Malonic nitro-, esters

Active methylene or methine compounds, to which two EWGs such as carbonyl, alko.xycarbonyl, formyl, cyano, nitro, and sulfonyl groups are attached, react with butadiene smoothly and their acidic hydrogens are displaced with the 2,7-octadienyl group to give mono- and disubstituted compounds[59]. 3-Substituted 1,7-octadienes are obtained as minor products. The reaction is earned out with a /3-keto ester, /9-diketone, malonate, Q-formyl ketones, a-cyano and Q-nitro esters, cya noacetamide, and phenylsulfonylacetate. Di(octadienyl)malonate (61) obtained by this reaction is converted into an... 

One effective method for synthesis of tryptophan derivatives involves alkylation of formamido- or acetamido- malonate diesters by gramine[l,2]. Conversion to tryptophans is completed by hydrolysis and decarboxylation. These reactions were discussed in Chapter 12. An enolate of an a-nitro ester is an alternative nucleophile. The products can be converted to tryptophans by rcduction[3,4],... 

The reaction was carried out with /3-keto esters, /3-diketones, malonate, a-formyl ketones, a-cyano and a-nitro esters, cyanoacetamide, and phen-ylsulfonylacetate. (PPh3)2PdCl2 was used with sodium phenoxide. Also, Pd(OAc)2 and PPh3 are good catalysts. When bidentate ligand was used, the 1 1 rather than 1 2 addition reaction took place (56). For example, bis(diphenylphosphino) 1,2-ethane (39) produced a mixture of the following 1,4- (59) and 1,2- (60) addition products ... 

Not only allyl j6-keto esters, but also the diallyl malonate derivative 580 underwent decaboxylation-allylation to give allyl o -allylcarboxylate 581. The nitro ester 582 is very reactive and the allylation proceeded even at —50 °C to give the a-allylnitroalkane 583 [209]. 

An earlier version of this reaction condensed 4.18 and malonic acid to give 4.19. Refluxing 4.19 led to the monomer 4.20), which decarboxylated under the reaction conditions to give 3-amino-3-phenylpropanoic acid, 4.21. Doebner condensation with malonic acid itself sometimes leads to very poor yields of product, as seen above. An improvement in the reaction used nitro-ester 4.22 rather than malonic acid, and 4.23 [ethyl 3-(N-phenylamino)-2-nitroprop-2E-enoate] was produced in good yield. 

In 1988 Reetz et al. introduced the concept of metal-free polymerization of acrylates, methacrylates and acrylonitrile [224,225]. Metal-free initiators are salts consisting of a carbanion (A ) having R4N as cationic counterions. They are synthesized by the reaction of neutral CH or NH-acidic compounds such as malonic acid esters, nitriles, sulfones, nitro-alkanes, cyclopentadiene, fluorene derivates, carbazoles and succinimide. Water is removed azeotropically using toluene. 

Carbon-Carbon Bond Formation. Direct coupling of an alcohol with a carbon acid by the use of DEAD/TPP has been limited to only a few examples because of the lack of carbon acids with pAa < 13. If enolizable carbonyl compounds are used, alkylation generally takes place on oxygen. Thus the reaction of 1,3-cyclohexanedione with isopropanol, DEAD, and TPP affords exclusively the O-alkylated product (eq 47). Cyanoacetate reacts at the carbon atom, while diethyl malonate is unreactive. However, the reaction of diethyl malonate with alcohols in the presence of ADDP and BU3P affords C-alkylated products in 3-56% yields (eq 48). Ethyl nitroacetate and nitromalonate oxidize the alcohol via an aci-nitro ester (eq 49). o-Nitroarylacetonitriles of general formula (50) undergo alkylation on carbon (eq 50). ... 

Z-Furan. 3-(5-Nitro-2-furanyl)-2-propenamide, is prepared by condensation of 5-nitro-2-furancarboxaldehyde diacetate with malonic ester followed by PCl chlorination and amination (29). The product was marketed in Japan as a food preservative. 

The Michael reaction occurs with a variety of a,/3-unsaturated carbonyl compounds, not just conjugated ketones. Unsaturated aldehydes, esters, thio-esters, nitriles, amides, and nitro compounds can all act as the electrophilic acceptor component in Michael reactions (Table 23.1). Similarly, a variety of different donors can be used, including /3-diketones, /3-keto esters, malonic esters, /3-keto nitriles, and nitro compounds. 

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. ... 

MALONALDEHYDE, NITRO-, SODIUM DERIVATIVE, 32, 95 Malonic acid, 31, 35 33, 20, 62 Malonic acid, ethylidene, diethyl ESTER, 32, 54... 

This reaction was easily performed with malonic ester derivatives using approaches described above for nitro carbanions. It should be noted that the anion of malonic ester can be prepared not only by the reactions of bases with malonates but also by desilylation of silyl ketene acetal (449) with fluoride anion. 

The carbanion derived from dimethyl malonate reacts with the cyclic nitro compounds 422 of ring size 5, 6, 7, 8 and 12 to afford the corresponding esters 423. Acyclic allylic nitro compounds 424 (R = Me, CH2OAC or CC Et) are attacked by bulky nucleophiles, such as dimethyl malonate anion, mainly at the terminal primary carbon atom to give rearranged products 425, whereas smaller nucleophiles, e.g. the anion derived from methyl cyanoacetate, react at the tertiary carbon atom to yield 426409a 453 455. 

In 2006, our research group reported a novel MCR based on the reactivity of a-acidic isocyano esters (1) toward 1-azadienes (84) generated by the 3CR between phosphonates, nitriles, and aldehydes [169]. Remarkably, the dihydropyridone products (85) for this 4CR contained the intact isonitrile function at C3. The exceptional formation of the 3-isocyano dihydropyridone scaffold can be explained by the Michael-attack of the a-deprotonated isonitrile (1) to the (protonated) 1-azadiene (84), followed by lactamization via attack of the ester function by the intermediate enamine. Although in principle the isocyano functionality is not required for the formation of the dihydropyridone (85) scaffold, all attempts using differently functionalized esters (e.g., malonates, ot-nitro, and a-cyano esters) gave lower yields of the dihydropyridone analogs [170] (Fig. 26). 

The carbon nucleophiles in amine-catalyzed reaction conditions are usually rather acidic compounds containing two electron-attracting substituents. Malonic esters, cyanoacetic esters, and cyanoacetamide are examples of compounds which undergo condensation reactions under Knoevenagel conditions.115 Nitroalkanes are also effective nucleophilic reactants. The single nitro group sufficiently activates the a hydrogens to permit deprotonation under the weakly basic conditions. Usually, the product that is isolated is... 

Melphalan and the racemic analog have been prepared by two general routes (Scheme I). In Approach (A) the amino acid function is protected, and the nitrogen mustard moiety is prepared by conventional methods from aromatic nitro-derivatives. Thus, the ethyl ester of N-phthaloyl-phenylalanine was nitrated and reduced catalytically to amine I. Compound I was reacted with ethylene oxide to form the corresponding bis(2-hydroxyethyl)amino derivative II, which was then treated with phosphorus oxychloride or thionyl chloride. The blocking groups were removed by acidic hydrolysis. Melphalan was precipitated by addition of sodium acetate and was recrystallized from methanol. No racemization was detected [10,28—30]. The hydrochloride was obtained in pure form from the final hydrolysis mixture by partial neutralization to pH 0.5 [31]. Variants of this approach, used for the preparation of the racemic compound, followed the same route via the a-acylamino-a-p-aminobenzyl malonic ester III [10,28—30,32,33] or the hydantoin IV [12]. 

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