CHEM 32 - CHAPTER REVIEW…. not everything you need toknow, but at least a summary ofthe beginning of what you needto know….Chapter 14: Delocalized !-SystemsR'RZRR'ZR RZ ZRZRZZRZR+! or Lewis Acid! or Lewis Acid++! or Lewis Acid! or Lewis Acid+R'RZRR'ZR'RZRR'ZR'RZ+! or Lewis Acid+! or Lewis AcidChapter 14: Delocalized !-SystemsChapter 15: Electrophilic Aromatic SubstitutionThe main criteria for aromaticity are:- high chemical stability- preference of substitution over addition reactions- ability to sustain an induced ring current ("NMR!) - meet Hückel' s rule [4n+2]Chapter 15: Electrophilic Aromatic SubstitutionThe mechanism of electrophilic aromatic substitution involves (a) the reaction between the aromatic ring and the electrophile to yield a pentadienyl cation intermediate (the -complex), and, (b) the loss of a proton from the pentadienyl cation to r egenerate the aromatic ring system. Chapter 16: Substituent Effects on Electrophilic Aromatic SubstitutionChapter 16: Substituent Effects on Electrophilic Aromatic Substitution Chapter 17: Aldehydes & KetonesChapter 17: Aldehydes & Ketones Reactant Reagent Intermediate Product R R'O H2O R R'HOOH hydrate “ R”OH, H+ R R'HOOR"hemiacetal R R'R"OOR"acetal/ketal “ HOCH2CH2OH, H+ “ OOR R' “ NaCN, H+ R R'HOCN cyanohydrin “ NaHSO3 R R'HOSO3Nabisulfite adduct “ H2NR” R R'HONHR" R R'NR" imine “ HNR*R” R R'HONR*R" R R'NR*R" enamine “ HONH2 R R'HONHOH R R'NOH oxime “ H2NNHR” R R'HONH-NHR" R R'N-NHR"hydrazone “ Ph3P CR*R" O PPh3RR'R"R* oxaphosphetane R R'R" R* alkene The Baeyer-Villiger reaction converts ketones to esters. Migratory aptitude increases in the series Me < primary alkyl < phenyl, secondary alkyl < tertiary. Chapter 18: Enols & EnonesR2CCOR'HR2C COR'H! carbon atom of enol is nucleophilic; it attacks electrophilic reagentscarbonyl group is electro-philic; nucleophilic reagents add to carbonyl group! proton is relatively acidic (pKa!20); it can be removed by bases -Halogenation. Halogens react with aldehydes and ketones by substitu-tion; An acid catalyst (or base) in-creases the rate of enolization (enolate formation), which is the rate- OOHOBrOBr BrCH3CO2H, Br2 determining step. T he reaction of a methyl ketone with a halogen in base is known as the haloform reaction. Once one of the -H's is replaced by a halogen atom, the remaining H's a re more acidic and are more easily substituted. C,C-bond cleavage is facilitated by the e--withdrawing effect of the halogens. OOBrOBrOBrBrHOOBrBrBrH+NaOH, H2O, Br2Chapter 18: Enols & EnonesRCH2R'OHORR'NaOCH2CH3RCH2R'ORR'NaOCH2CH3RCH2COR'(2 equiv)HOCH2CH3 -H2O HOCH2CH3 OOLiH2OCH3CH2CHOCH2CH3O OHCH2CH3O OLi85%(workup)THF, -78° CLDA OOO(MVK)46%+NaOCH2CH3,CH3CH2OH Chapter 19: Carboxylic AcidsR ClOR OO OR R OR'OR OHOR NH2OR O-Oreactivity>>>>> RO OROR2N NR2OR2N OR'ORO ClOcarbamate/urethaneureacarbonatechloroformateChapter 19: Carboxylic AcidsReagents for the interconversion of carboxylic acid derivatives: R ClO R OO OR R OR'O R OHO R NR2O R OO R-C!N R ClO - R OO R'OH, py H2O R2NH, py H2O, OH- - R OO OR - - R'OH, py H2O R2NH, py H2O, OH- - R OR"O - - R'OH, H+/B- H2O, H3O+ R2NH H2O, OH- - R OHO SOCl2 , -H2O R'OH, H+, - DCC, R2NH OH- - R NR2O - - - H2O, H3O+ - OH-, SOCl2 R OO - R ClO - H3O+ - - - R-C!N - - R'OH, H+,H2O H2O, H+ H2O, H+ OH-, - Chapter 20: Carboxylic Acids & Mass SpectroscopyThe Hofmann rearrangement involves:R NOnitrenes;R-N=C=O, isocyanates, andRHN OHOcarbamic acidsChapter20:CarboxylicAcids &MassSpectroscopyChemistry of carboxylic acid derivatives: R ClO R OO OR R OR"O R OHO R NR2O R OO R-C!N LAH RCH2OH RCH2OH RCH2OH, R”OH RCH2OH RCH2NR2 RCH2OH RCH2NH2 LiAl(Ot-Bu)3H RCHO RCHO [-] A/B - - RCHO$ DIBAL-H RCH2OH RCH2OH RCHO A/B - - RCHO$ Me2CuLi RCOMe - - A/B - - - MeNH2 RCONHMe RCONHMe, RCO2H RCONHMe, R”OH A/B - - - EtOH RCO2Et RCO2Et, RCO2H RCO2Et, R”OH^ RCO2Et^ [-] - [RCO2Et]* H2O RCO2H RCO2H RCO2H, R”OH^ - RCO2H, R2NH^ - RCO2H, R2NH^@ MeCO2H (RCO)O-(COMe) (RCO)O-(COMe), RCO2H - (RCO)O-(COMe)# - A/B - MeMgBr RMe2COH RMe2COH, RCO2H RMe2COH, R”OH A/B - - [-] MeLi RMe2COH RMe2COH RMe2COH, R”OH RCOR’ RMe2COH, R2NH RCOMe RCOMe$ *In the presence of acid and after hydrolysis ; #upon heating; $after hydrolysis; ^with acid; @can be stopped at amide stage. Chapter 21: Amines The Mannich reaction is of ten applied for t he preparation of functionalized amines, both in the lab and in natur e . NCH3OOCH3OOcocaineChapter 21: AminesPreparations of amines: Starting Material Reagent Intermediate Reagent in 2. Step Product R-XNH3R-NH3 X R-NH2R2NHR3NR4N+ X-R-XNKOON-ROOH2NNH2R-NH2R-X NaCN R-CN R-CH2NH2R-X NaN3R-N3R-NH2Ar-NO2H2/Pd or Fe/HClAr-NH2R R'OR R'NR"R R'HNR"R NHOR'RNR"R'R NOR'R"R NH2ONaOBrOH-, H2OR NHOBr R-NH2RX; OHR= prim. or sec. alkyl groupH2, Pd or LAHH2, Pd or LAH-R"-NH2H2, Pd or NaCNBH31. NaH2. R"-XLAH Chapter 22: Chemistry of Benzene SubstituentsElimination-Addition Mechanism: Benzyne is a reactive intermediate in the Dow phenol synthesis and other substitution reactions of haloarenes with strong bases. The presence of short-lived benzyne is implied by the scrambling of the isotope labels obs erved in reactions with labeled compounds. Alternatively, Diels-Alder reactions can be used to trap benzyne intermediates. BrKNH2benzyneKNH2NH2+NH21 : 1 In arenes with strong electron-withdrawing substituents, substitution occurs via an Addition-Elimination pathway, and a ne gatively charged, relatively stable intermediate (Meisenheimer complex) is formed. XNuN+-O-OMeisenheimer complex Three distinct mechanisms are generally found in nucleophilicaromatic substitution reactions:Chapter 22: Chemistry of Benzene SubstituentsA third route for introducing substituents on arenes with electron-donating substituents is via oxidation to benzoquinones. Subsequent addition of nucleophiles leads to rearomatization. OHOH- 2 e-OONu-OHOHNu Chapter 23: Ester Enolates and Acyl Anion EquivalentsThe Claisen co ndensation is the ester analog of the aldol reaction. Under standard conditions (sodium alkoxide, alkohol), the equilibrium is shifted to the -dicarbonyl compound as a consequence of the irreversible enolization to the highly resonance-stabilized dicarbonyl enolate. OROR'OR'O OR'O ONaOR, HORR'=OR, C+ OEtOTHFOEtOLiPh OEtO OPhCOClLDA, -78 °CChapter 23: Ester Enolates and Acyl