Chapter 7 Carbanions and Other Nucleophilic Carbon Species

1. Chapter 7 Carbanions and Other Nucleophilic Carbon Species

2. 7.1 Acidity of Hydrocarbons Determination of the relative acidity of most carbon acids is more difficult, because they are so weak acids. Very weakly acidic solvents such as DMSO and cyclohexyl amine are use as solvent for carbanion generation. Basicity constant H_: The basicity of base-solvent system. (Analogous to the Hammett acidity function HO. The value of H_corresponds essentially to the pH of strongly basic non-aqueous solutions. The larger values of H_, the greater is the proton abstracting ability of the medium. Advanced Organic Chemistry (Chapter 7) sh.Javanshir

3. Assignment of H_ to base-solvent system: Use of a series of overlapping indicators. Advanced Organic Chemistry (Chapter 7) sh.Javanshir

4. Determination the acidity (pK values) of hydrocarbon at a known H_ : If the electronic spectra of the neutral and anionic forms are sufficiently different, the concentrations of each can be determined directly. Advanced Organic Chemistry (Chapter 7) sh.Javanshir

5. If the electronic spectra of the neutral and anionic forms are not sufficiently different, one of the indicators used and its spectrum is monitored. Thermodynamic Acidity:Acidity of hydrocarbons in terms of the relative stabilities of neutral and anionic forms. In many cases it is not possible to obtain equilibrium data.

6. kinetic Acidity: Rate of deprotonation of hydrocarbons. Isotopic Exchange: In the presence of a source of deuterons, the rate of incorporation of D atom into an organic molecule is a measure of the rate of carbanion formation: There is often a correlation between the kinetic acidity and thermodynamic acidity.

7. Advantage of kinetic measurements: Not requiring the presence of a measurable concentration of the carbanion at any time. The relative ease of carbanion formation is judged from the rate at which exchange occurs. This method is therefore is applicable to very weak acids. disadvantage of kinetic measurements: complication due to the fate of the ion pair that is formed. If the ion pair separates and diffuses into the solution rapidly, so that each deprotonation result in exchange, the exchange rate is an accurate measure in exchange.

8. Basis for Using Kinetic Acidity Data Under many conditions, an ion pair may return to reactant at a rate exceeding protonation of carbanion by the solvent (internal return) and exchange has not been resulted. An evidence for occurring internal return: Racemization without Exchange at Chiral Center

9. Extent of Ion Pair or Dissociated Forms Solvent Polarity: Ion pairing is greatest in no-polar solvents such as ethers. In dipolar solvents , such as DMSO, dissociated forms are predominant. Structure: The identity of the cation present have significant effect if ion pairs are present.

10. The rate of tritium exchange (kinetic acidity) for a series of related hydrocarbons is linearly related to the equilibrium acidities of these hydrocarbons in the solvent system. e.g. Ph3CH > Ph2CH2 > PhCH3

11. Allylic Conjugation:

12. sp2 Hydrogens of benzene and Ethylene Ph-H (Benzene): pK = 43 Estimated on the basis of extrapolation from a series fluorobenzenes. Ethylene: pK = 46 Estimated by electrochemical methods.

13. Saturated Hydrocarbons: Exchange is too slow and direct determination of the pK values is not feasible. Measurement of the electrochemical potential for the reaction: From this value and known C-H bond dissociation energies, pK values can be estimated (semi quantitative method). Isobutane: pK = 71

14. sp Hydrogens in Acetylenes The relative high acidity of acetylenes associated with the large degree of s character (50%) of C-H bond. The sp orbital is more electronegative than sp2 and sp3.

15. Ab initio calculations: CH3- and Et- have pyramidal shape. The optimum bond angle of H-C-H is 97-100°. Carbanions are predicted to be pyramidal. In planar carbanion, the LP would occupy a p orbital. In pyramidal geometry, the orbital would have substantial s character. Since, the LP would be of lower energy in an orbital with some s character.

16. Stereochemistry of H-Exchange Low dielectric constant solvents: Retention of configuration. Increasing the amount of inversion with increasing the proton-donating ability and dielectric constant of the solvent.

17. Base: t-BuOK Solvent: Benzene 93% net retention of configuration Short lifetime for the carbanion in a tight ion pair. Carbanion does not symmetrically solvated before protonation by H-B or ketone. Base: KOH Solvent: Ethylene Glycol 48% net inversion of configuration Solvent is a good proton source and the protonation must be occurring on an unsymmetrically solvated species that favor back-side protonation.

18. Base: t-BuOK Solvent: DMSO 100% Racemization Sufficient lifetime for the carbanion to become symmetrically solvated.

19. The Stereochemistry of H-D exchange in 2-phenyl butane: Base: t-BuOK Solvent: t-BuOH retention of configuration Ion pair formation in which a solvent molecule coordinated to the metal ion acts as the proton donor. Base: t-BuOK Solvent: DMSO Racemization Symmetrical salvation is achieved prior to deuteration.

21. The most preparative method of organo lithium compounds: Although these compounds have some covalent character, but they react as would be expected of the carbanions derived from simple hydrocarbons.

22. The order of basicity and reactivity in H-abstraction: CH3Li > n-BuLi > t-BuLi Deprotonation of Ph-CH3 by t-BuLi is thermodynamically favor, but the reaction is quite slow in hydrocarbon as solvent. Organo lithiums exist as tetramer, hexamer and higher aggregation in hydrocarbons and other solvents. These species can be studied by low temperature NMR spectroscopy.

23. Increasing the reactivity of organo lithiums PhLi is tetrameric in 1:2 ether - cyclohexane, but dimeric in 1:9 TMEDA - cyclohexane.

26. 7.2 Carbanion Stabilized by Functional Groups Negative charge delocalization by functional groups to more electronegative element cause stabilization of the carbanion and increases the C-H bond acidity. Order for anion stabilization: NO2 > C=O > CO2R ≈ SO2 ≈ CN > CONR2

27. Both dipolar and resonance effects are involved:

28. Enolate Ions

29. Measuring the kinetic Acidity of C=O Compounds: Measuring the rate of halogenation of C=O compounds.

30. Rate of Deprotonation: Isotope exchange using D or T

32. Rate of deuteration of simple alkyl ketones: CH3 > RCH2 > R2CH Steric hindrance to the approach of the base is probably the major factor. Structural Effects on The Rate of Deprotonation Very strong bases such as LDA or HMDS in polar aprotic solvents such sc DME or THF gives solutions of the enolates whose composition reflect the rate of removal of the different protons in the unsymmetrical C=O compounds (kinetic control). The least hindered proton is removed most rapidly under these conditions. For unsymmetrical ketones the kinetic product is less substituted one.

33. Thermodynamic Control: Establishing the equilibrium between the various enolates of a ketone and formation the more stable enolate highly substituted. Ideal conditions for kinetic control of enolates formation are those in which deprotonation is rapid, quantitative, and irreversible. Experimentally: a) Using very strong base such as LDA b) Aprotic solvent c) Absence of excess ketone d) Low temperature

36. Kinetic and Thermodynamic Acidity in Nitroalkanes show opposite responses to alkyl substitution.

37. Umpolung Reactions: Formal reversal of the normal polarity of a functional group. Conjugate base of 1,3-dithiane (pK=31 in cyclohexyl amine): a) Negative charge delocalization involving 3d orbitals. b) MOT:Negative charge delocalization involving s* orbital of C-S bond.

38. Carbanion Derived from Sulfoxides

39. Phosphorous and Sulfur Ylides Ylides: Molecules for which one of the contributing structures has opposite charges on adjacent atoms when the atoms have octet of electrons.

40. Formation of Ylides Deprotonation of onium salts:

41. The stability of the resulting species is increased by substituents groups that can help to stabilize the electron-rich carbon. In the absence of any stabilizing group, the onium salts are much less acidic and strong bases such as amide ion is required. The addition of O atom in the sulfoxonium salts stabilizes these ylides considerably relative to the sulfonium ylides.

43. 7.3 Enols and Enamines Carbonyl compounds as nucleophile in acidic media: Enol form: Enols are not as reactive as enolate ions.

44. Enolization Mechanism: Isotope Exchange kH / kD ≈ 5 Measuring The Rate of Enolization: Halogenation

45. In contrast with base catalyzed removal of proton, the acid catalyzed enolization to result in preferential formation of the more substituted enol.

46. The amount of enol present in equilibrium with a C=O group is influenced by other substituents groups. In single ketones, aldehydes, or esters, there is very little of the enol present at equilibrium.

48. Effect of Solvent on the Extent of Enol Form Ethyl acetoacetate: The strong intramolecular H-bond in the enol form minimize the molecular dipole by reducing the negative charge on the oxygen of the C=O group. In the more polar solvents is less important, and in protic solvent such as water, H-bonding by the solvent is dominant.

49. Generation of Enols of Simple Ketones in high Concentration: Metastable species NMR: Half life at -20 °C is several hours Half life at +20 °C is 10 minutes In DMSO and DMF, in which the rate of exchange by H-binding is slow, metastable enols have increased lifetime.

50. Generation of Enols of Simple Ketones in Water: Addition of enolate solution to water: The initial protonation takes place on O atom, generating the enol form. Ketonization rate depends on pH. Acid Catalyzed Ketonization: C-protonation concerted with O-deprotination (General acid catalysis) Base-catalyzed Ketonization: C-protonation of the enolate