Decarboxylation malonic acid derivatives

A p-keto ester can be hydrolyzed to a p-keto acid, and heating leads to decarboxylation. Malonic acid derivatives, as well as P-ketone acids decarboxylate upon heating. 

A p-keto ester can be hydrolyzed to a P-keto acid, and heating leads to decarboxylation. Malonic acid derivatives, as well as P-ketone acids decarboxylate upon heating 63,109, 111, 135. Enolate anions react with alkyl halides by an S]v2 reaction to give alkylated carbonyl compounds 65, 67, 70, 84, 108, 116, 127,... 

The thermal decarboxylation of malonic acid derivatives is the last step m a multistep synthesis of carboxylic acids known as the malonic ester synthesis This synthetic method will be described m Section 21 7... 

The physical properties of cyanoacetic acid [372-09-8] and two of its ester derivatives are Hsted ia Table 11 (82). The parent acid is a strong organic acid with a dissociation constant at 25°C of 3.36 x 10. It is prepared by the reaction of chloroacetic acid with sodium cyanide. It is hygroscopic and highly soluble ia alcohols and diethyl ether but iasoluble ia both aromatic and aUphatic hydrocarbons. It undergoes typical nitrile and acid reactions but the presence of the nitrile and the carboxyUc acid on the same carbon cause the hydrogens on C-2 to be readily replaced. The resulting malonic acid derivative decarboxylates to a substituted acrylonitrile ... 

Converting the C-2 alkylated derivative to the conesponding malonic acid derivative by ester hydrolysis gives a compound susceptible to thermal decarboxylation. Temperatures of approximately 180°C are normally required. 

In this chapter, decarboxylation of disubstituted malonic acid derivatives and application of the transketolases in organic syntheses are summarized. Although decarboxylation may be seen as a simple C-C bond breaking reaction, it can be regarded as a carbaniongenerating reaction. As the future directions of this field, expansion of some unique decarboxylation reactions is proposed. In relation of carbanion chemistry, promiscuity of enolase superfamily is discussed. 

Just as /3 keto-acids or malonic acid derivatives, the /S-acid XLIII is easily decarboxylated 49). 

A frequently employed route comprises preparation of 3-alkoxycar-bonyltetramic acids from malonic acid derivatives and a-aminocarboxylic esters (77MI1 84CPB3724) or, alternatively, a-aminonitriles (86UP1) followed by hydrolysis and decarboxylation [72JCS(P1)2121 85AJC1847 86ZN(B)219]. 

Synthesis (Mayer and Testa, 1997 Cleij et al., 1999 Kleemann et al., 1999) a) Treatment of ethyl 4-isobutylphenylacetate and diethyl carbonate with sodium ethoxide gives diethyl 4-isobutylphenylmalonate, which is methylated using methyl iodide and sodium ethoxide. Saponification followed by decarboxylation of the resulting malonic acid derivative affords ibuprofen. 

SAMPLE SOLUTION (a) Thermal decarboxylation of malonic acid derivatives leads to the replacement of one of the carboxyl groups by a hydrogen. 

Another type of chiral Michael acceptor, the oxazepine derivatives (47), is prepared by condensation of the (-)-ephedrine-derived malonic acid derivative (46) with aldehydes (Scheme 18).51 52 Treatment of (47) with a variety of Grignard reagents in the presence of NiCh affords, after hydrolysis and decarboxylation, the 3-substituted carboxylic acids (48), in most cases with more than 90% ee. Diastereoselective Michael additions to (47) were also used for the preparation of optically active cyclopropane derivatives (49)53 and P-substituted-y-butyrolactones (50 Scheme 18).54 A total synthesis of indolmycin is based on this methodology.55... 

The conversion of acetyl-CoA into malonyl-CoA increases the acidity of the a-hydrogens, and thus provides a better nucleophile for the Claisen condensation. In the biosynthetic sequence, no acy-lated malonic acid derivatives are produced, and no label from [14C]bicarbonate is incorporated, so the carboxyl group introduced into malonyl-CoA is simultaneously lost by a decarboxylation reaction during the Claisen condensation (Figure 3.1). Accordingly, the carboxylation step helps to activate the a-carbon and facilitate Claisen condensation, and the carboxyl is immediately removed on completion of this task. An alternative rationalization is that decarboxylation of the malonyl ester is used to generate the acetyl enolate anion without any requirement for a strong base. 

Acid hydrolysis converts the diester in part (k) to a malonic acid derivative, which then undergoes decarboxylation. 

Malonic acid derivatives undergo decarboxylation on heating. 

The Mannich bases investigated are acctoacetic and malonic acid derivatives, Y-carboxyglutamic acid included. - Compounds having the lactone structure give preferably decarboxylation of the ester groups not involved in the lactone ring. - ... 

Lynn Zara, C., Jin, T., Giguere, R. J. Microwave heating in organic synthesis decarboxylation of malonic acid derivatives in water. Synth. Commun. 2000, 30, 2099-2104. 

Although some synthetic applications of enols are known, their main role is as reactive intermediates. Enols are intermediates in the hydration of alkynes (Section 9.12) and the decarboxylation of (3-keto acids and malonic acid derivatives (Section 18.16), for example. They are intermediates in a number of biochemical processes including glucose metabolism and malonyl coenzyme A biosynthesis. 

The key feature in the decarboxylation of malonic acid derivatives is that they are 1,3-dicarbonyl compounds with the acidic proton of the acid in close proximity to a carbonyl oxygen that is two carbon atoms away from the carboxyl unit. The proximity of these units is essential, which is why decarboxylation occurs with 1,3-dicarbonyl compormds and 7 o with 1,4-dicarbonyl compounds. This is a form of an elimination reaction (see Chapter 12). Going back to the expected product, 97 from 96, it is clear that this is a 1,3-dicarbonyl compound capable of decarboxylation upon heating. That is precisely what occurs, so the product is 98 rather than 97. Decarboxylation of malonic acid derivatives gives functionalized carboxylic acids. 

Malonic acid derivatives are not the only compounds capable of decarboxylation. At least one COOH unit is required, as well as a suitable basic atom such as the oxygen of a carbonyl that is attached to the a-carbon of the acid. Reexamining the Claisen condensation shows that the P-keto ester products (61 from Section 22.7.1) fit the criterion for decarboxylation. The requisite COOH unit is obtained by hydrolysis of the ester unit in 61 to give P-keto acid 101. 

It is possible to decarboxylate benzoic acid, but the reaction requires much higher temperatures than are required for dicarboxylate malonic acid derivatives. Explain. 

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