Vinyl phosphates, Perkow reaction

In spite of many previous studies on the mechanisms by which trialkyl phosphites interact with a -halogenocarbonyl compounds, the reactive intermediates which lead to ketophosphonate (Arbuzov reaction) and to vinyl phosphate (Perkow reaction) have in no cases been clearly identified. It is generally believed (JL), however, that the Arbuzov product 4 results from initial attack by phosphorus at the cf-carbon atom, whereas the Perkow product 7 is formed by initial attack at the carbonyl carbon atom, followed by migration of phosphorus from carbon to oxygen (Scheme 1). 

Tris(trimethylsilyl)phosphites, analogous to trialkylphosphites, undergo Perkow reaction with a-halo carbonyl compounds to give vinyl phosphates.223 Reaction of a-chloroketone 19 with trimethylphosphite produces dimethyl enol phosphate 20, which is further converted to b is [trimethyls ilyl] esters 21 using MeaSiBr. 21 is also produced directly from a-chloroketone 19 on reacting with P(SiMe3)3. 

Sal keeva et al. studied the reactions of ethyl and /-butyl phosphorodiamidites with chloroacetone, bromoacetone, and a-chloroethyl acetate. The reaction pathway is determined by the structure of the intermediate quasiphosphonium compound responsible for the formation of the Arbuzov products as well as for the occurrence of the anomalous reaction yielding vinyl phosphate (Perkow product).26 The yield of the Arbuzov product increases from chloroacetone to bromoacetone, because the anions of low basicity are more rapidly ionized, which facilitates the formation of the ionic form of the intermediate. Also /-butyl phosphorodiamidite forms via Arbuzov reaction as the major product, because the second stage of the S l reaction is accelerated.26... 

To obtain more information on the nature of the quasiphosphonium intermediates involved in these systems we have studied the reactions gf sterically hindered neopentyl esters by means of 1P nmr spectroscopy. Trineopentyl phosphite and a-bromoacetophenone gave rise to a peak at +41 ppm due to the ketophosphonium intermediate 3 (R = Me.CCH, R = Ph X = Br ) within half an hour of mixingJthe reactants in acetone-dfi at 27 °C ( p nmr shifts are relative to 85% H-PO. down-field positive). Peaks due to the ketophospnonate 4 +19 ppm and the vinyl phosphate 7 (-7 ppm) were also observed (compound 4 and 7 have satisfactory elemental analysis and spectroscopic data ). The concentration of the intermediate reached a maximum after about two hours when it was precipitated from acetone solution by the addition of anhydrous ether to give white crystals of trineopentyloxy (phenacyl)phosphonium bromide, identified by elemental analysis and nmr spectroscopy ( XP 6+41, in CDCl ). When redissolved in acetone-dg, deuterochloroform, acetic acid, or acetic acid-acetone mixtures, the intermediate decomposed to yield keto-phosphonate 4 but none of the vinyl phosphate 6 (Perkow product). Nor was the course of reaction affected by the addition of chloride ion or of a-chloro-acetophenone in acetonitrile. 

In all cases mentioned at that time, the products were assumed to be phosphonates of the type expected from a normal Michaelis-Arbuzov reaction. - However, in light of the Perkow reaction, all the P-ketophosphonates described in numerous papers and patents have to be formulated as the isomeric vinyl phosphates. 

These contradictory results were elucidated later when, in 1952, Perkow showed for a-halogenoaldehydes and Pudovik and Allen and Johnson for oc-halogenoketones that both the Michaelis-Arbuzov reaction, with formation of 2-oxoalkylphosphonates, and the Perkow reaction, with formation of vinyl phosphates, can take place independently or simultaneously. It is important to mention that the formation of vinyl phosphates by an anomalous Michaelis-Arbuzov reaction ... 

With the presence of more than one halogen atom in the a-position of the halo ketone, the formation of 2-oxoalkylphosphonates becomes more difficult, and the reactions proceed exclusively according to the Perkow reaction. Thus, dichloromethyl, dibromomethyl, and tribromomethyl methyl ketones, in reaction with trialkyl phosphites, lead to the corresponding vinyl phosphates... 

Ethyl 2-bromoacetoacetate reacts with triethyl phosphite to give a mixture of diethyl l-(ethox-ycarbonyl)-2-oxopropylphosphonate (29%, Michaelis-Arbuzov product) aud diethyl l-methyl-2-(ethoxycarbonyl)vinyl phosphate (31%, Perkow product). By contrast, the reaction of diethyl bromomalonate with trialkyl phosphites takes only one course, and the products formed at either temperature are the enol phosphates (Perkow product) ... 

Perkow reaction.1 Perkow2 noted that a-halo aldehydes and ketones react with trialkyl phosphites to give dialkyl vinyl phosphates ... 

Not only the a-polyhalogen aldehydes, but also the oc-polyhalogen ketones give the Perkow reaction with trialkyl phosphites, whereby vinyl phosphates are formed containing one chlorine atom less. In the reaction of triethyl phosphite with dichloromethyl-2,4-dichlorophenylketone, 0,0-diethyl-0-[l-(2,4-dichlorophenyl)-... 

Polish research workers prepared several analogues of chlorfenvinphos in order to develop a derivative with similar action but less toxic. The result of this work was 0,0-diethyl-0-[2-bromo-1 -(2,4-dichlorophenyl)vinyl] phosphate (bromfenvin-phos, 72). It is prepared by the Perkow reaction with triethyl phosphite and dibromoethyl-2,4-dichlorophenyl ketone (Fulde et al., 1974 Zwierzak, 1974). 

Based on the research work of Stiles (1952), one of the most important phosphorus ester insecticides, 0,0-dimethyl-0-[(l-methyl-2-carbomethoxy)vinyl] phosphate (mevinphos, 73) was introduced in 1957 under the trade name Phosdrin . It is prepared by the Perkow reaction from trimethyl phosphite and methyl a-chloroacetoacetate. 

The Perkow reaction has been used to generate a wide range of vinyl phosphates. Reaction of trialkyl phosphites with a-halogeno-ketones provide vinyl phosphates.1-5 Alkenes are produced via reduction of the dialkyl enol phosphate using either sodium or lithium in liquid ammonia. 

Many different mechanisms have been proposed for the Perkow reaction.2-4 It involves nucleophilic attack of the phosphite at the carbonyl carbon and affords a zwitterionic intermediate 5 which rearranges to form a cationic species 6 that subsequently dealkylates to give the corresponding vinyl phosphate 7. The conversion proceeds via a Michaelis-Arbuzov cleavage of an alkoxy group by halide ion as shown. 

Perkow reaction of ketone (16) with P(OEt>3 and P(OEt)Ph2 afforded the vinyl phosphate 17 and vinyl phosphinate 18, respectively.21... 

Perkow reaction of bromoketone 50 produces vinyl phosphate 51, which is stable and used for further reactions.21... 

The kinetics of the Perkow reaction to give vinyl phosphates (76) have been studied by both titration and n.m.r. methods. Both approaches... 

In 1952, Perkow reported (242) that a-haloaldehydes did not react with trialkyl phosphites according to the Michaelis-Arbuzov reaction, although this had been repeatedly reported, but that a new type of reaction occurred, yielding dialkyl vinyl phosphates isomeric with the expected phosphonates. 

A stirred mixture of diisopropyl 2-diloro-l-(2,4-didilorophenyl)vinyl phosphate and p-toluenesulfonic acid heated gradually whereupon vigorous gas evolution occurs at 165° and ceases after 1 hr. 2,2, 4 -trichloroacetophenone. Y 95.3%. -In combination with the Perkow reaction (s. Synth. Meth. 11, 173 12, 167), mono-ot-dedilorinated 0x0 compds. can be conveniently obtained by this method. F. e., also with H2SO4, s. K. Pilgram, F. Gorgen, and H. Ohse, J. Org. Chem. 34, 3558 (1969). 

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