Malononitrile ring closures with

In the presence of ammonium acetate, one of the Michael-acceptor systems in 4,5-bis(aryl-methylene)-4,5-dihydropyridazine-3,6-(l//,2//)-diones undergoes addition to ethyl cyanoac-etate at 160-170°C26 or malononitrile in refluxing ethanol.25 This is followed by ring closure with the appropriately situated oxo group and ammonia yielding the pyrido-fused moiety in... 

Treatment of 4//-l,2,4,6-thiatriazine 1,1-dioxide (295) with malononitrile anion leads to the formation of 5-amino-4-cyano-2/7-l,2,6-thiadiazine 1,1-dioxide (296 R = NH2) in 60% yield (see also Section 6.16.9.2.1.1) <84H(22)47i>. This ring transformation is proposed to go by a double carbanion addition at the 2,3- and 5,6- imine bonds followed by ring-opening and ring-closure, with... 

In a one-pot three-component reaction, aromatic aldehydes, malononitrile and 1,3-dicarbonyl compounds react to form 2-amino-5-carboxy-4-aryl-47/-pyran-3-carbonitriles 87. The reaction proceeds by an initial Knoevenagel condensation of malononitrile with the aromatic aldehyde to afford the 2-benzylidenemalononitrile intermediate 88. Michael addition of the activated methylene group forms the 1,5-dicarbonyl equivalent 89, which upon ring closure affords 477-pyrans (Scheme 29) <2004SL871, 1999H(51)1101 >. 

A variation on the cyclization of a-cyanomethylpyridines with a malonic ester (p. 566) is the ring closure of the acetate (104.7) with ethoxymethylene-malononitrile and of the quinolinone (104.8) with ethyl (ethoxymethylene)cya-noacetate. A methylene group in the succinic acid (104.9) readily forms an anion which attacks the electron-rich pyrrole ring on heating the compound in piperidine. COOEt... 

Condensation of an appropriately substituted malononitrile with guanidine yields a 5-alkyl-pyrimidine-2,4,6-triamine, 12, with a protected /1-formyl group.109 Deprotection of the aldehyde followed by ring closure and subsequent oxidation to give 13 is then achieved in dilute hydrochloric acid with air, with triphenylmethanol/trifluoroacetic acid, or with trifluoroperoxy-acetic acid.150... 

Thiadiazine 1,1-dioxides are also accessible by condensation of sulfamides with ethyl 3,3-diethoxypropionate in trifluoroacetic acid (Section 6.16.9.1.1), and by acid catalysed ring-closure of A-acetoacetylsulfamides (Section 6.16.9.1.2). Amino derivatives are obtained by acid-catalysed ring closure of A-(2,2-dicyanoethylidene)-sulfamide (Section 6.16.9.1.2) and by ring-contraction of 4i/-l,2,4,6-thiatriazine 1,1-dioxides in the presence of malononitrile or ethyl cyanoacetate anions (Section 6.16.10). 

Heterocyclic malononitriles. 2-Pyridylmalononitriles have been prepared from pyridinium iodides 3-pyridylmalononitriles were obtained by reacting 3-halopyridines with malononitrile anion. Other heterocyclic malononitriles like pyrazinemalononitrile and 2-thiazolemalononitrile have been prepared by direct ring-closure reactions from aliphatic precursors. 

Six-membered heterocycles Saturated as well as unsaturated nitrogen heterocycles have been prepared. The malononitrile derivative 139 underwent a ring-closure reaction with... 

If two equivalents of the 2-halo-carbonyl compound (or 2-halo-nitrile) are utilised to react with an enolate/carbon disulfide adduct, double S-alkylation and then double ring closure produce thieno[2,3-h]thiophenes [129] Scheme 82 shows how this works. Taking this idea further, if a malonate is used as the 1,3-dicarbonyl component, 3,4-dihydroxythieno[2,3-h]thiophenes are the final result (Scheme 83) [130], the ring closure steps then having the character of Claisen condensations. If malononitrile is used instead of a 1,3-dicarbonyl compound, the product is a 3,4-diaminothieno[2,3-6]thiophene - product 60 in Scheme 84 is the result of using chloroacetonitrile in the alkylation step [131]. 

Closure of the triazole ring can be achieved either by oxidative formation of the N-N bond, or condensation of an fV-aminopyridone. The latter was formed by iV-amination of pyridines with mesitylhydroxylamine (MSH), or by forming the pyridine ring, starting from cyanoacetic hydrazide with malononitrile or 2-cyanoacrylates. 

Ring synthesis from non-heterocycles by closure y to the heteroatom are reported. Sulfonium ylides (135) with active methylene compounds such as malononitrile give a C-phenacyl product (136) however, when reacted with /3-diketones and /3-ketonic esters they produce furans quantitatively (74CL101). In these cases O-phenacylation takes place followed by cyclization to give the 3-hydroxydihydrofuran (137), which is dehydrated to the furan (138) (Scheme 30). These furans differ from those formed by the reaction of the diketone or ketonic esters with phenacyl halides. The latter reaction takes place by C-phenacylation, yielding the isomeric furans (139). 

The reaction of diethyl 3,4-dimethylthieno[2,3-Z ]thiophene-2,5-dicarboxylate (117, R = Me, EWG = C02Et) with hydrazine hydrate afforded dihydrazide 231, which was subjected to various transformations. For example, the reactions with acetylacetone, ethyl acetoacetate or malononitrile (93BCJ2011) are accompanied by the closure of the exocyclic pyrazole ring to form the corresponding derivatives 232-234. The reaction of dihydrazide 231 with carbon disulfide in the presence of KOH followed by decomposition with dilute HCl or concentrated H2SO4 produces di(oxadiazole) (235) or di(thiadiazole) derivative (236). Condensation of di(oxadia-zolyl)thienothiophene 235 with hydrazine hydrate affords di(triazolyl)thienothio-phene 237. 

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