2- malononitriles

Malononitrile, obtained by the dehydration of cyanoacetamide with phosphorus pentachloride ... 

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). 

The TT-allylpalladiLim complexes formed as intermediates in the reaction of 1,3-dienes are trapped by soft carbon nucleophiles such as malonate, cyanoacctate, and malononitrile[ 177-179). The reaction of (o-iodophenyl-methyl) malonate (261) with 1,4-cyclohexadiene is terminated by the capture of malonate via Pd migration to form 262. The intramolecular reaction of 263 generates Tr-allylpalladium, which is trapped by malononitrile to give 264. o-[odophenylmalonate (265) adds to 1,4-cyciohexadiene to form a Tr-allylpalladium intermediate via elimination of H—Pd—X and its readdition, which is trapped intramolecularly with malonate to form 266)176]. 

Arylation or alkenylation of soft carbon nucleophiles such as malonate is carried out by using a copper catalyst, but it is not a smooth reaction. The reaction of malononitrile, cyanoacetate, and phenylsulfonylacetonitrile with aryl iodide is possible by using a Pd catalyst to give the coupling products. 

The presence of a cyano group seems to be important[649]. The reaction has been successfully applied to halides of pyridine, quinoline, isoquinoline, and oxazoles[650]. An interesting application is the synthesis of tetracyanoquino-dimethane (789) by the reaction of / -diiodobenzene with malononitrile[65l]. 

Malononitrile (133) undergoes Pd(0)-catalyzed dimerization to give 134[125,126]. The trimerization of malononitrile in boiling benzene catalyzed by potassium tetrakis(pentalluorophenyl)palladate gives 4.6-diamino-3,5-dicyano-2-cyanomethylpyridine (135)[127]. 

Physical Properties. The physical piopeities of malononitdle [109-77-3], NM3—(42) are hsted in Table 5. Table 5. Physical Properties of Malononitrile... 

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. 

Economic Aspects. Malononitrile of minimum 99% purity was available as a soHdifted melt for ca 30/kg in 1993 for ton quantities. Malononitrile is produced by Lon2a Ltd. (Swit2edand) using the cyanogen chloride process. 

Analytical and Test Method. Gas chromatography is appropriate for the quantitiative analysis of malononitrile. Typical analysis conditions are 3% Reoplex 400 on Chromosorb G 80—100 mesh 2 m, 2 mm diameter column temperature for column = 60 180° C injector, 200°C and detector, 200°C. The solidification point is usually measured also. 

Health and Safety Factors. Malononitrile is usually available as a soHdifted melt in plastic-Hned dmms. Remelting has to be done carefully because spontaneous decomposition can occur at elevated temperatures, particularly above 100°C, in the presence of impurities such as alkaHes, ammonium, and 2inc salts. Melting should be carried out by means of a water bath and only shordy before use. Occupational exposure to malononitrile mainly occurs by inhalation of vapors and absorption through the skin. Malononitrile has a recommended workplace exposure limit of 8 mg/m, an LD q (oral, rats) of 13.9 mg/kg, and is classified as slight irritant (skin irritation, rabbits). Transport classification RID/ADR 61, IMDG-Code 6.1, lATA/ICAO 6.1. 

Another compound of interest is adenine [73-24-5] or 6-aminopurine (53) derived from pheny1a 2oma1ononitri1e (92). The introduction of the dicyanostyryl moiety has led to the industriali2ation of several methine dyes such as the Cl Disperse Yellow [6684-20-4] (54) (93). The Cl Disperse Blue 354 [74239-96-6] (55) also represents a new class of anTinoarylneutrocyariine dyes with a brilliant blue shade (94). The dimer of malononitrile is also used for the synthesis of new dyes (95). 

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). 

A major type of reaction in this class is the cyclization of 4-amino- or 4-halo-pyrimidines carrying 5-cyanoethyl or 5-ethoxycarbonylethyl groups, which cyclize to 7-amino or 7-oxo derivatives of 5,6-dihydropyrido[2,3- f]pyrimidine, e.g. (131)->(63). The intermediates may sometimes be prepared by reaction of 4(6)-aminopyrimidines with acrylonitrile, or even via a pyrimidine ring synthesis from an amidine and a cyanoacetic ester or malononitrile derivative, e.g. (132) -> (133) (7lJOC2 85, 72BCJ1127). 

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]

Thiirane is more bactericidal than oxirane, and derivatives of 2-mei captomethylthiirane inhibit tuberculosis. The following pharmacological uses have been reported for compounds derived from thiirane derivatives gold complexes of the adducts of diethylphosphine and thiirane (antiarthritic), adducts of thiiranes and malononitrile (antibacterial, blood vessel dilators, muscle relaxants, sedatives), thermolysis products of thiirane 1-oxides and adducts of thiirane 1-oxides with sulfenyl chlorides (antibacterial), adducts of 2,3-diarylthiirene 1,1-dioxides with ynamines (antibacterial, parasiticidal), adducts of 2,3-diarylthiirene 1,1-dioxides with enamines (antifertility), adducts of p-aminophenylacetic esters with thiirane (immunosuppressants), adducts of amines and thiiranes (radioprotective drugs). 

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