Malononitrile complexes

Effective solvent-free peroxidative oxidations of 1-phenylethanol (Scheme 18.1) and/or some secondary aliphatic alcohols toward the corresponding ketones with tert-butylhydroperoxide (TBHP) under MW irradiation, catalyzed by copper(II)-alkoxy-triazapentadienato (Cu -TAP) [10, 11] complexes 1, 2, dicopper(II)-aminopolyalcoholate (Cu -APA) [12] complexes 3, 4, arylhydrazone-j8-diketonate (CuII-AHBD) complex 5 [13], mixed-N,S copper(II) and iron(II) complexes 6-11 [14] and by the tetranuclear copper(II) aryUiydrazone of malononitrile complex 12 [15], have been achieved (Scheme 18.2). 

C2 Ha aBrNOa 9 2-p-Bromophenyl-4a,5,5a,6,7,8,9,9a,10,10a-decahydro-5a-methyl-10a-morpholino-4H-naphtho[2,3-b]pyran, 40B, 336 C211H3fiNeO, N,N -Bis-(2-cyanoethyl)-l, 10-diaza-4,7,13,16-tetraoxa-cyclo-octadecane malononitrile complex, 45B, 417 C25H20CINO13, 6,7-Bis(methoxycarbonyloxy)-l,2,3,4-tetrahydro-iso-quinoline-[1,2-c]-oxazol-2-one-[3,4-b]-1-chloro-3-methoxycarbonyl-oxy-6,7-methylenedioxyindane, 45B, 418 C2 5H21 Cl2NO, 3-(3,5-Dichloro-2,4,6-trimethylphenyl)-4-diphenylmeth-ylene-2-isoxazoline, 42B, 283... 

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]. 

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). 

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). 

We employed malononitrile and l-crotonoyl-3,5-dimethylpyrazole as donor and acceptor molecules, respectively. We have found that this reaction at room temperature in chloroform can be effectively catalyzed by the J ,J -DBFOX/Ph-nick-el(II) and -zinc(II) complexes in the absence of Lewis bases leading to l-(4,4-dicya-no-3-methylbutanoyl)-3,5-dimethylpyrazole in a good chemical yield and enantio-selectivity (Scheme 7.47). However, copper(II), iron(II), and titanium complexes were not effective at all, either the catalytic activity or the enantioselectivity being not sufficient. With the J ,J -DBFOX/Ph-nickel(II) aqua complex in hand as the most reactive catalyst, we then investigated the double activation method by using this catalyst. 

As shown above, it was not so easy to optimize the Michael addition reactions of l-crotonoyl-3,5-dimethylpyrazole in the presence of the l ,J -DBFOX/ Ph-Ni(C104)2 3H20 catalyst because a simple tendency of influence to enantio-selectivity is lacking. Therefore, we changed the acceptor to 3-crotonoyl-2-oxazolidi-none in the reactions of malononitrile in dichloromethane in the presence of the nickel(II) aqua complex (10 mol%) (Scheme 7.49). For the Michael additions using the oxazolidinone acceptor, dichloromethane was better solvent than THF and the enantioselectivities were rather independent upon the reaction temperatures and Lewis base catalysts. Chemical yields were also satisfactory. 

The Knoevenagel reaction between o-hydroxyaryl aldehydes and ketones and substituted acetonitriles affords high yields of 3-substituted coumarins in aqueous alkaline media <96H(43)1257>, whilst 4-hydroxycoumarins have been elaborated to pyrano [3,2-c]benzopyran-5-ones by reaction with aromatic aldehydes and malononitiile <96P148>. The imine (10) resulting from the complex reaction of o-hydroxyacetophenone with malononitrile undergoes a 1,5-tautomeric shift in solution <96JCS(P1)1067>. 

Malononitrile over potassium tetrafluorocobaltate(III) gives a mixture of at least 35 products and the benzonitrile product is almost as complex." However, over cesium tetra-fluorocobaltate(III) at 300°C, benzonitrile gives100 a much simpler mixture and perfluorocyclo-hexanecarbonitrile (ca. 30%) is the major product, with perfluorocyclohexane and per-fluorobenzonitrile as minor ones. Perfluorobenzonitrile is converted, in over 50% yield, by both cobalt(III) fluoride (165-170°C) and potassium tetrafluorocobaltate(III) (210°C), into mainly the nonconjugated monoene perfluoro(cyclohex-3-enecarbonitrile). 

A. Dibromomalononitrile-potassium bromide complex. In a 2-1. three-necked flask equipped with an efficient stirrer, a dropping funnel, and a thermometer are placed 900 ml. of cold water, 99 g. (1.5 moles) of malononitrile (Note 1), and 75 g. (0.63 mole) of potassium bromide. The flask is then placed in an ice-water bath, the stirrer is started, and the thermometer is adjusted to extend into the liquid but not into the path of the stirrer. When the temperature of the mixture has dropped to 5-10° (much solid crystallizes), 488 g. (158 ml. at 25°, 3.05 moles) of bromine is added over a period of 2.5 hours. The stirring is continued for an additional 2 hours, while the temperature is held at 5-10°. The precipitated solid complex is collected on a Buchner funnel, washed with 150 ml. of ice-cold water and sucked as dry as possible for about 1 hour (Notes 2 and 3). The grainy product is then dried to constant weight in a vacuum desiccator over phosphorus pentoxide, at the pressure obtained with an aspirator (Notes 4 and 5). The yield of light-yellow product is 324 340 g. (85-90%) (Note 3). 

Trans acylations have been encountered in the acylation of 2-acylthiophenes. Thus the action of benzoyl chloride on 2-acetylthiophene in presence of excess A1C13 has led to a complex mixture, from which 2-benzoyl-, 2,4-dibenzoyl- and 2,5-dibenzoyl-thiophene were isolated (73ZOR1959). Other examples of ipso acylation including acyl-debromination and acyl-de-r-butylation have been recorded. Unexpected products have been reported in some intramolecular cyclizations. Thus cyclization of the acid (103) leads to (104) and not (105) (63AHCHH). Acid-catalyzed cyclization of ylidene-malononitriles has been reported (75JOC1840). Yields are in the range 30-60% (Scheme 19). 

Herz salts bearing chlorine at the 6-position 140 react with malononitrile to afford highly colored ylidenes 141 in low to moderate yields (Equation 31) <2002J(P1)315>. The reaction is general but complex few by-products were isolated. 

Nitro compounds are also useful starting materials, because a nitro group can be readily converted to a carbonyl group or to amino functionality. Addition reactions of nitroalkane have been reported by Yamaguchi [13b], Shibasald [6a], Bako and Toke, Corey, Hanessian, and Kanemasa [21]. For example, Kanemasa used their chiral Lewis acid complex 35 for the reaction of 36 with nitromethane (Scheme 18). The reaction proceeded with the aid of the amine co-catalyst, affording the product 37 with high enantioselectivity. This system was also applicable to the reaction of malononitrile [2 le]. 

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. 

Like / -keto esters, /3-keto nitriles react smoothly with hydrazine the latter give aminopyrazoles.78,310-321 Under the same conditions cyanoacetic ester and its derivatives give aminopyrazolones.322-325 The reaction of malononitrile is more complex, giving 1-substituted 3-cyanomethyl-4-cyano-5-aminopyrazole and products formed by further condensation.328... 

The presence of electron-withdrawing substituents at C(4) facilitates reactions with nucleophiles, which may well be initiated by attack at C(5). Thus oxazole-4-aldehydes undergo ring-fission on treatment with aqueous alkali to form (acylamino)malondialdehydes (equation 3), and 2-pentyloxazole-4-carboxylic acid yields 2-pentylimidazole, with concomitant decarboxylation, when heated with ammonia at 150 °C. An example of a more complex ring transformation is the formation of 3-aminopyridines (131) by the action of malononitrile on 4-acetyloxazoles under alkaline conditions (equation 4). 

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