Ring Claisen condensation

Dieckmann cyclization (Section 21 2) An intra molecular analog of the Claisen condensation Cy die p keto esters in which the ring is five to seven membered may be formed by using this reaction... 

The intramolecular Claisen condensation of diesters, or Dieckman reaction, occurs readily to give five- or six-membered rings, and it has been extensively used for cyclopentanone and cyclohexanone derivatives. 

Esters of dicarboxylic acids undergo an intranolecular version of the Claisen condensation when a five- or six-membered ring can be fonned. 

In 1910, Hinsberg described the reaction between benzil and diethylthiodiacetate, resulting in the preparation of the thiophene ring system. The reaction was run under Claisen condensation conditions, and after hydrolysis with aqueous acid at reflux, the free dicarboxylic acid 1 was produced. 

More recent work in this series demonstrated that a carbonyl group can be interposed between the side-chaincarrying aromatic ring and the ethylene function with full retention of activity. Claisen condensation of benzoate with 2-tetralone affords the e-diketone Reaction of... 

Dieckmann condensation is a cyclic Claisen condensation where a molecule attacks itself to form a ring structure. Figure 15-4 shows an excimple beginning with dimethyl hexanedioate, and Figure 15-5 shows what happens when the Ccirbon chain increases by one carbon atom. This process favors the formation of five- or six-membered rings because they re the most stable rings. 

As seen in many of the above examples, acetic anhydride and zinc chloride each make effective condensation catalysts for the free bases, presumably by efficient coordination with the ring nitrogen. The quaternary salts condense readily in the presence of piperidine. Potassium hydroxide, methoxide or piperidinium acetate are suitable for condensations with 2- and 4-methylpyridine AAoxides. For example, the Claisen condensation is effective with these Af-oxides using ethoxide catalyst (Scheme 45) but the reaction fails with the parent picolines unless activated by nitro substitution (69JHC775). 

Benzene and thiophene rings can of course often be interchanged in biologically active agents. The very broad structural latitude consistent with NSAID activity is by now a familiar theme as well. Preparation of the fused thiophene counterpart of the NSAID piroxicam (Chapter 11) starts with the reaction of thiophene (25-1), itself the product of a multistep sequence, with ethyl A-methylglycinate to give the sulfonamide (25-2). Treatment of that intermediate with a base leads to intramolecular Claisen condensation and thus the formation of the 3-ketoester (25-3). An amide-ester interchange with 2-aminopyridme (25-4) completes the synthesis of tenoxicam (25-5) [25]. 

In the case of a ketone with two active methylene groups, such as dibenzylketone, the reaction can take two courses. The pyranone results from Michael addition to the alkyne followed by normal ring closure. The second product, a resorcinol, arises from either Michael condensation followed by an intramolecular Claisen condensation or the order of these two reactions may be reversed (60JCS5153). 

An internal Claisen condensation of a diester forms a ring. Such an internal Claisen cyclization is called a Dieckmann condensation or a Dieckmann cyclization. Five- and six-membered rings are easily formed by Dieckmann condensations. Rings smaller than five carbons or larger than six carbons are rarely formed by this method. 

Dieckmann condensation) A Claisen condensation that forms a ring. (p. 1074)... 

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