Esters, carboxylic acid malonic

The direct fluorination with elemental fluorine at — 78 "C of trimethylsilyl enol ethers derived from diketones results in the formation of the corresponding monofluoro diketones 11 in moderate yield. The trimethylsilyl ethers from cyclic diketones undergo smooth fluorination to give the enol forms, c.g. 12, and not the keto forms.Higher yields are generally observed for the analogous reactions of silyl derivatives of esters, carboxylic acids, malonates, dimethyl amides and lactones (Table 4). ... 

Maleic acid, structure of, 753 Malic acid, structure of, 753 Walden inversion of, 359-360 Malonic ester, carboxylic acids from, 856-858... 

Trimethylsilyl esters Carboxylic acids are converted into the trimethylsilyl esters in generally high yield on reaction with 1 in CC14 even in the absence of a catalyst. The method is particularly useful for silylation of malonic acids without decarboxylation. 

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 malonic ester synthesis is a method for the preparation of carboxylic acids and is represented by the general equation... 

Among the methods for preparing carboxylic acids carboxylation of a Grignard reagent and preparation and hydrolysis of a nitrile convert RBr to RCO2H The malonic ester synthesis converts RBr to RCH2CO2H... 

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... 

Malonic ester synthesis (Section 21 7) Synthetic method for the preparation of carboxylic acids involving alkylation of the enolate of diethyl malonate... 

As noted previously, the overall effect of the malonic ester synthesis is to convert an alkyl halide into a carboxylic acid while lengthening the carbon chain by two atoms. 

Using the Malonic Ester Synthesis to Prepare a Carboxylic Acid... 

Strategy The malonic ester synthesis converts an alkyl halide into a carboxylic acid having two more carbons. Thus, a seven-carbon acid chain must be derived from the five-carbon alkyl halide 1-bromopentane. 

Alpha hydrogen atoms of carbonyl compounds are weakly acidic and can be removed by strong bases, such as lithium diisopropylamide (LDA), to yield nucleophilic enolate ions. The most important reaction of enolate ions is their Sn2 alkylation with alkyl halides. The malonic ester synthesis converts an alkyl halide into a carboxylic acid with the addition of two carbon atoms. Similarly, the acetoacetic ester synthesis converts an alkyl halide into a methyl ketone. In addition, many carbonyl compounds, including ketones, esters, and nitriles, can be directly alkylated by treatment with LDA and an alkyl halide. 

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 ... 

Compounds 137 and 138 are thus synthons for carboxylic acids this is another indirect method for the a alkylation of a carboxylic acid, representing an alternative to the malonic ester synthesis (10-104) and to 10-106 and 10-109. The method can be adapted to the preparation of optically active carboxylic acids by the use of a chiral reagent. Note that, unlike 132, 137 can be alkylated even if R is alkyl. However, the C=N bond of 137 and 138 cannot be effectively reduced, so that aldehyde synthesis is not feasible here. ... 

The alkylation of activated halogen compounds is one of several reactions of trialkylboranes developed by Brown (see also 15-16,15-25,18-31-18-40, etc.). These compounds are extremely versatile and can be used for the preparation of many types of compounds. In this reaction, for example, an alkene (through the BR3 prepared from it) can be coupled to a ketone, a nitrile, a carboxylic ester, or a sulfonyl derivative. Note that this is still another indirect way to alkylate a ketone (see 10-105) or a carboxylic acid (see 10-106), and provides an additional alternative to the malonic ester and acetoacetic ester syntheses (10-104). 

So do anhydrides and many compounds that enolize easily (e.g., malonic ester and aliphatic nitro compounds). The mechanism is usually regarded as proceeding through the enol as in 12-4. If chlorosulfuric acid (CISO2OH) is used as a catalyst, carboxylic acids can be ot-iodinated, as well as chlorinated or brominated. N-Bromosuccinimide in a mixture of sulfuric acid-trifluoroacetic acid can mono-brominate simple carboxylic acids. ... 

Malonic acid ester synthesis is a classic but still one of the most important C—C bond-forming reactions, because it is widely applicable to various types of compounds and the reaction can be performed under mild conditions without special care to remove the trace amount of water and oxygen contained in the solvent. This reaction is especially useful in the synthesis of carboxylic acids. One important class of carboxylic acids is arylpropionates because optically active ones are known to have anti-inflammatory activity and other interesting physiological... 

Examples of this approach to the synthesis of ketones and carboxylic acids are presented in Scheme 1.4. In these procedures, an ester group is removed by hydrolysis and decarboxylation after the alkylation step. The malonate and acetoacetate carbanions are the synthetic equivalents of the simpler carbanions that lack the additional ester substituent. 

Room temperature conditions affected only the conversion, the reaction rate being smaller (entry 6). Noticeably, cyclization of 2-prop-2-ynyl-malonic acid monomethyl ester le and 2-phenyl-pent-4-ynoic acid If, also occurred with very good results (entries 7, 8). The obtained results may be ascribed to the LDH support, which exhibits enough basic properties to activate the unsubtituted acetylenic carboxylic acids. Basically, the composition of the LDH exhibits only a very minor influence in these reactions. 

The synthesis of ethyl ester derivatives of imidazo[5,l-4][l,2,4]triazole-3-carboxylic acid 64 has been reported (Scheme 25) <1999CHE1349>. Starting from the known substituted 5-diazoimidazoles 276, their coupling with malonic acid derivatives afforded the azo compounds 277, which on treatment with triethylamine in DMF, upon prolonged heating time, gave products 64 in moderate yield. 

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