Mono-Ethyl malonate

Substitution Derivatives of Ethyl Malonate, Ethyl malonate resembles ethyl acetoacetate in that it gives rise to mono- and di-substituted derivatives in precisely similar circumstances. Thus when ethanolic solutions of ethyl malonate and of sodium ethoxide are mixed, the sodium derivative (A) of the enol form is produced in solution. On boiling this solution with an alkyl halide, e.g, methyl iodide, the methyl derivative (B) of the keto form is obtained. When this is treated again in ethanolic solution with sodium ethoxide, the... 

It follows therefore that ethyl malonate can be used (just as ethyl aceto- acetate) to prepare any mono or di-substituted acetic acid the limitations are identical, namely the substituents must necessarily be alkyl groups (or aryl-alkyl groups such as CjHjCHj), and tri-substituted acetic acids cannot be prepared. Ethyl malonate undergoes no reaction equivalent to the ketonic hydrolysis of ethyl acetoacetate, and the concentration of the alkali used for the hydrolysis is therefore not important. 

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)... 

Derivatives,—Of the salts of malonic acid only the alkali metal salts are soluble. The esters of malonic acid have been referred to as the most important derivatives. Di-ethyl malonate is a colorless insoluble liquid boiling at 198°. The mono-sodium di-ethyl ester, referred to in the above reactions, forms white glistening crystals. The disodium di-ethyl malonate forms gall-like masses and is easily decom-... 

From Malonic Ester.—The same constitution is also proven by an interesting synthesis from malonic ester. Mono-sodium di-ethyl malonate reacts with monobrom, or mono-iodo acetic acid, and yields the ester of a tri-carboxy acid which after hydrolysis to the acid loses carbon di-oxide and yields succinic acid. 

The acyl carbon of readily available amino acids such as alanine can be converted to a ketone moiety by activation of the acid with carbonyl diimidazole (CDI) and then condensation with an enolate, such as the magnesium enolate of malonic acid, mono ethyl ester. In this particular example, N-Boc alanine was converted to 1.206 using this method O Catalytic hydrogenation of the ketone moiety gave the alcohol group in 1.207, and conversion to the chloride and base induced dehydrohalogen-ation gave ethyl 4-(N-Boc amino)pent-2-enoate (7.205). 

The acid moiety of an amino acid can be activated for acyl substitution rather than converted to an aldehyde for acyl addition. Boc-alanine was converted to an acyl imidazole by reaction with carbonyl diimidazole (CDI see chapter two, section 2.4), and then condensed with the magnesium enolate of the mono ethyl ester of malonic acid to give keto-ester 5.9. Subsequent catalytic hydrogenation of the ketone moiety gave ethyl 3-hydroxy-5-(N-Boc amino)penlanoate, 5.10 Once the o... 

Ethane tetracarboxylic ethyl ester can be regarded as composed of two malonic ester residues, each acting as a mono-alkyl substituent to the other. The two remaining hydrogen atoms therefore still retain acidic properties, and consequently the ester gives with sodium ethoxide a di-sodium derivative. 

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 ... 

The preparation of malonic acid monoesters has been demonstrated using the microbial nitrilase activity of Corynebacterium nitrilophilus ATCC 21 419, Gordona terrae MA-1, or Rhodococcus rhodochrous ATCC 33 025 to hydrolyze methyl cyanoacetate, ethyl cyanoace-tate, M-propyl cyanoacetate, isopropyl cyanoacetate, M-butyl cyanoacetate, tertbutyl cyanoacetate, 2-ethylhexyl cyanoacetate, allyl cyanoacetate, and benzyl cyanoacetate [96]. By maintaining the concentration of nitrile in a reaction mixture at <5 wt%, significant inactivation of the nitrilase activity was avoided for example, a total of 25 g of M-propyl cyanoacetate was added in sequential 5g portions to a lOOmL suspension of Rhodococcus rhodochrous ATCC 33 025 cells (OD630 = 5.6) in 50 mM phosphate buffer (pH 7.0) over 30h at 25 °C to produce mono-M-propyl malonate in 100% yield (Figure 8.17). 

The synthesis of the moxifloxacin core (de Souza, 2006 Martel et al., 1997 Seidel et al., 2000) proceeds from a Grohe-Heitzer sequence as described earlier in the chapter. Unlike the traditional Grohe-Heitzer sequence, however, the opening step involved the reaction between acid chloride 101 with the mono potassium salt of malonic acid monoethyl ester (102) in the presence of triethylamine to deliver ketoester 103 (Scheme 4.18). Treatment of 103 with ethyl orthoformate furnished acrylate 104, which reacted with cyclopropyl amine to afford 105. Cyclization of 105 in the presence of sodium fluoride in DMF gave the moxifloxicin core 106. 

Reaction XLIV. (b) Condensation of Alkyl and Aryl Halogen Compounds with the Sodio- and other Metallo-derivatives of Ethyl Aceto-acetate and its Homolognes. (A., 186, 214 201, 143 213, 143.)—Like malonic ester, acetoacetic ester contains two 1 3-carbonyl groups with a methylene group in position 2. It is only to be expected then that it yields with metallic sodium or sodium alcoholate sodio-derivatives from which mono- and di-, alkyl and aryl homologues can be obtained by treatment with a suitable halide, including halogen esters. Acetoacetic acid... 

The Brown-Walker 1 method has been found to be of excellent service in the electrolysis of the potassium salts of the mono-esters of malonie acid. The formation of the diethyl ester of succinic acid from ethyl potassium malonate has already been mentioned fp. 103). 

Ethyl cyanoacetate is readily alkylated under the usual conditions employed for the malonic and acetoacetic ester syntheses (methods 299 and 213) to yield mono- and di-substituted cyano acetates. These substances may then be hydrolyzed and decarboxylated to furnish mono-carboxylic acids (method 265). In many instances, it is difficult to avoid the formation of the dialkylated ester, the yields may be low. Sev-... 

CsLa-MCM-41 catalyzes the Michael addition of ethyl cyanoacetate (2) to ethyl acrylate (14) (Scheme 9). Besides formation of the mono adduct (15), bis adduct 16, formed by a double Michael addition, is produced consecutively. Although the basicity of CsLa-MCM-41 is quite mild, its performance in this reaction is very good. Table 4 compares the activity and selectivity obtained with different catalysts. Although product selectivity is probably also controlled by the mesoporous MCM-41 support, the basicity of CsLa-MCM-41 is too weak to catalyze the Michael addition of diethyl malonate under the same conditions. 

Because initiation of vinyl ethers with HI/I2 yields polymers with extremely narrow poly-dispersities," " bifunctional vinyl ethers can be used in combination with HI/I2 to polymerize vinyl ethers and produce a,co-diiodo telechelics (Scheme 39). This method has been used to produce telechelics from ethyl vinyl ether, methyl vinyl ether and hexadecyl (cetyl) vinyl ether. Treatment of the living poly(ethyl vinyl ether) with mono- and di-amines yields telechelics with amino end groups (Scheme 39, equation 41). More jecently, telechelic poly(vinyl ether)s with terminal malonate or carboxy groups were synthesized using both a functional initiator and a functional terminator according to Scheme 40." ... 

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