Superbasic system

The technique of neutralization and the production of superbase systems from synthetic sulfonates are similar to those employed for the natural sulfonates. 

Trofimov has extended his previously reported heterocyclization of ketoximes 39 with acetylene to propyne or its isomer allene in superbase systems (MOR/DMSO M = K, Cs, R = H, t-Bu) to afford a facile synthesis of substituted pyrroles 40 and 41 . Due to a fast propyne to allene protropic isomerization under the reaction conditions, the product is the same regardless of which species is employed. 

Gusarova, N.K., Shaikhudinova, S.I., Dmitriev, V.I., Malysheva, S.F., Arbuzova, S.N., and Trofimov, B.A., Reaction of red phosphorus with electrophiles in superbasic systems. VII. Phospholanes and phosphorinanes from red phosphorus and a,co-dihaloalkanes in a single preparative step, Zhur. Obshch. Khim., 65, 1096, 1995. 

Benzofuranyl)pyrroles, 2-(2-thienyl)pyrroles , 2,2 -dipyrroles, 3-(2-pyr-rolyl)indoles , 2-(2-benzimidazolyl)pyrroles and2-(2-, 3- and4-pyridyl)pyrroles were prepared using this method. Reaction of alkynes (for example, propyne) or allene with ketoximes in a superbase system (MOH/DMSO) leads to 2,5-di- or 2,3,5-trisubstituted pyrroles Pyrroles and dipyrroles were synthesized also from corresponding dioximes and acetylene in a KOH/DMSO system It has also been shown that 1,2-dichloroeth-ane can serve as a source of acetylene in pyrrole synthesis. Oxime 52 in the system acetylene/RbOH/DMSO at 70 °C afforded a mixture of three pyrroles 53-55 in low yields (equation 23). The formation of product 53 occurred through recyclization of pyrrolopy-ridine intermediate. ... 

Acetylenic carbanions or anion-radicals generated by a superbase system can serve as reducing agents (66JOC248 81UK248). 

In conclusion, the experimental material is in accordance with the O-vinylation mechanism. It is probable, however, that depending upon the reaction conditions and the structure of reactants, some alternative routes shown in Scheme 84 are realized in particular cases. At the same time, it should not be ignored that any scheme, even those that seem to be most reasonable, cannot be considered as adequate unless they explain why the pyrrolization of ketoximes with acetylene succeeds only in the presence of specific superbase systems (strong base/DMSO). 

Wang C, Luo H, Luo X et al (2010) Equimolar C02 capture by imidazolium-based ionic liquids and superbase systems. Green Chem 12( 11) 2019—2023... 

Formation of thiophene derivatives on chalcogenation in multiphase superbase systems 92MI24. 

Ketoximes react with acetylene in the presence of superbase systems of the type KOH/DMSO to form pyrroles. When there is an excess of acetylene, one can directly obtain iV-vinylpyrroles (Scheme 44) <1998RJ01691, 1998ZOR967, 1999RCR459, 2002COR1121, B-2004MI121>. 

The regiochemistry of the addition of multident pyrrole anions to carbon disulfide has been theoretically analyzed. Results have been explained by the basic regularities of the pyrrole derivatives reactions in superbasic systems <2001SUL181, 2001ZSK645, 2002IJQ542, 2004IJQ360, 2004ZSK990>. 

Progesterone dioxime 51 reacted with acetylene in a superbasic system to afford dipyrrole 52 in 7% yield. The reaction was accompanied by prototropic migration of the double bonds in the steroid fragment and vinylation of the NH-pyrrole groups (Equation (14)) (03RJ01406). 

Isomerization of Alkenes. - Solid superbasic catalysts show remarkable activity in the isomerization of alkenes. At room temperature in the liquid phase the double-bond shift in pent-l-ene and hex-l-ene, and the isomerization of the initially formed 2-alkenes takes place. The highest activity in both types of isomerization is shown by catalysts that have been prepared by deposition of alkali metal by evaporation on MgO calcined below 973 K. In this case the isomerization proceeds on very strong superbasic centres. On MgO-alkali metal calcined at temperatures above 973 K, one-electron donor centres prevail this system causes double bond shift only (Table 7). The superbasic systems are also active in the isomerization of ( )-pent-2-ene to the mixture of (Z)-pent-2-ene and pent-l-ene. The systems for which one-electron donor character prevails are completely inactive in this transformation. 

Preparation of Phosphines by Addition of P-H to Unsaturated Compounds. -This route has not received much attention over the past year. A stereoselective synthesis of tris(Z-styryl)phosphine is offered by the addition of phosphine to phenylacetylene in a superbasic system (HMPA-H20-K0H)." In a similar vein, the reaction of phosphine with styrene and a-methylstyrene in a superbasic medium (DMSO-KOH) provides a route to the primary phosphines, (2-phenylethyl)phosphine and (2-methyl-2-phenylethyl)phosphine, respectively. 7 Transition metal phosphine complexes have been shown to catalyse the a-hydroxylation, P-cyanoethylation, and P-alkoxycarbonylethylation of phosphine. 71 Addition of primary phosphines to acrylic esters has been used for the synthesis of the phosphines (80).7 A similar addition of diphenylphosphine to acrylic esters and amides has given a series of hydrophilic phosphines (81). 72 The bis(phosphorinanyl)ethane (82) is formed in the photochemical addition of l,2-bis(phosphino)ethane to 1,4-pentadiene. ... 

In contrast to the inherent linearity exhibited by immodified low vinyl polybutadiene polymerized at moderate temperature, medium to high vinyl polybutadiene produced in continuous systems have the tendency to be highly branched. The common use of alkali metal alkoxides with or without additional polar modifiers to increase the vinyl content results in a superbasic system with a high tendency to metallate the polymer chain (137-141). The metallated site can reinitiate in the presence of continuously fed monomer and produce random... 

Currently, the most intensively developed method for the synthesis of NH- and N-vinylpyrroles is based on heterocyclization of ketones (in the form of ketoximes) with acetylene in the superbase system alkali metal hydroxide-dimethyl sulfoxide (DMSO) (Scheme 1.1). This reaction was discovered about 30 years ago. 

R, R2 = alkyl, alkenyl,aryl, hetaryl M = alkali metal SCHEME 1.1 Synthesis of pyrroles and N-vinylpyrroles from ketoximes and acetylene. 1.1.1 Superbase System Alkali Metal Hydroxide-Dimethyl... 

Superbase systems are known to contain a strong base and a solvent or reactant capable of specifically binding the cation baring the conjugated anion [138]. Such systems can be prepared on the basis of linear or cyclic glycol ethers, microcyclic polyethers (crown ethers), highly polar non hydroxylic solvents (sulfoxides, e.g., DMSO), sulfones (sulfolane), amides (N-methylpyrrolidone, dimethylformamide, hexametapol), and phosphine oxides as well as from liquid anunonia, amines, etc. For example, basicity of sodium methylate in 95% DMSO is by seven orders higher than in pure methanol [139]. 

A more careful study of superbase systems should account for cooperative effects of dielectric permeability alteration, hydrogen bonding, activity of water, dispersive interactions, and changes in water structure and ion hydration degree [140,142,143]. 

In DMSO-derived superbase systems, acetylene can be activated, at least, by three ways ... 

As a first approximation, all this leads to the decrease in energy of low-lying molecular orbitals of acetylene in such a complex as compared to similar orbitals of free acetylene, and, consequently, the triple bond becomes more available for the nucleophilic attack. The nucleophiles themselves in the superbase systems turn to supernucleophiles due to the dramatic increase of their free energy [157,158]. 

To synthesize pyrroles from ketoximes and acetylene, alkali metal hydroxides (LiOH, NaOH, KOH, CsOH, RbOH) are employed as strong bases, key component of the superbase system. 

SCHEME 1.66 Functionally substituted ketoximes studied in the reactions with acetylene in superbase system KOH/DMSO. 

To obtain dipyrroles bridged across the positions 2 and 3, the reaction of 1,3-diketone dioximes, acetylacetone, benzoylacetone, 5-ethylnonane-4,6-dione, and 5,5-dimeth-ylcyclohexane-l,3-dione (dimedone) with acetylene in the superbase system KOH/ DMSO has been studied [271]. 

Earlier, the adduct of DMSO with acetophenone C has been isolated and characterized as hydroxy derivative (after neutralization of the reaction mixture) [340]. In more active superbase system KOH/DMSO (140°C, 4 h), the yield of p-terphenyl increases to 14.6%. 

Probably, the systematic elaboration of the reaction of ketoximes with acetylene in the superbase systems will open a fundamentally new route to 2//-azirines, which, if necessary, can be used as intermediates without preliminary isolation. 

In attempting to prepare imidazole derivatives using this protocol, it has been found [396,397] that amidoximes quickly react with acetylene (5-7 min, 75°C) under pressure (12-14 atm) in the superbase system KOH/DMSO to deliver 0-vinylamidoximes in up to 90% yield (Scheme 1.192). A peculiarity of this reaction is that it (like the reaction of ketoximes with acetylene) proceeds unusually fast, almost instantly (5-7 min) and at a temperature of only 75°C. From two conjugated competing nucleophilic centers, amino and hydroxyl groups, the latter selectively participates in the reaction. 

It is not inconceivable that in the superbase system KOH/lCDjljSO, CH acidity of ketoximes plays an important role (Scheme 1.198). 

Nevertheless, concluding this section, one can state that all now available experimental data correlate better with the O-vinyl oxime mechanism. At the same time, it should be remembered that all, even the most plausible, mechanistic schemes cannot be considered adequate if they do not explain why the pyrrole synthesis from ketox-imes and acetylene successfully proceeds only in the presence of specific superbase systems KOH/DMSO. 

The reaction proceeds effectively in the presence of 30% KOH in superbase systems (KOH in aprotic polar solvents such as DMSO, sulfolane, and hexametapol). KOH/DMSO turned out to be the most effective systan. The use of the latter allows decreasing the reaction temperature to 80°C-100°C, which is almost lOO C lower than the temperature of classical vinylation of NH heterocycles. The application of this system makes it also possible to carry out the vinylation of pyrroles at the close-to-atmospheric acetylene pressure (1.1-1.5 atm). 

ESR study of the mechanism of pyrrole addition to acyl- and cyanophenylacet-ylenes in the superbase system KOH/DMSO evidences the formation of radicals [502]. One of the signals has been assigned to N-adducts of pyrrolyl radicals with... 

Systematic investigations of the reaction of pyrroles with carbon disulfide in the superbase system KOH/DMSO [537-541] have shown that pyrrole anions, generated in this system, attack CS2 (20°C-25°C, 2 h) exclusively or mainly by the position 2 to afford pyrrole-2-carbodithioates. The latter, after alkylation with alkylhalides (20°C-25°C, 2 h), give the corresponding pyrrole-2-carbodithionic acid esters in 46%-75% yields (Scheme 2.71, Table 2.9) [537-540]. The only exception is unsubstituted pyrrole, which gives only pyrrole-l-carbodithioate [540]. 

Fundamentally, new methods for the synthesis of phosphorus-containing pyrroles from easily available N-vinylpyrroles are developed. Among than is hydrophosphorylation of the vinyl group with secondary phosphines [674], which are now obtained in a one-stage manner from elemental phosphorus and electrophiles in the superbase systems [675,676]. 

VasH tsov, A.M., B.A. Trofimov, and S.V. Amosova. 1987. Mathematical model of superbase system alkah-DMSO in the region of low concentrations of water. B Acad Sci USSR Ch 8 1785-1791. 

Trofimov, B.A., A.M. Vasil tsov, A.I. Mikhaleva et al. 1989. Mechanoactivation of the superbase system KOH-DMSO Efficiency of application in the reaction with cyclohexanone. B Acad Sci USSR Ch 12 2879-2880. 

The investigations of the reaction of ketoximes with acetylene have shown that the superbase system KOH/DMSO essentially facilitates vinylation of pyrroles with acetylene. This finding constitutes the basis of a new efficient method for vinylation of componnds having the N-H-bond. The process fnndamentally differs from the known protocols since it is brought about under atmospheric pressnre at moderate temperatnres (80°C-100°C). The method is recommended for vinylation of any NH heterocycles (resistant to the action of alkalis) in simple reactors. Apart from the obvions promise for industry, the method is also indispensable for laboratories that do not have special operating building and equipment (autoclaves working with acetylene nnder pressure). 

Gusarova NK, Sukhov BG, Malysheva SF, Kazantseva Tl, Smetannikov YuV, Tarasova NP, Trofimov BA (2001) Reactions of elemental phosphorus and phosphines with electrophiles in superbasic systems XIII. phosphorylation of phenylacetylene with active modifications of elemental phosphorus. Russ J Gen Chem 71 721-723... 

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