TBR Organic CHEM 2518

*Units of unsaturation* (2cin - h-x + 2)/2

[(2C + N) (- H - X )+ 2]/2

Alpha protons deprotonation

Hs on alpha carbon are mildly acidic (pKa 19) A *strong base* can remove alpha Hs) *enolate* forms This enolate can a *proton at the oxygen* to form an *enol*

Ammonium

or NH4+

*Inter*molecular forces

Hydrogen bonds: (H-NOF), 4-8 kcal Polar interactions: (+ & -), 1-3 kcal VDW (all compounds), <1 kal.

Alcohol 1H NMR spectra *OH → 1-5*

Hydroxyl groups give a signal 1 to 5 ppm

Limonene formation

Identify the units

In a furanose ring, there are 4 chiral centers

If it was straight, there will be one less chiral center.

A compound not reacting with bases (strong or weak) cannot be an acid and has *no acidic protons*, such as *di-nitro-beneze*

It remains neutral throughout extraction.

How can a sugar be separated?

Like dissolves like (sugars have a lot of -OH groups) Use alcohols

Fat-soluble vitamins travel in the blood through low-density lipoproteins

Lipids bind to the *core* pockets of the carrier to be shuttled through the blood.

Best compound to make an inhaler

Liquid with good vapor pressure (low BP) Low MW

Oxidizing agents

Lots of Os Cause oxidation (get reduced) O-rich H-poor High oxidation state atom & high e- affinity Examples: KMnO4 RCO3H O3 NAD+ CrO3 ROOR FAD NADP+

Si(CH3)4

NMR shifts reference (0 ppm)

Terpenes & terpenoids

Natural hydrocarbons found in plants and animals with *5-C isoprene units*

Bases (NaOH) deprotonate species→ - - - - - -

Neutral acids would become anions when deprotonated (+++ → ---).

Splitting pattern (coupling)

Number of hydrogens in a neighboring atom.

Most AAs don't contain amide bonds. Only *gln & asn* have* amide bonds. *

Only AAs to contain *amide bonds* Glutamine & asparagine

Benzene NMR

Para: doublet of doublets (*dd*)

Plane vs point symmetry

Plane symmetry: mirror plane splits molecule into equal halves. Point symmetry: molecule has an inversion point at its center of mass X)

Question

Product has S config NaOCH3: strong base (good nuc) Good nuc → SN2 (needs good LG) *SN2 product: inversion (S to R or R to S)* Product is S → reactant R Cl is good LG, ammonia isn't (choice A)

What is the oxidation state of aluminum in LiAlH4? +3 +1 -3 -5

Remember, H here is not in the list, -1, this makes Al get a three.

Comparing carbonyl groups length Resonance C=O → single bond character → longer

Resonance (by *N donating electron pair to carbonyl*) makes the carbonyl group LONGER than a standard non-resonance C=O since the carbonyl in resonance takes some single-bond characteristic.

Biochemical REDOX reactions Retinol: trans → cis (via light) *Pay attention to carbons numbering*

Retinol to retinal redox (*trans → cis on C11*) Commonly involves NADH, NADPH, FAD with *methyl transfers*

*Combustion* of alkane hybridization

Sp3 (C with 4) to *Sp (CO2)*

Nitrogen lone pair of electrons

Sp3 hybrid orbital

As a molecule's symmetry increases

Spectroscopic signals decrease

Gabriel synthesis: Phthalimide added to alkyl halide. R group added for decarboxylation and forming AA

Strecker: Aldehyde to imine. Adds cyano to imine. Hydrolysis.

Weak acid removes strong bases only

Strong acid removes weak & strong bases

pKb = 14 - pKa

Strong acid: LOW pKa its conjugate base pKb is HIGH

*Mass Spectrometry* Determining organic molecules mass. 1. Energy added to covert molecules to cations. 2. Cations are accelerated to an electric field after which they're deflected along a circular path by perpendicular magnetic field.

The *circular path radius correlates with particle's mass-to-charge ratio.* Mass spectroscopy material should be in the gas phase (particles travel independently) & at low pressure (so reactive free radicals & cationic particles won't react).

Smaller central atom → shorter bond length

The *more s-character* in a hybrid orbital of the atom bonded to H, the *stronger the acid* *Acidity: sp>sp2>sp3*

AAs notes

α carbon w/: *H*, *CO2H*, *NH2*, *R* group

Sucrose structure

The only disaccharide that involves a *glycosidic linkage between 2 anomeric carbons*

*Reaction rate* vs. nucleophilicity

The reaction rate is *fastest with the best nucleophile* and *least inductive* withdrawal.

Protein primary structure

The sequence (connectivity) of AAs within a protein. Breaking the primary structure requires *cleaving the peptide N-C bond* Amino group to carboxyl group.

Dissolving in water requirements (1 or both): 1. Charged 2. Polar Shorter → more soluble

The shorter, the more soluble.

BP vp = atm

The temperature at which vapor pressure equals the atmospheric pressure.

Elution time

The time it takes a component to travel the length of the column and drips out.

Remember again, cell membranes with *phosphatidylcholine* or phossphatidyl*ethanolamine* are charged *balanced* and require no counter ions.

Their (+) charge offsets the negative charge of phosphate making it a zwitterion (a neutral species)

N-H bond is similar to O-H bond, both form H-bonds

Their IR values must be close ~3000 cm OH is broader because its H-bonding is stronger than NH

Water & alcohol form H-bonding when mixed

Their behavior is different if they were NOT mixed.

Ketal formation mechanism (from a ketone) under *acidic conditions.*

1. *Protonate* carbonyl oxygen. 2. *Break* the weakest bond (carbonyl pi) 3. Nuc attacks carbonyl carbon to *make* a new bond. 4. *Deprotonate* to form a neutral product. *Base-catalyzed* mechanisms: deprotonate, make, break, protonate (*opposite*)

Rf values can be used to estimate:

1. *Solubility* of a solute in a solvent. 2. *Elution time of a solute* from a column in a chromatography experiment. 3. The nature of the *intermolecular forces* between solute & solvent. It CANNOT measure reactivity

To be a good soap:

1. At least 8C organic chain. Longer chain oils would need longer chain soaps to remove them. 2. A *(-) charged* carboxylate. Carboxylate is a deprotonated carboxylic acid.

Bioorganic reactions

1. Biological substitution. 2. Biochemical alkene addition. 3. Biochemical pericyclic reactions 4. Biochemical oxidation-reduction reactions

Compare two stereocenters

1. OH & H exchange locations: does change 2. 4 substituents at the R end don't change locations, they just rotate. Change at only one center → diastereomers

Natural antioxidants (i.e. vitamin E) features

1. Phenol ring 2. Conjugation

Strecker synthesis

1. Starts with an aldehyde with desired R group (AA-specific). 2. Conversion into imine. 3. Addition of cyano group. 4. Hydrolysis of C-N triple bond using acidic water.

When asked for which cannot be optically active, look for the following:

1. Stereocenters (symmetric cannot be optical). 2. Meso (internal symmetry)

*Disulfide linkage* Oxidation makes it Hydration (SCCOH) breaks it

2 cysteines *lose thiol group H (oxidation).* *Form S-S bond*. Cystine *cross-link* is *removed* by a *reducing* agent (b-*mercaptoethanol*, SH-CH2-CH2-OH)

Elemental *bromine Br2* mass-spectroscopy

2 identical peaks (50% 50% isotopes) at 1:1 ratio

Isoprene unit characteristics

4 Sp2 carbons & a methyl Achiral Must be functionalized to be reactive. 2 units of unsaturation

How many π electrons does leukotriene A4 have? How many units of unsaturation?

4 π e- on the alkene (3 π bonds in conjugation: 6-π e- in a conjugated system). 1 π e- on the carbonyl. 1 π e- on the epoxide ring. Units of unsaturation: 4 (from = bonds) + 1 epoxide + 1 carbonyl = 6 units

Aspirin mechanism

Blocks COX so PGG2 won't form.

First areas to look at in an IR spectra

Broad 3400 peaks (*O-H*) Sharp 1700 peaks (*C=O*) Sharp 3000+/-: *C-H* (sp>sp2>sp3)

How do you ID D-sugars right away?

C6 is always pointing up, not sideways.

Overall odd mass number, you can see NMR spin

Can't see C12, D (deuterium) Can see C13, H1

Electrophoresis Note

Cathode: ------------ Anode: +++++++++++++++

Enzyme active sites

Chiral specific Size specific Funcational group specific NOT isotope specific

MW & intermolecular forces affect BP

Chirality affects MP & sublimation Chirality doesn't not affect BP because it doesn't affect packing.

*Affinity chromatography* Same charge as column → elute 1st Opposite charge as column → get stuck (pH change removes them)

Column (stationary phase) has (+) or (-) charged polymers that bind to anionic or cationic groups

Question: the following compound is made or not made from *isoprene units*?

Count the carbons, you need *multiples of 5*

Common oxidation agents PCC weak K2CrO7 strong

CrO4^2- MnO4- *PCC* (1 alcohol to aldehyde) *K2CrO7* (strong: 1 alcohol to all the way to carboxylic acid)

Cystine formation

Cross-like: cysteine residues forming a crosslink by undergoing dehydrogenation (loss of H) which is an oxidative process. pi-bond in FAs is hydrogenated to form aliphatic chains by undergoing reduction.

Protein primary structure determination

Cutting and sequencing

Tautomerization

Cyclic ketone tautomerizes to a phenol with gained aromaticity.

*Bonds between AAs* Lys-glu → *ion* pairs (*basic-acidic*) Ser-lys → ion polar bond. (philic & basic) Ser-asn → H-bonding (philic & N-containing)

Cys-cys → disulfide Ala-leu → hydrophobic effect (phobic-phobic) Lys-asp → *electrostatic*, ion pairs (*basic-acidic*)

Alkyl group

EDG by induction

EWGs (i.e. C=O) are less basic than NH2

EDGs (i.e. methoxy H3CO *pic*, alkoxy) are more basic than NH2 *Basicity: H3CO > NH2 > C=O*

*Chiral catalyst at TS* → avoid racemic product.

Enzymes (chiral catalysts) are enantiomerically specific in biological reactions.

Secondary sp3 example

Et (ethyl)

Number of stereoisomers in a structure

Example: 1 chiral center: 2 max (R or S) 2 chiral centers: 4 max (RR, SS ,RS, SR)

AAs stereochemistry

Exist in L-stereochemistry in biological systems (except bacterial cell wall D-alanine w/ glycine)

Question x2

Find water, connect it, remove it, then it's be.

*Nitrogen gas in distillation* ↓ Surface vapor partial pressure

Flown across liquid surface to reduce partial pressure of the *vapor* so it can *escape quickly* & vaporize. Nitrogen distillation causes the solvent to evaporate faster by *allowing new vapor to form.*

Pen-ultimate (before last) carbon determines D or L designation of a sugar.

For a 5-membered ring, penultimate is C4.

*Carboxylic acid* Weak acid: *2-5* pKa Less reactive than ester

Formation: 1. Saponification: *ester* w/ strong *base* in water. 2. Methyl *ketone* + I2 & strong *base*. 3. *Oxidizing primary* alcohols and aldehydes 4. *Amide* or *nitrile* hydro*lysis*.

Peptide bond

Formed between N & carbonyl carbon by *dehydration*

Lactones (cyclic ester) formation

Formed by *Ester & OH* on *same* molecule in *acidic* conditions.

To form a cyclic sugar

A hydroxyl group attacks the carbonyl carbon to form a hemiacetal (aldehyde) or hemiketal (ketone)

Identify the nitrogen compounds in the picture

A imine B amine C hydrazine D amide

How does sesquiterpene form, how many c-c bonds?

A linear form would need 2 C-C bonds. Sesquisterpene is made of 15 Cs (3 isoprene unites). 5C-5C-5C (2 carbon-carbon units). A cyclic one, would need 3 carbon-carbon bonds to form a ring.

How much SDS does a protein take?

A longer protein would take on more SDS than shorter proteins (& twice as much charge). Therefore, the *mass : charge ratio* is *constant*

Aliphatic

A structure with no rings or pi bonds.

SDS-PAGE

All proteins fragments incorporate SDS into their secondary structure. Every fragment gets a *(-) charge*. *Smaller* species migrate *faster* (less drag resistance).

Maltose vs. lactose

Alpha vs. beta *acetal* Look at C4

1. Biochemical SUBSTITUTION reactions

*Acetylcholine biosynthesis* (from *Ser*): Nucleophilic choline hydroxyl attacking acetyl-CoA carbonyl carbon. Thiol is a leaving group.

Protein pI *(# of KHRs) + 1*

*Add # of Lys, Arg, His + 1*

*β-D-Glucopyranose*

*All substituents* on the pyranose ring have *equatorial* orientation.

More about alpha & beta anomers

*Alpha*: anomeric oxygen is *trans* with last carbon (*CH3 at C6)*. *Beta*: anomeric oxygen is *cis* with the last carbon.

The *most reactive* compound is the *BEST nuc*leophile (-). Amine (best) ether, ester and amide → weaker nucs

*Amine* is a better nucleophile than ether, ester or amide

Carbonyl bond IR spec

*C=O → 1700* cm

Fluorine is more electronegative than chlorine

*F withdraws electron density *more than Cl and *makes the molecule more electron-poor* and a *stronger acid* (better electron acceptor)

Distillation boiling chip (stone)

*Rough surface for vapor to collect* while building near the flask bottom. Used to *avoid bumping*. Superheated solution from bottom (closest to heat source) rapidly migrates to top with a higher T than the boiling point & evaporates quickly causing a splash (bump). Increases effective surface area to *enhance volatility* in the distilling flask. It is NOT used for an even heat distribution.

*Take a picture of Page 191*

*Take a picture of page 197 question 19*

The *minimum number of bonds* required to hold a molecule together is always *one less* than the *number of atoms*

Atom1-Atom2: 1 bond Atom1-Atom2-Atom3: 2 bonds

Protein tertiary structure example

Beta pleated sheets involve H-bonding of amides between nearby AA moieties.

How does H-bonding happen in beta-pleated sheets?

Between C=O oxygen & Nitrogen's H.

Some AA characteristics

*Carboxyl* terminal always has the *lowest pKa* and gets *deprotonated 1st* (more acidic than amino terminal).

Waxes

*Esters* of FAs (*C-O-C*) Long chain alcohols *Highly hydrophobic* ester with high MP *Structural* component *Hydrolysis* of wax *via basic* water would form (*saponification*): 1. A *long* chain *alcohol* 2. A * long* chain *amphipathic carboxylate* (since environment is basic, COOH → COO- forming carboxylate)

Optical rotation *(+/-, d/l)*

(+) or (d): clockwise (-) or (l): counterclockwise Using a polarimeter +/- don't necessarily correspond to R/S

N (in ring) donates electrons thru resonance More e- (-) → *EDG* (lone pair or π) → *basic* No e- (+) → *EWG* (+ rich) → *acidic*

(-) charge on O is more basic (more electrons) *(+)* charge on *amide* is less basic (absence of electrons) → *acidic*

Polypeptide *hydrolysis* cleaves the *amide bond (N-C)*

N-C bond is broken

Chemical reactions of of carbohydrates

Nitric acid Osazone Tollen's Kiliani-Fischer synthesis Ruff degradation

Which AA is found in *protein channel core*? Leu Val Phe Ser

Notice 1st three are hydrophobic, give away, d is the answer. Exp: Outside protein channel contains hydrophobic aide chains. Inside (core) of channel must be hydrophilic to allow small charged species to traverse the channel.

Question 4

Notice aldehyde is becoming a primary alcohol. FADH2 is specific for pi bond hydrogenation. H2NNH2 aldehydes to alkanes. NaBH4 is specific to aldehydes and ketones (correct). LiAlH4 would turn it to ester.

2. Biochemical alkene ADDITION reaction

Notice on the sides of the double bonds, OH & H from water were added. FADH2 can be used for a hydrogenation reaction (where H & H get added to both sides of the = bond)

Histidine protonation

Notice that imine N remains sp2 hybridized at protonation (low pH) and deprotonation (high pH)

Phosphatidyl-choline

Notice that it is a *zwitterion* because it possesses a positive & a negative charge, so it won't need an outside ion to offset the charge on either the phosphate (-) or the choline (+). *Membrane component*

Attack at carbonyl carbon

Nuc attacks a carbonyl compound (at partially + C) to form a *tetrahedral intermediate*

In protic solvents, nucleophiles that form H-bonding are hindered

Nucs that don't have H-bonding are *unaffected*

Imine + acidic water break the ring at the = bond with equal sides. One side gets an O, the other gets H2

O= in choice A resulted from water addition.

OH + aldehyde (basic conditions) → hemiacetal

OH + aldehyde (acidic conditions) → acetal

Erythrulose

Only ketotetrose known D-

Glycolysis 1st step

Phosphorylated glucose carries a negative charge: it cannot cross the plasma membrane.

Electronegative atom de-shield things

Pi electrons can cause their own de-shielding.

*AAs* PKa Amino-terminal: 9.7 +/- 0.9 Carboxylic acids terminal: 2.2 +/- 0.4

Polyprotic acids where all the *protons are weakly acidic.* All chiral (except glycine) All naturally occurring AAs have *L-stereochemistry* (except *cys*teine which is *R* at the alpha).

Protecting groups 2

Reactant has multiple reactive sites, but only one site is needed to react. Aldehydes to acetals Ketones to ketals Alcohols to *silyl ethers*

Cholesterol Makes cholic acid (bile) & steroids

Regulates membrane fluidity, a *starting material for steroids* biosynthesis. A synthetic precursor to *cholic acid* (bile salt component)

Glycolysis step 4

Retro-aldol reaction 6C to 2 3C (DHAP & G3P) By *aldolase*

Higher yield

Simple distillation

Size-exclusion (Gel-filtration) chromatography

Smaller particles get caught within the pores of the column and larger ones elute faster.

Column Chromatography

Solvent flows DOWN (relies on gravity). If the compound migrates *quickly* down the column, it must experience a *minimum attraction to the stationary phase*. Top & bottom of column must be flat (same travel distance) and should be plugged to protect the top from disruptions in its flatness. *Faster migrating* compounds reach the bottom first, so they have *short elution times*.

TLC

Spotting a sample at the base of a plate and placing a solvent just below the level of the spots. Capillary action moves the solvent slowly up. A lid is placed to avoid evaporation of the solvent. Iodine crystals or UV light is used for visualization. Then the traveling species will be described as polar, semipolar or nonpolar based on the results. An unknown sample can be compared to a known one to determine its identity. The spot cannot migrate as far as the solvent because *Rf* is simply measuring its *affinity to the solvent. * TLC can be used to determine the number of *components in a mixture*, monitor a *reaction progress* or *id*entifying the *best solvent*.

Isolating terpenes

Steam distillation

Hydrogen bonding (*protic*) OH > amines > CHO

The H-bond strength can be estimated by 1. The base properties of the lone pair donor 2. The acid prosperities of the H-donor Protic: H capable of H-bonding is an acidic H H-bonding of alcohols is STRONGER than H-bonding of amines H-bonding compounds are ALSO dipole dipole since H-bonds are polar. Butanol (alcohol) has a higher BP than butanal (aldehyde) due to H-bonding in butanol only.

If given Rf values of solvents

The best solvent is the one that gives MUCH different Rf values. Good solvent: Rf values are .2 & .6 Bad solvent: Rf values .1 & .2 .07 & .21 are better than 0.58 & .29 because 1st are 3x different (just use a shorter column)

*Spectro*photometer

Uses *salt plates* to hold the sample because salt plates have ionic bonds that *don't interfere with* the sample molecule's *absorbances.*

UV spectroscopy

Visible: longer lambda, shortest to longest (VBGYOR). More conjugation >>> longer lambda & most colored (max wavelength of absorption).

Question x

Why is the 3rd choice the right one, see above.

Claisen condensation in FA synthesis

With thioester

Anomers

Have to be *CYCLIC* To compare, the name should have *alpha/ beta*

Hydrocarbons properties

Hydrophobic, nonpolar. Contain only C-C & C-H single bonds & are relatively inert. Molecular mass increases, MP, BP increase *Branching* increases, *BP decreases*

NMR allows distinguishing CIS & Trans

IR can't

Isoprene unit

Identify the cat

AAs with 2 chiral centers (*IT*)

Isoleucine I & threonine T

Column chromatography vs Rf

Low Rf (dot is still in the bottom): migrate slowly. High Rf (dot is up high): migrate quickly.

More volatile → higher vapor pressure

Lower BP, higher vapor pressure (weaker forces)

Kinetic product

Major product is selected to *minimize steric hindrance* in the transition state (low AE required to go through a less hindered TS)

Thermodynamic product

Major product selected to maximize stability of the intermediate or product. More substituted intermediate (more - delta G)

Partition coefficient

Max solubility ratio between two solvents.

What's this structure? How do you know?

β-D-Glucopyranose. ALLLLL pyranose subs are equatorial

Soaps & detergents molecular structures

*Amphipathic (amphiphilic)* with a *(-)* sign on the head Hydrophobic & hydrophilic Surfactant when added to water. Polar heads penetrate water surface. Soaps are derivates of carboxylic acids & carboxylates To form a *micelle*, they need: 1. *CHARGED end* 2. *Alkyl Carbons* (hydrophobic group).

Anomers vs. epimers

*Anomers* vary in chirality at the *most oxidized C*arbon (anomeric). *Epimers* vary in chirality at a less oxidized, backbone carbon.

Diastereomers

*At least 1*, but *not all chiral centers* differ.

Steroids biosynthesis

*Biosynthesis* starts with *pyrophosphate* (weak base, good leaving group) *added to a terpene* Two types of it are used in our bodies, isopentyl & dimethyl pyrophosphate. Then *geranyl*-pyrophosphate Then *Farnesyl* pyrophosphate* Then *Squalene* that turns to *cholesterol*.

Conjugate base pKa ↓ (acidic) → LG strength ↑ LG strength increases as the strength of the bond between C and LG decreases (i.e. Iodine is better than Fluorine)

*Carbon-LG bond* weak → strong leaving group. Ex: C-iodine bond is weaker than C-F → Iodine is a stronger LG

Chirality at TS of a reaction pathway (adding a chiral catalyst)

*Chiral catalyst @ TS → no racemic product*

*More conjugation, bigger wavelength* of maximum absorbance.

*Conjugation reduces the transition E* between energy levels.

Cysteine Affects 3° of one protein or 4° of two proteins. Can lose a proton in HIGH pH

*Cysteine* is involved in *cross-linkage* within a protein. It impacts the *tertiary* structure (within *one protein*) or the *quaternary* structure (between *2 proteins*). The formation of *cross-linkage* involves *thiol bonds oxidation* on both cysteine residues.

*Anion* Exchange (DEAE)

*DEAE-cellulose (+ *at neutral pH) Binds *acidic* AAs

Haworth projections

*DownRight UpLeft* at: C2 C3 C4

Electron withdrawing & donating groups (EWGs love acidity)

*EWG*: increase *acidity* (lower PKa) EDG: decrease acidity (increase PKa)

Stereoisomers physical properties

*Enantiomers*: identical BP, MP, density *Diastereomers*: slightly different physical properties. *Racemic mixtures* have stronger *intermolecular forces* than pure enantiomers (*higher MP & density* than either enantiomer alone).

Enantiomers vs diastereomers

*Enantiomers*: non-superimposable *MIRROR* images. Diastereomers: non-superimposable NONE-mirror images

Simple distillation vs Fractional distillation

*Fractional*: more efficient, more surface area, small BP differences (*less than 30 C*), greater distillate purity, the distillation column is filled with an inert solid to provide more surface area and should remain solid at the increased temperature, such as glass beads (to condensate & re-evaporate). *Simple*: faster, generates a *higher yield*.

Covalent bonds (σ & π) As electronegativity difference decreases, covalent nature of a bond increases. Types: *Sigma*: Most electrons are BETWEEN nuclei of two atoms. *pi*: above & below the internuclear region sharing, ONLY p orbitals.

*Sigma bond* is stronger than pi (*except in F2 (π only)* that has 1 pi & no sigma due to its small size & internuclear repulsion in single bonds, this explains why F2 has less bond disassociation energy than Cl2). On the contrary, BH3 has no pi bonds.

Sigma & pi bonds

*Sigma* orbital is *more stable* than *pi* bonding orbitals. *Sigma anti*-bonding orbitals are *LESS STABLE* than *pi anti*-bonding orbitals. Anti-bonding orbitals have no overlap between atoms.

*CHAD*

*Spectroscopy*

Amides (*neither* acidic *nor* basic)

*Substitutions* reactions. Their bonds are called *peptide bonds.* *Cyclic* amides are *lactams*

*Silyl ether* Alcohols need silly ethers to protect them.

*Take pic of p112 1. Alcohol to silyl ether to protect it. 2. Removal of protecting group by (NaF or H3O) to deprotect & bring alcohol back

Allylic vs. vinylic

*Vinylic*: functional group *directly linked to =*. *Allelic*: functional group *in*directly linked to the alkene.

Ruff degradation (-)

- 1C of aldose.

Gas chromatography (GC)

1. *Vaporize* a sample into gas phase. 2. Force organic vapor into column using elevated pressure from a cylinder of an inert gas. 3. Machine *measures retention time* on the column by recording *collisions as gas molecules* leave the end of the long coiled column and strike the detector (reads collisions). 4. Collisions get converted to *peaks* to determine their *relative abundance*. It graphs *collisions intensity vs. time*). 5. Greater signal area means greater quantity. 6. *Retention time* depends on the *column nature* and the *compound structure*. 7. The *purity of the product* mixture can be observed directly in the *total number of peaks*. 8. GC is used as both an ID tool for the reaction mixture and as a tool for *measuring reaction kinetics*

Which oxidation reaction is not possible? 1. 1-butanol to butanone 2. 2mehthyl-1-pentanol to a carboxylic acid. 3. 1-pentanol to an aldehyde 4. Cyclohexanol to a ketone.

1. 1 alcohol to ketone, not possible (correct) 2. Primary alcohol to carboxylic acid, possible. 3. Primary alcohol to aldehyde, possible. 4. Secondary alcholol to ketone, possible

SN2 Product features

1. A *single enantiomeric product* formed (no racemic mixture) 2. Exhibit 2nd order kinetics (*rate = k[nuc][elect]*) 3. *One-step reaction* with fast rates of formation

*Oxidation* C-O bonds ↑ → oxidation level ↑

1. Count number of *c*arbon*-o*xygen *bonds* to the carbon of interest in the reactant. Every C-O bond counts as one. If *1 C-H* bond is *lost* & *replaced* with *C-O bond*: Oxidation *level* increased *by1* Oxidation *state* increased *by 2*.

What can result from extreme heating during distillation?

1. Decomposition (denaturing) 2. Oxidation 3. Polymerization. Hydrogenation cannot happen because there should be a H-source

*SN2 reaction course* (usually faster than SN1, no intermediate)

1. Forms *5-ligand transition state* in the middle of the reaction. 2. 5-ligand TS is the *highest energy state* existing for a split of a second. 3. Steric forces destabilize the TS by forcing the bond to become <109.5

*Synthetic pathway analysis steps*

1. ID new bonds & functional groups by counting atoms and changes in bonds from reactants to products. 2. Break product into fragments that match reactant skeleton. 3. Reconnect fragments with the proper chemical reagent.

Extraction notes

1. If a basic solution was used, then the content of the tube can be neutralized by the addition of an acid. If the solution is a weak base, use a strong acid (to protonate it)

Radical reaction steps

1. Initiation: makes a radical 2. Propagation: same # of radicals on both sides. 3. Product is not a radical anymore.

NMR spectrum analysis

1. Integral (# of Hs making a signal) 2. Splitting pattern (coupling between Hs neighbors) 3. Shift value (local magnetic filed by lone electron pairs or electrostatic density with electronegative atoms)

Micelle2

1. Making aprotic compounds (i.e. ketones) soluble in protic solvents. 2. Making protic compounds soluble in aprotic solvents.

When asked to ID maltose structure, what do you consider?

1. Maltose is an alpha disaccharide, so anything beta is out. 2. It consists of 2 alpha-D-glucopyranose sugars.

Most nucleophilic nitrogen

1. Nitrogen with ready lone pair to share. a: amide electrons are tired up in resonance, can't give away. b. e-s shared with benzene ring thru resonance, can't c. free from conjugation (sp2). It carries a partial negative charge (more nuc than normal sp2). d. involved in aromaticity of 5-ring, tied up (can't).

SN2 reaction Transition state

1. Sn2 rxns form TS (not carbocation/intermediate). 2. TS has 5 bonds to electrophilic carbon. 3. Good nuc & LG are *colinear* in the TS. 4. Aprotic solvent (i.e. COC)

Mono-terpenes

10 carbons (2 isoprenes)

C3H8 bonds & electrons

10 minimum bonds & 20 bonding electrons. No extra bonding electrons, so propane has NO units of unsaturation

H (proton) NMR

13-0 ppm scale Alkane: 0-4.5 Alkene: 5-7 Aromatic: ~7-8 Aldehyde: 9-10 Carboxylic Acid: 10-12 For an alkane to go past 3 (3-4.5), it needs the following form *H-C-X*

*Resonance rules:* 1. The resonance structure should contain atoms with *filled octets* (except H) 2. The best structure *minimizes* the number of *formal charges* throughout the molecule.

3. If the molecule contains *(-) charge*, it is best placed on the *MOST* electro*negative* atom. If the molecule contains *(+) charge*, it is best placed on the *LEAST electronegative* atom.

Alcohols spectroscopy

3200 to 3600 cm broad (due to H-bonding)

Radicals stability

3>2>1. Tertiary, secondary, primary. Remember, quaternary radicals don't exist.

*SN2 vs. SN1* 1. *SN1* prefers tertiary & allylic electrophiles. Methyl & primary electrophiles: *SN2* 2. Nucleophile strength a) Strong: SN2 Weak: SN1 3. Better LG: SN1

4. Solvent. *Protic* (forms H-bonds): *SN1* *Aprotic* (i.e. ether): *SN2* 5. Rate If [nuc] changed reaction rate → SN2. 6. Intermediates in diagram (((((*SN2: NO intermediate*)))))) *SN1*: intermediate + 2 TS 7. *Product* *Sn2*: 100% inversion & *enantiomeric excess* (without racemic mixture) *Sn1*: *racemic mixture* & *zero* enantiomeric *excess* *More excess = SN2*

Aromaticity requirement

6 pi electrons inside the 6C ring.

*Glycolysis → reverse aldol* reaction (step 4), breaking

6C breaks between *C3-C4* forming DHAP & G3P

UV to visible spectroscopy (π to π*) Conjugation ↑ → λ max ↑

A compound has to have π to be UV-visible active. When more conjugation is added, the absorbance shifts into the visible range.

Tautomer vs. resonance structure

C=N: imine C-C=N: enamine Tautomer: H moves Resonance: only electrons (not atoms) move

Alkanes have the MOST shielded carbons Alkenes come next Aromatics come next

C=O: Anything past 160 ppm Most deshielded.

CH2Cl2 is polar (pointing to electronegative Cl direction)

CO2 is nonpolar

Molecular ion peak has the same mass as neutral compounds

Cations are detected by the machine, but electrons loss does NOT change its mass by a detectable amount.

*Gel electrophoresis* Migration based on size & charge. Polyacrylamide gel for resistance (slow particles down).

Cations to (-) cathode. Anions to (+) anode. Equation: *Ma = qE - F drag*

Reducing agents

Cause reduction (get oxidized) O-poor H-rich Low oxidation state atom with low ionization E Examples: LiAlH4 HCL/ Zn H2/ Pd NADH NaBH4 H2NNH2/OH- FADH2 NADPH

Stereoisomers separation

Chiral auxiliaries: introduce chirality or exaggerate existing chirality within a reactant molecule (similar action to enzymes). The reaction produces two enantiomers with different physical properties and can easily be separated, then the enzyme returns to its original form.

IR (stretching & bending of bonds)

Cm^-1 = wavenumber (1/lambda) 0 to 1400 = fingerprint region (c-c, c-o, c-x, c-n single bonds). First outside fingerprint (1400) in order, the further out, more E needed to stretch bond: C=O C=O Alkynes C-H O-H N-H *Not all bonds show on IR, esp if symmetrical.* i.e. internal alkynes & symmetrical (trans) alkenes don't show. Terminal alkynes, do show a peak.

TLC (i.e. silica stationary phase): Low Rf → big difference in the distance between solute and mobile phase → solute (being tested) has a high affinity for stationary phase and low affinity for mobile phase → solute is more likely polar. High Rf → small difference in distances traveled by mobile & tested solute → high mobile phase affinity. Solute here is more likely nonpolar since it's not attracted to silica.

Column: High elution time means less attraction. More elution time means more attraction

Meso compound 2

Contains a mirror plane Optically inactive Net optical rotation = 0 Its reflection looks identical to the original compound

Common monosaccharides

D-Glucose: Fu*# glucose (R hand). D-Mannose: man gun hand. (*C2* epimers of glucose) D-*R*ibose: ribose is all *R*ight. D-Galactose: *C4* epimer of glucose. D-Fructose: ketose of glucose.

*SN1 reaction* SP3 (109) → SP2 (120) → SP3 (109)

Does *NOT depend* on *[nuc]*. Nuc attacks from either side. LG leaves before nuc attacks.

Transesterification (acids or bases) On an ester: Exchanging one alkoxy group for another.

Driven by removal of product or addition of a reactant. Applications: 1. Membrane transport 2. Conversion of FAs into TAGs

Units of unsaturation note +C+N - H-X (*Plus CiN minus HeX*)

Each pi bond counts at 1 Each ring counts as 1

Conformers degrees of rotation

Eclipsed: 180° Staggered: 1. Gauche: 120° 2. Anti: 0° Staggered is MORE stable than eclipsed

3. Biochemical PERICYCLIC reactions.

Electrocyclic addition reaction *Repositioning of σ & π bonds* through a cyclic transition state with simultaneous *breaking/ forming* of all bonds. Can be both ring OPENING (*vitamin D synthesis*) & CLOSING

A diastereomeric mixture is optically active

Enantiomers equal mixtures are optically INACTIVE (racemic mixture)

Transesterification xy

Ester to another ester by exchanging alkoxy group (acidic or basic conditoins) In transesterification, a *sp3-hybridized tetrahedral intermediate forms with carbonyl O- & C+ (center)

Transesterification

Esters * only exchange* their alkoxy in the presence of *acid & alcohol*.

Describe how the substituents are aligned in a chair for the following compound

Ethyl is the bulkiest → goes equatorial. OH is next to it (can't be eq), so its axial. CN is on the opposite side, so it has to be the other equatorial side.

Spin Decoupled NMR

Every peak is a singlet (seen in H NMR)

Polar, *aprotic* Dipole-dipole VDW

Ex: Ketones (acetone) Ethers (COC) Alkyl halides (C-halogen) THF DMSO

If two *substituents attract one another*, the MOST stable conformation would have the attracted groups *gauche* to each other.

Example: Carboxylic acid COOH & NH2 (amino groups) tend to be in Gauche orientation (closer to one another) because they're attracted to each other via *H-bonding*. If they were anti, they won't be able to make out (H-bonding)

*FAD & FADH2* (H+ & H- gain = no charge change)

FAD: oxidizing agent, picks up: 1. *1 Hydrogen on the nitrogen of the central pyrimidine ring* 2. 1 H on imine nitrogen of 3rd ring. One H is gained as a hydride while other is gained as a proton (*no charge change*)

Hydrogenation: Adding H to pi carbon: C=C → C-C

For every pi-bond: 2H are added MW ↑ Flexibility ↑↑ MP ↑

*Geometrical* isomers (*cis/trans* ring, *E/Z* = bond)

Form *rigid* structures (less entropy than alkanes) *Rings/ alkenes* Nonsuperimposable *E/Z* 2 possible geometric isomers for an alkene? Can't rotate to become identical (due to ring or π-bond)

Example 2: propene (from picture above)

Hs on double bond are NOT-equivalent, so they each has a unique environment. 4 signals total. 3Hs on left is doublet (only one neighbor) Hs on double bond are unique. Top right hydrogen: doublet of doublet (|| ||) 2nd Hs on right: doublet of doublet (II II) Middle hydrogen: Mutliplet (too many neighbors)

Hydride

Hydrogen with a negative charge H is + if attached to the ones below *FONClBrISC*H If not, give it a negative charge

Hydrolysis under acidic conditions hydrolyzes acetals & hemiacetals

Hydrolysis does NOT affect ethers

What gets affected from taking a protein from a lipid to an aqueous environment? Primary Secondary Tertiary Quaternary structure

Hydrophobic to hydrophilic environments expose the hydrophilic side chains in the inner core. It breaks apart internal H-bonding affecting its secondary structure.

BP comparison question

I & II: geometric isomers (cis & trans) I: cis, polar: highest BP II: trans, nonpolar: lowest BP III: alkane, flexible, rotates (can be polar or nonpolar) ~ call it slightly polar (middle BP). MW is comparable: so only polarity is to compare: I polar (1) III slightly polar (2) II nonpolar (3)

Conformers (conformational isomers)

Identical bonds with different spatial orientations caused by: *Rotation about sigma* bonds, or *Contortion of ring structures* They are *at dynamic equilibrium* at room temperature

Lanosterol formation

Identify the reactants and how they connect to form a product

Carbonyl substitution via tetrahedral intermediate

If LG is poor, reaction gets stuck at tetrahedral intermediate.

Configurational isomers

If a molecule has *one chiral center only and two of its substituents are interchanged*, but the other two are the same, then it is a configurational isomer. Figure out why choice c is the right answer to this question.

The affinity for the adsorbent outweighs the affinity for the solvent. → *Adsorbent matters more*

If the species was nonpolar and the column was made of silica gel, the species will elute fast regardless since it simply has a low affinity to the column, *even if its affinity to the solvent was low*.

Ammonia (*NH3*) is a good nucleophile (*ring breaker*)

It can break open a 4-membered ring by attacking the carbonyl carbon. Amines react with esters to give amides. *Amine + ester → amide*

Phe exists as a zwitterion at pH of 7.4

It cannot be uncharged since it has charged sides that both add up to zero.

Describe: Trans-3-methylethylcyclohexane

It must be 1,3-trans, so substituents are on equatorial and axial orientations. Since *ethyl is bigger*, it assumes the *equatorial* position to be more stable

SN1 cont' Cationic *(+)* Intermediate forms after LG leaves (detectable by spectroscopy) Carbo*cation rearrange*ment & *racemic mixture produced*. 2-step reaction (1st is slowest), C & LG bond breaks, then *bond angles increase from 109.5 to 120 (Sp3 to Sp2)* increasing stability (Energy: intermediate <<< 1st TS in diagram)

After nuc attacks, Sp2 becomes Sp3 & stability decreases in the 2nd TS. Energy decreases as new bond forms until it reaches products level (bond formation is *exo*) *Nuc*leophile forms a *STRONGER bond* with C (*than LG*), so the *reaction is favored* If the chiral center is NOT at the electrophile, major and minor products form. The major would have the least steric hindrance. Major product: forms when nuc attacks the less hindered face of carbocation. Minor product forms when nuc attacks the hindered face or carbocation.

*IR examples* All the following have C=O peak at 1700. Ketone Ester

Aldehyde: C-H 2700 + 2800 peak Carboxylic acid (*COOH*): extra 2500-3500 *ugly O-H peak*. Amide: N-H at 3200-3600. Ester vs. ketone: Ketone is closer to 1710. Alcohol (OH): *smooth* broad peak at ~ 3400 Triple bond: 2200 sharp peak

Gluconeogenesis

Aldol condensation (formation)

Reverse → breaking

Aldol → making (condensation)

*Aliphatic* (straight chain) & *cyclic* alkenes

Aliphatic *CnH2n*+2 Cyclic: *CnH2n* (for each additional ring, the molecule has 2H less)

Structural flexibility

Aliphatic alkanes (straight; not aromatic) have structural flexibility. Units of unsaturation REDUCE flexibility.

Zero unit of unsaturation & 1 oxygen

Aliphatic ether or aliphatic alcohol (cannot be a ketone or a π structure)

Chlorine (EWG) increases acidity (lower pKa)

Alkyl groups (EDG) decrease acidity

*Muta*-rotation

Alpha interchanges to beta in equilibrium via a straight chain intermediate. The *conversion of beta to alpha or vice versa* is mutarotation (anomers stereoisomerization)

Malonic ester. Middle Hs are most acidic

Alpha protons (@ CH2 in the middle) between two carbonyls C=O, H, C=O are the most acidic

Vacuum distillation P↓ BP↓

Attaching the distillation apparatus to a vacuum pump to *reduce the apparatus pressure & lowering the BP*. This is done by lowering the atmospheric pressure so the vapor pressure required to boil is lowered (protecting species from decomposition) If one *species in a mixture decomposes at a temperature LOWER than the BP of the mixture BP*, then *vacuum distillation is best*

Protein *secondary* structure *Backbone H-bonding*

Backbone AAs interactions (H-bonding). Alpha helix & beta pleated sheets.

Extraction

Based on solubility. Drastic differences in the solubilities of components in 2 different (immiscible) solvents.

Steroids

Biomolecules containing *androstane ring* with alkyl & functional groups. Steriods: 1. *Emulsify fats*. 2. Regulate *membrane fluidity*. 3. Serve as *signal molecules*.

*Bent* bonds

Bonds formed to *relieve the ring strain* by *bending the σ bond* so electrons don't lie between the 2 nuclei. These bonds become *weaker and easier to break*

Bond enthalpy calculation

Breaking bond: needs energy Forming bonds: releases energy Homolytic breaking: forms free RADICALS

How does a chemical change of a molecule reduce its MP? *-OH breakout → BP ↓*

By weakening its intermolecular forces or reducing its mass. One method is *oxidizing hydroxyl groups* to get rid of them and reduce H-bonding and reduce MP.

Trisaccharide molecular formula

C17H30O15 2 glycosidic linkages formed removing 2 waters (notice 4Hs & 2Os are lost from a standard sugar formula)

Any *sp-hybridized* group makes the compound *linear* and offers *minimal-no hindrance*. An example is alkanes & ALKYNES

Stability: Double bonds (C=C) <<< alkynes ((disrupt packing (i.e. cis alkenes))

SN1 reaction features

Steric hindrance pushes LG off electrophile. *Intermediate* is planar, 3-ligand carbocation with *Sp2* carbon. Intermediate + transition states observed

Fatty acid synthesis

Straight-chain FAs are synthesized *from acetyl-CoA & malonyl-CoA* via a 5-step reaction *adding 2Cs* and repeating it until complete. Next step: 1. Adding a *glycerol-3p* to become a part of the *cell membrane*. 2. Adding *glycerol* to become a *triglyceride for storage*.

List of electrophilic compounds and their conjugate acids

Strongest (electrophile = conjugate acid): Acid anhydride = carboxylic acid (best) Ester = alcohol Aldehyde = H2 Amide = amine

Cis vs. trans around a = bond are geometrical isomers

Structural isomers around found with DIFFERENT connectivities.

Sterols

Subgroup of steroids, contain *hydroxyl* groups common in several hormones.

Atom oxidation state

Sum of the numbers from all the bonds and any formal charge it may have.

Testosterone vs. estrogen

Testosterone: oxidized (*OH & =O*) Estrogen: *OH & OH*

*Gas chromatography* Relative intensity (Y) vs. Retention Time (X) Fastest compound has the SHORTEST distance.

The *area of the peak* →*[Compound]* The biggest area → biggest [Compound] If all tested species were alcohols, then SMALLEST (lightest by mass) alcohol would have the SHORTEST retention time.

*Integral* # of Hs ↑, area under curve ↑

The area under curve is directly proportional to the number of hydrogens making that signal (CH3 has an area of 3, CH2 has an area of 2)

H-bonding in infrared spectroscopy *H-bond strength ↑, covalent bond ↓*

The broadening of the hydroxyl absorbance associated with H-bonding is caused by the *weakening of the covalent bond between H & the atom (NOF)* to which it is bonded. This lowers covalent bond energy and lowers the energy of absorption for the bond.

*TLC Rf values* 0 </= Rf < 1 Rf<1 → spot cannot migrate as far as solvent

The distance a spot travels compared to the solvent's distance of travel. It is measured from the *center of the spot from start to finish*. *Rf= d spot/ d solvent* Has no unit Cannot be >1 Different in different solvents. It depends on BOTH *adsorbent & solvent* Rf values of 0.1 & 0.2 are better than 0.3 vs. 0.2 (better to have a greater multiplicative difference).

Ketotetrose

Keto: ketone Tetr: 4C Ose: sugar

*Tautomer*ization

Ketone to enol Ketones & enols are tautomers (*structural isomers* that vary in the pi-bond position and a hydrogen)

Reduced to 1° alcohols ← *Aldehydes* → oxidized to carboxylic acids Carboxylic acids are the most oxidized.

Ketones (i.e. acetone) → reduced to 2° alcohol. Ketones cannot be oxidized.

*Rf vs. TLC*

Large Rf: solute migrating GREAT distances (*high affinity for mobile phase (solvent) & low affinity for the stationary phase (plate). Extra info: high affinity for the mobile phase means favorable interactions between solvent & solute, which translates to *high heat of coordination* between them.

*Reducing agents* and alcohols *Al* → strong (all C=O) *B* → weak (aldeh & ketones only)

Li*Al*H4 (more reactive): *reduces all* carbonyl compounds. Na*B*H4 (less reactive): *only* reduces ketones & aldehydes.

Light frequency Bond Energy ↑ → absorbance ↑

Light frequency depends on the two masses & bond strength (PE= 1/2*kx^2). Absorbance is proportional to bond energy. Wavelength is measured in cm^-1 (wavelength inverse). *The higher the wavenumber (cm^-1), the greater the energy*

Reduction

Losing Os (or gaining Hs) at the carbon attached to the electronegative atom. Count C-O bonds in the reactant to the carbon of interest. C-O bonds decrease, oxidation level decreases. Oxidation level decreases by 1 & oxidation state decreases by 2 (if C-O bond lost and replaced with C-H bond)

Enantiomers separation

Methods like chiral column chromatography. They have IDENTICAL physical properties (same MP, BP...etc).

Why is methyl amine a better nucleophile than ammonia? Thru resonance or inductive effect?

Methyl group → EDG There is no resonance, no. Inductive effect: e- delocalization thru pi network, yes

Methyl ketone NMR

Methyl ketone has an isolated methyl group neighboring C=O (which has no Hs). This results in no splitting making the peak a singlet. The picture is to be able to distinguish alpha hydrogens.

How many C-C bonds would a cyclic monoterpene need?

Mono = 2 units (10C) 1. C-C to connect two isoprenes (head-to-tail). 2. C-C bond to close the ring 2 bonds total.

Common H NMR peaks (ppm) Alkyl: 0.5-1.5 Benzylic/ ketone (alpha H): 2-2.5 *Alcohol/ ether* (alkoxy OCH3): 3.5-4

Vinylic (c=/): 5-6 *Amide*: 5-8 *Aromatic*: 7-8 *Aldehyde*: 9-10 *Carboxylic acid*: 10-12

Fat-soluble vitamins structures

Vitamin A: retinol (alcohol). It is the only alcohol of ADEK

Cyclohexane

Most stable structure of all cycloalkanes *Chair* conformation is the most stable Equatorial & axial positions Equatorial is MORE stable than axial. The *most stable chair* has the *highest* amount of *equatorial substituents*.

NAD+ & NADH

NAD+ is the oxidizing agent. It picks up a *hydride anion on its pyridine ring* to yield NADH. The oxidized species gives of H+ as a side product.

Which AA migrates to the *highest pH* in a pH-gradient gel? Aspartic acid? Lysine?

One with the *largest pI* value migrates to the high pH

Ultraviolet Spectroscopy

When UV or visible photons are absorbed, an electron is excited. Range: 200-800 nm

Saponification Carboxylate + -------------------OH

Outcome: 1. Long carboxylate (amphipathic) 2. Long alcohol

Oxidation and reduction

Oxidation: Gain of bonds to O Loss of bonds to H Increase in oxidation number Reduction: Loss of bonds to O Gain of bonds to H Decrease in oxidation state

Tollen's test (Ag+). Silver mirror test

Oxidizes *C1* of aldose: *aldose test* Does NOT oxidize ketoses

Permanganate *KMnO4* *adds OH to = both sides*

Oxidizes all sites possible. *Alkynes don't respond*

Nitric Acid H*NO3* (oxidizing agent) → *optical activity test*

Oxidizes terminal Cs to acids

Dimethylbenzene Proton NMR

Plane of symmetry: 2 CH3 are the same 2 same Hs 1 H above 1 H opposite to it 4 signals: All show in aromatic region. Methyl shows in alkene region.

Haworth projection *Up → out → bow* In Fischer (i.e glucose): *sides → out*

Point up → out of the page bowtie Point down → into the page ||||||

Protein denaturation Breaking 2° or 3°

When any molecular interaction that holds together secondary or tertiary protein structure is broken. *Denaturation → primary structure is INTACT*

*Basicity* is found on *(-) sites*

Positive sites are NOT basic.

Acidity notes CO2H > OH Carboxylic acids are more acidic than alcohols.

Presence of EWG (i.e. Fluorine "high e-neg") increases acidity via inductive effect

Alcohols to alkyl halides

Primary alcohol + Cl2S=O = 1° alkyl halide (no chirality) 2°alcohol + PBr3 = 2° alkyl halide (inversion) 3° alcohol + HBR = 3° alkyl halide (racemization)

Oxidation examples

Primary alcohol oxidizes to aldehyde (aldehyde oxidizes to carboxylic acid) Secondary alcohol oxidizes to a ketone. Tertiary alcohol (& *phenols*) CANNOT oxidize (no Hs to lose)

*Ketals & acetals* Aldeh & ketone protectors

Protecting groups for c=o groups in ketone & aldehyde synthesis. Hemiacetals & hemiketals aren't useful as protecting groups.

Polar protic vs. polar aprotic

Protic: capable of hydrogen bonding Aprotic: incapable of hydrogen bonding (only dipole interactions)

Biosynthesis of *steroids* begins with:

Pyrophosphate (*PPi) + terpene* PPi = P2O7^4-

Thumb rule

R: If thumb is pointed in direction of sub 4, the fingers of your RIGHT hand can be thought of as right handedness Left hand is used for S

Aldol condensation

Recognize the product Y Y connected together and call it a day

*LiAlH4* (Needs basic conditions in case it reacts with protic Hs)

Reduces everything including *esters*

Glucose structures Middle finger → upleft (only C3 is left, up)

Remember, you only look at C2, C3, C4 when converting from Fischer to Haworth

Retro (reverse) reactions → reactants *broken down*.

Reverse aldol → aldehyde & ketone. Reverse Claisen → 2 esters The last step of FA metabolism looks like a reverse Claisen rxn a little.

Naturally occurring *furanose* rings

Ribose & fructose

Ribose vs. deoxyribose

Ribose's C2 has 4 unique subs, deoxy doesn't, so ribose has more stereoisomers, more chiral centers. Deoxyribose doesn't have the same molecular formula, so we can't talk isomerism here.

Androstane → steroids

Ring *A* (left) is connected to ring *B* in a *cis* fashion. Ring *B* connects to ring *C* in a *trans* fashion. This controls *how steroids incorporate into lipid environments*, such as cell membranes.

*Aldehyde/ ketone* with a compound with at least *2 hydrogens on N* (i.e. ammonia, primary amine, hydroxylamine, hydrazine), *C=O* is converted *to C=N* (imine)

With excess water, the REVERSE reactions is observed.

Humans cannot reduce lactate

Yeast & bacteria can convert pyruvate to ethanol

If fragments were treated with SDS-PAGE, the observation would be that all fragments migrate to the anode

SDS PAGE gives uniform negative charge to all fragments. Since all fragments get (-) charges, they get loaded by the cathode to migrate the greatest distances to anode.

What reaction has no observed optical rotation

SN1 (racemic product)

Aldol vs. Claisen condensation

Same except Claisen uses *ester instead of ketone or aldehyde* as a LG (substitution reaction).

Na*B*H4

Selective *aldehydes/ ketone* reducing agent *only*

Chiral column

Selects a specific enantiomer (S not R or vice versa)

To give a C in a ring a carbonyl, oxidize the C

Separate info: FADH2 hydrogenates π bond in a ring without impacting C=O π bonds.

Chromatography

Separation based on solubility in a migrating solvent & affinity for a polymer.

Hydrophilic (not acidic or basic) AAs

Serine Threonine Cysteine (R-stereo) Tyrosine Glutamine Gln (Q) Asparagine Asn (N)

Tautomerization 2

Shifting of π-bond

Upfield

Shifts at a lower ppm value

How is aldosterone less water soluble even with the carbonyls and hydroxyl groups?

Side chain ketones & OH groups form H-bonding. This prevents their interactions with water.

Alkyl groups bonds

Sigma (*sp3-sp3*). They *only s-orbitals* to form bonds

Concerted reaction: 1 step (i.e. SN2)

Sigmatropic rearrangement: one molecule product. If concerted & sigmatropic rearrangement occur together, then one molecule forms with no cross products.

Splitting pattern: *# of neighboring Hs + 1*

Singlet: 1 peak (0 neighbors) Doublet: 2 peaks (1) Triplet: 3 peaks (2) Quartet: 4 peaks (3) Quintet: 5 peaks (4) Sextet: 6 peaks (5) Septet: 7 peaks (6 neighbors)

*Chapter 2*

*Isomerism*

Different terpenes isomers (α, β, γ) prefixes

*Similar physical* properties. *Different *conjugation* → varied absorption

(*Cation-exchange* Chromatography)

*Sulfonated-poly*styrene *Carboxy*methyl-cellulose (-CMC, -cellulose gum) These bind *basic (+)* AAs

C=C is of a higher priority than C-C

*TBR I Ch 2 P. 91 for R & S trick*

Calculating *number of isoprenes*

*carbons/5*

Isoelectric pH

*pH* at which the *[zwitterion]* is *highest*

Kiliani-Fischer synthesis (+)

+ 1C forming epimers.

Prostaglandin structure

1 = bond

How many degrees of unsaturation are present in tyrosine?

1 ring 3 = bonds within ring 1 carbonyl pi 5 total Every benzene ring has 4 units of unsaturation (think AAs w/ benzene ring).

Which of the following can H-bond? 1. Aldehydes 2. Ketones 3. *Esters* (can't) 4. Primary amines

1,2,3 are bonded to carbon, they cannot H-bond.

Aldehydes & ketones reactivity

1. Aldehydes can be oxidized to carboxylic acids, ketones cannot.

Chemical shift ranking

1. Carbonyls are the most de-shielded (a). Downfield. 2. Aromatics (b) 3. C & D will be in the alkane region. Since d is near fluorine, it is more deshielded. C is the last.

Alcohol properties

1. High BP & water solubility due to H-bonding. 2. Hydrophilic decreases as their C-chain increases. 3. Polar, liquid at room T. 4. MW up, BP up (unclear MP) 5. Branching up, MP down.

Alcohol reactivity OH → poor nuke

1. Poor nucleophiles. 2. Get deprotonated to alkoxides under basic conditions which are strong bases & better nucs than alcohol

Determining the *absolute configuration (R/S)*

1. Rank 4 substituents directly attached to the chiral center by molecular mass. 2. The lowest priority sub goes behind the page 3. Draw a circle from subs 1 to 3. Clockwise: R Counterclockwise: S

Aldehyde proton

9-10 ppm

Nucleophilic substitution

A *negative* charge (nucleophile or *Lewis base*) seeking a (+) charge by *hunting* the electron-deficient electrophile (*Lewis acid*) to attach to it and *kick LG* out.

Vicinal diol

2 OHs in vacinity of each other

Diene

2 double bonds with a single bond in between.

Sester-terpenes

25 carbons (5 isoprenes)

Example 3 (from picture)

3 unique hydrogens: 3 signals The H on OH has no neighbors, so the H doesn't count.

Why is 1, 1- difluoro, 2,3-diphenylcyclopropane highly reactive?

3-membered rings are highly reactive. F groups are small and their hindrance effect is minimal compared to the ring strain.

What happens if 3-methylaniline was added to an extraction mixture that only uses bases to separate mixture components?

3-methylaniline is a base. It won't get protonated by a base. It dissolves in water (stays in the organic layer).

Tri-terpene

30 carbons

Aldehyde = CHO Carboxylic acid = CO2*H*

Ester - CO2*R*

Sex hormones

Estrogen Progesterone Androgens (testosterone & androsterone)

NMR Special features

Exchanging of deuterium for protons (peak disappearance) Solvent must be invisible

3:2 ratio

CH3Ch2-

Most susceptible carbon to nuc attacks is the one attached to a LG

Carbon at position 4 (*most electrophilic carbon*)

Fatty acids

Carboxylic acid + long aliphatic chain. Naturally occurring are straight due to biosynthesis (by adding acetyl-CoA).

Only aldehydes and ketones undergo aldol condensation

Carboxylic acids can't

Carboxylic acid example CO2H

H3CCH2Ch2*CO2H* *-ic acid*

Micelle

Has an *ionic* (charged) head & *a long* carbon chain tail.

Primary alcohols

Have 2 Hs to lose, can get oxidized twice (1st into aldehyde, 2nd into carboxylic acid). Carboxylic acid can be reduced back to primary alcohol by *LiAlH4*) 2ndary alcohols have 1 hydrogen to lose, oxidize once to ketone.

Intermolecular forces Physical properties (i.e. MP, BP) are dependent on intermolecular forces (i.e. H-bonds, dipole-dipole, VDW).

Have NOTHING to do with covalent bonds. Covalent bonds change by chemical means, not physical means.

Best leaving group characteristics

Have conjugate acids with *lowest* pKa. LG's conjugate acid acidity ↑ → reactivity ↑

Basic AAs (KHR)

Have side chains that *gain a proton +* from their neutral state. They all have *nitrogen-containing R groups*

Question xx

Heat dehydrates it, then seals it. The reverse reaction is the addition of water, see choice A.

NMR integration

Height of signal of H's graph is related to how many Hs added up. It is translated as a function of area (6H integration to 1H is 6:1)

FADH2

Hydrogenates π bonds

*Presence yields an anion, absence yields a cation*

If oxygen makes 3 bonds and has one lone pair, it will carry a (+) charge. If nitrogen makes 2 bonds & has 2 long pairs, it will carry a (-) charge.

Units of unsaturation 3

Ignore the O2

*Acid anhydride* formation Heat → remove water from carboxylic acid

Condensation of carboxylic acids (find the water, remove it, then glue them).

Rotamers

Conformational isomers that vary in orientation in space because of sigma bond rotation

D-glucose vs. L-glucose

D: middle finger the Right hand L: middle finger the L hand

Mixed melting point test

A sharp MP means the compound is pure. Adding a different compound would cause a *broad MP*

Diels-Alder reaction Makes a ring w/ alkene inside

Diene + alkene → *cyclohexene product* If you reverse it, it would make terpenes with no fragments

Lactams

Amide is a part of a cyclic structure. Antibiotics are examples of beta-lactams (i.e. penicillin)

*Amides* more *basic* than aldehydes?

Amide's carbonyl oxygen has more of a partial negative charge b/c *N donates electron* density to oxygen.

Compare BP of propane, amide, acetone

Amide: H-bonding: strongest of 3 Acetone (ketone): no H-bonding, only d-d. Propane: VDW only, less massive than acetone.

Amides

Amine or ammonia with a carbonyl carbon (primary, secondary, tertiary). Substitutions degree changes physical properties.

Density ↑, packing ↑ (lattice)

Enantiomers pack the same (same density). *Racemic mixtures* may have a lower density, which means *pack less tightly*.

Biological redox

Anabolism: reductive process (i.e. FAs synthesis & gluconeogenesis). Catabolism: oxidative process Examples: Glycolysis & beta oxidation (releases energy by breaking down a molecule).

Sp3 carbon

Any carbon bonded to 4 atoms (including H)

Chiral molecule

Asymmetric structure At least one stereogenic center Chiral carbons are Sp3 hybridized with 4 different groups

Primary sp3 carbon example

Me (methyl)

Forces holding organic tails of micelle are VDW

Micelle needs 1. Polar head 2. Alkyl tail

Esters

More reactive than ketones & aldehydes (Alkoxy LG)

*Distillation* Removes liquid from either another liquid or from solute by exploiting their BP differences.

More volatile evaporates 1st. Condensation amount depends on wall temperature. The distillation apparatus is an *open system*. An *opening* to the atmosphere is *located after the collection flask*. If the system was closed, it would explode!

Rigidity Flexibility π-bonds

More π-bonds → more rigidity (but contribute to more membrane fluidity!). No π-bonds → greater backbone flexibility (ability to rotate into different conformations)

Cellulose → (beta-linear 1,4 only)

Most abundant of all polysaccharides. ONLY 1,4 linkage. No 1,6 linkage: it *cannot branch* (only linear polymers)

Where is the STRONGEST H-bond can be found? *MOST basic lone* pair → *Strongest H-bond*ing

Most basic lone pairs (least e-negative atom's *"N's"*) donated to MOST protic Hs (bonded to oxygen).

*Acid halide* Halogen & carbonyl together: very reactive

Most reactive carbonyl groups (*halides are excellent LGs) Some are too reactive: intermediate products in a synthetic pathway

Borane

Octet rule *exception*. Examples: BH3, BF3, BR3 *B*oron has *Sp2* hybridization, *no pi* bonds.

Histidine

Only 1 chiral center.

Protecting groups

Prevent a reagent from reacting at an undesirable site. Acetals & ketals are less reactive than aldehydes and ketones = ideal protecting groups. *Notice protection happens at the same carbon*

1, 2, 3 & 4 amines (how many Cs attached to N)

Primary: connected to 1C Secondary: connected to 2C and so on.

Broad peaks

Protic hydrogens

Under basic conditions

Protonated product ROH ROR

Under acidic conditions = deprotonated product

ROR ROR

Product has 0 optical activity

Racemic mixture → SN1

Isoleucine & threonine have 2 chiral centers.

Random thing

Infrared Spectrscopy

Range: 2.5k to 17k nm or 600-4,000 cm^-1 Correlates bond-stretching & bond-bending to absorbance

Nucleophiles (negatives)

Rank of nucleophiles in water from best: *SH-* *CN-* *I-* OR- OH- *Br-* NH3 C6H5O Ch3CO2 Cl F *ROH* *H2O*

*Imines* (R2*C=N*R)

React like aldehydes & ketones. Are @ *eq*uilibrium *with enamines (C=C-N).*

Penicillin absolute configuration Priority assignment: I > Br > Cl > S > O > N > C > H

Remember, D-amino acids are R configured. This means all their configurations are RRRRR

Electrocyclic reaction

Results in *change in rings #s* Example: vitamin D (ring opening requires heat or light "hint sunlight is needed to synthesize it".

Bond lengths examples

Single bonds: C2H6 Double bonds: C2H4 Triple bonds: C2H2 *The more substituents on the bonds sides, the weaker the bond*.

Rf values & elution time

Small Rf = slow elution High RF = Fast elution

Solubility and miscibility

Solubility: a solute (solid) dissolving into solution Miscibility: liquid mixing with another liquid

Find the configuration on penicillin

Solution is attached to the next note

Meso compound

Symmetric with an *even number of chiral centers* equally displaced about an internal mirror plane (i.e. *R* on *one side* & *S on the other* side)

Butane energy diagram

Symmetrical

Shift value

Tells what functional groups are present.

Protein placed in a pH greater than its PI

The environment is high pH: deprotonated *(-)* Anions more to (+) anode

Cross-linkage

Increases rigidity of polymer by losing both flexibility & entropy (driven by enthalpy).

Quaternary structure

Interactions between 2 different primary strands.

Septet & a doublet (1:6 ratio)

Isopropyl group

Edman's Reagent

It removes each AA 1 @ a time from N terminal

If asked about how many isoprene units a compound is made of, count the carbons and divide them by 5.

It should be made of multiples of 5.

*Ether* has a lower density than water

It would float *atop water* during extraction.

Question 3

KMnO4 oxidizes everything. 1 alcohol to carboxylic acid all the way. 2 alcohol to ketone.

Aldolase cleaves C-C bond

Kinase transfers P (i.e. from ATP to ADP)

Sucrose structure 2

Left side (osyl prefix): C1 (anomeric) & C6 are trans: alpha. Right side (oside prefix): C1 (anomeric) & C6 are cis: beta Linkage: alpha 1 - beta 2

Glycosidic linkage left & right *Syl (left)-------side* (right)

Left → glycosyl Right → glycoside

Sp2-C-to-H bond is shorter/ stronger than sp3-C-to-H bond.

The stronger bond has a higher dissociation energy and a higher energy absorbance

Chiral compounds have ASYMMETRIC energy diagrams

They also have more energy values than butane

Tertiary alcohols &* phenols* cannot be oxidized

They lack Hs to lose.

Fractional distillation

Used for mixtures with small vapor pressure differences.

Nonpolar, aprotic

VDW only. Ex: Oils, lipids, Petroleum.

Epimers C2 epimer → flip index finger C4 epimer → flip ring finger

Vary *only at one carbon* (at one stereocenter in the carbon backbone)

Sp2 hybridization atom example

Vinyl: (C=C) alkene.

Amines characteristics

Weak bases Good nucleophiles

Why is only 25% of synthesized isoleucine is biologically active?

When synthesized, the 2 chiral centers result in 4 stereoisomers, only 1 in 4 is biologically active.

High altitude

↓ atm Gas molecules per volume ↓ ↓ BP (less energy to make vapor P = atm)

Coplanar Ns in caffeine

e- density delocalization throughout the pi-network of the caffeine molecule achieved by resonance (correct overlapping of p-orbitals).

*Ester* functional groups need *2 oxygens*

mhm

Isoelectric focusing

pH gradient in gel in which charged species migrate until reaching pH=pI pI<*pH*: *basic* envir., *(-)* species. *pH*<pI: *acidic* env., *(+)* species. Higher charge, higher electric force, higher acceleration.

Amines are weak bases

pKb: 3-5 pKa: 9-11 sec>tert>1 basisty Common reagent in buffers: pH: 10 +/- 1

Constitutional isomers = structural isomers

# of possible structural isomers depends on molecular formula. It increases for each extra carbon. No formula to determine it: C4H10 has 2 C-C-C-C (1) C-C-C with another C at 2C (2)

Heat of hydrogenation (∆H) Smaller ∆H → more stable

(*∆H↓, stability ↑*) → higher energy to break

2nd proton is LESS acidic than 1st proton

(2nd pKa >> 1st pKa)

In amides, increased substitution decreases BP & MP, why?

(Amide substitution *UP*, MP/BP *down*) Because subs *decrease H-bonding* between *Oxygen's lone* pairs and *Nitrogen's Hs*.

Relative basicity of methyl amines (biggest to smallest) Basicity ↑, pK*b* ↓

(CH3)*2*NH *(highest basicity)* (CH3)*1*NH2 (CH3)*3*N NH3 *(0 lowest)*

6:1 ratio

(CH3)2CH-

pI of all AAs (except basic)

(pKa1+pKa2)/2

Basic AAs pI

(pKa2+pKa3)/2

Cycloalkanes

*1 ring* alkanes are *CnH2n* with *no π* electrons Its stability comes from *109.5° of SP3* *3-4 membered rings* are *reactive* (ring *strain* of its 60 angles) *5-6 membered* rings are *stable* (common in *biomolecules*) Cyclopentane 5 & cyclohexane 6 do NOT undergo hydrogenation

Cyclopentane envelope

*108°* angles *Envelope shape* to relieve *torsional strain*.

*Sesqui*-terpenes

*15 C* (3 isoprenes)

SN2 reactant features

*1>2>3 electrophiles* preference. Favors a *good nucleophile* Polar, *aprotic* solvents (*ethers & ketones*)

*EICOsanoids* 20C locals

*20-carbon local* hormones *acting on* the *cell that produces them or the neighboring cells* by inflammation, clotting, blood flow, ion or synaptic transport. Examples: *Prostaglandins* *Thromboxanes* *Leukotrienes*

SN1 reactant features

*3>2>1 electrophile* reactivity (similar to radicals) *Protic* solvents favored (i.e.*OH*) Prefers *POOR nucleophiles* (b/c nuc comes after LG broke off already)

*Poly*saccharides

*4+ monos*accharides. Mostly 1,4 glycosidic linkage or 1,6.

Electronegativity difference between two atoms

*<1.5* covalent bond *1.5-2* polar-covalent (partially ionic) bond. *2+* ionic bond

Enantiomers

*ALL* of the *chiral centers* MUST *DIFFER* between the two configurational isomers

Kiliani-Fischer synthesis

*Adds 1C to aldose* I.e. 5C becomes 6C. Usually a major-minor product mixture.

*Take a picture of imine reactions page 240*

*Aldehydes* are more *electrophilic* than ketones. Their carbonyl *+C*=O gets attacked.

Monosaccharides *isomerization*

*Aldose into a ketose* via an enediol intermediate

Axial vs. equatorial in a chair

*Axial (straight vertical lines in chairs)*: up or down Equatorial: not straight lines: pointing down is eq down and pointing up is eq up.

What's the most stable LG? HCN CN- H2CCH2S- H2CCH2SH

*LG needs e- long pair* (after heterolytic cleavage from electrophile). HCN: no lone pair (no) Most stable LG is the weakest base (CH3CH2SH), has strongest conj acid (d)

*Ruff* degradation

*Removes 1C from the aldose chain* Decarboxylation

What is optically inactive

1. Achiral 2. Meso

GC Data Analysis

1. BP does not affect the elution time. 2. Heavier gases move slower and have longer elution times. 3. *Heavier* gases & *polar* gases typically have *higher BPs*

Units of unsaturation

1. Double bonds 2. RINGs

Gabriel Amino Acid Synthesis

1. Phthalimide with malonic ester 2. Addition of side chain (R) 3. Acid-catalyzed decarboxylation

Carboxylic acid reactions

1. Reduction (LiALH4/ NH4Cl) = 1° alcohol 2. Heat = acid anhydride 3. ROH (alcohol & acidic condition) = ester 4. SoCl2 = acid halide (Cl-carbonyl-R)

Glycolysis notes

1. Regulatory steps involve ATP 2. Multi-step pathways produce intermediates that feed into other pathways. 3. Oxidation breaks molecules & requires oxidizing agents (i.e. H-poor species, such as NAD+). 4. Oxidation releases energy.

*INTRA*molecular features

1. Resonance 2. Inductive effect 3. Steric interactions 4. Aromatcity 5. Hybridization

Oxidation state calculation

1. Secondary alcohol: Carbon shares electrons equally with both CH3 groups, so 0 to each. O in OH, more electronegative, gives C +1 H is less electronegative, gives C -1 Overal = 0 + 0 + 1 - 1 = 0 2. Ketone: Both O2 give carbonyl C +1 each Carbonyl C shares electrons equally with CH3 (0) 0 + 0 + 1 + 1 = +2

Prostaglandins arachinDONATE -derived

1. Share *5-membered ring* from C8-C12 2. Named as PGA to PGI (letters refer to functional groups and stereochemistry) 3. *Numerical subscript* refers to the *number of pi bonds* NOT in the ring (C5-C6). 4. Eicosanoids are ALL derived from *arachinDONATE* through PGG2 & PGH2 oxidation.

Carbohydrates C:H2:O ratio

1:2:1 (one carbon hydrated by one water)

Alkyl halides to alcohols

1° + OH- = 1° alcohol 2° + RCO2 = 2° alcohol 3° alkyl halide + H2O & acetone = 3° alcohol

Conjugation UV

2 = bonds separated by - bond (diene). Conjugation ↑, UV *λmax* ↑ Carbonyls have a higher λmax than alkenes

Hydroquinones redox

2 e- exchange

Tetra-terpene

40 carbons

Terpenes MUST be *multiples of 5*

5 C, 10 C, 15C...etc. A 16C molecule CANNOT be a terpene.

Dimethyl benzene

5 signals in alkane region 4 signals in aromatic region

Important question

A. Protein in higher pH than its pi → deprotonated, ------- goes to anode. B. Gel to resist quick migration, true. C. Glycine has almost no charge at pH 6, but lysine is ++++ to cathode quickly. D. 100 AA is x2 mass, but x2 charge, so mass-charge ratio is the same

*AA (L) & carbs (D): stereochemistry* Natural AAs are in L configuration

AA Natura*L* *L*ife Cysteine is the exception (R) *Sugars: D*

*Gel* filtration chromatography

AAs by* size* (*big* elutes* fastest*).

Acetamide > acetic acid BP. MW or H-bonding?

Acetamide H3CCONH2 has a comparable MW to acetic acid H3CCO2H. Amide's (*-O*) due to resonance gives it better H-bonding. H-bonding proton is more attracted to amide's O than carboxylic acid (*explains proteins higher H-bonding*)

Acetyl coenzyme A

Acetyl group is transferred from a reactant to a thiol when acetyl-CoA forms

LG reactivity Good LG = weak bases

Acid anhydrides & acid halides > ester. Ester > amides

Basic AAs increase pI of a protein

Acidic AAs decrease pI of a protein

Alk*en*e *+* alcoh*ol → enol*

Acidic conditions: Alpha-H deprotonated & *carbonyl oxygen protonated*

AA average MW is 110 D. N-terminus pKa is 9...................... C-terminus pKa = 2

Acidic: *E & D → pKa 4* Basic: *His 6 ....................Lys 10.5.....................Arg 12.5*

*AAs PIs* 55 or 75

Acidic: <5.5 (<5) Basic: >7.5 (>7) Neutral: 5.5-7.5 (~6)

Percent yield

Actual moles/ theoretical moles

Anhydrous means without water

Adding it to a mixture is used for removing water residues.

Hemiketal formation

Alcohol + Ketone

SOCl2

Alcohol to alkyl halide. Replaces OH with a better LG

H-bonding comparison

Alcohols H-bonding: Primary > secondary > tertiary Ammonia (NH3) → least hindered → most H-bonding.

Reverse aldol reaction

Aldehyde & ketone

Enamine

Aldehyde/ ketone + secondary amine. Picture is showing formation of: *Ena*mine (from a *secondary* amine) *Imine* (from a *primary amine*)

Aldohexose

Aldo: aldehyde Hex: 6C Ose: sugar

Carboxylic acids are NOT peroxides (no O-O bond)

All free radicals are 2°

Enolate (basic conditions)

Alpha H deprotonated.

Amylopectin & glycogen branch (alpha)

Amylose does NOT branch.

Multiple charges (charged sites -, +) → more water solubility

An *end with Hs is more soluble in water than an end with CH3*s. Hs can hydrogen bond, but CH3s make a lipid environment and reduce affinity to water.

Imp Q answer

Association with triple bonds gives bond more strength.

Atoms with *lone pairs* are generally *EDGs*

Atoms with *pi-bonds* & no pairs are *EDGs* generally

In aldoses

C1 bonds to two O2

Proton NMR examples

CH3CH2CH2Cl (3 NMR signals) Most deshielded. 1. One next to chlorine 2. Next then farthest. CH3 has 2 neighbors = triplets. CH2 (next to Cl) = triplet. CH2 (middle has 5 neighbors) = multiplet (sextet) Multiplet is used when having non-equivalent neighbors.

Adrenal cortex hormones

Cortisone Cortisol Aldosterone

Acidity of a proton increases with H-bonding *H-bonding ↑ → proton acidity*

Covalent bond is weakened. This is why acidity is higher in water than other solvents.

Lactone

Cyclic ester (O-C=O)

Proton NMR

Determine number of equivalent Hs by identifying the symmetry.

*Diene protonation* Reactive outer carbons Non-reactive inner carbons

Diene → protonated at its terminals. Less-hindered end → protonated (i.e. 2° than 3°) The *inner* ends are *resonance* stabilized → *not* reactive

Diluting a compound to half of its original concentration can yield an optical activity half the original amount

Diluting a compound with an optical rotation of +233 would show an optical rotation of +116.5

Alcohol have protic hydrogens

Distinguished by its broadness that results from H-bonding in solution. *Alcohols* are distinguished from ethers by b*road peaks in their H NMR*.

*How to count Sp2-hybridized carbons?*

Double bonds have two Sp2-hybridized carbons each.

*Enzymes* do NOT denature AAs

Enzymes cleave AAs (i.e. to prepare for sequencing)

Ethers are hydrophobic

Example: Tetrahydrofuran (THF)

Wax formation → water out

Fat and beer → wax (ester bonds)

Lipids FAs → hydrocarbons + COO- Mono, di, triglycerides.

Fats, fat-soluble vitamins (ADEK) Hormones Ster*ols* (steroid alcoh*ols*) Waxes (*esters* with long chain *FAs* with long chain *alcohols*)

Phenyl-hydrazine (HNNH2)

Forms an *osazone: C2 epimer* test.

Higher purity

Fractional distillation

Alpha D fructofuranose 6 phosphate

Fructose is a ketohexose (ketone on carbon 2). Carbon 2 is anomeric (not 1C). Phosphate would be located on C6, not 2

Type O blood 3 sugars

Glc-Gl-Fuc

L vs D glucose Haworth

Glucose is an aldehyde. All of its linkages involve anomeric carbons that are part of an acetal functional group.

Stronger LGs make for a more reactive carbonyl compound.

Good LG form stable compound upon leaving. Stronger LG = more stable = less basic = stronger conjugate acid. Good LGs have conjugate acids with low pKa

Greatest equilibrium constant Keq is where most product is form and least reactant is left behind.

Good LG: Weak base Stable High pKb Conjugate acid with small pKa

2OH + ketone in base → hemiketal

Hemiacetals & acetals are formed from aldehydes.

*BF3*

High electronegative Fs with empty p-orbitals. *Extremely electron-deficient.* Excellent e-acceptor → *Lewis acid*

Mass spectrometry

Hitting with particles (i.e. electrons) to knock an e out of the molecule giving it a positive charge (resulting 2 things: a radical and a cation). The radical doesn't show on mass spec because it is charge-less X axis: m/z ratio =~mass (since z = +1) Y axis: I The peak is called (M+) molecular ion and it represents the MW, this is called a *parent peak*. M+: Furthest peak to the right as a cluster, the tall peak is MW.

Phenol pKa

10

Acetal linkage

Involves two OR groups

Hydrazine

*N-N* by a sigma bond

Glucose & stereochemical arrangement

2 right: 2R 3 left: 3S 4 right: 4R 5 right: 5R *2R, 3S, 4R, 5R*

Trans pack better than cis

They have higher MPs than cis

Beta carotene

Highly conjugated Orange region (lambda max)

Terpenes characterisitcs

Highly volatile Distinct odor Fluid at room T NOT water soluble

Electronegativity ↑, *Inductive effect ↑ *

*Increases* with electronegativity (*pulls electrons density away* from neighbors & make them *less nucleophilic*) Electronegativity: *F>ONClBrISC>H* Inductive effect *diminishes with distance* (negligible after 4 carbons)

Terpenes are synthesized using:

*Iso-pentenyl ppi* *Dimethyl-allyl ppi* Both animals & plants synthesize it. *Cholesterol synthesis* involves *terpenes & terpenoids*

Cholesterol synthesis

*Iso-pentenyl* PPi → *squalene* (c*30*) → Lano-*sterol* (c*30*) → cholesterol (c*27*)

Terpenes Small: plants Large: plants and animals

*Larger* terpenes (i.e. *b-carotene*, 40C source of vit. A) are found in *plants and animals*

Acidic AAs (DE)

*Lose a proton* in their *neutral* state *3 acidic sites*: 1. N-terminal 2. C-terminal 3. Side chain Acidity: Asp >>> Glu

Nitric acid (HNO3) sugar oxidation

*Makes both sugar terminal carboxylic acids* (since it is an oxidizing agent with lots of Os)

Mobile phase (solvent) vs. stationary phase properties

*Mobile phase*: can be nonpolar (hexane) or polar (ethanol) or a mixture of both. *Stationary phase*: polar alumina (Al2O3) or silica gel (*polar*). Polar species have the SLOWEST migration rate. The solvent binds to the silica gel or alumina may make it less interactive with the migrating solute. *Polar* species *in nonpolar solvents* have *SLOW* migration rates. Nonpolar species in nonpolar solvents have a fast migration rate.

Imine N=C

*N=C*

*Deoxy*Glucose

*No oxygen bonded to C2*

*SN2 reaction (bond-LG gets shaken & weakened* Rate depends on BOTH the [nuc] and [electrophile]

*Nuc attacks prior to LG leaving* with a backside hit (stretches and weakens the bond between elect & LG) and *pushes LG off* the electrophile. This *backside attack* causes an *inversion* of the chiral carbon

*D vs L sugar* absolute configuration

*OH @ 5th carbon (last chiral C)* D: right L: left *ALL c*hiral centers should be *switched.*

Glycosidic linkage

*OH* group attacking *hemiacetal* carbon to form *acetal* *Dehydration* involving two OH groups. OH + hemiacetal C → acetal

*L*-fucose

*Only non-D-sugar* in the body used in blood typing A reduced form of L-galactose in blood glycoproteins.

*SN1 Product features * (racemic w/ no excess)

*Racemic mixture forms* when electrophile has chirality. Rate= *k[elect]* Slow *2-step* reaction

If *base is too strong, elimination* occurs (OR- & OH-), so nucleophiles that can H-bond are *hindered in protic solvents* because they are solvated (to *reduce its nucleophilicity* by binding its e- pair)

*SH-, CN- & I- are stronger nucleophiles* than OH in water

Ethyl chloride NMR

2 signals (3Hs are equivalent, the other 2 are equivalent)

Isopropyl chloride NMR

2 signals: (Sides are identical making a doublet of 6 protons). The one next to Cl is unique.

Sa*N*ger's reagent

2, 3 Di*Nitro*fluorobenzene Reacts with *N* of the *amino terminal*

Carboxylic acid pKa

2-5 range

Oligosaccharides

2-8 monosaccharides

Isoprene units (5C)

2-methyl-1, 3-butandiene

Aldehydes & ketones 1. No H-bonding = similar BP to alkanes of equal mass.

2. Slight water solubility due to carbonyl polarity. 3. Polar aprotic with less hydrophilicity with MW increase. MW ↑→ Water solubility ↓ (3Cs are water soluble).

Diterpenes

20 carbons (4 isoprenes)

Chemical shift, delta (in ppm)

200 to 0 To the left: Downfield, Deshielded. To the right: Upfield, shielded.

Acetone

3 carbons

Leukotriene structure

3 conjugated = bonds

Trisaccharide formation

3 monosaccharides minus 2 waters (lost upon forming linkage)

Is the following statement true? Biological isoprene is derived from 3 acetyl-CoA molecules and requires a decarboxylation reaction.

3 x 2C = 6C Decarboxylation: 6C-1C= 5 C (isoprene) Then the statement is true.

Alcohols are more volatile than carboxylic acids

A molecule with a hydroxyl dissolves better in an alcohol (like dissolves like)

Amines react with *nucleophiles*, so they won't react with an ether.

Amines can react with anhydrides, benzoic acid, alkyl halide. *Amines WON't react* with *ethers* R-O-R*

Which distillation sequence is possible? Distillation of propanol from THF Distillation of ethyl formate from acetone Distillation of ethanol from diethyl ether Distillation of THF from acetic acid

Analysis: Distillation of X means that X has to have a lower BP to be a distillate, so the 1st compound in the sequence has to be the 1st to evaporate and the 2nd to stay in liquid phase (choose the last option)

Nuclear Magnetic Resonance

Any nucleus with an odd number of protons (Z) or an odd number of nucleons (A) has a net spin.

Terpenes are *UV active* due to their pi-bonds (~225 nm for a conjugated diene)

As *conjugation* increases, *max absorbance* (lambda max) and *intensity* of absorbance *increase*).

AAs with *amide* in their *side chain*

Asparagine(*asn,N*) & glutamine(*gln,Q*)

Ionic vs. covalent bonds

Ionic: complete transfer of electrons from one atom to another (*no "sharing"*). Covalent: electrons *shared evenly* between two atoms

*Hydroxyl*amine (NH2OH)

H is replaced with a hydroxyl group to the N

Fischer projection

H on sides → out of the page Reverse stereochemistry Up or down → into page

Polar, protic molecules

H-bonding Dipole-dipole VDW Ex: Water, alcohol, amines, carboxylic acid

Aldehyde example CHO

H3CCH2Ch2*CHO*

In a pH of 6 solution, only negatively charged proteins would bind DEAE-cellulose (+ charged)

In a solution with pH of 6, proteins with pI<6 will be negative.

Steric hindrance

In cyclohexane, *axial* experiences *greater hindrance* than equatorial. *Bulky* substituents assume the *equatorial* orientation.

From the structure in previous card, figure out why A is its enantiomer

In enantiomers, configuration at every stereoisomer changes

Maltose (disaccharide)

In maltose in the picture, the *glycoside* is the sugar on the *right* *C5* on Haworth of a 6 sugar is within the ring, automatically *RIGHT*

Hydrophobic AA (i.e. alanine) is a zwitterion in water. In aprotic → uncharged (or in basic sln) In protic → zwitterion

In polar aprotic solvents (i.e. DMSO), it cannot be stabilized and cannot form a zwitterion → AA remains uncharged in aprotic solvent. Remains uncharged in high pKa (protons won't dissociate in basic).

*Ionic bonds characteristics* Formed between opposite charged ions Between metals & nonmetals Per Coulomb's law, the greater the charge of the ion, the stronger and shorter the bond.

Ionic bonds are typically stronger than covalent, but when solved in a polar protic solvent, they are easily cleaved (more than covalent bonds). Ionic bonds break in a* heterolytic* fashion.

Which form of caffeine has higher MP and BP, ionized or unionized?

Ionic forces are stronger than polar forces due to the full charge, so the ionized one is stronger (higher MP, BP) than the only polar neutral one.

*Charge on basic sites* on a molecule is *(-)*

Nitrogen (less e-negative) donates more e- density to carbonyl oxygen, this makes it less basic.

Conditions needed to *form an enamine C=C-N*

Nitrogen with 2 hydrogens on it

Rotating plane-polarized light needs *stereogenic centers*

No chirality, no rotation

At what pH is the tripeptide serine-cysteine-isoleucine perfectly neutral? 1. 5.3 2. 6.1 3. 8.4 4. 9.4

None of the AAs is basic → find pKa1 & pKa2 average. 3 & 4 pHs are too high (eliminate them) Cysteine has acidic properties, so expect pH to be a little low. C-terminal pKa is always pKa1.

Ligroin (petroleum)

Nonpolar solvent

Steric product → thermodynamic enolate

Not hindered product? kinetic product enolate

How many D-aldopentoses are there?

Notice that the question specifies (D-) sugars, so if the 2^n gives you the number of possible stereoisomers, it gives you D & L, so half of which will be D & half of which will be L. 3 stereogenic centers means 8 possible stereoisomers (4 D & 4 L). *Humans* are enzymatically programmed to *digest D-sugars*

Formaldehyde

Notice the H-C bond angle in formaldehyde is less than 120 in this sp2 carbon atom. Why? The lone pairs on the oxygen cause the electron density to repel the electrons in the two carbon-hydrogen bonds making the two bonds closer together. So it is slightly smaller than 120 (~118.5)

*Histidine* Notice that the amine (*NH*) *shares* its electrons *with the ring*, so it cannot be protonated. The imine (*N* within ring "N=C), *gets protonated*.

Ns in the ring can be protonated at a low pH with only one H each. Its ring is planar (due to hybridization) and *aromatic* (6 pi electrons).

*Amides reactivity* Reduced to amines

Nucleic acids (DNA, RNA) Proteins Amind bonds link AAs by peptide bonds Amide + LiAlH4 (reduction) = amines

Which of the following doesn't contain amide bond? Guanine Uracil Isoleucine Cytochrome

Nucleic acids have it. Proteins have it. Only AAs to have it are gln & asn The third choice is the correct answer.

Peroxyl OOH can be converted to hydroxyl OH by a reducing agent (removing 1 O)

OOH to OH (peroxyl to hydroxyl) by a reducing agent

Column chromatography

Ochem: aim is for all compounds to elute at different rates. Biochem: aim is to one compound stuck and not elute, but all the rest elute.

Leaving groups

The more stable, the weaker it is More stable LG → less basic→ more acidic its conjugate base is

Which of the following structures is one of *four possible stereoisomers*?

The question is asking you to find which structure has *2 stereocenters* (2^n)

In a pH 7 solution, proteins with pI>>> 7 will be (+)

These would bind a negative column. You can elute them using NaCl- aq added to solution because *Na+* has the same positive charge yet *smaller* so *its (-) column affinity is stronger.*

When Arctic salmon is mentioned, think of cold, cold solidifies the membrane

They compensate by having UNSATURATED fats in their membrane (FAs with most pi bonds)

*Squalene to cholesterol*

Through a *cyclization rxn* the body makes *cholesterol* out of squalene.

Fischer projections

Top view of a compound in a fully eclipsed conformation, derived from the straight chain form. *Right or left* side chains of the main backbone is *projecting out* (bow ties)

Anomeric carbon

Two bonds to Oxygens

Acid anhydride O-Coco

Two carboxylic acids combine in a dehydration reaction.

Anomers 2

Two diastereomers of alpha or beta at the *anomeric carbon*. Alpha: axial Beta: equatorial (more stable)

*Spectroscopic evidence of aldehydes and ketones* Aldehydes IR: 1720 to 1740 cm Ketones: 1710 to 1725 cm

Two medium C-H stretches around 2700 & 2900. NMR: aldehyde Hs (9-10 ppm)

Elemental *chlorine Cl2* mass spectrometry

Two peaks with 3: 1 ratio (57% & 24% isotopes)

Type A vs. Type B blood

Type A: has carbon 2 hydroxyl replaced by N-acyl. Type B: Has a galactose residue at its 4th sugar & OH at C2

Blood types glycoprotein stuctures

Type-*O*: *lacks the 4th* sugar. Types *A & B*: Have a *5th* sugar. Adding a fourth sugar to O makes it foreign. O + 4C = foreign

UV light & conjugation π bonds ↑, *Sp2 ↑*, conjug ↑, absorbance ↑, stability ↑

UV spectroscopy detects π bonds. Conjugation (alternating = bonds) increases absorbance. More π bonds, more Sp2-hybridization. *Conjugation increases stability*

Singlets (NMR protons)

Unique Hs with no bonds to them (i.e. CH3). *Each 3Hs count as 1 singlet* Notice the 3 singlets in the attached picture.

Fragmentation

Unstable species formed upon ionization undergoes chemical processes to form a more stable species.

Sequencing steps (N-C)

Urea breaks H-bonds & b-mercaptoethanol breaks cross-linkages. 1. Labeling the beginning of the sequence (1st AA) with *Sanger's reagent* (24 DNFB). 2. Hydrolyze the protein using 6M HCl. 3. Using enzymes to cut at specific locations.