From Aminomalonates

Diethyl aminomalonate reacts with 1,3-diketones in boiling acetic acid to the corresponding pyrrolecarboxylates 11 (87JOC3986). From N-ac t-amidomalonate and acroleins, pyrrolidines were prepared and they were further transformed into functionalized pyrroles, which are a part of the antibiotic lyncomycin and an antimalarial agent (67JA2459 72JMC1255). 

A substituted acetamidomalonic ester, tetraethyl 1 -acetamido-4-hydroxy-butane-l,l,3,3-tetracarboxylate, was used in the preparation of cis- and frans-pyrrolidine-2,4-dicarboxylic acids, cyclic analogs of glutamic acid (91TL3049). 

A new synthetic method for 4-hydroxyproline was devised from N-acylated diethyl aminomalonate. In the first step this reacts with acrolein in the presence of a base to give 12 (90JHC507). 

In connection with the synthesis of cytohalasin B, a pyrrole derivative 13 was prepared from methyl (5)-3-aminophenylbutyrate (78JA7775). In connection with the synthesis of l,2,4-triazolo[4,3-a]pyrazine derivatives with human Renin inhibitor activity, a /3,y-diamino acid derivative was transformed into a pyrrolidin-2-one (91JMC151). 

From Ser via methyl 2-benzamido-3-chloropropionate, an azahexadiene was prepared which was photocyclized and hydrolyzed to the bicyclic amino acid 14 which is found in the Atelia Herbert Smithii plant (88JOC4793). 

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An intramolecular ring expansion of aziridine esters can be accomplished by installing an appropriate nucleophilic entity in these substrates. Conversion of the ester moiety into carboxamides derived from aminomalonate ester gives compounds 44 containing the requisite nucleophilic site in the malonate moiety (Scheme 35). 

Formation of chiral a-amino acids from aminomalonic acids via decarboxylative protonation is readily accomplished in the presence of thiourea 1 (ex quinidine)/ The diaster-eomeric 2 (ex quinine) has been employed to generate monomethyl esters in chiral form by methanolysis meso-cydic anhydrides ... 

Amides can be easily prepared under mild conditions from acid chlorides with ammonium acetate and from oximes by a mild modification of the Beckmann rearrangement Lactams can be prepared by this method from cyclic oximes. and 7-Lactams have been synthesized in a simple manner from aminomalonates a-Aminoacids can be converted into a-ketoacids and related compounds through 2-trifluoromethyl-5-oxazolones... 

Lactams from aminomalonic acid esters and y-Lactams... 

B. Diethyl aminomalonate hydrochloride. The crude diethyl aminomalonate is diluted with 80 ml. of dry ether and filtered to remove a small amount of white solid. The filtrate is collected in a 250-ml. Erlenmeyer flask and cooled in an ice bath. Dry hydrogen chloride is passed just over the solution while it is being stirred mechanically (Note 6). The fine white crystals which precipitate are collected by suction filtration and washed three times with a total of 60 ml. of dry ether (Note 7). The filtrate and washings are treated again with hydrogen chloride, and a second crop of diethyl aminomalonate hydrochloride is collected and washed as before. This process is repeated until no further precipitation results from passing hydrogen chloride into the solution. A total of 16.5-17.4 g. (78-82% yield based on diethyl malonate) of diethyl aminomalonate hydrochloride, m.p. 162-163°, is obtained. Recrystallization from alcohol-ether affords a purer product, 164-165°. 

Intermediate carbenes are also involved in the alkylation by haloforms of carbanions derived from Schiff bases of a-ammo esters [126] or aminomalonates... 

Diethyl aminomalonate, from reduction of diethyl isonitrosomalonate, 40, 2 ... 

A. G. Ogston in 1948 explained the dilemma of how an enzyme can enan-tiospecifically produce a chiral product from a prochiral molecule such as citric acid or 2-aminomalonic acid. He pointed out two requirements three-point contact at three active sites (a, b, and c ) and catalytic dissimilarity between the two active sites (a and b ) associated with the pro-R and pro-5 groups (a and b) of the prochiral molecule as shown in Fig. 3.2. 

Diethyl acetylenedicarboxylate as di-eneophile, 40, 86,87 Diethylamine, condensation with tri-chloroacetyl chloride, 41, 21 Diethyl aminomalonate, from reduction of diethyl isonitrosomalonate, 40, 24... 

The stereoselective Michael addition of the anion derived from diethyl acetyl-aminomalonate with chalcone has been found to be most effective under soliddiquid two-phase conditions in the absence of an added solvent [62]. For optimum overall conversion and enantiomeric excess (56% with 60% ee), A-benzyl-V-methyl-... 

The synthesis of 3-carboxyalkyl oxadiazoles, starting from acyl-aminomalonic acid monoesters has been described p. 8l6 33a). 

With the same protocol, a heterocyclic dibenzoate 86 derived from furan in one step has been efficiently desymmetrized to provide facile entry to either D or L nucleosides (see Scheme 8E.10). As depicted in Scheme 8E.10, the catalyst derived from ligand 71 gave rise to high enantioselectivities in the alkylation with both a purine 83 and a pyrimidine 87 [62], Subsequent allylic alkylations with an achiral ligand introduced the tartronate and aminomalonate moieties to furnish enantiomerically pure Ci s-2,5-disubstituted-2,5-dihydrofurans 89 and 91, respectively. Only six steps from furan were required to synthesize the alio and talo isomers of the nucleoside skeleton of the polyoxin-nikkomycin complexes. It should be noted that the corresponding enzymatic desymmetrization of substrate 86 is impossible because the product is labile. 

Two approaches to the 2-benzazepine system, in particular the 2-benzazepinone 142, have been reported by Le Diguarher et al. The first started from (acid-catalyzed cyclization to 141 N-alkylation and carbamate deprotection then afforded 142. The second route was based on A-HOC aminomalonate 144 and 2,2 -dibromo-o-xylene, and then steps via 145 and... 

Acylaminomalonic esters and related reagents are widely used for the synthesis of a-amino acids. The method differs from those syntheses already discussed in that the amino group is incorporated into the system from the outset. A popular reagent is diethyl acetamidomalonate (35). The acetamido group can readily be introduced into the reactive methylene position in diethyl malonate by first converting the latter into the hydroxy-imino derivative (33) by reaction with nitrous acid or an alkyl nitrite (cf. Section 4.2.7, p. 413). This derivative is then reduced catalytically to diethyl aminomalonate (34) which is acetylated using acetic anhydride. 

B) Preparation of 7-Chloro-3-Methoxycarbonyl-5-Phenyl-2-Oxo-2,3-Dihydro-lH-Benzo[f]-l,4-Diazepine (4347 CB) A solution of 9.2 g (0.04 mol) of compound 4356 CB in 20 ml of methanol is added dropwise, in the course of one hour and 30 minutes, to a boiling solution of 9.2 g (0.05 mol) of the hydrochloride of methyl aminomalonate in 30 ml of methanol. When this is completed, heating under reflux is continued for 30 minutes and the product then concentrated to dryness under reduced pressure. The residue is taken up in water and ether, the ethereal layer separated, the product washed with water and dried over sodium sulfate. The solvent is evaporated under reduced pressure. The residue, which consists of the methyl ester, could not be obtained in the crystalline state. It is dissolved in 25 ml of acetic acid, heated under reflux for 15 minutes, the product evaporated to dryness and the residual oil taken up in ether. A colorless solid separates which is filtered by suction and recrystallized from methanol. Colorless crystals are obtained (4.7 9) MPk (Kofler block) 226°C. A second crop (1.5 g) is obtained on concentration of the mother liquor MPk (Kofler block) 222°C total quantity 6.2 g, corresponding to a yield of 47%. 

A mixture of 2.0 g of l-(2-nitro-3-chlorophenyl)-l,3-butanedione, 1.9 g of diethyl aminomalonate, 1.5 ml of absolute ethyl alcohol and two drops of piperidine was refiuxed for 5 hours. After cooling, the reaction mixture was allowed to stand and then crystals were separated. The crystals were collected by filtration and then dried to obtain 2.5 g of colorless crystals. The crystals were recrystallized from a mixed solvent of benzene and ether to obtain diethyl N-[ 1-methyl-3-(2-nitro-3-chlorophenyl)-3-... 

A solution of 0.8 g of diethyl N-[l-methyl-3-(2-nitro-3-chlorophenyl)-3-oxopropylidene]aminomalonate in 4 ml of absolute tetrahydrofuran was added dropwise with stirring to a solution prepared with 8 ml of absolute ethanol and 100 mg of metallic sodium. After the reaction mixture was refluxed for 4.5 hours, the solvents were distilled off under reduced pressure. The residue was added with an ice-water and the solution was extracted with ether. The extract was washed with water, dried over anhydrous magnesium sulfate, after which ether was distilled off. The residue was recrystallized from benzene to obtain ethyl 3-(2-nitro-3-chlorophenyl)-5-methylpyrrole-2-carboxylate as colorless needles having MP 220°-223°C. 

OMe was found by Fujino et al.(11) to be 22000 33000 times sweeter than sucrose. It is not exactly known whether the sweettasting isomer has the L-L(or S-R) or the L-D(or S-S) configuration because of ready racemization. From the examination of its projection formula, it could be predicted that the L-L(or S-R) isomer (42), in which aminomalonic acid diester takes an L(or R)-configuration, would be sweet. This prediction agreed with that reported in the literature (14). 

An inspection of the IR spectra of the condensation products derived from 4-phenyl-2-ethoxy-A1 -pyrroline with diethyl aminomalonate indicates that the hydroxyimidazole (25a) predominates (82JHC193). 

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