Cyanides malononitrile

In addition to malonic, acetoacetic, and cyanoacetic esters, compounds furnishing the active hydrogen atom are nitro paraffins,benzyl cyanide, malononitrile, cyanoacetamide, sulfones, methyl-pyridines, and ketones. ... 

Malonic acid has been made by the hydrolysis of malononitrile with concentrated hydrochloric acid,2 by the hydration of carbon suboxide,3 and by the hydrolysis of cyanoacetic acid4 and its esters5 with potash. A method for the preparation of calcium malonate from chloroacetic acid and potassium cyanide is described by Fischer.6 Conrad7 liberated malonic acid from calcium malonate, so prepared, with oxalic acid. v. Miller,8 Grimaux and Tscherniak, and Bourgoin10 prepared malonic acid from chloroacetic acid and potassium cyanide, Petriev11 from... 

Czech workers have examined displacements in substituted malononitriles in which the double bond transmits the double effect of the cyanide groups... 

Aminomalononitrile (6), an HCN trimer, no doubt forms as an intermediate in the base-catalyzed formation of DAMN from HCN (Section II,C,1). However, its rate of formation is slower than its reaction with an additional 1 mol hydrogen cyanide. Aminomalononitrile has been synthesized from malononitrile and shown to give DAMN upon treatment with cyanide (730SC33 730SC344). 

Dicyanomethane or Malononitrile (called Malonsaure-dinitril, Malonitril or Methylen-cyanid in Ger), NC.CH2.CN mw 66.06, N 42.41% col crysts, mp 31.6-32.4°, bp 108-09° at 17mm press, cryst d 1.191 at 20°, liq d 1.0494 at 35°, nfi 1.4139 at 34.2° prepd by esterification of cyanoacecic acid, and treatment of the ester with NH3 which leads to cyanoacetamide which, on reaction with phosphorous oxychloride or pentachloride, gives Dicyanomethane (Ref 1)... 

Reaction of anthranilonitrile or methyl anthranilate with 3-hydroxy-2-butanone followed by malononitrile gave the pyrrolo [1,2-a] quinazoline 16 (79AP552). Both of the diazine and azole rings of pyrroloquinazolines were also simultaneously formed by cyclization of the anilide 17 derived from 3-chloropropionic acid and 2-aminobenzophenone with potassium cyanide to afford the pyrrolo [1,2-a] quinazoline 18 (68JHC185 71USP3595861). 

Benzo[6]thiophene aldehydes have been condensed with a variety of active methylene compounds, including cyclic511, 644 and open-chain645-647 ketones, aliphatic aldehydes,90 benzyl cyanides,93-436 malononitrile,487 rhodanine,144,648 hippuric acid,477 barbituric acid,487 diethyl malonate,487 and malonic acid (Section VI,M). Aliphatic nitro compounds condense smoothly with most benzo[6]-thiophene aldehydes03,141,337,343, 556,640,650 (except 5-hydroxy- and... 

Intermolecular addition of carbon nucleophiles to the ri2-pyrrolium complexes has shown limited success because of the decreased reactivity of the iminium moiety coupled with the acidity (pKa 18-20) of the ammine ligands on the osmium, the latter of which prohibits the use of robust nucleophiles. Addition of cyanide ion to the l-methyl-2//-pyr-rolium complex 32 occurs to give the 2-cyano-substituted 3-pyrroline complex 75 as one diastereomer (Figure 15). In contrast, the 1-methyl-3//-pyrrolium species 28, which possesses an acidic C-3-proton in an anti orientation, results in a significant (-30%) amount of deprotonation in addition to the 2-pyrroline complex 78 under the same reaction conditions. Uncharacteristically, 78 is isolated as a 3 2 ratio of isomers, presumably via epimerization at C-2.17 Other potential nucleophiles such as the conjugate base of malononitrile, potassium acetoacetate, and the silyl ketene acetal 2-methoxy-l-methyl-2-(trimethylsiloxy)-l-propene either do not react or result in deprotonation under ambient conditions. 

Ruthenium(II) Treatment of [Ru(NH3)5(OH2)]2+ or [Ru(NH3)5(acetone)]2+ with L or [RuCl(NH3)5]2+ with zinc amalgam in the presence of L yields [RuL(NH3)5]2+ (L = acetonitrile, benzonitrile,358 substituted benzonitrile,196 358 359 acrylonitrile,360 hydrogen cyanide,36,37 ethyl cyano-formate,361 dicyanamide, malononitrile, substituted malononitrile, tricyanomethanide,362 4-cyano-l-methylpyridinium196). Reaction of a hundred-fold excess of RCHO (R = Ph, Me) with [Ru(NH3)6]2+ under alkaline conditions yields [Ru(NH3)sNCR]2+.363-365 The likely mechanism of this reaction is given in Scheme 12. An alternative route to nitrile complexes is by reaction of [Ru(NH3)sOH2]2+ with aldoximes, e.g. RMeC=NOH, to afford [Ru(NH3 )5 (NCMe)]2 + and... 

In mammalian species, CS rapidly hydrolyzes to form 2-chlorobenzaldehyde and malononitrile (Leadbeater, 1973 Paradowski, 1979 Rietveld et a/., 1986). The malononitrile intermediate is further metabolized from two cyanide moieties, which are converted to thiocyanate (Cucinell et al, 1971). The aldehyde intermediate undergoes oxidation to 2-chlorobenzoic acid or reduction to 2-chlorobenzyl alcohol. These metabolites are conjugated and excreted in the urine. 

The following examples illustrate different aspects of Scheme 1 in operation. p-Chlorophenyl azide, malononitrile, and methanolic sodium methoxide, set aside, gave 4-amino-5-cyano-3-p-chlorophenyltriazole (rC, 1 hr, 98%) (60CB2001). Methanolic sodium methoxide was added dropwise to a mixture of p-tolyl azide and phenylacetonitrile (benzyl cyanide) next day, the temperature was raised to 25°C, and the preparation set aside for 10 hr, giving 4-amino-5-phenyl-3-p-tolyltriazole (92%) (57JOC654). 

CS reacts covalently with plasma proteins to form compounds that may be antigenic. On contact with water, it hydrolyses into o-chlorobenzaldehyde and malononitrile. The kidney excretes o-chlorobenzal-dehyde as the metabolites o-chlorohippuric acid (major) and o-chlorobenzoic acid (minor). The malononitrile is metabolized to thiocyanate. The cyano groups of 2-chlorobenzylidene malononitrile are unlikely to cause systemic cyanide toxicity since no significant amounts of free cyanide appear in the plasma. 

CS is absorbed very rapidly from the respiratory tract, and the half-lives of CS and its principal metabolic products are extremely short. The disappearance of CS follows first-order kinetics and spontaneously hydrolyses to malononitrile, which is transformed to cyanide in animal tissues. Metabol-ically, CS undergoes conversion to 2-chlorobenzyl malononitrile (CSH2), 2-chlorobenzaldehyde (oCB), 2-chlorohippuric acid, and thiocyanate. CS and its metabolites can be detected in the blood after inhalation exposure, but only after large doses. Following inhalation exposure of CS in rodent and nonrodent species, CS and two of its metabolites, 2-chlorobenzaldehyde and 2-chlorobenzyl malononitrile, were detected in the blood. In another study, human uptake by the respiratory tract, only 2-chlorobenzyl malononitrile was detected in trace amounts in the blood. CS and 2-chlorobenzaldehyde were not detected, even after high doses of CS of up to 90 mg min m. This finding is consistent with the... 

Frankenberg, L. and Sorbo, B. 1973. Formation of cyanide from o-chlorobenzyhdene malononitrile and its toxicological significance. Archives of Toxicology, 31 99-108. 

There is evidence that, due to its malononitrile component, the major cause for mortality following acute intraperitoneal dosing is cyanide intoxication. The evidence for acute lethal cyanogen-esis by this route is as follows (Ballantyne, 1983 Cucinell et al, 1971 Jones and Israel, 1970) ... 

By heating pyrimido[4,5-c/]pyrimidin-4-amine with malononitrile in acetic acid, 4,7-diaminopy-rido[2,3-d]pyrimidine-6-carbonitrile and hydrogen cyanide are formed.469 The presumed mechanism implies opening of the unsubstituted pyrimidine moiety by malononitrile, producing a 4-amino-6-[(aminomethylene)amino]-5-(2,2-dicyanovinyl)-substituted pyrimidine, which, after recyclization, loses hydrogen cyamide. 

Malononitrile (in THE at 20-25 °C overnight) and cyanoacetamide (in water at 20-25 °C for 5 days) react with pteridines, e.g. I, to give pyrido[2,3-6]pyrazines, e.g. 2, by addition across the 3,4-bond followed by scission of that bond and a nitrogen-eliminating recyclization. The intermediate of the reaction with cyanoacetamide can be isolated by addition of aqueous sodium hydroxide. Because the product from malononitrile can be generated under anhydrous conditions, it can be concluded that the reaction takes place by a concerted cyclization of the amidine intermediate with elimination of hydrogen cyanide, rather than via a pyridazinamine which could arise by hydrolysis of this amidine (cf. similar reactions in other fused pyrimidine series).56,64-66... 

Nash, J.B., Doucet, B.M., Ewing, P.L., and Emerson, G.A., Effects of cyanide antidotes and inanition on acute lethal toxicity of malononitrile in mice. Arch. Int. Pharmacodyn., 84, 385, 1950. 

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