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Unite States ‘atet ice E,?57,864 Patented Oct. 9, 1962 1 ' 3,057,864 ALPHA AMINO SUBSTHTUTED METHYLENE MALONONITRILES Alexander T. Shulgin, Berkeley, Calif., assignor to The Dow Chemical Company, Midland, Mich, a corpora tion of Delaware 5 No Drawing. Filed Aug. 28, 1959, Ser. No. 836,581 4 Claims. (Cl. 260-247) This invention concerns certain new substituted malo 10 nonitriles, and particularly certain monocyclic N-hetero cyclic methylene malononitriles having a structure cor responding to the formula N ’-tert-butylpiperazinylmethylenernalononitrile It will be apparent from the foregoing de?nition that ‘ON when the heterocyclic group contains a second nitro -CH=O/ gen atom, such second nitrogen atom is invariably a ON tertiary, that is to say, a fully substituted nitrogen atom having a lower alkyl group as substituent thereupon. wherein the free valence is occupied by a nitrogen atom, When the only nitrogen atom in the heterocyclic group the said occupying nitrogen being a member of a hetero cyclic group having a total of not more than two ring 20 is the nitrogen atom which is attached to the methylene nitrogen atoms, free of imino nitrogen atoms and hav malonitrile group, such lower alkyl substituent, if pres ing from three to six members in the ring and not more than one ring substituent additional to the methylene malononitrile group, each such additional substituent be heterocyclic group. ent, may be present in any available location upon the These new compounds are crystalline solids somewhat ing a lower alkyl group; each valence of said occupying 25 soluble in many common organic solvents and of very low solubility in ethanol and in water. They are useful nitrogen atom being attached to a separate carbon atom. as parasiticides and are adapted to be employed for the The term lower alkyl is used throughout the present speci?cation and claims to designate an alkyl group con taining from 1 to 5 carbon atoms, inclusive. In View control of many household pests such as insects and lowing: heterocyclic secondary amine having a total of not more than 2 ring nitrogen atoms one of which is an amino agricultural parasites such as weeds and fungus diseases. The new compounds may be prepared by causing a of the present de?nition, it is apparent that compounds 30 lower alkoxymethylenemalononitrile to react With a representative of the present invention include the fol H20 ON nitrogen atom, and having from 3 to 6 members in the 35 ring and not more than one ring substituent, each such H20 0N Ethyleniminomethylenemalononitrile ON 40 substituent being a lower alkyl group; the imino nitro gen being joined in the ring by the presence, upon each ring valence bond thereof, of a separate carbon atom which is also a member of the ring. Representative heterocyclic secondary amines include ethylenimine, tri methylenimine, pyrrolidine, piperidine, morpholine, thi T1-imethyleniminomethylenemalononitrile HzC—OH2 \ H / /N—G=O\ HQC~CH3 CN Hg Hz 0-0 H2O /CN C-O H2 H2 ON Piperidinylmethylenemalononitrile CHT‘CH; ON H / ylenemalononitrile. In the present speci?cation and claims, the term lower alkoxy is used to designate an alkoxy group containing from 1 to 5 carbon atoms, in clusive. ‘ In carrying out the reaction, the lower alkoxy methyl enemalononitrile is intimately contacted with a hetero cyclic secondary amine of the sort hereinbefore de?ned. Preferably, the contacting is carried out in an inert sol 55 vent which may conveniently be a lower \alkanol such as methanol, or ethanol. The reaction is exothermic and initiates readily atrtemperatures from 0° C. to 50° C.; therefore, the contacting of the reactants is conveniently carried out initially within such temperature range. Heat evolved from the reaction raises the temperature of the resulting reaction mixture, which may conveniently be limited by the boiling temperature of the reaction solvent, by regulating the rate of contacting of the reactants, by external cooling, andrthe like. The desired products ON Thiamorpholinylmethylenemalononitrlle / clude ethoxymethylenemalononitrile, methoxymethylene malononitrile, isopropoxymethylenemalononitrile, 3,3 dimethylpropoxymethylenemalononitrile, n-propoxymeth CN . Pyrrolidinyhnethylenemalononitrile / amorpholine, N-lower alkyl piperazine, and the like. Representative lower alkoxymethylenemalononitriles in 65 prepared in the present method are stable under tem ON peratures at least somewhat greater than the melting tem perature of the said product, at least to temperatures such as ISO-175° C. The reaction by which the present CN products are obtained takes place between equimolecular 70 proportions of the heterocyclic secondary amine and the HaC-N lower alkoxymethylenemalononitrile reactant. However, N’ -methylpiperazinylmethylenemalononitrile the reactants may be employed in any proportions. If 3,057,864 3 4 Thiamorpholinylmethylenemalononitrile, from the re employed proportions of reactants differ from equimo action of thiamorpholine and ethoxymethylenemalono lecular proportions, in general the reactant in excess nitrile. Thiamorpholinylmethylenemalononitrile has a thereof will appear as an impurity in, and may be removed molecular weight of 179.2. The starting thiamorpholine from, the resulting product. Upon completion of the reaction, which is easily recog reactant may be prepared in the manner set forth in the Journal of the American Chemical Society, vol. 76 (June 1954), page 2902. nized by the cessation of evolution of further heat of reaction, the reaction mixture may be cooled to a tem perature between room temperature and 0° C., where N’-methylpiperazinyhnethylenemalononitrile, from the reaction of N’-methylpiperazine and methoxymethylene upon the desired product usually separates by crystallizing from the reaction mixture. Alternatively, the reaction 10 malononitrile. N’-methylpiperazinylmethylenemalononi mixture may be warmed under subatmospheric or atmos trile has amolecular weight of 176.2. pheric pressure to vaporize and remove reaction solvent as well as lower alkanol by-product of reaction, to obtain the reaction of N’-n-pentylpiperazine and n-propoxymeth the desired product. When the desired product contains, ylenemalononitrile. puri?ed by conventional techniques such as by washing with further portions of lower alkanol, and recrystalliza enemalononitrile. N’ - n - pentylpiperazinylmethylenemalononitrile, from N’ - n - pentylpiperazinylmethylene as impurity, unreacted starting material such material may 15 malononitrile has a molecular weight of 232.33. N’ - tert - butylpiperazinylmethylenemalononitrile, from be removed by washing with portions of a lower aikanol the reaction of N’-tert-butylpiperazine and ethoxymethyl such as ethanol. The resulting product may be further N’ - tert - butylpiperazinylmethylene malononitrile has a molecular weight of 218.3. The N-loweralkylpiperazines to be employed as re 20 tion from various organic solvents. actants according to the present invention may be pre The following examples merely illustrate the present pared in the general method set forth in the Journal of invention but are not to be construed as limiting it. the Pharmaceutical Society of Japan, vol. 74, pages1049 EXAMPLE 1 51 (1954). Piperidinylmethylenemalononitrile The new monocyclic N-heterocyclicmethylenemalono nitriles of the present invention have been found to be useful as parasiticides and are adapted to be employed milliliters ethanol was added as a single portion to a for the control of many pests. For such use, the products solution of 4.1 grams (0.034 mole) of ethoxymethylene may be dispersed on inert ?nely divided solids and em malononitrile in 10 milliliters of ethanol warmed to ployed as dusts. Also, such mixtures may be dispersed approximately 40° C. A reaction resulted with the im 30 in water with the aid of a wetting agent and the resulting mediate evolution of heat, as the resulting reaction mix aqueous suspensions used as sprays. In other proce ture became darker in color. The reaction mixture dures, the products may be employed in oil, as oiI-in-water achieved an upper limit temperature of somewhat less emulsions, or water dispersions with or without the aid than 80° C. The reaction mixture was then chilled over of dispersing or emulsifying agents. In a representative an ice bath for about 4 hours, during which time the operation, the application as a thorough wetting spray to desired product separated out of the reaction mixture as young tomato plants of a composition containing piperi~ crystals, which were removed by ?ltration and recrystal dinylmethylenemalononitrile at the rate of one half pound 25 A solution of 2.8 grams (0.033 mole) piperidine in 5 lized from further ethanol. As a result of these opera tions there was obtained a piperidinylmethylenemalono nitrile product as a tan, crystalline solid melting at 90° 92° C., and having a nitrogen content, by analysis, of 25 .54 weight percent as compared with a theoretical value of 26.07 percent. EXAMPLE 2 l -Pyrr0lidinylmethylenemalononitrile In procedures exactly like the foregoing except that the employed heterocyclic reactant was pyrrolidine there was prepared a l-pyrrolidinylmethylenemalononitrile product as a light tan crystalline solid melting at 88-90” C. EXAMPLE 3 Marpholinylmethylenemalononitrile The present example was carried out in all respects in the same manner as was Example 1 except that the em per hundred gallons of ultimate composition afforded 40 commercially satisfactory protection against subsequent innoculation with viable spores of the fungus Alternaria solani whereas plants similarly innoculated with the fungus but without protection from the present com~ pound were uniformly and heavily infested. Similar re sults were obtained when employing, as sole toxicant, at the same rate, the compound morpholinylmethylene malononitrile. Similarly, the compound pyrrolidinyl methylenemalononitrile at the rate of one half pound per hundred gallons afforded substantial protection against subsequent innoculation with the spores of, on tomato plants, Alternaria solani; and on young wheat plants, Puccinia graminis tritici. I claim: 1. A monocyclic N-heterocyclic methylenemalono nitrile having a structure corresponding to the formula ON ployed heterocyclic reactant was morpholine. As a result of these operations there was obtained a morpholinyl methylenemalononitrile product as tan crystals melting ON 60 wherein the free valence is occupied by a nitrogen atom, at 148~150° C. the said occupying nitrogen atom having each of its two When the same preparation is carried out except that other valences attached to a separate carbon atom and there is employed isopropoxymethylenemalononitrile in an amount equimolecular with the employed morpholine there is obtained the same morpholinylmethylenemalono nitrile product together with isopropanol of reaction. In preparations similar to the foregoing the following being therewith a component of ‘a saturated heterocycle free from imino nitrogen and having a total of from 3 to 6, inclusive, ring atoms of which the said occupying nitrogen is in the number 1 position; when the said hetero cycle contains from 3 to 5, inclusive, ring atoms the ring products are obtained: comprises one trivalent nitrogen atom, all other ring Ethyleniminomethylenemalononitrile, from the reac atoms being carbon atoms; and when the said heterocycle tion of ethylenimine (boiling at 56—57° C.) and ethoxy methylenemalononitrile. Ethylenirninomethylenemalono 70 contains 6 ‘atoms, the atom in the number 4 position is selected from carbon, trivalent nitrogen, oxygen, and nitrile has a molecular weight of 119.13. sulfur, all ring atoms other than those numbered 1 and Trimethyleniminomethylenemalononitrile, from the re 4 being carbon atoms; said heterocycle having up to 1 action of azetidine (boiling at 66—69° C.) and 3,3-dimeth lower alkyl substituent additional to the methylenemalono ylpropoxymethylenemalononitrile. Trimethylenamino methylenemalononitrile has a molecular weight of 133.2. 75 nitrile group. 3,057,864 5 6 '2. Pyrrolidinylmethylenemalononitri-le corresponding 4. Morpholinylmethylenemalononitrile corresponding to the formula to the formula Hue-CH2 H2 GET-0H2 0N \ H / N~O=O\ 0N -0§, 5 H Hz E20 10 H /CN N——C=O \C—-O/ H’ H’ ON References Cited in the ?le of this patent UNITED STATES PATENTS 3. Piperidinylmethylenemalononitrile corresponding to the formula /0-0\ H 0/ \N—-O=O/ \ OH‘F'C é’ \ ON 2,425,693 Cook et a1. __________ __ Aug. 12, 1947 2,883,368 Middleton ____________ __ Apr. 21, 1959 OTHER REFERENCES \CN Price et aL: Journal of the American Chemical Society, 15 vol. 68, page 1249 (1946).