Cyclohexylamino vinylphosphonate

DIETHYL 2-(CYCLOHEXYLAMINO)VINYLPHOSPHONATE (Phosphonic acid, [2-(cyclohexylamino)vinyl]-diethyl ester) 

Submitted by Wataru Nagata,1 Toshio Wakabayashi,1 and Yoshio Hayase2 

Diethyl 2,2-Diethoxyethylphosphonate (Note 1). Into a 2-1., three-necked round-bottomed flask fitted with a magnetic stirrer, dropping funnel, and nitrogen inlet is placed 410 g. (2.08 moles) of bromoacetaldehyde diethyl acetal (Note 2), and a gentle stream of nitrogen is then passed continuously through the system. To the stirred solution is added dropwise 316 g. (1.90 moles) of triethyl phosphite (Note 3) over a period of 30 minutes, at 110-120°. The mixture is then stirred for 3 hours at 160°. The ethyl bromide evolved is trapped by a condenser and a receiver cooled in an ice bath. The low-boiling 

Diethyl Formylmethylphosphonate (Note 5). A mixture of 192 g. (0.755 mole) of diethyl 2,2-diethoxyethylphosphonate and 670 ml. of 2% aqueous hydrochloric acid is refluxed for 10 minutes under a nitrogen atmosphere. 

To the cooled (20-30°) mixture is added 240 g. of sodium chloride (Note 6). The resulting mixture is extracted with three 500-ml. portions of methylene chloride. The combined organic extracts are first washed with 40 ml. of 5% aqueous sodium bicarbonate solution (Note 7), and then with 300 ml. of saturated aqueous salt solution, dried over anhydrous sodium sulfate, and the solvent is distilled under reduced pressure (35 mm.) on a water bath (60-70°). The resulting residue weighing approximately 125 g. is fractionated under reduced pressure, and the fraction boiling at 100-103° (0.8 mm.) is collected yield 104 g. (76%) (Notes 8 and 9). 

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DIETHYL 2-(CYCLOHEXYLAMINO) VINYLPHOSPHONATE, 53, 44 Diethyl 2,2-diethoxyethylphos-phonate, 53, 44 Diethyl formylmethylphospho-nate, 53, 45... 

Diethyl 2-(cyclohexylamino)vinylphosphonate has proved to be an excellent reagent for conversion of aldehydes and ketones into the corresponding a,/J-unsaturated aldehydes.4,B Preparation of formylmethylenetriphenylphosphorane8 and diethyl 2,2-(diothoxy)ethylphosphonate7 have been reported and used for the conversion of aldehydes, but not ketones and hindered... 

The present procedure also illustrates an excellent general method for the conversion of ketones and aldehydes12 into the corresponding a,/9-unsaturated aldehydes using diethyl 2-(cyclohexylamino)vinylphosphonate.3 The yield of product is usually high, and the reaction proceeds stereoselectively to afford only the trans isomer. In the reaction of 3-ketosteroids with this reagent, no /9,y-isomers were formed.12 Recently... 

Into a 1-1. three-necked round-bottomed flask, fitted with a magnetic stirrer, dropping funnel, and nitrogen inlet, are placed 5.45 g. (0.12 mole) of sodium hydride (51% oil dispersion) (Note 1) and 30 ml. of dry tetrahydrofuran (Note 2). The system is flushed with nitrogen and a solution of 30.2 g. (0.12 mole) of diethyl 2-(cyclohexylamino)vinylphosphonate in 90 ml. of dry tetrahydrofuran is added dropwise to the stirred mixture over a period of 15 minutes. During the addition the temperature is maintained at 0-5° with an ice bath. The mixture is further stirred for 15 minutes at 0-5° to ensure complete reaction. A solution of 10.3 g. (0.11 moles) of cyclohexanone (Note 3) in 70 ml. of dry tetrahydrofuran is added dropwise to the mixture over a period of 20 minutes so that the temperature does not... 

The distillation was carried out in the presence of powdered anhydrous potassium carbonate to prevent dimerization of diethyl 2-(cyclohexylamino)vinylphosphonate. 

Reagent grade pentane passed through Merck anhydrous neutral alumina was used. Crystallization was carried out at 0° using 50 ml. of dry pentane. Filtration of the crystals was carried out under dry nitrogen. The submitters succeeded in crystallizing diethyl 2-(cyclohexylamino)vinylphosphonate only after the publication of its preparation. The crystalline product is stable for several months, if stored at 0° under anhydrous conditions. 

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