Now all you need to figure out how to turn benzene

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Now all you need to figure out how to turn benzene into a 4-nitro haloaromatic. You only know one method for putting a halide on a benzene ring: electrophilic aromatic halogenation. The 1,4 relationship tells you that, starting from benzene, you need to halogenate first, then use the o/p-directing nature of the halide to direct nitration to the para position. * You could use the industrial synthesis of phenol from benzenesulfonic acid that you saw a a couple times in lecture. This would give you sulfonation/nucleophilic aromatic substitution an alternative to the bromination/nitration/nucleophilic aromatic substitution sequence described here.
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One viable synthetic route (synthetic intermediates not shown) is: Starting with benzene: 1. brominate (Br 2 /FeBr 3 ) to form bromobenzene; 2. nitrate (HNO 3 /H 2 SO 4 ) to form 1-bromo-4-nitrobenzene; 3. heat with HO (nucleophilic aromatic substitution) to replace the bromine with a hydroxyl group, forming 4- nitrophenol; 4. reduce the nitro group (with H 2 /Ni, e.g.) to make 4-aminophenol; 5. acylate with Ac 2 O and heat. Remember that you were not asked to show mechanisms. Problem 2. Start by carefully reading the problem. The problem tells you that olopatadine can be made from a benzophenone intermediate, the structure for which is given. The preparation of this intermediate via a condensation reaction under acidic conditions is shown. The problem is intended to help you understand how this condensation works, so start by taking a look at the condensation reaction. Focus first on the new C-C bond and a new C-O bond that must be formed during the reactions, shown in bold in the structure below. (Initially, there are two C-O bonds you should notice. The rest of the problem will help you decide which one of these is formed.) Now focus on the two reactions you are asked about. In the first reaction, a new C-C bond is formed: This is a C-C bond connecting an aromatic ring to a carbonyl. You only know one reaction for forming a new C-C bond between an aromatic ring and a carbonyl: electrophilic aromatic acylation. You know that the mechanism of electrophilic aromatic acylation involves the reaction of an aromatic nucleophile with an acylium ion electrophile. Since the phenol starting material is a good nucleophile for electrophilic aromatic substitution, the only thing that is missing is the acylium ion. This question is then reduced to, “How do I convert a methyl ester to an acylium ion in the presence of acid?” O O HO 2 C one of these is a new C-O bond new C-C bond OH H 3 CO O new C-C bond
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You know that acyl chlorides can be converted to acylium ions in the presence of AlCl 3 via coordination of AlCl 3 to the chlorine atom, after which a lone pair on the carbonyl oxygen can kick out AlCl 4 to form an acylium ion. By analogy, you can protonate the methoxy oxygen of the methyl ester to make an oxonium ion, after which a lone pair on the carbonyl oxygen can kick out methanol to form an acylium ion.
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  • Summer '10
  • S
  • Benzene, H3C, Aromatic hydrocarbon

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