Chemistry 52, Organic 2 Prerequisite: Chemistry 51 Grading Scheme

1. Chemistry 52, Organic 2 Prerequisite: Chemistry 51 Grading Scheme Recitation Grade: 100 pts average 75 Laboratory Grade 100 pts average 75 Lecture Exams 100 pts Final 100 pts Total 400 pts Old exams and quizzes: academic.brooklyn.cuny.edu/chem/howell/jhowell.htm Safety: goggles, pregnancy Cheating: F jhowell@brooklyn.cuny.edu

2. Goals of the course: • Structure of organic molecules, relation of structure to reactivity • Organic reaction patterns • Mechanism of reactions • Synthesis of organic compounds • Techniques of the trade

3. Scaling of Raw Grades for Recitation and Lab 1. Omit the student, B, that dropped the course. 2. Get the average to 75 Multiply these sums by 4.9342 Note that student D was absent from two labs and will be low for that reason. We will deal with D later. or Multiply these sums by 0.49342 In both cases get the same result…….

4. Now we have to spread the grades out so that there is a reasonable distribution about the desired average of 75. This is done by expanding or contracting the set of grades around the average so that the maximum turns out to be 95. Now for the student D who is outside of the desirable limits (50 – 95). We move his raw grade up to 70 so that D does not skew the scaling process. D receives a scaled grade of about 51.

5. Totally unionized in aqueous solution Aqueous Solution Trends for Relative Acid Strengths Totally ionized in aqueous solution.

6. Example pKa = 15.9 Weaker acid pKa = 9.95 Stronger acid H2O + PhOH H3O+ + PhO- H2O + EtOH H3O+ + EtO- Ka = [H3O+][EtO-]/[EtOH] = 10-15.9 Ka = [H3O+][PhO-]/[PhOH] = 10-9.95 Ethanol, EtOH, is a weaker acid than phenol, PhOH. It follows that ethoxide, EtO-, is a stronger base than phenolate, PhO-. For reaction PhOH + EtO- PhO- + EtOH where does equilibrium lie? Weaker base. Stronger base K = 10-9.95 /10-15.9 = 106.0 Query: What makes for strong (or weak) acids?

7. Increasing basicity of anion. Increasing basicity of anion. What affects acidity? 1. Electronegativity of the atom holding the negative charge. Increasing electronegativity of atom bearing negative charge. Increasing stability of anion. Increasing acidity. 2. Size of the atom bearing the negative charge in the anion. Increasing acidity. Increasing size of atom holding negative charge. Increasing stability of anion.

8. What affects acidity? - 2 3. Resonance stabilization, usually of the anion. Increasing resonance stabilization. Increased anion stability. Increasing basicity of the anion. Acidity No resonance structures!! Note that phenol itself enjoys resonance but charges are generated, costing energy, making the resonance less important. The more important resonance in the anion shifts the equilibrium to the right making phenol more acidic.

9. An example: competitive Bases & Resonance • Two different bases or two sites in the same molecule may compete to be protonated (be the base). Acetic acid can be protonated at two sites. Pi bonding electrons converted to non-bonding. Which conjugate acid is favored? The more stable one! Which is that? Recall resonance provides additional stability by moving pi or non-bonding electrons. No valid resonance structures for this cation. Non-bonding electrons converted to pi bonding.

10. An example: competitive Bases & Resonance Comments on the importance of the resonance structures. All atoms obey octet rule! The carbon is electron deficient – 6 electrons, not 8. Lesser importance All atoms obey octet rule!

11. What affects acidity? - 3 4. Inductive and Electrostatic Stabilization. Increasing anion stability. Increasing anion basicity. Acidity. d+ d+ Due to electronegativity of F small positive charges build up on C resulting in stabilization of the anion. Effect drops off with distance. EtOH pKa = 15.9

12. What affects acidity? - 4 Note. The NH2- is more basic than the RCC- ion. 5. Hybridization of the atom bearing the charge. H-A  H+ + A:-. sp3 sp2 sp More s character, more stability, more “electronegative”, H-A more acidic, A:- less basic. Increasing Acidity of HA Increasing Basicity of A- Know this order.

13. Example of hybridization Effect.

14. What affects acidity? - 5 6. Stabilization of ions by solvents (solvation). Solvation provides stabilization. Comparison of alcohol acidities. 17 18 pKa = 15.9 Crowding inhibiting solvation (CH3)3CO -, crowded Solvation, stability of anion, acidity

15. Example para nitrophenol is more acidic than phenol. Offer an explanation The lower lies further to the right. Why? Could be due to destabilization of the unionized form, A, or stabilization of the ionized form, B. B A

16. Examine the equilibrium for p-nitrophenol. How does the nitro group increase the acidity? Examine both sides of equilibrium. What does the nitro group do? First the unionized acid. Note carefully that in these resonance structures charge is created: + on the O and – in the ring or on an oxygen. This decreases the importance of the resonance. Structure D occurs only due to the nitro group. The stability it provides will slightly decrease acidity. Resonance structures A, B and C are comparable to those in the phenol itself and thus would not be expected to affect acidity. But note the + to – attraction here

17. Now look at the anion. What does the nitro group do? Remember we are interested to compare with the phenol phenolate equilibrium. In these resonance structures charge is not created. Thus these structures are important and increase acidity. They account for the acidity of all phenols. Structure D occurs only due to the nitro group. It increases acidity. The greater amount of significant resonance in the anion accounts for the nitro increasing the acidity. Resonance structures A, B and C are comparable to those in the phenolate anion itself and thus would not be expected to affect acidity. But note the + to – attraction here

18. Carboxylic Acid Structure • The functional group of a carboxylic acid is a carboxyl group. • The general formula for an aliphatic carboxylic acid is RCOOH; that for an aromatic carboxylic acid is ArCOOH.

19. Nomenclature - IUPAC • IUPAC names: drop the -e from the parent alkane and add the suffix -oic acid. • If the compound contains a carbon-carbon double bond, change the infix -an- to -en-.

20. Nomenclature - IUPAC • The carboxyl group takes precedence over most other functional groups.

21. Nomenclature - IUPAC • Dicarboxylic acids: add the suffix -dioic acid to the name of the parent alkane containing both carboxyl groups.

22. Nomenclature - IUPAC • If the carboxyl group is bonded to a ring, name the ring compound and add the suffix -carboxylic acid. • Benzoic acid is the simplest aromatic carboxylic acid. • Use numbers to show the location of substituents.

23. Nomenclature-Common • When common names are used, the letters etc. are often used to locate substituents.

24. Physical Properties • In the liquid and solid states, carboxylic acids are associated by hydrogen bonding into dimeric structures.

25. Physical Properties • Carboxylic acids have significantly higher boiling points than other types of organic compounds of comparable molecular weight. • They are polar compounds and form very strong intermolecular hydrogen bonds. • Carboxylic acids are more soluble in water than alcohols, ethers, aldehydes, and ketones of comparable molecular weight. • They form hydrogen bonds with water molecules through both their C=O and OH groups.

26. Physical Properties • Table 17.2

27. Physical Properties • Water solubility decreases as the relative size of the hydrophobic portion of the molecule increases.

28. Acidity • Carboxylic acids are weak acids. • Values of pKa for most aliphatic and aromatic carboxylic acids fall within the range 4 to 5. • The greater acidity of carboxylic acids relative to alcohols (both compounds that contain an OH group) is due to resonance stabilization of the carboxylate anion.

29. Acidity • Electron-withdrawing substituents near the carboxyl group increase acidity through their inductive effect.

30. Acidity • The form of a carboxylic acid present in aqueous solution depends on the pH of the solution.

31. Reaction with Bases • Carboxylic acids, whether soluble or insoluble in water, react with NaOH, KOH, and other strong bases to give water-soluble salts. • They also form water-soluble salts with ammonia and amines.

32. Reaction with Bases • Carboxylic acids react with sodium bicarbonate and sodium carbonate to form water-soluble salts and carbonic acid. • Carbonic acid, in turn, breaks down to carbon dioxide and water.

33. Reaction with bases • The acid-base properties of carboxylic acids allow an easy separation of carboxylic acids from water-insoluble nonacidic compounds.

34. Preparation • Carbonation of Grignard reagents • Treatment of a Grignard reagent with carbon dioxide followed by acidification gives a carboxylic acid.

35. Oxidation Primary alcohol Na2Cr2O7 Na2Cr2O7 RCH2OH RCH=O RCO2H Na2Cr2O7 (orange)  Cr3+ (green) Actual reagent is H2CrO4, chromic acid. Secondary Na2Cr2O7 KMnO4 (basic) can also be used. MnO2 is produced. R2CHOH R2C=O Tertiary The failure of an attempted oxidation (no color change) is evidence for a tertiary alcohol. R3COH NR

36. Oxidation: Aldehyde  Carboxylic Recall from the discussion of alcohols. Milder oxidizing reagents can also be used Tollens Reagent test for aldehydes

37. Haloform Reaction, overall The last step which produces the haloform, HCX3 only occurs if there is an a methyl group, a methyl directly attached to the carbonyl. a methyl If done with iodine then the formation of iodoform, HCI3, a bright yellow precipitate, is a test for an a methyl group (iodoform test).

38. Example…

39. Oxidation using PCC Primary alcohol Stops here, is not oxidized to carboxylic acid PCC RCH2OH RCH=O Secondary PCC R2CHOH R2C=O

40. Periodic Acid Oxidation

41. Hydrolysis of Nitriles, RCN Work on mechanism of hydrolysis

42. Methanol to Acetic Acid • Acetic acid is synthesized by carbonylation of methanol. • The carbonylation is exothermic. • The Monsanto process uses a soluble rhodium(III) salt and HI to catalyze the reaction.

43. Mechanism for Monsanto Process: methanol to acetic acid. Reactant Product Complicated process. Let’s look in some detail.

44. Mechanism for Monsanto Process: methanol to acetic acid. • Tetra coordinate complex • Iodide negative, CO neutral. Thus Rh(I) First. Look at the Rh complexes • Hexa coordinate complex • Iodide negative, CO neutral, CH3CO negative. Thus Rh(III). • Hexa coordinate complex • Iodide negative, CO neutral, CH3 negative. Thus Rh(III). Rh oxidized. • Penta coordinate complex • Iodide negative, CO neutral, CH3CO negative. Thus Rh(III).

45. Some Inorganic Chemistry: Oxidative addition-reductive elimination Vaska’s compound - - Ox. Addn Reduc. Elim. Very important in activation of hydrogen

46. Insertion-deinsertion Very important in catalytic C-C bond forming reactions (polymerization, hydroformylation) Also known as migratory insertion for mechanistic reasons

47. Mechanism for Monsanto Process: methanol to acetic acid. Second: Look at the reactions • Tetra coordinate complex • Rh(I) Reductive Elimination. Oxidative Addition. • Hexa coordinate complex • Rh(III). • Hexa coordinate complex • Rh(III). • Rh(III). Insertion Reaction, Migratory Insertion

48. Reduction of Carboxylic Acids • The carboxyl group is very resistant to reduction. • It is not affected by catalytic hydrogenation under conditions that easily reduce aldehydes and ketones to alcohols, and reduce alkenes and alkynes to alkanes. Nor is it reduced by NaBH4. • Lithium aluminum hydride reduces a carboxyl group to a 1° alcohol. • reduction is carried out in diethyl ether, THF, or other nonreactive, aprotic solvent.

49. Selective Reduction • Carboxyl groups are not affected by catalytic reduction under conditions that reduce aldehydes and ketones. • Nor are carboxyl groups reduced by NaBH4.

50. Fischer Esterification • Esters can be prepared by treating a carboxylic acid with an alcohol in the presence of an acid catalyst, commonly H2SO4, ArSO3H, or gaseous HCl.