Highest Occupied
Molecular Orbitals (HOMO).
- Cyclic Pi systems behave like drum heads.
- The lowest energy orbital is called the fundamental
motion and is when electrons move in unison up and down
through the sigma framework plane.
- Higher molecular orbitals have increasing numbers of
nodes splitting the Pie into ever increasing pieces and are
referred to as harmonics.
- The full range of motion in an orbital is called the
envelop.
- Molecular orbitals (MO) are combinations of atomic orbitals with either color coding or
signs (±) denoting the relative position of electron
density. These signs are not charges but rather phases
of the waves.
- The energy of the orbitals is distributed around
the zero energy level as a circumscribed polygon with the
number of edges and vertices as the number of p orbitals,
one vertex at the -2 energy level and an upper bound of +2
for the circumscribing circle.
- The molecular orbitals are populated with the number of
Pi electrons in the system to determine the Highest Occupied
Molecular Orbitals (HOMO).
- Other Pi systems must be explicitly caculated using the
Huckel method.
- Delocalization of electron density can stabilize or
destabilize some Pi systems.
- Linear Pi systems are more stable than isolated Pi
systems.
- Benzene is around 30 kcal/mole more stable than
cyclohexatriene.
- See the section of the definition aromatic,
anti-aromatic, and non-aromatic molecules.
- Shape
- Tetrahedral
- Trigonal
- Linear
- Hybridization: The ratio of s to p atom orbital character in
an atom.
- sp3: Tetrahedral atoms including non-bonding electrons.
- sp2: Trigonal atoms including non-bonding electrons.
- sp: Linear atoms including non-bonding electrons.
- s: The only orbital used by hydrogen to make molecular
orbitals.
- Charge: Determined by
- Oxidation State
- Stereochemistry
- Symmetry
- Plane Symmetry
- Point Symmetry
- Axis and Reflection Symmetry
- Asymmetry
- Functional Groups: A collection of atoms.
- Carbohydrates, Sugars, Saccharides, Polyhydroxylated aldehyde and
ketone derivatives
- Simple sugars have a molecular formula of Cn(H2O)n.
- Open form carbohydrates are aldoses and ketoses
- Fischer projections
- Most oxidized group at the top
- Bowtie technology for horizontal lines
- The last chiral center determines D or L designation
- epimers are diastereomers that vary by one chiral center
- Triose
- glyceraldehyde, an aldotriose
- Tetrose
- erythrose, an aldotetrose
- threose, an aldotetrose
- Pentose
- ribose, the R of RNA, an aldopentose
- 2-deoxyribose, the D of DNA, an aldopentose derivative
- Hexose
- glucose, an aldohexose
- galactose, an aldohexose
- fructose, a ketohexose
- Furanoses and Pyranoses are hemiacetals and hemiketals
- Characterization
- Physical Properties
- Melting Point
- Boiling Point
- Solubility
- Spectroscopy
- Nuclear Magnetic Resonance: The use of radio to invert the
magnetization of nuclei in a magnetic field.
- Infrared Spectroscopy:
- Ultraviolet-Visible Spectroscopy
- Absorption of ultraviolet and visible electromagnetic radiation
in organic molecules is due to movement of electrons from Pi to Pi
anti-bonding orbitals (Pi -> Pi*) or non-bonding to Pi anti-bonding
orbitals (n -> Pi*).
- Movement of electrons from sigma bonds to sigma anti-bonding
orbitals is higher in energy.
- The longest wavelength of absorption is due to moving an
electron from the Highest Occupied Molecular Orbital (HOMO) to the
Lowest Unoccupied Molecular Orbital (LUMO).
- The absorption of isolated Pi bonds is below 200 nm and has to
be measured in the absence of nitrogen and oxygen which also absorb
below 200 nm. The HOMO is the bonding orbital. The LUMO
is the Pi anti-bond.
- The absorption of conjugated or extended Pi systems is above 200
nm because the HOMO-LUMO gap decreases with increased conjugation.
- The absorption of visible light is possible with a molecule like
Carotene because the HOMO-LUMO gap corresponds to absorptions above
400 nm.
- The color that is observed is the complement of the color that
is absorbed, thus Carotene absorbs in the blue to look orange.
- Pi systems with access to non-bonding electrons may have half
the HOMO-LUMO gap and thus require less alternating double and
single carbon bonds than Carotene to absorb in the visible. An
important example is retinal.
- Examples:
- pH indicators work by altering conjugation.
- Bleach works by disrupting conjugation.
- Bluing agents work by complementing the yellow of clothes.
- Mass Spectrometry
- Optical Rotation: Observed by placing an a chiral molecule
between two optical polarizers.
- Reactivity
- Addition: The addition of two groups (one may be a charge)
across a Pi bond or un-saturation.
- Electrophilic Addition to Alkenes: Additions initiated by an electrophile.
- A mechanism that involves using Pi electrons to bond an atom
of the un-saturation to an electrophile, followed by bonding a
nucleophile to the intermediate carbocation or transition state
on the other atom of the un-saturation.
- Regio-chemistry is on which atom of an unsaturation (double
bond) to connect the electrophile and nucleophile, which
constitutional isomer is formed preferentially.
- Because of the stability of the carbocation intermediate or
transition state, the electrophile seems to bond to the atom
with the least hydrogens.
- When the electrophile is a proton and adds to the carbon
with the most hydrogens then this is called a Markovnikov
addition, "The rich get richer."
- When the nucleophile is a hydrogen and adds to the
carbon with the least hydrogens then this is called an anti-Markovnikov
addition, "The poor get richer."
- Relative stereochemistry is on which relative side (same
side or opposite side) of the plane formed by the atoms of the
un-saturation and the atoms directly bonded to the un-saturation
do the electrophile and nucleophile connect, which diastereomer
is formed.
- When the electrophile and nucleophile connect on the
same side this is called a syn addition.
- Syn addition tends to happen when the electrophile
and nucleophile are bonded together or when the
electrophile is converted to a nucleophile (has a lone
pair of electrons) upon bonding and bonds to both atoms
of the un-saturation forming a three-membered ring.
- When the electrophile and nucleophile connect on
opposite sides this is called a trans addition.
- Anti addition tends to happen when the electrophile
is converted to a nucleophile (is neutral and has lone
pairs of electrons) upon bonding and then is attracted
to the carbocation intermediate blocking approach of the
nucleophile from the same side as the electrophile.
- Absolute stereochemistry is on which side of the plane
formed by the atoms of the un-saturation and the atoms directly
bonded to the un-saturation do the electrophile and nucleophile
connect, which enantiomer is formed.
- Electrophilic Addition to Conjugated Butadiene Systems
- Electrophiles add to butadiene systems to make the more stable
allylic cation over an isolated cation and may thus violate
Markovnikov's rule.
- Because allylic cations have electron deficiency at both ends of
the Pi system, an electrophile may add 1,2 or 1,4 on the butadiene
carbons.
- 1,2 addition is favored by low temperatures because it is the
first formed kinetic product.
- The thermodynamic product may be 1,2 or 1,4 addition depending
on the stability of the alkene product because elevated temperatures
create reversible reaction conditions.
- Nucleophilic Addition: Additions initiated by a
nucleophile.
- 1,2-Additions
- Hydrates
- Hemiacetals and Hemiketals
- Hemiaminals, Carbinol Amines, Amino Alcohols
- Carbanion Additions
- Grignard Additions
- Alkyl Lithium Additions
- Aldol Additions
- 1,4-Additions
- Aldol addition reactions
- Enolates add to carbonyl compounds to make beta-hydroxycarbonyl
compounds.
- Concerted additions
- Cycloadditions
- Two isolated Pi systems may cyclize in a Pericyclic
manner to gain two sigma bonds and loose two Pi bonds.
- This intramolecular reaction may be viewed as
- 2+2 Photo-Additions
- 2+4 Diels-Alder
- Electrocyclic reactions
- Extended Pi systems may cyclize in a Pericyclic manner
to gain a sigma bond and loose a Pi bond.
- By the reverse of the same mechanism, cyclobutenes will
revert to butadiene systems but can be created by using
ultraviolet light on butadienes.
- Hexatrienes and Octatetraenes favorably form
cyclohexadienes and cyclooctatrienes, respectively, with
heat or light.
- Because the phases of the ends of the HOMO (the
molecular equivalent of a valence shell) of the Pi system
must match to undergo this intra-molecular reaction, the
groups at the end of the Pi system rotate con-rotatory for
4n Pi electron systems and dis-rotatory for 4n + 2 Pi
electron systems with heat (some times spontaneously without
light).
- Because light converts the LUMO into the HOMO for
extended Pi systems, the groups at the end of the Pi system
rotate dis-rotatory for 4n Pi electron systems and con-rotatory
for 4n + 2 Pi electron systems with light.
- Radical reduction of the carbonyl
- Metals and proton source form same products as hydride reagent
and hydronium workup.
- Without the proton source:
- Carbonyls go to Pinacole product (vicinal diols).
- Esters go to Acyloin product (alpha-hydroxy ketone).
- The Birth Reduction
- Elimination
- E1: Elimination Uni-Molecular
- A mechanism that involves removing a group (called the leaving
group) and shared electrons from a carbon to form a carbocation
followed by forming a Pi bond between the carbocation and a vicinal
carbon by removing a vicinal hydrogen.
- This reaction shares its first step with the SN1
mechanism.
- The kinetics are pseudo-first-order because it is more difficult
to form a carbocation than to eliminate the vicinal hydrogen.
- This reaction only occurs on tertiary and secondary carbons or
rearrangements occur.
- Elimination over substitution is favored by heating and lack of
a good nucleophile.
- If more than one vicinal hydrogen is available, tetra > tri >
1,2-di > 1,1-di > mono substituted alkenes are favored because of
induction, hyper-conjugation, and steric reasons.
- The choice of vininal hydrogen to removed is summarized by
Saytzeff's rule, "The poor get poorer", remove the vicinal hydrogen
from the carbon that has the least hydrogens.
- Don't assume that (E) is always favored over (Z),
draw it out.
- E2: Elimination Bi-Molecular
- A mechanism that involves using a base to remove a hydrogen and
a vicinal group (called a leaving group) to form a Pi bond between
two carbons.
- The rate of the reaction is second order in substrate and base.
- The hydrogen and the leaving group must be anti on a Newman
projection to undergo an intra-molecular SN2
substitution.
- The reaction is favored by strong bases and steric
congestions.
- The reaction follows Saytzeff's rule with small bases.
- The reaction follows Hofmann's rule ("The rich get poorer",
remove the vicinal hydrogen from the carbon with the most
hydrogens) with large bases
(potassium tertiary-butoxide, lithium diisopropylamide) and in
the elimination of ammonium groups.
- Don't assume that (E) is always favored over (Z),
draw it out.
- E1cb: Elimination Uni-Molecular Catalyzed by Base
- A mechanism that involves using a base to remove a hydrogen
vicinal to a leaving group and form a carbanion followed by
eliminating the leaving group and forming a Pi bond between the
carbanion and the carbon that had the leaving group.
- Substitution: Mechanisms that look like one group has simple
just been replaced by another group.
- SN1: Substitution Uni-molecular
-
A mechanism that involves removing a group (called the leaving
group) and shared electrons from a carbon to form a carbocation
followed by bonding the carbocation with a new group (called the
nucleophile) with a new set of electrons.
- The hybridization of carbon in the carbocation intermediate is
sp2.
- This reaction shares its first step with the E1 mechanism.
- The kinetics are pseudo-first-order because the rate appears to
depend only on the concentration of the substrate and not on the
concentration of the nucleophile because it is more difficult to
form the carbocation intermediate than to bond the carbocation and
the nucleophile.
- The truth is that the rate also depends on the solvent and its
polarity.
- When the solvent is the nucleophile the reaction is called a
solvolysis.
- Because of the stability of the intermediate carbocation
(induction and hyper-conjugation), the
reactions is faster for tertiary over secondary carbons.
- The mechanism does not occur on primary or methyl carbons,
unless they are stabilized as oxoniums, allylic, benzylic, etc.
systems.
- The reaction is catalyzed by protic solvents and acids.
- The reaction is slowed by less polar solvents including aprotic
solvents.
- The mechanism gives racemization of chiral substrates, though
not perfectly because of cage effects.
- Being better able to stabilize negative charge, the reaction occurs faster for sulfonate > iodo > bromo > chloro
leaving groups, the stronger the conjugate acid of the leaving group
the better the leaving group.
- The major product is the result of reaction with the best nucleophile.
- For allylic systems, substitution may occur on the other end
of the extended Pi-system to create the more stable alkene.
- Bases promote E2 elimination over substitution.
- SN2: Substitution Bi-molecular
- A mechanism that involves direct displacement (from the back to
interact with the sigma anti bonding orbital and avoid the electrons
on the side of the leaving group) of one atom
(called the leaving group) with another atom with lone pair of
electrons (the nucleophile) on carbon.
- The hybridization of carbon in the transition state is sp2.
- Because of steric reasons this reaction is only seen
on tetrahedral carbons.
- The rate of the reaction is second order in substrate and nucleophile.
- Because of steric hinderance, the reaction is faster for methyl
over primary over secondary carbons.
- The mechanism does not occur on tertiary carbons.
- The nucleophiles work best in polar aprotic solvents.
- The mechanism gives inversion of configuration of chiral
substrates.
- Being better able to stabilize negative charge, the reaction occurs faster for sulfonate > iodo > bromo > chloro
leaving groups, the stronger the conjugate acid of the leaving group
the better the leaving group.
- The major product is the result of reaction with the best nucleophile.
- Negatively charged atoms are better nucleophiles than the
corresponding neutral atom.
- Too strong bases promote E2 elimination over substitution.
- Acyl Substitution: Substitution on a acyl group or
carbonyl carbon leaving the carbonyl intact.
- Substitution among carboxylic acid derivatives
- Haloform reaction
- Claisen condensation reaction.
- The enolate of an ester is used to do acyl substitution on
another ester and thus form beta-keto esters.
- Esters are treated with the alkoxide as the ester already
has to avoid any net acyl substitution change.
- The equilibrium to beta-keto esters is favored by forming a
doubly allylic enolate and thus the alkoxide is added
stoichiometrically and the alpha carbon of one of the esters
must have two alpha carbons.
- Reacting a mixture of esters can give a mixture of
constitutional isomers unless:
- One ester does not have two alpha hydrogens.
- You condense a ketone with an ester.
- You react an ester with a beta-keto carbonyl compound.
- Intramolecular Claisen condensation reactions give five and
six membered rings, the Dieckmann reaction.
- Carbonyl Substitution
- Substitution of the Carbonyl Oxygen
- Amine Condensations
- Wittig Reaction
- Aldol Condensation Reactions
- Enolates add to carbonyl compounds to make beta-hydroxycarbonyl
compounds which in turn eliminates water to make alpha,beta-unsaturated
carbonyl compounds.
- The net reaction is condensation of an alpha carbon on the
carbonyl of another molecule, thus loosing two hydrogens from
the alpha carbon and the oxygen of the other carbonyl compound
to make water.
- Aldehydes are more reactive than ketones to the addition
step because they are less sterically congested and because they
are more electron deficient.
- Reacting a mixture of carbonyl compounds (Mixed Aldol) can
give a mixture of constitutional and stereoisomers unless:
- One carbonyl compound does not have two-alpha hydrogens and
is added in excess to the other carbonyl compound that does.
The result is condensation of the alpha carbon of the carbonyl
compound with two alpha hydrogens on the carbonyl of the
compound without alpha-hydrogens.
- One carbonyl compound is a ketone with two alpha-hydrogens
and is added in excess to an aldehyde. The result is
condensation of the alpha carbon of the ketone on the carbonyl
of the aldehyde.
- The enolate of one carbonyl compound is so favored that it
condenses on the carbonyl of compounds that do not form enolates
as easily. An example is the enolate of beta-keto carbonyl
compounds, the Knoevenagle reaction.
- Intramolecular Aldol condensation reactions give five and
six membered rings.
- Substitution on the Alpha Carbon of a Carbonyl
- Via the Keto-Enol equilibrium
- The haloform reaction
- Alkylation or acylation of beta-keto carbonyl compounds
- Via Enolates
- Kinetic enolate-with excess strong bases like LDA (lithium
diisopropyl amide) at low temperature, the first formed enolate
results from deprotonation at the less sterically hindered
- Thermodynamic enolate-with excess ketone and higher
temperatures, equilibration gives the most stable enolate.
- Via Enamines
- Secondary amines react with carbonyl compounds via iminiums
to make thermodynamic enamines that can be alkylated to make
iminiums that can be hydrolyzed to give alpha-alkylated carbonyl
compounds.
- Via Enol Ethers
- Kinetic and Thermodynamic enolates can be trapped with silyl
chlorides to make silyl enol ethers.
- Silyl enol ethers react with carbocations to make
alpha-alkylated carbonyl compounds.
- Substitutions on Benzene
- Electrophilic Aromatic Substitution
- Nucleophilic Aromatic Substitution
- Benzyne Reactions
- Sandmeyer Reactions
- Free Radical Substitution
- Free Radical Halogenation
- Halogenation of alkanes
- Initiation: Halogens absorb light by n to sigma*
transitions to split into radicals.
- Propagation I: Halogen radicals abstract hydrogen from an
alkane to form a hydrohalide (mineral acid) and a carbon radical.
- Propagation II: A carbon radical reacts with a halogen
molecule to form an alkyl halide and a halogen radical.
- Propagation steps I and II form a chain reaction that occurs
hundreds of times before termination.
- Termination Steps: The reaction ends by repairing radicals
such as halogen halogen, carbon carbon, or halogen carbon.
- Enthalpy Difference: The overall reaction can be analyzed
using bond disassociation energies
- Initiation: Iodine weakest bond followed by fluorine
followed by bromine followed by chlorine
- Propagation I: HF strongest bond
- Propagation II: CF bond the strongest, hence Teflon
- Termination Steps: All exothermic
- Overall Reaction: Fluorine most exothermic reaction,
Iodine most endothermic reactions
- Selectivity:
- Fluorine least selective, gives statistical products
- Bromine most selective, gives tertiary over secondary over
primary substitution
- Use selectivity factors for chlorine
- Remember that iodine does not work because it is an endothermic
reactions
- Costs: Chlorine produced from salt
- Safety: Bromine is a volatile liquid but chlorine and
fluorine are gases
- Allylic and Benzylic Halogenation
- N-bromosuccinimide (NBS) insoluble in carbon tetrachloride is
treated with heat, light or peroxides to form small amounts of
bromine and hence mostly bromine radicals to abstract hydrogen from
allylic positions.
- The reaction is a form of negative feedback because the NBS does
not release bromine unless HBr is produced by substitution rather
than addition reactions.
- The allylic radicals lead to a mixture of products.
- Hydroperoxides
- Rancid Oils
- Synthesis of Acetone and Phenol
- Rearrangement
- Cationic Rearrangements
- Anionic Rearrangements
- Radical Rearrangements
- Sigma tropic Rearrangements
- Insertion Reactions
- Pinacole Rearrangements
- Beckmann Rearrangement
- Bayer-Villiger Reactions
- Multi-Step Reactions
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