Organic Chemistry (MCAT)

nomenclature

methane, ethane propane, butane, pentane, hexane, heptane, octane, nonane, decane

methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, t-butyl

longest carbon chain, numbered based on lowest carbon substituent or OH, alphabetize substituents (ignore prefixes except iso),

functional groups

memorize them pg. 34

alkane, alkene, alkyne, alkyl halide
alcohol, phenol, thiol, epoxide, ether
aldehyde, ketone, hemiacetal, acetal, ester
amine, imine, enamine, amide
lactone, lactam

acetate

ethanoic acid

acetic acid

formic acid

formaldehyde

degree of unsaturation

U = (2C - H + N + 2)/2

molecule is saturated if it contains no pi bonds or rings

saturated alkaline has a formula of CnH2n+2

ring strain

ideal bond angle is 109.5, ring strain creates reactive molecules with high heats of combustion

carbocations/carbanions

positive/negative charge on carbon
more substituted carbocations are more stable
less substituted carbanions are more stable

since alkyl groups are EDG

inductive effect

EDG stabilize carbocations, EWG stabilize carbanions

the stronger acid has the more stable conjugate base, what groups will stabilize the charge?

resonance stabilization

delocalization- electrons allowed to interact with orbitals on adjacent atoms

conjugated systems give rise to strong colors

electrons in unhybridized p orbitals can participate in resonance, atoms (N) can switch from sp3 to sp2 to free up a p orbital for resonance

major resonance contributor is determined by:

1. octet rule
2. minimized separation of charge
3. charges on electronegative atoms

the stronger acid has the more stable conjugate base, what groups can delocalize the charge?

functional group acidity

strong acids > sulfonic acids > carboxylic acids > phenols > alcohol and water > aldehydes and ketones > sp CH > sp2 CH > sp3 CH (more s character is better at stabilizing conjugate base)

electronegative groups or positive charges can have inductive effect to increase acidity, stronger the close they are to the acidic proton

on benzene rings, para EWG can stabilize conjugate base, para EDG can destabilize conjugate base

acidity determined by stability of conjugate base:

1. electronegativity of adjacent atom
2. resonance stability
3. induction

nucleophilicity

increases from top right to bottom left (opposite of electronegativity)

nucleophilicity increases with:

1. increased negative charge
2. going down a group, increased polarizability for larger atoms since they want to donate their electrons
3. across a period, decreased electronegativity since less protons means they want to donate their electrons

leaving groups

good LGs:

1. resonance stabilized
2. weak bases
3. neutrals (start with positive charge)

bad LGs:

1. strong bases
2. but protonating them can make them good

ugly LGs:

1. hydrogens
2. alkanes

constitutional isomers

different atomic connectivity, same molecular formula

different properties

stereoisomers

same molecular formula and atomic connectivity, different spatial orientation

umbrella term for conformational, enantiomers, diastereomers

conformational isomers

same atomic connectivity, differ by rotation about sigma bond

identical properties

Newman projection

anti- two groups that are 180 apart
gauche- two groups that are 60 or 120 apart
syn- two groups that are eclipsing each other

anti is lowest energy state, but gauche can be more stable if some hydrogen bonding is going on

ring stability

chair is more stable than boat

equatorial position for substituents is more stable than axial position

1,3-diaxial interactions- sterics that are less stable

chiral center

chiral center is a sp3 carbon with four different substituents

of possible isomers = 2^n, where n = # of chiral centers

chiral molecules are not superimposable on its mirror image, no plane of symmetry

absolute configuration- assign priority with lowest in the back, heavier isotopes have higher priority

enantiomers

nonsuperimposable mirror images
opposite configuration at all chiral centers

each enantiomer has optical rotation of equal magnitude, but different signs

all other properties are identical

optical activity

chiral molecules are optically active
d = (+) = dextrorotatory = clockwise
l = (-) = levorotatory = counterclockwise

this cannot be predicted by structure, must be measured by polarimeter

diastereomers

nonsuperimposable nonmirror images, always compares two

opposite configuration at least one chiral center, but not all

unrelated optical activity, different properties, can be physically separated

geometric isomers

subset of diastereomers, restriction in rotation about a double bond or ring

do not require chiral centers, different properties

cis (Z) vs. trans (E) compares the two highest priority groups

epimers

subset of diastereomers, differ only at one chiral center

anomers

subset of epimers that are sugars

meso compounds

subset of diastereomers, symmetrical chiral centers have opposite R/S

achiral, have internal plane of symmetry

chromatography vs. spectroscopy

chromatography is used to separate compounds (including distillation and resolution as well)

spectroscopy is used to analyze compounds (including MS and polarimetry)

chromatography

stationary phase supports the mixture and retains compounds

mobile phase carries mixture while traveling

two big questions:

1. what's the best way to separate two compounds?
2. what compound will be isolated first?

size-exclusion chromatography

porous beads, smaller compounds enter beads and elute last

separate proteins from peptide fragments

can be used to estimate molecular mass

exclusion limit- compounds with sizes too large will all pass through at the same time

longer column leads to better separation

TLC

stationary phase is polar (paper), so polar travels slower

mobile phase is solvent bath in development chamber, can be polar or non-polar

moves from down to up

retention factor (Rf) = spot distance/solvent distance

eluting strength- how strong the mobile phase is at pulling stuff away from the stationary phase, the more polar the solvent, the stronger its eluting strength

column chromatography

stationary phase is polar (silica gel), so polar elutes last

same as TLC, but upside down

move from up to down

HPLC

most common form is reverse phase, stationary phase is nonpolar, so nonpolar elutes last

moves from left to right

ion exchange chromatography

separates based on overall net charge, stationary phase is anionic/cationic resin, with counterions attached

mobile phase is buffer solution, keeps pH constant

cation exchange retains cations (positive charge)

need to be flushed out by high concentration of counterions or to change the pH of the solution

affinity chromatography

stationary phase is resin linked to antibody-binding protein

elute target protein with competitive antibody-binding protein

separate proteins from cell lysate or blood

metal ion affinity chromatography

stationary phase is resin linked to Ni2+ ions

mobile phase is protein tagged with his-tag, which binds Ni

elute target protein by changing pH

gas chromatography

separates based on boiling point

gas chromatogram- plot of intensity over time

3 pieces of information:

1. number of compounds is number of peaks
2. relative quantity of each compound is determined by area each peak
3. higher BP compound (lower volatility) will elute later

distillation

separate large amounts based on boiling point

boiling chips- provide nucleation sites for bubbles to prevent superheating

two methods:

1. simple distillation- remove impurities, difference in BP is > 30 C
2. fractional distillation- separate diastereomers, difference in BP is < 30 C

vacuum distillation- lower Patm to lower boiling points

boiling point

higher BP molecules:

1. are larger and heavier (more IMFs)
2. have less branching (more compact)

determined generally by 3 intramolecular forces: H-bonds, dipole-dipole, Van der Waals

solubility in water

factors that determine solubility:

1. polar dissolves in polar, nonpolar dissolves in nonpolar (organic)
2. compounds with less than 5 carbons and a polar group are water soluble (exception, sugars are water soluble)
3. charged functional groups are soluble in water

separatory funnel, extraction

aqueous layer and organic layer (contains compounds you want to separate, use an ether)

organic layer- ether is not very polar, so amides and other ethers will go there
aqueous layer- water is polar, so carboxylic acids, amines, and alcohols will be there

1. to extract amine: add strong acid to protonate amine and turn into a salt to extract
2. to extract carboxylic acid or phenol: add weak base to deprotonate carboxylic acid or phenol and turn into a salt to extract

add weak acid to extract strong base
add strong acid to extract weak base
add weak base to extract strong acid
add strong base to extract weak acid

resolution

enantiomers have same physical and chemical properties, separate racemic mixture

1. add a chiral resolving agent (acid) to convert enantiomers to diastereomer salt
2. separate with regular means (recrystallization, distillation)
3. revert salt to enantiomers by adding a base

make sure they don't become meso compounds!

mass spectrometry

determine the molecular weight of compounds, determines elemental and isotopic composition

cannot separate isomers

UV/Vis spectroscopy

indicates presence of conjugated pi system

red shift- more resonance means more red

complementary wavelength- wavelength absorbed is opposite the one that is perceived (Christmas, Portal, Lakers)

red is 700 nm, violet is 300 nm

IR spectroscopy

IR light causes bonds to vibrate at different frequencies, shows which functional groups are present

peaks expressed as wavenumbers (cm-1)

does not show where the functional group is or how many, good for separating constitutional isomers but not stereoisomers

O-H is 3200-2600
C=O is 1700
C=C is 1600
CN/alkyne is 2100-2260
C-H appearance/disappearance does not help!

NMR spectroscopy

Hs are equivalent when there is free rotation or symmetry, each set of non-equivalent Hs give one NMR signal

splitting pattern indicate number of Hs on adjacent carbons, subtract one

multiplet for multiple splitting patterns

integration indicates number of equivalent Hs represented by peak, can be a multiple of the number of Hs

chemical shift is in ppm:

1. EDG shifts right/upfield/low ppm (alkyl groups)
2. EWG shifts left/downfield/high ppm (halogen, vinyl, aromatic, aldehyde, etc.)

common NMR peaks:

1. carboxylic acid- 11 ppm
2. aldehyde- 9 ppm
3. aromatic- 7 ppm
4. vinyl- 5 ppm
5. alcohol/halide/ketone- 3 ppm
6. alkyl- 1 ppm

SN1/SN2

SN1 involves carbocation formation which is the rate-limiting step, nucleophile can attack on either plane of sp2 C, so both enantiomers can form

SN2 involves backside attack, so inversion of configuration with pentavalent transition state

SN1 on 2/3 degree carbons only (carbocation stability!), SN2 on 0/1/2 degree carbons only

SN1 considerations:

1. doesn't consider nucleophile size/conc. in rate law
2. polar, protic solvent
3. 2/3 degree carbons only

SN2 like polar, aprotic solvents: acetone, DMF, DMSO

alcohols and ethers undergo substitution only with an acid catalyst or conversion to a better leaving group (something resonance stabilized maybe)

tautomerism

keto form to enol form, goes through enolate, tautomers are constitutional isomers

keto form is more stable

since tautomerism occurs, adding D2O will cause deuterium exchange until all Hs are Ds, no signal on NMR, this shows that those Hs are acidic

carbonyl chemistry

carbonyl carbon is electrophilic

alpha hydrogen is acidic

resonance can occur

nucleophilic addition

weak nucleophile needs an acid catalyst to make the carbonyl C more electrophilic

hydride reduction (nucleophilic addition)

NaBH4 or LiAlH4 are reducing agents that donate an H to attack a carbonyl, reducing it to an alcohol

cannot produce tertiary alcohols

organometallic reagents (nucleophilic addition)

act as carbanions to attack a carbonyl, grinard reagent uses a halide with essentially a carbanion next to it

hemiacetals/acetals (nucleophilic addition)

alcohol is nucleophile, forms hemiacetal first (with one alcohol one ether group), then forms acetal (two ether groups)

acid catalyst for both steps so weak nucleophile can attack

imine/enamine formation (nucleophilic addition)

primary amine is nucleophile, reaction is similar to acetal formation, except instead of 2 attacks, carbonyl C is just double bonded to N to form imine

secondary amine is nucleophile, positive charge is left on N, so alpha H is eliminated to form an enamine

enamines are nucleophilic at their alpha-carbon, can do SN2 reaction to add something to the alpha position

adding H2O to enamine will reform carbonyl

aldol condensation (nucleophilic addition)

enolate reacts with ketone or aldehyde

SN2 reaction to add at alpha carbon of enolate

elimination to form double bond on newly attached ketone or aldehyde

enolates (kinetic vs. thermodynamic)

use a base on a ketone, which alpha proton will be taken to form which enolate?

kinetic enolate- forms faster, less steric hindrance for accessing the acidic H
you can select the kinetic enolate using a bulky base (LDA) and cold temperatures (-78 C)

thermodynamic enolate- forms more substituted double bond, more stable
select thermodynamic enolate using small base (MeOH) and high temperatures

carboxylic acids

3 quick points:

1. highly polar, form many hydrogen bonds
2. can be reduced to primary alcohol by LiAlH4
3. reactions involve nucleophilic addition-elimination with a tetrahedral intermediate

esterification (ester formation)

1. alcohol attacks carbonyl carbon on carboxylic acid
2. proton transfer
3. eliminate OH, form ester

a compound with both carboxylic acid and alcohol groups can form a cyclic ester if the ring is stable

saponification (ester hydrolysis)

1. OH attacks ester
2. ester piece is eliminated, nabs an H before leaving
3. form carboxylate anion

hydrolysis

cyanohydrins are prone to hydrolysis

ATP -> ADP + P hydrolysis can either activate or inactivate the enzyme its bound to

pretty much everything can be broken down with hydrolysis

carboxylic acid derivatives

derivatives from most reactive to least:

1. acid halide (add SOCl2 or PBr3 to carboxylic acid)
2. acid anhydride (add another carboxylic acid)
3. ester (add an alcohol)
4. carboxylic acid
5. amide (cannot be made, adding amine to carboxylic acid just does a little proton transfer lol)

Strecker amino acid synthesis

1. imine formation from aldehyde and NH4Cl
2. nucleophilic addition by KCN
3. convert to carboxylic acid with acid

nonstereoselective!

simpler than gabriel synthesis

Gabriel malonic ester synthesis

1. deprotonate phthalimide with KOH
2. SN2- phthalimide attacks alpha carbon in malonic ester
3. deprotonate center carbon and attack a new alkyl halide (which will have the desired R group)
4. hydrolysis of esters and imide with acid
5. decarboxylation with heat

nonstereoselective

charge on amino acids

when pH > pKa, group is more than 50% deprotonated
when pH > pI, the amino acid is net negative

1. pI is the isoelectric point, zwitterion
2. pI = the pH at which amino acid has no net charge
3. average the two nearby pKas

pI help you determine amino acid separation in a gel

peptide bond formation

amide bond formed by amino group attacking carboxyl group and eliminating the OH

non-spontaneous process that needs enzymes!

characteristics of peptide bond:

1. planar and cannot rotate!
2. partial double bond character due to resonance
3. amide H slightly acidic

peptide bond hydrolysis

also non-spontaneous process that needs proteases

denaturation

changes 3D structure without breaking peptide bonds

denaturing agents:

1. high temperature
2. high/low pH
3. changing salt concentration
4. urea

carbohydrate nomenclature

In Fischer projection (horizontal is out of page, vertical in into page, end OH is at the bottom):
OH on the right- D (+), penultimate carbon is R
OH on the left- L (-), penultimate carbon is S

penultimate carbon- second carbon from the end OH
anomeric carbon- carbonyl carbon, alpha/beta

carbohydrate cyclization (mutarotation)

OH on penultimate carbon attacks anomeric carbon

alpha anomer- OH on anomeric carbon is down
beta anomer- OH on anomeric carbon is up

these are epimers

Benedict's test, Tollen's test, silver deposition (mutarotation)

positive test (red, silver deposited) indicates reducing sugar present (hemiacetal/aldehyde present, all monosaccharides have hemiacetals)

negative test (no precipitate, no silver) indicates no reducing sugar (disaccharides usually have acetals)

maltose is a reducing sugar
sucrose is a nonreducing sugar

glycosidic linkage

acetals connecting two sugars

glycogen usually has an alpha-1,4-glycosidic bonds
but branching of glycogen occurs with alpha-1,6-glycosidic bonds

notation involves alpha/beta of left most sugar and carbon numbers

change in alpha/beta tells you an SN2 reaction occurred at the anomeric carbon

fatty acids

fat fun facts:

1. triacylglycerol can be converted to glycerol and 3 fatty acids by saponification
2. fatty acids are amphipathic, forming micelles in aqueous environment
3. phospholipids have two hydrophobic tails with a hydrophilic head, form lipid bilayers
4. saturated fatty acids pack better (form solids)
5. unsaturated fatty acids increase fluidity (form liquids)