Malonic acid decarboxylative

Olefinic esters may be obtained directly by the Knoevenagel reaction. Alkyl hydrogen malonates are used in place of malonic acid. Decarboxylation then gives the ester directly as in the preparation of ethyl 2-heptenoate (78%) and methyl m-nitrocinnamate (87%). Alkyl hydrogen malonates are readily available by partial hydrolysis of dialkyl malonates. The use of malonic ester in the condensation leads to olefinic diesters, namely, alkylidenemalonates such as ethyl heptylidenemalonate (68%). A small amount of organic acid is added to the amine catalyst since the salts rather than the free amines have been shown to be the catalysts in condensations of this type. Various catalysts have been studied in the preparation of diethyl methylenemalonate. Increased yields are obtained in the presence of copper salts. Trimethylacetalde-hyde and malonic ester are condensed by acetic anhydride and zinc chloride. Acetic anhydride is also used for the condensation of furfural and malonic ester to furfurylidenemalonic ester (82%). ... 

The data for this solvent were not used to calculate the parameters in Table 54. Similarly the data for decarboxylation of oxanilic acid in anisole were not used for the AH -AS correlation. With the reported AH value of 32.6 kcal.mole , the entropy of activation is calculated to be 3.59 0.03 eu compared to the reported value of 11.1 eu. In the decarboxylation of malonic acid, the data obtained with pyridine and ) -mercaptopropionic acid solvents deviated considerably from the plots and were not included in the correlation. The data for malonic acid decarboxylation appeared to be best correlated by two lines. One line was described by the following solvents acids, phenols, nitro-aromatics, benzaldehyde, and the melt the other line involved amines, alcohols, dimethylsulfoxide and triethyl phosphate. The latter line was not as well defined as the former. However, it was our intention to correlate as many solvents as possible with a minimum number of lines. The data for decarboxylation of malonic acid in water and in benzyl alcohol fell between these two lines and were not included in either correlation. The data for decarboxylation of benzylmalonic acid also appeared to be best correlated with two lines. One line was defined by the cresols, acids and the melt, while the other line was defined by the amines. Decarboxylation of cinnamalmalonic acid was correlated by two lines as indicated in Table 54. Similarly j8-resorcylic acid was correlated by two lines. The separation of data into parallel lines is presumably due to multiple solvation mechanisms . In support of this interpretation it is seen that when two lines are observed, acids fall into one line and amines into the other. It is not unexpected that the solvation mechanisms for these two classes of solvents would differ. It is interesting to note that all of the nitrogen containing acids are correlated reasonably well with one line for both basic and acidic solvents. Also the AHq values fall in a rather narrow range for all of the acids. From the values of p in Table 54, there appears to be little correlation between this parameter and the melting point of the acids, contrary to prior reports " ... 

CioHi802, Mt 170.25, rep0 1.440-1.444, dgj 0.902, is a colorless to pale yellow liquid with a green, floral note. It imparts freshness to floral fragrance compositions and is recommended as a substitute for methyl 2-octynoate. The synthesis consists of a condensation of heptanal with malonic acid, decarboxylation and subsequent esterification with methanol. 

Step 3 The mono- or dialkylmalonic ester can then be hydrolyzed to a mono- or dialkylmalonic acid, and substituted malonic acids decarboxylate readily. Decarboxylation gives a mono- or disubstituted acetic acid ... 

Malonic acid decarboxylates by way of a similar transition state to give an enol of acetic acid that tautomerizes to acetic acid. 

An extensive study of the rate of malonic acid decarboxylation in aqueous solutions of pH 0.5 to 5 (Hall 1949) yielded a rate expression involving rate constants for both the undissociated species (HOOCCH2COOH) and the monovalent anion (HOOCCH2COO ) ... 

The role of the base is apparently primarily that of a proton remover from the reactive methylene group thus if B represents the base, reaction (i) gives the carbanion, which then combines with the positive carbon of the carbonyl group (reaction ii) the product regains a proton from the piperidinium ion, and then by loss of water followed by mono-decarboxylation of the malonic acid residue gives the final acid. 

Synthesis No control is needed in the first step there is only one enolisable H atom on eitlier aldehyde. If we use malonic acid for the second step, cychsation and decarboxylation will be spontaneous (Monatshefte, 1904, 2 13). 

Compounds that readily undergo thermal decarboxylation include those related to malonic acid On being heated above its melting point malonic acid is converted to acetic acid and carbon dioxide... 

Transition state in thermal decarboxylation of malonic acid... 

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 19 17 11 Dicarboxylic acids (malonic acids) and p keto acids undergo thermal decarboxylation by a mechanism m which a p carbonyl group assists the departure of carbon dioxide... 

Converting the C 2 alkylated derivative to the corresponding malonic acid deriva tive by ester hydrolysis gives a compound susceptible to thermal decarboxylation Tern peratures of approximately 180°C are normally required... 

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 ... 

Reactions. Heating an aqueous solution of malonic acid above 70°C results in its decomposition to acetic acid and carbon dioxide. Malonic acid is a useful tool for synthesizing a-unsaturated carboxyUc acids because of its abiUty to undergo decarboxylation and condensation with aldehydes or ketones at the methylene group. Cinnamic acids are formed from the reaction of malonic acid and benzaldehyde derivatives (1). If aUphatic aldehydes are used acryhc acids result (2). Similarly this facile decarboxylation combined with the condensation with an activated double bond yields a-substituted acetic acid derivatives. For example, 4-thiazohdine acetic acids (2) are readily prepared from 2,5-dihydro-l,3-thiazoles (3). A further feature of malonic acid is that it does not form an anhydride when heated with phosphorous pentoxide [1314-56-3] but rather carbon suboxide [504-64-3] [0=C=C=0], a toxic gas that reacts with water to reform malonic acid. 

Uses. Malonic acid is used instead of the less expensive malonates for the introduction of a CH—COOH group under mild conditions by Knoevenagel condensation and subsequent decarboxylation. The synthesis of 3,4,5-trimethoxycinnaniic acid, the key intermediate for the coronary vasohdator Cinepa2et maleate [50679-07-7] (5) involves such a pathway (13). 

With active methylene compounds, the carbanion substitutes for the hydroxyl group of aHyl alcohol (17,20). Reaction of aHyl alcohol with acetylacetone at 85°C for 3 h yields 70% monoaHyl compound and 26% diaHyl compound. Malonic acid ester in which the hydrogen atom of its active methylene is substituted by A/-acetyl, undergoes the same substitution reaction with aHyl alcohol and subsequendy yields a-amino acid by decarboxylation (21). 

Order of thermal stabiUty as determined by differential thermal analysis is sebacic (330°C) > a2elaic = pimelic (320°C) > suberic = adipic = glutaric (290°C) > succinic (255°C) > oxahc (200°C) > malonic (185°C) (19). This order is somewhat different than that in Table 2, and is the result of differences in test conditions. The energy of activation for decarboxylation has been estimated to be 251 kj/mol (60 kcal/mol) for higher members of the series and 126 kJ/mol (30 kcal/mol) for malonic acid (1). 

After hydrolysis, fluonnated derivatives of alanine are obtained in both cases because decarboxylation of the substituted malonic acid occurs (equation 109)... 

In contrast to other acids, anhydrous hydrogen fluoride does not cause hydroly SIS and decarboxylation of the malonic acid residues in these reactions [5]. It is a good reagent for the cyclization of a-benzamidoacetophenones to 2,5 diphenyl-oxazoles [6] (equation 7) The same reaction with concentrated sulfuric acid gives cyclic product with only a 12% yield [6]... 

The protons attached to C-2 of malonic acid are not duectly involved in the process and so may be replaced by other substituents without much effect on the ease of decarboxylation. Analogs of malonic acid substituted at C-2 undergo efficient thermal decarboxylation. 

Notice that the caiboxyl group that stays behind during the decarboxylation of malonic acid has a hydroxyl function that is not directly involved in the process. Compounds that have substituents other than hydroxyl groups at this position undergo an analogous decarboxylation. 

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