Diethyl malonate derivatives, reaction

The activated Ba(OH)2 catalyst was successfully used for the Michael reactions of chalcone with active methylene compounds 290), as well as for the Michael reaction of other benzylidene derivatives of acetone, butanone, 3-methylbutanone, 4-methyl-2-pentanone, and 3,3-dimethylbutanone with ethyl acetoacetate and diethyl malonate. The reaction with diethyl malonate gave good yields of the Michael adduct (between 65 and 93%), whereas with ethyl acetoacetate various products were obtained, depending on temperature and amount of catalyst (Scheme 43) 291). Thus, by varying the reaction conditions, it was possible to obtain a single product with practically 100% selectivity, the yields being higher than those obtained with soluble catalysts, such as KOH, NaOH, or piperidine. 

The reaction of the 2-pyridylvinyl ketone 28 with DMAD could take place in several ways, but nucleophilic attack from the nitrogen and Michael-type addition to the conjugated system gives the indolizine 30.251 A similar cyclization occurs with the diethyl malonate derivative 29 yielding 31, but in the case of 32 an unexpected rearrangement... 

The electrophilic reactivity of [W=CH2(Tp )(CO)(PhC=CMe)]-[PF ] was tested with both neutral nucleophiles and anionic nucleophiles to give [W-CH2-Nu(Tp )(CO)(PhC=CMe)]+-0. The phthalimide and diethyl malonate derivatives were structurally characterized. Reaction of [W=CH2(Tp )(CO)(PhCsCMe)][PFg] with cyclohexene sulfide produces a sulfur atom transfer to form a tt-bound thioformaldehyde complex. The structure of [W=CH2(Tp )(CO)(PhC=CMe)][BArF] has also been reported.148... 

Diethyl malonate derivatives are the most used diesters for these reactions. The R group on diethyl malonate in the reaction shown above can contain other functional groups such as a secondary amine or an alcohol. Diesters containing internal amine functions have also been used in these reactions. 

Nucleophilic addition of diethyl malonate derivatives 68 to the glucosyl isothiocyanate 58 in the presence of sodium hydride afforded the corresponding A-thioacylglucosylamines 69 in 40-60% yields.170 Adducts incor-porting an a-phenacyl substituent (68, R Ar) were further cyclodehy-drated using phosphoric acid and acetic anhydride to give JV-nucleoside derivatives of 2-pyrroline 70. Under identical reaction conditions, the a-acetonyl derivative (68, R Me) led to the tetrahydropyridine helerocycle 71 (Scheme 21). 

Palacios and coworkers used a ring-opening reaction of a 2H-azirine to generate cis y-amidoesters (Scheme 10 2011JOC9472). Treatment of 2H-azirine 84 with the diethyl malonate derivative 85 and sodium hydride gives the amidoester 86. Subsequent heating of 86 in the presence of sodium hydride then led to the formation of 5-phosphoryl 3-pynolin-2-one 87. This overall transformation can also be accompHshed in one step without isolation of intermediate 86. 

Stabilized anions exhibit a pronounced tendency to undergo conjugate addition to a p unsaturated carbonyl compounds This reaction called the Michael reaction has been described for anions derived from p diketones m Section 18 13 The enolates of ethyl acetoacetate and diethyl malonate also undergo Michael addition to the p carbon atom of a p unsaturated aldehydes ketones and esters For example... 

Most of the reactions of ester enolates described so far have centered on stabilized eno lates derived from 1 3 dicarbonyl compounds such as diethyl malonate and ethyl ace toacetate Although the synthetic value of these and related stabilized enolates is clear chemists have long been interested m extending the usefulness of nonstabilized enolates derived from simple esters Consider the deprotonation of an ester as represented by the acid—base reaction... 

Section 21 8 Alkylation of diethyl malonate followed by reaction with urea gives derivatives of barbituric acid called barbiturates, which are useful sleep promoting drugs... 

Reaction of o-toluidine with chloral hydrate in presence of hydroxylamine hydrochloride and subsequent treatment with H2SO4 gave the isatin derivative 337. Bromination of 337 followed by reaction with sodium diethyl malonate gave 338. Catalytic reduction with Pd/C gave the oxoindole derivative 339 that upon hydrolysis with aqueous NaOH followed by... 

Although heating benzene-1,2-diamine with malonic acid in aqueous hydrochloric acid affords the parent dione 26 (R = H) in 62% yield,277 the method cannot be extended to substituted malonic acids because decarboxylation intervenes however, the reaction of benzene-1,2-diamines with diethyl malonate and its derivatives constitutes a general procedure for the synthesis of l,5-benzodiazepine-2,4-diones 26 selected examples are given.278... 

Monoanions derived from nitroalkanes are more prone to alkylate on oxygen rather than on carbon in reactions with alkyl halides, as discussed in Section 5.1. Methods to circumvent O-alkylation of nitro compounds are presented in Sections 5.1 and 5.4, in which alkylation of the a.a-dianions of primary nitro compounds and radial reactions are described. Palladium-catalyzed alkylation of nitro compounds offers another useful method for C-alkylation of nitro compounds. Tsuj i and Trost have developed the carbon-carbon bond forming reactions using 7t-allyl Pd complexes. Various nucleophiles such as the anions derived from diethyl malonate or ethyl acetoacetate are employed for this transformation, as shown in Scheme 5.7. This process is now one of the most important tools for synthesis of complex compounds.6811-1 Nitro compounds can participate in palladium-catalyzed alkylation, both as alkylating agents (see Section 7.1.2) and nucleophiles. This section summarizes the C-alkylation of nitro compounds using transition metals. 

Chloro-l,2,3-thiadiazole-4-carboxamides 38 react with the sodium salt of diethyl malonate to give the corresponding malonic acid derivatives 39. The yield in these reactions falls as the electron-releasing properties of the 4-substituents in the aromatic ring increase (Equation 8) <1997JCM396>. 

In a Vilsmeier-Haack-Amold reaction, A/,Ar-disubstituted amino-methylenemalonates (329) were prepared in good yields from the sodium derivative of diethyl malonate or from diethyl malonate in the presence of triethylamine in benzene or toluene at a temperature below 20°C with imidoyl chlorides, which were prepared in situ from N./V-disubstituted formamides and phosphoryl chloride (63BRP917436). Instead of diethyl malonate, diethyl ethoxymagnesiummalonate could also be used (63 BRP917436). 

A/,/V-Dimethylaminomethylenemalonate (329, R = Me) was obtained in 81% yield from the reaction of diethyl malonate and its sodium derivative with DMF and phosgene in benzene at 60-70°C for 2 hr (61CB2278). 

The reaction of an imidazolinium salt (413) and diethyl malonate in THF in the presence of sodium hydride at room temperature gave the aminomethylenemalonate derivative (414) in 65% and 82% yields... 

The reactions of l,4-diacetyl-3-methylsuphonyl-4,5-dihydro-1//- 1,2,4-triazoles (477) with diethyl malonate in THF in the presence of sodium hydride at room temperature or at reflux temperature for 30-60 min led to the formation of diethyl (l,2,4-triazol-3-yl)malonates (478) in 42-69% yields (88CPB96). 1,2,4-Triazole derivatives (479-481) were also isolated from the reaction mixtures by use of column chromatography in 13-16% yields. 

A diethyl 2-pyrimidinylidenemalonate derivative was prepared in the reaction of the appropriate 2-pyrimidinethione and diethyl malonate (82MI2). 

The reactions of the sodium salt of diethyl malonate and 4-(triisopropyl-phenylsulfonyloxide) derivatives of tris-(fe/7-butyldimethylsilyl)uridine (487, R = H) and di-(rm-butyldimethylsilyl)thymidine (487, R = Me) in THF at 0°C afforded the corresponding diethyl 4-pyrimidinylidenemalo-nates (488) in 88-89% yields (87TL2821). 

In its original form, the Michael addition consisted on the addition of diethyl malonate across the double bond of ethyl cinnamate in the presence of sodium ethoxide to afford a substituted pentanedioic acid ester. Currently, all reactions that involve a 1,4-addition of stabilized carbon nucleophiles to activated 7i-systems are known as Michael additions. Among the various reactants, enolates derived from p-dicarbonyl compounds are substrates of choice due to their easy deprotonation under mild conditions. Recently, Michael addition-based MCRs emerged as highly potential methodologies for the synthesis of polysubstituted heterocycles in the five- to seven-membered series. 

Recently, Smulik and Vedejs have reported that amination of ester enolates and enim-inates with 0-(p-nitrobenzoyl)hydroxylamine 21 takes place with good yields . However, reaction of enolates derived from ethyl phenylacetate and phenylacetonitrile gave lower yields compared with stabilized enolates derived from diethyl malonate, diethyl 2-phenylmalonate and 2-phenyl-2-cyanopropionate (Scheme 23). 

In contrast, when the reaction was conducted using diethyl malonate instead of bromomalonate in the presence of Na2C03 under the HSVM conditions, there was obtained not the cyclopropanated product but a C o derivative having two bis(ethoxycarbonyl)methyl groups at the 1,4-positions 46 in 18% yield (82% based on consumed Cgo) (Scheme 21) [52]. Previously it was reported that... 

When ethyl acetoacetate was employed instead of diethyl malonate in a similar solid-state reaction, dihydrofuran-fused Cgo derivative 47 was obtained in 22% yield (49% based on consumed Cgo). Again, the initially formed anion is supposed to be oxidized by oxygen to the corresponding radical, which undergoes intramolecular cyclization with release of a hydrogen radical as shown in Scheme 22 [52]. 

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