Reaction Mechanisms (see p. 310) A. Recognizing/Classifying as Radical, Cationic, or Anionic 1. Radical initiation requires both energy (either hv or ) and a weak, breakable bond Cl-Cl, Br-Br, O-O (peroxide), N-Br, etc.. 2 Guides for That are Usually Reliable: hv radical mechanism peroxides radical mechanism 2. Anionic a strong anion/base appears in the recipe no strong should appear in the recipe mechanisms should involve anionic intermediates and reactants, not strongly cationic ones (except for do-nothing spectators like metal cations) The first step in the mechanism will involve the strong anion/base that appears in the recipe 3. Cationic a strong acid/electrophile appears in the recipe no strong anion/base should appear in the recipe mechanisms should involve cationic intermediates and reactants, not strongly anionic ones (except for do-nothing spectators like halide or hydrogen sulfate anions) The first step in the mechanism will involve the acid that appears in the recipe. The last step will often involve a deprotonation step. Often the main step occurs in between the proton-on and proton-off steps B. Miscellaneous Mechanism Tips Keep track of hydrogens on reacting carbons Each step in a mechanism must balance The types of intermediates involved (cation, anion, or radical) should be consistent with the reaction classification above If the reaction is cationic, don’t show anionic intermediates If the reaction is anionic, don’t show cationic intermediates Usually conditions are ionic. Use a reactive species, whether strong or an acid, to start the first step If acidic, first step will involve protonation of the organic If anionic, the step will involve the anion attacking the organic. it isn’t always easy to figure out what is a good mechanism, you should often be able to eliminate an unreasonable mechanism. heteroatom
Summary of Alcohol Syntheses, Ch. 10 (and Review of Old Ones). 1 Potassium (K) analogous. Key way to convert alcohol to alkoxide, reactive as SN2 nucleophile and E2 base. 2 Alkoxide formation-SN2 route to ether The electrophile R'-X must be SN2 reactive, preferably 1º with a good leaving group Mech? 3 -Li is analogous for making RLi, which also act analogously. -MgBr is spectator: R is key. 4 1 carbon extension Mech 5 Mech 6 All three R groups can be different. Mech 7 At least 2 R groups must be the same Mech 8 2-Carbon chain extension Mech 9 Mech 10 Mech 11 NaBH4 will not react with esters Mech Review Routes to Alcohols 10 11
the “Oxygen Zones” for Oxygenated Systems 220-160 Zone 100-50 Zone One-Oxygen Formulas Ketone, Aldehyde 180-220 Alcohol One Two Two-Oxygen Formulas Acid 180-220 160-180 One Aldehyde/Ketone And Alcohol 180-220 One Aldehyde/Ketone And Ether 180-220 Two Splitting in a coupled carbon NMR spectrum. C13 NMR’s are normally acquired as “decoupled” spectra, in which each carbon signal appears as a singlet, for reasons of speed and simplicity. However, at the cost of extra time and at the expense of some simplicity, it is also possible to get “coupled” C13 NMR’s with splitting. The C-13 atoms are split by directly attached hydrogens. These splitting values are very useful, and follow the N+1/N-1 rules (the number of lines is one greater than the number of attached H’s). Quartert (q) CH3 Triplet (t) CH2 Doublet (d) CH Singlet (s) C (no attached hydrogens) Coupled C-13 has at last two drawbacks: The signal to noise ratio and thus the sensitivity is a lot worse. Overlap: With coupled C-13 NMR, there are a lot more lines, and overlapping of lines becomes normal and confusing for non- simple molecules. Aromatics, Symmetry, Splitting. Most aromatics have symmetry, and both the number of aromatic lines and the splitting of the aromatic lines can be indicative of the substitution pattern on a benzene. Mono- and para-disubstituted benzenes have symmetry. 4 lines s, d, d, d Monosubstituted benzene. (Has symmetry) 4 s, s, d, d Para-disubstituted benzene. (Has symmetry) 6 lines s, s, d, d, d, d Ortho- or meta-disubstituted benzene. (Has no symmetry) Signal Height/Size Unlike 1H-NMR, where integration is really important, signal size is not very important in C-13 NMR.
Synthesis of Ketones and Aldehydes 1 11.2 2 11.2 3 8.7 4 8.4 5 8.15 6 10.9 7 10.11 8 6.8 9 6.8 10 9.9F 11 9.9F 12 18.9 13 18.11 14 18.11 15 18.10 16 18.10 Reactions of Ketones and Aldehydes 19 Anionic Mech: Addition-Protonation. Strong nucleophile, Strongly anionic. Irreversible. 18.12, 10.9
Anionic Conditions (when a strong is involved) General principles review for strongly anionic/basic conditions apply In an anionic mechanism, a strong anion will drive the first step In an anionic mechanism, intermediates should positive charges Recognize anionic species even when they are disguised by a cationic metal counterion. Anionic additions to ketones Strong nucleophile required (R, H, HO, …) Intermediates have negative charge Addition first, protonation second Cationic Conditions (acid is involved) General principles review for acid/cartionic conditions apply Recipes that involve acid will be cationic In a cationic mechanism, the first step will routinely involve protonation In a cationic mechanism, the last step will frequently involve deprotonation to return to neutral Normally the main step or steps are sandwiched in between the protonation and deprotonation events Cationic additions to ketones Weak, neutral nucleophile involved (ROH, HOH…) Intermediates have positive charge Protonation addition second Weak nucleophile is not strong enough to add to neutral carbonyl Protonation activates the carbonyl as an electrophile A deprotonation step is routinely required following addition, to get back to neutral Addition is normally reversible Nucleophile can come back off Nucleophile is normally a reasonable leaving Buffer Conditions (both weak acid and weak base/nucleophile are present at same time) RNH2/H+, KCN/HCN… Reversibility again applies Whether addition before protonation, or protonation precedes addition depends on the exact case Anion Conditions: Nucleophilic addition versus deprotonation (enolate chemistry) Sometimes an will function as a base and remove a proton rather than functioning as a nucleophile and adding to the carbonyl Comparable to SN2 versus E2 reactions