1. Radical Substitution on Alkanes. 2. Radical Substitution with Alkenes. 3. Electrophilic Addition

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1 1. Radical Substitution on Alkanes Only Cl and Br are useful at the laboratory level. Alkane reactivity: tertiary > secondary > primary > methyl Numbers below products give their relative yield. Relative yield is derived by multiplying number of hydrogens to replace by selectivity factor: Br Cl F Radical Substitution with Alkenes Benzene cannot be substituted under normal conditions. However, it does stabilize radical positions: Reacting an alkene with Br 2 /uv results in electrophilic addition instead of radical substitution: 3. Electrophilic Addition 4. Radical Substitution with NBS (N-bromosuccinimide) NBS is a source of radical bromides that do not undergo an electrophilic addition.

2 5. Electrophilic Addition of Bromide Addition is anti because there is a halonium intermediate 6. Electrophilic Conjugate (1, 4) addition Addition to a conjugated system produces a stable carbocation that can move around. In the presence of heat, the intermediate is long lived enough to form the most stable (most substituted) alkene. 7. Electrophilic Direct (1, 2) addition 8. Halohydration of Alkenes 9. Halogenation of Alkynes Anti-addition due to formation of cyclic halonium ion.

3 10. Reaction of Alkyne with 1 equivalent of hydrogen halide Both cis and trans are formed. Regioselectivity of reaction is Markovnikov for the Br. With excess HBr, the germinal dihalide is produced. 11. Radical Halogenation of Alkynes The presence of HBr and peroxides causes anti-markovnikov regioselectivity. If there is an excess of HBr with peroxides, the vicinal dihalide is produced. Note that reacting the haloalkene with HBr produces a vicinal dihalide also. Reactions of Alkenes with Hydrogen Halides Reaction proceeds through a carbocation intermediate. Rearrangement is possible. Addition of halide follows Markovnikov s rule and reactivity is HI > HBr > HCl > HF (parallels acidity). HBr reaction is usually performed in the dark to avoid radical reaction. Probability of most carbocation rearrangements can be lowered by dropping the temperature.

4 12. E 2 Elimination The Br and H must be anti (molecule MUST rotate) for reaction to occur properly. The stereochemistry of the conformation wherein Br and H are anti defines whether the final product is cis/trans, etc. Larger alkoxides prefer elimination of a less sterically hindered H. The larger the alkoxide, the greater the proportion of anti-zaitsev product. 13. Forming an Alkyne through Elimination *I would expect a diene in the above scenario but I m checking some references. The chem 351 e-text specifies an alkyne is formed so go with that for now. 14. Hydration of Alkenes - Acids With the addition of acid, a carbocation is formed. The presence of a nucleophile (such as water or an alcohol) produces an alcohol or ether. Carbocation reaction is prone to rearrangement. Probability of most carbocation rearrangements can be lowered by dropping the temperature. Regioselectivity is Markovnikov.

5 15. Hydration of Alkenes Oxymercuration-Demercuration Regioselectivity is Markovnikov because of a cyclic mercury adduct. 16. Hydration of Alkenes Hydroboration Regioselectivity is Anti-Markovnikov because of a cyclic addition of B-H across the alkene. Note that 9-BBN is more selective than BH 3 /B 2 H 6 for anti-markovnikov product. 17. Forming Ethers - Using Acids With the addition of acid, a carbocation is formed. The presence of a nucleophile (such as water or an alcohol) produces an alcohol or ether. Carbocation reaction is prone to rearrangement. Probability of most carbocation rearrangements can be lowered by dropping the temperature. Regioselectivity is Markovnikov. 18. Forming Ethers Oxymercuration-Demercuration Regioselectivity is Markovnikov because of a cyclic mercury adduct. 19. Forming Ethers Hydroboration

6 20. Hydration of Alkynes Using H 3 O +, typically with Mercury A Markovnikov enol is formed and rapidly tautomerizes to a ketone. 21. Hydration of Alkynes Hydroboration An anti-markovnikov enol is formed and tautomerizes to an aldehyde. 22. Hydroxylation of Alkenes Syn addition. 23. Formation of an epoxide 24. Forming a syn-diol through Epoxide Ring-opening The nucleophile (OH- or H3O+) attacks from behind and an anti-diol is formed.

7 25. Other Reactions of Epoxides Under acidic conditions, a nucleophile adds on the more substituted site that can support a more stable carbocation. Examples of acidic conditions include NH 4 +, HCN, etc. Under basic conditions (neutral or anionic), the nucleophile attacks the least hindered (least substituted) side of the epoxide. Examples include NaOEt, RMgBr, RLi, NH 3 etc. 26. Reaction of Alcohols with other Halogenating agents Reaction follows SN 2 mechanism with inversion of stereochemistry on 1 and 2 substrates. Can occur (but is rare) on tertiary substrates. 27. E 1 Elimination of Alcohols Formation of a carbocation means a 1,2-hydride shift is likely. 1,2-methyl shifts can also occur. Concentrated sulfuric acid can cause double bonds to shift and the molecule to rearrange to a more thermodynamically stable state.

8 28. Hydrogenation of Alkenes and Alkynes Lindlar s catalyst turns alkynes into cis alkenes. Ammonia and sodium metal turn alkynes into trans alkenes. Remaining reactions are found in slides 48-60: Grignard Diels Alder cyclization Ozonolysis Oxidation and Reduction Formation of Cyclopropanes And perhaps nucleophilic attack of alkyl halides with a deprotonated alkyne. They are actually quite concise and well summarized in those slides (had I a couple more hours I would add them but its 1:40 am on 6/03/2017 and I d rather get this out sooner than later)