Cyano compounds synthesis

Another widely used method involves hydrolysis of cyanopyrida-zines. These are usually obtained from cyclizations of open-chain cyano compounds (synthesis of 4-cyano-3(2/7)-pyridazinone and its methyl analogs ), since replacement of a halogen atom by cyano group proceeds with pyridazines in low yields or not at all. Many cyanopyridazines have been obtained by dehydration of amides, such as 3- or 4-cyanopyridazine, 3-chloro-6-cyanopyridazine or 6-cyano-2-methyl-3(2.ff)-pyridazinone, and 3-chloro-4-cyano-... 

Unsaturated hydrazones, unsaturated diazonium salts or hydrazones of 2,3,5-triketones can be used as suitable precursors for the formation of pyridazines in this type of cyclization reaction. As shown in Scheme 61, pyridazines are obtainable in a single step by thermal cyclization of the tricyanohydrazone (139), prepared from cyanoacetone phenylhydrazone and tetracyanoethylene (76CB1787). Similarly, in an attempted Fischer indole synthesis the hydrazone of the cyano compound (140) was transformed into a pyridazine (Scheme 61)... 

Methylenesulphones are more acidic than the simple esters, ketones and cyano compounds and are more reactive with haloalkanes [e.g. 48-57] to yield precursors for the synthesis of aldehydes [53], ketones [53], esters [54] and 1,4-diketones [55] (Scheme 6.4). The early extractive alkylation methods have been superseded by solidtliquid phase-transfer catalytic methods [e.g. 58] and, combined with microwave irradiation, the reaction times are reduced dramatically [59]. The reactions appear to be somewhat sensitive to steric hindrance, as the methylenesulphones tend to be unreactive towards secondary haloalkanes and it has been reported that iodomethylsulphones cannot be dialkylated [49], although mono- and di-chloromethylsulphones are alkylated with no difficulty [48, 60] and methylenesulphones react with dihaloalkanes to yield cycloalkyl sulphones (Table 6.5 and 6.6). When the ratio of dihaloalkane to methylene sulphone is greater than 0.5 1, open chain systems are produced [48, 49]. Vinyl sulphones are obtained from the base-catalysed elimination of the halogen acid from the products of the alkylation of halomethylenesulphones [48]. 

While the usual method for preparing a fused pyrimidinedione involves cyclization of ortho amino and carboethoxy groups (see Equation 12), an unusual synthesis of a fused pyrimidinedithione 46 has been obtained by treating the ortho amino and cyano compound 45 with CS2 (Equation 17) <2003BKC1181>. 

Ferris, J. P, and Hagan, W. J. (1984) HCN and Chemical Evolution The Possible Role of Cyano Compounds in Prebiotic Synthesis, Tetrahedron, 40, 1093-1120. It should be kept in mind that the compounds described in this paper do not have the foundation attached. 

The selective synthesis of the 2-allyltetrazoles 55 by the three-component coupling reaction of the cyano compounds 54, allyl methyl carbonate 5b, and trimethylsilyl azide 42 was accomplished in the presence of Pd2(dba)3.CHCl3 and P(2-furyl)3 (Scheme 19) [55,56]. Most probably, the formation of (r)3-allyl)( ]5-tetrazoyl)-palladium complex 56 took place through [3 + 2] dipolar cycloaddition of 7r-allylpalladium azide 44 with the nitrile 54. The complex 56 thus formed would undergo reductive elimination to form the products 55. 

This is a new reaction for the preparation of N-alkyl amides. Nitriles and various substituted cyano compounds are treated with active olefins in the presence of sulfuric acid. Reaction occurs at room temperature in glacial acetic acid or dibutyl ether solution. The use of hydrogen cyanide in the reaction leads to the formation of N-alkylformamides. /-Butyl alcohol and sodium cyanide are used in place of the olefin and hydrogen cyanide in the preparation of N-/-butylfotmamide (50%). The reaction has been extended to the synthesis of N-alkyl diamides from dinitriles and olefins or alcohols. ... 

Seubert et al. [25] have reported the first synthesis of praziquantel from the intermediate 37 obtained by the Reissert reaction of isoquinoline and followed by high pressure hydrogenation of the cyano compound 36 [36], Acylation of 37 followed by base catalysed cyclisation of the diacylated product affords praziquantel [25,37,38] (Scheme 2). 

Nakano, M., and Okamoto, Y, A convenient synthesis of 2-cyano-l,3-butadienes by the reaction of diethyl 2-cyano-2-trimethylsilylethanephosphonate with carbonyl compounds. Synthesis, 917, 1983. 

Ferris JP, Hagan J (1984) HCN and chemical evolution the possible role of cyano compounds in prebiotic synthesis. Tetrahedron 40 1093-1125... 

Sandmeyer reaction, synthesis, of bromo compound, 36, 39, 45, 48, 52, 75, 217 of chloro compound, 48, 110, 113 of cyano compound, 90, 91, 216 of iodo compound, 182, 183, 184, 185 use of mercuric nitrate in, 52 Saponification of an ester, 113, 152 Schiemann reaction, 165, 167 Schotten-Baumann reaction, 145 Skraup reaction, 28, 85, 193, 204, 235 Sommelet reaction, 281 Sulfenyl chloride, formation from chlorine and disulfide, 214... 

An interesting reaction sequence based on 1-tetralone (26) leads to an unambiguous synthesis of 2-amino-3-cyano-5,6-dihydro-benzo[/]-quinoxaline (27). The isomeric 3-amino-2-cyano compound is similarly obtained from 2-tetralone. ... 

Preparation and Synthetic Applications of Cyano Compounds, A. J. Fatiadi, 1983 This comprehensive book chapter (1236 references) deals with synthesis of nitriles and some of their reactions. Synthetic methods and reactions involving cyano substrates are also... 

Route 2 Synthesis of Compound 241 Employing Vinyl Ketone 264 Compound 270 of Scheme 30.51 was treated with cuprous cyanide in DMF at reflux to furnish a cyano compound (275) in 65% yield (Scheme 30.52). Following established methods, 275 was converted to the corresponding vinyl ketone (264), which was condensed with aldehyde (262) under Stetter conditions to provide a diketone (276). A regular sequence has been employed to convert 276 to the final urea (229). 

The Gewald reaction involves synthesis of 2-aminothiophenes via multicomponent condensation of a-methylene carbonyl compounds, cyano compounds, and sulfur. Recently, Tayebee et al. (2013) have successfully accomplished a rapid and efficient synthesis of 2-aminothiophenes (105) from ketones or aldehydes (103), malononi-trile (16), and sulfur (104) via a one-pot three-component Gewald reaction in the presence of a catalytic amount of ZnO nanoparticles (Scheme 9.31). The catalyst required for the reaction was synthesized through sedimentation of zinc acetate dihydrate in ethanol. 

The synthesis of the 3-C-carbonyl-3-C-cyano compound 72 has been desaibed following foe addition of 2-cyanoacetamide to the dialddiyde obtained by periodate oxidation of methyl a-D-glucopyranoside. ... 

The Mitsunobu reaction has also been employed for the synthesis of substituted tetrazoles. The reaction proceeds via a cyano compound in the presence of trimethylsilyl azide and the DEAD/TTP couple. The activated phosphonium intermediate 238 is thought to react with the azide to give the desired tetrazole derivative. The ethylcyano sidechain on the tetrazole can be removed with 2 N NaOH in THF. ° This reaction has found application in the preparation of tetrazole based growth hormone sccretagogues. ... 

Compounds containing a double or triple bond, usually activated by additional unsaturation (carbonyl, cyano, nitro, phenyl, etc.) In the ap position, add to the I 4-positions of a conjugated (buta-1 3-diene) system with the formation of a ax-membered ring. The ethylenic or acetylenic compound is known as the dieTwphile and the second reactant as the diene the product is the adduct. The addition is generally termed the Diels-Alder reaction or the diene synthesis. The product in the case of an ethylenic dienophile is a cyctohexene and in that of an acetylenic dienophile is a cyctohexa-1 4-diene. The active unsaturated portion of the dienophile, or that of the diene, or those in both, may be involved in rings the adduct is then polycyclic. 

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