Friedel-Crafts acylation Clemmensen reduction

Show how you would use the Friedel-Crafts acylation, Clemmensen reduction, and/or Gatterman-Koch synthesis to prepare the following compounds ... 

Friedel-Crafts acylation followed by Clemmensen or Wolff-Kishner reduction is a standard sequence used to introduce a primary alkyl group onto an aromatic ring... 

Problem 15.58 Translate the following description into a chemical equation Friedel-Crafts acylation of resorcinol( 1,3-dihydroxybenzene) with CH,(CH2)4COCI produces a compound which on Clemmensen reduction yields the important antiseptic, hexylresorcinol. 

The key here is to recognize that an ethyl substituent can be introduced by Friedel-Crafts acylation followed by a Clemmensen or Wolff-Kishner reduction step later in the synthesis. If the chlorine is introduced prior to reduction, it will be directed meta to the acetyl group, giving the correct substitution pattern. 

Aryl alkyl ketones are readily prepared by the Friedel-Crafts acylation process (see Section 6.11.1, p. 1006) and their Clemmensen reduction constitutes a more efficient procedure for the preparation of monoalkylbenzenes than the alternative direct Friedel-Crafts alkylation reaction (see below). Alternatively aldehydes and ketones may be reduced to the corresponding hydrocarbon by the Wolff-Kishner method which involves heating the corresponding hydrazone or semicarbazone with potassium hydroxide or with sodium ethoxide solution. 

Alternatively, benzene could have been subjected to Friedel-Crafts acylation with benzoyl chloride to give benzophenone. Clemmensen or Wolff-Kishner reduction of benzophenone would then furnish diphenylmethane. 

The orientation is right attack is para to one of the methoxy groups and ortho to the methyl. The substrate for the Friedel-Crafts acylation reaction, 3,4-dimethoxytoluene, is prepared from compound A by a Clemmensen or Wolff-Kishner reduction. Compound A cannot be acylated directly because it bears a strongly deactivating —CH substituent. 

The desired sequence may be carried out by a Friedel-Crafts acylation, followed by Clemmensen or Wolff-Kishner reduction of the ketone. 

The Friedel-Crafts Alkylation may give polyalkylated products, so the Friedel-Crafts Acylation is a valuable alternative. The acylated products may easily be converted to the corresponding alkanes via Clemmensen Reduction or Wolff-Kishner Reduction. 

Polyalkylation was an advantage in the synthesis of BHT 13 it is the rearrangement that is chiefly unacceptable here. Friedel-Crafts acylation avoids both problems. The acyl group does not rearrange and the product is deactivated towards further electrophilic attack by the electron-withdrawing carbonyl group. We have an extra step reduction of the ketone to a CH2 group. There are various ways to do this (see chapter 24)—here the Clemmensen reduction is satisfactory.4... 

These catalytic reactions provide a unique pathway for addition of aromatic C-H bonds across C=C bonds. In contrast with Friedel-Crafts catalysts for olefin hydroarylation, the Ru-catalyzed hydrophenylation reactions of a-olefins selectively produce linear alkyl arenes rather than branched products. Although the selectivity is mild, the formation of anti-Markovnikov products is a unique feature of the Ru(II) and Ir(III) catalysts discussed herein. Typically, the preferred route for incorporation of long-chain linear alkyl groups into aromatic substrates is Friedel-Crafts acylation then Clemmensen reduction, and the catalysts described herein provide a more direct route to linear alkyl arenes. 

How do we synthesize alkylbenzenes that cannot be made by Friedel-Crafts alkylation We use the Friedel-Crafts acylation to make the acylbenzene, then we reduce the acylbenzene to the alkylbenzene using the Clemmensen reduction treatment with aqueous HC1 and amalgamated zinc (zinc treated with mercury salts). 

Clemmensen Reduction (Review) The Clemmensen reduction commonly converts acylbenzenes (from Friedel-Crafts acylation, Section 17-1 IB) to alkylbenzenes, but it also works with other ketones and aldehydes that are not sensitive to acid. The carbonyl compound is heated with an excess of amalgamated zinc (zinc treated with mercury) and hydrochloric acid. The actual reduction occurs by a complex mechanism on the surface of the zinc. 

Aldehydes and ketones can be reduced to hydrocarbons by the action (a) of amalgamated zinc and concentrated hydrochloric acid, the Clemmensen reduction or (b) of hydrazine, NH2NH2, and a strong base like KCm or potassium teh-butoxide, the Wolff-Kishner reduction. These are particularly important when applied to the al faTryl ketones obtailTed from Friedel-Crafts acylation, since this reaction sequence permits, indirectly, the attachment of straight alkyl chains to the benzene ring. For example ... 

In the laboratory of K. Krohn, the total synthesis of phytoalexine (+)-lacinilene C methyl ether was completed. In order to prepare the core of the natural product, an intermolecular Friedel-Crafts acylation was carried out between succinic anhydride and an aromatic substrate, followed by an intramolecular acylation. After the first acylation, the 4-keto arylbutyric acid was reduced under Clemmensen reduction conditions (to activate the aromatic ring for the intramolecular acylation). 

Benzene underwent a Friedel-Crafts acylation reaction followed by a Clemmensen reduction. The product gave the following... 

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