MCAT Organic chemistry

Chemoselectivity

-preferential reaction of one functional group in the presence of other functional groups Reactive Locations: *Redox reagent tends to act on highest priority functional group (Reducing agent more likely to act on carboxylic acid than alcohol *the more oxidized the functional group, the more reactive it is in both nucleophile-electrophile and oxidation-reduction reactions *Carboxylic acids and derivatives first to be targeted by nucleophile, followed by aldehyde then ketone, then alcohol or amine *Carbon of carbonyl has positive polarity (makes it an electrophile, becomes a target for nucleophiles) because of electronegative oxygen -Also, alpha hydrogens are more acidic becuase they are resonance stabilized in enroll form (easily deprotonated with strong base, forming enolate) -Enolate becomes strong nucleophile, can result in alkylation

deutrium

1 proton and 1 neutron

What would be the effect on the Rf values if the thin-layer chromatography (TLC) described below were run with hexane rather than ether as the eluent? Compound Retardation Factor in Ether Benzyl alcohol 0.10 Benzyl acetate 0.26 p-Nitrophenol 0.23 1-Naphthalenemethanol 0.40 If benzyl alcohol, benzyl acetate, p-nitrophenol, and naphthalene were separated by column chromatography with ether on silica gel, which compound would elute first according to the Rf values from question 3? A. Benzyl alcohol B. Benzyl acetate C. p-Nitrophenol D. 1-Naphthalenemethanol

Hexane is less polar than ether and, therefore, is less likely to displace polar compounds adsorbed to the silica gel. This would decrease the distance these polar compounds would travel, decreasing Rf values. Correct Answer: D Explanation: In column chromatography, as in TLC, the less polar compound travels most rapidly. This means that 1-naphthalenemethanol,with the highest Rfvalue, would travel most rapidly and would be the first to elute from the column.

Quinones and Hydroxyquinones

Phenol + oxidizing agents (like NaCr2O7) Quinones : Resonance stabilized electrophiles (not necessary aromatic) -Produced by oxidation of phenols -Resonance stabilized Electron acceptors -Used in electron transport chain -Phylloquinone and menaquinone = Vitamins K1 and K2 (important for photosynthesis and carboxylation of clotting factors) Quinones can be further oxidized into Hydroxyquinones -> same ring and carbonyl, but have one or more additional hydroxyl groups -Electron donating, less electrophilic, but still reactive A hydroquinone is a benzene with two hydroxyl groups, but a hydroxyquinone contains two carbonyls and a number of hydroxyl groups

Saponification

Process by which fats are hydrolyzed under basic conditions to produce soap Treating triacylglycerols (storage form of fats) with NaOH will produce fatty acid salts (soap) and glycerol Long-chain carboxylic acids react with sodium or potassium hydroxide and a salt is formed (soap) Mixing fatty acids with lye (sodium or potassium hydroxide) Can solvate non polar organic compounds in aqueous solutions because they have non polar tail and polar carboxylate head When placed in aqueous solution, molecules form sphere called micelles (polar heads face out, so non polar hydrophobic inside of sphere is protected) The structure as a whole in hydrophilic Can dissolve non polar molecules deep in its core

Alkene with Br2 and CH2Cl2

anti addition of Brs on either side of double bond (Cyclic intermediate) If you add Br2 over H2O, you get anti-addition with ZBr on less substituted and OH on more substituted If it was Br2 / CH3OH, you get Br on less substituted, and OCH3 on more substituted

Electrophiles

"Electron-loving" atoms with a positive charge or positive polarization; can accept an electron pair when forming new bonds with a nucleophile. (think of Lewis acids, but remember that electrophilicity is kinetic process which acidity is thermodynamic process) More positive charge = more electrophilicity Anhydrides are most reactive, then carboxylic acids and esters, then amides (derivatives of higher reactivity can form derivatives of lower reactivity but not vice versa SN2 favors electrophiles with less steric hinderance

1) Hg(OAc)2, H2O 2) NaBH4

"Oxymercuration- demercuration": Treatment with an alkene gives a Markovnikov addition of H and OH across the alkene, without any carbocation rearrangements.

Conformational Isomers

)Stereoisomers that differ by rotation about one or more single bonds (σ) -Most similar form of isomer -Different levels of strain -usually represented using Newman projections. Newman projections: Wedges on right, dashes on left *Low energy = not reactive = more stable *Anti-confirmation is most stable (least energy): farthest apart as possible (180 degrees apart) *Gauche is second most stable (steric strain only)(60 degrees apart and 300 degrees apart) (more gauche interactions, which occur when non-hydrogen things are next to each other = more unstable) , followed by eclipsed (torsional and steric strain) (120 and 240 degrees), least stable (most energy) is when big groups are overlapping (total eclipse) -In the image, anti-staggered is the first isomer and the last (where CH3s are as far away as possible = lowest energy (least stressed out -> happiest) -> oriented 180 degrees away, least steric hindrance ) -Anti staggered because anti means largest groups are antiperiplanar (in the same plane but opposite sides) and staggered because there is no overlap (most energetically favorable type of staggered conformation) *LOWEST ENERGY = MOST ENERGETICALLY FAVORABLE -Other type of staggered confirmation: Gauche (2 largest groups are 60 degrees apart) -To go from anti- to gauche confirmation, molecule passes through eclipsed formation where methyl groups are 120 degrees apart and H are aligned -When methyl groups overlap with 0 degree separation (synperiplanar) = totally eclipsed (least favorable energetically = highest energy) *The higher the energy, the less time the molecule will spend in the energetically unfavorable state (High potential energy systems are unstable and if possible, they are likely to change to adopt a more stable situation -Conformational interconversion barriers are small (19 kcal/mol) between anti-staggered and totally eclipsed butane) and are easy to overcome at room temp, but at low temp interconversions are VERY slow (may not rotate at all (no rotational at absolute 0))

Gas Chromatography (GC)

- Also known as vapor-phase chromatography (VPC) *Sample injected into column and moves with gaseous mobile phase through stationary liquid or solid phase -Eluent is gas (usually helium or nitrogen) instead of liquid - The adsorbent is a crushed metal or polymer inside a 30 foot column. -Mixture injected into column and vaporized - The gaseous compounds travel through the column at different rates because they adhere to the adsorbent in the column to different degrees and will separate in space by the time they reach the end of the column. - The injected compound must be volatile: low melting point, sublimable solids or vaporizable liquids. -Compounds registered by detector: Records them as peaks on a chart (Computer identifies sample components) - It is common to separate molecules using GC and then to inject the pure molecules into a mass spectrometer for molecular weight separation (Ionization and fragmentation of compounds -> run through a magnetic field, which separates them by mass to charge ratio) -> identified by comparing to reference value

Ubiquinone ubiquinone to ubiquinol (reduction)(Ketone to alcohol is a reduction)

- Biologically active quinone (electron acceptor in photosynthesis and aerobic respiration) -Coenzyme Q (vital electron carrier with complexes 1, 2, and 3 in ETS) - Reduced to ubiquinol upon the acceptance of electrons. -Main player in Q cycle -> gives you proton motive force - Long alkyl chain = lipid soluble = act as an electron carrier within the phospholipid bilayer. -Conjugated rings help it stabilize

Thin-Layer And Paper Chromatography

- Both very similar -> Varying only in the medium used for the stationary phase. - For thin layer Chromatography (TLC), a thin layer of silica gel or alumina adherent to an inert carrier sheet is used - For paper chromatography, paper composed of cellulose is used - Sample we want is placed directly on the adsorbent -> Spotting: well defined spot of the sample directly onto the silica or paper plate -Spots must be above level of the solvent - Plate is then developed: Adsorbant placed upright in developing chamber -> Eluent (shallow pool of solvent at the bottom of the jar): solvent will creep up the plate by capillary action -silica gel which is polar and hydrophilic - Mobile phase: organic solvent of weak to moderate polarity (doesn't bind well to gel) -Nonpolar compounds dissolve in organic solvent and move up quickly -more non polar the sample, further up the plate it will move. Samples placed at X mark in image shown Nonpolar solvent moves up the plate via capillary action, non polar samples move further up, polar dont move so far Reverse phase chromatography: Everything is opposite (stationary phase used is non polar, so polar molecules move up quickly, and non polar move slowly *The solvent system is polar, which means that the most polar compound will travel the furthest up the card, resulting in the largest Rf. This gives compound III the largest Rf, which corresponds to spot A. Developed plate placed under UV light (Iodone, phosphomolybdic acid, or vanillin can also be used to stain spots Rf value (Retardation factor): Distance dot moves (from the start line) divided by distance from start line to solvent from (top of the strip (the stop line)) -Can be used as preparative TLC technique too

Amides

- Carboxylic acid derivative May or may not participate in hydrogen bonding depending on number of alkyl groups bonded, so BP varies - OH is replaced with an amino group (Contains Nitrogen)(-Oic suffix replaced with -amide) -Can be bonded to 0,1, or 2 alkyl groups -Substituents attached to nitrogen labeled with capital N (included as substituents, not numbered) Carboxylic acids can be converted into amides if the incoming nucleophile is ammonia or an amine (NH2) (image shown) Resonance between the carbonyl and lone pair on the N stabilizes bond (restricts motion) Amides that are cyclic are called LACTAMS Anhydrides are most reactive towards nucleophilic attack because of resonance stabilization and presence of 3 electron withdrawing oxygen atoms, followed by esters (lack one of the electron withdrawing carbonyl oxygen) and carboxylic acids, then amides (electron donating)

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 - Height of each peak is proportional to the number of protons it contains. -> chemically equivalent - Integration: Area under the peak (a) to (b) is 1:3 - The position of the peak (upfield or downfield) is due to shielding or deshielding effects and reflects the chemical environment of the protons - (a) is downfield due to electronegative cl atoms and an oxygen atom that pull electron density away from the surrounding atoms, deshielding the proton *DESHIELDING PUSHED H TO THE LEFT (increasing frequency shift), SHIELDING PUSHES H TO THE RIGHT

Lactones

- cyclic esters - named by the number of carbons in the ring and the Greek letter of the carbon forming the bond with the oxygen

Column chromatography

- uses an entire column filled with silica or aluminum beads as an adsorbent, allowing for much greater separation. *TLC uses capillary action to move solvent up the plate whereas column chromatography uses gravity to move solvent and compounds down the column - To speed this up: Flash Column Chromatography: one can force the solvent through the column using gas pressure. Solvent polarity can also be changed to help elute desired compound Sample added to top, solvent poured over it - The more similar the sample is to the mobile phase, the faster it elutes; the more similar it is to the stationary phase, the more slowly it will elute - Used in biochemistry to separate and collect macromolecules such as proteins or nucleic acids. -Techniques used to isolate specific materials: Ion Exchange, Size Exclusion, and Affinity chromatography

Cyanohydrins

--HCN is a nucleophile that attacks the carbonyl carbon and generates a cyanohydrin --HCN has both triple bonds and an electronegative nitrogen atom, rendering it relatively acidic w/ pKa of 9.2. *H dissociates so cyanide anion (nucleophile) can come in and attack carbonyl --Rxns w/ aldehydes and ketones produce stable compounds called cyanohydrins once the oxygen has been reprotonated. --gains its stability from the newly formed C-C bond.

Imine and Enamine

--primary amine + aldehyde or ketone = imine --secondary amine + aldehyde or ketone = enamine Imines can undergo tautomerization to form enamels, which contain both a double bond and a nitrogen containing group

Anhydrides (acid anhydrides)

-MOST reactive toward nucleophiles -carboxylic acid derivative Formula of RC(O)OC(O)R -Condensation dimers of Carboxylic acids -had water molecule removed during formation -Very electrophilic: resonance stabilization and presence of 3 electron withdrawing oxygen atoms -formed from 2 carboxylic acid molecules via nucleophilic acyl substitution (shove two carboxylic acids together by removing water)(image shown) -Many are cyclic (Formed by applying heat) (increased stability of ring) Often have higher BP than COOH just because they have greater weight Anhydrides are most reactive towards nucleophilic attack because of resonance stabilization and presence of 3 electron withdrawing oxygen atoms, followed by esters (lack one of the electron withdrawing carbonyl oxygen) and carboxylic acids, then amides (electron donating)

Esters

-carboxylic acid derivatives -Dehydration synthesis product of carboxylic acid or anyhdride and alcohol -Hybrid between CA and ether (ROR) -hydroxyl group (-OH) is replaced with an alkoxy group (OR where R is a hydrocarbon chain) -No hydrogen bonding so they usually have lower boiling point than COOH -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 *-oate sometimes shortened to -ate Esters that are cyclic are called lactones *Methanoic acid (formic acid) would form butyl methanoate

Leaving Groups

-molecular fragments that retain e- after heterolysis -Heterolytic reactions are the opposite of covalent bond formation: bond is broken, and both electrons go to one product -Best leaving groups stabilize extra electrons -Weak bases are more stable w/ extra electrons, so they make good leaving groups (Conjugate bases of strong acids make good leaving groups, like I-, Br-, and Cl-) -Good leaving groups Delocalize/ Stabalize negative charge -Alkanes and hydrogen ions will not serve as leaving groups -Substitution: weak base (LG) replaced by stronger base (nucleophile) ALDEHYDES AND KETONES LACK LEAVING GROUPS, BUT CARBOXYLIC ACIDS AND DERIVATIVES HAVE LEAVING GROUPS WITH VARYING DEGREES OF STABILITY

Naming Anhydrides

-named by replacing acid with anhydride in the name of the carboxylic acid if anhydride is formed from only 1 type of carboxylic acid (symmetrical, just replace -acid for -anhydride) -if anhydride is not symmetrical, both carboxylic acids are named before the anhydride is added to the name (ex: ethanoic propanoic anhydride) Common name of ethanoic anhydride (symmetrical): Acetic anhydride ex: pentanoic acid becomes pentanoic anhydride

Diastereomers

-non mirror image configurational isomers -not superimpossable -differ at some of their multiple chiral centers -For any molecule with n chiral centers, there are 2^n possible stereoisomers (4 stereoisomers with 2 chiral centers ) -They will rotate plane polarized light, but we don't need to know specifics Cis-trans isomers (geometric isomers) are special type of diasteromer in which substituents differ in their position around immovable bond (double bond) or ring structure (one substituent on each side: same side = cis, different side = trans)

Jones Oxidation Na2Cr2O7 and K2Cr2O7 (over H2SO4)

-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 Another strong oxidizing agent is Na2Cr2O7 and K2Cr2 O7 (over H2SO4) Basically Chromium is just really strong

IUPAC Naming Rules

1. Identify the longest carbon chain (parent chain) containing the highest-order functional group (If two or more chains are equal length, more substituted (more bonds) gets priority)(Highest priority functional group (one with the most oxidized carbon) will provide suffix) *For example, 2-methyl-2-butanol is named such because there is a methyl and alcohol on C2, and even though it is usually 2-hydroxy, it is named on the end because it is highest priority 2. Number the chain (carbon 1 is closest to highest priority functional group / make the numbers on substituted carbons as low as possible *More oxidized = higher priority (Oxidation state increases with more bonds to heteroatoms (atoms besides carbon and hydrogen) and decreases with more bonds to hydrogen ) *If there is tie between double and triple bond, double bond gets lower number 3. Name the substituents (functional groups not part of parent chain) -Placed as prefix, but the highest priority functional group determines suffix for the compound -Carbon chain substituents = alkanes (suffix -yl instead of -ane) Methyl: CH3- Ethyl: CH3CH2- n-propyl: CH3CH2CH2- -If there are multiple substituents of the same type, use prefix (di, tri, tetra) before substituents name 4. Assign a number to each substituent 5. Complete the name -Names always begin with substituents in alphabetical order (ignoring hyphenated prefixes, but not unhyphenated prefixes (like iso, Neo, cyclo still count in alphabetical order))(each substituent has their own number, even if on the same carbon)

Geminal Diol

A functional group with two hydroxyl groups on the same carbon; also called a hydrate. 1,1 diol Pretty unstable, easily oxidized to carboxylic acid

Fischer Projection

A method of drawing organic molecules in which horizontal lines are coming out of the page (wedges) and vertical lines are going into the page (dashes) -Points of intersection = carbon -If H is horizontal (on a wedge), whatever you find the confirmation to be, switch it (if you get R, switch to S) *Rotating 90 degrees inverts stereochemistry, rotating 180 maintains it Look at bottom chiral center OH on right = D OH on left = L

Nucleophilic substitution

A type of substitution reaction in which a nucleophile is attracted to an electron-deficient centre or atom, where it donates a pair of electrons to form a new covalent bond.

Hybridization

A way of making al of the bonds to a central atom equivalent to each other Hybridized orbitals mix different types of orbitals SP3: Tetrahedral geometry (no unhybridized p-orbitals to form pi bonds) -Takes one of the electrons from 2s into 2p and makes 4 equal valence orbitals, each with 1 electron SP3 bond has 25% S character and 75% p character SP2: 3 sp2 hydridized orbitals (120 degrees apart): 33% s character, 67% p character -Trigonal planar -Seen in alkenes, third p orbital left empty, this orbital participates in double bond SP (image shown): Triple bond, 2 of the p-orbitals form pi bonds and the third combines with s to form two sp orbitals 50% S and 50% P character (180 degrees apart, linear) -Can form triple bond between carbon and 1 other atom or two pi bonds between carbon and 2 other atoms

1. Hg(OAc)2, CH3OH 2. NaBH4

Add OCH3 instead of OH

Acidic and Basic Side Chains

Acid - Base Properties of Amino Acids: Acidic Side Chains: If the side chain contains an acid functional group, the whole amino acid produces an acidic solution. Normally, an amino acid produces a nearly neutral solution since the acid group and the basic amine group on the root amino acid neutralize each other in the zwitterion. If the amino acid structure contains two acid groups and one amine group, there is a net acid producing effect. The two acidic amino acids are aspartic and glutamic. Basic Side Chains: If the side chain contains an amine functional group, the amino acid produces a basic solution because the extra amine group is not neutralized by the acid group. Amino acids which have basic side chains include: lysine, arginine, and histidine. Amino acids with an amide on the side chain do not produce basic solutions i.e. asparagine and glutamine. Neutral Side Chains: Since an amino acid has both an amine and acid group which have been neutralized in the zwitterion, the amino acid is neutral unless there is an extra acid or base on the side chain. If neither is present then then the whole amino acid is neutral. Amino acids with an amide on the side chain do not produce basic solutions i.e. asparagine and glutamine. You need to look at the functional groups carefully because an amide starts out looking like an amine, but has the carbon double bond oxygen which changes the property. Amides are not basic. Even though tryptophan has an amine group as part of a five member ring, the electron withdrawing effects of the two ring systems do not allow nitrogen to act as a base by attracting hydrogen ions.

Review of acid and base strength

Acid dissociation constant (Ka) measure strength of acid in solution Ka = [H+][A-]/[HA] pKa = -log Ka More acidic = lower pKa (below -2 = strong acid, dissociate completely) (weak acids = pKa between -2 and 20) Generally bond strength decreases down the periodic table, and acidity increases Also the more electronegative, the higher the acidity When these 2 trends oppose each other, low bond strength takes precedence More basic = higher pKa Amides and amines act as bases (donates lone pair to Lewis acid) Alpha hydrogens (on alpha carbons (adjacent to carbonyl)) are easily lost (BL acid) *More acidic alpha hydrogen more likely to leave because more electronegative effects on Alpha carbon weaken the bond Functional groups that act like acids: CARBOXYLIC ACIDS (and derivates), alcohols, aldehydes and ketones: Easier to target with basic (nucleophilic) reactants because they accept lone pair

Would acid dissolve better in aqueous acid or aqueous base?

Acid dissolves better in aqueous base because it will dissociate to form the conjugate base and, being more highly charged, will become more soluble. Note that like dissolves like applies to polarity , acids and bases dissolve more easily in solutions with the opposite acid-base characteristics

Review: Anhydrides can be cleaved by the addition of a nucleophile Addition of ammonia or an amine results in Addition of an alcohol results in Addition of water results in

Addition of ammonia or an amine results in amide and carboxylic acid (Reverse: amides can be hydrolyzed to carboxylic acids under strongly acidic or basic conditions, with water or hydroxide anion as attacking nucleophile) Addition of an alcohol results in ester and carboxylic acid Addition of water results in 2 carboxylic acids

1. B2D6 2. H2O2, OH

Adds deuterium atom and OH in syn (same side, both wedge or both dash) -Get pair of enantiomers, both with sin addition (one product both wedges, one product both dashes If there is a methyl group already on ring, don't get confused because the carbon is in the back, its still sin reaction becuase the H is on wedge (image shown)

If ethanol is reacted in acidic solution with potassium dichromate, what will the end product be? CH3CH2OH with K2Cr2O7/H2SO4

Alcohol jumps over aldehyde all the way to carbonic acid becuase only things like pyridinium chlorochromate (PCC) can take alcohol one step up to aldehyde

Transesterification

Alcohols can act as nucleophiles and displace the esterifying group on an ester Ester transformed into different ester (alcohol chain swapped into ester position so you get new ester and new alcohol)

Nucleophilic Acyl Substitution: Anhydride to Ester and Carboxylic Acid

Alcohols can act as nucleophiles toward anhydrides Nucleophilic substitution results in formation of esters and carboxylic acids Anhydrides can also be reverted to 2X carboxylic acids after exposure to water through similar method (if anhydride is symmetric)

Aldehydes and Ketones

Aldehyde: Carbonyl group (Carbon double bonded to oxygen) at the end of the carbon chain (chain terminating / terminal functional group) -Carbonyl group + H on carbon -Carbonyl on carbon 1 (don't need to include this in name) -Name by replacing e on alkane with suffix -al -Common (not IUPAC) names for aldehydes: Formaldehyde (1 carbon, 2 H, and carbonyl group), acetaldehyde (C-C bonded to H and carbonyl group), propionaldehyde Ketone: Carbonyl group (Carbon double bonded to oxygen) found in the middle -Name by listing alkyl groups in alphabetical order, followed by -one suffix *Aldose = aldehyde sugar, ketose = ketone sugar *Use prefixes -oxo and -keto when group takes precedence over carbonyl *Carbon next to carbon of aldehyde = alpha (if C of carbonyl is C1, alpha is C2), then moving away from carbonyl (C3) is beta, then gamma (y), then delta -Carbon on both sides of ketone are alpha (there is only one alpha carbon in aldehydes Aldehydes are in the middle of the oxidation-reduction spectrum (more oxidized than alcohols, less than carboxylic acids) Ketones are as oxidized as a secondary carbon can get

Reduction by Hydride Reagents

Aldehydes and Ketones can undergo reduction to form alcohols Performed by : Hydride Reagents Lithium Aluminum Hydride - LiAlH4 Sodium Borohydride -NaBrH4

Acetals and Hemiacetals

Aldehydes and ketones treated with alcohols (nucleophile) When one equivalent of alcohol is added -> hemiacetal or hemiketal formed (Halfway step, still has 1 hydroxyl group) When 2 equivalents are added, the reaction goes to completion, forming acetal or ketal (can be used as protecting groups) Proceeds by nucleophilic substitution (SN1), catalyzed by anhydrous acid Hydroxyl group eventually protonated and lost as water to form final product

Protecting groups

Aldehydes and ketones would readily react with strong reducing agents like LiAlH4 but this can be prevented. by first reacting with 2 equivalents of alcohol (Produces nonreactive ketal or acetal) Aldehydes and ketones can be reacted with two equivalents of an alcohol or idol (dialcohol) forming acetals (primary carbon with two -OR groups ) and Ketals (secondary carbon with 2 -OR groups) (image shown) Carbonyls are very reactive with strong reducing agents (LiAlH4) but acetals and metals do react , so it protects aldehyde or ketones from reaction After reducing other stuff, you can take off protective cap with aqueous acid (deprotection)

Proton Chemical Shift Range

Alkyl groups: 0-3 ppm Alkynes: 2-3 ppm Alkenes: 4.6 - 6 ppm Aromatic: 6-8.5 ppm Aldehydes: 9-10 ppm Carboxylic acids: 10.5 - 12 ppm

Hydrolysis of Amides

Amides can be hydrolyzed under highly acidic conditions via nucleophilic substitution. The acidic conditions allow the carbonyl oxygen to become protonated, making the molecule mores susceptible to nucleophilic attack by a water molecule. The product of this reaction is a carboxylic acid and ammonia. (reverse of condensation reaction by which amides are formed) Don't forget hydrolysis can also occur if conditions are basic enough. The reaction is similar to an acid-catalzed reaction, except that the carbonyl oxygen is not protonated and the nucleophile is a hydroxide ion. The product of this reaction would be the deprotonated carboxylate anion. Strongly acidic conditions catalyze amide hydrolysis by protonating oxygen in the carbonyl. Increases electrophilicity of the carbon making it more susceptible to nu attack Strongly basic conditions greatly increase concentration of OH- which can act as nucleophile on amide carbonyls Image: Strong acid or base is needed to catalyze hydrolysis of amides, which are normally pretty stable

Amino Acids -> Peptides -> Proteins

Amino acids are dipolar molecules that come together through condensation reactions forming peptides Larger, folded peptide chains are considered proteins Amino acids contain amino group and carboxyl Group on one (alpha) carbon the other 2 substituents of the alpha carbon are a hydrogen atom and side chain (R-Group) Alpha carbon is chiral (stereogenic) -Exception: glycine is the simplest amino acid anti does;t have chiral center because the R group is another Hydrogen All naturally occurring amino acids in eukaryotes (except for glycine) are optically active and L-isomers *Fischer projection for amino cid is drawn with amino group on the left *All L amino acids have S configuration , expect for cysteine which is (R) because of the change in priority caused by sulfur in R group (technically sulfur is slightly higher priority than carbon, if it were (S), the R group would be on dash and you need it on wedge) Amino acids are amphoteric molecules (can act as acids and bases) -Amino groups can take on positive charge when protonated, carboxylic acid side can take on negative charge when deprotonated (so + = basic and - = acidic When both charges are taken on (in neutral solution), forms dipolar ion or zwitterion (amino is + charged, carboxylic acid is O-) How amino acid acts depends on pH (Acidic solution = fully protonated, basic solution = fully deprotonated) like other carbonyl containing functional groups, amides have two resonance structures: Partial double bond character between the N atom and carbonyl carbon -> limits rotation around CN bond: adds to rigidity/stability of backbone However, the single bond on either side of the peptide bond allows full rotation (image shown)

Peptide bond formation and cleavage

Amino acids undergo condensation reactions to form peptide bonds -> form polypeptides, which are the base unit for proteins *Reverse reaction: hydrolysis of peptide bond catalyzed by strong acid or base

Nucleophilic Acyl Substitution: Anhydride to Amide and Carboxylic Acid

Ammonia and carboxylic acid or any derivate Cleavage reaction shown: Splits anhydride in two Ammonia is nucleophile, one carbonyl compound is electrophile (carboxylic acid is leaving group)

Specific rotation equation

Amount of rotation determined by concentration of optically active compound and length of tube -Standard conditions of 1 g/mL concentration and 1 dm (10 cm) for length Standardized specific rotation = | alpha | = alpha / c * l where | alpha | = specific rotation in degrees, alpha is observed rotation in degrees, c is concentration (in g/ mL) and l is path length (in dm)

Review of acids and bases

An acid-base reaction will only proceed if the products (conjugate base of acid and conjugate acid of base) are weaker than original reactants Lewis definition focuses on transfer of electrons (formation of coordinate covalent bonds: both electrons came from Lewis base) Bronsted focuses on transfer of protons Lewis acid = electron acceptor (tend to be electrophiles)(have vacant p orbitals into which they can accept electron pair, or are positively polarized atom) Lewis base = electron donor (tend to be nucleophiles)(often anions, carrying negative charge) *Arrow from base to acid In bronsted lowry, arrow goes from acid to base (transferring H)(Acid donates H, base accepts H) Amphoteric: can be either acid or base (like water, Al)OH)3, HCO3^- = carbonate, HSO4^- = dihydrogen phosphate) *water can only act as base in acidic solution, and can only act as acid in basic solution

Size Exclusion Chromatography (SEC) Affinity Chromatography

Beads used in column have tiny pores of varying sizes -Allow small compounds to enter beads, slowing them down -Large compounds can't fit into pores, so they will move through column faster *kinda backwards thinking: smaller move slower, larger go faster Affinity Chromatography : Specific receptors or antibodies can trap target in column (target must be washed out using other solutions) -Protein of interest is bound by creating column with high affinity for the protein -Coating beads with receptor that binds protein or specific antibody to the protein (so protein is retained in column) Common stationary phase molecues include nickel (used in separation of genetically engineered proteins with hissing tags), antibodies or antigens, and enzyme substrate analogs (mimic natural substrate) Once protein is retained in column, it can be eluted by washing the column with a free receptor (or target or antibody) which will compete with the bead-bound receptor and ultimately free the protein from the column Eluents can also be created with varying pH or salinity levels that disrupts the bonds between the ligand and the protein of interest (but, recovered substance might be bound to eluent -> if the fluent was an inhibitor , it could be difficult to remove)

Acidity of the alpha-hydrogen in beta-dicarboxylic acids

Beta dicarboxylic acids are dicarboxylic acids in which each CA is positioned at the beta of the other ( 1 carbon apart) -Alpha hydrogens have high acidity (pKa of 9-14) Applies to alpha hydrogens in a beta diketone, beta ketoacids, beta dialdehydes, ect (anything with 1,3 dicarbonyl structure) A dicarboxylic acid would be most acidic, as the 2nd carboxyl group is electron withdrawing and contributes to even higher stability of anion after the loss of the first hydrogen. However, a monocarbocylate anion is electron donating and destabilizes the product of the second deportation step, resulting in decreased acidity

1) H2SO4

Bisulfate group oxygen (Negative charge after H leaves) Puts OSO3H on most substituted carbon

Retro-Aldol Reaction

Bond is broken between alpha and beta carbon of a carbonyl, forming 2 aldehydes, 2 ketones, or 1 ketone and 1 aldehyde Aqueous base added and heat is applied Reaction facilitated if intermediate can be stabilized in enolate form

Carbonyl

Can behave as either nucleophile (condensation reactions) or as electrophile (Nucleophilic addition reactions) Amides, esters, and anhydrides are all formed by a condensation reaction with carboxylic acid -Water is the small molecule that is lost (comes from hydroxyl group on COOH) Both ketone and aldehyde have carbonyl group, but ketone will always be internal, and aldehyde is terminal functional group If an aldehyde is attached to a ring, the suffix -carbaldehyde is used instead The carbonyl carbon is a super common electrophile: Oxygen is more electronegative and pulls electrons away from the carbon, making the carbon electrophilic (partial positive charge) and a good target for nucleophiles The dipole of carbonyl is more electronegative than dipole of alcohol because double bond to oxygen is more electron withdrawing -However, alcohols still have higher boiling points because they have hydrogen bonding Aldehydes and ketones can be produced by primary alcohol + PCC Ketones can be obtained from secondary alcohol + PCC or CrO3 or Na2Cr2O7 or K2Cr2O7

Review of atomic orbitals and quantum numbers

Carbon is tetravalent (can bond with 4 other atoms, has a lot of versatility Organic chemistry focuses on covalent bonds (electrons re shared), not ionic bonds (electrons are transferred) The first three quantum numbers, n, l, and ml described size, shape, number, and orientation of atomic orbitals The principal quantum number, n, can be 1-7 (CANT BE 0) (for the MCAT, actually goes from 1- infinity) and measures size The smaller the number, the closer the shell is to the nucleus, and the lower its energy (because it doesn't have as far to fall) l (azimuthal quantum number ) describes the subshells/ shape, which range from 0 to (n-1) 0 = s subshell (least energy) 1 = p 2 = d 3= f Within each subshell there can be several orbitals (ml) = magnetic quantum number -> ranges from -l to +l *to determine ml, draw out possible electron orbitals (p has three, s has 1, d has 5, f has 7, and draw in electrons (following hands rule)) Whatever orbital you draw your last electron in = value of ml Note: A node is an area of an orbital where the probability of finding an electron is 0 Each orbital can hold 2 electrons (-1/2 or +1/2) -> spin quantum number = ms If the electron is pointed down, it is negative, up is positive

Major Functional Groups in order of priority

Carboxylic acid > anhydride > ester > amide > aldehyde > ketone > alcohol > alkene/alkyne > alkane *Alkenes and alkynes tied for highest priority except in cyclic compounds, where alkenes have highest priority Use suffix if the functional group is the highest priority, otherwise name group as substituent Functional group priority is correlated with oxidation state Alkanes have lowest priority Functional group, prefix and then suffix: Carboxylic acid: Carboxy- : -oic acid Anhydride: alkanoyloxycarbonyl- : anhydride Ester: alkoxycarbonyl- : -oate (sometimes -ate) Amide: carbamoyl- or amido- : -amide Aldehyde: oxo- : -al Ketone: oxo- or keto-: -one Alcohol: Hydroxy- : -ol Alkene/Alkyne: alkenyl/alkynyl-: -ene/-yne Alkane: alkyl- : -ane

Oxidation-Reduction (Redox) Reactions

Carboxylic acids are more oxidized than aldehydes, ketones, and imines, which are more oxidized than alcohols, alkyl halides, and amines Oxidation: Increase in oxidation state (decrease in electrons)(fewer bonds to hydrogen -> replaced with bond to more electronegative atom) Reduction: Increase in reduction state, decrease in oxidation state (increase in electrons) Oxidation: number of bonds to oxygen or other heteroatom (not C and H) Reduction = decrease in oxidation state, gain in electrons, usually increase in number of bonds to hydrogen No bonds to heteroatom: Alkanes (Most reduced) Then, in order of increasing oxidation, we have alcohols, alkyl halides, and amines, then aldehydes, ketones and imines, then carboxylic acids and anhydrides and esters and amides, then carbon dioxide (4 bonds to heteroatms) is most oxidized Oxidizing agent gains electrons and is reduced High affinity for electrons (O2, O3, Cl2) or high oxidation states (Think of Mn and Cr) Alcohols can be oxidized one level to become aldehyde or another level to become carboxylic acids *Strong oxidizing agents: CrO3, Na2Cr2O7 and K2Cr2O7 *PCC stops reactions at the aldehyde level *Secondary alcohols can be oxidized to ketones

Synthesis of Carboxylic Acids: Nucleophilic Acyl Substitution

Carboxylic acids can be prepared with oxidation of aldehydes and primary alcohols with Potassium permanganate (KMnO4), dichromate salt (Na2Cr2O7 or K2Cr2O7) or chromium trioxide (CrO3) Secondary and tertiary alcohols cant be oxidized to carboxylic acids You can also get carboxylic acids from Grignard reagents and hydrolysis of nitriles (dont worry about this) Carbonyl is opened via nucleophilic attack, forming tetrahedral intermediate, but this time there is a leaving group (OH becomes OH2+ when H+ is added and then leaves as water), so carbonyl can reform and Nu:- takes the place of OH group Nu molecule replaces LG of acyl derivative (includes CA, amides, esters, anhydrides... ) Weak bases (conjugate bases of strong acids) make good leaving groups

Nuclear Magnetic Resonance (NMR) Spectroscopy

Certain atomic nuclei have magnetic moments that are oriented at random -Magnetic moments align either with or against direction of applied field (aligned with field = alpha state (lower energy) and then radio frequency pulses that match the energy excite some lower energy nuclei into the beta state (higher energy)) -Magnetic moments also affected by nearby atoms *Magnetic Resonance imaging (mri) uses proton NMR *Protein structure can be determined thorough X-ray crystallography (more reliable and used) and NMR spectroscopy NMR spectrum plots frequency vs absorption of energy *Arbitrary value called chemical shift (gamma) in units of parts per million (ppm) of spectrometer frequency: Plotted on x-axis, increases towards the left (downfield) *Use tetramethylsilane (TMS)as reference peak / calibration standard at gamma = 0 ppm (skip this peak when counting) NMR mostly used for protons, but any atom with nuclear spin (with odd atomic number or odd mass number or both) can be studied (like C^13 NMR, 19F, 17O) *Not all nuclei have atomic moments (C12 doesn't) MCAT only tests HMNR

Propanone (IUPAC name)

Common Name: Acetone Type of ketone

Molecular orbitals can contain a maximum of: A. one electron. B. two electrons. C. four electrons. D. 2n2 electrons, where n is the principal quantum number of the combining atomic orbitals.

Correct Answer: B Explanation: Like atomic orbitals, molecular orbitals each can contain a maximum of two electrons with opposite spins. The 2n2 rule in choice (D) refers to the total number of electrons that can exist in a given energy shell, not in a molecular orbital.

Isomers

Compounds with the same molecular formula but different structures. Structural Isomers/ constitutional isomers: Least similar of isomers, same molecular weights and formula, but different chemical and physical properties (C6H14 has 5 different structural isomers) Stereoisomers: Same chemical formula AND same atomic connectivity / same structural backbone (but differ in dashes or wedges: how atom are arranged in space) -All isomers that are not structural isomers are sterioisomers -Split into conformational (Conformers: differ in rotation around sigma (single) bonds) and configurational (can only be converted by breaking bonds) *All single bonds are σ bonds; double and triple bonds each contain one σbond and one or two π bonds Each single bond has one σ bond, and each double bond has one σ and one π bond

Relative and absolute configurations

Configuration of stereoisomer = spatial arrangement of atoms/molecules Relative configuration: configuration relating to another chiral molecule (compare to another chiral molecule) Absolute configuration describes exact spatial arrangement of atoms or groups, independent of other molecules (R and S)

A mixture of sand, benzoic acid, and naphthalene in ether is best separated by: A. filtration, followed by acidic extraction, followed by recrystallization. B. filtration, followed by basic extraction, followed by evaporation. C. extraction, followed by distillation, followed by gas chromatography. D. filtration, followed by size-exclusion column chromatography, followed by extraction..

Correct Answer: B Explanation: In this question, three substances must be separated using a combination of techniques. The first step should be the most obvious: remove the sand by filtration. The remaining compounds—benzoic acid and naphthalene—are still dissolved in ether. If the solution is extracted with aqueous base, the benzoate anion is formed and becomes dissolved in the aqueous layer, while naphthalene, a nonpolar compound, remains in the ether. Finally, evaporation of the ether will yield purified naphthalene

Carboxylic Acids

Contain both a carbonyl group (C double bonded to O) and hydroxyl group (-OH) -Terminal functional groups (like aldehydes) -Usually numbered 1 (most oxidized functional group, with 3 bonds to oxygen ) -Naming: Replace -e with -oic acid -Salts of carboxylic acids are named beginning with the cation, ending -oate replacing -oic acid (like in sodium hexanoate) -Common names used more than IUPAC -Carboxylic acid derivatives: Esters, amides, and anhydrides *Note: Formaldehyde and formic acid refer to aldehyde and carboxylic acid with methane as parent, acetaldehyde and acetic acid have ethane as parent Can react as nucleophiles and electrophiles Found in AMINO ACIDS Strong, unpleasant odors Like to give away protons (they are acids) because this lets the negative charge resonate between the 2 oxygen atoms (stabilizes it) pKa around 3-6 (compared to pka 17 for alcohols) means that they are REALLY acidic (acidity from resonance stabilization, enhanced by addition of electronegative groups or greater ability to delocalize charge) Large IMF and boiling point due to H bonding Tend to form dimers: Pairs of molecules connected by 2 hydrogen bonds (more H bonds = higher BP and MP , also increase with increasing molecular weight) Carboxylic acids can be reduced to to aldehydes to primary alcohols with LiAlH4, but NaBH4 is not strong enough to reduce them

Which of the following will convert a cyclic acetal to a carbonyl and a dialcohol? A. Aqueous acid B. LiAlH4 C. CrO3 D. Acetone

Correct Answer: A Explanation: An acetal can be converted to a carbonyl and a dialcohol by treatment with aqueous acid. This is the final step when using alcohols as protecting groups, called deprotection.

Rank the following in order of decreasing leaving group ability: H2O, HO-, Br-, H- A. H2O > Br- > HO- > H- B. H2O > HO- > Br- > H- C. HO- > Br- > H2O > H- D. HO- > H- > H2O > Br-

Correct Answer: A Explanation: Good leaving groups are weak bases, which are the conjugates of strong acids. Leaving groups must also be stable once they leave the molecule. H2O is, by far, the most stable leaving group and will be extremely unreactive once it leaves the molecule through heterolysis. Br- is the conjugate base of HBr; HO- is the conjugate base of water. HBr is a much stronger acid than water, so Br- is a better leaving group than HO-. Finally, hydride (H-) is a very poor leaving group because it is extremely unstable in solution.

Treating 2-methyl-1-propanol with methylsulfonyl chloride in base, followed by reaction with pyridinium chlorochromate, and a final step in strong acid, will give an end product of: A. 2-methyl-1-propanol. B. 2-methylpropanal. C. 2-methylpropanoic acid. D. 2-methyl-1-propane.

Correct Answer: A Explanation: Methylsulfonyl chloride serves as a protecting group for alcohols, which are converted into mesylates. Reacting with this reagent before continuing with what would normally be an oxidation reaction keeps the alcohol from reacting; when the protecting group is then removed using strong acid, the resultant product is the same as the initial reactant. Neither of the oxidation products in choices (B) or (C), nor the reduction product in choice (D), will be formed.

Reaction of 1-phenylethanone with ethylene glycol, also known as ethane-1,2-diol, in aqueous H2SO4 will result in the formation of: A. a ketal. B. a carboxylic acid. C. an aldehyde. D. a ketone.

Correct Answer: A Explanation: This reaction will create a ketal. This is the first step of the protection of aldehydes or ketones using dialcohols.

Suppose an extraction with methylene chloride (density = 1.33) is performed, with the desired compound initially in brine (density - 1.04) In a separatory funnel, which layer will be the organic layer? A. Top layer B. Bottom layer C. No layers are observed; methylene chloride and brine are completely miscible. D. More information is needed to answer the question.

Correct Answer: B Explanation: Because methylene chloride is denser than brine (salt water), the organic layer will settle at the bottom of the funnel. Methylene chloride is nonpolar, so it cannot mix with brine, eliminating choice (C).

Which of the following will convert CH3CH2CH2OH to CH3CH2CHO? I. CrO3 II. PCC III. K2Cr2O7 A. I only B. II only C. I and III only D. I, II, and III Which of the following will convert cyclohexanol to cyclohexanone? I. Chromium trioxide II. Pyridinium chlorochromate III. Sodium dichromate A. I only B. II only C. I and III only D. I, II, and III

Correct Answer: B Explanation: CH3CH2CH2OH is 1-propanol, a primary alcohol. The desired end product, CH3CH2CHO, is propanal, an aldehyde. The only reactant capable of oxidizing primary alcohols to aldehydes is pyridinium chlorochromate (PCC). Chromic trioxide and dichromate salts will both oxidize primary alcohols to carboxylic acids. Correct Answer: D Explanation: Cyclohexanol is a secondary alcohol, so any of the oxidizing agents listed will convert it to a ketone.

The gas eluent in gas chromatography and the liquid eluent in paper chromatography are examples of which component of these systems? A. Stationary phase B. Mobile phase C. Column D. Fraction

Correct Answer: B Explanation: Each of these is the mobile phase of the system, in which the solutes are dissolved and move. The stationary phase in gas chromatography is usually a crushed metal or polymer; the stationary phase in paper chromatography is paper.

The common names for the aldehydes and carboxylic acids that contain only one carbon start with which prefix? A. Para- B. Form- C. Meth- D. Acet-

Correct Answer: B Explanation: Form- is a prefix shared by the common names of methanoic acid (formic acid) and methanal (formaldehyde).

Which of the following correctly lists hexanol, phenol, and cyclohexanol by increasing acidity of the hydroxyl hydrogen? A. Phenol < hexanol < cyclohexanol B. Cyclohexanol < hexanol < phenol C. Cyclohexanol < phenol < hexanol D. Phenol < cyclohexanol < hexanol

Correct Answer: B Explanation: Phenols have significantly more acidic hydroxyl hydrogens than other alcohols, so this will be the most acidic hydroxyl hydrogen. The acidity of hexanol and cyclohexanol are close, but the hydroxyl hydrogen of hexanol is slightly more acidic because the ring structure of cyclohexanol is slightly electron-donating, which makes its hydroxyl hydrogen slightly less acidic.

Omeprazole is a proton pump inhibitor commonly used in gastroesophageal reflux disease. When omeprazole, a racemic mixture, went off-patent, pharmaceutical companies began to manufacture esomeprazole, the (S)-enantiomer of omeprazole, by itself. Given 1 Msolutions of omeprazole and esomeprazole, which solution(s) would likely exhibit optical activity? A. Omeprazole only B. Esomeprazole only C. Both omeprazole and esomeprazole D. Neither omeprazole nor esomeprazole

Correct Answer: B Explanation: Racemic mixtures like omeprazole contain equimolar amounts of two enantiomers and thus have no observed optical activity. Each of the two enantiomers causes rotation in opposite directions, so their effects cancel out. Esomeprazole only contains one of the two enantiomers and thus should cause rotation of plane-polarized light.

Consider (E)-2-butene and (Z)-2-butene. This is a pair of what type(s) of isomers? I. Cis-trans isomers II. Diastereomers III. Enantiomers A. I only B. II only C. I and II only D. I and III only

Correct Answer: C Explanation: (E)-2-butene can also be called trans-2-butene; (Z)-2-butene can also be called cis-2-butene. As such, they are cis-trans isomers. Remember that cis-trans isomers are a subtype of diastereomers in which the position of substituents differs about an immovable bond. Diastereomers are molecules that are non-mirror-image stereoisomers (molecules with the same atomic connectivity). These are not enantiomers because they are not mirror images of each other.

Which of the following correctly lists methanol, isobutyl alcohol, and propanol by decreasing boiling point? A. Methanol > isobutyl alcohol > propanol B. Isobutyl alcohol > methanol > propanol C. Isobutyl alcohol > propanol > methanol D. Methanol > propanol > isobutyl alcohol

Correct Answer: C Explanation: All else being equal, boiling points increase with increasing size of the alkyl chain because of increased van der Waals attractions. Isobutyl alcohol has the largest alkyl chain and will thus have the highest boiling point; methanol has the smallest chain and will thus have the lowest boiling point.

If 2-butanol was treated with dichromate, what reaction would occur? A. Reduction, resulting in the formation of butene B. Oxidation, resulting in the formation of butanoic acid C. Oxidation, resulting in the formation of butanone D. No reaction would occur

Correct Answer: C Explanation: Because 2-butanol is a secondary alcohol, oxidation by a strong oxidizing agent like dichromate will result in a ketone, 2-butanone.

3-methylpentane and hexane are related in that they are: A. enantiomers. B. diastereomers. C. constitutional isomers. D. conformational isomers.

Correct Answer: C Explanation: Because they have the same molecular formula, but different atomic connectivity, 3-methylpentane and hexane are constitutional isomers.

Which of the following compounds would be most effective in extracting benzoic acid from a diethyl ether solution? A. Tetrahydrofuran B. Aqueous hydrochloric acid C. Aqueous sodium hydroxide D. Water

Correct Answer: C Explanation: By extracting with sodium hydroxide, benzoic acid will be converted to its sodium salt, sodium benzoate. Sodium benzoate, unlike its conjugate acid, will dissolve in an aqueous solution. The aqueous layer simply has to be acidified to retrieve benzoic acid. Choice (A) is incorrect because diethyl ether and tetrahydrofuran are both nonpolar and are miscible. Hydrochloric acid will not transform benzoic acid into a soluble salt, so choice (B) is incorrect. Finally, choice (D) is incorrect because protonated benzoic acid has low solubility in water.

Consider the name 2,3-diethylpentane. Based on the structure implied by this name, the correct IUPAC name for this molecule is: A. 2,3-diethylpentane. B. 1,2-diethylbutane. C. 3-ethyl-4-methylhexane. D. 3-methyl-4-ethylhexane.

Correct Answer: C Explanation: Draw out the molecule, and you will see that the longest carbon chain with the substituents at the lowest possible carbon numbers is actually different from the one chosen in the original name. The correct IUPAC name for this molecule is 3-ethyl-4-methylhexane.

(2R,3S)-2,3-dihydroxybutanedioic acid and (2S,3R)-2,3-dihydroxybutanedioic acid are: I. meso compounds. II. the same molecule. III. enantiomers. A. I only B. III only C. I and II only D. I and III only

Correct Answer: C Explanation: Draw out these structures. The two names describe the same molecule, which also happens to be a meso compound because it contains a plane of symmetry. These compounds are not enantiomers because they are superimposable mirror images of one another, not nonsuperimposable mirror images. These compounds are better termed meso-2,3-dihydroxybutanedioic acid:

If the methyl groups of butane are 120° apart, as seen in a Newman projection, this molecule is in its: A. highest-energy gauche form. B. lowest-energy staggered form. C. middle-energy eclipsed form. D. highest-energy eclipsed form.

Correct Answer: C Explanation: In butane, the position at which the two methyl groups are 120° apart is an eclipsed conformation. This has a moderate amount of energy, although not as high as a totally eclipsed conformation in which the two methyl groups are 0° apart.

Rank the following in order of decreasing nucleophilicity in an aprotic solvent: RO-, RCOOH, ROH, HO- A. RCOOH > ROH > RO- > HO- B. HO- > ROH > RO- > RCOOH C. RO- > HO- > ROH > RCOOH D. RCOOH > RO- > HO- > ROH Rank the following in order of decreasing electrophilicity: CR3+, CH3OH, CH3OCH3, CH3Cl A. CH3OCH3 > CR3+ > CH3OH > CH3Cl B. CR3+ > CH3OH > CH3OCH3 > CH3Cl C. CH3OCH3 > CH3Cl > CR3+ > CH3OH D. CR3+ > CH3Cl > CH3OH >CH3OCH3

Correct Answer: C Explanation: Remember, good nucleophiles tend to have lone pairs or π bonds and are negatively charged or polarized. Alkoxide (RO-) and hydroxide (OH-) anions are strong nucleophiles. Alcohols (ROH) and carboxylic acids (RCOOH) are weak nucleophiles. The alkyl group of an alkoxide anion donates additional electron density, making it more reactive than the hydroxide ion. The carboxylic acid contains more electron-withdrawing oxygen atoms than the alcohol, making it less nucleophilic. Correct Answer: D Explanation: Good electrophiles are positively charged or polarized. CR+3 is a tertiary carbocation; it has a positive charge, which makes it very electrophilic. CH3Cl and CH3OH are both polarized; however, the leaving groups differ between these two. Cl- is a weaker base than OH- (HCl is a stronger acid than H2O). As such, Cl- will be more stable in solution than OH-, which increases the electrophilic reactivity of CH3Cl above CH3OH. CH3OCH3has a much less stable leaving group, CH3O-, and is therefore significantly less electrophilic.

The following reaction results in: (image on next slide) A. retention of relative configuration and a change in the absolute configuration. B. a change in the relative and absolute configurations. C. retention of the relative and absolute configurations. D. retention of the absolute configuration and a change in the relative configuration.

Correct Answer: C Explanation: The relative configuration is retained because the bonds of the stereocenter are not broken; thus the positions of groups around the chiral carbon are maintained. The absolute configuration is also retained because both the reactant and product are (R).

An electron is known to be in the n = 4 shell and the l = 2 subshell. How many possible combinations of quantum numbers could this electron have? A. 1 B. 2 C. 5 D. 10

Correct Answer: D Explanation: An electron in the n = 4 shell and the l = 2 subshell can have five different values for ml: -2, -1, 0, 1, or 2. In each of these orbitals, electrons can have positive or negative spin. Thus, there are 5 × 2 = 10 possible combinations of quantum numbers for this electron.

A scientist takes a 0.5 M solution of an unknown pure dextrorotatory organic molecule and places it in a test tube with a diameter of 1 cm. He observes that a plane of polarized light is rotated 12° under these conditions. What is the specific rotation of this molecule? A. -240° B. -24° C. +24° D. +240°

Correct Answer: D Explanation: Remember that the equation for specific rotation is | alpha | = alpha of abs / C*l. In this example, α obs is +12° (remember that dextrorotatory, or clockwise, rotation is considered positive), c = 0.5 M, l = 1 cm = 0.1 dm. Remember that path length is always measured in decimeters when calculating specific rotation. Therefore, the specific rotation can be calculated as: +12 / 0.5 * 0.1 = 12 / 0.05 = 1200/ 5 = +240

Which conversion between carboxylic acid derivatives is NOT possible by nucleophilic reaction? A. Carboxylic acid to ester B. Ester to carboxylic acid C. Anhydride to amide D. Ester to anhydride

Correct Answer: D Explanation: Remember, there is a hierarchy to the reactivity of carboxylic acid derivatives that dictates how reactive they are toward nucleophilic attack. In order from highest to lowest, this is anhydrides > carboxylic acids and esters > amides. In practical terms, this means that derivatives of higher reactivity can form derivatives of lower reactivity but not vice-versa. Nucleophilic attack of an ester cannot result in the corresponding anhydride because anhydrides are more reactive than esters.

All of the following are true with respect to carbonyls EXCEPT: A. the carbonyl carbon is electrophilic. B. the carbonyl oxygen is electron-withdrawing. C. a resonance structure of functional group places a positive charge on the carbonyl carbon. D. the π electrons are mobile and are pulled toward the carbonyl carbon.

Correct Answer: D Explanation: The reactivity of the carbonyl can be attributed to the difference in electronegativity between the carbon and oxygen atoms. The more electronegative oxygen atom attracts the bonding electrons and is therefore electron-withdrawing. Thus, the carbonyl carbon is electrophilic, and the carbonyl oxygen is nucleophilic. One resonance structure of the carbonyl pushes the π electrons onto the oxygen, resulting in a positively charged carbonyl carbon.

Which of the following solvents would be LEAST useful for a nucleophile-electrophile reaction? A. H2O B. CH3CH2OH C. CH3SOCH3 D. CH3CH2CH2CH2CH2CH3

Correct Answer: D Explanation: To carry out a nucleophile-electrophile reaction, the nucleophile must be able to dissolve in the solvent. Nucleophiles are nearly always polar, and often carry a charge. Polar solvents are therefore preferred for these reactions. Hexane is a nonpolar solvent and will not be useful for a nucleophile-electrophile reaction.

Gabriel (Malonic-ester) Synthesis Which of the following would be formed if methyl bromide were reacted with pthalimide and followed by hydrolysis with an aqueous base?

Don't over complicate it: Final product: Whatever R group is attached to Br + NH2 mashed together. (Answer is CH3NH2) A method of synthesizing amino acids that uses potassium phthalimide (acidic, nucleophilic anion) reacted with diethyl bromomalonate (Secondary carbon bound to bromine = good leaving group -> think of this as electrophile) followed by an alkyl halide; two substitution reactions (SN2) are followed by hydrolysis and decarboxylation. Generates phthalimidomalonic ester Large nucleophile = steric hinderance = substrate carbon doesn't undergo multiple substitutions , so instead, it is easily protonated with base and heat Phthalimide moiety removed as ophthalmic acid with 2 carboxylic acids Malonic ester hydrolyzed to dicarboxylic acid (1,3 dicarbonyl) with amine on alpha carbon -Decarboxylated with acid and heat -> carbon dioxide lost and complete amino acid fomred Like striker synthesis. Gabriel synthesis starts with a planar molecule, so product is also racemic mixture of L and D amino acids

Area Ratios for Peaks Split by Adjacent Hydrogens

Doublet: 2 peaks of identical intensity (equally spaced around true chemical shift (alpha and beta state)) The splitting of peak represents the number of adjacent hydrogens. A peak will be split into n+1 sub peaks, where n is the number of adjacent hydrogens *Do not include protons split into n+1 peaks *The magnitude of splitting measured in hertz: Coupling constant (J) Dont over complicate it, if it is around 2 protons, its a triplet (n+1) (how many H connected to carbon connected to carbon with H you are looking at) Proton NMR is good for: Determining the relative number of protons and their relative chemical environments *Showing how many adjacent protons there are by splitting patterns Inferring certain functional groups Outliers: deshielded aldehyde at 9-10 ppm and even more desuhielded carboxylic acid between 10.5-12 ppm Hydrogen of aromatic ring between 6-8.5 ppm SP3 hybridized carbons : 0-3 ppm, higher if e- withdrawing groups are present) SP2 hybridized carbons (4.6-6.0 ppm ) and SP hybridized carbons 2-3 ppm Electronegative groups pull electrons higher (more deshielded)

keto-enol tautomerization

Due to acidity of Alpha H, aldehydes and ketones have 2 isomer: Keto and enol form Tautomers: Differ in placement of hydrogen and double bond Any ketone or aldehyde with chiral alpha carbon will become racemic mixture of the two Keto = more common, traditional form of C double bond to O (thermodynamically favored) ENol -> think ENE + ol as in alkENE + alcohol Deprotonated enolate can act as nucleophile *Keto form more thermodynamically stable (less energy) (acts as electrophile) TAUTOMERS ARE NOT RESONANCE STRUCTURES because they differ in connectivity *Enol tautomer is less thermodynamically stable and has higher energy than keto Enols are important intermediates -> enolate carbanion from deprotonation of of alpha carbon by strong base (like hydroxide ion, LDA (lithium diisopropyl amide) and KH (potassium Hydride) ) More carbonyls = more delocalized negative charge = more acidic -> good for forming enolate carbanion (nucleophilic, readily reacts with electrophiles) This is seen in aldol (1,2 addition) condensation and Micheal addition (1,4 addition) 1. Hydroxide grabs alpha proton, forms enolate 2. In Michael addition , you have a pi bond on the substrate in an alpha beta position (unsaturated double bond between alpha and beta carbon) Double bond shifts some charge to the partially positive carbon, so the enolate no longer attacks the carbonyl carbon, it attacks the beta carbon instead (also partially positive / electrophilic)

High Performance Liquid Chromatography (HPLC) (previously called high pressure liquid chromatography)

Eluent is liquid and travels through a column of defined composition Stationary Phase varies depending on the compound of interest Small sample is injected into column and separation occurs as it flows through Compounds pass through detector and are collected as solvent flows out of the end of the apapratus Interface is silar to GC (entire process is done by computer) Highly sophisticated

Filtration and Recrystallization

Filtration: Isolates solid from liquid (solvent passes through filter, leaving solid residue and the flask full of liquid passed through filter = filtrate) Gravity filtration: solvent's weight pulls it through the filter (more commonly used when filtrate is product of interest (vacuum filtration more often used when solid / residue is what you are after) Recrystallization: Further purifying crystals in solution: Dissolve product in minimum amount of hot solvent and let it recrystallize -Solvent should be one in which the product is only soluble at high temperatures, so when solution cools, only the desired product will recrystallize out of solution, excluding the impurities

Common Names

For aldehydes: - formaldehyde for methanal - acetaldehyde for ethanal - propionaldehyde for propanal *Same trend for carboxylic acids Ketones: Name alkyl groups on either side of carbonyl (2-butanone is called ethylmethylketone) Alcohols: Name the carbon chain + alcohol (ethanol becomes ethyl alcohol)

Alkene with H2 / Pt

Get rid of double bond You might also see isotope of hydrogen (D2) / Pd, basically still the same thing Syn addition of D, becomes alkane

Common Name Prefixes for Aldehydes and Carboxylic Acids:

Form: One carbon -Methanoic acid = formic acid Acet: Two carbons -Ethanoic Acid = Acetic Acid Propion: Three carbons -Propanoic acid = propionic acid

Phosphoric acid (Phosphate group, inorganic phosphate, Pi)

Forms high-energy bonds that carry energy in adenosine triphosphate (ATP) Inorganic phosphate contains very negative charge (resonance stabilized) -> creates repulsion when bonded to other phosphate groups in a nucleotide triphosphate, increasing energy in bond Includes molecules of both hydrogen phosphate (HPO4^2-) and dihydrogen phosphate (H2PO4^-) Phosphorous also found in DNA backbone in phosphodiester bonds linking sugar moieties of nucleotides When a new nucleotide is joined to growing strand of DNA by DNA polymerase, it releases ester dimer of phosphate called pyrophosphate (P2O7^4-, called PPi) ->Hydrolytic release of PPi provides energy for formation of new phosphodiester bond Pyrophosphate is unstable in aqueous solution, hydrolyzed to form 2 molecules of inorganic phosphate, recycled to form high-energy bonds in ATP or for other purposes Nucleotides, such as ATP, GTP and those in DNA are called organic phosphates because bonded to carbon containing molecule *Nucleotide triphosphates are added to the growing daughter strand, with the release of pyrophosphate (PPi) Phosphoric acid (form that dominates in strongly acidic conditions = H3PO4) is an excellent buffer excuse it has 3 acidic hydrogens with pKa values that span nearly the entire pH scale In mildly acidic conditions, it loses a proton to become dihydrogen phosphate (H2PO4^-) It will readily lose second proton to become hydrogen phosphate (HPO4^2-) in weakly basic solutions In strongly basic solutions, the form that predominates is phosphate (PO4^3-) pKa for the loss of the first hydrogen is 2.15, 7.20 for the second, and 12.32 for the third at pH 7.4, dihydrogen phosphate and hydrogen phosphate are equal in proportion Phosphates are good buffers because they can pick up or give off protons depending on the pH of the solution Adjacent phosphate groups on a nucleotide triphosphate experience large amount of repulsion because they are negatively charged This combined with the ability of phosphate to stabilize up to three negative charges by resonance means that the energy released when a phosphate or pyrophosphate is cleaved is quite high

1. MCPBA 2. RCO3H 1. OSO4 2. NaHSO3

Gives you epoxide The you add H2O / H+ Gives you anti addition One OH in front, one OH in back (1 OH on wedge, one on dash) -Enantiomers = 2 products OSO4 gives you syn addition, so you might get meso compound ( 1 product) *Both OH on wedge, or both on dash

Naming Amides

Highest priority: "amide" suffix Name of R group as prefix with "N-" (for example, N-ethyl-N-methylbutanamide ) Lower priority: "carbamoyl or amido" prefix

1) BH3 (Or B2H6 or BD3), THF 2) H2O2, NaOH

Hydroboration Puts OH on less substituted carbon (H or D on more substituted carbon) Syn addition

Hydrocarbons (Alkanes, alkenes, alkynes) and Alcohols

Hydrocarbons- contain only C and H Alcohols- contain at least 1 -OH (more reactive) Alkanes are simple hydrocarbon molecules with formula Cn H(2n+2) -Methane has 1 carbon, butane has 4, heptane has 7, and so on, all fully saturated with hydrogens -Halogens are common substituents, indicated by prefix (fluoro-, chloro-) -Alkenes (double bonds) and alkynes (triple bonds): Indicated by the lower numbered carbon in bond Alcohols: Named by replacing -e end of the name of corresponding alkane with suffix -ol -Carbon attached to OH (hydroxyl group) gets lowest number possible (Takes precedence over multiple bonds) -Alcohols with 2 hydroxyl groups are called diols or glycols (suffix -diol)(Diols with hydroxyl group on the same carbon are called geminal diols (hydrates), on adjacent carbons = vicuna diols)

In a protic solvent, which of the following halogens would be the best nucleophile? A. Br- B. Cl- C. F- D. I-

Hydrogen binds to the smallest (top, most electrophilic) so you have to go with the bottom In a protic solvent, which of the following halogens would be the best nucleophile? A. Br- B. Cl- C. F- D. I- Correct Answer: D Explanation: In a protic solvent, the protons in solution can attach to the nucleophile, decreasing its nucleophilicity. The larger the nucleophile, and the stronger its conjugate acid, the stronger the nucleophile will be. Of the options given, I- will therefore be the strongest nucleophile because it is least likely to associate with the protons in solution.

CHCl3, KOH

Hydroxide (strong base) attack H on Carbon and forms H2O and -:CCl3 Then, one Cl leaves to stabilize the carbon, leaving you with CCl2 (Carbine) Alpha elimination Leaves you with cyclopropane ring with 2 chlorine *If you have N2, it leaves as gas -> nitrogen is more electronegative, and N gas is stable and leaves, leaving us with carbine with H2

Graphing IR Spectrum

IR spectra are plotted as percent transmittance (amount of light that passes through the sample and reaches the detector vs wavenumber Percent transmittance on Y axis, Wavenumber (Cm^-1) on x axis) from 400 to 4000 Equation relating absorbance (A) and percent transmittance (%T) is A = 2 - log %T Maximum absorptions appear as the bottoms of valleys

Chromatography

In all cases for MCAT: The more similar a compound is, the more it will stick to and move slowly through its surroundings Chromatography separates compounds based on how strongly they adhere to the solid (stationary) phase (or in other words, how easily they come off into the mobile phase) First, place sample onto solid medium (situation phase or adsorbent) Then, run mobile phase (usually liquid (or gas in gas chromatography)) This will displace (elute) the sample and carry it through stationary phase Partioning: Different substances migrate at differing speeds, depending on how well it adheres to stationary phase -> Represents equilibrium between 2 phases TLC: Thin layer chromatography: uses silica gel -> highly polar substance -> this is our stationary phase Cellulose: polar substance, may also be used Any polar compound will adhere well to gel and move through (elute) slowly = won't move as far *If it moves farther from start, it is not attracted to stationary phase = more attracted to mobile phase = non-polar In column chromatography, size and charge both pay a role in how quickly compound moves through stationary phase Chromatography can even use strong interactions, like antibody-ligand binding

Meso Compounds

In order for molecule to be optically active, it has to have chiral centers and CAN NOT have plane of symmetry. If it has chiral centers and plane of symmetry, it is optically inactive and called meso compound

Solvent Effects

In polar protic solvents, nucleophilicity increases down the periodic table (can hydrogen bond) Common protic solvents are carboxylic acids, ammonia/amines, and water/alcohols. *Protic: Nucleophilicity decreases in order: I- > Br- > Cl-> F- ( I- is the conjugate base of strong acid so it is less affected by protons and can react with electrons) (HF is weak acid) In polar aprotic solvents, nucleophilicity increases up the periodic table. Common aprotic solvents are DMF, DMSO, and Acetone. *Protic = can hydrogen bond (stabilizes carbocation, hinders nucleophiles)(SN1 and E1 -> stabilize the carbocation) *Aprotic can't hydrogen bond (SN2 and E2 -> starts with nucleophilic attack) Aprotic: Nuclecophilicty decreases in order: F- > Cl- > Br-> I- (no protons to get in the way of nucleophile) *If the solvent is not given assume polar solvent *won't use non polar solvents because nucleophile needs to dissolve (charged particles = polar)

Hydration

In the presence of water, aldehydes and ketones react to form geminal diols (1,1-diols) Nucleophilic O in water attacks carbonyl We can increase rate of reaction by adding catalytic acid or base

In vivo

In vivo refers to when research or work is done with or within an entire, living organism In vitro is used to describe work that's performed outside of a living organism (in lab)

Configurational Isomers

Isomers that can only interconvert by breaking bonds; include enantiomers, diastereomers (both considered optical isomers because they affect rotation of plane polarized light) (different connectivities) -For example, one of the bonds in the double bond has to be broken in cis-trans isomers for them to rotate (Subclass of diastereomers) -Chirality: No plane of symmetry (mirror image cant be superimposed) (left hand can't fit into right handed glove)(non-superimposable mirror image = e enantiomers )(4 different substituents on a carbon) -Chiral molecules that are not mirror images = diasterosmers (some dashes become wedges but some dashes stay dashes) *Enantiomers: Nearly identical physical properties and chemical properties, but rate plane-polarized light in opposite way (all wedges become dashes and all dashes become wedges) -Achiral: can be superimposed

Kinetic and Thermodynamic Enolates

Ketone has 2 different alkyl groups/ alpha carbons and alpha hydrogens Enolate carbanions act as nucleophiles Double bond can form between more substituted carbon (thermodynamic product) or less substituted carbon and carbonyl (Kinetic product) The kinetic enolate forms more quickly (think kinetic energy) but it is less stable (rapid, irreversible, likes low temperatures)(Wants strong statically hindered base) Thermodynamic enolate favored for higher temp, reversible, weaker and smaller bases If the reaction is reversible, kinetic product can revert back to original and react to form thermodynamic product

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 torsional strain from eclipsing interactions and strain from compressing the normal sp3 angle of 109.5 degrees. The ring strain and therefore the reactivity is increased by fusion to a second ring. Reduced resonance / more ring strain makes hydrolysis more likely Many antibiotic families have beta lactase (including penicillins, cephalosporins, carbapenems, and monobactams) Many bacteria have developed beta lactamases (break lacteal rings so antibiotic cant work) SO, antibiotics sometimes given with better lactase inhibitors

PCC

Mild anhydrous oxidant (mild oxidizing agent) Can take primary alcohols to aldehydes, but not further because it lacks water to fully hydrate Secondary alcohols can be oxidize to ketones by PCC, or any other STRONG oxidizing agent (they can't reach carboxylic acid, stops at ketone because they only have 1 H to work with) (remember, oxidizing means more bonds to oxygen) With other oxidizing agents, aldehydes are rapidly hydrated to geminal diols Aldehyde with any oxidizing agent stronger than PCC (like Potassium permanganate KMnO4, chromium trioxide CrO3, silver (I) oxide (Ag2O), hydrogen peroxide (H2O2)) will become carboxylic acids *Ketones (like butanone) will not react with PCC or KMnO4 because ketones cant be oxidized with common oxidizing stuff that cant break the C-C bond However, butanal could be oxidized by KMnO4 to butanoic acid (but PCC wouldn't do anything) Both ketones and aldehydes can be reduced (ketones to secondary alcohols and aldehydes to primary alcohols) with LiAlH4 and NaBH4

Weak Bases

NH3, CH3NH2

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 (small molecule lost) and because nitrogen replaces the carbonyl oxygen this is also an example of a nucleophilic subsitution. Common ammonia derivatives: hydroxylamine, hydrazine, semicarbazide, -> form oxides, hydrazones, and semicarbazones Imines and similar stuff can undergo tautomerization to form enamines (just like eons are tautomers of carbonyls *Tautomerization: structural isomers (constitutional isomers) of chemical compounds that readily interconvert *-rearrangement of bonds in a compound , usually by moving a Hydrogen and forming a double bond IMINE IS MORE THERMODYNAICALLY FAVORED

The 20 eukaryotic proteogenic amino acids are grouped into 5 categories:

Nonpolar nonaromatic (hydrophobic): Tend to have side chains that are saturated hydrocarbons (alanine, leucine, isoleucine, proline (cyclic), glycine, methionine) Nonpolar Aromatic (hydrophobic): Tryptophan, phenylalanine, tyrosine (polar, aromatic) Polar: Tend to have terminal groups containing oxygen, sulfur, and nitrogen: Tyrosine (aromatic), threonine, serine, glutamine, asparagine, cysteine Negatively Charged (acidic): Aspartic acid and glutamic acid (terminal carboxylic anions in R groups) Positively Charged (basic): Arginine, lysine, and histidine (protonated amino in R group) Polar, acidic, and basic amino acids are all hydrophilic and tend to form H. bonds in water in aqueous solution Reside on surface of proteins

Benzaldehyde

Note: Alpha carbon has no alpha hydrogens because alpha carbon is quartenary

Nucleophile Only Base Only Weak nucleophile/ base Strong Nucleophile/Strong Base

Nu only: Cl-, Br-, I-, HS-, H2S, RS-, RSH Base only: H-, NaH, DBN, DBU, tert butyl Weak: (favors SN1 and E1) : H2O, MeOH, EtOH Strong both: HO-, MeO-, EtO-

SN1 and SN2

Nucleophile forms bond with substrate carbon and leaving group leaves Nucleophile must be more reactive than leaving group SN1: Unimolecular nucleophilic substation -> 2 steps 1. Rate limiting step (leaving group leaves, generating carbocation) 2. Nucleophile attacks carbocation -> substitution product More substituted carbocation = more stable because alkyl groups act as e- donor, stabilizing positive charge of carbocation Rate of reaction depends on rate limiting step/ concentration of substrate: rate = k[R-L] where R-L is alkyl group with Leaving group Varied stereochemistry/ Racemic mixture SN2: Bimolecular nucleophilic substitution reactions: 1 step 1. Nucleophile attacks compound at same time as LG leaves (concerted) Single rate limiting step Backside attack Nucleophile must be strong, substrate can't be statically hindered rate = k [Nu:][R-L] Stereospecific reaction / Inversion of absolute configuration

Aldol condensation (still called aldol reaction even when reactants are ketones)

Nucleophilic addition to carbonyl Aldehyde or ketone acts like electrophile (keto form) and nucleophile (enol form) Forms C-Cbond Base attacks alpha hydrogen and enolate is formed, which then attacks carbonyl carbon, forming an aldol (contains both aldehyde and alcohol functional groups) The nucleophilic enolate ion can react with electrophilic carbonyl group or another acetaldehyde (ethanal) molecule With strong base and high temp, E1 or E2 reaction ->The OH is removed as water(dehydration), forming double bond + H2O on the side Produces beta unsaturated carbonyl This is a condensation reaction (2 molecules are joined and small molecule lost) and dehydration (small molecule that is lost is water) reaction

UV spectroscopy

Obtained by passing UV light through sample that is usually dissolved in an inert, nonabsorbing solvent Absorbance caused by electronic transitions between orbitals -> tells us wavelength of maximum absorbance (tells us extent of conjugation within conjugated systems: more conjugated = lower energy of transition and greater wavelength of maximum absorbance Most useful for studying compounds containing double bonds or heteroatom with lone pairs that create conjugated systems (could be used for propene and propane but not propane) Molecules with pi electrons or nonbonding electrons can be excited by UV light to higher energy anti bonding orbitals Molecules with lower energy gap between highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) are more easily excited and can absorb longer wavelengths (lower frequencies) with lower energies *SMALLER DIFFERENCE BETWEEN HOMO AND LUMO = LONGER WAVELENGTH THAT CAN BE ABSORBED (Closer to visible light spectrum?) *red = longest wavelength, shortest frequency Conjugated molecules (unhybridized p-orbitals) can also be excited by UV light -Higher max wavelength (lower frequency) -Lager conjugated molecules may even absorb light in visible range (color range)

Optical Activity

Only optically active if it can rotate plane-polarized light Ordinary light is unpolarized (goes in all directions) Polarizer (like a filter) only lets one direction of light to pass through, producing plane polarized light Optical Activity: rotation of plane polarized light by chiral molecule (enantiomer rates light in same magnitude but opposite direction) -Light rotated to the right (clockwise) = d (dextrorotatory) is positive (+) -Compound that rates light to the left (-)(counterclockwise) = Levorotatory (l) -d or l not related to absolute configuration , must be determined experimentally *DO NOT CONFUSE WITH D OR L LABLES ON CARBS OR AMINO ACIDS OR R AND S CONFIGURATION (these are based on absolute configuration/determined by structure) -When both + and - enantiomers are present in equal concentrations, they form racemic mixture (rotations cancel out and no optical activity is observed)

Ortho, Para and Meta on benzene ring

Ortho, para: tend to be e- donating meta: tends to be e- withdrawing (positive charge) Two groups on adjacent carbons in benzene rings called ortho (o) Two groups on opposite side are called para (p)

A chemist discovers through bond enthalpy experiments that a novel compound will react with a double bond functional group, break multiple C-H bonds, and form at least one C-O bond. Based on these observations, the chemist can conclude that the compound is:

Oxidizing Agent

Physical Properties VS Chemical Properties

Physical properties: No change in composition / do not produce change in chemical composition (melting point, BP, solubility, odor, color, density) Chemical Properties: deal with reactivity of molecule, change in chemical composition, generally attributable to functional groups

Nucleophilic Addition Reactions

Polarization of the C=O bond allows for partial positive charge on carbon making it an electrophile susceptible to nucleophilic attack When the nucleophile attacks, covalent bond forms with carbon This breaks the pi bond and electrons are pushed into the oxygen atom The oxygen accepts these electrons. If a carbonyl cannot reform O- will accept a proton from the solvent to form - OH group making alcohol If good leaving group is present, that carbonyl double bond can form pushing of the leaving group, reforms carbonyl

Mesylates and Tosylates

Protonates hydroxyl groups of alcohols because they are poor leaving groups for nucleophilic substitution Mesylate contains functional group -SO3CH3 derived from methanesulfonic acid Prepared from methylsplfonyl chloride and alcohol with base Tosylates have -SO3C6H4CH3 derived from toluenesulfonic acid -> formed from stars of acid Both make alcohols better leaving groups and can serve as protecting groups when we don't want alcohols to react (they react with reagents that would attack alcohols (especially oxidizing agents)

Esterification: Reaction of a Carboxylic acid with an alcohol under acidic conditions (Condensation reaction)

Protonating the C double bond O makes the electrophilic carbon even more ripe for nucleophilic attack (enhances polarity of bond, additional positive charge on carbonyl carbon) Occurs most rapidly with carbonyl carbons Water is side product

NBS Reaction

Put bromine atom one carbon away from double bond

1. H2O 2. H+ or H3O+

Puts OH on most substituted carbon

Reducing agents and Reactions

Reduction decreases oxidation state Bond between carbon and atom more electronegative replaced by carbon and bond less electronegative -Usually means increasing number of bonds to hydrogen Good reducing agents: Low electronegativity and ionization energy, metal hydrides: sodium, magnesium, aluminum, zinc, NaH, CaH2, LiAlH4, NaBH4 Aldehydes and ketones reduced to primary and secondary alcohols (exergonic but slow without catalyst) Carboxylic acids to primary alcohols and esters to pair of alcohols Reducing agents often are medials bonded to a bunch of hydrides *So, REDUCING AGENTS ARE METALS WITH ALOT OF H-, OXIDIZING AGENTS ARE METALS WITH A LOT OF O'S

Resonance

Resonance delocalization of electrons occurs in molecules with conjugated bonds Conjugation: alternating single and multiple bonds (implies unhybridized p orbitals because all atoms must be sp2 or sp hybridized -> parallel unhybridized p orbitals combine to form delocalized electron clouds above and below the plane of the molecule) Adds to stability , more resonance structures = more susceptible to nu attack Resonance and conjugation are much more powerful than induction (distribution of charge across sigma bonds) No equilibrium, so the actual electron density is an average of all of the resonance structures But, if the stability of different resonance structures differs, true electron density favors stable form Favored resonance for structures that lack formal charge or make full octet on highly electronegative atoms or stabilize charge through induction and aromaticity Alpha-beta unsaturated carbonyls (enomes) -> image shown

SN2 reaction

SN2 prefers primary or methyl substrate Methyl can't undergo E1 or E2 because they form double bonds, and you need two carbons to form a double bond With strong bulky base, E2 is more likely than SN2, but both can occur Strong bases favor E2 for everything (except. methyl) Anytime you have unhindered, accessible carbon atoms favor SN2 Polar aprotic favors SN2 Polar protic favors SN1 and E1 because hydrogen bonding stablaizes nucleophile and carbocation Aprotic: nucleophile free to react (stronger nucleophile = faster reaction) Tertiary: Favors SN1 and E1 (heat favors E1 over SN1) SN2 = inversion: Start with S end with R SN1: racemic mixture: end up with R and S SN1 and SN2 have no rearrangements, but E1 and E2 do SN2 and E2 have no rearrangements, but SN1 and E1 do because they form carbocation intermediate (2 steps) E2: Zaitsev (small, strong base) and Hoffman (Strong bulky base, less stable, less substituted) E attacks H SN attacks carbon Weaker the base, better the leaving group Polar protic: OH Polar aproitc: no OH Type of substrate: Quick N' Dirty Rule #1: If the substrate is primary, we can rule out SN1 and E1, because primary carbocations are unstable* (see below for exceptions). You cannot definitively rule out E2 yet, although I will spill the beans and say that it's almost certainly going to be SN2 unless you are using a very sterically hindered ("bulky") base such as tert-butoxide ion (e.g. potassium t-butoxide KOtBu). For Tertiary Carbons, Rule Out The SN2 Quick N' Dirty Rule #2: If the substrate is tertiary, we can rule out SN2, because tertiary carbons are very sterically hindered. If the substrate is secondary, we can't rule out anything (yet). SN1/SN2/E1/E2 reactions tend not to occur on alkenyl or alkynyl halides. Charged bases/nucleophiles will tend to perform SN2/E2 reactions. (even if you cant see the charge, like NaCN, you know CN- is a strong base so you rule out Sn1 and E1) Reactions where neutral bases/nucleophiles are involved tend to go through carbocations (i.e. they tend to be SN1/E1) (HsSO4, Ch3OH). (concerted step of SN2 and E2 requires more energy = stronger nucleophile/base Polar protic solvents tend to favor elimination (E2) over substitution (SN2). Polar aprotic solvents (acetone, DMF, Ch3CN, DMSO) tend to favor substitution (SN2) relative to elimination (E2)

Acidity

Substituents on carbon atoms near carboxyl group influence anion stability and acidity NO2 or halide groups are electron withdrawing (increase acidity of the anion) NH2 and OCH3 are electron donating groups that destabilize negative charge, decreasing acidity (less stability = less acidity) Closer the groups are to carbonyl = stronger effect

Cyclic Conformations (cycloalkanes)

Stability depends on ring strain: Ring strain arises from 3 factors: angle strain, torsional strain, and non bonded stain (steric strain) -Angle strain: bond angles deviate from their ideal values by being stretched or compressed -Torsional strain: Eclipsed or gauche interactions -Nonbonded strain/ steric strain /steric hindrance: (van der Waals repulsion): nonadjacent atoms or groups compete for same space (non-dominant source of steric strain in the flagpole interaction)(look for 2 big molecules in each others space, isn't resolved by rotating around sigma bond, but torsional strain is) -To alleviate strain, cycloalkanes adopt nonplanar conformations -Most stable is chain confirmation (minimizes all three types of strain) -Hydrogen atoms sticking straight up or down (perpendicular to ring) = axial, ones that are parallel = equatorial -Alternates around ring (wedge on C 1,3,5 will be axial, but wedge on C 2,4,6 will be equatorial) -Can undergo chair flip (briefly goes through half chair confirmation) -> all dashes remain dashes and wedges remain wedges (up remains up, down remains down), but all axial become equatorial and vice versa (can be slowed by bulky (test-butyl) groups) -In rings with multiple substituents, if they are on same side (both dashes or both wedges) = cis, opposite sides (one dash and one wedge) = trans -Get bulkiest group in equatorial position

Triacylglycerols

Storage form of fat in the body Include 3 ester bonds between Esters of long chain carboxylic acids (fatty acids) and glycerol (1,2,3- propanetriol) Saponification = fats are hydrolyzed (broken down with water) under basic conditions to produce soap -> Saponification of triacylglycerol shown Acidification of soap regenerates fatty acid

Distillation

Tale advantage of differences in boiling point When product is a liquid that is already soluble in solvent, you can't use extraction or filtration or recrystallization, you need distillation Distillation uses differences in boiling point to separate by evaporation and condensation Liquid with lower BP will vaporize first and rise into condenser -> this condensate then drips down into vessel -> end product = distillate Temperature kept where liquid with higher boiling point won't boil *Process fro making liquor at distillery (ethanol boils at lower temp than water) Simple distillation (described above) should only be used to separate liquids that boil below 150 degrees Celsius and have at least 25 deg C between Boiling points *Uses distilling flask containing combined liquids, distillation column with thermometer and condenser, and receiving flask to collect the distillate Other things might be added to prevent super heating: Liquid heated to temp above boiling point without vaporization because gas bubbles within a liquid can't overcome atmospheric pressure and surface tension combination

Steric protection of Leaving Group When an aldehyde is mixed with a diol (2 equivalents of alcohol), it forms an: When a ketone is mixed with a diol, it forms a:

Temporarily mask reactive leaving group with statically bulky group during synthesis Nonreactive acetal or ketal serves as protecting group When an aldehyde is mixed with a diol (2 equivalents of alcohol), it forms an: Acetal When a ketone is mixed with a diol, it forms a: Ketal

Nucleophile (nucleus loving)

Tend to have .one pairs or pi bonds that can be used to form covalent bonds to electrophiles *Look for Carbon, Hydrogen, Oxygen, or Nitrogen with minus sign or lone pair *Tend to be good bases, but nucleophilic strength depends on rates of reactions with electrophiles (kinetic property) and base strength depends on equilibrium position of reaction (thermodynamic property) *look for anions, pi bonds, and atoms with lone pairs *the more basic the nucleophile, the more reactive it is Determined by 4 major factors: *Charge: increases with increasing electron density / more negative charge *Electronegativity: nucleophilicity decreases as electronegativity increase (atoms less likely to share electron density) *Steric Hindrance: Bulkier molecules are less nucleophilic Solvent: Solvents hinder nucleophilicity by protonating nucleophile or through H bonding Strong nucleophiles: HO-, RO-, CN-, N3- NH3 and RCO2- are okay H2O, ROH, and RCOOH are weak amine groups tend to make good nucleophiles

SN1 prefer: Sn2 prefer:

Tertiary over secondary over primary carbons Methyl and primary preferred over secondary, and tertiary won't react because of steric hindrance

Alpha Hydrogens of Alpha carbons on Carbonyls

The alpha hydrogen on ketones and aldehydes allows them to act as nucleophiles and electrophiles Oxygen of carbonyl pulls some electron density out of C-H bond, making it easier to deprotonate alpha carbon (when in basic solution) producing carbanion Alpha H on ketones slightly less acidic, Alpha H on aldehydes slightly more acidic because additional alkyl groups (on ketone) destabilize carbanion (make it less acidic) *Alpha H on aldehyde more acidic = wants to leave (more reactive) *electron withdrawing groups (like oxygen) stabilize organic anions (like carbanions) *Electron donating groups like alkyl groups destabilize organic anions Extra alkyl groups increase steric hinderance, making ketone less likely to react with nucleophile because carbanion is unstable Aldehydes slightly more reactive to nucleophiles Ketone has higher energy, more crowded, LESS REACTIVE intermediate step (higher energy means reaction is less likely to proceed

Strecker synthesis

The carbonyl carbon intimately becomes alpha carbon of amino acid. Any remaining alkyl chain becomes the R group. So, take R group on aldehyde and shove it on amino acid (R + CH2NH2COOH) Start with an aldehyde, ammonium chloride (NH4Cl), and potassium cyanide (KCN). The ammonium attacks forming an imine. Imine susceptible to Nu:- addition reactions so CN- anion from KCN attacks, forming nitrile group (Triple bond between N and C) Then the cyanide anion attacks such that you form an aminonitrile (contains amino group (NH2) and nitrile group (C triple bond N)). (Step 1: Aminonitrile generated from aldehyde or ketone) Step 2: Amino acid generate from aminonitrile: Nitrile Nitrogen is protonated, increasing electrophilicity Acid is added along with water and heat. Ammonia kicked off -> Will lead to creation of carboxylic acid from the nitrile group. Starting material was planar carbonyl compound, so product is racemic mixture---generates L and D amino acids. Condensation Reaction: formation of immune from carbonyl-containing compound and ammonia with loss of water, followed by nucleophilic addition: Addition of nitrile group, followed by hydrolysis

Decarboxylation

The complete loss of a carboxyl group as carbon dioxide 1,3 dicarboxylic acids and other beta keto acids may spontaneously decarboxylate with heat Proceeds via 6 membered ring transition state Enol that is initially formed from the destruction of the ring tautomerizes to more stable keto form

How many stereoisomers exist for the following aldehyde? (image on next slide)

The maximum number of stereoisomers of a compound equals 2^n, where n is the number of chiral carbons in the compound. In this molecule, C-1 (the aldehydic carbon) is not chiral, nor is C-5 (because it is attached to two hydrogen atoms). Therefore, with three chiral centers, there are 2^3 = 8 stereoisomers.

Molecular Orbitals Rank in order of decreasing bond strength: double bond, sigma bond, pi bond, triple bond

Triple bond > double bond> sigma > pi Molecular orbital: When two atomic orbitals combine Obtained by adding and subtracting wave functions If the sign of the wave functions are the same, a lower energy (more stable) bonding orbital is produced Different signs = high energy (less stable, higher energy) anti-bonding orbital Head to head or tail to tail overlap results in sigma bond (most common, all single bonds)(accommodates 2 electrons) When p orbitals line up side by side, they overlap, creating pi bond Pi bond + sigma = double bond 2 pi bonds + sigma = triple bond Single bonds are free to rotate, double and triple bonds are not SIGMA BOND HAS TO FORM FIRST (you cant have pi bond without sigma first) More bonds formed = shorter bond length (shorter bonds are stronger and require more energy to break) However, though double bonds are stronger than single bonds (breaking a single bond requires a lot more energy), individual pi bonds are weaker than sigma bonds, but the strength is additive, making double and triple stronger overall -There fore, you can only break one bond in double bond, leaving single bond (Causes cis-trans isomers) *S-orbital is spherical, p-orbital is dumbbell shaped s-orbitals have more overlap than p-orbitals

(R) and (S) Isomers

Used for chiral (stereogenic )centers in molecules First, assign priority , then arrange in space so lower priority (usually H) is on dash. If you switch H to dash from wedge, then switch R to S or S to R -Draw circle (R = clockwise, S = counterclockwise)

Fractional Distillation

Used to separate 2 liquids with similar boiling points (less than 25 deg C apart) Fractional column connects the distillation flask to the condenser Fractionation column is a column in which the surface area is increased by the inclusion of inert objects (glass beads or wool) As vapor pressure rises up the column, it condenses on these surfaces until rising heat causes it to evaporate again, only to condense again higher in the column. Each time the condensate evaporates, the vapor consist of a higher proportion if the compound with the lower boiling point. By the time the top fo the column in reached, only the desired product drips down to receiving flask *Temperatrues goes from super high at bottom to cool at top, so stuff with lowest boiling point condenses at the top

Pyruvic acid, one of the end products of glycolysis, is commonly called acetylformic acid. Based on its common name, the structure of pyruvic acid must be:

We can use the name acetylformic acid to figure out what our functional groups are. The prefix acet- refers to a two-carbon unit with one carbon in a carbonyl group—think of acetic acid, acetic anhydride, or acetaldehyde. The carbonyl carbon is the point of attachment to another functional group. Formic acid is a single-carbon carboxylic acid. Therefore, acetylformic acid is an acetyl group directly attached to formic acid

Alcohols

When its not highest priority group, it is names as substituent with prefix hydroxy- Aromatic alcohols are called phenols Resonance makes hydroxyl hydrogens more acidic than other alcohols, but hydroxyl hydrogens are still weak in general Have HIGH melting points and boiling points because of hydrogen bonding (pulls e= density towards oxygen)(type of non-covalent bonding force More hydroxyls = higher boiling points Hydrogen bonding = higher MP, BP, and more solubility pKa = -log Ka (strong acids have high Ka values and low pKa values) -Phenol has the lowest pKa due to resonance (out of the alcohols), so it is the most acidic (slightly soluble) (can form salts) -t-BuOH has pKa of about 17, so it is the most basic Electron withdrawing substituents increases acidity (stabilize the charge, so does resonance), donating groups (like alkyl groups) decrease acidity *Longer chain (with or without OH) = higher boiling point

ion exchange chromatography

beads in the column are coated with charged substances, so they attract or bind compounds that have an opposite charge *Example: positively charged compound will attract and hold negatively charged backbone of DNA (increasing retention time because it won't move through as quickly, and then when everything else has run through a salt gradient can be used to elute the charged molecules that have stuck behind)

Vacuum Distillation

distill liquids that boil over 150 degrees use a vacuum to lower the ambient pressure *decreasing the temperature that the liquid must reach in order to have sufficient vapor pressure to boil* *liquids boil when their vapor pressure = ambient pressure* - lower the ambient pressure so that the liquid can boil at lower temperatures allows to distill compounds with higher boiling points at lower temperatures so that we do not have to worry about degrading the product The initial solution is placed in the heated distilling flask, where the components of the solution with the lowest boiling points will vaporize first. The vapor then condenses in the water-cooled condenser, and this distillate drips into the receiving flask

Induction (Electronic Effect)

distribution of charge across sigma bonds Electrons are attracted to more electronegative atoms (electronegative atoms end up with slightly negative charge) Effect is relatively weak, and gets weaker as you move farther from electronegative atom Responsible for dipole character of carbonyl group and increased dipole character on carboxylic acids (making them more susceptible to nu:- attacks ) Nitrogen is less electronegative than oxygen, so amides are not as reactive

Enol and Enolate

enol = -OH, substituted directly onto alkenes, C=C, hence "alkene-ols" or enols (image shown). Enols can be viewed as alkenes with a strong electron donating substituent. Since alkenes themselves typically react as nucleophiles, the -OH group makes them even more reactive than a simple alkene. Enolates are the conjugate bases or anions of enols and can be prepared using a base (Enol + base = enolate)

Nonpolar, nonaromatic amino acids (7) (hydrophobic)

glycine, alanine, valine, leucine, isoleucine, methionine, proline Usually sequestered inside proteins

Dicarboxylic Acids

have a carboxylic acid at each end of the molecule common in biological systems normal alkane name (ethane) with dioic acid as the suffix More acidic than normal because of more electron withdrawing groups, but the second proton is actually less acidic (harder to remove) than the analogous proton of a mono carboxylic acid The hydroxyl group is the most acidic proton on carboxylic acid, but in 1,3 di-carbonyls, the alpha hydrogen is also pretty acidic Oxalic acid: 2 carbons -> ethanedioic acid (then Malonic (propanedioic) acid, succinic (butanediodic acid), glutamic, adipic, pimelic

Anti-Markovnikov Addition

if peroxides (ROOR or H2O2) are present, the bromine, not the hydrogen, will add to the least substituted carbon. the other halogens still follow Markovnikov's rule even in the presecense of peroxides. If you have Her over H2O2, Br goes on less substituted carbon! But, HCl over H2O2 will still put Cl on most substituted carbon (no anti-maokovnikov product)

Infrared (IR) Spectroscopy

measures molecular vibrations, which can be seen as bond stretching, bending, or combinations of different vibrational modes Infrared light passed through sample, and absorbance is measured Infrared light ranges from wavelength = 700 nm to 1 mm (1,000,000 nm) but useful range is from 2500 to 25000 nm (corresponds to 4000 to 400 cm^-1 Analog of frequency called wavenumber used When light of these wavenumbers is absorbed, molecules enter excited vibrational states Twisting and folding (bending and stretching), and 4 types of vibrational states can occur (symmetric bend (towards the middle), Asymetric bend (both bend to the right, or to the left), symmetric stretch (away from the middle), or asymmetric stretch (both stretch to the right or to left) Wavenumbers are the analog of frequency (frequency = c / wavelength, and wavenumber = 1 / wavelength, measured in cm^-1 More complex vibration patterns, caused by the motion of the molecule as a whole can be seen in 1500 to 400 cm^-1 = fingerprint region(won't need this for MCAT) Symmetric stretches do not show up on IR because involve NO NET CHANGE IN DIPOLE MOMENT (no form O2, Br2, symmetric bonds like C2H2) Most important IR absorptions to memorize: Hydroxyl group (OH) *Around 3300-3600 for alcohols (broad peak) and 3000 for carboxylic acids (broader, longer, more jagged) because the carbonyl pulls it down little bit (towards the sharp carbonyl peak at 1700) Carbonyl: sharp peak at 1700 N-H in same region as OH: around 3300 (primary: 2 dips for 2 H, secondary = 1 dip for 1 H) IR spectra are plotted as percent transmittance (amount of light that passes through the sample and reaches the detector vs wavenumber

melting points are much lower for :

melting points are much lower for unsaturated fatty acids (oil) *some double bonds, can't pack as tight together Melting points are higher for saturated (butter) *Al C and H, can pack together super tight/dense, harder to melt them

Aromatic Amino Acids (3)

phenylalanine (non polar, hydrophobic), tyrosine (polar), tryptophan (non polar, hydrophobic) Usually sequestered in interior of proteins

polar protic solvents and polar aprotic solvents

polar solvents that can hydrogen bond H2O, CH3OH, EtOH Aprotic: Acetone, DMF, I-, SH-, -CN

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

Polar Amino Acids (6)

serine, threonine, cysteine, asparagine, glutamine, tyrosine (aromatic)

sp hybridization

sp hybridization is observed when one s and one p orbital in the same main shell of an atom mix to form two new equivalent orbitals. The new orbitals formed are called sp hybridized orbitals. It forms linear molecules with an angle of 180° This type of hybridization involves the mixing of one 's' orbital and one 'p' orbital of equal energy to give a new hybrid orbital known as an sp hybridized orbital. sp hybridization is also called diagonal hybridization. Each sp hybridized orbital has an equal amount of s and p character, i.e., 50% s and p character. Examples of sp Hybridization: All compounds of beryllium like BeF2, BeH2, BeCl2 All compounds of carbon-containing triple Bond like C2H2. Beryllium has only two electrons in its valence shell. When it forms bonds to two hydrogens, it requires two hybridized orbitals, meaning that its hybridization must be sp. Note that the presence of only single bonds does not mean that the hybridization must be sp3; this is a useful assumption for carbon, but does not apply to beryllium because of its smaller number of valence electrons. The two unhybridized p-orbitals around beryllium are empty in BeH2, which takes on the linear geometry characteristic of sp-hybridized orbitals.

low pKa, high Ka

stronger acid (less stable) Conjugate base is weak (more stable) the more stable a lone pair of electrons is, the less basic it will be. (weak base) the less stable a lone pair of electrons is, the more basic it will be. (strong base) The more stable the conjugate base is (the weaker the base), the easier it is for the proton to leave (= the stronger the acid) pKa is constant, but a low pka will have low pH (high concentration of H+) pKa of carboxylic acid from 3-6 (usually around 5) pKa of Hcl = -8 pKa of HSO4^- = 1.99

Rank the following molecules in order of increasing nucleophilicity: methoxide, t-butoxide, isopropanolate, ethoxide

t-butoxide < isopropanolate <ethoxide < methoxide Larger / bulkier = more steric hinderance = worse nucleophile

Extraction 3 Intermolecular forces that affect solubility:

the transfer of a dissolved compound (desired product) from a starting solvent into a solvent in which the product is more soluble Simple way to separate out a desired product Like dissolves like: Polar associates with polar (aqueous phase)(polar substances dissolve in polar solvents, non-polar associates with non polar (Organic phase) Two solvents need to be immiscible (layers don't mix, even though they temporarily mix when shaken) Two solvents also must have different polarity or acid base properties that allow a compound of interest to dissolve more easily in one than the other *Isobutyric acid is more polar than diethyl ether and can exhibit hydrogen bonding, so it will congregate in the aqueous layer Diethyl ether will remain in the organic layer After the 2 layers are mixed together, the water (aqueous) and there (organic) phases will separate on their own in time -> use seperaratory funnel to isolate two phases (organic layer usually on top, but it just depends on density: denser solvent drained first) 3 Intermolecular forces that affect solubility: *Hydrogen bonding: alcohols and acids will move most easily into aqueous layer (like dissolves like) *Dipole-Dipole interactions: Compounds are less likely to move into the aqueous layer *Van der Waals (London forces): With only these interactions, compounds are least likely to move into aqueous layer Multiple extractions with fresh water are more effective than single extraction with larger volume of water -> when desired product is isolated, product can be obtained by evaporating solvent using rotary evaporator (rotovap) You can use properties of acids and bases to your advantage: HA + base -> A- + H-base+ When acid dissociates, the anion formed will be more soluble in aqueous layer because it is charged. Thus, adding a base will help extract an acid into the aqueous base Reverse extraction to remove unwanted impurities: Small amount of solute used to extract and remove impurities, rather than compound of interest: Called a wash

Fischer esterification

under acidic conditions, mixtures of carboxylic acids (or anhydrides) and alcohols will condense into esters Replace OH with O+ whatever carbon chain was attached to the alcohol

E and Z Isomers

used for compounds with polysubituated double bonds (simpler double bond configurations just use cis trans) -Split double bond in half (perpendicular to double bond) -First identify highest priority substituent attached to each side of double bond: Higher atomic number = higher priority (if they are equal, use next atom outward to compare) used the Cahn-Ingold Prelog priority rules E - 2 highest priority substituents on opposite sides (If line drawn through middle of double bond) Z - same sides (in Russian accent: on zee zame side = on the same side) priority is based on molecular weight go atom to atom - not weight of entire group use when there are not 2 hydrogens so cannot classify as trans or cis