New Feature of Friedel-Crafts Phosphonation of Anisoles: Unexpected In Situ Methylphosphorylation Reaction

Abstract

Anisoles 1, reacting with AlCl 3 and PCl 3 with appropriate reagent ratios, give, in good yields, the corresponding diaryl methylphosphonates 2 or the methylphoshinates 3b,c and the methylphosphine oxides 4b,c. This unexpected in situ methylphosphorylation explains the reported limited and conflicting results to obtain methoxy-substituted arylphosphonous dichloride with the same reagents. A suggested mechanism is also reported.Since the last century, the Friedel-Crafts-type reaction 1 using PCl 3 and AlCl 3 has been of interest for the direct phosphonation of an aromatic ring. However, this reaction is very sensitive to the type of substituents present on the aromatic ring. 2 In particular, very limited success and conflicting results have been reported when the reaction is carried out with anisoles. For example, anisole, 3,4 upon treatment with PCl 3 and AlCl 3 gave complex reaction mixtures depending on the quality of AlCl 3 with poor yields of methoxy-substituted arylphosphonous dichloride or phenylphosphorodichloridite and large amounts of undistillable residues:To increase the yield and the selectivity of this phosphonation reaction the use 4a of SnCl 4 and very recently the use 4c of BiCl 3 have been reported. In the past years we discovered 5 an unusual reaction of PCl 3 and AlCl 3 with thioanisoles which gave a new heterocyclic system (fused 1,2,3-benzothiadiphosphole) containing the P-PS 2 unit. Recently, the course of this unexpected diphosphonation reaction has been studied 6 and we have found that the reaction follows a complex multistep pathway which was a priori unpredictable and that the outcome of the reaction is very dependent on the ratio of the reagents and on the good quality of AlCl 3 (sublimated prior to use) which in this reaction is a true reagent and not a catalyst.Then, we thought to study again the reaction of anisoles 1 with AlCl 3 and PCl 3 , in order to find results which might explain the reported 3,4 formation of large amounts of undistillable residues. Several reactions were carried out with various molar proportions of reagents and different reaction conditions. The reaction of 1b with an appropriate ratio of the reagents, afforded a mixture containing as major products the corresponding diaryl methylphosphoryl derivatives 2b, 3b and 4b arising from an unexpected in situ methylphosphorylation (Scheme1). Scheme 1After several repeated attempts with small variations of reagent ratios and reaction conditions we could control the regiochemistry of this methylphosphorylation reaction in order to obtain mainly the diaryl methylphosphonates 2 (see Scheme 1). The best results were obtained with a 1: AlCl 3 : PCl 3 ratio of 1:0.6:1, at 70-80°C in atmosphere of dry nitrogen and without solvent (Table 1). In the case of 1c the reaction was complete in 7 h while in the other cases in about 10-15 h. A stoichiometric excess of PCl 3 was useful also to ease the stirring and the homogeneity of the reaction mixture. Compounds 2 have been fully characterised 7 by 1 H and 31 P NMR and spectral data...

General and Efficient One‐Pot Synthesis of Tertiary Phosphane–Borane Complexes Containing Different Alkyl Groups and In Situ Facile Recycling of the Phosphorus Donor Reagent

“…The formation of such intermediates is favoured by the "dibenzo-butterfly" structure of 1, as we reported for the synthesis of cyclic tertiary phosphanes. [31] It is noteworthy that previously [25,31] we thought that the hexacoordinate intermediate AЈ required a nucleophilic attack, for example, by water or an acid in order to decompose it. During this study, however, we observed by 31 P NMR spectroscopy that AЈ is unstable and spontaneously collapses to give the corresponding tertiary phosphanes, presumably due to its high steric hindrance.…”

“…[31] It is noteworthy that previously [25,31] we thought that the hexacoordinate intermediate AЈ required a nucleophilic attack, for example, by water or an acid in order to decompose it. During this study, however, we observed by 31 P NMR spectroscopy that AЈ is unstable and spontaneously collapses to give the corresponding tertiary phosphanes, presumably due to its high steric hindrance. Consequently, about 30-40 min after the addition of the last Grignard reagent, BH 3 ·THF can be added to the reaction mixture to form complexes of the tertiary phosphanes formed by the spontaneous decomposition of AЈ.…”

“…To gain more information about the mechanism of this reaction, we performed the reaction between compound 1 and n-butylmagnesium bromide in an NMR tube and monitored the progress of the reaction using 31 1 J P-P = 225 Hz) and -48.7 (d, 1 J P-P = 225 Hz) ppm were ascribed to the P 2 and P 1 atoms, respectively, of the intermediate AЈ [32] and were observed only during the initial stage of the reaction because this intermediate readily decomposes to form the tertiary phosphane 5a and the magnesium salt of 3.…”

A New Performance of the Reaction of PCl3/AlCl3 with Anisoles − One-Pot and Multi-Step Syntheses of a New Fused-Ring System [1,2,3]Benzoxadiphospholo[2,3-b][1,2,3]benzoxadiphosphole

“…Recently, after several studies on the structure of the other products, we found [7] that, when the reaction is carried out under appropriate reaction conditions, an unexpected ''insertion'' of a phosphorus moiety into the OϪMe bond of anisole 4 occurs, to give compound 8 as the major product in place of the expected FriedelϪCrafts phosphonation (Scheme 4). The best selective formation of 8 (50Ϫ70% yield) was obtained with an anisole 4/AlCl 3 /PCl 3 ratio of 1:0.6:1, at 70Ϫ80°C for 7Ϫ10 h under dry nitrogen and without solvent.…”

“…Results obtained from the reaction of anisole and AlCl 3 / PCl 3 in different ratios of the reagents A suggested mechanism, depicted in Scheme 5, for this phosphorus insertion reaction was also reported. [7] The insertion of a P moiety is explained by the attack of a molecule of PCl 3 on an anisoleϪAlCl 3 complex and subsequent migration of the methyl group to the same P atom giving the intermediate AЈ. Subsequent nucleophilic attack of free anisole on phosphonium salt AЈ gives BЈ which, after quenching with water, gives phosphonate 8.…”