Cyanoacetic acid derivatives

Economic Aspects. In order to avoid the extraction and evaporation steps, most of the cyanoacetic acid derivatives are made directiy from solution therefore, only a small portion of the acid produced is traded. Cyanoacetic acid is produced by Boehringer-Tngelheim and Knoil ia Germany, Juzen ia Japan, as well as Hbls ia the United States. When sold ia tons, the price of cyanoacetic acid was 9/kg ia 1993. 

As CH-acids in the MCRs with aldehydes and aminoazoles, other classes of organic compounds were used as well. Cyanoacetic acid derivatives, acetoyl(aroyl) acetonitriles, ketosulfones, acetophenones, and other reagents were successfully introduced into these three-component heterocyclizations. For example, synthesis of pyrazolo[3,4-b]pyridine-5-carbonitriles 40 was carried out as the multicomponent treatment of 5-aminopyrazole, aldehyde, and benzoylacetonitriles solvent-free by fusion either in ammonium acetate at 120°C or in boiling ethanol with EtsN (Scheme 17) [69]. The second approach gave the worst results from the viewpoint of yields and purity of the target compounds. 

A series of cyanoacetic acid derivatives 96 (94TA1435, 95TA255) was used for the introduction of a chiral moiety into position 3 of a pyran ring Oppolzer s sultam (a), (—)-menthol (b), (IS)-endo-(-)-borneol (c), ethyl (S)-(—)-lactate (d), diisopropylidene-o-glucofuranose (e). Both Methods 1 and... 

Acetylacetone derivatives of bis-dithiolobenzoquinone 232 show remarkable reactivity (95M615) with cyanoacetic acid derivatives 27 in ethanol with piperidine. They proceed via symmetrical elimination of two acetyl groups and subsequent cyclization to bis-pyrano derivatives 233 (Scheme 89). 

Some assumptions about a sequence of reactions of unsaturated ketones and cyanoacetic acid derivatives can be drawn from the results of [146], which described several reaction products 134-140 and their isolation (Scheme 3.43). In the same publication it was also established that the presence of an excess of a, 3-unsaturated ketone 24 in the reaction mixture led to the addition of the initially formed tetrahydropyridine to the ethylene bond of the enone system. 

There are publications devoted to a study of the mechanism of the treatment of unsaturated carbonyls with cyanoacetic acid derivatives [134, 153]. According to these communications, the sequences of such reactions are similar to those of urea-like binucleophiles. Using piperidine as the catalyst, Al-Hajjar and Jarrar [134] and Otto [153] isolated a series of known intermediates. 

Another synthesis of pyrimido[5,4-c]cinnolin-4(3//)-ones (59) via 4-aminocinnolines (56) starts with arylhydrazono-cyanoacetic acid derivatives (58). Upon heating in the presence of A1C13 4-aminocinnolines (56) are formed. Cyclocondensation with formamide or triethyl ort/io-formate affords the pyrimido[5,4-c]cinnolin-4(3/7)-ones (59) (Scheme 10) <92JPS365>. 

Reaction of ketones with cyanoacetic acid derivatives and sulfur under MW irradiation gives tetrasubstituted thiophenes 558 (Equation 25) <2005SG1351>. 

Decorboxylation Acyl and Cyanoacetic acid derivatives (7-Piperidones included) Carboxy group elimination 473.617.1036, (see text)... 

The reaction of 2-amino-3-nitrosopyridines with compounds containing an activated methylene group permits unambiguous synthesis of various derivatives of pyrido[2,3-b]pyrazine. For example, the pyridine 58 reacts in the presence of sodium ethoxide with a variety of arylacetonitriles and cyanoacetic acid derivatives to provide various 2-substituted 3-amino compounds (59). " " Diethyl malonate reacts similarly to give the 2-carboxylic acid 60, its ester being presumably hydrolyzed in the alkaline reaction conditions. Ethyl acetoacetate yields the 2-acetyl-3-oxo compound 61, and acetylacetone ° provides the 2-acetyl-3-methyl compound 62. The latter condensation proceeds poorly in ethanolic sodium ethoxide, but heating the nitroso compound with acetylacetone under reflux in pyridine gives a 59% yield of the product 62. °... 

Thiadiazoles. - Synthesis. 5-Amino-1,2,3-thiadiazole is prepared from N CCN and I S in the presence of a tertiary amine327 Similarly, 2-diazo-2-cyanoacetic acid derivatives react with H S/... 

Other derivatives containing two electron-withdrawing groups can be used in the reaction, including malononitrile (200). When condensed with 2,3-benzocycloheptanone (199), the dicyanoalkylidene product (201) was isolated in 46% yield. Cyanoacetic acid derivatives (such as ethyl 2-cyanoacetate) are also common partners in the Knoevenagel condensation. 120... 

Fenpiclonil (1) can be prepared (Scheme 15.2.2) by Knoevenagel condensation of 2,3-dichlorobenzaldehyde (8) with a cyanoacetic acid derivative 9, providing an a-cyanocinnamate intermediate 10 that is then reacted with TosMIC in the presence of a base to produce the desired IH-pyrrole 1 in high yield. 

An atom economic route for the preparation of fludioxonil (2) has been patented [18]. Known 2,2-difluorobenzodioxole 12 is regioselectively lithiated to form 13 (Scheme 15.2.3). In a one-pot reaction intermediate 13 is directly quenched with 14 followed by conversion of the formed intermediate 15 with TosMIC into the desired fludioxonil (2). Alternatively intermediate 13 can be quenched with DMF to form aldehyde 16 which is, similar to the above process, stepwise reacted with a cyanoacetic acid derivative to obtain 15 followed by ring formation using TosMIC to deliver fludioxonil (2). Table 15.2.1 lists the chemical and physical properties of fenpiclonil (1) and fludioxonil (2). 

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