Sodium hydride, reaction with malonates

The solid tricarbonyl(pentadienylium)iron salt (231 mg, 0.5 mmol) is added in one portion to a solution of sodium dimethyl malonate (77 mg, 0.5 mmol, freshly prepared from excess sodium hydride and dimethyl malonate) in tetrahydrofuran (25 mL) at 0 °C. The reaction mixture is stirred for 1 h, then poured into saturated aqueous sodium chloride (50 mL) and extracted with ether (2 x 25 mL). The combined extracts are dried, the solvent is evaporated and the residue is purified by chromatography (hexanes/ethyl acetate, 9 1) to afford the product as a yellow oil 151 mg (68%). ... 

Reaction of 1,3-dicarbonyl compounds with IVJV-dimethylformamide dimethyl acetal followed by malonamide in the presence of sodium hydride gives 5,6-disubstituted 1,2-dihydro-2-oxopyridine-3-carboxamides, whereas reaction of the intermediate enamines with cyanothioacetamide or cyanoacetamide in the presence of piperidine provides 2-thioxopyridine-3-carboxamides and 4,5-disubstituted l,2-dihydro-2-oxopyridine-3-carboxamides, respectively <95S923>. P-Enaminonitriles 14 react with p-ketoesters and alkyl malonates, in the presence of stoichiometric amounts of tin(IV) chloride, to afford 4-aminopyiidines 15 and 4-amino-2-pyridones 16 <95T(51)12277>. 

Dimethyl malonate was first treated dropwise with phenyl isothiocyanate in the presence of sodium hydride in N,7V-dimethylacetamide at 0°C. The reaction mixture was stirred at ambient temperature for 1.5 hr and then cooled to 0°C, and methyl iodide was added dropwise. After stirring for 4 hr at room temperature, (methylthio)(phenylamino)methy-lenemalonate (341) was obtained in 79% yields (69T4649). 

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. 

Diethyl sodiomalonate, prepared from diethyl malonate and sodium hydride, was reacted with isothiocyanate (528) in DMF by dropwise addition at 5°C. The reaction mixture was then stirred at ambient temperature for 1 hr to give (l,3,5-thiadiazepin-2-ylidene)malonate (529) in 76% yield (86S817). 

The reaction product (543) of diethyl malonate and diethyl chlorophos-phate was reacted with 1,4-benzodiazepin-2-ones in the presence of sodium hydride in THF at ambient temperature to give (l,4-benzdiazepin-2-ylidene)malonates (544) (81EUP38423). 

Acetone cyanohydrin nitrate, a reagent prepared from the nitration of acetone cyanohydrin with acetic anhydride-nitric acid, has been used for the alkaline nitration of alkyl-substituted malonate esters. In these reactions sodium hydride is used to form the carbanions of the malonate esters, which on reaction with acetone cyanohydrin nitrate form the corresponding nitromalonates. The use of a 100 % excess of sodium hydride in these reactions causes the nitromalonates to decompose by decarboxylation to the corresponding a-nitroesters. Alkyl-substituted acetoacetic acid esters behave in a similar way and have been used to synthesize a-nitroesters. Yields of a-nitroesters from both methods average 50-55 %. 

The synthetically useful a,/J-unsaturated [nC]-labelled precursors, [nC]acrylonitrile (192) and [11C]cinnamonitrile (193), have been prepared189-191 with potassium [nC]cyanide (equation 101). The substitution reactions have been performed in MeCN, benzene, 1,2-dichlorobenzene, DMSO and THF solvents, but the highest radiochemical yields were obtained in acetonitrile. 192 was used in a model reaction (equation 102) to synthesize 2-cyano[nC]ethyldimethyl malonate 194 from sodium hydride/dimethyl malonate. 

Alkylation and nitration of malonic esters. Zaugg, using sodium hydride for conversion of n-butylmalonic ester into its sodio derivative, found that the rate of alkylation of this substance with -butyl bromide in dimethylformamide is 1,000 times the rate in benzene. Emmons and Freeman developed a procedure for the nitration of active methylene compounds with acetone cyanohydrin nitrate by conversion to the sodio derivative with sodium hydride. The reaction product (3)... 

Reaction of 2-methyl-1,2,3-triazinium iodides with diethyl malonate in the presence of sodium hydride in tetrahydrofuran afforded diethyl (2-methyl-2,5-dihydro-l,2,3-triazin-5-yl)malonates in good yields.355... 

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