Organic Chemistry Problem Solving: Carbon Intermediate Types

1. CH105.2Part 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… SN1 and E1 • Key step in both: formation of carbocation • SN1: 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 • X2 addition; halohydrin formation; oxymercuration

8. Carbocations in reactions… Addition to Alkenes • Variations of carbocation formation: 4-membered ring transition state (Henson, pakidrawingnalang, hindikoalampaanosachemsketch 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… • SN2 with CN- as nucleophile • Nucleophilic aromatic substitution • Carbanion intermediate formed: Meisenheimer complex • Grignard reagent • + H2O = alkane • + aldehyde, ketone, ester = alcohol • + RCΞN = ketone

14. Carbanions in reactions… • Gilman reagent (diorganocopper lithium) R2CuLi + 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 (Br2, PBr3) • If 2nd step is H2O = α-brominated carboxylic acid • If 2nd step is ROH = α-brominated ester • If 2nd step is excess NH3 = α-amino acid

16. Carbanions in reactions… • Carbonyl α-substitution reactions • Common reactions: • Alkylation of α-position • Direct alkylation (SN2 with CH3I) • 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• + CO2

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