Malonic esters decarboxylation

A mixture of lupinine and epilupinine is obtainable by the following series of reactions. The betaine XXVI on cyclic hydrogenation and subsequent decarboxylation with 20 % hydrochloric acid gives a mixture of epimeric lupininic acids (XXIX). The dicarboxylic ester XXVIII is also obtained by the mercuric acetate dehydrogenation of the piperidine derivative XXX and by the alkylation of monomeric piperideine with a y-bromopropylmalonic ester. The last route is presumably a first Mannich condensation followed by an alkylation. Hydrolysis of the malonic esters, decarboxylation (XXIV), esterification, and reduction with lithium aluminum hydride complete the synthesis of a mixture which consists of 80% dZ-epilupinine and 20% dMupinine. Thermal... 

By hydrolysis of substituted malonic esters with 50 per cent, potassium hydroxide, followed by decarboxylation of the resulting malonic add by heating above the m.p. or, better, by rendering the aqueous solution of the potassium salt of the dibasic acid strongly acid and refluxing the mixture, for example ... 

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... 

Section 21 7 The malonic ester synthesis is related to the acetoacetic ester synthesis Alkyl halides (RX) are converted to carboxylic acids of the type RCH2COOH by reaction with the enolate ion derived from diethyl mal onate followed by saponification and decarboxylation... 

NaCN (for decarboxylation of malonic esters) DMSO, 160°, 4 h, 70-80% yield ... 

The Gould-Jacobs reaction is a sequence of the following reactions (1) condensation of an arylamine 1 with either alkoxy methylenemalonic ester or acyl malonic ester 2 providing the anilidomethylenemalonic ester 3 (2) cyclization of 3 to the 4-hydroxy-3-carboalkoxyquinoline 4 (3) saponification to form acid 5, and (4) decarboxylation to give the 4-hydroxyquinoline 6. All steps of this process will be described herein with emphasis on the formation of intermediates like 3 and 4. 

The synthetic importance of the malonic ester synthesis follows from the fact that the substituted malonic ester can easily be hydrolyzed, and subsequently decarboxylates to yield a substituted acetic acid 9. This route to substituted acetic acids is an important method in organic synthesis ... 

An analogous sequence on acid, 29 (obtained by decarboxylative hydrolysis of the malonic ester), leads to carbromal (30). Dehy-drohalogenation of 30 by means of silver oxide affords the corresponding olefin, ectylurea (31), itself a sedative-hypnotic. 

On heating with aqueous hydrochloric acid, the alkylated (or dialkylated) malonic ester undergoes hydrolysis of its two ester groups followed by decarboxylation (loss of C02) to yield a substituted monoacid. 

The malonic ester synthesis can also be used to prepare cydoalkane-carboxvlic acids. For example, when 1,4-dibromobutanc is treated with diethyl malonate in the presence of 2 equivalents of sodium ethoxide base, the second alkylation step occurs intrcunotecidariy to yield a cyclic product. Hydrolysis and decarboxylation then give cvclopentanecarboxylic acid. Three-, four-, five-. 

A more general method for preparation ofa-amino acids is the amidotnalmatesynthesis, a straightforward extension of the malonic ester synthesis (Section 22.7). The reaction begins with conversion of diethyl acetamidomalonate into an eno-late ion by treatment with base, followed by S 2 alkylation with a primary alkyl halide. Hydrolysis of both the amide protecting group and the esters occurs when the alkylated product is warmed with aqueous acid, and decarboxylation then takes place to vield an a-amino acid. For example aspartic acid can be prepared from, ethyl bromoacetate, BrCh CCHEt ... 

Malonic ester synthesis (Section 22.7) The synthesis of a carboxylic acid by alkylation of an alkyl halide, followed by-hydrolysis and decarboxylation. 

An important example of this reaction is the malonic ester synthesis, in which both Z groups are COOEt. The product can be hydrolyzed and decarboxylated (12-38) to give a carboxylic acid. An illustration is the preparation of 2-ethyl-pentanoic acid from malonic ester ... 

Reaction of malonic esters with 1,2-dibromoethane and 1,3-dibromopropane under liquiddiquid two-phase conditions produces the cyclopropane- and cyclobutane- 1,1 -dicarboxyl ic esters, which can be hydrolysed under the basic conditions (6.2.24.C) [e.g. 75, 109] and decarboxylated to give the monocarboxylic acid [e.g. 109]. 

Esters are hydrolysed under basic conditions in the presence of quaternary ammonium salts [e.g. 1-7], Microwave activation of basic soliddiquid systems without an added solvent enhances the rate of saponification and the reaction is not affected by steric factors [3], Microwave irradiation has also been used in the hydrolysis and decarboxylation of malonic esters [8] and p-keto esters [9] (>90%). Lactones... 

Method D (hydrolysis and decarboxylation of malonic esters and fi-keto esters) LiBr (1.73 g), TBA-Br (0.32 g, 1 mmol), the malonic ester or p-keto ester (10 mmol) and H20 (360 ml) are subjected to microwave irradiation for 15 min. The cooled mixture is extracted with EtOAc (50 ml) and the organic solution is filtered through Florisil and evaporated to yield the decarboxylated compound. 

With malonic esters and amides substituted at the central carbon, triazole formation is accompanied by decarboxylation and 4-alkyl-or 4-aryl-5-hydroxytriazoles are isolated. ... 

Acetone cyanohydrin nitrate, a reagent prepared from the nitration of acetone cyanohydrin with acetic anhydride-nitric acid, has been used for the alkaline nitration of alkyl-substituted malonate esters. In these reactions sodium hydride is used to form the carbanions of the malonate esters, which on reaction with acetone cyanohydrin nitrate form the corresponding nitromalonates. The use of a 100 % excess of sodium hydride in these reactions causes the nitromalonates to decompose by decarboxylation to the corresponding a-nitroesters. Alkyl-substituted acetoacetic acid esters behave in a similar way and have been used to synthesize a-nitroesters. Yields of a-nitroesters from both methods average 50-55 %. 

In most cases, the product of the malonic ester synthesis isn t the final product you re looking for. Commonly, the next step after the reaction in Figure 15-15 is hydrolysis and decarboxylation. Figure 15-16 shows this step. 

Relatively acidic carbon acids such as malonic esters and jS-keto esters were the first class of carbanions for which reliable conditions for alkylation were developed. The reason being that these carbanions are formed using easily accessible alkoxide ions. The preparation of 2-substiuted /i-kcto esters (entries 1, 4, and 8) and 2-substituted derivatives of malonic ester (entries 2 and 7) by the methods illustrated in Scheme 1.5 are useful for the synthesis of ketones and carboxylic acids, since both /1-ketoacids and malonic acids undergo facile decarboxylation ... 

The use of /i-ketocstcrs and malonic ester enolates has largely been supplanted by the development of the newer procedures based on selective enolate formation that permit direct alkylation of ketone and ester enolates and avoid the hydrolysis and decarboxylation of ketoesters intermediates. Most enolate alkylations are carried out by deprotonating the ketone under conditions that are appropriate for kinetic or thermodynamic control. Enolates can also be prepared from silyl enol ethers and by reduction of enones (see Section 1.3). Alkylation also can be carried out using silyl enol ethers by reaction with fluoride ion.31 Tetraalkylammonium fluoride salts in anhydrous solvents are normally the... 

Step 3 Hydrolysis of the substituted malonic ester gives the malonic acid, which undergoes decarboxylation (loss of COi) to form a substituted acetic acid. 

---