Claisen condensations compounds

The acetoacetic ester condensation (involving the acylation of an ester by an ester) is a special case of a more general reaction term the Claisen condensation. The latter is the condensation between a carboxylic ester and an ester (or ketone or nitrile) containing an a-hydrogen atom in the presence of a base (sodium, sodium alkoxide, sodamide, sodium triphenylmethide, etc.). If R—H is the compound containing the a- or active hydrogen atom, the Claisen condensation may be written ... 

Before describing how p keto esters are used as reagents for organic synthesis we need to see how these compounds themselves are prepared The mam method for the prepa ration of p keto esters is the Claisen condensation... 

The 1,3-dicarbonyl components can be replaced by an enol ether, which can be prepared by Claisen condensation from an ortho ester and a reactive methylene compound. ... 

In the presence of strong bases, carbonyl compounds form enolate ions, which may be employed as nucleophilic reagents to attack alkyl halides or other suitably electron-deficient substrates giving carbon-carbon bonds. (The aldol and Claisen condensations... 

As summarized in Figure 27.7, the mevalonate pathway begins with the conversion of acetate to acetyl CoA, followed by Claisen condensation to yield acetoacety) CoA. A second carbonyl condensation reaction with a third molecule of acetyl CoA, this one an aldol-like process, then yields the six-carbon compound 3-hydroxy-3-methylglutaryl CoA, which is reduced to give mevalonate. Phosphorylation, followed by loss of C02 and phosphate ion, completes the process. 

It was unfortunate that we did not detect any product derived from a diketone in the reaction of w-dimethoxybenzene with tetrafluoroben-zyne. We therefore carried out a reaction of tetrafluorobenzyne with 1,3,5-trimethoxybenzene. The di-enol ether (80) could not be isolated, and after the removal of unreacted 1,3,5-trimethoxybenzene we isolated the phenolic acid (81) in good yield. This compound is undoubtedly formed by the hydrolysis of (80) followed by a retro-Claisen condensation, and aromatisation as shown below. 

In the course of the first total synthesis of (+)-halichlorine <1999TL6513, 1999AGE3542>, the spiroquinolizidine unit 460 was constructed by a two-carbon chain extension in compound 458 through a crossed Claisen condensation, leading to 459, and an intramolecular Mannich reaction of this compound with formaldehyde (Scheme 109). 

TiIV compounds also work well at promoting cross-aldol reactions between two different aldehydes and/or ketones without prior activation or protection (Scheme 19).74 Claisen condensation and Knoevenagel condensation are promoted by TiX4, an amine, and trimethylsilyl triflate.75-77... 

CLAB underground spent fuel disposal facility, 17 549 Cladinose, 4 713 Claflin refiner, 15 105 CLAIMS-Citation database, 15 238 CLAIMS-Citation files, 15 247, 248 CLAIMS Compound Registry, 15 247 CLAIMS databases, 15 237, 247 Claisen condensation, 10 505 Claisen-Cope rearrangement, 24 479,... 

Claisen condensation org chem 1. Condensation, in the presence of sodium ethox-ide, of esters or of esters and ketones to form p-dicarbonyl compounds. 2. Condensation of arylaldehydes and acylphenones with esters or ketones In the presence of sodium ethoxide to yield unsaturated esters. Also known as Claisen reaction. klas-3n kand-on sa-shon ... 

The term condensation refers to the joining of two molecules with the splitting out of a smaller molecule. The Claisen condensation is used extensively in the synthesis of dicarbonyl compounds. In biochemistry it is used to build fatty acids in the body. The Dieckmann condensation, the crossed Claisen condensation, and others (with other carbanions) cire variations of the Claisen condensation. In this section we briefly look at these variations. 

The Claisen condensation is one method of synthesizing (3-dicarbonyl compounds, specifically a (3-keto ester. This reaction begins with an ester and occurs in two steps. In the first step, a strong base, such as sodium ethoxide, removes a hydrogen ion from the carbon atom adjacent to the carbonyl group in the ester. (Resonance stabilizes the anion formed from the ester.) The anion can then attack a second molecule of the ester, which begins a series of mechanistic steps until the anion of the (3-dicarbonyl compound forms, which, in the second reaction step (acidification), gives the product. 

Ace advanced topics — take a closer look at nitrogen compounds, organometallic compounds, the Claisen Condensation and its variations, and biomolecules, such as carbohydrates, lipids, and proteins... 

The method described is that of Hampton, Harris, and Hauser6 and is an improvement over the benzyne method, which gives poor yields.6,7 This /J-diketone has been prepared by Claisen condensation of ethyl phenylacetate with acetone,8 but the yield is poorer and the product has been shown by gas chromatography to be impure.6 The j8-diketone has also been prepared by the hydrolysis of 4-methoxy-5-phenyl-3-penten-2-one and by hydrolysis and decarboxylation of ethyl a-acetyl-/3-oxo-y-phenylbutyrate10 but these compounds are more difficult to obtain than the starting materials used in the present synthesis. 

Lithium amide is used in synthesis of histamine and analgesic drugs. The compound also is used in many organic synthetic reactions including alkylation of ketones and nitriles, Claisen condensation, and in synthesis of antioxidants and acetylenic compounds. 

When two molecules of ester undergo a condensation reaction, the reaction is called a Claisen condensation. Claisen condensation, like the aldol condensation, requires a strong base. However, aqueous NaOH cannot be used in Claisen condensation, because the ester can be hydrolysed by aqueous base. Therefore, most commonly used bases are nonaqueous bases, e.g. sodium ethoxide (NaOEt) in EtOH and sodium methoxide (NaOMe) in MeOH. The product of a Claisen condensation is a P-ketoester. As in the aldol condensation, one molecule of carbonyl compound is converted to an enolate anion when an a-proton is removed by a strong base, e.g. NaOEt. 

In the typical old-fashioned Reformatsky protocol12a d, a mixture of a-bromoester, carbonyl compound and zinc powder is heated in a solvent, generally benzene, for several hours. Under these conditions, the chemical yields often suffer from the concurrence of side-reactions, such as self-condensation of enolizable aldehydes, Claisen condensation of bromoesters or crotonization of the Reformatsky products. However, ever since the outset of Reformatsky studies, chemists have been aware about the need to activate the zinc surface in order to get higher reaction rates and shorter induction times before the process starts, with lower by-product formation. Thus, it became common practice to... 

These heterocyclic compounds undergo many reactions which are similar to those of the acetone enolate. Thus, Claisen condensation and o-sulfonylation are exemplified by Scheme 57. 

Amino groups in compounds of type (23, Z=NH) are frequently derived from nitro groups. In the Reissert indole synthesis, o-nitrotoluene undergoes Claisen condensation with oxalic ester to yield the pyruvic ester (24). When this is reduced with Zn-AcOH the corresponding amino derivative spontaneously cyclizes to the 2-ethoxycarbonylindole (25) (63OS(43)40). 

Other Claisen condensations are involved in synthesis of fatty acids and polyketides217 (Chapter 21) and in formation of 3-hydroxy-3-methylglutaryl-CoA, the precursor to the polyprenyl family of compounds (Chapter 22). In these cases the acetyl group of acetyl-CoA is transferred by a simple displacement mechanism onto an -SH group at the active site of the synthase to form an acetyl-enzyme.218 219 The acetyl-enzyme is the actual reactant in step b of Eq. 17-5 where this reaction, as well as that of HMG-CoA lyase, is illustrated. 

Except for some vitamin B12-dependent reactions, the cleavage or formation of carbon-carbon bonds usually depends upon the participation of carbonyl groups. For this reason, carbonyl groups have a central mechanistic role in biosynthesis. The activation of hydrogen atoms (3 to carbonyl groups permits (3 condensations to occur during biosynthesis. Aldol or Claisen condensations require the participation of two carbonyl compounds. Carbonyl compounds are also essential to thiamin diphosphate-dependent condensations and the aldehyde pyridoxal phosphate is needed for most C-C bond cleavage or formation within amino acids. 

Most of the pigments of flowers arise from a single polyketide precursor. Phenylalanine is converted to trans-cinnamic acid (Eq. 14-45) and then to cinnamoyl-CoA. The latter acts as the starter piece for chain elongation via malonyl-CoA (step a in the accompanying scheme). The resulting (3-polyketone derivative can cyclize in two ways. The aldol condensation (step b) leads to stilbenecar-boxylic acid and to such compounds as pinosylvin of pine trees. The Claisen condensation (step c) produces chalcones, flavonones, and flavones. These, in turn, can be converted to the yellow fla-vonol pigments and to the red, purple, and blue anthocyanidins.3 c... 

The conversion of the substituted 1,3-dicarbonyl compound into homophthalic acid is remarkably facile loss of the acetyl group by a retro-Claisen condensation and hydrolysis of the ester group are complete in a few minutes in aqueous sodium hydroxide. The overall synthesis of homophthalic acids from o-bromobenzoic acids occurs in high yield and provides an attractive route. 

C-Acylations of C,H-acidic compounds have also been realized on insoluble supports. The few examples that have been reported include the C-acylation of support-bound ester enolates with acyl halides [9], Claisen condensations of polystyrene-bound ketones with benzoic acid esters, the C-acylation of nitriles with acyl nitriles or anhydrides, and the C-acylation of phosphonates with acyl halides (Entries 5-9, Table... 

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