Intramolecular Claisen condensations the Dieckmann reaction

Ethyl 2,2,4-trimethyl-3-oxopentanoate (cannot form a stable anion formed in no more than trace amounts) 

At least two protons must be present at the a carbon for the equilibrium to favor product formation. Claisen condensation is possible for esters of the type RCH2CO2R, but not for R2CHCO2R.  

Esters of dicarboxylic acids undergo an intramolecular version of the Claisen condensation when a hve- or six-membered ring can be formed. 

This reaction is an example of a Dieckmann cyclization. The anion formed by proton waiter Dieckmann was a 

PROBLEM 21.2 Write the structure of the Dieckmann cyclization product formed on treatment of each of the following diesters with sodium ethoxide, followed by acidification. 

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Intramolecular Claisen condensations, called Dieckmann condensations, are ringclosing reactions that yield 2-cyclopentanone carboxylic esters (Figure 10.52) or 2-cyclohexanone carboxylic esters. The mechanism of the Dieckmann condensation is, of course, identical to the mechanism of the Claisen condensation (Figure 10.51). To ensure that the Dieckmann condensation goes to completion, the presence of a stoichiometric amount of base is required. As before, the neutral /3-ketoester (B in Figure... 

The Claisen reaction is a carbonyl condensation that occurs between two ester components and gives a /3-keto ester product. Mixed Claisen condensations between two different esters are successful only when one of the two partners has no acidic a hydrogens (ethyl benzoate and ethyl formate, for instance) and thus can function only as the acceptor partner. Intramolecular Claisen condensations, called Dieckmann cyclization reactions, provide excellent syntheses of five- and six-membered cyclic /3-keto esters starting from 1,6- and 1,7-diesters. 

The intramolecular condensation of ester enolates provides efficient access to 5- and 6-member ring P-keto esters. Similar to the Claisen condensation, the Dieckmann condensation is driven to completion by deprotonation of the initially formed P-keto ester. Thus, at least one of the ester groups must have two a-hydrogens for the reaction to proceed. 

Intramolecular Claisen condensations can be carried out with diesters, just as intramolecular aldol condensations can be carried out with diketones (Section 23.6). Called the Dieckmann cyclization, the reaction works best on 1.6-diesters and 1,7-diesters. Intramolecular Claisen cyclization of a 1,6-diester gives a five-membered cyclic /3-keto ester, and cyclization of a 1,7-diester gives a six-membered cyclic /3-keto ester. 

Esters of dicarboxylic acids having hydrogen on the 8 or e carbon atoms undergo intramolecular cyclisation when heated with sodium or with sodium ethoxide. This cyclisation is known as the Dieckmann reaction. It is essentially an application of the Claisen (or acetoacetic ester) condensation to the formation of a ring system the condensation occurs internally to produce a... 

The synthesis may thus be seen to be an intramolecular Claisen ester condensation, which is known as the Dieckmann reaction. The procedure is an important method for the synthesis of five- and six-membered ring systems, and the cyclic /2-keto ester product may be converted into the corresponding cyclic ketone by hydrolysis followed by decarboxylation (ketonic hydrolysis, see Section 5.8.5, p. 619). The base catalyst used in Expt 7.8 is sodium ethoxide, but sodium hydride as a 50 per cent dispersion in oil is a recommended alternative. 

The intramolecular version of the Claisen ester condensation is sometimes known as the Dieckmann reaction, It provides an excellent route to heterocyclic ketones (cyclic ketones with heteroatoms in the ring very important in. . 

Dieckmann reaction (Section 23.9) the intramolecular Claisen condensation reaction of a 1,6-or 1,7-diester, yielding a cyclic p-keto ester. 

The Claisen and Dieckmann condensations are reactions in which an ester enolate acts as a nucleophile toward an ester. The Dieckmann condensation is simply the intramolecular variant of the Claisen condensation. In these reactions, the alkoxy part of the ester is substituted with an enolate to give a jS-ketoester. A stoichiometric amount of base is required for this reaction, because the product is a very good acid, and it quenches the base catalyst. In fact, this quenching reaction is what drives the overall reaction to completion. The Claisen condensation is especially useful when one of the esters is nonenolizable (e.g., diethyl oxalate, ethyl formate, or diethyl carbonate). 

In the Claisen condensation, the anion is formed from an ester directly by the action of a base, e.g. the corresponding alkoxide of the ester, and this stabilised carbanion then reacts with another ester to form a 3-ketoester. If both ester groups are in the same molecule, then an intramolecular condensation reaction is possible, which is called the Dieckmann cyclisation this works best when the ring formed contains five, six or seven members. 

The Dieckmann, Thorpe and Thorpe-Ziegler reactions all involve intramolecular cyclization of a stabilized anion to form a cyclic ketone. The Dieckmann reaction is the intramolecular equivalent of the Claisen condensation and yields cyclic 2-alkoxycarbonyl ketones as primary products, whereas the primary products of the Thorpe reaction are 2-cyanoenamines (Scheme 13). Sub quent hydrolysis affords cyclic ketones but the primary products, particularly those from the Dieckmann reaction, have a useful synthetic role (see Section 3.6.3.S.1). 

In an aldol addition, the enolate of an aldehyde or a ketone reacts with the carbonyl carbon of a second molecule of aldehyde or ketone, forming a j8-hydroxyaldehyde or a jS-hydroxyketone. The new C—C bond forms between the a-carbon of one molecule and the carbon that formerly was the carbonyl carbon of the other molecule. The product of an aldol addition can be dehydrated to give an aldol condensation product. In a Claisen condensation, the enolate of an ester reacts with a second molecule of ester, eliminating an OR group to form a j8-keto ester. A Dieckmann condensation is an intramolecular Claisen condensation. A Robinson annulation is a ring-forming reaction in which a Michael reaction and an intramolecular aldol addition occur sequentially. 

An intramolecular Claisen condensation is called a Dieckmann condensation. For example, when diethyl hexanedioate is heated with sodium ethoxide, subsequent acidification of the reaction mixture gives ethyl 2-oxocyclopentanecarboxylate ... 

There are few mechanistic studies for the Dieckmann condensation. " The reaction can simply be described as an intramolecular Claisen condensation and hence entirely reversible. The summation of the consensus for its mechanism is as follows the reaction is initiated by anion formation through the abstraction of the most acidic proton on the a-carbon to one of the di-... 

There are several variations of the Claisen condensation. The intramolecular variation is called the Dieckmann condensation. A crossed Claisen condensation is possible between two different esters, but this reaction can lead to multiple products. Claisen condensations can operate in the forward direction or in the reverse direction, and these two processes lead to the construction and deconstruction of fatty acids. 

Notice once again that the product is just a P-keto ester. This reaction has its own name (the Dieckmann condensation). But it is really just an intramolecular Claisen condensation. Therefore, the steps of this mechanism are identical to the steps of a regular Claisen condensation. Propose a mechanism for the Dieckmann condensation. Try to do it without looking back at your previous work. You will need a separate piece of paper to record your answer. 

Two cyclic products are possible from the Dieckmann (intramolecular Claisen) condensation shown below, but only one of them actually forms. Describe and explain briefly the outcome of this reaction. 

We recall that intramolecular aldol condensation reactions can occur to give five- or six-membered ring compounds (Section 22.9). An intramolecular Claisen condensation, known as the Dieckmann condensation, can also occur to give five- or six-membered ring compounds. The Dieckmann condensation is more favorable than the bimolecular Claisen condensation because it converts a single molecule of reactant into two molecules of product. 

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