Organic Chemistry

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Organic Chemistry

• Courtney Eichengreen
• courtney.eichengreen_at_ucdenver.edu
• 719.321.4187

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Remember last time?

• Organic Chemistry is 35 of the Biological
  Sciences section
• With GOOD STRATEGY and GOOD REVIEW you can earn
  points without memorizing every tedious reagent
  and reaction mechanism!
• Things to remember so far

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Remember last time?

• VOCAB and NOMENCLATURE
• Know these words Alkane Alkene Alkyne Alkyl
  Alcohol Ether Amine Aldehyde Ketone Carboxylic
  Acid Ester Amide Acyl Halide Anhydride Carbonyl
  Benzyl Phenyl
• IUPAC just know enough to match!
• Find parent hydrocarbon chain (longest OR has
  functional group)
• Identify functional groups most important most
  O (or N)
• Number chain for min of primary group, then
  other substituents
• Assemble name in alphabetical order

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Remember last time?

• BONDING
• Sigma bonds s (or hybrid) orbitals, end-to-end
• Pi bonds aligned P ORBITALS ONLY
• No rotation
• Occupied P orbitals cant participate in
  hybridization!
• Hybridization blend S unoccupied P orbitals
• Pi bonds occupy Ps!

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Remember last time?

• STRUCTURE AND GEOMETRY
• Geometry especially tetrahedral (109.5) trigonal
  planar (120) linear (180)
• Remember lone pairs compress other angles
  eg trigonal pyramidal, bent geometries
• Additional geometry cyclic molecules
• 6-membered rings have least ring strain

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Remember last time?

• INTERMOLECULAR INTERACTIONS
• London dispersion forces/Van Der Waals
• Dipole-induced dipole interactions
• Dipole-dipole interactions
• H bonding
• Think Boiling point, solubility

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Remember last time?

• RESONANCE FORMAL CHARGE
• Resonance structure move electrons only
• (real structure is resonance hybrid)
• remember to look at resonance stabilization in
  conjugate bases to assess acidity!
• Formal charge e- per periodic table - e-
  actual

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Remember last time?

• ISOMERISM

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Remember last time?

• CHIRALITY
• Chiral center 4 different substituents
• R vs S (priority by atomic number)
• Molecules w chiral centers rotate polarized light
  or (EXCEPT meso internal symmetry)
• Racemic mix 50/50 enantiomers

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Remember last time?

• REACTIONS
• Electrophile wants electrons, or d
• Nucleophile donates electrons, - or d-
• Substitution one substituent replaces another
• Elimination substituent lost, double bond made

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Remember last time?

• REACTIONS
• SN1 (uni-molecular kinetics, 2 step mechanism)
• Carbocation intermediate. Need good LG. Protic
  solvent stabilize C. See racemization of chiral
  reactants.
• E1 (uni-molecular kinetics, 2 step mechanism)
• SN2 (bi-molecular kinetics, 1 step mechanism)
• Need strong nucleophile. APROTIC solvent to
  protect nucleophile. See inversion of relative
  configuration.
• E2 (bi-molecular kinetics, 1 step mechanism)

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Remember last time?

• REACTIONS
• Electrophilic aromatic substitution
• Electron donating groups (?? next to ring)
  activate the ring and are ortho-para directors
• Electron withdrawing groups ( or d next to
  ring)deactivate the ring and are meta directors
• Halogens are electron withdrawing BUT are
  ortho-para directors

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Organic Chemistry II today!

• Oxygen-containing compounds
• Amines
• Organic molecules
• Spectroscopy
• Lab Techniques separation and purification

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Oxygen-containing compounds

• Applying what we know about reactions to

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Oxygen Containing Compounds

• Alcohols
• Aldehydes and Ketones
• Carboxylic Acids
• Acid Derivatives
• Acid Chlorides
• Anhydrides
• Amides
• Keto Acids and Esters

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Practice!

• One of the most common reactions of alcohols is
  nucleophilic substitution. Which of the following
  are TRUE in regards to SN2 reactions
• Inversion of configuration occurs
• Racemic mixture of products results
• Reaction rate k Snucleophile
• I only
• II only
• I and III only
• I, II, and III

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Alcohols

• Physical Properties
• Polar
• High MP and BP (WHY?)
• More substituted less acidic
• (CH3)3COH pKa 18.00
• CH3CH2OH pKa 16.00
• CH3OH pKa 15.54
• Electron withdrawing substituents stabilize
  alkoxide ion, lower pKa.
• Tert-butyl alcohol pKa 18.00
• Nonafluoro-tert-butyl alcohol pKa 5.4
• General principles
• H bonding
• Acidity weak relative to other O containing
  compounds

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AlcoholsNomenclature

• Select longest C chain containing the hydroxyl
  group and derive the parent name by replacing e
  ending of the corresponding alkane with ol.
• Number the chain beginning at the end nearest the
  OH group.
• Number the substituents according to their
  position on the chain, and write the name listing
  the substituents in alphabetical order.

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Alcohols-Oxidation Reduction
Oxidation
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Reduction
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Alcohols-Oxidation Reduction

• Common oxidizing and reducing agents
• Generally for the MCAT
• Oxidizing agents have lots of oxygens
• Reducing agents have lots of hydrogens

Oxidizing Agents Reducing Agents
K2Cr2O7 LiAlH4
KMnO4 NaBH4
H2CrO4 H2 Pressure
O2
Br2
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How do you make Alcohols? Reduction!

• Aldehydes, ketones, esters, and acetates can be
  reduced to alcohols w strong reducing agents such
  as NaBH4 and LiAlH4
• Electron donating groups make the carbon less
  partially positive, so less susceptible to
  nucleophilic attack.
• Reactivity AldehydesgtKetonesgtEsters/acetates
• Only LiAlH4 is strong enough to reduce esters and
  acetates

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Reactions of Alcohols remember SN reactions?

• Alcohols can be converted to Alkylhalidesvia a
  strong acid catalyst
• R-OH HCl ? RCl H20
• WHY? -OH is converted to a better LG when
  protonated by a strong acid
• For tertiary alcohols HCl or HBr
• Primary/secondary alcohols are harder (why?),
• need SOCl2 or PBr3 (stronger nucleophiles!)

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• In the reaction above, if the reagents in the
  first step were replaced with LiAlH4, what
  product would result?
• a) c)
• b) d)

O
OH
OH
OH
OH
OH
OH
HO
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CARBONYLS!!

• Extra special oxygen-containing compounds

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Carbonyl compoundsCarbon double bonded to Oxygen

• Planar geometry
• Partial positive charge on Carbon (susceptibility
  to nucleophilic attack)
• Aldehydes Ketones nucleophilic addition
• Carboxylic Acids nucleophilic substitution
• its really more like addition then elimination
  but the same rules we already know!
• Carboxylic acid derivatives

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Carbonyl reaction addition

• 1. Nucleophilic attack at carbonyl C
• 2a. Protonation of O- (net addition)

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Carbonyl reaction substitution

• 1. Nucleophilic attack at carbonyl C
• 2b. LG leaves, elimination restores carbonyl
  (net substitution)

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Aldehydes and KetonesNomenclature surprise its
the same!

• Naming Aldehydes
• Replace terminal e of corresponding alkane with
  al.
• Parent chain must contain the CHO group
• The CHO carbon is C1
• When CHO is attached to a ring, we say
  carbaldehyde
• Naming Ketones
• Replace terminal e of corresponding alkane with
  one.
• Parent chain is longest chain containing ketone
• Numbering begins at the end nearest the carbonyl
  C.

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Aldehydes and Ketones

• Physical properties
• Carbonyl group is polar
• Higher BP and MP than alkanes, lower than
  alcohols (WHY?)
• More water soluble than alkanes, less soluble
  than alcohols (WHY?)
• Trigonal planar geometry, reduction yields
  racemic mixtures

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Aldehydes and Ketones

• General principles
• Effects of substituents on reactivity of CO e-
  withdrawing make that C even more positive (aka
  more reactive!)
• Steric hindrance ketones are less reactive than
  aldehydes
• Acidity of alpha hydrogen carbanions
• a, b unsaturated carbonyls resonance structures

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Aldehydes and Ketones-Acetal and Ketal
Formation nucleophilic addition
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Aldehydes and Ketones

• Keto-enol Tautomerism
• Keto tautomer is preferred (alcohols are more
  acidic than aldehydes and ketones).

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Guanine, the base portion of guanosine, exists as
an equilibrium mixture of the keto and enol
forms. Which of the following structures
represents the enol form of guanine?
Practice!
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Aldehydes and Ketonesacidity of the a carbon

• Aldol (aldehyde alcohol) condensation
• Occurs at the alpha carbon (wait, what?)
• Base catalyzed condensation (removal of H2O)
• Can use mixtures of different aldehydes and
  ketones

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Aldehydes and Ketones Oxidation (Aldehydes ?
Carboxylic acids)

• Aldehydes are easy to oxidize because of the
  adjacent hydrogen. (In other words, they are good
  reducing agents.)
• Examples used as indicators
• Potassium dichromate (VI) orange to green
• Tollens reagent (silver mirror test) grey ppt.
• Fehlings or benedicts solution (copper solution)
  blue to red
• Ketones are resistant
• to oxidation (no adjacent H).

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Aldehydes and Ketones

• Organometallic reagents
• Nucleophilic addition of a carbanion to an
  aldehyde or ketone to yield an alcohol

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Carboxylic Acids

• General Principles
• Electrophilic carbonyl C susceptible to
  nucleophilic attack!
• Fairly strong acids (compared to other organic
  Oxygen containing compounds)
• Acidity of terminal H increases with EWG,
  decreases with EDG always consider stability of
  conjugate base
• Planar, polar, H bonding

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Practice!

• Which class of compounds would have a higher
  boiling point, Acyl Chlorides or Carboxylic
  Acids? Why?

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Carboxylic AcidsNomenclature what do you think?

• Carboxylic acids derived from open chain alkanes
  are systematically named by replacing the
  terminal e of the corresponding alkane name with
  oic acid.
• Compounds that have a CO2H group bonded to a
  ring are named using the suffix carboxylic acid.
• The CO2H group is attached to C 1 and is not
  itself numbered in the system.

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Carboxylic Acids nucleophilic substitution!

• Carboxyl group reactions
• Nucleophilic attack
• Carboxyl groups and their derivatives undergo net
  nucleophilic substitution.
• Aldehydes and Ketones undergo net addition (WHY?)
• Must contain a good leaving group or a
  substituent that can be converted to a good
  leaving group.

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Carboxylic Acids Reduction

• Carboxylic acids can undergo reduction like other
  oxygen-containing compounds
• Form a primary alcohol
• LiAlH4 is the reducing agent

LiAlH4
CH3(CH2)6COOH
CH3(CH2)6CH2OH
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Carboxylic Acids Decarboxylation

• Biologically important reaction (TCA cycle!)
• Decarboxylation - know that it happens (-CO2)

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Carboxylic AcidsEsterification

• Fischer Esterification Reaction
• Alcohol Carboxylic Acid ? Ester Water
• Acid Catalyzed protonates OH to H2O (excellent
  leaving group)
• Alcohol pulls a nucleophilic attack on carbonyl
  carbon

H
These bonds are broken
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Carboxylic Acidsreactions at two positions

• Most substitution reactions happen to the keto
  carboxylic acid (nucleophilic attack at carbonyl
  C)
• Remember enol reactions acidity of the a H,
  extra e- at a C have a mind of their own

To make -gt
SOCl2    or PCl3 Heat, -H2O R'OH, heat, H - R2NH heat HO-
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Carboxylic Acidsreactions at two positions

• Halogenation enol tautomer undergoes
  halogenation (addition across CC)

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Acid Derivativesnoooomenclaaature

• Acid Halides (RCOX)
• -oyl halide instead of -oic acid ex ethanoyl
  chloride
• Acid Anhydrides (RCO2COR)
• Just replace the word acid with anhydride.
• 2 acetic acid ? acetic anhydride
• Unsymmetrical anhydrides cite the two acids
  alphabetically.
• Acetic acid benzoic acid ? acetic benzoic
  anhydride
• Esters (RCO2R)
• R (on the O side) gets -yl, R (on the O
  side) gets -oate ex isopropyl propanoate
• Amides (RCONH2)
• Just use the suffix amide
• Acetic acid ? acetamide
• If the N is further substituted, first identify
  the substituent groups and then the parent amide.
  Substituents are numbered by the letter N.
• Propanoic acid methyl amine ?
  N-Methylpropanamide

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Acid DerivativesRelative Reactivity

• A more reactive acid derivative can be converted
  to a less reactive one, but not vice versa!
• Only esters and amides commonly found in nature.
• Acid halides and anhydrides react rapidly with
  water and do not exist in living organisms

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Practice!
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Acid Derivatives Reactions

• Hydrolysis- water ? carboxylic acid
• Alcoholysis- alcohol ? ester
• Aminolysis- ammonia or amine ? amide
• Reduction- H- ? aldehyde or alcohol
• Grignard- Organometallic ? ketone or alcohol

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Acid DerivativesTransesterification

• Transesterification exchange alkoxyl group with
  ester of another alcohol
• Alcohol Ester ? Different Alcohol Different
  Ester

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NITROGEN-CONTAINING COMPOUNDS

• Whew. Ok. One last class we need to know for Test
  Day

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Amines

• General principles
• Lewis bases (when they have a lone electron pair)
  
• NR3 gt NR2 gt NR gt NH3 (least basic)
• Stabilize adjacent carbocations and carbanions
• Effect of substituents on basicity of aromatic
  amines
• Electron withdrawing are less basic
• Electron donating are more basic

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Amines

• Important functions in amino acids, nucleotides,
  neurotransmitters
• 1o, 2o, 3o, 4o by number of carbons bonded
• Can be chiral (rarely have 4 side groups)
• Physical properties
• Polar
• Similar reactivity to alcohols
• Can H bond, but weaker H bond than alcohols
• MP and BP higher than alkanes, lower than
  alcohols

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Amines act as nucleophiles!

• Amines are basic and fairly nucleophilic
• Amide formation proteins!!

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Amines Alkylation

• ? Alkylation SN2 with amine as the nucleophile
  and alkyl halides as the electrophile
• Reaction with 1 alkyl halide
• Alkylation of 1 and 2 are difficult to control
  and often lead to mixtures of products
• Alkylation of 3 amines yield quaternary ammonium
  salts

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Practice!

• Drug classes

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Biological MoleculesAmino acids and
proteinsCarbohydratesLipidsPhophorous
containing compounds

• Ready for real-life applications?

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Amino Acids and Proteins

• Amino acids are the basic structural units of
  proteins
• amino group, carboxyl group, H, unique R group
  (side chain)
• AA have acidic and basic properties (zwitterions
  can be both proton acceptors and donors)
• Because they are dipolar at physiological pH (
  and charges) they have unique isoelectric
  points, but there is no net charge on the molecule

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AA and Proteinsabsolute configuration at the a
position

• Amino acids have a chiral carbon (except
  glycine), and are all L stereo-isomers.
• Amino acids in solution

Amino acid general structure
Low pH High pH
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Amino AcidsTitrations and Isoelectric Point (pI)

• Isoelectric point of a protein is the pH at which
  the amino acid exist as a zwitterion
• Amino acids are essentially diprotic acids at low
  pH, their titration curves resemble those of
  diprotic acids.

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AA and Proteins-classification

• Polar side groups- hydrophilic
• Face aqueous solution
• Nonpolar side groups- hydrophobic
• Face interior of protein

Polar Nonpolar Acidic Basic
Asparagine Cysteine Glutamine Serine Threonine Tyrosine Alanine Glycine Isoleucine Leucine Methionine Phenylalanine Proline Tryptophan Valine Aspartic Acid Glutamic Acid Arginine Lysine Histidine
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AA and Proteins-reactions

• Peptide linkage (formation of an amide)
• the covalent bond that links amino acids is
  formed by a condensation reaction (Dehydration
  synthesis)
• Alpha-amino group of one amino acid attacks the
  alpha-carboxyl group of another amino acid
• Hydrolysis the reverse reaction

Water
?  
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Practice!
Is there free rotation around the peptide bond in
an amino acid?
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AA and Proteins-reactions

• Peptides chains and proteins have direction
  because the chains have different ends, an
  amino end and a carboxyl end. By convention
  the amino end is taken as the beginning of a
  chain.
• N C alpha C carboxy N C alpha C carboxy
  
• gly-ala-leu ? leu-ala-gly

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AA and proteins

• 1o structure the amino acid sequence of a
  protein written from the amino to the carboxy
  terminus.
• 2o structure highly regular, local folding
  structures -alpha-helix and beta-pleated sheet (H
  bonding)
• 3o structure the full 3D folded structure of
  the protein (hydrophobic interactions, H bonds
  disulfide bonds)
• 4o Structure protein polymers
• e.g. hemoglobin is tetramer

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Which structure of a polypeptide is most likely
affected by the double bond character of the
peptide bond?

1. Primary
2. Secondary
3. Tertiary
4. Quarternary

Practice!
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Biological Molecules Carbohydrates

• Polyhydroxy aldehyde or ketone
• Empirical formula often (CH2O)n
• Monosaccharide (1 unit), oligosaccharide (2-10),
  polysaccharides (10)
• Glucose and Fructose most common on MCAT

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Carbohydratesnomenclature, classification
Named according to the number of carbons they
possess and existence as polyhydroxy aldehydes
(Aldoses) or polyhydroxy ketones (Ketoses)
Carbons Category Name Relevant examples
3 Triose Glyceraldehyde, Dihydroxyacetone
4 Tetrose Erythrose
5 Pentose. Furanoses (bent ring) Ribose, Ribulose, Xylulose
6 Hexose, Pyranoses (chair) Glucose, Galactose, Mannose, Fructose
7 Heptose Sedoheptulose
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Carbohydratescommon names

• Common disaccharides and polysaccharides
• Sucrose glucose fructose (a 1,4)
• Maltose glucose glucose (a 1,4)
• Cellulose (glucose)n (ß 1,4)
• Lactose galactose glucose (ß 1,4)
• Amylose (glucose)n (a 1,4)
• Amylopectin (plants) branched glucose chains (a
  1,4)
• Branching (a 1,6)
• Glycogen (animals) branched glucose chains (a
  1,4)
• Branching (a 1,6)

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Carbohydrates- absolute configuration

• Chiral center farthest from the aldehyde group
  determines D / L designator site
• D hydroxyl group in the projection formula
  points right
• L hydroxyl group in the projection formula
  points right
• D and L are absolute configuration not the
  same as d/l (dextra/levarotary /-) relative
  configuration by rotation of light.
• D sugars are the natural form we can assimilate
  following digestion biological systems are
  chiral!

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How many stereoisomers does D-glucose have?

• 4
• 16
• 32
• 64

Practice!
D-glucose
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Carbohydrates Cyclic structure and
conformations

• Cyclization OH as nucleophile, carbonyl C as
  electrophile!
• (only if you can make 5 or 6 membered ring min
  strain)
• The ring form is favored in aqueous solutions

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CarbohydratesEpimers and Anomers

• Epimers diastereoisomer that differs at ONLY ONE
  stereogenic center.
• Ex/ Mannose and a-glucose (C2)
• Anomers a type of epimer. point of difference
  C at new C-O bond (anomeric C)
• Ex/ a-glucose and ß-glucose (C1)

a-D-Glucose
Mannose
a-D-Glucose
ß-D-Glucose
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Practice!
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Carbohydrates-hydrolysis of the glycoside linkage

• Hydrolysis of polysaccharides happens in
  digestion! Glycosidase or amidase cleave acetal
  functional groups with the addition of H2O
• In saliva our enzymes can only attack alpha
  glycoside linkages (D sugars)
• Hydroxyl group attacks anomeric carbon
• Produces many molecules of glucose

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Lipids

• Lipids have hydrophobic (long hydrocarbon tails)
  and hydrophilic (charged heads) ends
• Lipid bi-layers
• (phospholipids)
• make up cell
• membranes
• Molecules with
• polar and non-polar
• groups are called
• amphipathic

http//kvhs.nbed.nb.ca/gallant/biology/phospholipi
d.jpg
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LipidsFree Fatty Acids

• Fatty acids- long carbon chain with carboxylic
  acid end.
• Serve as hormones and messengers- eicosanoids
• Components of cell membranes
• Fuel for body
• Triacylglycerols - store more than twice the
  energy of carbohydrates and proteins

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Triacyl Glycerols (fats and oils)

• Glycerol backbone with three carboxylic acid
  derivatives

http//www.oliveoilsource.com/images/triglyceride.
jpg
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Triacyl Glycerols (fats and oils)

• Saturated no double bonds i.e. saturated with
  hydrogen
• Unsaturated has double bonds. Double bonds can
  be cis or trans and are bent. The more
  unsaturated means more irregular structure and a
  lower MP
• Shorter chains also have a lower MP (fewer vDW
  interactions)
• Lipases and phospholipases are enzymes that break
  up lipids
• Treatment with NaOH (saponification making
  soap) breaks the fat into glycerol and fatty
  acids.

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The salts of fatty acids are used as soaps
because the salts

1. have a polar region and a nonpolar region and are
   thus insoluble in water.
2. have a polar region and a nonpolar region and are
   thus help organic materials become water soluble.
3. are exclusively polar and thus dissolve in
   aqueous solutions.
4. are exclusively nonpolar and thus dissolve
   organic materials.

passage 28
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Phosphorus Compounds

• ATP, ADP, TTP, GTP, CTP, UTP, Insecticides,
  phosphatidyl choline, protein phosphorylation,
  cell signaling
• There is a large amount of energy stored in
  phosphoric acid bonds, so it is used for energy
  storage
• P-O-P is the phosphoric
• anhydride bond (high
• energy). C-O-P is the
• phosphoester bond.

http//users.rcn.com/jkimball.ma.ultranet/BiologyP
ages/A/ATP.html
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SPECTROSCOPY AND LAB TECHNIQUES

• Last section!!

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Spectra, Separations, and Purifications

• Spectra
• IR spectroscopy
• NMR spectroscopy
• Separations and Purifications
• Extraction
• Distillation
• Chromatography
• Recrystallization

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IR -Absorption

• When a compound is exposed to infrared radiation,
  the polar bonds stretch and contract in a
  vibrating motion different bonds vibrate at
  different frequencies
• IR Spec records frequencies of absorption
• No dipole moment no energy is absorbed
• KNOW CO sharp 1700, C-OH broad 3600

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IR -Absorption

• wave number 1/l 4000-625 cm-1
• Detects functional groups polar bonds stretch at
  characteristic frequencies (KNOW CO sharp
  1700, C-OH broad 3600)
• Divide IR (4000 to 400 into 4 regions)
• 4000-2500 N-H, C-H, O-H
• 2500-2000 Triple bonds (CtbC, CtbN)
• 2000-1500 Double bonds (CO, CC, CN)
• 1500-400 Fingerprint region (most complex region
  of IR)

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NMR nuclear magnetic resonance

• Can tell the protons and their environment.
• Nuclei align with a magnetic field.
• Bombarded with electromagnetic energy.
• Resonance frequency, the nuclei turn against the
  magnetic field.
• Shielding e- environment of the proton
  (surrounding groups donate or steal electron
  density)
• Integral value of equivalent protons

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NMR nuclear magnetic resonance
Spin-spin splitting peaks splits into n1. n
is the number of adjacent, different protons
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NMR nuclear magnetic resonance

• Shielding- EWG shield less and shift the peak
  downfield, EDG shield more and shift the peak
  upfield.
• CC withdraw slightly 1-3
• X withdraw more 4
• Aromatic Hs will have a characteristic cluster
  at 6-8
• H next to an aldehyde SUPER deshielded at 9.5

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NMR
Electron withdrawing shift downstream Electron
donating shift upstream
Integral Values ?
http//www.cem.msu.edu/reusch/VirtualText/Spectrp
y/nmr/nmr1.htmnmr1
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Separations and Purifications

• Extraction separate by solubility
• Recrystallization separate by solubility
• Distillation separate by boiling point
• Chromatography separate by size or polarity
• Column, Gas, Thin-layer
• Electrophoresis separate by size or charge

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Separations and Purifications

• Extraction distribution of solute between two
  immiscible solvents. Solvents dissolve
  impurities and move them to aqueous layer for
  removal. Products remain in the organic layer.
  Like dissolves like.
• Add strong acid protonates amines and bases to
  make them polar
• Add weak base deprotonates strong acids to make
  them non-reactive
• Add strong base deprotonates any remaining
  acids
• Dilute acids make organic bases soluble in
  water
• Dilute bases make organic acids soluble in
  water.

http//orgchem.colorado.edu/hndbksupport
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Separations and Purifications-recrystallization

• Recrystalliztation
• Impurities stay in solution and the pure product
  crystallizes separate by solubility
• Solvent must dissolve product at high temperature
  and dissolve impurities at low temperature (or
  exclude impurities at high temperature)

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Separations and Purifications

• Distillation Purification based on
• boiling points
• Lower boiling point will distill first
• Maintain constant T as energy goes to phase
  transition
• After first compound is boiled off, T rises
• Exception
• Azeotrope A liquid mixture of two or more
  substances that retains the same composition in
  the vapor state as in the liquid state when
  distilled or partially evaporated under a certain
  pressure.

http//www.tiscali.co.uk/reference/encyclopaedia/h
utchinson/m0020819.html
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Simple vs. Fractional Distillation

• Simple distillation- separates components by
  differences in BP of entire sample.
• Fractional distillation- initial sample of
  distillate is continuously redistilled, thus at
  each point the sample boils at a lower and lower
  temperature, ultimately approaching the boiling
  point of the pure substance with the lower
  boiling point.
• fractional distillation column causes repeating
  vaporization-condensation cycles until a pure
  substance emerges.

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Separations and Purifications-chromatography

• Column chromatography
• Column full of adsorbent (stationary phase)
• Liquid solvent (eluent, mobile phase) is passed
  over the column
• Different interactions with the column (based on
  size, polarity, etc.) leads to separation
• Components are collected as the solvent drips
  from the column

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Why does an increasing salt gradient release
molecules from an ion-exchange column?

1. It increases the molecular weight of the
   molecules, causing them to move through the
   column faster.
2. It displaces sample molecules from the stationary
   phase with stronger charge interactions.
3. It increases the charge differences between the
   sample molecules and the stationary phase.
4. It fills the porous beads, thereby excluding
   entrance by the molecules into the column.

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Separations and Purifications-chromatography

• Gas-liquid chromatography
• The sample is vaporized and injected into the
  head of the chromatographic column, and
  transported across a liquid stationary phase by
  an inert gaseous mobile phase

101
Separations and Purifications-chromatography

• Thin-layer chromatography
• an adsorption chromatography in which samples are
  separated based on the interaction between a thin
  layer of adsorbent and a selected solvent
• Degree of retention of a component is called the
  retardation factor
• (Rf)      distance migrated by an analyte (Da)
             distance migrated by the solvent (Ds)

http//www.agsci.ubc.ca/fnh/courses/food302/chroma
to/schromato03.htm
102
Separations and Purifications-Electrophoresis

• Gel Electrophoresis separate by size and charge
• Sample is loaded onto one end of a gel matrix
• Electric current passes through matrix
• Compounds separated by size smaller particles
  travel faster, move farther in given time
• Compounds separated by charge neutral molecules
  arent attracted to either pole
• Example amino acids! Have characteristic pKa
  where functional groups gain/lose protons,
  lose/gain charge