Malonates, alkylation

The mono-alkyl malonic ester may be hydrolysed by alcoholic potassium... 

Condensatron between lithium acetylides and dibromodifluoromethane [124] or dichlorofluoromethane [125] leads to fluorohaloacetylenes (equation 107) Sodium alkyl malonates are also alkylated by dihalogenodifluoromethanes [124] (equation 108) These reactions involve difluorocarbene as intermediate (for the mechanism of the Cp2Br2 condensation, see equation 15)... 

The rate of the alkylation reaction depends on the enolate concentration, since it proceeds by a SN2-mechanism. If the concentration of the enolate is low, various competitive side-reactions may take place. As expected, among those are E2-eliminations by reaction of the alkyl halide 2 with base. A second alkylation may take place with mono-alkylated product already formed, to yield a -alkylated malonic ester however such a reaction is generally slower than the alkylation of unsubstituted starting material by a factor of about 10. The monoalkylation is in most cases easy to control. Dialkylated malonic esters with different alkyl substituents—e.g. ethyl and isopropyl—can be prepared by a step by step reaction sequence ... 

CH3.(CH2)2.C(C02.C2H5XC0.N3) mw 198.23 N 21.20% OB to C02 -153.36% ypl oil, expl. Sol in eth and CC14. Prepn is by reacting the K salt, of the half (or mono) ethyl ester of propyl malonic acid with nitrous acid Refs 1) Beil, not found 2) T. Curtius W, Lehmann, Transformation of alkylated malonic acids into a-amino acids. III. Synthesis of cr-aminovaleric acid, propylmalonylazidic acid. . JPraktChem 125, 211-302 (1930) CA 24, 3215(1930)... 

Reaction of 1,3-dicarbonyl compounds with IVJV-dimethylformamide dimethyl acetal followed by malonamide in the presence of sodium hydride gives 5,6-disubstituted 1,2-dihydro-2-oxopyridine-3-carboxamides, whereas reaction of the intermediate enamines with cyanothioacetamide or cyanoacetamide in the presence of piperidine provides 2-thioxopyridine-3-carboxamides and 4,5-disubstituted l,2-dihydro-2-oxopyridine-3-carboxamides, respectively <95S923>. P-Enaminonitriles 14 react with p-ketoesters and alkyl malonates, in the presence of stoichiometric amounts of tin(IV) chloride, to afford 4-aminopyiidines 15 and 4-amino-2-pyridones 16 <95T(51)12277>. 

Ketoesters from Imidazolides and Magnesium Bis(alkyl malonates) or Bis(alkyl thiomalonates)... 

Method C The malonic ester (15 mmol) is stirred with aqueous NaOH (50%, 30 ml) and TEBA-CI (3.54 g, 15 mmol). The alkylating agent (0.25 mmol) is then added and the mixture is stirred for 1 h at room temperature. The mixture is diluted with H,0 (75 ml) and extracted with Et,0 (3 x 25 ml). The dried (MgS04) extracts are evaporated to give the alkylated ester. Acidification of the aqueous phase with cone. HCI and extraction with Et,0 (3 x 25 ml) yields the alkylated malonic acid or r-butyl ester. 

Method E (microwave reaction) An intimate mixture of CH2(C02Et), (1.62 g, 10 mmol), the alkylating agent (10-25 mmol), TBA-Br (0.32 g, 1 mmol), and anhydrous K2CO, (5.48 g, 40 mmol) is irradiated in a 650 W microwave oven for 2 min. Et20 (50 ml) is added, and the mixture is filtered and evaporated to yield the alkylated malonate. 

CH CH CH COOH CHjCHjCHjBr is used to alkylate malonic ester. 

In the next stage the introduction of a fluorine atom onto the chiral center was examined with some 2-fluoro-2-alkyl malonic acid diesters with lipases. When the hydrolysis of 2-fluoro-2-methyl malonic aicd diester was examined with pig... 

Shinoda examined the variation of the CMC of various potassium alkyl malonates, RCH(COOK)2, with the addition of univalent salts. For R = C8, C,2, CM, and C16, the log-log plots of CMC verus counterion concentration produce parallel straight lines of slope -1.12. Criticize or defend the following proposition According to the analysis presented in Example 8.1, the slope of this type of plot equals —(1 — a), meaning that a = —0.12 this negative function apparently means that the micelle binds an excess of counterions and has the opposite charge from that expected. 

Now clearly there will have to be some functional group adjustment in the synthesis because a hydrolysis of the alkylated malonate must be carried out in order to give decarboxylation to the acetic ester derivative. Either an unsymmetric... 

In the presence of 10 mol% of this catalyst, the malonates 56 could be added to several nitroolefins 57 with up to 93% ee. Apolar solvents such as toluene are crucial for high ee values. It is also noteworthy that (i) good ee can be achieved with catalyst 55 even in the absence of solvents, i.e. with a mixture of the neat starting materials 56 and 57, and that (ii) the range of Michael donors/acceptors includes aryl- and alkyl-substituted nitroolefins and 2-alkylated malonates. 

A few years later, Conrad showed that an alcoholic solution of sodium ethoxide would suffice, in place of metallic sodium or the dry ethoxide, for this type of reaction , he applied his method in particular to the preparation of alkyl malonic esters.10... 

If the enolization has enough time to proceed, the transformation in Figure 12.4 completely leads to a brominated /J-ketoester. Basically, the same method can be employed to also a-brominate ketones (Figure 12.5), alkylated malonic acids (Figure 12.6), acid bromides (Figure 12.7,12.8) and acid chlorides (not shown). The mechanistic details are detailed in the cited figures. Look at how similar they are. 

According to Figure 12.6, the bromination of alkylated malonic acids A initially furnishes oc-brominated alkyl malonic acids B. Upon heating they decarboxylate to form the a-bromo-carboxylic acids C. This two-step approach to C can be managed without using the expensive phosphorus tribromide, which would be required in the alternative single-step Hell-Volhard-Zelinsky synthesis of this compound (Figures 12.7, 12.8). 

Fig. 12.6. Bromination of malonic acids or alkylated mal-onic acids. The figure shows the mechanisms of the acid-catalyzed enolization (alkyl) malonic acid enol of (alkyl) malonic acid (E) and the actual bromination (E —> B).

Fig. 13.36. Malonic ester synthesis of altylated acetic acids I preparation of alkylated malonic esters.

Oxidative coupling occurred in several isopropylidene-5-alkyl malonates (Meldrum s acid derivatives) on treatment with DIB under phase transfer catalysis [34] ... 

Synthesis of Fluorinated Propane-1,3-diol from Alkyl Malonates. . 160... 

Zhao XY, Janda KD, Synthesis of alkylated malonates on a traceless linker derived soluble polymer support, Tetrahedron Lett., 31 5437-5440, 1997. 

Fig. 10.34. Malonic ester synthesis of alkylated acetic acids II hydrolysis and decarboxylation of the alkylated malonic ester.

The product of a malonic ester synthesis is a substituted acetic acid, with the substituent being the group used to alkylate malonic ester. In effect, the second carboxyl group is temporary, allowing the ester to be easily deprotonated and alkylated. Hydrolysis and decarboxylation remove the temporary carboxyl group, leaving the substituted acetic acid. 

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