Carboxylic acid amid malonic

Eutectics formed between quaternary ammonium salts and hydrogen bond donors (HBD) have potential windows that tend to be controlled by the stability of the carboxylic acid, amide or alcohol. In general the potential windows depend upon the pfCa of the HBD. Figure 4.13 shows the potential windows of eutectics formed between ChCl with ethylene glycol, urea and malonic acid. 

Carboxylic acid amides and cyclobutanones from malonic acids via cyclic keteneacylals s. 19, 285... 

Esters, amides, and primary alcohols are obtained from benzo[6]-thiophene carboxylic acids by standard procedures.337 481,585 692 093,695 Acid chlorides undergo the Arndt-Eistert reaction,337,568,689 react with diethyl ethoxymagnesium malonate to give the corresponding methyl ketone,144 557 and are reduced to the aldehyde with 1 ithium tri-ferf-butoxy aluminohydride.33 7... 

First all three ester bonds and both amide bonds are hydrolyzed to carboxylic acid groups by the aqueous acid. The mechanisms for these reactions are discussed in Section 19.5. The ester hydrolyses follow the exact reverse of the Fischer esterification mechanism shown in Figure 19.3, and the amide hydrolysis occurs by a very similar mechanism. The product of these hydrolysis steps has three carboxylic acid groups and one amino group. Two of these acid groups are attached to the same carbon so that one can be eliminated as carbon dioxide by the cyclic mechanism described in Section 20.4 for the malonic ester synthesis ... 

If we copy Nature rather more exactly, the Claisen ester condensation can be carried out under neutral conditions. This requires rather different reagents. The enol component is the magnesium salt of a malonate mono-thiol-ester, while the electrophilic component is an imidazolide—an amide derived from the heterocycle imidazole. Imidazole has a pK of about 7, Imidazolides are therefore very reactive amides, of about the same electrophilic reactivity as thiol esters. They are prepared from carboxylic acids with carbonyl diimidazole (CDI). 

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). ... 

The heterocoupling of carboxylic acids bearing chiral auxiliaries has been used to study the diastereoselectivity of the coupling of Kolbe radicals [204b]. For that purpose, 2-substituted malonic acid amides bound to seven different chiral auxiliaries were coelectrolyzed with different coacids [Eq. (200]- The yields in heterodimer ranged between 13 to 69%, and the diastereoselectivities between 20 and 86% de. 

The second target, 4-oxo-4H-l-benzopyran-3-carboxylic acids (3) were obtained by Jones oxidation of or hydrolysis of the 3-carbonitrile derivatives ( ) described below (14). The third target, 3-(4-oxo-4H-1-benzopyran-3)acrylic acids (4) were synthesized generally by the Knoevenagel reaction of 3-carboxaldehydes (2) with malonic acid ( 1 ). In the meantime, it was found that the 3-carboxaldehydes ( ), which were able to function as P-dialdehyde compounds, were attacked by amide groups in some cases, to give 2(IH)-pyridone derivatives after condensation with malonic acid derivatives. Thus, condensation of 2 with malonodiamide in pyridine gave initially acrylamide derivatives which were converted into 3-carbamoyl-5-(2-hydroxybenzoyl)-2(IH)-pyridones ( ) (24) ... 

Now acid (or base) is used to convert the esters into carboxylic acids and to hydrolyze the amide. Heating decarboxylates the malonic acid and liberates the amino acid. 

Other electrophiles, such as Michael acceptors, can also be involved in the a-alkylation step. This has been exploited in the conjugate addition of enantiopure lithium amides 60 to unsaturated esters 61, followed by trapping of the resulting enolate with alkylidene malonates. This constitutes a useful methodology for the asymmetric synthesis of p-amino-a-substituted carboxylic acid derivatives 62 (Scheme 11.24) [65]. 

One of the most attractive options for asymmetric aldol reactions available to the synthetic chemist is to use enolates of carboxylic acid derivatives (inter alia ester, amide, or imide) with an appended chiral auxiliary (alcohol, amine, urethane). An early example of this approach dates back to 1938, when McKenzie reported that benzaldehyde undergoes addition by (-)-menthyl malonate (42) to give propanoic acid derivative 43 in 21 % ee (Equation 4) [43]. The modest selectivity was attributed to the conformational flexibility of ester enolates (cf. 44). 

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