Ethyl benzylmalonate

Uses for benzyl cyanide (p. 137), ethyl benzylmalonate (p. 255), the Grignard reaction. 

The Nature of the Condensation Produkt from Ethyl Benzylmalonate and Ethyl Fumarate. J. chem. Soc. (London) 193, 42. 

Phenylacetaldehyde from Benzylinalonic Ester. A mixture of 100 g. of ethyl benzylmalonate, 50 g. of hydrazine hydrate, and 10 cc. of absolute ethanol is refluxed for six hours on a steam bath. The dihydrazide is filtered from the cooled mixture and washed with a little ethanol and ether after drying on a clay plate and then in vacuum, the crude product weighs 91-91.5 g. (ca. 100%) and melts at 164°. A solution of 11.1 g. of this dihydrazide in a cold solution of 9.8 g. of concentrated sulfuric acid in 44 cc. of water is covered with 50 cc. of ether and cooled to —5° in an ice-salt bath. A solution of 10.35 g. of sodium nitrite in 21 cc. of water is added slowly with stirring, the ether layer is then separated, and the aqueous phase is extracted once with ether. After the combined ethereal extracts have been dried for one hour over sodium sulfate at 0°, 100 cc. of absolute ethanol is added, and the mixture is refluxed for three hours during this time most of the ether is allowed to escape. The resulting solution of the srewi-diurethan is concentrated to a syrup and allowed to crystalhze in vacuum over sulfuric acid yield, 10.5 g. (75%) m.p. 166°. (If the next step is to be performed immediately, the crystallization is unnecessary.)... 

The latter effect is presumed to result from oxidation by CH(C02H)2. Of relevance also are the kinetics of the Mn(III) pyrophosphate oxidation of ethyl-and benzylmalonic acids the order in Mn(III) is approximately one, no retardation by Mn(II) is found and induced oxidations do not occur. This has been explained in terms of a lowering by R of the redox potential of RC(C02H) to a value insufficient to reoxidise Mn(II) pyrophosphate in reaction (58). 

The second of the resonance structures is the source of the radical reactivity displayed during oxidation and the Mn(III) in this structure must be low-spin to preserve multiplicity. Substitution at the meso-position could provide steric hindrance to analogous decompositions and reactions of the Mn(IV) complexes of ethyl- and benzylmalonic acids, and a conventional one-equivalent oxidation step becomes dominant. 

Treatment of the hydrazide 59 with ethyl orthoformate causes an intramolecular N-acylation resulting in the tetracycle 60. The conversion of 1,4-diphenylcarbazole into 61 using N-methylformanilide-phosphorus oxychloride at 95°C must involve an oxidation at some stage. Heating car-bazole with diphenyl 2-benzylmalonate, diethyl 2-ethylmalonate, or malonic acid-phosphorus oxychloride produced the tetracycles 62 (R = PhCH2, Et, and H, respectively). It is not clear whether the N-9 or the C-1 acylations required for the formation of 62 occur first, although it is likely that the initial attack is at the nitrogen. 

Benzylmalonic Acid.—When this acid in the form of its ethyl-potassium salt was submitted to electrolysis by Brown and Walker 8 it exhibited a behavior materially different from that of malonic acid. The solution became dark-colored, but contained no new compound. If oxidation occurred, it was a complete oxidation into carbon dioxide and carbon monoxide, such as has been observed in the case of unsaturated acids. 

An ethanolic solution of sodium ethoxide is prepared by the addition of 11.5 g. (0.5 gram atom) of sodium to 160 ml. of absolute ethanol (p. 142) under a reflux condenser. After cooling to room temperature, 160 g. (1.0 mole) of ethyl malonate is added to the solution, and this is followed by the dropwise addition of 63.2 g. (0.60 mole) of benzyl chloride. The resulting mixture is refluxed for 1 hour, and then most of the ethanol is distilled off. The residue is treated with water, and the organic layer is separated and distilled. There is collected 80 g. of unreacted malonic ester, b.p. 91-96°/12 mm, pressure and 107 g. (85 yield based on malonic ester consiuned) of benzylmalonic ester, b.p. 163-170°/12 mm. 

Ethyl y5-mercaptocrotonate added to a soln. of benzylmalonic chloride in abs. toluene, refluxed 5-6 hrs. until HCl-evolution ceases, allowed to stand at room temp, overnight, and again refluxed 0.5 hr. 6-methyl-3-benzyl-4-hydroxy-5-carbethoxy-2-thiopyrone. Y 64%. F. e. s. F. K. Splinter and H. Arold, J. pr. 38, 142 (1968). 

In almost all preparations the hydrazoic acid is dissolved in chloroform or benzene. Since chloroform is completely inert towards hydrazoic add it may be preferable, but imder most conditions benzene is just as satisfactory. Trichloroethylene also has been used successfully as a solvent. The addition of dioxane has been found to be of value in the preparation of dZ-phenylalanine from benzylmalonic acid." Ethyl ether is not a satisfactory solvent, although its use has been mentioned in patents. ... 

Also, the fluorination of methyl (l/J,3/J,45)-8-phenylmenthyl methyl malonates using lithium hexamethyldisilazide and 2 gave the (/ )- and (S) isomers in a 3.8 1 ratio, while fluorination of ethyl, propyl, and benzylmalonates provided (R)- or (S)-isomers ina l 1.6-2.0ratio(eq lO). ... 

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