Malononitrile, reaction with substituted

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>. 

Nucleophilic attack of hydroxide ion on the a-carbon atom, with subsequent cleavage of the Ca—Cp bond, has been proposed to account for the kinetics of retro-aldol reaction of substituted benzylidene malononitriles with hydroxide ion in 90%... 

Aldehydo nitriles are readily available and can be used to prepare 4-amino-6-unsubstituted pyrimidines carrying one or more substituents in any of the other positions. Equivalents of the formyl group are also often used, for example, a 3-ethoxy-, 3-amino-, or 3-haloacrylonitrile. Most syntheses with /3-keto nitriles are carried out with equivalents thereof Such equivalents are /3-substituted /3-alkoxy-, /3-amino-, or /3-haloacrylonitriles. /3 -Ester nitrile reactions are also well established. Malononitriles and substituted malononitriles react readily with thiourea and N-substituted thioureas in refluxing ethanolic sodium ethoxide to form pyrimidine-4,6-diamines. An example is the reaction of N2-malononitrile 680 with N2-thiourea 681 to give N4- 4,6-diamino-2-(l//)-pyrimidinethione 682 which was then used in the synthesis of Ns-labeled adenine derivatives <2001JOC5463>. 

Compound 63, the 2-formyl derivative of compound 61, undergoes a series of side-chain reactions at the carbonyl group including reduction with sodium borohydride and condensation reactions with hydroxylamine or malononitrile. The reactions afford the appropriately 2-substituted products in excellent yields <2004CHE1477>. 

Replacement of a chloro group on the pyrazine by nucleophilic substitution with the anion of an activated methylene species is the major pathway in the synthesis of pyrrolo[2,3-3]pyrazines. The symmetrical pyrazine 250a undergoes reaction with malononitrile and K2CO3 in acetonitrile to form 251a (Scheme 24). Reaction of this intermediate with benzylamine in acetonitrile affords 252a <2001MC152>. 

Multicomponent one-pot reactions continue to be the focus of heterocyclic synthesis when multi-bonds are formed. Malononitrile condenses with 3-pyridinecarbaldehyde and a ketone to form a substituted bipyridine (Equation 179) <1995JCM146>. In another condensation, with aniline being the ultimate source of the tetrahydroquinoline nitrogen atom, iodine is used as a catalyst in a reaction that was optimized for yield and diastereoselectivity (Equation 180) <2005SL2357>. 

In the reaction of 2-, 3- and 4-bromobenzophenones with electrogenerated PhZ" ions (Z = Se,Te) in MeCN, with azobenzene as a redox catalyst and with the addition of carbon acids such as fluorene or malononitrile, good yields of substitution products 255a (62-86%) were obtained in the reaction with PhSe" ions, and no symmetrical selenide 256a... 

A synthesis of electrochemically amphoteric TTFAQ-ct-A derivatives 917 and 918 (TTFAQ = 9,10-bis(l,3-dithiol-2-ylidene)-9,10-dihydroanthracene, ct = saturated spacer, A = polynitrofluorene acceptor) involved esterification of the acid chloride 916 with the hydroxymethyl-substituted TTFAQ derivative 915 in pyridine. To increase acceptor properties, 917 was converted into the dicyanomethylene derivative 918 by reaction with malononitrile in DMF (Scheme 138) <2002JA14227>. 

The Knoevenagel condensation was also performed with MCM-41-(6112)3-NH-(CH2)2-NH2 catalyst prepared through post-modification methodology/ utilizing (2-aminomethylaminopropyl)trimethoxysilane. Various aldehydes and ketones were reacted with malononitrile and ethyl cyanoacetate (Scheme 3.21, R =R = CN and R CN, R = EtOCO) in all the reactions total conversions were achieved in toluene with exclusive formation of dehydrated products (75-100% yield). Interestingly, both aliphatic and aromatic carbonyl compounds showed identical reactivity in the reaction with ethyl cyanoacetate and the substitution on the aromatic ring did not influence the reactivity. 

Ethoxybutadiene-l,l-dicarbonitriles 11 are used as malonaldehyde equivalents. In a vinylic substitution reaction with the nucleophilic 5-position of 2,6-diaminopyrimidin-4(3i/)-one, the ethoxy group is replaced and the resultant intermediate cyclizes to a dihydropyrido[2,3-d]pyrimidine. Aromatization in the last step then occurs by loss of malononitrile to yield 12.227... 

Ethoxy-5,6-dihydro-4//-l,3-oxazines (111) react with enolates and related compounds at C-2 ethanol is lost and the corresponding 2-substituted dihydro-1,3-oxazine is formed. Depending upon the nature of the substituent endo-exo double bond, tautomerism can be observed. Thus, a reaction with the anion of malononitrile yields the 2-alkylidene-3,4,5,6-tetrahydro-l,3-oxazine (112) rather than the 2-alkyl-5,6-dihydro-1,3-oxazine (113) (Scheme 27) <86JHC701>. 

Vinylsilanes 132 have been reacted with bromomalononitrile to yield the intermediate 133, which was used for the synthesis of cyclopropane derivatives Addition reactions of dichloromalononitrile with substituted alkenes and alkadienes can also be used for the preparation of intermediates in carbo- and heterocyclic synthesis. 2-Arylmalononitriles 135 have been produced by coupling malononitriles with aryllead(IV) triacetates like 134163. 

In the synthesis of coumarins by the von Pechmann reaction, a spiro-compound (251) was simultaneously formed from 4-chloro-2-methylphenol (and from 2,3,5-trimethylphenol). A possible mechanism for this reaction involves the formation of the lactone (252), which reacts with another molecule of the phenol. The condensation of the dicyano-ester (253) [obtained from malononitrile and ethyl cyanoacetate] with substituted o-hydroxybenzaldehydes yields substituted coumarinimines, e.g. (254).A series of 4,6,7-substituted coumarins have been prepared and assessed for their suitability in fluorescence labelling of polymers. Esters of the type PhCH CRCOaAr react with AICI3 to give coumarins, which are probably formed via dihydrocoumarins (255) by dearylation. ... 

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