1 YSU YSU YSU YSU 2 YSU YSU YSU YSU 3 Completely - PDF document

H C H H H H ~1800 – Organic Chemistry : the chemistry of natural products based on carbon 2010 – Organic Chemistry : “molecular engineering” YSU YSU 12 Reactions of benzene – electrophilic aromatic substitution 13 Spectroscopy – how do you know what the structure is? 14 C-C bond formation using organometallic compounds 15 Chemistry of alcohols, diols and thiols 16 Chemistry of ethers, epoxides and sulfides 17 Aldehydes and ketones – preparation and uses 18 18 Enols and enolates in the formation of C-C bonds Enols and enolates in the formation of C C bonds 19 Carboxylic acids – preparation and uses 20 Nucleophilic acyl substitution 21 Ester enolates – formation and uses in C-C bond formation 22 Chemistry of amines 25 Overview of carbohydrate chemistry 26 Overview of lipid chemistry YSU YSU 27 Overview of amino acid, peptide and protein chemistry 1

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Completely delocalized (6) pi system lends stability ( aromatic ) YSU YSU YSU YSU 4

Alkenes react by addition YSU YSU Benzene reacts by substitution Resonance-stabilized cation YSU YSU 5

Energy diagram for EAS in benzene Figure 12.1 YSU YSU 12.3 Nitration 12.4 Sulfonation H Br Br 2 , Fe 12.5 Halogenation YSU YSU 6

Problems: Alkyl groups may rearrange during reaction Products are more reactive than benzene Uses: Alkyl benzenes readily oxidized to benzoic acids using KMnO 4 YSU YSU CH 3 H C CH 3 (CH 3 ) 3 CCl CH 3 AlCl 3 H 3 C CH 3 Cl H C CH 3 CH 3 CH 3 AlCl 3 YSU YSU 7

Products react more slowly than benzene - cleaner reaction YSU YSU No carbocation rearrangements Make the acyl benzene first (clean, high yielding reaction) Reduce the ketone group down to the methylene (C=O to CH 2 ) Avoids rearrangement problems, better yields YSU YSU 8

Make the acyl benzene first (clean, high yielding reaction) Reduce the ketone group down to the methylene (C=O to CH 2 ) Intermolecular and intramolecular variants both useful YSU YSU Make the nitro benzene first, clean high yielding reaction Reduce the nitro group down to the amine YSU YSU Difficult to introduce the amino group by other methods 9

YSU YSU Relative rates in nitration reaction; now bringing in a second substituent CH 3 is said to be an ortho / para director ( o / p director) - Regioselectivity YSU YSU 10

CF 3 CF 3 CF 3 CF 3 HNO 3 , H 2 SO 4 NO 2 + + NO 2 NO 2 6% 91% 3% CF 3 is said to be a meta director ( m director) - Regioselectivity YSU YSU Fig. 12.5 – Energy diagrams for toluene nitration (vs. benzene) YSU YSU 11

Fig. 12.6 – Energy diagrams for CF 3 C 6 H 5 nitration (vs. benzene) YSU YSU Definitions: Activating = reacts faster than benzene in EAS Deactivating = reacts slower than benzene in EAS In General : all activating groups are o / p directors g g p p halogens are slightly deactivating but are o / p directors strongly deactivating groups are m directors Typical: -OH, -NO 2 , -NH 2 , -Br, -Cl, -CH 3 , -CO 2 H, -COCH 3 YSU YSU 12

O RO RCO R HO alkyl hydroxyl alkoxy acyloxy OCH 3 OCH 3 OCH 3 Example: HNO 3 , H 2 SO 4 NO 2 + NO 2 Alkyl groups stabilize carbocation by hyperconjugation YSU YSU Lone pairs on O (and others like N) stabilize by resonance YSU YSU 13

Second substituent goes meta by default – best carbocation Carbocations for o/p processes destabilized YSU YSU Reactivity (i.e. rate) is a balance between inductive effect (EW) and resonance effect (ED) – larger Cl, Br, I do not push lone pair into pi system as well as F, O, N, which are all first row (2p) YSU YSU 14

Regioselectivity - second substituent goes o/p – better carbocations o / p processes stabilized by lone pairs YSU YSU CH 3 O NHCH 3 CH 3 NHCH 3 O O Br 2 , acetic acid Br H 3 C O CH 3 CH 3 AlCl 3 CH 3 Cl CH 3 Cl 99% 99% 87% 87% CH 3 CH 3 CH 3 CH 3 Br NO 2 Br 2 , Fe HNO 3 , H 2 SO 4 NO 2 C(CH 3 ) 3 NO 2 C(CH 3 ) 3 YSU YSU 86% 88% 15

Have to be careful about when to introduce each substituent YSU YSU Remember – isomers (e.g. o / p mixtures) may be separated O CH 3 12.17 Naphthalene O O CH 3 CCl CH 3 but not AlCl 3 90% SO H SO 3 H SO 3 , H 2 SO 4 12.18 Heterocycles HgSO 4 , 230 o C N N O O H 3 C O CH 3 CH 3 O BF 3 O YSU YSU O 16