A-Cyano carbonyl compounds

Most solid-phase syntheses of pyrazoles are based on the cyclocondensation of hydrazines with suitable 1,3-dielectrophiles. The reported examples include the reaction of hydrazines with support-bound a,(3-unsaturated ketones, 1,3-diketones, 3-keto esters, a-(cyano)carbonyl compounds, and a, 3-unsaturated nitriles (Table 15.19). Pyrazoles have also been prepared from polystyrene-bound 3-(hydrazino)esters, which are generated by the addition of ester enolates to hydrazones (Entry 7, Table 15.19 see also Section 10.3). Benzopyrazoles can be prepared from support-bound hydra-zones using the reaction sequence outlined in Figure 15.11. Oxidation of a polystyrene-bound benzophenone hydrazone yields an a-(acyloxy)azo compound. Upon treatment with a Lewis acid, this intermediate is converted into a 1,2-diazaallyl cation,... 

P-Dicarbonyl compounds are sometimes called active methylene compounds because they are more reactive towards base than other carbonyl compounds. Iy3-Dinitriles and a-cyano carbonyl compounds are also active methylene compounds. 

Isoxazoles 1, unsubstituted in the 3-position, undergo a synthetically useful ring-cleavage (cf. p. 191) on treatment with a base to give the isomeric a-cyano carbonyl compounds 3 ... 

Cyanopyrazine A -oxides have been prepared from a-amino nitriles and a-hydroxyimino carbonyl compounds as summarized in Section III. 1 (528-530, 532-534, 537, 540, 542). Oxidation of 2-cyanopyrazine with perhydrol gave 3-cyanopyrazine 1-oxide (575), 2-cyano-5-ethoxy-3,6-dimethylpyrazine with 30% hydrogen peroxide in acetic acid at 55° gave 2-cyano-5-ethoxy-3,6-dimethylpyrazine iV-oxide (288), and the oxidations of 2-amino-3-cyanopyrazine 1-oxide (538) and... 

Aqueous sodium cyanide converts a,jS-unsaturated carbonyl compounds into i -cyano carbonyl compounds. The reaction amounts to addition of the elements of HCN to the carbon-carbon double bond. For example ... 

JV-Boc protected a-amino carbonyl compounds are prepared by treatment of the lithium enolates of ketones, esters, and amides with AT-Boc 3-(4-cyanophenyl)oxaziridine (53b) <93JOC479i>. The modest yields (33-38%) are ascribed to aldol-type reactions of the enolate with the 4-cyano-benzaldehye (62) by-product (Equation (9)). In one example, the lithium enolate of propiophenone gave A-Boc-cathione (61), the pharmacologically active constituent of the leaves of khat. 

Conjugated aldehydes or ketones can add HCN by a 1,4-addition pathway ( conjugate addition or Michael addition ) and produce (J-cyano carbonyl compounds. For example, 1-phenyl-propenone (CgH5C(0)CH=CH2) adds HCN to afford 4-oxo-4-phenylbutanenitrile (CeH5C(0) CH2CH2CN) in approximately 65% yield. 

The synthesis of a -unsaturated carbonyl compounds and nitriles Pd-catalyzed reaction P45] of allyl P-oxo esters and allyl a-cyano esters is an oxidative process. With the contra-polarizability of the metal ion, elimination of a hydride from the P-position is electronkaUy favorable. 

TABLE 20. ENOLATES OF a-CYANO CARBONYL AND 3-DICARB0NYL COMPOUNDS (Continued)... 

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. 

Remarkably, the base does not attack the isoxazole ring by addition, but by deprotonation at C-3 and ring-opening of the (relatively weak) O-N bond (probably via an E 2-type process). Intermediate is the (Z)-a-cyano enolate 2, which on reprotonation affords the cyano carbonyl compounds 3. 

In Summary a,jS-Unsaturated aldehydes and ketones are synthetically useful building blocks in organic synthesis because of their ability to undergo 1,4-additions. Hydrogen cyanide addition leads to j8-cyano carbonyl compounds oxygen and nitrogen nncleophiles also can add to the j8-carbon. 

Active methylene or methine compounds, to which two EWGs such as carbonyl, alko.xycarbonyl, formyl, cyano, nitro, and sulfonyl groups are attached, react with butadiene smoothly and their acidic hydrogens are displaced with the 2,7-octadienyl group to give mono- and disubstituted compounds[59]. 3-Substituted 1,7-octadienes are obtained as minor products. The reaction is earned out with a /3-keto ester, /9-diketone, malonate, Q-formyl ketones, a-cyano and Q-nitro esters, cya noacetamide, and phenylsulfonylacetate. Di(octadienyl)malonate (61) obtained by this reaction is converted into an... 

A new stable sulfenylating reagent 3-phenylsulfenyl-2-GV-cyano-imino)thiazolidine 57 has been described. It reacts with amines or thiols to give sulfenamides or disulfides in excellent yields. a-Sulfenylation of carbonyl compounds also proceeds smoothly and if an optically active 4-diphenylmethyl substituent is attached to the thiazolidine ring (58), the cyclic (3-ketoester 59 can be sulfenylated in high yield with an ee of 96% to give the sulfide 60 <00SL32>. 

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