1. CH105.2 Part 1: Problem Solving in Organic Chemistry Carbon Intermediate Types

2. Before anything else… Remember that organic reactions, no matter how difficult they may seem, simply involve the reaction between positive/partial positive and negative/partial negative sites. After determining these sites, three- dimensional steric considerations come into play. Ok?

3. One way of looking at reactions… What type of intermediate is formed? Carbocation Carbanion Radical Special Intermediate: Benzyne

4. CARBOCATIONS in reactions… Combine with nucleophiles (positive + negative or partial negative) Lose proton (elimination) Rearrangement (more stable carbocation) General observation: mainly (but NOT exclusively) involves alkenes

5. Carbocations in reactions… S N 1 and E1 Key step in both: formation of carbocation S N 1: combine with nucleophile E1: lose proton

6. Carbocations in reactions… Addition to Alkenes Straightforward carbocation formation: hydrogen halide addition

7. Carbocations in reactions… Addition to Alkenes Variations of carbocation formation: cationic 3-membered ring intermediate The more substituted carbon can then be attacked by a nucleophile to form the addition product – X 2 addition; halohydrin formation; oxymercuration

8. Carbocations in reactions… Addition to Alkenes Variations of carbocation formation: 4- membered ring transition state (Henson, pakidrawing nalang, hindi ko alam paano sa chemsketch eh. Haha) HYDROBORATION

9. Carbocations in reactions… Acid catalyzed dehydration of alcohols Electrophilic aromatic substitution

10. Carbocations in reactions… Hydrolysis of tert-butyl esters (vs. usual mechanism) Diazotization – Carbocation may undergo each of the 3 processes

11. Carbocations in reactions… Pinacol rearrangement Acid-catalyzed polymerization of alkenes

12. CARBANIONS in reactions… Acts as base (abstracts proton) Acts as nucleophile (reacts with electrophiles) General observation: involves – Substitution with carbon nucleophiles – Organometallic reagents – Carbonyl chemistry

13. Carbanions in reactions… S N 2 with CN - as nucleophile Nucleophilic aromatic substitution – Carbanion intermediate formed: Meisenheimer complex Grignard reagent – + H 2 O = alkane – + aldehyde, ketone, ester = alcohol – + RCΞN = ketone

14. Carbanions in reactions… Gilman reagent (diorganocopper lithium) R 2 CuLi + R’X → R-R’ 1,2 and 1,4 addition to α,β-unsaturated carbonyls: governed by HARD-HARD/SOFT- SOFT chemistry – Carbonyl, C=O: hard (direct 1,2-addition by hard :Nu) e.g. Grignard reagent – Alkene, C=C: soft (conjugate 1,4-addition by soft :Nu) e.g. Gilman reagent

15. Carbanions in reactions… Carbonyl α-substitution reactions – Usually by aldehydes, ketones, and esters, especially β-DIKETONES and β-KETO ESTERS – Common reactions: Halogenation of α-position – Monohalogenation in acidic medium – Multiple halogenation in basic medium (excess halogen: Haloform reaction occurs) – Hell-Volhard-Zelinski Reaction (Br 2, PBr 3 ) » If 2 nd step is H 2 O = α-brominated carboxylic acid » If 2 nd step is ROH = α-brominated ester » If 2 nd step is excess NH 3 = α-amino acid

16. Carbanions in reactions… Carbonyl α-substitution reactions – Common reactions: Alkylation of α-position – Direct alkylation (S N 2 with CH 3 I) – Malonic and acetoacetic ester synthesis

17. RADICALS in reactions… Combine with another free radical Br + Br → Br–Br Abstract an atom from a molecule RO + H–Br → ROH + Br Add to an unsaturated molecule Decompose into 2 fragments R–COO → R + CO 2

18. Radicals in reactions… Indicators of a radical reaction: – Radical initiators: benzoyl peroxide or AIBN – Heat or light may also initiate radical formation