SU324742A1 - METHOD OF OBTAINING 1-CYANO-O-CARBAMOILFORMOXIMA - Google Patents

Description

The invention relates to the field of the preparation of new derivatives of carbamoyl foroximes, which can be used as biologically active compounds. In the literature, there is a known method for the preparation of carbamoyl oximes of the general formula N C - C NO - C - N O SR where Rl is lower alkyl, chloro or bromoalkyl, alkenyl, chloro or bromealkenyl, lower alkoxyalkyl, alkylthioalkyl, dialkylaminoalkyl, phenyl, benzyl or phenyl or benzyl substituted with chromium or bromine and / or lower alkyl; R2-Nb - hydrogen or lower alkyl, which consists in the interaction of the formoxime with isocyanate, with the acid chloride of carbamic acid or with phosgene and the amine. A method is proposed for the preparation of a novel 1-cyano-0-carbamoyl formoxime of the general formula 25

CN gd RI to mdg g

Rinco

(Iv) e RI is hydrogen, a substituted or unsubstituted lower alkyl group with 1-5 carbon atoms; R2 is a lower alkyl group with 1-5 carbon atoms, a cycloalkyl group with 3-6 carbon atoms or a phenyl group or a tetrahydrofurfuryl residue; and R2 is adjacent to the nitrogen atom of a 5-6-membered heterocyclic residue; Rs is hydrogen or petroleum alkyl group with 1-5 carbon atoms; Ri is a lower alkyl group with 1-5 carbon atoms or an alkenyl group with 2-4 carbon atoms; Second is that 1-cyanophoxime of the general formula N - c :: NOH e Ri and R2 - have the above meaning, they react with isocyanate, both formulas of the general formula Hal-C-N II O, where Hal is chlorine or bromine; Rs and R4 have the above meaning, or with phosgene and an amine of the general formula (VI) where Rs and R, have the above meaning, in the presence of an inert solvent relative to the participants of the reaction solvent. The reaction is carried out in the presence of acid-binding substances, namely inorganic bases, for example, hydroxides, oxides and carbonates of alkali and alkaline-earth metals, organic nitrogen bases, namely, tertiary amines, for example pyridine, triethylamine, triethylenediamine, organic tin compounds. The reactions are carried out in inert to the participants of the reaction solvents, nanoparticles of ethers and ether-like compounds, ketones, amides, halogenated hydrocarbons, or aliphatic and aromatic hydrocarbons. The new carbamoyl foroximes in the above-mentioned method are obtained with good yield. They are soluble in common organic solvents and in water and are stable. The compounds of general formula HI used as starting materials are partially known. Neonisan compounds can be obtained by reacting 1-chloro-1-cyanoformoxime with primary and secondary amines. Oximes are known to be in two stereoisomeric forms, syn and anti form. The 1-cyano-O-carbamoyl formoximes of structural formula II also occur in these two species. Therefore, when using the term "1-cyano-carbamoylformals of structural formula II, both stereoisometric species should be kept in mind. The proposed method allows to obtain new derivatives of carbamoyl foroximes with valuable biologically active properties. Example 1. a) 200 ethyl 33% strength dimethylamine solution in absolute ethanol is added to 500 ml dioxane; then 24 g of 1-chloro-1-cyanoformoxime in 100 ml of absolute dioxane are added dropwise under a stream of nitrogen with vigorous stirring. The temperature then rises to 40 ° C and a precipitate of dimethylamine hydrochloride forms. (V) to 60 ° C. The solvents are filtered off with suction in vacuum1, the residue is dissolved in a small amount of water, acidified slightly with phosphoric acid (pH 3-4) and extracted with diethyl ether. The ether extracts were dried with anhydrous sodium sulfate, and the ether was removed in vacuo. Thus, 21.4 g of 1-dimethylamino-1-cyanoformoxime are obtained in the form of brownish crystals with T. Il. 112 ° C. b) 3 1-diethylamino-1-cyanoforoxime is dissolved in 50 ml of dioxane, then 0.25 ml of triethylamine and then 7.5 ml of methyl isocyanate are added. This mixture is incubated for 15 hours at 40-50 ° C. After cooling, the dioxane is filtered off with suction under vacuum and the residue is recrystallized from ethanol. Thus, 6.9 g of white crystals (mp. 114-117 ° C.) of 1-dimethyl-diamino-1-cyano-0- (N methylcarbamoyl) -formoxime are obtained. Another 4.5 g can be obtained from the mother liquor; m.p. 112-115 ° C. Example 2. 42.8 g of 1-morpholino-1-cyanoformoxime (prepared analogously to example 1a) and 33.2 g of dimethylcarbamic acid chloride are dissolved in 700 ml of dioxane, then 44.2 g of anhydrous potassium carbonate are added. For 16 hours, it is maintained at 80 ° C and vigorously stirred under a nitrogen atmosphere, after cooling, the solid is filtered off and the dioxane is distilled off in vacuo. The residue is recrystallized from water. Thus, 39.5 g of 1-morphonic-1 cyano-0- (M-dimethylcarbamoyl) -formaxime are obtained. Mp. 120-121 ° C. Example 3. Under nitrogen atmosphere, 9.6 g of 50% suspension of sodium hydride in paraffin oil is stirred up in 100 ml of dry tetrahydrofuran; then, at room temperature, a solution of 31 g of L-morpholin-O1-cyanoformoxime in 200 ml of dry tetrahydrofuran-iri is added dropwise to strong stirring. Then incubated for 30 min at 35-40 ° C. This mixture is added in portions at 0-5 ° C to a solution of 39.6 g of phosgene in 400 ml of dry ether and then kept at room temperature for 30 minutes. The excess phosgene is sucked off in vacuo. Then, a solution of 22.5e of dimethylamine in 100 ml of dry tetrahydrofuran is added dropwise at room temperature, kept at room temperature for 16 hours, heated to 60 ° C for 1 hour, the solution is filtered after cooling and the solvents are filtered off with suction. In order to remove the paraffin oil, the remaining solution is washed with hexane and recrystallized from ethanol / water. Thus obtained 1-formolino-1iano-0- (N-dimethylcarbamoyl) - formoxime has so pl. 120-121 ° C.