2- malononitrile, reaction

When the precursor is derived from malononitrile, reaction with maleimide leads to the expected a-cyano pyrrolidine adduct. However, methyl propiolate gives 3-carbomethoxy pyrrole, probably due to the acidity of hydrogen a- to the cyano group in the intermediate A3-pyrrolinic adduct first formed.171... 

Because of the huge importance of pyridine derivatives, a considerable amoimt of effort has been directed to the development of multicomponent routes for their synthesis, including reactions performed in water. For instance, a one-pot four-component condensation of aldehydes, malononitrile and thiophenols in the presence of boric acid as catalyst in aqueous medium afforded high yields of 2-amino-3,5-dicaibonitrile-6-thiopyridines 46 [29], either by conventional heating or under ultrasound-aided conditions (Scheme 1.21). This reaction can also be performed in an aqneons snspension of basic almnina [30] or in water with microporous mo-lecnlar sieves as catalysts [31]. Mechanistically, this transformation involves an initial Knoevenagel condensation of the aldehyde with a molecule of malononitrile, followed by the Michael addition of the second molecule of malononitrile, reaction of one of the nitrile groups with the thiol, cyclization and a final air oxidation step. 

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]. 

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. 

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). 

Fluorinated esters may also act as electrophiles in reactions with nonfluori-nated ketones [28] (equation 23) or malononitrile [29] (equation 24). Unfortunately, the yields of -diketones may be modest, but those of p-keto nitnles are excellent (Table 9)... 

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. 

Recyclization reactions of heterocycles with participation of malononitrile and its derivatives 99UK45. 

Cycloaddition of 2-styryl-4/7-3,l-benzoxazines and malononitrile gave 1 -amino-3-aryl-2-cyano-1 //,6//-pyrido[l, 2-n][3, l]benzoxazin-4-ones (99ZN(B)923). These tricyclic derivatives were also prepared in the reaction of 2-methyl-4//-3,l-benzoxazin-4-one and arylidenemalononitrile in AcOH in the presence of NaOAc. 

Reaction of malononitrile and quinazolinone 429 in the presence of three drops of NEts yielded pyrido[2,l-Z)]quinazolinone 430 (97MI7). 9,11-Dioxo-5,9-dihydro-l l//-pyrido[2,l-Z)]quinoline-8-carboxylates 432 were prepared in the reaction of anthranilonitrile and 2-piperidones 431 in boiling EtOH in the presence of AcOH (00JCS(P1)3686, 00PS133). 

Cycloaddition of 4-acylsubstituted fulvene 425 with the imine 427 in boiling toluene gave the tricyclic pyrroline 428. Treatment of 426 with 427 and subsequent reaction of the product 429 with malononitrile gave 428 (86S908) (Scheme 72). 

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. 

A variety of amine bases were used in 10 mol%, equivalent amount to that of the J ,J -DBF0X/Ph-Ni(C104)2 3H20 catalyst, in the reaction between malononitrile and l-crotonoyl-3,5-dimethylpyrazole in dichloromethane (Scheme 7.48). Not only... 

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. 

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