Peculiarities of the reaction of 1-substituted isatins with tris(diethylamino)phosphine in ethanol

Reactions of substituted isatins with tervalent phosphorus compounds provide a convenient synthetic route to isoindigo derivatives. 1-Methylisatin is converted into 1,1′-dimethylisoindigo in ~40% yield by the action of sodium diethyl phosphite [1] or triphenylphosphine [2] in boiling benzene. It is presumed that the reaction involves intermediate generation of carbenes. If more nucleophilic tris(diethylamino)phosphine was used instead of triphenylphosphine under mild conditions (in methylene chloride), symmetrically substituted isoindigo derivatives were obtained in high or nearly quantitative yield [3–6]. Intermediate formation of carbene species was proved experimentally by trapping them with fullerene C60 [7]. In order to reveal how the solvent nature affects the result of the above reaction, weakly polar aprotic methylene chloride was replaced by more polar ethanol. In the reactions of 1-methyland 1-ethylisatins 1 and 2 with tris(diethylamino)phosphine in ethanol at 20°C we isolated red solids. Analysis of the H and C NMR spectra of the products unambiguously showed that they are mixtures of isoindigo derivatives 3 and 4 with epoxy compounds 5 and 6. The latter are likely to result from dimerization of intermediate carbenes or their insertion into the C=O bond of initial isatin. In all cases, the P NMR spectra of the reaction mixtures contained one major signal belonging to tris(diethylamino)phosphine oxide (δP 25.1 ppm) and two minor signals due to its alcoholysis [8] and hydrolysis products (Et2N)2P(O)H (δP 21.9 ppm) and EtO(O)P(H)OH (δP 8.9 ppm). The formation of some amount of oxirane derivatives was observed by us previously in reactions of some alkylisatins with tris(dimethylamino)phosphine [9]; the same process in the examined reaction is related to the effect of ethanol. Presumably, in our case epoxides could be formed via reaction of isatins 1 and 2 with the alcoholysis products of tris(diethylamino)phosphine, ethyl N,N,N′,N′-tetraethylphosphorodiamidite (EtO)P(NEt2)2 and diethyl N,N-diethylphosphoramidite (EtO)2PNEt2 [8, 10]. Reaction of 1-methylisatin (1) with tris(diethylamino)phosphine in ethanol. Tris(diethylamino)phosphine, 1.26 mL (4.78 mmol), was added dropwise over a period of 10 min at room temperature to a solution of 0.77 g (4.78 mmol) of isatin 1 in 7 mL of anhydrous ethanol, and the mixture turned dark brown. Evaporation of the solvent left a red powder which was a mixture of 1,1′-dimethylisoindigo (3) and