Primary amines lead to carbocations Chapter 22 Benzene Substituents Radical Halogenation Solvolysis SN1 SN2 Acidity of Benzylic Hs Oxidation selective benzylic oxidation of OHs Reduction of the Benzylic Carbon Benzyl Ethers as Protecting Groups Nucleophilic Aromatic Substitution NAS NO2 is a strong deactivating group and electron withdrawing this reaction will not go through SN2 because there is no backside attack available and it will not go through SN1 because the ring is very high in energy would go by addition elimination mechanism Rate of Formation F 312 small and electronegative Cl 1 0 Br 0 8 I 0 4 best LG NAS Benzyne elimination addition do not need electron withdrawing groups need very extreme conditions for reaction to occur Aryl Diazonium Ions mechanism nitrosyl cation formation see above Diazonium Ions as Electrohphiles in EAS Reactions mechanism Acidic Cleavage of Aryl Ethers mechanism Formation of Ethers mechanism Phenols as Nucleophiles in EAS phenol is a strong activator sometimes can observe multiple additions of electrophile Base Mediated Substitution Claisen Rearrangement mechanism Cope Rearrangement Radical Oxidation of Phenols makes benzoquinone Reactions of Benzoquinones Biological Reactions certain vitamins can stabilize free radicals all has to do witty resonance Chapter 25 Heterocycles Common Names to Memorize Reactivity of Nonaromatic Heterocycles 5 membered rings are unreactive towards nucleophiles and are usually used as bases and solvents 3 and 4 membered rings undergo ring opening ring strain drives this reaction Nuc attacks least substituted side bc of sterics and basic conditions Nuc attacks more substituted side bc of acidic conditions Properties of 5 Membered Aromatic Heterocycles only one lone pair counts towards aromaticity more electronegative atoms are less aromatic S N O other heteroatoms in the ring do not contribute to resonance Neutral sp2 lone pairs do NOT contribute to resonance Neutral sp3 lone pairs DO contribute to resonance Paul Knorr Synthesis Conditions X R NH2 N R P2O5 O P2S5 S Example EAS Analogs C2 Substitution mechanism attack at C2 produces three resonance structures with the last being the most stable as it has all octets attack at C3 produces two resonance structures again with the last being most stables as it has all octets the attack at C2 is the major product because it produces more resonance structures than attack at C3 making it the most stable Rates of Reaction Benzene S O N Indole will attack at C3 will attack at C3 because the aromaticity of benzene is retained however attack at C2 would destroy the aromaticity of the benzene ring this is why indole attacks at C3 Acidity and Basicity Pyrrole is a weak base Pyrrole is a good acid the nitrogen on pyrrole is considered to be sp3 sp2 because it can resonate between the two forms H Hydrolysis of Furan Desulfurization of Thiopene Diels Alder of Furan furan is least aromatic because O is the most electronegative Aromaticity of Pyridine lone pairs are NOT part of the pi system The Hantzch Pyridine Synthesis condensation of ammonia an aldehyde and 2 beta dicarbonyls the pink circles indicate the 6 atoms that make up the ring the arrows show where the substituents came from respectively Reactions of Pyridine pyridine is electron poor EAS is slow and di cult and occur at C3 addition of electron donating groups make it a better electrophile Why C3 C3 intermediate will NOT put a on N Pyridines undergo easy NArS reactions at C2 and C4 puts on N Chichibabin mechanism with alkyl anions Good LGs make for faster reactions must be at C2 and C4 position Quinolines and Isoquinolines EAS Reaction occurs on benzene position NArS work well attack at C5 and C8 due to stability of intermediates see chapter 16 for review Alkaloids Chapter 24 Carbohydrates Cn H2O n D and L Sugars D OH is on the right L OH is on the left D Sugar Series 14 total sugars Sugars from Cyclic Hemiacetals Hawthorn Projection Chair Conformations C1 is called anorexic C MutaRotation of Glucose Oxidation of COOH Oxidative Cleavage Reduction Glycosides ester and ether derivatives of sugar Acetal Protecting Groups Building Sugars Kiliani Fischer Synthesis cyanohydrin R H3O Degrading Sugars Ru or Wohl Degradation Determination of Structure by Synthetic Modi cation Disaccharides 2 sugars are linked via an acetal Polysaccharides sugar polymers Chapter 26 Amino Acids and Peptides Natural Amino Acids are 2 amino COOHs about 20 essential amino acids 500 known Acidity and Basicity amino acids exist as zwitterions have two opposite charges in the same molecule pH dependent isoelectric point pI zwitterion max Synthesis of Racemic AAs HVZ Adapted Gabriel Synthesis Streaker Synthesis Synthesis of Enantiomerically Pure AAs resolution of rac AAs asymmetric hydrogenation Polypeptides