Chapter 09 Benzene and Its Derivatives Benzene First isolated in 1825 from whale oil by Michael Faraday Unsaturated hydrocarbon but did not have the typical reactivity of alkenes or alkynes. CM 240: Fall 2016 Prof. Greg Cook 2 C 6 6 or KMn 4 no reaction prismane Dewar benzene 2 Benzene In 1865 Kekulé proposed a structure having a sixmembered ring with alternating double bonds. 1.54 Å 1.34 Å Aromatic eactivity 2 T formed Kekulé structures 2 Fe 3 catalyst bonds identical 1.39 Å modern view of benzene's structure fully conjugated SAC - not equilibrium 3 4 Aromatic Stability Aromatic Stability To have aromatic stabilization, a molecule must have three things: A planar ring A fully conjugated pi-system (a p orbital on every atom in the ring) ave 4n2 number of electrons in the pisystem (ückel ule) 5 6
Aromatic Stability Aromatic Compounds C benzaldehyde almond C2 C 3 C 3 AMATIC 6 pi electrons AMATIC 6 pi electrons cinnamaldehyde toluene xylene phenol aniline polyaromatic hydrocarbons (PA's) carcinogens formed from combustion This PA is the main carcinogen found in Tobacco smoke (so quit for goodness sake!) naphthalene cinnamon moth balls S 8 pi electrons estrone 3C C2C 3 sildenafil (viagra) 7 8 Aromatic eterocycles 2 Adenine lone pair in resonance with aromatic pi system Fused Aromatic ings Guanine 2 3C 2 lone pair in resonance with aromatic pi system lone pair in resonance with aromatic pi system Thymine Cytosine 9 10 Aromatic Carbon - Graphite Aromatic Carbon - Graphite 11 C 3 C 3 2 C 3 benzoic acid C AMATIC 4 pi electrons 4 pi electrons AMATIC 2 pi electrons 6 pi electrons 12
aming Aromatic Compounds Aromatic Carbon - other forms carbon nanotubes buckminsterfullerene 13 14 aming Substituted Benzenes aming Substituted Benzenes C 3 C2 2 2 2 paranitrobenzoic acid 2,4,6-trinitrotoluene orthodichlorobenzene or 1,2-dichlorobenzene 2 Ph 4-phenyloctane we often abbreviate phenyl with Ph when we draw structures 4-phenyloctane biphenyl 15 16 xidation and eduction C3 KMn4 C or 2Cr4 lectrophilic Aromatic Substitution KMn4 C Fe 3 or 2Cr4 KMn4 C KMn4 o eaction or 2Cr4 T formed or 2Cr4 benzylic carbon 2 2 Pd/C 2 Pt, ethanol 130 atm 17 18
lectrophilic Aromatic Substitution Chlorination and Iodination Fe 4 - Fe 3 2 Fe 4 e n e r g y ate Determing Step (DS) T formed Fe 3 2 CuI I 2 I 2 I reaction progress 19 20 itration Sulfonation 2 S 4 2 3 S 3 2 S 4 S 3 21 22 Friedel-Crafts Alkylation Limitations of the Friedel-Crafts Alkylation Al 3 Al 3 nly alkyl halides work, not aryl or vinyl halides. Aromatic rings with electron withdrawing groups already on them will not work (-2, -C, - S3, -C, -C2). Aromatic rings with amine groups will not work (-2) because the amine will react with the alkyl halide. 23 24
Friedel-Crafts Acylation Summary of AS 2 Fe 3 2 Fe 3 Al3 2 Fe 3 Fe 4 2 Fe 3 Fe 4 I2 CuI2 I I2 CuI3 I CuI2 3 2S 4 2 2S 4 S3 2S 4 S 3 S 2S 4 S - Al3 Al4 Al3 Al3 Al3 25 Al4 26 Substituent ffects Substituent ffect on eaction ate 2 > relative reactivity ow does affect the reactivity of the benzene ring? ow does affect the ratio of products? > > 1 1000 6x10-8 0.033 Activating lectron Donating Groups Deactivating lectron Withdrawing Groups alkyl 2 S X C 2 S3 27 28 Substituent ffect on egioselectivity lectron Density in the ing 29 30
lectron Donating Groups lectron Withdrawing Groups 2 2 2 ortho addition ortho addition para addition especially stable especially stable para addition meta addition especially Ustable especially Ustable meta addition none especially stable 31 none especially Ustable - the lesser of the evils 32 alogens - deactivating, but o,p-directors? Summary of Substituent ffects Deactivating lectron Withdrawing Groups Activating lectron Donating Groups meta directors ortho, para directors 2 strongest (resonance) strongest (resonance) halogens, while inductively electron withdrawing groups, they can stabilze plus charge through resonance. Thus, they are an exception and are ortho-para directors S 3 C X weak ortho, para directors but deactivating 2 S alkyl weakest (inductive) 33 34 rganic Synthesis Create molecules by design Compare target and starting material Consider reactions that allow you to build molecules - may need to change functional groups along the way etrosynthetic Analysis Work backwards from the product - immediate precursors rganic Synthesis Starting from benzene, how would you synthesize p- C 2 35 36
rganic Synthesis Starting from benzene, how would you synthesize p- C 2 rganic Synthesis Starting from benzene, how would you synthesize p- C 3 2 S 3 36 37 rganic Synthesis Starting from benzene, how would you synthesize p- C 3 2 S 3 37