Diethyl malonate hydrogenation

Labeled erythroskyrin was also obtained from the mold fed separately with sodium [l-R C]- and [2-R"RC]acetates and with [l-R C]- and [2-R"RC]-diethyl malonates. Hydrogenation of this material furnished a decahydro... 

The carbopalladation is extended to homoallylic amines and sulfides[466. Treatment of 4-dimethylamino-l-butene (518) with diethyl malonate and Li2PdCl4 in THF at room temperature leads to the oily carbopalladated complex 519, hydrogenation of which affords diethyl 4-(dimethylamino) butylmalonate (520) in an overall yield of 91%. Similarly, isopropyl 3-butenyl sulfide (521) is carbopalladated with methyl cyclopentanonecarboxylate and Li2PdCl4. Reduction of the complex affords the alkylated keto ester 522 in 96% yield. Thus functionalization of alkenes is possible by this method. 

The properties of diethyl malonate that make the malonic ester synthesis a useful procedure are the same as those responsible for the synthetic value of ethyl acetoacetate The hydrogens at C 2 of diethyl malonate are relatively acidic and one is readily removed on treatment with sodium ethoxide... 

Fig. 2. Synthesis of uma2enil (18). The isonitrosoacetanihde is synthesized from 4-f1iioroani1ine. Cyclization using sulfuric acid is followed by oxidization using peracetic acid to the isatoic anhydride. Reaction of sarcosine in DMF and acetic acid leads to the benzodiazepine-2,5-dione. Deprotonation, phosphorylation, and subsequent reaction with diethyl malonate leads to the diester. After selective hydrolysis and decarboxylation the resulting monoester is nitrosated and catalyticaHy hydrogenated to the aminoester. Introduction of the final carbon atom is accompHshed by reaction of triethyl orthoformate to...

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°. 

Fluorenylamine, 40,5 Formaldehyde, reaction with diethyl malonate to form diethyl bis-(hydroxymethyl)malonate, 40,27 Formamide, condensation with 4,4-dimethoxy-2-butanone to give 4-methylpyrimidine, 43, 77 Formic acid, and hydrogen peroxide, with indcne, 41, 53... 

Diethyl malonate reacts with iodine under basic soliddiquid conditions (procedure 6.4.20 omitting the alkene) to produce tetraethyl ethane-1,1,2,2-tetracarboxylate (Scheme 6.28) [110] the ethenetetracarboxylate is also formed, presumably from the reaction of the initially formed iodomalonate with its carbanion and subsequent elimination of hydrogen iodide. 

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]. 

Scheme 6.61 Mechanistic proposals of the 12-catalyzed asymmetric Michael addition of diethyl malonate to trans-P-nitrostyrene proposed by the Takemoto group (A, B, and C) and initial enolate complex (D) with the ammonium group as additional hydrogen-bond donor initiating an alternative mechanism suggested by Sods, Ptipai, and coworkers.

Condensation, of paraldehyde with diethyl malonate, 32, 54 of a-phene thyl chloride with diphenylacetonitrile, 39, 74 of phenylacetylene with ethyl orthoformate, 39, 59 of 1-phenylbiguanide with ethyl chloroacetate, 38,1 of potassium diphenylacetonitrile with benzyl chloride, 39, 73 of potassium trithiocarbonate with potassium chloroacetate, 39, 77 of sodium acetylacetonate to tetraacetylethane, 39, 61 of sodium formylacetone with cyano-acetamide, 32, 32 of tetracyanoethylene with N,N-dimethylaniline, 39, 68 of thiophene, paraldehyde, and hydrogen chloride, 38, 86 of thiourea with furfuryl alcohol, 36,66... 

Ethyl hydrogen malonate may be prepared from diethyl malonate by controlled hydrolysis with potassium hydroxide (see also Expt 5.147, Note (1)). 

The synthesis starts with the preparation of diethyl (2-cyanoethyl)malonate (Expt 5.161) by the Michael addition of diethyl malonate to acrylonitrile. Hydrogenation over Raney nickel converts the cyanoethyl compound to the corresponding primary amine (41) which is converted into proline (isolated initially as the hydrochloride) by the reaction sequence shown. Liberation of the free amino acid from its salt is achieved in this case by treatment with triethyl-amine (cf. serine, Expt 5.183). 

Grossman, R. B. Vamer, M. A. Selective monoalkylation of diethyl malonate, ethyl cyanoacetate, and malononitrile using a masking group for the second acidic hydrogen. 

The tricyclic furo-fused 1,2,4-triazinium salt (74 X= O) reacts with nucleophiles such as sodium hydrogen sulfide, sodium diethyl malonate, or sodium ethyl cyanoacetate to yield the new ring systems thieno[2,3-e pyrido[l,2-Z>]-l,2,4-triazinium perchlorate (74 X= S) and cyclopenta(e]pyrido[ 1,2-b -1,2,4-triazines (75) [94CB1799]. 

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