Organic Chemistry

1. Organic Chemistry Courtney Eichengreen courtney.eichengreen@ucdenver.edu 719.321.4187 1

2. Organic Chemistry I • From atoms to molecules and beyond • Functional Groups • Bonding and Molecular Structure • Resonance and Isomers • Intermolecular interactions • Hydrocarbons • Substitution and Elimination Reactions • Oxygen Containing Compounds • Amines 2

3. Lewis Dot Structures • Rules for writing • Find total # valence e- • 1 e- pair = 1 bond; Arrange remaining e- per octet rules • Except: Period 3 can have expanded octet (vacant d orbital required for hybridization) • Formal Charge • # valence e- (isolated atom) - # valence e- (lewis structure) • Sum of formal charge for each atom is the total charge on the molecule • ACTUAL charge distribution depends on electronegativity 3

4. Structural Formulas • Dash Formula • Condensed Formula • Bond-line Formula • Fischer projection • Newman projection • Dash-line-wedge • Ball and stick • All Images courtesy of Exam Krackers 4

5. Functional GroupsList #1- Critical for the MCAT • Alkane C-C • Alkene C=C • Alkyne CΞC • Alcohol R-OH • Ether R-O-R • Amine R-N-R2 • Aldehyde R-CHO • Ketone R2C=O • Carboxylic Acid RCOOH • Ester RCOOR • Amide RCONH2 5

6. Alkyl Halogen Gem-dihalide Vic dihalide Hydroxyl Alkoxy Hemiacetal Hemiketal Mesyl group Tosyl group Carbonyl Acetal Acyl Anhydride Aryl Benzyl Phenyl Hydrazine Hydrazone Vinyl Vinylic Allyl Nitrile Epoxide Enamine Imine Nitro Nitroso Functional GroupsList #2- Also Useful 6

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8. Bonds • Types: • Ionic • Covalent • Coordinate covalent • Polar covalent • Hydrogen Bonds complete transfer of electrons shared electrons One atom provides both electrons in a shared pair. unequal sharing of electrons bonds between polar molecules containing H and O, N, or F 8

9. Covalent Bonds • Sigma s • Between s orbitals • Small, strong, lots of rotation • Pi P • Between p orbitals • Discreet structure, weaker than sigma, no rotation 9

10. Covalent Bonds 10

11. Bonds • In the pi bond of an alkene, the electron pair have: • 33% p character and are at a lower energy level than the electron pair in the s bond. • 33% p character and are at a higher energy level than the electron pair in the s bond. • 100% p character and are at a lower energy level than the electron pair in the s bond. • 100% p character and are at a higher energy level than the electron pair in the s bond. 11

12. Hybridization 12

13. Hybridization • Remember: • All pi bonds are between P orbitals • “Leftover” P and S orbitals hybridize, participate in sigma bonds • Ex: H2C=CH2

14. Hybrid Bonds 14

15. Hybrid Bonds

16. Special Cases – O and N • Know typical bonding for C, N, O • Bond angles in N compounds • Lone pair occupies more space than sigma bond • Bond angles 107.3 • Bond angles in O compounds • Bond angles 104.5 16

17. For the molecule 1,4 pentadiene, what type of hybridization is present in carbons # 1 and # 3 respectively? A) sp2, sp2 B) sp2, sp3 C) sp3, sp3 D) sp3, sp2 17

18. VSEPR: molecular geometry • valance shell electron pair repulsion • GEOMETRY = Minimize electron repulsion 18

19. VSEPR 1. Draw the Lewis dot structure 2. Place electron pairs as far apart as possible then large atoms, then small atoms 3. Name the molecular structure based on the position of the atoms 19

20. We’ve seen static properties of atoms and molecules… NOW LET’S MOVE STUFF AROUND!

21. Delocalized e- and Resonance • Resonance forms differ only in location of e- • To be a significant resonance form, must be stable • Remember octet rule, and consider formal charge • Real structure = blend of possible resonance structures, “resonance hybrid” 21

22. Resonance: Acids and Bases • Conjugate stabilized by RESONANCE • Organic Acids- Presence of positively charged H+ • present on a OH such as methyl alcohol • present on a C next to a C=O such as acetone (alpha C) • Organic Bases- Presence of lone pair e to bond to H • Nitrogen containing molecules are most common • Oxygen containing molecules can act as bases w strong acids 22

23. Stereochemistry • Isomers: same molecular formula, different spatial arrangements • Different spatial arrangements  different physical and chemical properties! 23

24. Stereochemistry: Isomers CONNECTIVITY • Structural (constitutional) isomers: Different connectivity. • C4H10 - Isobutane vs n-butane • Same connectivity, different spatial arrangement: Stereoisomers

25. Stereochemistry: Isomers ROTATION • Conformational isomers: Different spatial arrangement of same molecule, but doesn’t require bond breaking to interconvert! • “rotational” isomers • Chair vs. boat, Staggered vs Eclipsed, Gauche vs Anti • DOES require bond breaking to interconvert: configurational isomers

26. Stereochemistry: Isomers DOUBLE BOND • Geometric isomers: differ in arrangement about a double bond • Cis vs. trans • Stereoisomers that are not rotational and have no double bond: OPTICAL isomers

27. Stereochemistry: Isomers CHIRAL ARRANGEMENT • Enantiomers: non-superimposable mirror images • Same physical properties (MP, BP, density, solubility, etc.) except rotation of light and reactions with other chiral compounds • Chiral centers that are all opposite each other (R/S) • Diastereomers: chiral molecules with other than exactly opposite stereocenters (not mirror images) 27

28. Stereochemistry: Isomers What kind of isomers are the two compounds below? A. Diastereomers B. Enantiomers C. Constitutional isomers D. Geometric Isomers 28

29. Stereochemistry: Rotating Light • Enantiomers differ in rotation of plane-polarized light • Excess of one enantiomer causes rotation: • Right, clockwise, dextrarotary (d), or + • Left, counterclockwise, levarotary (l), or – • Specific rotation [a] = a / (l*d) • Racemic: 50:50 mixt of enantiomers, NO net rotation • Same as R and S? NO • Meso molecule – NO net rotation, internal symmetry 29

30. Stereochemistry: Chirality • R and S: 1. Assign priority by atomic number • If attachments are the same, look at the b atoms 2. Orient lowest priority (#4) away from the observer 3. Draw a circular arrow from 1 to 2 to 3 • R = clockwise • S = counterclockwise • E and Z: Different than cis and trans • Z= same side of high priority groups • E=opposite side of high priority groups 30

31. Now we know everything about what happens WITHIN molecules… WHAT ABOUT BETWEEN MOLECULES?

32. Intermolecular interactions • Due to DIPOLE MOMENTS • Charge distribution of bond is unequal • Molecule with dipole moment = polar • Molecule without dipole moment = nonpolar • Possible to have nonpolar molecules with polar bonds • Induced Dipoles • Spontaneous dipole moment in nonpolar molecule • Occurs via: polar molecule, ion, or electric field • Instantaneous Dipole • Due to random e- movement

33. Intermolecular interactions • London Dispersion Forces • Between 2 instantaneous dipoles • Dipole-dipole interactions • Dipole-dipole or dipole-induced dipole • Hydrogen Bonds • Strongest dipole-dipole interaction

34. When albuterol is dissolved in water, which of the following hydrogen-bonded structures does NOT contribute to its water solubility? 34

35. The first and simplest class of molecules we need to get friendly with for Test Day: HYDROCARBONS

36. IUPAC Naming Conventions • IUPAC Rules for Alkane Nomenclature 1.   Find + name the longest continuous carbon chain.  2.   Identify and name groups attached to this chain. 3.   Number the chain consecutively, starting at the end nearest highest priority (oxidation) substituent group. 4. Name the compound listing groups in alphabetical order, preceded by their number in the compound. (di, tri, tetra etc., don’t count for alphabetizing). • MCAT secret: on Test Day, you’ll only ever have to MATCH to the correct name! 36

37. Hydrocarbons 37

38. Hydrocarbons • Saturated: CnH(2n+2) • Unsaturated: one or more pi bonds; each pi bond decreases # of H by 2 • Primary, secondary, tertiary, and quaternary carbons • Know and be able to recognize the following structures n-propyl Iso-propyl n-butylsec-butyl iso-butyltert-butyl 38

39. Alkanes • Physical Properties: • Straight chains: MP and BP increase with length • Branched chains: • BP decreases (less surface area, vDW forces) • MP – a little more complicated due to crystal structure • When compared to the straight chain analog, the straight chain will have a higher MP than the branched molecule. BUT, amongst branched molecules, the greater the branching, the higher the MP. 39

40. Alkanes-Important ReactionsPretty Darn Unreactive • Combustion: • Alkane + Oxygen + High energy input (fire) • Products: H2O, CO2, Heat • Halogenation • Initiation with UV light • Homolytic cleavage of diatomic halogen • Yields a free radical • Propagation (chain reaction mechanisms) • Halogen radical removes H from alkyl • Yields an alkyl radical, which can make more radicals • Termination • Radical bonds to another radical • Reactivity of halogens: F > Cl > Br >>> I • Selectivity of halogens (How selective is the halogen in choosing a position on an alkane): • I > Br > Cl > F • more electronegative means less selective • Stability of free radicals: more substituted = more stable, so halogenation @ most sub’d C • aryl>>>alkene> 3o > 2o > 1o >methyl 40

41. Cycloalkanes • General formula: (CH2)n or CnH2n • Nomenclature: It’s the same! • As MW increases BP increases; MP fluctuates (crystal stacking with different geometry) • Ring strain in cyclic compounds: • Zero for cyclohexane (All C-C-C bond angles: 111.5°) • Increases as rings become smaller or larger (up to cyclononane) 41 http://www.chem.uh.edu/Courses/Thummel/Chem3331/Notes/Chap3/

42. Cycloalkanes • Cyclohexane • Exist as “chair” and “boat” conformations • Chair conformation preferred because it is at the lowest energy. (WHY?) • Substituents can occupy axial and equatorial positions. • Axia (6) - perpendicular to the ring • Equatorial (6)- roughly in the plane of the ring • Big substituents prefer to be equatorial – less “crowding”! • When the ring reverses its conformation, substituents reverse their relative position 42

43. Cyclohexanes • In a sample of cis-1,2-dimethylcyclohexane at room temperature, the methyl groups will: • Both be equatorial whenever the molecule is in the chair conformation. • Both be axial whenever the molecule is in the chair conformation. • Alternate between both equatorial and both axial whenever the molecule is in the chair conformation • Both alternate between equatorial and axial but will never exist both axial or both equatorial at the same time 43

44. Things start getting more exciting once we start substituting H for more interesting functional groups… so let’s get ready for some REACTIONS!!

45. Substitutions • Substitution: one functional group replaces another • Electrophile: wants electrons, has partial + charge • Nucleophile: donates electrons, has partial – charge 45

46. Eliminations • Elimination: functional group lost, double bond made • Often, a Lewis base is responsible for taking H leaving behind an extra pair of e- for the = • The opposite of elimination is addition 46

47. Substitution and Elimination • SN1: substitution, nucleophilic, unimolecular • Mechanism: two-step • 1. spontaneous formation of carbocation (SLOW) • 2. Nucleophile attacks carbocation • Kinetics: rate depends only on the substrate, R=k[reactant] • Stereochemistry: racemization of chiral substrates • Favored with weak or bulky Nu, good LG, stable carbocation • Protic solvents stabilize carbocation • Can see carbocation rearrangement 47

48. Substitution and Elimination • E1: elimination, unimolecular • Mechanism: two-step • 1. spontaneous formation of carbocation (SLOW) • 2. Base abstracts beta H • Kinetics: rate depends only on the substrate, R=k[reactant] • Favored with good LG, stable carbocation, weak base • Protic solvents stabilize carbocation • Can see carbocation rearrangement 48

49. Which of the following carbocations is the most stable? 49

50. Substitution and Elimination • SN2: substitution, nucleophilic, bimolecular • Mechanism: CONCERTED • Kinetics: rate depends on substrate+nucleophile, R=k[Nu][E] • Stereochemistry: inversion of configuration • (but watch your R and S!) • Favored with poor LG, small + strong Nu • Polar, APROTIC solvents don’t obstruct Nu 50