Y-Cyanoacetals

Sodium hypophosphite s. under Ni Hydrogen peroxide nitric acid a, c-Disubst. succinic acids from nitriles via y-cyanoacetals... 

Syntheses with halogenacetals y-Cyanoacetals from nitriles... 

Reactions. The chemical properties of cyanoacetates ate quite similar to those of the malonates. The carbonyl activity of the ester function is increased by the cyano group s tendency to withdraw electrons. Therefore, amidation with ammonia [7664-41-7] to cyanoacetamide [107-91-5] (55) or with urea to cyanoacetylurea [448-98-2] (56) proceeds very easily. An interesting reaction of cyanoacetic acid is the Knoevenagel condensation with aldehydes followed by decarboxylation which leads to substituted acrylonitriles (57) such as (29), or with ketones followed by decarboxylation with a shift of the double bond to give P,y-unsaturated nitriles (58) such as (30) when cyclohexanone [108-94-1] is used. 

A convenient method leading to pyrans (38) consists in the nucleophilic addition of R anions to 2,6-disubstituted pyrjdium salts, in which the y-position (secondary carbonium ion) is more reactive than the a-positions (tertiary carbonium ions), in opposition to the reactivity of 2,4,6-trisubstituted pyrylium salts.Krohnke and Dickore as well as Dimroth and WolH showed that 2,6-diphenyl-pyrylium salts add the anions R of nitromethane, 1,3-diketones, malonodinitrile, ethyl cyanoacetate, and benzoylacetonitrile. Similar reactions are known in the flavylium series. -Nonactivated R ... 

Ethanol, 2-(cyclohexyloxy)-, 47, 37 Ether, l butyl phenyl, 46, 89 fi-Ethoxyphenyl isothiocyanate, 46, 21 Ethyl acetoacetate, 46, 82 Ethyl benzoyloxy cyanoacetates, 46, 38 Ethyl y-bromobutyrate, 46, 42 Ethyl 2-bromocyclopentane acetate, 46, 44... 

Carrie and co-workers studied the cycloaddition of oxime esters derived from methyl cyanoacetate and malonate esters 82 (Scheme 8.20) with diazomethane and some monosubstituted derivatives. Thermally labile 1,2,3-triazolines 83 were obtained when tosyloxy- and benzoyloxyimines were used (141), while methyl acetoxyimino-cyanoacetate (82, X = CN, Y = C02Me, = Ac) gave products derived from both a 1,2,3- and a 1,2,4-triazoline, depending on the stmcture of the diazo compound (142). Not unexpectedly, diazomethane reacted with the corresponding imino-malononitrile (82, X = Y = CN) system at the nitrile function rather than at the C=N bond (143). 

Synthesis of tetrahydropyrido[2,3-,y pyrimidin-7-ones 537 in a microwave-assisted one-pot cyclocondensation of a,/3-unsaturated esters with active methylene compounds (malononitrile or methyl cyanoacetate) and amidine salts (guanidine or benzamidine) in NaOMe/MeOH for 10min has been reported <2003TL5385>. 

The condensation of benzaldehyde with ethyl cyanoacetate, ethyl malonate and ethyl acetoacetate were carried out with high rates and selectivity promoted by lithium-, sodium, potassium-, and caesium-exchanged X and Y zeolites and on sodium-Germanium substituted faujasite. 

The results in Table 2 show that the pyridine is less active than any of the X zeolites and Ge faujasite except the lithium form which shows slightly lower activity, whereas all Y zeolites show lower activity than pyridine. Piperidine, however, is more active than any of the zeolite samples studied here. From this comparison, it appears that, most of the basic sites of the zeolites must have pK<10.3. However, the fact that zeolites are also active for catalyzing the condensation of benzaldehyde with ethyl malonate, indicate that these samples have some basic sites with pK< 13.3. On a quantitative bases, and comparing the activity of zeolites for condensation with ethyl cyanoacetate, ethyl acetoacetate and ethyl malonate (Fig. 2), we can conclude that most of the basic sites of the zeolite have pK<9.0 with a sensible amount with 9.0basic strength of different solid base catalysts. 

The enantio-determining step of nucleophilic additions to a-bromo-a,y -unsaturated ketones is mechanistically similar to those of nucleophilic epoxidations of enones, and asymmetry has also been induced in these processes using chiral phase-transfer catalysts [20]. The addition of the enolate of benzyl a-cyanoacetate to the enone 31, catalysed by the chiral ammonium salt 32, was highly diastereoselective and gave the cyclopropane 33 in 83% ee (Scheme 12). Good enantiomeric excesses have also been observed in reactions involving the anions of nitromethane and an a-cyanosulfone [20]. 

While the Reissert reaction is a convenient method for introducing a cyano substituent into the position a to the nitrogen atom in thienopyridines, a method has been developed to introduce substituents into the position y to the nitrogen atom. Thus, acetic anhydride/ethyl cyanoacetate or benzoyl chloride/cyclohexanone enamine reagents were useful for preparing ethyl 2-(4-thieno[2,3-6]pyridyl)cyanoacetate (53) or 2-(4-thieno[2,3-6]pyridyl)cyclohexanone (54), respectively (Scheme 13) <84JHC1135, 87JHC1467). 

Cesium-exchanged zeolite X was used as a solid base catalyst in the Knoevenagel condensation of benzaldehyde or benzyl acetone with ethyl cyanoacetate [121]. The latter reaction is a key step in the synthesis of the fragrance molecule, citronitrile (see Fig. 2.37). However, reactivities were substantially lower than those observed with the more strongly basic hydrotalcite (see earlier). Similarly, Na-Y and Na-Beta catalyzed a variety of Michael additions [122] and K-Y and Cs-X were effective catalysts for the methylation of aniline and phenylaceto-nitrile with dimethyl carbonate or methanol, respectively (Fig. 2.37) [123]. These procedures constitute interesting green alternatives to classical alkylations using methyl halides or dimethyl sulfate in the presence of stoichiometric quantities of conventional bases such as caustic soda. 

Simple saturated nitriles are seldom prepared by the decarboxylation of cyano acids derived from the cyanoacetic ester synthesis (cf. method 265). However, difunctional compounds are frequently obtained by this route, as in the preparation of a-methyl-y-phenoxybutyronitrile from /3-phenoxy-ethyl bromide and ethyl methylcyanoacetate (52% over-all). ... 

Ethyl /3-oxovalerate, a Q-keto ester, is prepared from ethyl Grignard reagent and ethyl cyanoacetate (58%). Amino ketones are conveniently made by the action of aromatic Grignard reagents on y-diethyl-aminobutyronitrile, (CjH5)jNCHjCH2CHjCN, in 80-90% yields. ... 

The reacton of quinazoline with active methylene compounds 6 such as phenylacetonitrile (X = Ph Y = CN), ethyl cyanoacetate (X = COjEt Y = CN), or nitromethane (X = II Y = NOj) in the presence of sodium methoxide results in the formation of 4,4 -biquinazolinyl and small amounts of the corresponding 4-substituted quinazolines 7. ° ... 

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