1- pyrrole, phosphorylation

The most generally useful method for acylation or formyl a ti on of pyrroles is the Vil smeier-Ha ack reaction (32,33). The pyrrole is treated with the phosphoryl complex of A/ A -dialkjlamide and the intermediate imine salt is hydroly2ed. 

The most useful general method for the C-acylation of pyrroles is the Vilsmeier-Haack procedure in which pyrrole is treated with the phosphoryl chloride complex (55a, b) of an AiA-dialkylamide (54). The intermediate imine salt (56) is hydrolyzed subsequently under mildly alkaline conditions to give the acylated pyrrole (57). On treatment of the imminium salt (56 R =H) with hydroxylamine hydrochloride and one equivalent of pyridine and heating in DMF, 2-cyanopyrrole (58) is formed (80CJC409). 

The phosphorylation of alcohols by CEP-imidazole (41 X=N) with CEP-ring retention is already well-established. Following from the observation that CEP-pyrrole (41 X=CH) phosphorylates alcohols with CEP-ring opening, an explanation has been advanced based upon the differences in apicophilicities of the pyrrole and imidazole moieties in pentaco-ordinate intermediates (Scheme 10). A scale of relative reactivities based upon the reactions in the equations... 

Poor stirring during formylation of 2,5-dimethylpyrrole with the preformed complex of dimethylformamide with phosphoryl chloride caused eruption of the flask contents. Reaction of the complex with a local excess of the pyrrole may have been involved. 

The central point of another approach involves an electrophilic attack on a pyrrole system. Under the influence of phosphoryl chloride, pyrrole reacts... 

In the expectation that phosphazenyl and phosphoryl groups would behave similarly, we have prepared the l-methyl-2-(fluoro-phosphazenyl)pyrroles NnPnF2n-l-C I NMe (n = 3-6 2,a-d) and have measured their electronic spectra. Figure 1 illustrates possible modes of conjugation to phosphoryl and N3P3 rings. 

The synthesis of indoles by the Fischer method has been the subject of a review, where phosphorus trichloride and polyphosphoric acid were used as cyclizing agents [6], Although the first publication on the synthesis of phosphorus-containing indoles appeared in 1930 [7], reviews on this subject are few. The treatment of the subject in [8] was fragmentary, while the review [9] covered the literature up to 1975. It is also possible to mention [10], which was devoted to the phosphorylation of pyrrole and its carbonyl derivatives. 

The present review is timely in the light of the foregoing and covers publications from 1976 to 1998. The material is arranged according to the nature of the agent that phosphorylates indole and pyrrole. 

A special place in the series of phosphorylation reactions of pyrroles is occupied by the syntheses of phospholane structures containing pyrrole ring as substituent at the phosphorus atom. These compounds, obtained from potassiopyrrole and cyclic chlorophosphites, are convenient subjects for the study of transamidation, alcoholysis, etc. [24]. 

In the opinion of the authors in [10], one of the first reactions in the synthesis of phosphorylated pyrroles (the reaction of potassiopyrrole with phosphorus trichloride) leads to tris(2-pyrrolyl)phosphine, from which the corresponding thioxide and a complex with copper(I) chloride were obtained. However, the authors of [21] repeated the transformations and on the basis of a study of the 13C NMR spectra came to the conclusion that tris(N-pyrryl)amidophosphite (29) is formed in this reaction ... 

Data on the N-phosphorylated derivatives of pyrrole have been reported [29], and the synthesis of 1-methyl-2-diphenylphosphinyl-3-formylindole dimethylhydrazone 31 and tetrahydroindole derivative 32 has also been mentioned [30] ... 

Phosphorylation of Carbonyl Group in Derivatives of Indole and Pyrrole... 

Several publications have been devoted to the synthesis of phosphorylated derivatives of pyrrole by cyclization and condensation reactions. Diphenylphosphinylaminopyrroles 176 were obtained [193] by the cyclization of dicarbonyl compounds in the presence of diphenylphosphinous acid hydrazide ... 

The combination of tertiary amides, such as dimethylformamide, and phosphoryl chloride generates reactive electrophiles capable of being attacked by electron-rich nucleophiles and is widely used as the Vilsmeier formylation process. The Vilsmeier process has become more general, with the use of more varied amides, and has been particularly successful for the functionalization of pyrroles and indoles. Greater flexibility has been achieved with the replacement of phosphoryl chloride by trifluoromethanesulfonic anhydride. 

The Vilsmeier-Haack reaction (herein, Vilsmeier reaction ) provides an effective method for the formylation of aromatic systems. The combination of phosphoryl chloride with V-methylaniline or dimethylformamide generates an iminium phosphorus derivative or chloro-iminium cation that is the active electrophile in an electrophilic substitution reaction. The resulting substitution product is an iminium salt 1, which is hydrolyzed on workup with alkali to give the carbaldehyde product 2 (Scheme l).1,2 The method is particularly useful with activated arenes or electron-rich heterocycles, such as pyrroles, furans, thiophenes, and indoles. We had a special interest in the preparation of indole-7-carbal-dehydes, namely, their properties as isosteres of salicylaldehyde. Thus, we became involved in a wide-ranging investigation of 4,6-dimethoxy-... 

Chlorfenapyr (Phantom ), a trifluoromethyl-containing pyrrole ring insecticide, belongs to a new class of uncouplers of oxidative phosphorylation [80], The original insecticidal lead that resulted in chlorfenapyr was the fermentation product dioxapyrrolomycin, isolated from a Streptomyces strain [81], The presence of the trifluoromethyl group is essential for a broad spectrum of insecticide and acaricide activity. 

The reactions of iminium complex 668, generated in the reaction of 4-(dimethylamino)-l,l,l-trifluorobut-3-en-2-one 667 with phosphoryl chloride or trifluoromethanesulfonic anhydride, with pyrroles proceeded stereospecifically to give finally (after hydrolysis of intermediates 669) the ( )-isomers of 2-vinylpyrroles 670 (Scheme 133) <1998T119, 1999RCR437>. The reactions with trifluoroacetyl alkenes depicted in Equation (160) and Schemes 132 and 133 are also applied to indole systems <1999RCR437>. 

Hunt, D.A. and Tracy, M.F., Pyrrole insecticides A new class of agriculturally important insecticides functioning as uncouplers of oxidative phosphorylation, in Insecticides with novel modes of action, Ishaaya, I. and Degheele, D., Eds., Berlin Spriner-Verlag, 1998, p. 138. 

Pyrrole reacts with malonamides in phosphoryl chloride giving pyrroli-zines in moderate yields (Scheme 6).15 Benzimidazole-2-propionic acid undergoes cyclization and subsequent formylation under Vilsmeier conditions at room temperature (RT) (Scheme 7).16... 

D. The calculations confirm that the negative end of the dipole is towards phosphorus. - The calculated dipole moments of phosphole (1.9 D) and pyrrole (2.0 D) are similar, and, unlike furan, the positive ends of the dipoles are towards the heteroatoms. Dipole moments have been used, in combination with results from other methods of study, to estimate the preferred conformations of the dichloride (179), of the phosphites (180), and of triarylphosphine oxides. The use of dipole moments to aid stereochemical studies of compounds has been reviewed. Additive polarizability parameters should not be used in the calculations, and it has been recommended that data should be obtained from model compounds containing identical environments for the phosphorus atoms. The sensitivity of bond moments to structural changes has been studied perfluoroalkyl groups lower the phosphoryl bond moment, and the P—N bond moment is very sensitive to the valence state of the phosphorus atom. The conformational analyses of phospho-nates, phosphonamides, silyl phosphates, and a number of dioxaphosphori-nans (181) - have been reported. The P—Se bond moment has been estimated to be 1.24 D. The zwitterionic structure (182) was identified by its high dipole... 

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