Phosphonous halides

Primary phosphines are unpleasant and toxic reagents. They can be prepared from phosphonous halides, RPCI2, using LiAlILt. As is the case for secondary phosphines, easy access to pure phosphonous halides are required to make this route efficient. It has been found that compound 28 can be reduced to primary phosphine 29 using a mixture of UAIH4 and Me3SiCl (Scheme 13).31 This procedure appears useful, as phosphinates of type RP(0)(0Et)2 are often robust compounds that can be prepared in a number of ways. (e.g. Michaelis-Arbusov reaction, palladium-catalysed coupling of diethyl phosphite with aryl bromides, etc.)... 

A complementary approach to the above method has recently been reported.35 Bis(diethylamino)chlorophosphine can be protected with borane, and then treated with lithium naphthalenide to generate 35, which reacts with organic electrophiles. These can be treated with HCI to yield the phosphonous halide borane compounds, RPCl2 BH3 (Scheme 15). These need not be isolated and can be treated directly with an organolithium and deprotected to yield a tertiary phosphine, R1R22P. 

Substituted phosphonous halides condense rapidly with excess Grignard reagents to give good yields of unsymmetrical tertiary phosphines. The reaction is often exothermic and is conducted at low temperatures under nitrogen to avoid the formation of phosphine oxides. 

Phosphorus trichloride reacts rapidly with pure oxygen, even at low temperatures. It appears that various trace impurities can inhibit this reaction, although it is the conunercial route to POCI3. With ammonia, various amides are formed (7.31, 7.32), and with other nitrogen compounds, the reaction products include dialkylamino-substituted phosphonous halides, phosphazenes and cage compounds (Chapter 7). 

Phosphonyl halides may be obtained from the phosphonous halide by oxidation with sulphuryl chloride, nitrogen dioxide or oxygen (6.184). With some compounds direct oxidation of a solution may be effected with blown air (6.185). 

Fluorinated hydrocarbon polyphosphines can be obtained from the corresponding phosphonous halide on heating with mercury. 

Thiohalides of the type RP(S)X2 and R2P(S)X can be made by heating sulphur with the corresponding phosphonous or phosphinous halides. Phosphonothioic (thiophosphonic) halides can be obtained by the action of hydrogen sulphide on tetrachlorophosphoranes (9.425), or phosphonous halide-aluminium trichloride complex (Chapter 6), or P4SJ0 on the corresponding phosphonic dihalide (9.426), or by reaction (9.427) in which PSCI3 acts as a sulphur donor. Monophenyl phosphine and thionyl chloride produce phenyl phosphonothionic dichloride, which can also be obtained by thermal isomerisation (9.428). 

According to the different donor properties found in this group of solvents a distinction may be made between (a) oxyhalides with low donor numbers including carbonyl chloride, nitrosyl chloride, thionyl chloride, sulphuryl chloride, acetyl and benzoyl halides and (b) oxyhalides with medium donor numbers, namely phosphorus oxychloride, selenium oxychloride and phenyl phosphonic halides, the latter having donor properties approaching those of water or of the ethers. 

Dialkyl arylphosphonates and alkenylphosphonates are prepared by the coupling of halides or triflates with the dialkyl phosphonate 783[64l-643]. 

ARBUZOV MICHAELIS Phosphonale Synihesis Ni catalyzed phosphonate synthesis from phosphites and aryl halides Reaction of alkyl halides with phosphites proceeds without nickel salts... 

With acyl halides, the corresponding acyl phosphonates are obtained. Furthermore allylic and acetylenic halides, as well as a-halogenated carboxylic esters and dihalides, can be used as starting materials. If substituents R and R are different, a mixture of products may be obtained, because the reaction product RX 5 can further react with phosphite 1 that is still present ... 

Ailyl sulfides, sulfonates, halides, phosphonates, silanes... 

Table 6.9 Transfer Constants for Ally Halides, Phosphonates, Silanes and...

Diesters of phosphorous acid are in general neutral because the phosphorous acid exists mostly in the phosphonate form with one hydrogen directly attached to the phosphorus. But with alkali metals the H can be changed against the alkali and reactive intermediates formed. Such alkali metal derivatives of dialkyl phosphites react with alkyl halides to give dialkyl alkanephosphonates, according to Eqs. (45) and (46). 

Phosphonous acid diesters undergo the Arbusov reaction with a wide variety of organic halides, giving esters of secondary phosphinic acids, as is demonstrated in Eq. (88) ... 

Examples of the intermolecular C-P bond formation by means of radical phosphonation and phosphination have been achieved by reaction of aryl halides with trialkyl phosphites and chlorodiphenylphosphine, respectively, in the presence of (TMSlsSiH under standard radical conditions. The phosphonation reaction (Reaction 71) worked well either under UV irradiation at room temperature or in refluxing toluene. The radical phosphina-tion (Reaction 72) required pyridine in boiling benzene for 20 h. Phosphinated products were handled as phosphine sulfides. Scheme 15 shows the reaction mechanism for the phosphination procedure that involves in situ formation of tetraphenylbiphosphine. This approach has also been extended to the phosphination of alkyl halides and sequential radical cyclization/phosphination reaction. ... 

B. Reactions.—(/) Nucleophilic Attack at Phosphorus. A reinvestigation of the reaction between phosphorus trichloride and t-butylbenzene in the presence of aluminium chloride has shown that the product after hydrolysis is the substituted phosphinic acid (11), and not the expected phosphonic acid (12). Bis(A-alkylamino)phosphines have been reported to attack chlorodiphenyl phosphine with nitrogen, in the presence of a base, to give bis-(A-alkyl-A-diphenylphosphinoamino)phenylphosphines (13). In (13), the terminal phosphorus atoms are more reactive than the central one towards sulphur and towards alkyl halides. 

A. Nucleophilic Reactions.—(/) Attack on Saturated Carbon. The Arbusov reaction has been used to prepare organosilicon-substituted phosphonates (1) and phosphorylated ethers (2a) and sulphides (2b). Bromo- and chloro-derivatives of the cyclic phosphite (3) do not react with ethyl halides... 

Dielectric relaxation studies of phosphorylated polyethers from — 180° to 200 °C have been used to study their structures. The magnitude of the dielectric constants of high-phosphonic-acid-content polymers is much larger than predicted, which suggests a microphase-separated structure. Conductance studies on some aryl- and alkyl-phosphonium salts showed a higher conductance for the halides than for the nitrate. ... 

Olefination Reactions Involving Phosphonate Anions. An important complement to the Wittig reaction involves the reaction of phosphonate carbanions with carbonyl compounds 253 The alkylphosphonic acid esters are made by the reaction of an alkyl halide, preferably primary, with a phosphite ester. Phosphonate carbanions are generated by treating alkylphosphonate esters with a base such as sodium hydride, n-butyllithium, or sodium ethoxide. Alumina coated with KF or KOH has also found use as the base.254... 

Both neutral and anionic phosphorus compounds are good nucleophiles toward alkyl halides. We encountered examples of these reactions in Chapter 2 in connection with the preparation of the valuable phosphorane and phosphonate intermediates used for Wittig reactions. 

Preparation of dimethyl (4-methoxybenzyl)phosphonate — Reaction of a benzyl halide with a trialkyl phosphite... 

Hoerold, S., Weferling, N., and Breuer, H.-R, Preparation of phosphonic acid esters from alkyl halides and elemental phosphorus, and their use, Ger. DE 19,828,861, 2 Dec. 1999 Chem. Abstr., 132, 12410r, 2000. 

In the instances of phosphorous and phosphonous acid systems, the generation of a new C-P bond via the classical Michaelis-Arbuzov reactions as noted above leads to products that are esters themselves. Isolation of the free acid product requires cleavage of the ester linkage in a separate reaction step, generally after isolation and purification of the initial product. The advent of silyl phosphorus reagents for the Michaelis-Arbuzov reaction allowed free acid products to be isolated simply by water workup of the reaction system. Further, since the byproduct was a silyl-halide, the general concern that the by-product halide would participate in an extraneous Michaelis-Arbuzov reaction was obviated. 

Several methods for the preparation of the parent compound in this system, tris(trimethylsilyl)phosphite, have been reported.114 118 The application of this and related reagents in reaction with alkyl halides has been reported and used for the preparation of a variety of phosphonic acid analogues of phospholipids.114119-124 Interestingly, alkyl chlorides appear to be more reactive with the silyl reagents than do alkyl iodides, a reversal of the normally observed trend with alkyl esters of the phosphorus acids. (The particular use of silyl phosphorus reagents for the synthesis of biologically significant compounds has... 

The reaction is performed most simply by the addition of the propargylic alcohol to a solution of the phosphorus halide. Rearrangement of the phosphorus ester proceeds at ambient temperature or with mild heating. When phosphorus trihalides are used, the product can be isolated as the phosphonic dichloride.168169 Aqueous workup provides the phosphonic acid.162 In most instances, however, a dialkyl phosphorochloridite with only a single halogen on phosphorus available for reaction with alcohol has been used.165 170 174... 

Corresponding replacement of halide from an unconjugated vinylic site has also been reported. The use of the sodium salts of dialkyl phosphites in tetrahydrofuran at low temperature has been found to provide the vinylic phosphonate in good yield,72 (Figure 6.22) and triisopropyl phosphite serves similarly to replace a fluoride of trifluoroiodoethene (Figure 6.23).91 The reaction proceeds ste-reospecifically to replace the fluoride cis to the iodide, and in continuing reaction the iodide is replaced. 

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