MCAT Organic Chemistry

doublet splitting pattern

2 peaks of equal intensity, equally spaced caused by nearby protons influencing shielding by being in alpha or beta, which causes slight variation upfield or downfield

number of possible stereoisomers from chiral centers equation

2^n = number of possible stereoismers n = number of chiral centers

fingerprint region

In an IR spectrum, the region of 1500 to 400 cm-1 where more complex vibration patterns, caused by the motion of the molecule as a whole, can be seen; it is characteristic of each individual molecule.

spin-spin coupling (splitting)

In an NMR spectrum, the interaction between spin states of non-equivalent nuclei that are adjacent to the atom attached to the proton of interest that results in the splitting of a signal.

Alcohols functional group

-OH (hydroxyl group)

Oxidation of Aldehydes

-When aldehydes are further oxidized, they form carboxylic acids -they will use oxidizing agents stronger than PCC, such as potassium permanganate (KMnO4), chromium trioxide (CrO3), silver (I) oxide (Ag2O) or hydrogen peroxide (H2O2) -ketones cannot be oxidized further

heterolytic reactions

-a bond is broken and both e- are given to one of the 2 products

anhydride cleavage

-anhydrides are most reactive bc of resonance stabilization and e- withdrawing oxygens -nucleophilic acyl substitution reaction where nucleophile reacts with electrophilic carbonyl, and the other carboxylic acid acts as a leaving group -nucleophiles: ammonia, alcohol, or water -CLEAVES to form new product + carboxylic acid ammonia produces carboxylic acid and amide alcohol produces carboxylic acid and ester water produces two carboxylic acids

SN2 reaction

-bimolecular nucleophilic substitution reactions - only 1 step (concerted reaction) -nucleophile attacks the compound at the same time as the leaving group leaves -Nucleophile actively displaces the leaving group in a backside attack for this to occur, nucleophile must be strong & substrate can't be sterically hindered -concentrations of substrate & nucleophile have role in determining the rate --> rate = k[Nu][R-L] -Position of the substituents around the substrate carbon is inverted (stereospecific)

esters

-carboxylic acid derivatives -hydroxyl group is replaced with an alkoxy group (OR where R is a hydrocarbon chain) -first term in the alkyl name based on the identity of the R group (like an adjective describing the ester) -the second term is the name of the parent acid with -oate replacing -oic acid cyclic esters are known as lactones and in naming, "-oic acid" is replaced with "-lactone" formed by nucleophilic acyl substitution reaction between alcohol and carboxylic acid, known as esterification lack hydrogen bonding, thus will have lower boiling points than carboxylic acids

geminal diols (hydrates)

-diols with 2 hydroxyl groups on the same carbon these will normally be oxidized into carboxylic acids

para/p

on opposite sides of the ring

3 factors that influence cyclic compounds

angle strain - deviation from ideal angle torsional strain - newman projection overlap (eclipsed or gauche) steric strain - nonadjacent atoms interact with each other due to position in space

alpha-racemization

any aldehyde or ketone with a chiral alpha carbon will rapidly become a racemic mixture as the keto and enol forms interconvert

alpha carbon

any carbon attached directly to a carbonyl carbon

Extraction

aqueous phase (layer that is polar, more dense) and organic phase (layer that is nonpolar. less dense), the two layers immiscible. like dissolves like, solute will preferentially dissolve in one of the layers depending on hydrogen bonding, dipole-dipole interactions, and van der waals interactions layers will be mixed and then layer with solute desired will be separated by draining it via a separatory funnel the solvent can then be evaporated by using a rotary evaporator (rotovap)

acyl derivatives

encompass all molecules with a carboxylic acid-derived carbonyl, including carboxylic acids, amides, esters, anhydrides, and others.

Partitioning Coefficient

equilibrium constant between the mobile phase and stationary phase will determine the speed at which a substance will move through a column or gel specific for each eluent

carboxylic acid derivatives

esters, amides, anhydrides, carboxylate

nucleophilicity in polar protic solvent

increases going down the periodic table occurs due to ability to make hydrogen bonds, protons get in way of nucleophile bonding with electrophile water, alcohols, ammonia

nucleophilicity in polar aprotic solvent

increases going up periodic table occurs because it cant make hydrogen bonds, no protons get in the way of bonding DMSO, DMF, acetone

anhydride with water

nucleophilic acyl substitution that results in cleavage of the anhydride results in two carboxylic acids

specific rotation equation

observed rotation / [solution] x tube length (dm) alpha = specific rotation in degrees alpha obs = observed rotation in degrees c = concentration in g / mL l = path length in dm

Bronsted-Lowry acid

proton (H+) donor

Bronsted-Lowry base

proton acceptor (H+)

chemical equivalence

protons in the same magnetic environment, giving same chemical shift in NMR

R stereocenter

when an asymmetric center is clockwise = right determined by cahn-ingold-prelog priority rules

S stereocenter

when an asymmetric center is counterclockwise = sinister = left determined by cahn-ingold-prelog priority rules

order of highest priority functional groups

carboxylic acid > anhydride > ester > amide > aldehyde > ketone > alcohol > alkene > alkyne > alkane

characteristics of carboxylic acids

carboxylic acids contain both a carbonyl group and a hydroxide group bound to the same carbon, making it one of the most oxidized in all of organic chemistry always terminal groups highly reactive as nucleophiles, electrophiles, or as acids (low pKa around 3 to 6) highly polar and are excellent H bonders, giving it high boiling point and melting point have strong, unpleasant odors and are involved in many biological processes

3 cyclohexane conformations

chair- most stable boat - most unstable twist/skew boat - intermediate

reduction

gain of electrons decrease in oxidation state increasing the number of bonds to hydrogens

Amphoteric

a substance that can act as both an acid and a base examples are water, Al(OH)3, HCO3-, HSO4

filtration

a technique that uses a porous barrier to separate a solid from a liquid solid left is known as the residue the liquid that passed though, including any remain dissolved particles, is known as the filtrate

percent transmittance (%T)

percent of radiation that passes through a sample and reaches detector

electrophiles

"Electron-loving" atoms with a positive charge or positive polarization; can accept an electron pair when forming new bonds with a nucleophile. kinetic property better leaving group increases electrophilicity good examples are carboxylic derivatives

enolate

- results from deprotonation of alpha carbon that is stablized by resonance with the carbonyl - good nucleophiles -formed by adding strong base to a carbonyl

pKa

- log of acid dissociation constant low values are more acidic high values are more basic

Tosylate

*contain functional group -SO3C6H4CH3 -derived from toluenesulfonic acid -tosyl groups can serve as protecting groups when we don't want alcohols to react, replaces alcohol with ester of tosylate -tysyl groups also make alcohols better leaving groups for nucleophilic addition reactions -will not react with many of the other reagents that would attack alcohols

Mesylate

*contain functional group -SO3CH3 -derived from methanesulfonic acid -prepared using methylsulfonyl chloride and an alcohol in presence of a base -mesyl groups can serve as protecting groups when we don't want alcohols to react -mesyl groups also make alcohols better leaving groups for nucleophilic addition reactions -will not react with many of the other reagents that would attack alcohols (oxidizing agents)

anhydrides

- Carboxylic acid derivative (acid anhydrides) - formed by dehydration of 2 carboxylic acids (nucleophlic acyl reaction), also known as carboxylic acid dimers -Symmetric = same acid - asymmetric = two different acids, name the two chains alphabetically -leaving group will be carboxylate ion - replace "acid" of parent acid with "anhydride"

Proton NMR is good for:

- Determine the relative number of protons and their relative chemical environments - Showing how many adjacent protons there are by splitting patterns. - Inferring certain functional groups

nucleophiles

- Electron Donor; Good Bases - Tend to have lone pairs or pi bonds that cane be used to form covalent bonds to electrophiles ( electron acceptors) - Nucleophile strength is based on relative rates of reaction with a common electrophile; therefore, kinetic property.

reverse phase chromatography

- Exaction opposite of Thin Layer (TLC) - stationary phase is non polar and mobile phase is polar polar molecules move up the plate quickly and nonpolar molecules move slowly

Simple distillation

- Liquids that boil below 150 C and have at least 25C difference in boiling temperature. -low temp is to prevent degradation of product and difference is to prevent contamination of disillate - Consists of a distilling flask (containing combined solution), distillation column ( thermometer, condenser, and receiving flask to collect the distillate. -include chips or stir bars to prevent superheating, when temp is above boiling point but liquid will not vaporize due to air pressure or surface tension

recrystallization

- Method for further purifying crystals in solution. - Solvent chosen should be one in which the product is soluble only at high temperatures; when the solution cools, only the desired product will recrystallize

Proton NMR (1H-NMR)

- Most hydrogen (1H) nuclei come into resonance 0 to 10 ppm downfield from TMS. - Each nuclei gives rise to a separate peak, number of peaks = protons in different environment - Integration: height of each peak / area under peak is proportional to the number of protons it contains. - The position of the peak (upfield or downfield) is due to shielding or deshielding effects and reflects the chemical environment of the protons -electronegativity (withdrawing) desheilds electrons and makes them more downstream (requires higher frequency to change state)

Kinetic and Thermodynamic Enolates

- The kinetic enolate forms more quickly, irreversible,interacts with less sterically hindered alpha carbon, and is less stable than the thermodynamic enblate. It is favored at low temp and when using a sterically hindered base - Thermodynamic forms more slowly, reversible, occurs at the more substituted alpha carbon, and is more stable. It is favored when using weaker or smaller bases or when at higher temperature

Ubiquinone (coenzyme Q)

- biologically active quinone -vital electron carrier associated w/ complexes I, II, and II of the e- transport chain -most oxidized form, can be reduced to ubiquinol -long alkyl chain allows it to be lipid soluble and rest within the phospholipid bilayer

intramolecular anhydride formation

- ortho-phtalic acid to ophthalmic anhydride - Heat and the increased stability of the newly formed ring drive his intramolecular ring formation reaction forward.

Hydroxyquinones

-have 2 carbonyls and a variable number of hydroxyl groups -named by indicating the position of the OH group with a number & indicating the total number of OH groups by a prefix (di- or tri-) with the substituent name hydroxyl- (ex: 1,2-dihydroxyanthraquinone) - To convert phenols to hydroxyquinones, they must be converted to quinones to an oxidation step first and then another oxidation is required to further oxidize the quinones (total of 2 oxidation steps) to add hydroxy groups -less electrophilic than quinones, however many still function in biological roles

meso compounds

-have chiral centers -overall molecule is achiral -have internal plane of symmetry -not optically active --> don't rotate plane polarized light -each chiral center rotates light in opposite directions so overall the rotations cancel out (molecular equivalent of a racemic mixture)

leaving groups

-molecular fragments that retain e- after heterolysis -Weak bases are more stable w/ extra electrons -->good leaving groups I-, Br-, Cl- = good leaving groups due to being very weak bases

Deshielding

-occurs when electron-withdrawing groups pull electron density away from the nucleus, allowing proton to be more easily affected by the magnetic field, requiring higher frequency of radio waves to change state -the more electronegative atoms attached to the C that the proton is attached to, the more deshielded or to the left it will be TMS is used as reference because it is the most shielded possible because Si donates electrons to the hydrogens

IR spectra plot

-percent transmittance vs. wavenumber (1/ λ) -normal range is 4000 to 400 cm^-1 (fingerprint region)

Quinones

-phenols treated with oxidizing agents (OH turned into O=) -Named by indicating the position of the carbonyls numerically & adding quinone to the name of parent phenol -Serve as electron acceptors in e- transport chain as they are highly electrophilic and are resonance stabilized -some may be aromatic, but not always the case

physical properties of carboxylic acids

-polar and hydrogen bond very well, resulting in high boiling points and melting points -often exist as dimers in solution (two carboxylic acids connected by 2 hydrogen bonds -hydroxyl hydrogen is quite acidic due to both inductive effects from oxygens and also from resonance stabilization of the anion -acidity enhanced by substituents that are electron-withdrawing, and decreased by substituents that are electron-donating (because EWG stabilize negative charge after H is lost)

chemoselectivity

-preferential reaction of one functional group in the presence of other functional groups

Size Exclusion Chromatography

-stationary phase contain tiny pores -small molecules enter the pores & get stuck so they elude later -large molecules don't fit in the pores so they move around taking a shorter path & elude faster

ion exchange chromatography

-stationary phase is made of either negatively or positively charged beads (attract & bind compounds that have opposite charge) -useful for charged proteins or DNA -salt or base/acid is added to elute proteins stuck to column

affinity chromatography

-uses a bound receptor or ligand and an eluent with free ligand or a receptor for the protein of interest -the specific interactions to slow down select molecules

Jones oxidation

-uses chromium trioxide dissolved in dilute sulfuric acid and acetone (stronger oxidizing agent) to oxidize primary alcohols to carboxylic acids or secondary alcohols to ketones

sp

1 S orbital, 1 P orbital creates 2 SP orbitals and leaves 2 unhybridized p orbitals found in triple bonds, pi bonds from 2 p orbitals 180 degrees, linear 50% S character

sp2

1 S orbital, 2 P orbitals creates 3 SP2 orbitals and leaves 1 unhybridized p orbital found in double bonds, pi bond from 1 p orbital 120 degrees 33% S character

sp3

1 S orbital, 3 P orbitals creates 4 SP3 orbitals found in tetrahedral, single bonds 109.5 25% S character

standard optic rotation testing conditions

1 g / ml of sample concentration 10 cm / 1 dm long tube

Triplet splitting pattern

1:2:1 ratio, 3 peaks AA , AB/BA, BB causes ratio

Absorbance and % Transmittance

A = 2 - log %T

H2CrO4 (Chromic acid)

A VERY STRONG OXIDIZING AGENT. a primary alcohol or aldehyde to carboxylic acid a secondary alcohol to ketone

High Performance Liquid Chromatography (HPLC)

A form of chromatography in which a small sample is put into a column that can be manipulated with sophisticated solvent gradients to allow very refined separation and characterization; formerly called high-pressure liquid chromatography. A pumping unit causes a pressurization of the mobile phase. The sample is solubilized and injected by syringe and then the mobile phase carries the sample to the column. the sample is separated into components and is analyzed by detectors and recorded Eluent can later be isolated with evaporation of solvent.

phosphate group

A functional group consisting of a phosphorus atom covalently bonded to four oxygen atoms referred to as inorganic phosphate (Pi) or phosphoric acid at physiological pH, it is mainly found as hydrogen phosphate and dihydrogen phosphate has high energy bonds, making it good for energy storing compounds like ATP or GTP found in backbone of DNA in phosphodiester bonds, linking sugar molecules together (intermediate form is pyrophosphate) Phosphoric acid has 3 different pKas that span the whole pH spectrum, making it a really good buffer repulsion of negative charge and resonance stabilization make phosphate in ATP high energy, and releases high amounts of energy when cleaved

protecting group

A group that is used during synthesis to protect a functional group from the reaction conditions. example is using acetal or ketals to protect an aldehyde or ketone from reacting during synthesis

beta state

A magnetic state seen in NMR spectroscopy in which nuclei have been irradiated with radiofrequency pulses to bring them to a higher-energy state.

alpha state

A magnetic state seen in NMR spectroscopy in which nuclei have magnetic moments that are aligned with an incident magnetic field, thus having lower energy.

Strecker Synthesis of Amino Acids

A method of synthesizing amino acids that uses condensation between an aldehyde, ammonia, and cyanide, followed by hydrolysis. Step 1: protonate carbonyl, making it more electrophilic. Then have nucleophilic ammonia attack carbonyl to form imine. Then have nucleophilic cyanide attack imine to form aminonitrile Step 2: nitrile nitrogen is protonated, increasing electrophilicity, allowing for a water molecule to attack it, causing for an imine and hydroxyl to exist at the same time. Then the imine is attacked by another equivalent of water and the carbonyl is formed, kicking off the ammonia and creating carboxylic acid. This step is done in acid and with help of heat resulting product is racemic mixture of D and L amino acids

racemic mixture

A mixture that contains equal amounts of the (+) and (-) enantiomers. Racemic mixtures are not optically active. spin cancels each other out for each of the enantiomers cannot separate enantiomers, must react them to form diastereomers, separate them, then react them back to form enantiomers

NMR spectrum

A plot of absorbance of radio frequency energy versus chemical shifts chemical shift δ, in parts per million (ppm) determines how far downfield (left) a peak is 0 δ is defined by tetramethylsilane (TMS) as a calibration, make sure to skip this peak, and is found upfield, to the right most commonly used to study 1H (protons) but can be done fro any other atom possessing a nuclear spin (odd atomic number or odd mass number)

oxidation state

A positive or negative whole number that represents the "charge" an atom in a compound would have if all shared electrons were assigned to the atom with a greater attraction for those electrons. pretends all bonds are ionic

Distillation

A process that separates the substances in a solution based on their boiling points temp is kept low so only lower bp liquid will vaporize low bp liquid will vaporize, rise to condenser, become condensate, drip down the vessel, and then become the end product, known as the disillate

Retardation Factor (Rf)

A ratio used in thin-layer chromatography to identify a compound; calculated as how far the compound traveled relative to how far the solvent front traveled.

Michael addition

A reaction in which a carbanion attacks an alpha, beta-unsaturated carbonyl. alpha, beta-unsaturated carbonyl is essentially an aldehyde/ketone that has a double bond adjacent to the alpha carbon

aldol condensation

A reaction in which an aldehyde or ketone acts as both the electrophile (keto form) and nucleophile (enolate form), resulting in the formation of a carbon-carbon bond in a new molecule called an aldol. nucleophilic alpha carbon anion (enol) adds to the electrophilic carbonyl carbon (ketone), forming new C-C bond. H+ can be added to protonate the O- of the electrophile to make it into an alcohol remember that the enol is formed by reacting a aldehyde or ketone with a strong base aldol stands for aldehyde (or ketone) with an alcohol dehydration via strong anhydrous base and high temp results in hydroxide group leaving (cannot be done in water) acid = alcohol, base =alpha,beta unsaturated carbonyl

chromatography

A technique that is used to separate the components of a mixture based on the tendency of each component to travel or be drawn across the surface of another material. separates compounds based on how strongly they adhere to the stationary phase or the mobile phase

ultraviolet (UV) spectroscopy

A technique that measures absorbance of ultraviolet light of various wavelengths passing through a sample suspended in an inert, nonabsorbing solvent. Ideal for studying compounds containing double bonds or heteroatoms with lone pairs that create conjugated systems UV light is absorbed and will move Pi and nonbinding electrons from highest occupied molecular orbital (HOMO) to the lowest occupied molecular orbital (LUMO), which is the excited state. the smaller the gap between HOMO and LUMO, the longer the absorbance wavelength with lower energies wavelength of maximum absorbance tells us the extent of conjugation with conjugated systems, longer wavelength = more conjugation - Most useful for studying compounds containing double bonds and/ or heteroatom with lone pairs, or pi bonds or non bonding electrons that create conjugated systems (molecules with unhybridized p-orbitals).

paper chromatography

A type of chromatography that uses cellulose paper as the medium for the stationary phase sample is spotted directly onto stationary phase mobile phase is nonpolar and it will creep up stationary phase through capillary action nonpolar solvents move furthest and polar substances do not move as far

Thin Layer Chromatography (TLC)

A type of chromatography that uses silica gel or alumina on a card as the medium for the stationary phase sample is spotted directly onto stationary phase mobile phase is nonpolar and it will creep up stationary phase through capillary action nonpolar solvents move furthest and polar substances do not move as far

Gas Chromatography (GC)

A type of chromatography used to separate vaporizable compounds; the stationary phase is a crushed metal or polymer and the mobile phase is a nonreactive gas (He or H2) eluents will be volatile and will travel through at different rates depending on interactions with the stationary phase once they reach the end, they will be registered by a detector, which records them as a peak on the chart

anti conformation

A type of staggered conformation in which the two largest groups are antiperiplanar to each other; the most energetically favorable conformation

oxidizing agent

Accepts electrons and becomes reduced oxidizes another molecule will have high affinity for electrons or will have unusually high oxidation states contain metals bonded to a large number of oxygen atoms

Reduction of Aldehydes and Ketones by Hydride Reagents

Aldehydes and ketones can also undergo reduction to form alcohols. This is performed with hydride reagents. -Lithium Aluminum Hydride (LiAlH4) -Sodium Borohydride (NaBH4), mainly used in milder conditions

enone

Alpha beta unsaturated carbonyl. Stable compound because multiple resonance structures. More susceptible to nucleophilic attack.

acid catalyzed hydrolysis of amides

Amides can be hydrolyzed to give carboxylic acids in the presence of aqueous acid, but the process is slow and requires heating occur at an appreciable rate electrophile: amide, carbonyl becomes protonated to make it more electrophilic nucleophile: water leaving group: amine or ammonium

Gabriel Synthesis

An amino acid is generated from phthalimide (nucleophile) and diethyl bromomalonate, using two SN2 reactions, hydrolysis, and decarboxylation. steps: 1. nitrogen on phthalimide acts as nucleophile and substitutes the bromide on diethyl-bromomalonate 2. hydrogen leaves the alpha carbon of diethyl-bromomalonate. This carbon becomes a carbanion and is very nucleophilic - stabilized by carboxylic acids on either side 3. nucleophilic carbon undergoes SN2 with a new alkyl halide to add a R group to the amino acid 5. nitrogen is hydrolyzed from the phthalimide by acid and water 6. resulting molecule is decarboxylated using acid and heat to release CO2 and amino acid generates a racemic mixture of D and L amino acids useful because it allows addition of R groups

wavenumber

An analog of frequency used for infrared spectra instead of wavelength. inversely proportional to wavelength directly proportional to frequency units are cm^-1

Synthesis of Carboxylic Acids

Carboxylic acids can be prepared via oxidation of aldehydes and primary alcohols. The oxidant used for this is usually dichromate salt (Na2Cr2O7 & K2Cr2O7), chromium trioxide (CrO3) or potassium permanganate (KMnO4) other methods include grignard reagents and hydrolysis of nitriles

Reduction of Carboxylic Acids

Carboxylic acids can be reduced to primary alcohols by the use of Lithium Aluminum Hydride (LiAlH4 - LAH) Aldehyde intermediates may be formed in the course of this of this reaction, but they to will be reduced to alcohol. -occurs by nucleophilic addition of hydride (H-) to the carbonyl group. LAH is a strong reducing agent that can successfully reduce a carboxylic acid. NaBH4 is not strong enough.

column chromatography

Chromatography in which the substances to be separated are introduced onto the top of a column packed with an adsorbent (as silica gel or alumina), pass through the column at different rates that depend on the affinity of each substance for the adsorbent and for the solvent or solvent mixture, and are usually collected in solution as they pass from the column at different times

stereoisomers

Compounds with the same structural formula but with a different arrangement of the atoms in space. can be conformational or configurational

physical properties of aldehydes and ketones

Dipole of the carbonyl is stronger than the dipole of an alcohols because of the double bonded oxygen is more electron withdrawn than the single bond to oxygen in the hydroxyl group. however the boiling point is not as high as alcohols because there is no H bonding present - so the dipole of a ketone is stronger than aldehyde Aldehyde and ketones both act as electrophiles making good targets for nucleophiles. this is due to the election withdrawn properties of the carbonyl oxygen, which leaves a partial positive charge on the carbon. Aldehydes are more reactive toward nucleophiles than ketones because they have less steric hindrance and fewer electron donating alkyl groups.

reducing agent

Donates electrons and becomes oxidized reduces another molecule will have low ionization energies and low electronegativities many times include sodium, magnesium, aluminum, and zinc contain metals bonded to a large number of hydrides

Gravity filtration vs vacuum filtration

Gravity filtration is used for when the desired product is in filtrate/solution (usually hot) and the solid impurities are removed. Gravity filtration relies on the gravitational force of the solution to pull itself through the filter vacuum filtration has the desired product being a solid / residue. Relies on vacuum forces to pull solution through filter

weak nuclophiles

H2O, ROH, RCOOH

strong nucleophiles

HO-, RO-, CN-, N3-

nomenclature of carboxylic acids

IUPAC system of nomenclature carboxylic acids are named by adding -oic acid to the parent root when the carboxylic acid is the highest priority functional group. The carbonyl carbon becomes number 1 when this is true. cyclic carboxylic acids are named by listing cycloalkane with suffix "carboxylic acid" salts of carboxylic acids are named by replacing "-ic acid" with the ending -oate dicarboxylic acids are named with suffix "-dioic acid"

configurational isomers

Isomers that can only interconvert by breaking bonds; include enantiomers, diastereomers, and cis-trans isomers.

acid dissociation constant

Ka the ratio of the concentration of the dissociated form of an acid to the concentration of the undissociated form measure of a strength of an acid

Strain in cyclic derivatives

Lactams and lactones are cyclic amides and esters. Certain lactams and lactones are more reactive to hydrolysis because they contain more strain. ex; B-lactams are four membered cyclic amides and are highly reactive due to significant ring strain; four membered rings have both compressing the norma sp3 angle of 109.5 degrees. most strain comes from non-ideal angles, resulting in angle strain or from eclipsing interactions (newman projection), resulting in torsional strain The ring strain and therefore the reactivity is increased by fusion to a second ring.

LiAlH4

Lithium aluminum hydride is a very strong reducing agent. It will reduce aldehydes, ketones, esters, and carboxylic acids to alcohols amides and nitriles to amines It will also open epoxides. reduce aldehydes to primary alcohols reduce ketones to secondary alcohols

Infrared (IR) Spectroscopy

Measures molecular vibrations that can be seen as bond stretching, bending, or combinations. (does not tell anything about chirality) infrared light is passed through a sample and the absorbance is measured absorption spectrum runs from wavelengths of 2500 to 25,000 nm or wave number 4000 to 400 cm ^-1 when bonds absorb the infrared light, they enter excited vibrational state, causing them to bend and stretch to different states only bonds that experience a change in dipole and those that are asymmetrical will exhibit absorption

chirality

Molecule that has non-superimposable mirror image, often because of a asymmetric carbon atom. When molecule lacks internal plane of symmetry achiral can have superimposed mirror image

fair nucleophiles

NH3, Cl-, F-, RCO2-

common strong bases to form enolates

NaOH Lithium diisopropyl amide (LDA) potassium hydride (KH)

aldehyde nomenclature

Name longest parent chain with carbonyl group; replace "e" with "al"; # parent chain so carbonyl group has lowest #; determine location of substituents and add in front of parent chain when they are not highest priority group, they are oxo- prefixes

Imines and Enamines

Nitrogen and nitrogen based functional groups act as good nucleophiles due to the lone pair of electrons on nitrogen, and readily react with the electrophilic carbonyls of aldehydes and ketones. Ammonia adds to the carbon atom and water is lost, producing an imine, a compound with a nitrogen atom double bonded to a carbon atom. This is a condensation reaction and because nitrogen replaces the carbonyl oxygen this is also an example of a nucleophilic subsitution. imine can undergo tautomerization to form enamine (double bond in carbons) depending on stability

staggered conformation

No overlap of atoms along the line of sight

nomenclature of alcohols

Nomenclature in the IAPUC system for alcohols follows as relaxing the -e ending of alkane with -ol if alcohol is not highest priority group, it becomes a prefix, hydroxy- if alcohol is on an aromatic ring, then the overall ring becomes a phenol

amides

Organic compounds whose molecules have a carbonyl nitrogen bond. They are the product formed in a nucleophilic acyl substitution reaction between a carboxylic acid and an ammonia (NH3) or an amine (NR2) note that one H+ is lost from the nucleophile during the reaction name replaces "-oic acid" with "-amide" and any alkyl groups attached to nitrogen start with prefix N- amides that are cyclic are called lactams and -"amine" is replaced with "-lactam" may or may not participate in hydrogen bonding, depends on if there are hydrogens present or not

pyridinium chlorochromate (PCC)

Oxidizing agent Oxidizes primary alcohols into aldehydes Oxidizes secondary alcohols into ketones

Chromium trioxide (CrO3) with pyridine

Oxidizing agent oxidizes primary alcohols into aldehydes oxidizes secondary alcohols into ketones

n+1 rule

Peaks on a H NMR spectrum always split into the number of hydrogens on the neighboring carbon(s), plus one.

Multiplet splitting pattern

Peaks that have more than four shifts in NMR spectroscopy.

molecular orbital

Region in a molecule where atomic orbitals overlap, resulting in either a stable low-energy bonding orbital or an unstable high-energy antibonding orbital.

azimuthal quantum number

Second quantum number, designated l. Tells us the shapes of the electron orbitals ranges from 0 to n-1 angular momentum 0=s 1=p 2=d 3=f

vacuum distillation

Separates liquids when boiling points are GREATER than 150C lower air pressure from vacuum decreases temperature needed for vapors from liquid to overcome air pressure to boil, effectively lowering temp to reach boiling point lower temp is important so that you do not degrade your product of interest

optical isomers

Stereoisomers that are non-superimposable mirror images of each other (ie chiral, enantiomers and diastereomers) spatial arangement of groups affects the rotation of plane-polarized light

conformational isomers

Stereoisomers that differ by rotation about one or more single bonds, usually represented using Newman projections.

steric protection

Steric hindrance is the prevention of reactions at a particular location within a molecule due to the size of substituent groups. Example being, how SN2 reaction won't occur with tertiary substrates, because they possess bulky CH3 groups this causes it impossible for the nucleophile to reach the most reactive electrophile, making it more likely to attack another region.

aldose

Sugar that contains an aldehyde group

conjugation system

System with connected p-orbitals with delocalized electrons in compounds with alternating single and multiple bonds, which in general may lower the overall energy of the molecule and increase stability. common example is benzene

preparative TLC

TLC on a larger scale, larger plate develops with a larger spot the sample splits into bands of individual compounds which can then be scrapped off to yield pure compounds

peptide bonds

The bonds connecting amino acids together to form polypeptide chains. formed from condensation reaction (releases water) and broken by hydrolysis reaction (catalyzed by acid or base) partial double bond resonance in C-N bond, resulting in it being planar, rigid, and limited in rotation surrounding single bonds are free to rotate

Decarboxylation

The complete loss of a carboxyl group as carbon dioxide and replacement with a hydrogen common for 1,3 carboxylic acids spontaneously will cleave into ketone and carbon dioxide upon the addition of heat (thermodynamically favored) transition state is 6 membered ring due to the fact that the electrophile and nucleophile is in the same molecule

coupling constant (J value)

The energy difference between spin states caused by spin-spin coupling. Also the chemical shift difference between the lines in a split NMR signal due to spin-spin coupling.

steric hindrance

The prevention of a reaction at a particular location in a molecule by substituent groups around the reactive site. interference by bulky groups that slow a reaction or prevent it from occurring

spin quantum number

The quantum number that has only two possible values, +1/2 and -1/2, which indicate the two fundamental spin states of an electron in an orbital

retro-aldol reaction

The reverse of an aldol condensation reaction, in which a carbon-carbon bond is cleaved with heat and aqueous strong base, yielding two aldehydes, two ketones, or one of each. must be done in water for reaction to occur (or else it would be a dehydration reaction)

Nucleophilic Acyl Substitution

The substitution of a nucleophile for the leaving group of a carboxylic acid or carboxylic acid derivative. Step 1: Nucleophilic Addition (such as an alcohol or an amine), forming tetrahedral intermediate Step 2: Elimination of the leaving group and reformation of the carbonyl.

acidity of alpha hydrogens

Through induction oxygen pulls electron density out of alpha C-H bonds, weakening them, and also thus stabilizes the anion of the conjugate. The conjugate anion is also stabilized by resonance between anion, carbonyl carbon, and oxygen, making it more acidic. the resonance forms enolate ion, which is a good nucleophile this acidity makes it relatively easy to deprotonate the alpha carbon of aldehyde or ketone Ketones less acidic than aldehydes due to extra carbons donating electrons, destabilizing the conjugate anion and the extra alkyl group increases steric hendrance

SN1 reactions

Unimolecular nucleophilic substitution reactions. two steps: 1- leaving group leaves, forming carbocation (rate limiting step) 2- nucleophile attacks carbocation from either of two directions and forms bond products are racemic because the nucleophile can attack top or bottom first order reaction, any thing that accelerates rate of formation of carbocation, the faster the reaction rate = K[R-L] carbocation is stabilized by more substitutions on the carbon

pyrophosphate (PPi)

[phosphorous-containing compounds] P2O7-4; released during formation of phosphodiester bonds in DNA; unstable in aqueous solution and is hydrolyzed to form 2 molecules of Pi to be later recycled into ATP

pi bond

a bond that is formed when parallel orbitals overlap to share electrons.

carbonyl group

a chemical group consisting of a carbon atom linked by a double bond to an oxygen atom C=O found in many chemicals, including aldehydes, ketones, carboxylic acids, esters, etc unique because it can act as nucleophile or electrophile

eclipsed conformation

a conformation about a carbon-carbon single bond in which the atoms or groups on one carbon are as close as possible to the atoms or groups on an adjacent carbon overlapped on newman projection highest energy can be partially eclipsed (120 degrees) or totally eclipsed (0 degrees) for the two largest groups

coordinate covalent bonds

a covalent bond in which one atom contributes both bonding electrons (lewis base)

bonding orbital

a molecular orbital that can be occupied by two electrons of a covalent bond formed when the signs of two atomic orbitals are the same lower energy, more stable

oxidation-reduction reactions

a reaction that involves the transfer of electrons between reactants oxidation state of the reactants change may involve simple electron transfers or gain or loss of a proton

amino acids

a simple organic compound containing both a carboxyl (—COOH) and an amino (—NH2) group. optically active and chiral (except glycine) all are L isomers in Fischer projection are all S configuration (except cysteine) amphoteric: act as acid or base zwitterionic: positive (N terminus) and negative (C terminus)

stereospecific reaction

a special type of stereoselective reaction in which the stereochemistry of the product is dependent on the stereochemistry of the starting material

gauche conformation

a staggered conformation with a 60 degree dihedral angle between the largest groups more stable than eclipsed

dehydration of aldol

a strong anhydrous base at high temperature (heat) added to aldol causes OH to become a water leaving group and leave to form an alpha,beta unsaturated carbonyl where there is a new C=C double bond alpha, beta unsaturated cabonyl is known as an enone, and it is a conjugated system that is extremely stable, due to resonance this reaction cannot be done in water water is produced in reaction, which is why its known as dehydration

order of electrophilicity for carboxylic derivatives

acid chloride > anhydride > carboxylic acid > ester > amide

ortho/o

adjacent to each other on the ring

geometric isomers

aka - cis / trans isomers Compounds that have the same molecular formula but differ in the spatial arrangements of their atoms around an immovable bond, like in a double bond or cyclic compound trans = opposite sides cis = same side Z = same side for polysubstituted E = opposite sides for polysubstituted

conjugated system

alternating single and multiple bonds one or more resonance structures each atom must have P orbital for resonance

magnetic resonance imaging (MRI)

brain-imaging method using radio waves and magnetic fields of the body to produce detailed images of the brain essentially hydrogen NMR but applied to medicine

O-H wavenumber in infrared spectroscopy

broad band around 3300 cm^-1 for alcohols 3000 cm^-1 for carboxylic acids

Carbonyl Nucleophilic Addition

carbonyl carbon is partially positive, making it site for nuclephilic attack when nucleophile forms covalent bond with carbonyl carbon, the pi electrons move from double bond to the electronegative oxygen, causing for the formation of the tetrahedral intermediate if leaving group is present: oxygen double bond will reform and the leaving group will be pushed off if leaving group is not present: tetrahedral shape will remain and the negatively charged oxygen will often accept a proton to become an alcohol

Lithium Diisopropylamide (LDA)

common strong base to remove alpha hydrogen from the alpha carbon to turn carbonyls into enolates, making them good nucleophiles

anhydride formation

condensation of two carboxylic acids via nucleophilic acyl substitution, one molecule of water is lost

Hemiacetal and hemiketal formation

created by an aldehyde/ketone with one equivalent of alcohol alcohol is nuclephile that adds to electrophilic carbonyl carbon forms tetrahedral with two R, one hydroxyl group and one ether endpoint in basic conditions can further go onto a ketal or acetal if more equivalents of alcohol were added

Lewis acid

electron pair acceptor has vacant p orbital and will be electron poor, usually with a positive charge electrophile

resonance

delocalization of electrons to create new structures of a molecule through a conjugated system

Reactive locations

depends on the chemistry occurring A redox reagent tends to act on the highest priority functional group. If a molecule has an alcohol and a carboxylic acid, the reducing agent will act upon the carboxylic acid vs. alcohol. for a reaction using Nucleophiles and Electrophiles the reactions tend to occur at the highest priority functional group because it contains the most oxidized carbon due to it having the largest partial positive charge -Carbon of a carbonyl: acquires + polarity due to EN of O. carbonyl carbon becomes electrophilic and is targeted by nucleophiles *α-hydrogens are more acidic than regular C-H bonds, can be deprotonated easily w/ strong base, turning it into an enol which becomes a good nucleophile (negative charge) *SN1 reactions: prefer tertiary to secondary carbons as reactive sites and secondary to primary *SN2 reactions: methyl & primary carbons are preferred over secondary; tertiary carbons don't react

nucleophilicity

determined by 4 factors: charge - increases with more negative charge electronegativity - decreases with more electronegativity steric hinderance - bulkier molecules are less nucleophilic solvent - protic solvents decreases by protonating or stabilization through hydrogen bonding

E-stereoisomer

determined by cahn-ingold-prelog priority rules E - entegen - means if highest priority groups across a polysubstituted double bond are opposite to one another

Z-stereoisomer

determined by cahn-ingold-prelog priority rules Z - zusammen - means if highest priority groups across a polysubstituted double bond are on the same side as each other

beta-dicarboxylic acids

dicarboxylic acids in which each carboxylic acid is positioned on the beta carbon of the other the two carboxylic acids are separated by a single carbon very acidic due to the alpha carbons located between the two and the alpha carbon will be stabilized by resonance and inductive effects from both carboxylic acids loss of an alpha carbon produces a carbanion - which is stabilized by the electron withdrawing effect of both carboxyl groups

Lewis base

donates electron pair to form covalent bond has P orbital, lone pairs, and will be electron dense, usually with a negative charge nucleophile

physical properties of alcohols

follow same trends as alkanes, BP increases with molecular mass and decreases with branching. BP are higher due to H bonding, more soluble in water than alkanes and alkenes longer carbon chain= less soluble alcohol hydroxyl group is weakly acidic and will give up proton at relatively high pH (however phenols are more acidic due to resonance stability)

antibonding orbital

formed when the signs of the 2 atomic orbitals are different higher energy, less stable

anhydride with amine

nucleophilic acyl substitution that results in cleavage of the anhydride results in amide and carboxylic acid

base catalyzed hydrolysis of amides

highly basic conditions electrophile: amide nucleophile: OH- (deprotonated water) leaving group: amine or ammonia

common nitrogen containing derivatives

hydrazine : H2N-NH2 hydroxylamine: H2N-OH semicarbazide: H2N-NH-C(O)NH2

Imine-Enamine Tautomerization

imine is carbon double bonded to nitrogen, most commonly found when nitrogen is bound to 0 or 1 substituents enamine is single bond to nitrogen but double bond to another adjacent carbon, most commonly found when nitrogen is bound to 2 substituents imine will naturally undergo tautomerization (electrons will move to form new bonds) to form enamines

anhydride with alcohol

nucleophilic acyl substitution that results in cleavage of the anhydride results in ester and carboxylic acid

Cyanohydrin Formation

ketone or aldehyde reacts with hydrogen cyanide HCN (in basic solution to produce anion) or with KCN cyanide anion acts as nucleophile to attack electrophilic carbonyl carbon, form tetrahedral intermediate, then the oxygen will become protonated to form cyanohydrin compound is very stable because the carbonyl forms a new C-C bond

acetal and ketal formation

ketone/aldehyde + 2 equivalents of alcohol + anhydrous acid carbonyl carbon electrophile is reacted to with one alcohol to form hemiacetal/hemiketal hydroxyl group of hemiacetal/ketal group is protonated and then lost as leaving group, leaving oxonium/carbocation to be attacked by a second alcohol nucleophile, forming the acetal/ketal acetals/ketas are often used as protecting groups for carbonyl functions since they are relatively inert and can be easily reverted back to carbonyls by adding anhydrous acid and heat

Steric Effects on electrophilicity of carboxylic acid derivatives

larger leaving groups = harder for nucleophile to attack = larger steric effects = decrease reactivity/electrophilicity

Why are aldehydes more reactive than ketones?

less steric hindrance

mobile phase of chromatography

liquid or gas will carry the eluent through the column or gel

oxidation

loss of electrons increase in oxidation state increasing the number of bonds to a oxygen or other heteroatom replacing hydrogens bonded to carbons with other carbons, nitrogens, oxygens, or halides

Nuclear Magnetic Resonance (NMR) Spectroscopy

magnetic field is applied to molecules and nuclei with magnetic moments (odd numbered protons/mass number) will allign with field in alpha state (with field) or beta state (against field) Radio frequencies (EM radiation) are then absorbed by the molecules, causing some of the alpha state nuclei to align their magnetic moments to the beta state. The absorption of the radio frequency is what is measured the absorption frequency depends on the atom's magnetic environment, allowing us to determine the atom's identity and how it is bonded to the other atoms in the molecule

proton chemical shift ranges

main ones to remember are: alkyl groups: 0-3 ppm alkynes: 2-3 ppm alkenes: 4.6 -6 ppm aromatics: 6-8.5 ppm aldehydes: 9-10 ppm carboxylic acids: 10.5-12 ppm

relative reactivity of carboxylic acid derivatives (nucleophilic addition)

most reactive to least reactive Acid chlorides Acid anhydrides: resonance stabilization and many electron withdrawing groups, high inductive effect Esters and carboxylic acids: electron withdrawing groups Amides: electron donating groups, less inductive effect

common names for aldehydes

methanal=formaldehyde ethanal=acetaldehyde propanal=propionaldehyde butanal = butylaldehyde pentanal = valeraldehyde

Amino acid types

nonpolar aromatic aromatic polar negatively charged (acidic) positively charged (basic)

Hydrogen Cyanide (HCN)

nucleophile triple bonds and electronegative nitrogen atom acidic (pKa 9.2), becomes nucelophile after deprotonation

transesterification reaction

nucleophilic acyl substitution ester is electrophile and different alcohol is a nucleophile. The attached alcohol is the leaving group the reaction of an ester with an alcohol to form a different ester essentially the alcohols swap places

fisher esterification reaction

nucleophilic acyl substitution reaction where an alcohol replaces the -OH group of a carboxylic acid takes place under acidic conditions step 1: protonation of the carbonyl group (makes it more electrophilic) step 2: nucleophilic attack, forming tetrahedral intermediate step 3: protonation of hydroxyl group and reformation of the carbonyl and leaving group (H2O) step 4: deprotonization of the carbonyl group

chair flip

one chair conformation is converted to the other briefly passes through the half chain conformation all axial groups become equatorial all equatorial groups become axial dashed lines remain dashed wedges remain wedges conversion is slowed if there is bulky groups attached (tert-butyl) bulkiest group will favor the equatorial position

double bond

one sigma bond and one pi bond no free rotation 4 electrons

triple bond

one sigma bond and two pi bonds no free rotation 6 electrons

Common Names of Dicarboxylic Acids

oxalic acid = ethandioic acid malonic acid = propandioic acid succinic acid = butandioic acid glutaric acid = pentanedioic acid adipic acid = hexanedioic acid pimelic acid = heptanedioic acid

pyridinium chlorochromate (PCC) with alcohol

oxidizes primary alcohol to an aldehyde but will not turn it into a carboxylic acid because it lacks water to hydrate it oxidizes secondary alcohol to a ketone

acetals

primary carbons with two -OR groups and a hydrogen atom formed by reacting aldehydes with two equivalents of alcohols or diols will serve as a protecting group by preventing carbonyl reactions with reducing agents (like LiAlH4) can be removed or deprotected, and revert the acetal back to carbonyl by adding aqueous acid

Cahn-Ingold-Prelog priority rules

priority is given by looking at the atoms connected to the chiral carbon or double-bonded carbons - whichever has the highest atomic number gets highers priority - if there is a tie, one moves outward from the chiral carbon or double bond until the tie is broken -branching atoms are considered higher atomic number

nucleophilic substitution reactions

reactions in which one functional group is replaced by another as the result of nucleophilic attack

relative configuration vs absolute configuration

realative configuration = must be compared to other molecules (enantiomer, analagous, diastereomer) absolute configuration = spatial arrangement independent of other molecules (R and S, E and Z)

CaH2

reducing agent reduce aldehydes to primary alcohols reduce ketones to secondary alcohols

NaH

reducing agent reduce aldehydes to primary alcohols reduce ketones to secondary alcohols

NaBH4

reductant reduce aldehydes to primary alcohols reduce ketones to secondary alcohols not as reactive as LiALH4 (no carboxylic acids or nitriles)

levorotatory

refers to a substance that rotates the plane of polarized light to the left (counterclockwise) (-)

cis - trans for cyclohexane

refers to groups added on to cyclohexane cis is both dash / wedge on the ring trans is one dash one wedge on the ring

ketone nomenclature

replace -e with -one when they are not highest priority group, they are oxo- or Keto- prefixes

dextrorotatory

rotates plane-polarized light in a clockwise direction (+)

Ketals

secondary carbons with two -OR groups formed by reacting ketones with two equivalents of alcohols or diols will serve as a protecting group by preventing carbonyl reactions with reducing agents (like LiAlH4) can be removed or deprotected, and revert the acetal back to carbonyl by adding aqueous acid

constitutional isomers

structural isomers, have same molecular formula but differ in the covalent arrangements of their atoms least similar of isomers

C=O wavenumber in infrared spectroscopy

sharp band around 1750 cm^-1

N-H wavenumber in infrared spectroscopy

sharp band around 3300 cm^-1

keto-enol tautomerization

shift from a carbonyl to an alkene with an alcohol. It is a reaction at equilibrium; these structures are not resonance structures when the alpha carbon is deprotonated, the enol form is favored and the equilibrium shifts

acetal/ketal reversion

simply add anhydrous acid and heat to the acetal/ketal and it will revert back to original carbonyl (aldehyde or ketone)

sigma bond

single covalent bonds; occurs when the pair of shared electrons is in an area centered between the two atoms either head to head, tail to tail, or two s orbitals overlap

single bond

single sigma bond free rotation 2 electrons

Stationary phase of chromatography

solid medium usually polar substance, like silica gel in TLC or cellulose

enantiomers

stereoisomers that have same connectivity but have opposite configurations at all chiral centers identical physical and chemical properties except optical activity and reactions on chiral environments

diastereomers

stereoisomers that have same connectivity different configurations at some but not all chiral centers different physical properties and chemical properties (optical rotation)

ketose

sugar containing ketone

magnetic quantum number

symbolized by m, indicates the orientation of an orbital around the nucleus ranges from -l to +1

Principle quantum number

symbolized by n, indicates the main energy level occupied by the electron dictates period on periodic table, corresponds with size and energy level

molecular vibrations measured by infrared (IR) spectroscopy

symmetric bend asymmetric bend symmetric stretch asymmetric stretch

mass spectrometry

technique based of the detection of vaporized molecules and their ionized (charged) fragments; detection and display of the spectra are based on the mass-to-mass charge ratios of the ions; method is specific for qualitative analysis and useful for quantitative analysis

hydrogen bonding

the intermolecular force in which a hydrogen atom that is bonded to a highly electronegative (O,F, or N) atom is attracted to an unshared pair of electrons of an electronegative atom in a nearby molecule

hybridization

the mixing of several atomic orbitals to form the same total number of equivalent hybrid orbitals

optical activity

the rotation of plane-polarized light by a chiral molecule left = counterclockwise = levorotatory (l-) = - right = clockwise = dextorotatory (d-) = + enantiomers rotate with same magnitude but in opposite direction of mirror image diastereomers will have different magnitude and direction as other diastereomers

Formation of aldehydes and ketones

to form aldehyde, primary alcohol can be oxidized by PCC to form ketone, secondary alcohol can be oxidized by dichromate salts, chromium trioxide (CrO3) or PCC

Saponification

triacylglycerols are esters of long chain carboxylic acids and glyceral that is the storage form of fats in the body. These have the ability to undergo saponification the reaction between a fat (long chain carboxylic acid) and a strong base (sodium hydroxide) to produce a salt, which we know as soap the soap forms micelles which have polar outsides and nonpolar insides nonpolar insides dissolve grease, and the whole micelle is dissolved by water, allowing us to wash grease and dissolve it in water

meta/m

two groups separated by a carbon

fisher projections

vertical lines are assumed to be oriented into the page (dash). horizontal lines are assumed to be oriented out of the page (wedge)

Fractional distillation

used to separate two liquids with similar boiling points (less than 25 C apart) uses a fractional column that has increased surface area, using glass projections, glass beads, or steel wool as vapor rises, condenses, and falls back into the distilling flask, it will purify more and more so when it evaporates again, it will reach higher up into the column because it consists of a higher proportion of the lower bp liquid by the time it reaches the top of the column and reaches the receiving flask, it will be nearly all lower bp liquid

Hydration of carbonyls

water + carbonyl react to form geminal diols where water is nucleophile and carbonyl is electrophile reaction rate is increased if in the presence of a catalytic base or acid

Cr2O7 2- (dichromate)

will oxidize secondary alcohols into ketones will oxidize primary ketones into carboxylic acids