Reaction claisen

Claisen reaction Condensation of an aldehyde with another aldehyde or a ketone in the presence of sodium hydroxide with the elimination of water. Thus benzaldehyde and methanal give cinnamic aldehyde, PhCH CH-CHO. 

This Condensation should not be confused with the Claisen Reaction, which is the condensation of an aldehyde with (i) another aldehyde, or (ii) a ketone, under the influence of sodium hydroxide, and with the elimination of water. For details, see Diben zal-acetone. p, 231. 

Other reactions similar to the aldol addition include the Claisen and Perkin reactions. The Claisen reaction, carried out by combining an aromatic aldehyde and an ester in the presence of metallic sodium, is useful for obtaining a,P-unsaturated esters. 

Claisen reaction is the condensation of benzaldehyde with aliphatic aldehydes and ketones containing a-hydrogen C6H5CHO -r CH3CHO C6H5CH=CH CHO -r HjO... 

Ethyl chlorodifluoroacetate has been used in a silicon-induced Reformatsky-Claisen reaction of allyl chlorodifluoroacetates in the presence ot zinc as a route to 2,2-difluoro unsaturated acids [( S] (equahon 58) When this methodology is applied to chlorodifluoropropargylic esters, the corresponding allenic esters are formed [SS]... 

Tables 12.1-12.3 below give some examples of the magnitude of each term for two bimolecular reactions (Diels-Alder and Sn2 reactions, forming either one or two molecules as the product) and a unimolecular rearrangement (Claisen reaction). All values have been calculated at the MP2 level with the 6-31G(d) basis for the Diels-Alder and Claisen reactions, and the 6-31+G(d) basis for the S l reaction. The values are given in kcal/mol at a temperature of 300 K (RT = 0.60 kcal/mol).

Tire mechanism of the Claisen condensation is similar to that of the aldol condensation and involves the nucleophilic addition of an ester enolate ion to the carbonyl group of a second ester molecule. The only difference between the aldol condensation of an aldeiwde or ketone and the Claisen condensation of an ester involves the fate of the initially formed tetrahedral intermediate. The tetrahedral intermediate in the aldol reaction is protonated to give an alcohol product—exactly the behavior previously seen for aldehydes and ketones (Section 19.4). The tetrahedral intermediate in the Claisen reaction, however, expels an alkoxide leaving group to yield an acyl substitution product—exactly the behavior previously seen for esters (Section 21.6). The mechanism of the Claisen condensation reaction is shown in Figure 23.5. 

Problem 23.12 As shown in Figure 23.5, the Claisen reaction is reversible. That is, a /3-keto ester can be cleaved by base into two fragments. Using curved arrows to indicate electron flow, show the mechanism by which this cleavage occurs. 

The mixed Claisen condensation of two different esters is similar to the mixed aldol condensation of two different aldehydes or ketones (Section 23.5). Mixed Claisen reactions are successful only when one of the two ester components has no a hydrogens and thus can t form an enolate ion. For example, ethyl benzoate and ethyl formate can t form enolate ions and thus can t serve as donors. They can, however, act as the electrophilic acceptor components in reactions with other ester anions to give mixed /3-keto ester products. 

Diethyl oxalate, (CCqEt, often gives high yields in mixed Claisen reactions. What product would you expect to obtain from a mixed Claisen reaction of ethyl acetate with diethyl oxalate ... 

Strategy A mixed Claisen reaction is effective when only one of the two partners has an acidic cy hydrogen atom. In the present case, ethyl acetate can be converted into its enolate ion, but cliethyl oxalate cannot. Thus, ethyl acetate acts as the donor and diethyl oxalate as the acceptor. 

The Claisen reaction is a carbonyl condensation that occurs between two ester molecules and gives a /3-keto ester product. Mixed Claisen condensations... 

In the mixed Claisen reaction of cyclopentanone with ethyl formate, a much higher yield of the desired product is obtained by first mixing the two carbonyl components and then adding base, rather than by first mixing base with cyclopentanone and then adding ethyl formate. Explain. 

The four steps of the /3-oxidation pathway, resulting in the cleavage of an acetyl group from the end of the fatty-acid chain. The key chain-shortening step is a retro-Claisen reaction of a /3-keto thioester. Individual steps are explained in the text. 

Step 4 of Figure 29.3 Chain Cleavage Acetyl CoA is split off from the chain in the final step of /3-oxidation, leaving an acyl CoA that is two carbon atoms shorter than the original. The reaction is catalyzed by /3-ketoacyl-CoA thiolase and is mechanistically the reverse of a Claisen condensation reaction (Section 23.7). In the forward direction, a Claisen condensation joins two esters together to form a /3-keto ester product. In the reverse direction, a retro-Claisen reaction splits a /3-keto ester (or /3-keto thioester) apart to form two esters (or two thioesters). 

The retro-Claisen reaction occurs by initial nucleophilic addition of a cysteine -SH group on the enzyme to the keto group of the /3-ketoacyl CoA to yield an alkoxide ion intermediate. Cleavage of the C2-C3 bond then follows, with expulsion of an acetyl CoA enolate ion. Protonation of the enolate ion gives acetyl CoA, and the enzyme-bound acyl group undergoes nucleophilic acyl substitution by reaction with a molecule of coenzyme A. The chain-shortened acyl CoA that results then enters another round of tire /3-oxidation pathway for further degradation. 

The initial reaction in Problem 29.42, conversion of two molecules of acetyl CoA to one molecule of acetoacetyl CoA, is a Claisen reaction. Assuming that there is a base present, show the mechanism of the reaction. 

The Ireland-Claisen reaction of ( )-vinylsilanes has been applied to the stereoselective synthesis of syn- and c/nti-2-substituted 3-silyl alkcnoic acids. a R-2-Alkyl-3-silyl acids are prepared by rearrangement of ( )-silyl ketene acetals which are generated in situ from the kinetically formed (Z)-enolate of the corresponding propionate ester40. Chelation directs the stereochemistry of enolization of heteroelement-substituted acetates in such a way that the syn-diastereomers are invariably formed on rearrangement403. 

The polymerization of terephthaldehyde in the presence of triethoxyalu-minum391 or Uialkylaluminum392 (Tischchenko-Claisen reaction) yields random copolyesters containing ca. 1 1 mol ratio of p-methylenebenzoate and / -xyleneterephthalate units (Scheme 2.43). The reaction does not take place with sterically hindered aldehydes.392... 

In the presence of a strong base, the ot carbon of a carboxylic ester can condense with the carbonyl carbon of an aldehyde or ketone to give a P-hydroxy ester, which may or may not be dehydrated to the a,P-unsaturated ester. This reaction is sometimes called the Claisen reaction,an unfortunate usage since that name is more firmly connected to 10-118. In a modem example of how the reaction is used, addition of tert-butyl acetate to LDA in hexane at -78°C gives the lithium salt of ferf-butyl acetate, " (12-21) an enolate anion. Subsequent reaction a ketone provides a simple rapid alternative to the Reformatsky reaction (16-31) as a means of preparing P-hydroxy erf-butyl esters. It is also possible for the a carbon of an aldehyde or ketone to add to the carbonyl carbon of a carboxylic ester, but this is a different reaction (10-119) involving nucleophilic substitution and not addition to a C=0 bond. It can, however, be a side reaction if the aldehyde or ketone has an a hydrogen. 

There had been doubts about the utility of palladacycles in asymmetric catalysis, raised by the failure to achieve enantioselectivity as a result of a slow release of low ligated Pd(0) (naked Pd) [54]. However, recent success of several planar chiral palladacycles in highly enantioselective aza-Claisen reactions and in a number of other applications proves that the coordination shell of the Pd(II) species is not necessarily destroyed during the catalytic action. 

Grogan G, GA Roberts, D Bougioukou, NJ Turner, SL Flitsch (2001) The desymmetrization of bicyclic P-diketones by an enzymatic retro-claisen reaction. J Biol Chem 276 12565-12572. 

Allyl aryl ethers undergo accelerated Claisen and [1,3] rearrangements in the presence of a mixture of trialkylalanes and water or aluminoxanes. The addition of stoichiometric quantities of water accelerates both the trimethylaluminum-mediated aromatic Claisen reaction and the chiral zirconocene-catalyzed asymmetric carboalumination of terminal alkenes. These two reactions occur in tandem and, after oxidative quenching of the intermediate trialkylalane, result in the selective formation of two new C-C bonds and one C-0 bond (Eq. 12.70).153 Antibodies have also been developed to catalyze Claisen154 and oxy-Cope155 rearrangements. 

---