Pyrans malononitrile

J.H. Kim and H. Lee, Synthesis, electrochemistry, and electroluminescence of novel red-emitting poly(p-phenylene vinylene) derivative with 2-pyran-4-ylidene-malononitrile obtained by the Heck reaction, Chem. Mater., 14 2270-2275, 2002. 

Q. Peng, Z.-Y. Lu, Y. Huang, M.-G. Xie, S.-H. Han, J.-B. Peng, and Y. Cao, Synthesis and characterization of new red-emitting polyfluorene derivatives containing electron-deficient 2-pyran-4-ylidene-malononitrile moieties, Macromolecules, 37 260-266, 2004. 

Subsequent studies on thioamide pyrans with application of the competitive reactions method contribute to our understanding of the mechanisms of heterocyclizations with cyanothioacetamide 114 (89ZOR1331). 2,6-Diaminothiopyrans 115, on heating in benzene, open their thiopyran ring reversibly forming intermediate 116, which can eliminate cyanothioacetamide 114 or malononitrile 27a with formation of UNs 30 or 117, respectively. The direction of the subsequent reaction with... 

Under the action of phenylhydrazine or 5-amino-3-phenylpyrazole on pyran 59b only benzaldehyde phenylhydrazone 271 is formed, probably, as the result of pyran retro-cleavage (82M53). A similar reaction with malononitrile, leading to pyran 59a, a product of formal displacement of a cyanoacetic moiety, possibly results from a similar cleavage (82M53) (Scheme 108). 

The reaction of pyrylium salts with Grignard reagents or organolithium compounds leads to the pseudobase by attack at C-2 (59CB2042). A similar reaction occurs with the anions derived from malononitrile and diethyl malonate, although the pyran derivatives were not always isolated (59CB2046). 

The cyclization of 5-oxonitriles offers an attractive route to 2-amino-4//-pyrans (Scheme 18) (78JHC57). The starting materials, a-benzoylcinnamonitriles, are available from benzoyl-acetonitrile and an aromatic aldehyde. Michael addition of ethyl cyanoacetate or malononitrile to the benzoylcinnamonitrile affords the oxonitrile and is followed by cyclization to the imine. The reaction proceeds at room temperature in the presence of either piperidine or sodium ethoxide. 

In all instances, a necessary condition for successful formation of the pyran is the presence of an electron-withdrawing group at C-4 of the oxonitrile. For example, the ketone (148) derived from benzylideneacetophenone and malononitrile does not cyclize. 

When methylene activation is provided by a nitrile group, 2-aminoM//-pyrans are formed (Equation 44) <2001T10163>. Likewise, malononitrile reacts with oi,[l-unsatu rated carbonyl systems to provide 2-amino-3-cyanoM//-pyrans (Equation 45) <2004SC1425>. Acrylonitrile derivatives also react with carbonyl activated methylene groups to afford 2-amino477-pyrj ns (Equation 46) <2003SC119>. 

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 >. 

Likewise, 1,3-cyclohexanediones react with 3-methyloxazolidines 93 to afford tricyclic 477-pyrans (Equation 48) <1996T14273>. In the presence of malononitrile or ethyl 2-cyanoacetate, 1,3-cyclohexanediones react with oxazinanes 94 to afford bicyclic 2-amino-4/7-pyrans (Equation 49) <1996T14273>. 

Aminonaphtho[l,2-b]pyrans are converted into 5,6-dihydrobenzo[h]quinolines under basic conditions through a Dimroth rearrangement. The oxygen heterocycle is formed by a Michael addition of malononitrile to a 2-arylidene-l-tetralone and the whole sequence provides an... 

When malononitrile was utilized, due to its higher acidity (pA 11.5) with respect to dimedone (pAa 12.0), the reaction could be carried out in a three-component manner by adding the reagents all at once the corresponding tetrahydrobenzo[ ]pyrans were isolated in 77-99% yield. 

Pyrazol-3-one 392 reacts with arylidene malononitriles 393a-c in basic ethanolic medium to yield the 6-(3-oxopyrazol-4-yl)-2-oxo-l,2,3,4-tetrahydropyridine/ 2-hydroxy-6-(3-oxopyrazol-4-yl)-3,4-dihydropyridine adducts 397 398a-c in a 1 1 ratio (87AP140) (Scheme 109). The mechanism is assumed to proceed via intermediate 396 formed from Michael adduct 394 or possible isomer 395. The pyran derivative 396 rearranges to the pyrid-2(l//)-one/2-hydroxypyridine tautomeric mixture 397/398. 

The ionic liquid [bmim] [OH] has also been used as an efficient catalyst for the synthesis of a variety of 4H-benzo[b]pyran derivatives by a one-pot three-component condensation of aldehydes, cyclohexa-l,3-diones, and malononitrile/ethyl cyanoacetate at room temperature (Fig. 12.28) [20]. 

The synthetic routes to 1,6-naphthyridones 78 and 79 make use of the reactions of pyrans 80 with malononitrile or its derivatives. The reactions are carried out in ethanol in the presence of piperidine (1989LA585, 1995JCR(S)490, 1996JCS(P1)1067). 

Amino-4-aryl-3-cyano-7,7-dimethyl-5,6,7,8-tetrahydro-4H-benzo[f>]pyran 281 were reacted with benzylidene malononitrile in the presence of piperidine at 160 °C to afford pyrido[3,4-frJqu inclines 341 (89JPR971) (Scheme 65). 

Condensation of the malononitrile (85 R=H or Ar) with dimethone or acetoacetate gave good yields of the 4H-chromene (86) or 4H-pyran (87).98 Another approach to chromenes from aliphatic compounds is provided by condensation of citral with cyclo-hexanediones to yield the reduced chromene (88) which may be aroma-tised in a one-pot process to the 2H-chromene (89).99... 

Oxygen derivatives. Pyran derivatives 232 were prepared from pyridine-3-ylidene-malononitriles 230 and 1,3-dicarbonyls 231. Dicyanopyran 234 was obtained from 43 and 233 95. 

Photolysis of 2-amino-4//-pyrans, readily obtained from malononitrile and enones, offers a useful route to substituted cyclobutenes <97JCS(P1)3401>. 

Naimi-Jamal et al. reported that anhydrous piperazine is an efficient organocata-lyst for the preparation of 2-amino-4ff-pyrans 158 and tetrahydro //-chromenes 159 via a three-component condensation under solvent-free ball-milling conditions at ambient temperature [47]. Without the presence of the catalyst, the reaction of p-chlorobenzaldehyde, malononitrile, and ethyl acetoacetate did not take place, even by heating at 80°C. However, an excellent yield of products was obtained by ball milling... 

A one-pot three-component reaction of malononitrile, ethyl aceto-acetate, and various aromatic aldehydes using a few drops of piperidine and deionized water as solvent led to 2-amino-4-aryl-3-cyano-4ff-pyrans in good-to-excellent yields (14JHC106). Similar derivatives arise from the condensation of 3-[l,4-dioxo-3,4-dihydrophthalazin-(lfi)-yl]-... 

Cyclocondensation of 3-methyl-l-(5-substituted-3-phenyl-lH-indol-2-ylcarbonyl)-5-(4fi)-pyrazolones with arylidene derivatives of malononitrile using a catalytic amount of triethylamine in refluxing ethanol affords heterocycle [ ]-fused 6-amino-4-aryl-5-cyano-4H-pyrans (14JHC303). Other fused 6-amino-4-aryl derivatives arise from the three-component reaction of benzaldehydes, active methylene compounds (malononitrile/ ethyl cyanoacetate) and 1,3-dicarbonyl compounds catalyzed by 1,8-diaz-abicyclo[5.4.0]undec-7-ene (DBU) in refluxing water (14JHC618). Similar pyrazole[f)]-fused derivatives are obtained from the reaction of benzaldehydes, malonitrile, and 3-substituted-2-pyrazolin-5-ones using sodium... 

The heterocyclic spiro-oxindole moiety is found in a large number of alkaloids, which are important pharmaceutical compounds [44]. Several synthetic protocols are reported in the literature for the synthesis of these compounds [45]. Recently, Tao et al. [46] developed a direct asymmetric domino Michael/reduction/cychzation sequence for the construction of spiro[2H-pyran-3,4 -indohne] 99 from isatyhdene malononitrile 97 and acetone 98 in the presence of the chiral compound 100 (Scheme 9.20). 

Dibenzylidenecyclopentanone and malononitrile in methanol heated to reflux, a little Na-methoxide added, and refluxed 0.5 hr. 2-methoxy-7-benzylidene-3-cyano-4-phenyl-6,7-dihydro-5H-l-pyrindine. Y 48%. F. e. s. H.-H. Otto, Arch. Pharm. 307, 422 (1974) 2-amino-4H-pyran ring s. a. ibid. 307, 444. 

A selective method for benzylic metalation of o-, m-, and p-substituted toluenes has been reported using BuLi/f-BuOKVTMP and rationalized by the ability of the mixed metal amide base to facilitate an anion migration from the kinetic (o-aryl) to the benzylic metalation site. Reaction of 2-(l-phenylethylidene)malononitrile and 2,2,2-trifluoro-1 -phenylethanone gives (2 ,4 )-2-cyano-6,6,6-trifluoro-3,5-diphenyl-hexa-2,4-dienamide via a vinylogous aldol reaction followed by rearrangement of the 2/f-pyran intermediate (Scheme 52). °°... 

Very recently, an environmentally benign method for the synthesis of 2-amino-4,8-dihydropyrano[3,2-fc]pyran-3-carbonitrile derivatives (131) via a three-component reaction of arylaldehydes (130), malononitrile (60), and kojic acid (129) in water at 50°C under ultrasound irradiation was achieved by Banitaba et al. (Scheme 8.44). In comparison to conventional methods, this method provides several advantages such as experimental simplicity, good functional group tolerance, excellent yields (85%-98%), a short routine (5-30 min), and selectivity, without the need for a transition metal or base catalyst (Banitaba et al. 2013). 

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