Introduction to Organic Chemistry UWorld

Carbocations

Molecules containing a positively charged carbon atom, are strong electrophiles and are common intermediates of an SN1 and E1 reactions.

Carboanions

Molecules containing a negatively charged carbon atom, are strong nucleophiles due to the lone pair of electrons on the charged carbon

Alkyl Groups

Nearby alkyl groups are electron donors and stabilize nearby carbocations (make them lsss reactive) but destabilize carboanioons

Factors that influence stabliiity of carbocations

Resonance and conjugation, induction, and hybridization.

Order of Decreasing Stability (Carbocations)

Tertiary > Secondary > Primary > Methyl

Order of Decreasing Stability (Carboanions)

Methyl > Primary > Secondary > Tertiary

Stereoisomers

Molecules with the same molecular formula and atom connectivity but different spatial arrangements. Contain one or more stereocenters/chiral centers. Priority around the stereocenters determine R or S configuration.

Enantiomers

Nonsuperimposable mirror images containing one or more stereocenters in which all corresponding stereocenters have opposite configuration. Rotating a compound 180 degrees can show it is nonsuperimposable.

Stereocenter

Any atom when two substituents switch positions, a stereocenter is formed (has wedges and dashes). An sp3 carbon is a stereocenter if it is bonded to four unique groups. The sp2 in alkenes are stereocenters if they can be classified E/Z or cis/trans.

E isomer

High priority groups on opposite sides

Z isomer

Highest priority groups on same sides

Cis

Hydrogens on the same side of the double bond (Z Conformation)

Cahn-Ingold-Prelog Priority Rules

Atoms with the highest atomic number have highest priority. If two atoms are the same, look at what atoms they are bonded to.

Trans

Hydrogens on the opposite side of the double bond (E Conformation)

Diastereoisomers

Stereoisomers that are not mirror images. Contain at least two stereocenters where one or more (but not all) are in opposite configurations.

Enantiomers (Plane Polarized Light)

Enantiomers rotate plane polarized light in opposite directions but by the same magnitude. No correlation exists between diastereomers and the magnitude direction of rotation. Racemix mixtures have a rotation of zero because they consist of equal amounts of each enantiomer.

A molecules with n stereocenters can have:

2^n stereoisomers

Constitutional Isomer/Structural Isomers

A molecule that contains the same molecular formula as another molecule The atoms in each molecule differ in their connectivity.

Condensed Structural Formaulas

CH2C(CH3)CO

Allow structures to be written with a line of text using parenthesis to denote branch points or substituents. Line angle formulas further simplify molecular structures and greatly deemphasize hydrogens and carbons. Everything between two C’s is connected to the first C.

Chiral Molecule

R configuration = Clockwise

S configuration = Counterclockwise

If H is on the wedge then it goes in the opposite direction

The first element that is directly bonded is the one that determines priority.

IUPAC Rules of Naming Organic Compounds

A compound’s parent chain is the longest continuous chain of carbon atoms that contain the highest priority functional groups; Alkenes and alkynes have the same priority and are listed alphabetically when naming -ene-yne

Conformational Isomers

Structures that have the same formula and connectivity, and can be interconverted by the rotation of sigma bonds (chair flip). They are identical besides structural bond rotations so they are the same molecule.

Epimers

A type of diastereomer that differ in spatial arrangement at only one stereocenter

SN2 Reaction -

A concerted substitution reaction. A nucleophile attacks electrophile on the opposite side of the leaving group and if the electrophilic center is a chiral center, the stereochemistry of the chiral center is inverted. Only the carbon attacked by the nucleophile undergoes inversion (wedge to dash)

Specific Rotation [a]

Describes the direction (+ or -) and magnitude (degrees) a chiral molecule rotates plane polarized light. A clockwise rotation is denoted as positive and a counterclockwise rotation is negative.

Specific Rotation Equation

[ a ] = a obs / (C)(L)

a obs = observed rotation

c = sample concentration (g/mL)

L = path length

Reaction Optimization

Determines under what conditions the desired product readily forms while preventing or minimizing side product formation.

Thin Layer Chromatography (TLC)

A separation technique commonly used to visually monitor reaction progress when the starting material have different relative polarities. Determines whether products, side products, or starting material is present.

Thin Layer Chromatography Plate

On a TLC plater, the starting material is closest to the bottom of the plate/line. The desired product is above starting material but below overoxidized product, and overoxidized product is on the top. The bigger the circle the better the yield.

IUPAC Naming

Alkanes are hydrocarbons containing only single bonds and are named using the suffix -ane and the parent chain is always the longest most continuous chain. The prefix of the carbon chain indicates the number of carbons in the parent chain.Substituents are listed in alphabetical order preceding the parent chain name.

Tautomerization

Type of isomerization that involves the transfer of hydrogen from one position to another within a molecule and the movement of a double bond to an adjacent atom. These two forms are called tautomers and are in equilibrium. Tutomerization involves a keto form (C=O) as the major tautomer and the enol form is the minor tautomer.

Tautomers

Labelled as constitutional isomers because a bond is broken during hydrogen transfer. Resonance structures are forms of the same compound in which electrons are moved without breaking any bonds.

Nucleotide Tautomerization

Nucleotides can tautomerize, with guanine and thymine shifting between keto (major) and enol (minor) forms whereas adenine and cytosine shift between amines and imines.

Degree of Unsaturation

Degree of Unsaturation = 2C + 2 + N - H - X(halogen) / 2

C = number of carbons N = number of nitrogens H = number of hydrogens X = number of halogens

Amino Acids (Stereocenters)

All amino acids except glycine have stereocenters. Isoleucine and Threonine both have side chains with a stereocenter and can exist as several diastereomeric forms At least one but not all the stereocenters in a pair of diastereomers have opposite configurations.t .

The parent chain is numbered to give substituents:

the lowest numerical position

Substitution Reaction

A functional group in the substrate is replaced with a new functional group. The lost group is called the LG Leaving Group and makes the carbon electrophilic. The new functional group is the nucleophile, and creates a new sigma bond by donating electrons, Substitution reactions can be SN1 or SN2

SN1 Reaction (First Order)

Proceed through a carbocation intermediate which is formed when the leaving group leaves/breaks off. The nucleophile then attacks the carbocation and creates a sigma bond. Carbocation formation is the slowest/rate limiting step in a SN1 reaction and is favored for weak nucleophiles (structures that stabilize carbocation intermediates) and heated reactions (use heat)

(If there is a pi bond, the carbocation can be on either side of the pi bond where the nucleophile will attack)

Methanol Chemical Formula

CH3OH

Atomic Hybridization

Can be determined by the number of substituents, 4 = sp3, 3 = sp2

Carbocation Stability

Molecular features that impact carbocation stability impact both the rate of carbocation formation and the overall rate of an SN1 reaction.

Inductive Effect

Adjacent alkyl groups donate electron density along their sigma bonds as a manifestation of the inductive effect. Alkyl groups stabilization of carbocations is additive, so 1 (primary) carbocations have the least stability and 3 (tertiary) carbocations have the most stability

Hyperconjugation

Adjacent alkyl groups stabilize the electron deficient p orbital of a carbocation through hyperconjugation, where alkyl group sp3 orbitals provide secondary overlap with the unhybridized p orbital.

Carbocations with higher stability have:

an inherently lower relative energy, and a greater rate of formation according to Arrhenius Equation.

Tertiary Carbocations:

Have the greatest stability and provide the highest rate of SN1 reactions

Steric Hinderance

Nucleophiles with fewer branch points near the nucleophilic atom are stronger nucleophiles

Primary carbons are least sterically hindered and tertiary carbons are the most sterically hindered

Methanol is a:

Weak Nucleophile (SN1)

First Order (SN1) Substitution Reactions are:

Zero order with respect to the nucleophile, and the identity of the nucleophile will not effect the rate of SN1 product formation.

Structural/Constitutional Isomers

Differ in how the atoms are connected at one or more points within the structure

SN1 Reactions

SN1 reactions are nucleophilic substitutions that occur in two steps: Formation of a carbocation and nucleophilic attack of a carbocation. Reactivity of alkyl halide substrates depends on the alkyl halides’ substitution. Tertiary alkyl halides are the fastest to react because they form a stable cation; as substitution decreases, the alkyl halide will react more slowly because it forms a less stable carbocation.

Functional Groups

Represent recurring bonding patterns between atoms and are the reactive portions of a molecule used for classification.

Ethers

Oxygen containing group with the formula R-O-R where R area the alkyl groups. Are the single O in a CH3CH2OCH2 strcuture.

Condensed Structural Formula

Ex: CH3CH2CHOCH2

Show all the atoms present in a molecule but not every bond. Branch points are indicated by parenthesis, and non bonding electrons and multiple bonds are inferred based on the octet rule.

Condensed Structure (CO2)

Ester

Condensed Structure (OH)

Alcohol

Condensed Structure (COH)

Aldehyde

Ring Strain

Determines the reactivity of cycloalkanes because of the differences in ring size. Encompasses two structural components: angle strain and torsional strain. Angle strain is present when cycloalkanes have bond angles that deviate significantly from the preferred 109.5 degree bond angles and is the cycloalkane with the greatest strain.

Sigma Bond (Electron Density)

The electron density in a sigma bond lies on the axis between nuclei

Banana Bonds

Electron density extends outward from the axis and are weaker then sigma bonds because of a decreased overlap between sp3 orbitals.

Torsional/Conformational Strain results from:

Eclipsed bonds

Boiling point has no effect on:

Reactivity

Tertiary Alkyl Halides are un reactive in an SN2 reaction because:

they are more sterically hindered which prevents a nucleophilic attack and the breaking of a leaving group in one step.

Nucleophilels

Nucleophiles donate electrons to electrophiles in nucleophilic substitutions. As the electronegativity of a negatively charged atom decreases, its nucleophilicty increases because less electronegative atoms stabilize a negative charge less effecitvely, have a weaker hold on electrons, and more readily donate electrons to an electrophile.

Steric Hinderance

Steric hinderance is a characteristic of bulkiness in compound structures that either blocks a portion of a molecule so that it cannot react or keeps a reaction from occurring altogether.

Inductive Effect

Occurs with the donation of electron density through sigma bonds. Electronegative atoms or electron withdrawing groups (EWG) pull electrons away from an adjacent atom, creating a dipole with a partial negative charge on the electronegative atom and a partial positive charge on the adjacent atom.

Carbocations are stabilized by:

Electron donating groups EDG, such as alkyl groups, because they donate electrons towards the positively charged atom. EWG have the opposite effect because the electronegative atom draws electrons towards it.

SN2 reactions require:

easily accessible electrophiles on a primary carbon.

Chair Conformations

Orientation of a cyclohexane

Axial: Perpendicular to the plane of the ring

Equatorial: Slightly above or below the plane of the ring

Wedge = Up Dash = Down

Newman Projection

A structural representation of molecular conformation. Groups on either the front or the back atom can be rotated in increments of 60 degrees to generate conformations.

Eclipsed Conformation (Newman Projection)

Bonds are aligned and have higher energy.

R group 1 is next to R group 2 = total eclipsed and 0 degree bond angle

R group is 120 degrees next to R group 2 = eclipsed and 120 degree bond angle

Staggered Conformation (Newman Projection)

Bonds not aligned and have lower energy.

R group 1 is 60 degrees next to R group 2 = Gauche and 120 degree bond angle

R group is 180 degrees next to R group 2 = Anti and 180 degree bond angle

CH3-H vs CH3-CH3

Eclipsed CH3-H bonds are lower in energy than eclipsed CH3-CH3 bonds so the H3C between CH3-H will have lower energy than the one between CH3-CH3

SN2 reaction -

A concerted substitution reaction where a nucleophile forms a bond with an electrophile while a leaving group is displaced.If the electrophile is a chiral center, its stereochemistry will be inverted in the product (R → S) or (S → R)

When counting chair conformation substituents:

count to the right

Pi Bond vs Sigma Bond

A pi bond is created by side to side overlap by p orbitals whereas sigma bond is formed by direct end to end overlap of atomic orbitals. A single bond contains one sigma bond, a double bond contains one sigma bond and one pi bond, and a triple bond contains two pi bonds and one sigma bond.

Hybrid Orbital Theory

Combines bound atomic orbitals into mixed hybrid orbitals of equivalent energy and shape. To determine an atom’s hybridization, count the number of lone electron pairs and sigma bonds. sp = 2 things, 2p² = 3 things, sp³ = 4 things

Epoxide = sp^³

Proton Nuclear Magnetic Resonance Spectroscopy (H NMR)

H NMR detects hydrogen atoms (protons) in a molecule by applying external magnetic field and radio frequencies to a sample. NMR measures the relative resonance frequencies of protons, which are displayed as chemical shifts on an NMR spectrum.

Protons surrounded by high electron density:

are shielded from magnetic effects and have small chemical shifts (they are upfield/right on the spectrum)

Protons with low electron density:

Are denshielded and have large chemical shifts (they are downfield/left)

Protons within or near methyl groups are:

Shielded and have small (upfield) chemical shifts

Electronegative atoms (Oxygen and Nitrogen:

Pull electron density away from (deshield) protons and have a large (downshield) chemical shift

High Performance Liquid Chromatography (HPLC)

A column based analytical technique used to separate, quantify, and identify components of a mixture. Compounds are separated based on their affinity for the stationary and mobile phase. Compounds with longer retention times have a greater affinity for the stationary phase and a lower affinity for the mobile phase compared to those with shorter retention times.

Valence Shell Electron Pair Repulsion (VSEPR)

Atoms within a molecule achieve a geometry that minimizes reoulsion between electrons by maximizizng distance between lone pairs and bonds

sp³, sp², and sp hybridized atoms have:

bond angles of 109.5, 130, and 180 degrees respectively. Lone electron pairs or ring strain can distort bond angles.

Carboxylatiohn

Addition of a carboxyl group

Amino Acids with Carboxylic Acid in their Side Chain:

Glutamate and Aspartate (D and E)

Halide leaving group ability increases:

As the size of the halide ion increases. because the increase of surface area stabilizes the negative charge on the departing ion. The ion that leaves is not included in the IUPAC name of the product

Constitutional Isomers

Molecules with the same molecular formula that differ in atom connectivty and have different physical properties and are superimposable images.

2^n

The maximum number of stereoisomers possible for a compound is determined by the expression 2^n, where n is the number of stereocenters. The actual number of stereoisomers for a compound can be less than 2^n if two of the possible stereochemical configurations have an internal mirror plane of symmetry (meso compound) making them conformations of the same compound

The major product of the reaction is dependent on the reaction conditions:

The more stable product will predominate under thermodynamic conditions and the less stable product will predominate under kinetic conditions

Of the 20 amino acids, all have:

A L and S configuration except cysteine. Glycine is achiral.

The side chains of Aspartate (D) and Glutamate (E) are the only amino acids with:

A carboxylic acid side chain (O=C-OH)

Imine

Comparable to that of a ketone in that they both contain a carbon heteroatom double bond. Composed of a carbon nitrogen double bond (C=N) with either a hydrogen or an R group attached to the nitrogen atom.

Amide

Carboxylic acid derivative with a carbonyl carbon atom bonded to an an amine group instead of a hydroxyl group

Enamines

Functional groups that contain an amine group bonded to an alkene. Imines can be converted to Enamines via tautomerization if a hydrogen atom is available on the carbon adjacent to the C=N to migrate to the nitrogen atom.

Imide

a functional group with a nitrogen atom N bound to two acyl groups (Ex: two carbonyl atoms). Imides are structurally similar to acid anyhdrides but include bonds with the acyl groups isntead of oxygen atoms.

Schiff base

a compound formed by the condensation of a primary amine with an aldehyde or ketone, resulting in an imine

Planar Intermediate

Conversion of one chiral molecule to its enantiomer requires the formation of a planar intermediate (stereospecific reaction). The planar intermediate is formed from the removal of hydrogen and the product after is formed from the addition of hydrogen to the opposite side. The reaction is stereospecific if a side group is added to one side of this intermediate.

L and D are enantiomer configurations

Conjugated System

Can be identified by alternating single, double, and tripled bonds (alternating pi bonds/p orbitals by sigma bonds). A conjugated system is stabilized through electron delocalization via resonance and can stabilize the molecule.

Decarboxylation

The removal of a carboxyl group from a compound, the removed carboxyl group is converted to CO2.