Malononitrile, acidity

The only acid-resistant protective group for carbonyl functions is the dicyanomethy-lene group formed by Knoevenagel condensation with malononitrile. Friedel-Crafts acylation conditions, treatment with hot mineral acids, and chlorination with sulfuryl chloride do not affect this group. They have, however, to be cleaved by rather drastic treatment with concentrated alkaline solutions (J.B. Basttis, 1963 H. Fischer, 1932 R.B. Woodward, 1960, 1961). 

Removal of maleic and fumaric acids from the cmde malononitrile by fractional distillation is impractical because the boiling points differ only slightly. The impurities are therefore converted into high boiling compounds in a conventional reactor by means of a Diels-Alder reaction with a 1,3-diene. The volatile and nonvolatile by-products are finally removed by two vacuum distillations. The by-products are burned. The yield of malononitrile amounts to 66% based on cyanogen chloride or acetonitrile. 

Tetracyanoethylene is colorless but forms intensely colored complexes with olefins or aromatic hydrocarbons, eg, benzene solutions are yellow, xylene solutions are orange, and mesitylene solutions are red. The colors arise from complexes of a Lewis acid—base type, with partial transfer of a TT-electron from the aromatic hydrocarbon to TCNE (8). TCNE is conveniendy prepared in the laboratory from malononitrile [109-77-3] (1) by debromination of dibromoma1 ononitrile [1855-23-0] (2) with copper powder (9). The debromination can also be done by pyrolysis at ca 500°C (10). 

Other pyrimidine starting materials include 5-amino-6-methyl derivatives, which with oxalates give 6,7-dihydroxypyrido[3,2-acid derivatives, which with malononitrile are converted into 5,6-dihydro-7-aminopyrido[2,3-[Pg.227]

The first reaction can be conducted using various derivatives of methylenemalonic ester, such as malononitriles 7, malonamides 8, P-keto-esters 9 or Meldrum s acid 10. Substitutions of the aryl ring (including fused rings) and within the aryl ring are well tolerated for this reaction. 

Similar results are observed in the conjugative addition of CH-acidic methylene compounds with the metal derivatives of 2-nitro-5,10,15.20-tetraphenylporphyrin (6). The nickel porphyrin 6 (M = Ni) yields with an excess of dimethyl malonate the cyclopropane derivative 7 whereas the copper porphyrin 6 (M — Cu) forms with two equivalents of malononitrile the bisadduct 8.111... 

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... 

As stated above under TNMe, in Ger during WWII, the prepn of TeNMe by this process was scaled up for use as an intermediate and as a substitute for nitric acid in the V-2 rocket (Ref 26). A pilot plant was built at Newark, NJ for prodn using this procedure. It was destroyed by an expln in 1953 and not rebuilt (Refs 33 44). Other prepns of lesser importance are by the action of Ag nitrite on iodotrinitro-methane (Ref 3) by the action of 90% nitric acid and 25% oleum on malononitrile, yield 45% (Ref 40) by the action of mixed acid on a number of aromatic nitrocompounds, of which nitrobenzene, dinitrobenzene, and nitronaphtha-lene gave the best yields (Ref 13a) and by the action of nitryl chloride on salts of TNMe. 

The biocatalytic differentiation of enantiotopic nitrile groups in prochiral or meso substrates has been studied by several research groups. For instance, the nitrilase-catalyzed desymmetrization of 3-hydroxyglutaronitrile [92,93] followed by an esterification provided ethyl-(Jl)-4-cyano-3-hydroxybutyrate, a useful intermediate in the synthesis of cholesterol-lowering dmg statins (Figure 6.32) [94,95]. The hydrolysis of prochiral a,a-disubstituted malononitriles by a Rhodococcus strain expressing nitrile hydratase/amidase activity resulted in the formation of (R)-a,a-disubstituted malo-namic acids (Figure 6.33) [96]. 

To evaluate properties of basic catalysts, the Knoevenagel condensation over aluminophosphate oxynitrides was investigated [13]. In this reaction usually catalysed by amines, the solid catalysts function by abstraction of a proton from an acid methylene group, which is followed by nucleophilic attack on the carbonyl by the resultant carbanion, re-protonation of oxygen and elimination of water. The condensation between benzaldehyde and malononitrile is presented below. 

A method of general utility is the classical condensation of appropriate reactive methylene compounds (like malononitrile or cyanoacetate) with cyclopropenones73 74 — improved by bifunctional acid-base catalysis67 - in acetic anhydride solution ... 

The thiadiazolo[3,4-g] indole 100 was prepared from 4-amino-5-chlorobenzothiadiazole 99 by treatment with pyruvic acid in the presence of [Pd(But3P)2] (Equation 14) <2004AGE4526>. The Herz reaction of 4-aminoben-zothiadiazole 101 with disulfur dichloride gave the fused 1,2,3-dithiazolium chloride 102, which was condensed with malononitrile to give the ylidene 103 (Scheme 15) <2002J(P1)315>. 

Malonic ester syntheses, 30, 7 Malononitrile, 37, 53 Malonyl dichloride, 33, 20 Mandelic acid, 36, 3 Mandelic acid, />-bromo, 35,11 Mannich reaction, with acetone, 37,18 Mercaptoacetaldehyde, diethyl ACETAL, 35, 51... 

Methanal, f31 Methanoic acid, f36 Methenamine, h49 Malononitrile dimer, a267 Methone, d596... 

Malononitrile, purification of, 48, 3 reaction with sodium nitrite and acetic acid, 48,1... 

A. Oximinomalononitrile. Malononitrile (Note 1) (25 g., 0.38 mole) is dissolved in a mixture of 20 ml. of water and 100 ml. of acetic acid in a 1-1. round-bottomed flask equipped with a stirrer, a thermometer, and a powder funnel. The solution is cooled to —10° with a dry ice-acetone bath, and 50 g. (0.72 mole) of granulated sodium nitrite is added in approximately 2-g. portions over a 30-minute period while the temperature is maintained at 0° to —10°. After the addition is complete a wet ice bath is used to maintain the temperature below 5° while the mixture is stirred for 4 hours. Four hundred milliliters of tetrahydrofuran (Note 2) and 400 ml. of ether are added in separate portions, and the mixture is stored at —40° overnight. The mixture is filtered rapidly, and the solid is washed with a mixture of 200 ml. of tetrahydrofuran (Note 2) and 200 ml. of ether. The filtrate and washings are combined and concentrated by distillation to a volume of 250 ml. by the use of a water aspirator and a bath at 40° (Note 3). This solution of oximinomalononitrile is used directly in the next step. 

One can check for complete precipitation of the amino-malononitrile by adding -toluenesulfonic acid to the clear supernatant liquid. 

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