Some new observations on an old reaction: disproportionation and the formation of P-O-P intermediates in the Michaelis-Arbuzov reaction of triaryl phosphites with alkyl halides

Thermolysis of methyltriaryloxyphosphonium halides (ArO) 3 PMeX (X = Br or I) in the molten state (> 175 o C) was accompanied by disproportionation, with the formation of structures of the general type (ArO) n PMe 4-n X (X = Br or I; n = 0-4). Further decomposition to give the corresponding aryl halides and phosphoryl derivatives became progressively slower as aryloxy groups were replaced by methyl. Thermal decomposition in CDCl 3 (sealed tube) additionally confirmed the formation of novel species containing a P-O-P linkage. Products were identified by a combination of 31 P and 1 H NMR spectroscopy. Possible reaction mechanisms are discussed.


Introduction
The Michaelis-Arbuzov reaction is one of the best known and most fundamental reactions of organophosphorus chemistry encompassing, in its widest aspects, all reactions of phosphorus (III) esters with electrophilic reagents.The reaction proceeds via an alkoxy-or aryloxyphosphonium intermediate 1, leading to the formation of a tetrahedral P(V) product containing a P=O bond (Scheme 1). 1 The applications of this type of reaction in the synthesis of phosphonates, phosphinates, and phosphine oxides are legion 2 and include methods for the synthesis of a wide range of useful organophosphorus compounds.Recent examples include the synthesis of α-aminophosphonates by the interaction of phosphite esters with N-substituted trifluoroacetimidoyl chlorides. 3ome of the earliest examples involved the reactions of triaryl phosphites with alkyl halides, giving 1:1 adducts, the so-called quasiphosphonium salts 2, which on hydrolysis or thermolysis yielded the corresponding diaryl alkylphosphonates (Scheme 2). 4 (ArO) 3 P + RX (ArO) 3 PRX (ArO) 2 P(O)R + ArONa ∆ NaOH aq.
6][7][8] Examples of the latter are rare but have been detected in certain special cases such as the reactions of ethyl ophenylene phosphite with halogens or phenylsulfenyl chloride at low temperatures. 9n the course of structural and spectroscopic studies of quasiphosphonium salts we prepared the methyl bromide and methyl iodide adducts of triphenyl phosphite (2, Ar = Ph, R = Me, X = Br or I) by heating the reactants together at 90-100 o C. 5 We also found that extended periods of heating at higher temperatures (up to 170 o C in a sealed tube) led to the isolation of the unexpected dimethyldiphenoxyphosphonium bromide 3 (18% yield), together with diphenyl methylphosphonate, triphenyl phosphate, and bromobenzene (Scheme 3). 7hO) 3  This result was reminiscent of the disproportionations reported by Nesterov who found that thermal decomposition of the methyl iodide adducts of diphenyl phenylphosphonite and phenyl diphenylphosphinite above 200 o C yielded phosphonates devoid of methyl substituents (Scheme 4).

Scheme 4
No other examples of the redistribution of aryloxy and methyl groups at phosphorus in the course of Michaelis-Arbuzov reactions appear to have been reported.We have therefore monitored the thermal decomposition of selected quasiphosphonium salts by 1 H and 31 P NMR spectroscopy 11,12 and we present our results and conclusions below.

Results and Discussion
Although the initial formation of a 1:1 complex 2 between a triaryl phosphite and methyl bromide or methyl iodide (Scheme 2) occurs readily at 100 o C, further reaction to give the aryl halide and phosphonate ester requires significantly higher temperatures.Under these conditions other competing reactions, not previously generally recognized, may occur.Thus, we have found that the thermal decomposition of methyltriphenoxyphosphonium bromide 4a or iodide 4b in the molten state at 175 o C, or higher, is accompanied by the formation of disproportionation products (Scheme 5), identified by a combination of 1 H and 31 P NMR spectroscopy (Tables 1 and 2, and Experimental Section); and similar results were obtained by the thermolysis of dimethyldiphenoxyphosphonium bromide 5a or iodide 5b.

Scheme 5
Only the tetraphenoxyphosphonium species 6a or 6b were not detectable directly but these are the least stable and presumably undergo dearylation relatively quickly to give triphenyl phosphate 9 (Scheme 6).Methyltri-o-tolyloxyphosphonium bromide 13a and iodide 13b underwent disproportionation to a lesser extent when heated at 200 o C, the principal products being di-o-tolyl methanephosphonate 14 and the corresponding o-halogenotoluene 15 (Scheme 7). 13-MeC 6 H 4 O) 3 PMeX 13a ( X = Br); 13b (X = I) 14 15 However, detection of the hydrolysis products, o-tolyl dimethylphosphinate 16 and trimethylphosphine oxide 12, after exposure of the total products obtained by the pyrolysis of 13a to moisture (Scheme 8), showed that the transfer of two or of three methyl groups to phosphorus had occurred to some extent.

Scheme 8
The mechanism by which the methyltriaryloxyphosphonium halides undergo disproportionation is considered to be different from that reported some years ago for the related triphenoxy(halogeno)phosphonium halides, (ArO) 3 PX 2 , obtained by the addition of halogen to triaryl phosphite.In these cases, disproportionation occurs relatively easily to give species of the general formula (ArO) n PX 5-n or [(ArO) x PX 4-x ] + [(ArO) y PX 6-y ] -and can readily be explained by anionic dissociation of the ligands (phenoxide or halide) and their re-association with phosphorus. 14However, in the present examples, the involvement of free methyl carbanions is implausible.We propose, therefore, a sequence of bimolecular processes, initiated by nucleophilic attack of halide ion either on carbon (to give the phosphite ester 17) or on phosphorus to give the halogenophosphonium ion 18 (Scheme 9).

Scheme 9
Transfer of halogen from 18 to 17 will then give the diaryl methylphosphonite 19 and triaryloxy(halogeno)phosphonium ion 20 (Scheme 10), from which the disproportionation products 21 and 22 can readily be formed as shown (Scheme 11).

Scheme 11
Similar sequences can account for the further exchange of methyl and aryloxy groups, leading to structures of the general type (ArO) n PMe 4-n X.
During the thermal decomposition of molten methyltriphenoxyphosphonium iodide 4b (Table 2), we also observed the initial formation and subsequent decomposition of a small amount (ca. 4 mol %) of an intermediate containing the Me-P-O-P structure.This intermediate became much more evident if the decomposition was carried out in CDCl 3 (8-10 % w/v solution, sealed tube) and was observed under these conditions as a major feature in the thermolysis of all four quasiphosphonium halides 4a, 4b, 13a, and 13b, rising to a maximum concentration of 40-50 mol % in some cases but ultimately disappearing with the formation of the normal Arbuzov product 10 or 14, together with triaryl phosphate.Typical results are shown for the bromides 4a, 13a in Tables 3 and 4. The iodides 4b, 13b behaved similarly (see Tables 5 and 6), although the reactions were not forced to completion in these cases as dark brown tarry by-products were formed at higher temperatures.present based on integration of the methyl proton signals.b δ H 3.17 (d, 2 J PCH = 15.9Hz).c Not detectable.d δ H 2.28 (dd, 2 J PCH = 14.0 Hz, 4 J POPCH ~2 Hz), e δ H 1.81 (d, 2 J PCH = 18.0 Hz).
In the case of methyltri-o-tolyloxyphosphonium bromide 13a, the P-O-P intermediate was isolated in the form of white crystals from the residue obtained after heating the molten compound (200 o C) in a distillation apparatus and removing volatile by-products under reduced pressure (see Experimental).Although unstable on storage in vacuo, this intermediate was sufficiently stable in solution (CDCl 3 ) for analysis by NMR spectroscopy, which confirmed the results already deduced from NMR studies of the total reaction products derived from both the phenyl and o-tolyl systems during thermal decomposition in CDCl 3 , viz. that intermediate 23 was formed by nucleophilic attack of triaryl phosphate on the quasiphosphonium salt (Scheme 12).
Two differently substituted phosphorus atoms were clearly present (δ P 32.3 and 77.0 ppm) with a coupling constant (ca.32 Hz) indicative of an anhydride (P-O-P) structure. 15One of the phosphorus atoms only (that at lower field) carried a methyl group, giving rise to a doublet of quartets in the proton-coupled spectrum (J PCH 16.0 Hz, J POPCH ~2 Hz), whereas the other remained as a simple doublet.Closely similar NMR parameters were observed for both the phenyl and tolyl compounds.Integration of the o-methyl protons of the isolated o-tolyl derivative confirmed the presence of two different types of phosphorus-bonded o-tolyloxy group (δ H 2.02 and 2.18, both doublets, with 5 J PH = 0.9 Hz) in 3:2 ratio, in agreement with formulation 23.
The origin of the triaryl phosphate involved (Scheme 12) is uncertain.In part it may result from disproportionation (Scheme 11) although the absence of equivalent quantities of the corresponding dimethyl substituted disproportionation products 21 suggests that it is also an oxidation product resulting from the interaction of triaryl phosphite, produced by dissociation (Scheme 9), with adventitious oxygen.Such a process would be relatively more significant in a sealed tube in dilute solution than for the neat compound, as observed.

Scheme 12
Intermediate 23 is of interest in that it suggests the possibility of an alternative route to the formation of the Arbuzov product 24 (Scheme 13), involving dearylation via the more reactive tetra-aryloxyphosphonium species and the regeneration of triaryl phosphate, in which case the latter could be acting catalytically. 16t is perhaps surprising that we detected none of the analogous P-O-P species which would have been formed by the attack of phosphonate 10 or 14 on the quasiphosphonium ion.Such an intermediate, Me(ArO) 2 P + (O)OP + (O)(OAr) 2 Me, being symmetrical, would exhibit only a single peak in the 31 P NMR spectrum and would therefore be less conspicuous.However, we did not observe significant amounts of any unidentified species during the course of the reaction.

Experimental Section
General Procedures.Because of the sensitivity to moisture of the phosphonium salts under investigation, and of the phosphites to oxidation, all transfers were made in an atmosphere of dry nitrogen.Deuterochloroform was stored over molecular sieves.Analytical methods.Elemental analysis (C, H, N) was carried out on a Perkin-Elmer 240 instrument.Halogens (Br or I) were determined by Volhard titration after dissolving the sample in aqueous potassium hydroxide (2% w/v, 100 mL) and acidification of the solution with nitric acid (2M, 25 mL).Phosphorus was determined by digestion of the sample for 10-20 h (Kjeldahl flask) in concentrated sulfuric acid (10 mL) containing selenium catalyst, followed by further heating with concentrated nitric acid (10 mL) until nitrous fumes were no longer evolved.The solution was then carefully diluted, made alkaline by the addition of 0.88 ammonia, and then just acidified (HCl).The so-formed inorganic phosphate was precipitated and weighed as magnesium ammonium phosphate hexahydrate by standard gravimetric procedure.Spectroscopy. 1 H NMR spectra were recorded on a Perkin-Elmer R12B 60 MHz instrument. 13C and 31 P NMR spectra were obtained on a Bruker WP80 spectrometer operating at 20.12 MHz or 32.395 MHz, respectively.Chemical shifts are reported downfield from TMS (internal standard) for 1 H and 13 C spectra and from 85% phosphoric acid (external standard) for 31 P spectra.Quantitative data are based on the integration of proton NMR signals.Gas chromatography.Volatile products (containing o-bromotoluene) were analyzed at 115 o C on a 5m x 1 cm glass column containing 10% PEGA on Celite (60-80 mesh), with N 2 carrier gas (inlet pressure 17 psi; flow-rate 20 mL/min) and a flame-ionization detector (Perkin-Elmer F11 apparatus).

phosphate 9 and diphenyl methanephosphonate 10, the
other possible Arbuzov products, viz.phenyl dimethylphosphinate 11 and trimethylphosphine oxide 12 were obtained in relatively small amounts.
Isolation of P-O-P intermediate from the products of thermal decomposition of methyltrio-tolyloxyphosphonium bromide (13a).The dark brown residue from the above experiment ISSN 1424-6376 Page 32 © ARKAT USA, Inc(