Alkylation of Cyanoacetic Ester.

Abstract

In a study of alkyl malonic nitriles, carried out some years ago,' the writer found that the Conrad-Limpach reaction, which was used for the preparation of ethylcyanoacetic ester, gave a mixture containing about 30% of diethylcyanoacetic ester. In this experiment ethyl iodide was used as the alkylating-material. Recent experiments by Hadley,2 carried out under the writer's direction, show that when ethyl bromide is used, practically the same amount (28%) of diethylcyanoacetic ester is formed. The present paper describes the results obtained in the alkylation of cyanoacetic ester by means of methyl, isopropyl, and isoamyl iodides. The investigation is being extended to include the alkylation of several esters of cyanoacetic acid and the use, as solvents, of other alcohols than ethyl alcohol, especially methyl and isoamyl alcohols. Experimental. Derivatives of Methylcyanoacetic Ester. (a) Preparation of the Crude Ester.-The method was that of Henry:3 20 grams of cyanoacetic ester, dissolved in 80 grams of absolute alcohol, were treated with 4.07 grams of sodium, also dissolved in 80 grams of absolute alcohol, and to the resulting sodium salt there was added a slight excess (26.2 grams) of methyl iodide. The mixture became hot, and was cooled with running water. I t was neutral to litmus in five minutes. The alcohol was then distilled off, water was added, and the product was extracted with ether. The ether was dried with calcium chloride. When the ether solution was fractionated, there were obtained 17.1 grams of a fragrant liquid boiling a t 8 7 '-90 O under I 2 mm. This is 72 % of the theoretical amount, (b) Dimethylcyanoacetic Ester.-The crude ester obtained in the methylation of cyanoacetic ester was shaken four times, in ether solution, with 10% sodium hydroxide solution, and the ether solution was dried with calcium chloride. When it was fractionated, it gave 2.1 grams, i. e., 12.3%) of dimethylcyanoacetic ester. This is a colorless, ethereal liquid boiling a t 7 7 O under 9 mm., and a t 185 O under ordinary pressure. An analysis gave the following result :

Efficient and scalable synthesis of α,α-disubstituted β-amino amides

“…The dialkylation of cyanoacetate esters is well known. [26][27][28][29][30] In the course of our work, several of the reported protocols were investigated. A modification of Oedigers method, 30 the 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU) mediated dialkylation of methyl cyanoacetate (2) in CH 2 Cl 2 , was found to be a fast and convenient procedure providing the dialkylated cyanoacetates (3a-j) in almost quantitative yields (>95% for all derivatives, except 3g) (Scheme 3).…”

Phosphoramidites Are Efficient, Green Organocatalysts for the Michael Reaction. Mechanistic Insights into the Phosphorus‐Catalyzed Michael Reaction of Alkynones and Implications for Asymmetric Catalysis.

“…Starting materials were prepared by literature procedures. 2 In cases where the E and Z isomers were separated, the reported elemental analysis is of one of the pure isomers.…”

Phosphoramidites Are Efficient, Green Organocatalysts for the Michael Reaction. Mechanistic Insights into the Phosphorus-Catalyzed Michael Reaction of Alkynones and Implications for Asymmetric Catalysis

“…Ethyl 2-Cyano-5-methyl-2-(3-oxobutyl)hexanoate. Methyl vinyl ketone (2.0 mL, 24 mmol) was added dropwise to a stirred solution of ethyl 2-cyano-5-methylhexanoate (3.67 g, 20 mmol) and HMPT (182 μL, 1 mmol). (Caution: HMPT is slowly oxidized by air to HMPA, a known carcinogen.…”