Ketones, reaction with cyano-esters

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. 

Rann et al. reported the dramatic influence of a new tailor-made, task-specific, and stable ionic liquid, butyl methyl imidazolium hydroxide ([bmim][OH]), in Michael addition. They have discovered that a task-specific ionic liqnid [bmim][OH] efficiently promoted the Michael addition of 1,3-dicarbonyl compounds, cyano esters, and nitro alkanes to a variety of conjugated ketones, carboxylic esters, and nitriles withont reqniring any other catalyst and solvent (Fig. 12.21) [16]. Very interestingly, all open-chain 1,3-dicarbonyl componnds such as acetylacetone, ethyl ace-toacetate, diethyl malonate, and ethyl cyanoacetate reacted with methyl vinyl ketone and chalcone to give the usual monoaddition products, whereas the same reactions with methyl acrylate or acrylonitrile provided exclusively bis-addition products. 

Steroidal ketones have been used extensively in the Knoevenagel reaction. Thus, die transformation of 17-oxoandrostane derivatives (309), which are readily available by microbiological degradation of sitosterin, are employed for the synthesis of enantiomerically pure cardiotonic steroids such as bufa-dienolide and cardenolide (311). In toth syntheses the substitutent at C-17 is introduced by a Knoevenagel reaction of the 17-oxoandrostane derivative (309) with ethyl cyanoacetate in the presence of ammonium acetate to give the cyano ester (310), presumably as a mixture of the ( )- and (Z)-isomers, in 89% yield.5 5... 

The ketone 59 was converted into the aldehyde 60 which was submitted to a Strecker reaction with -<-butyl 3-methyl-4-aminobutyrate and potassium cyanide to give, after benzoylation, the cyano ester 61 as a mixture of stereoisomers. This mixture was cyclized and saponified to afford the enamino ester 62 which was transformed into the ketone... 

The reaction of N-aminoazonium salts with aliphatic and aromatic aldehydes in the absence of base gives the Schiff base type compounds 28.151,153-156 Some aliphatic ketones also react with N-aminoazonium salts.40,155 Hexane-2,5-dione reacts with N-aminopyridinium perchlorate to give l-(l -pyrrolyl)pyridinium cation 29 together with some of the bisper-chlorate 30.157 Certain esters such as diethyl malonate and ethyl cyano-acetate react with N-aminopyridinium salts in the presence of base to give the corresponding N-acylimines 31.48 However, the reaction of ethyl aceto-acetate and acetylacetone with N-aminoazonium salts in the presence of base gives 1,3-dipolar cycloaddition products (Section IV,C,1).36,154,158 The reaction of ethyl acetoacetate with 1-alkyl-l,2,4-triazole 4-imine affords zwitterionic triazolo[4,3-/>]pyridazines 32.139,159... 

The reaction of the ester 51 with MeLi (55) in the presence of trimethylsilyl chloride cannot be performed on a large scale in a reproducibly high yield. For the synthesis of the Ci8-ketone 51 on a large scale, an alternative, a three-step route is used (Scheme 18). First the geranylacetone (52J is coupled in an Horner-Emmons reaction with diethyl cyano-methylphosphonate (4) with NaH as a base. Reduction of the nitrile by DEB AH then gives the aldehyde 56 in 73% yield. Aldol condensation of 56 with acetone (57) in the presence of a... 

The cuprate reagents can also convert acid chlorides to ketones, and are alternatives to alkylcadmium reagents in this regard/ The add chlorides can contain such functional groups as cyano, ester, and ketone without interfering with successful reaction/ ... 

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