Trialkyl phosphites triethyl phosphite

Triethyl phosphite is a colourless mobile liquid, insoluble in water. Trialkyl phosphites are valuable intermediates in the preparation of many organophosphorus compounds they readily form dialkyl esters of alkylphosphonic acids by the Arbusov reaction (p. 311). 

Sulfonic esters are most frequently prepared by treatment of the corresponding halides with alcohols in the presence of a base. The method is much used for the conversion of alcohols to tosylates, brosylates, and similar sulfonic esters. Both R and R may be alkyl or aryl. The base is often pyridine, which functions as a nucleophilic catalyst, as in the similar alcoholysis of carboxylic acyl halides (10-21). Primary alcohols react the most rapidly, and it is often possible to sulfonate selectively a primary OH group in a molecule that also contains secondary or tertiary OH groups. The reaction with sulfonamides has been much less frequently used and is limited to N,N-disubstituted sulfonamides that is, R" may not be hydrogen. However, within these limits it is a useful reaction. The nucleophile in this case is actually R 0 . However, R" may be hydrogen (as well as alkyl) if the nucleophile is a phenol, so that the product is RS020Ar. Acidic catalysts are used in this case. Sulfonic acids have been converted directly to sulfonates by treatment with triethyl or trimethyl orthoformate HC(OR)3, without catalyst or solvent and with a trialkyl phosphite P(OR)3. ... 

Orthophosphoric and benzylphosphonic acids have been selectively alkylated with triethyl phosphite in a new synthesis of mono-, di-, and triethyl phosphates and of mono- and di-methyl phosphonates.62 A-Methylol carboxamides and sulphonamides react with trialkyl phosphites to give the phosphonate derivatives (78) and (80), respectively.63 However, the mechanism appears to be quite different in each case while the carboamides react by a transesterification-rearrange-ment pathway, the sulphonamides undergo elimination-addition via the imine (79). 

Of trialkyl phosphites the most frequently used is triethyl phosphite (EtO)3P (M.W. 166.16, b.p. 156°, density 0.969) which combines with sulfur in thiiranes [291, 294] and gives alkenes in respectable yields. In addition, it can extrude sulfur from sulfides [295], convert a-diketones to acyloins [296], convert a-keto acids to a-hydroxy acids [297], and reduce nitroso compounds to hydroxylamines [298] Procedure 47, p. 111). 

Among the more recent approaches to phenoxazines and phenothiazines the reductive cyclization of 2-nitrodiphenyl ethers and sulfides with trialkyl phosphites is the most interesting. Here too a spiro intermediate is involved, produced by attack of an initially formed aryl nitrene on the second aromatic ring. The sulfide (252), for example, reacts with triethyl phosphite to yield 1-methylphenothiazine (253) and it is clear that in this case ring opening of the spiro intermediate also proceeds with a rearrangement of the Smiles type (Scheme 113) (75JCS(P1)2396). 

The protected methyl glycoside 3 is converted to the corresponding aldehyde by Swern oxidation using oxalyl chloride activated DMSO. Further reaction with triethyl phosphonoacetate and sodium hydride -known as the Horner-Wadsworth-Emmons reaction - provides selectively the trans et /Tun saturated ester 4 in 72 % yield. This valuable alternative to the Wittig olefination protocol uses phosphonate esters as substrates which are readily available from alkyl halides and trialkyl phosphites via the Arbuzov rearrangement.9 co2Et Reaction of the phosphonate with a suitable base gives the... 

The allyl complex [Rh(i/3-C3H5)(cod)] reacts with trialkyl phosphites to form [RhHL2] complexes. The dimeric triisopropyl phosphite complex has already been mentioned. Trimethyl and triethyl phosphite, however, form trimeric products.64,100 The structure of the trimethyl phosphite complex (14) has been determined by X-ray crystallography.100-102... 

Dialkyl 1-alkynylphosphonates (22) were formed in good to high yields by treatment of 1-alkynyliodonium tosylates (23) with trialkyl phosphites the reaction is exothermic with trimethyl phosphite but requires heating with triethyl or triisopropyl phosphite. The addition of trimethyl or triethyl phosphite to 3-alkylene-2-oxindoles (24) has led to new product types for a, -unsaturated carbonyl compounds, i.e. a stable tri-alkoxyphosphonium zwitterion (25), and a C-alkylated phosphonate (26). ... 

A new method of cyclization has been developed, through the reaction of suitably or//ru-substituted diethyl benzoylphosphonates (41), or their acid chloride precursors, with trialkyl phosphites. An analogous reaction takes place with (42) to give the fluorenylphosphonate (43). The mechanism suggested involves initial attack on carbonyl oxygen, and gains support from the formation of the benzofuranylphosphon-ate (45) in the reaction of (44) with triethyl phosphite. 

The treatment of propargyl bromide with trialkyl phosphites is reported to give complex reaction mixtures. For example, from the reaction between triethyl phosphite and propargyl bromide at 90 C, diethyl 1-propynylphosphonate is isolated only in low yields (15%). ... 

Possibly the most frequently used and most widely known phosphonylated aldehyde is diethyl l-formylmethyIphosphonate. A vaiiety of methods for the preparation of this aldehyde are reported in the literature. The oldest employs tlie Michaelis-Arbuzov reaction between triethyl phosphite and bromoacetaldehyde diethyl acetal, which yields diethyl 2,2-diethoxyethylphosphonate on heating to 160°C (Scheme 5.5). Subsequent acid hydrolysis gives diethyl 1-formylmethylphosphonate. The aldehyde function requires protection because it is known that a-haloaldehydcs react with trialkyl phosphites in a Perkow reaction affording dialkyl vinylphosphates isomeric with the expected phosphonates. " ... 

Harvey, R.G., Reactions of triethyl phosphite with activated olefins. Tetrahedron, 22, 2561, 1966. Okamoto, Y, A convenient preparation of dialkyl 3-(dialkoxyphosphinyl)-l-propenyl phosphate derivatives. Addition of the mixed reagent trialkyl phosphite/diaUcyl phosphorochloridate to a,P-unsaturated aldehyde, Chem. Lett., 87, 1984. 

Dawson and Burger first demonstrated that the Michaelis-Arbuzov reaction of chloroacetonitrile and triethyl phosphite furnishes diethyl cyanomethylphosphonate. In its most general form, it involves the addition of triethyl phosphite to chloroacetonitrile at 150-170°C to give diethyl cyanomethylphosphonate in up to 80% yields (Scheme 6.2). ° This procedure has been developed on an industrial scale The use of bromo- or iodoacetonitrile (X = Br, I, Scheme 6.2) was also reported. The reaction may be used to prepare any dialkyl cyanomethylphosphonate, and a variety of trialkyl phosphites have produced the corresponding phosphonates in reasonable to good yields (29-90%, Scheme 6.2). " Cyclic phosphites, 4,5-dimethyl-2-methoxy-l,3,2-dioxaphos-pholane (meso and racemic) and 5,5-dimethyl-2-methoxy-l,3,2-dioxaphosphorinane, react with chloroacetonitrile to produce 5- and 6-membered cyclic phosphonates in 50% and 72% yields, respectively. ... 

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) ... 

The preparations and properties of diethyl 1-(ethoxycarbonyl)-1-oxomethylphosphonate (triethyl phosphonoglyoxylate) have recently been described. The dialkyl 2-ethoxycarbonyl-l-oxoeth-ylphosphonates are prepared in moderate yields by a Michaelis-Arbuzov reaction between trialkyl phosphites and ethyl 3-chloro-3-oxopropionate (Scheme Dialkyl 3-methoxycarbonyl-... 

Another attractive route to co-amino-(o-(hydroxycarbonyl)alkylphosphonic adds involves the use of the classical Michaelis-Arbuzov and Michaelis-Becker reactions. For example, the suitably protected 2-amino-(o-bromoalkanoates are readily converted into 3-amino-3-carboxypropylphosphonates (Scheme 8,82) ° or substituted 6-amiuo-6-c trboxyhcxylphosphonatcs by the Michaelis-Arbuzov rearrangement with trialkyl phosphites. However, it appears that, when enantiomerically pure bromide is used, the Michaelis-Arbuzov reaction is responsible for some racemization. It has been found that the extent of racemization is greater when the reaction is run at 150°C using triethyl phosphite than with trimethyl phosphite at 110°C for only the required amount of time. ... 

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)-... 

Trialkyl phosphites which are unable to undergo intramolecular Arbuzov rearrangement can be isomerized by heating them at about 80° with an equimolar amount of a trialkylaluminum e. g., triethyl phosphite and triiso-... 

Essentially all the simple geminal di- or poly halides studied have been derivatives of methane. Reaction of diiodomethane (25,103) with triethyl phosphite proceeds normally, to furnish tetraethyl methanedi-phosphonate and iodomethanephosphonate. However, the reaction between carbon tetrachloride and trialkyl phosphite, first investigated by Kamai and Egorova (156,181), is catalyzed by peroxides or ultraviolet light, and accordingly it has been formulated by Kamai and Kharrasova (157) as a radical-chain process. 

Normally, trialkyl phosphite esters are stable in alcoholic or phenolic solutions except for transesterification (134). However, at 210-215°, trimethyl phosphite is isomerized to dimethyl methylphosphonate, and triethyl phosphite is converted to diethyl methylphosphonate by methanol (79). The formation of these substances has been rationalized as proceeding via the intermediate [AIeOP(i Ie)(OR)2]+ OH. 

Trialkyl phosphites attack / - and 7-lactones at the terminal carbon atom (82,184,219). For example, reaction of triethyl phosphite with /3-propiolactone yields diethyl jS-carbethoxyethylphosphonate. Suitable adjustment of the ratio of reactants leads to various mixtures of telo-meric products which are thought to arise by further reaction of the intermediate (R0)3P" "CH2CH2C02 with additional molecules of the lactone. The use of basic catalysts allows the reaction to proceed at lower temperatures but favors telomer formation. The role of the catalyst has not been established. 

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