Sergey P. Ivonin

Reactions of 1-aryl-2,5-dimethylpyrroles with ketones

Abstract1-Aryl-2,5-dimethylpyrroles react with acyclic ketones with acid catalysis to give geminal di-2-pyrrolyl derivatives independently of the ratio of the reagents. The reaction of cyclohexanone and cycloheptanone occurs analogously with 2∶1 ratio of pyrrole to ketone. With an excess of cyclohexanone a cycloheptanone 1-aryl-2,5-dimethyl-3,4-dicyclohexenylpyrroles and substituted 4,5,6,7,8,9-hexahydro-2H-azulene[1,2-c]pyrrol-4-spirocycloheptane are produced respectively.

Reaction of hydrazones derived from active methylene compounds with Vilsmeier–Haack reagent

Reaction of hydrazones derived from active methylene compounds with the Vilsmeier–Haack reagent was studied. Compounds with sulfone, ester, nitrile, triphenylphosphonium, and phthalimide moieties were evaluated. It was found that electron-withdrawing and steric effects provided by the substituent at α position strongly influenced the regioselectivity of the reaction. Increasing mesomeric electron-withdrawing effect of this group favors the formation of functionalized 1,3,4-trisubstituted pyrazoles as compared to 1,3-disubstituted pyrazole-4-carbaldehydes. On the contrary, enhanced steric hindrance and lowered electron-withdrawing effect shift the balance toward 1,3-disubstituted pyrazole-4-carbaldehydes. Other factors such as substituent at the nitrogen atom of the hydrazone, as well as reagent ratio, can affect the outcome of the reaction dramatically, so that in certain cases acyclic products are obtained.Graphical abstract

Reaction of hydrazones derived from electron-deficient ketones with Vilsmeier-Haack reagent

Abstract Reaction of hydrazones derived from ketones bearing an acceptor substituent adjacent to the carbonyl group (α,α,α-trifluoroacetone and ethyl pyruvate) with Vilsmeier-Haack reagent was studied. In most cases, the method allows for regioselective preparation of 1,3-disubstituted pyrazole-4-carbaldehydes – the products of initial C-electrophilic attack, although in one case, the product resulting from concurrent N- and C-attacks of the electrophile at the hydrazone moiety is observed. Under analogous conditions, the reaction of N-arylhydrazone derived from butanedione leads to the formation of 3-chloro-3-(1-arylpyrazol-3-yl)acrylaldehyde – the product of double formylation at both ketone and hydrazone moieties of the starting material.

Phosphorylation of 2-Alkoxycarbonyl-5-(1',3'-diaza-1'-butenyl-3'-methyl)thiophenes and 2-alkoxycarbonyl-5-(1',3'-diaza-1'-butenyl-3'-methyl)furans by Trivalent Phosphorus Halides

In previous work [1], we have demonstrated the feasibility of using the 3-methyl-1,3-diaza-1-butenyl (N,N-dimethylformamidine) substituent as a protective and activating group in the phosphorylation of 2-aminothiazoles, which permits to prepare phosphorus derivatives of thiazole with a free amino function. The use of this approach for the synthesis of phosphorylated derivatives of other types of amino heterocycles holds considerable preparative interest. We have found that the electron-donating properties of the N,N-dimethylformamidine substituent permits the regioselective phosphorylation of 5-amino-2-alkoxycarbonylthiophenes and 5-amino-2alkoxycarbonylfurans by trivalent phosphorus halides under mild conditions at the position C(3) of heterocycle to give 3-dihalophosphines 3a, 4a, and 4b, which are valuable reagents for the synthesis of various 3-phosphorylated thiophene and furan derivatives, in particular, 5-8.

Heterocondensed 1,2,3-diazophosphorines

It is has been shown that the interaction of phenylhydrazones of pyrrolecarbaldehydes and indolecarbaldehydes with trivalent phosphorus halides results in annelation of the 1,2,3-diazophosphorine ring.