Ethyl a-cyanoacetate

A dodecakis(NCN-Pdn) catalyst, synthesized in the group of Van Koten (Figure 4.24), was applied in the a continuous double Michael addition reaction between methyl vinyl ketone (MVK) and ethyl a-cyanoacetate.[34] The reaction was performed in the deadend reactor discussed in paragraph 4.2.1. Two catalytic runs were performed differing in the amount of catalyst and in the applied flow (both increased by a factor 2.5). Both runs showed high productivity for more than 24 h (Figure 4.25). 

The yields of reaction products from thermal nucleophilic substitution reactions in DMSO of 0- and p-nitrohalobenzenes (Zhang et al. 1993) or p-dinitrobenzene (Liu et al. 2002) with the sodium salt of ethyl a-cyanoacetate were found to be markedly diminished from the addition of small amounts of strong electron acceptors such as nitrobenzenes. At the same time, little or no diminution effects on the yields of the reaction products were observed from the addition of radical traps such as nitroxyls. These results are consistent with the conclusion that such reactions proceed via a nonchain radical nucleophilic substitution mechanism (Scheme 4.26). 

In 2007, Chen and co-workers reported the 122-catalyzed (10mol% loading) enantioselective Michael addition [149-152] of ethyl a-cyanoacetate to various electron-rich and electron-deficient trans-chalcones [283]. The reaction was performed for a broad spectrum of chalcones and gave the corresponding adducts in yields of 80-95% and in ee values of 83-95%, but at low sy /a ti-diastereoselectiv-ities as shown for representative products 1-8 in Scheme 6.125. 

Transformation of both the ester and nitrile derivatives 726 or 727 into pyrano[2,3-t7 pyridazines 728 or 729, respectively, by treatment with dilute HCl at room temperature involved nucleophilic displacement of the morpholine group by the hydroxyl group with an acidic hydrolysis followed by intramolecular iminolactonization and then hydrolysis of the formed imino group to a carbonyl group. Compounds 726 and 727 were prepared by Vilsmeier-Haack formylation of 2-methyl-5-morpholino-3(2/7)-pyridazinone 724 followed by condensation of the resulting product 725 with either ethyl a-cyanoacetate or malononitrile in EtOH (Scheme 34) <1994H(37)171>. 

Keywords aldimine, ethyl-a-mercaptoacetate, ethyl-a-cyanoacetate, basic alumina, microwave irradiation, /Mactams... 

Double Michael addition reactions between methyl vinyl ketone (MVK) and ethyl a-cyanoacetate under continuous conditions (dead-end reactor) were performed with a dodecakis (NCN-Pd") catalyst by the van Koten group (12). A high productivity and retention (99.5%) of the catalyst for more than 24 h was observed, but slow deactivation of the system occurred after a stable conversion level had been reached [23]. 

Normally, aqueous acid hydrolysis liberates the imine, which is converted to a carbonyl under the reaction conditions by loss of ammonia. If the intermediate imine is reduced in situ, an amine product such as 1.60 is generated. If the cyano group is conjugated to an ester (or another carbonyl group), the imine isomerizes to the enamine form (an enamine ester). This latter process is illustrated by the reaction of ethyl a-cyanoacetate and ethylmagnesium bromide, and the product was ethyl 3-aminopent-2-enoate, 7.67.33... 

A variation of this method prepared the Grignard of 3 bromotoluene and reacted it with the magnesium enolate of ethyl a-cyanoacetate to give ethyl 3-amino-3-(3-methylphenyl)prop-2-enoate, 1.62. Ethyl 3-amino-3-phenylprop-2-enoate was prepared in 60% yield by this method, using bromobenzene as the source of the Grignard reagent. Other aryi derivatives were prepared as well. Although the... 

In another variation, keto-ester 7.14 reacted with ethyl a-cyanoacetate to give 7.143. Subsequent reaction with ammonium hydroxide led to 7.116 in good yield.85 Amines were also reacted with 7.143 to give N-alkyl derivatives of 7.116. 

A Pt pincer complex is able to be bonded to the optically active hyperbranched polyglycerol as pendant groups 594. The CD spectra of the polymer complex with different absolute configuration of the monomer units show opposite signs of the peak at 262 nm. The polymer-bonded complex catalyzes asymmetric addition of ethyl a-cyanoacetate to methyl vinyl ketone." " ... 

The formation of ethyl isopropylidene cyanoacetate is an example of the Knoevenagel reaction (see Discussion before Section IV,123). With higher ketones a mixture of ammonium acetate and acetic acid is an effective catalyst the water formed is removed by azeotropic distillation with benzene. The essential step in the reaction with aqueous potassium cyanide is the addition of the cyanide ion to the p-end of the ap-double bond ... 

Into a 500 nil. round-bottomed flask, provided with a double surface condenser, place 50 g. (63 ml.) of pure, dry acetone, 50 g. (47 ml.) of ethyl cyanoacetate (Section 111,131) and 0 -5 g. of piperidine. Allow to stand for 60 hours and heat on a water bath for 2 hours. Treat the cold reaction mixture with 100 ml. of ether, wash with dilute hydrochloric acid, then with water, and dry over anhydrous sodium or magnesium sulphate. Distil under diminished pressure and collect the ethyl fsopropylidene cyanoacetate (ethyl a-cyano-pp-dimethylacrylate) at 114-116°/14mm.(l). The yield is 39 g. 

The above is an example of the Guareschi reaction. It is applicable to most dialkyl ketones and to alicyclic ketones (e.g., cyclohexanone, cyc/opentanone, etc.). The condensation product (I) is probably formed by a simple Knoe-venagel reaction of the ketone and ethyl cyanoacetate to yield ethyl a-cyano-pp dimethylacrylate (CH3)2C=C(CN)COOCjHj, followed by a Michael ad tion of a second molecule of ethyl cyanoacetate finally, the carbethoxyl groups are converted to the cyclic imide structure by the action of ammonia. 

Ethylbenzoic acid was converted to the acid chloride, which was treated with AICI3 and benzene to give 4-ethylbenzophenone in 90% yield overall. Condensation with ethyl cyanoacetate afforded ethyl 4-ethyl-a-cyano-B-phenylcinnamate as an essentially 50/50 mixture of the Z- and E-isomers. The yield of the condensation was highly sensitive to reaction conditions, and was optimized at 75% with portionwise addition of the ammonium acetate catalyst. Bromination and dehydrobromination as described earlier then completed the preparation. The overall yield of ethyl 4-vinyl-a-cyano-p-phenylcinnamate was 20%. 

N-(4-hydroxycyclohexyl)-3-mercapto-3-cyano-4-arylazetidine-2-ones were synthesized from N-(4-hydroxycyclohexyl)aryldiimine by reaction with ethyl a-mercapto-a-cyanoacetate on basic alumina under microwaves. The reaction time was reduced from hours to minutes in comparison to conventional heating and, moreover, the yield was improved [121]. 

P-keto esters with a,p-unsaturated aldehydes liquidrliquid two-phase conditions [20] but, in contrast, under analogous conditions a-cyanoacetic esters produce aldol adducts with a,p-unsaturated aldehydes [20], Ethyl acetoacetate undergoes a catalysed Michael reaction addition with trans but-2-en-l,4-diones the products are generally insufficiently stable for isolation, but can be converted into furans [21 ]. 

Elimination of hydrogen bromide from a-bromo-y-butyrolactone with triethylamine, 46,22 Epichlorohydrin, 46, 24 Ether, /-butyl phenyl, id, 89 /j-Ethoxyphenyl isothiocyanate, 46, 21 Ethyl acetoacetate, 46, 82 Ethyl benzoyloxy cyanoacetates, 46, 38 Ethyl y-BROMOBUTYRATE, 46, 42 Ethyl 2-biomocyclopentane acetate, 46, 44... 

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