Diethyl chlorophosphite

The reaction between the cyclic orthoester 8 and diethyl chlorophosphite 9 leads via transesterification to the two acetals 4 and 5, which cannot be separated by distillation. 

Alternative, also stereoselective, routes to allenic steroids take advantage of cationic cyclization reactions [108] or [2,3]-sigmatropic rearrangements [109]. For example, the allenic Michael acceptor 112 was prepared with 57% chemical yield by reaction of mestranol (111) with diethyl chlorophosphite and was found to inhibit the sterol biosynthesis of the pathogen responsible for Pneumocystis carinii pneumonia (PCP), the most abundant AIDS-related disease (Scheme 18.36) [110]. 

Gramine - 3-(dimethylaminomethyl)indole (14) - is a readily obtainable derivative of indole and is produced with a quantitative yield by the Mannich reaction. In [19] it was phosphorylated with diethyl chlorophosphite. 3-(Dimethylaminomethyl)-l-(triethoxyphosphito)indole (15) was obtained also by the method in [20] using diethyl penten-3-on-2-yl phosphite. Compound 15 readily adds sulfur with the formation of the corresponding gramine 1-thiophosphate 16 and reacts with chloral according to the scheme of the Perkow reaction, forming phosphate 17 ... 

ArOH —s- ArH. In a procedure for the removal of the phenolic hydroxyl group of estrone by the method of Kenner and Williams, a G. D. Searle group found it preferable to use diethyl chlorophosphite itself rather than to generate it in situ from diethyl phosphonate. 

The synthesis of diethyl ethynylphosphonate has recently been described using lithium few(diisopropyl unino)boracetylide as a synthetic equivalent for lithium acetylide. After reaction with diethyl chlorophosphate in THF at -TS C, the protected diethyl ethynylphosphonate is hydrolyzed with a 3 M1 ICl solution to produce diethyl ethynylphosphonate in good overall yield (72%), comparable with those previously obtained (Scheme I.IO). Synthesis of diethyl ethynylphosphonate has also been reported with an overall yield of 68% by a three-step synthesis including the reaction of lithium trimethylsilylacetylide with diethyl chlorophosphite (83%) followed by oxidation with MCPBA and deprotection with KF in EtOH (82%). ... 

Two variants of this rearrangement have been reported. One uses triethyl phosphite instead of diethyl chlorophosphite. Thus, in the presence of a catalytic amount of para-toluenesulfonic acid, triethyl phosphite reacts with propargyl alcohol in DMF at room temperature to give a mixture of diethyl allenylphosphonate (51%) and diethyl 1-propynylphosphonate (14%). The second variant is based on the conversion of dialkyl allenylphosphonates (R , R H, R = H, Scheme 1.19) into dialkyl 1-alkynylphosphonates by a photochemically allowed [l,3s]-sigmatropic shift in ( ,11, with 46-50% yields. ... 

The reaction of diethyl chlorophosphite with ketone enolates has been explored as a direct route to P-ketophosphonates (Scheme 7.41). Instead of attempting isolation of phosphite intermediates, an in situ oxidation of the intermediate products is accomplished by leaving the products open to air. The use of these standard conditions results in the formation of a mixture of C-P and 0-P products. The effect of solvents on the C-P/O-P ratio has been explored, and in many cases the use of Et2O/HMPA improves the ratio. By application of the chlorophosphite/oxidation approach a variety of ketones have been converted into their respective p-ketophophonates in attractive yields. ... 

A new approach to diethyl 2-methoxycarbonyl-2-alkenylphosphonates is based on the thermally indnced Michaelis-Arbnzov rearrangement of diethyl allyl phosphites withont added alkyl halide (Scheme 8.39). The procednre involves treatment of the readily accessible allyl alcohols with diethyl chlorophosphite followed by heating of the crude intermediates for several hours at 7O-IOO"C. The presence of a methoxycarbonyl group facilitates the rearrangement, the optimum temperatures being lower than those reported for unfunctionalized analogues. 

An attractive procedure for the preparation of 2-oxo-m-(alkoxycarbonyl)alkylphosphonatcs involves the C-phosphonylation of p-keto ester dianions with dialkyl chlorophosphate (45-67%) or C-phosphirylation of the monoanion of substituted dioxinones with diethyl chlorophosphite followed by oxidation ... 

There are two possibilities for converting polymer-bound 3-hydroxy-2-methylidene propionic acids into 2-diethoxy-phosphorylmethyl acrylic acids. One is the treatment of these substrates with diethyl chlorophosphite and Et3N followed by an Arbuzow rearrangement. The other method, which resulted in higher purities [28], is the reaction of acetylated 3-hydroxy-2-methylidene propionic acids with triethylphosphite in DMF for 5 h at 60°C (Fig. 6.12). Table 6.6 shows the variation of the aldehydes in this reaction. All compounds were analyzed by ES-MS and analytical HPLC. 

Diethyl phosphorochloridate, (C2H50)2P0C1, 1, 248 (formerly known as Diethyl chlorophosphite). 

Simple aliphatic aldehydes are also said to yield products which contain the equivalent of 2-3 mol of RCHO per phosphorus atom, some of which have been shown to have an oxyphosphorane structure. (For an introductory account of this fascinating area of phosphorus chemistry, the reader should consult early reviews by Ramirez . ) The phosphite ester obtained from 2-hydroxybenzaldehyde and diethyl chlorophosphite cyclizes with rearrangement to the l,2-benzoxaphosph(V)ole derivative 205 (R = H, R = EtO), and a similar process was observed in the case of phosphites and phosphonites derived from 2-hydroxyacetophenone to give 205 (R = Me) . 

An ethereal soln. of diethyl chlorophosphite added gradually at -20° with vigorous stirring during 3-4 hrs. to a-ethynylbenzyl alcohol and triethylamine in anhydrous ether, stirring continued several hrs., allowed to warm to room temp, with continued stirring, and the product isolated after 18 hrs. diethyl... 

Mixed anhydride (e.g. with pivaloyl chloride diethyl chlorophosphite or diphenylphosphoryl chloride)... 

Phosphonates and phosphonothioates which are separated from the ortto-carborane core by a methylene bridge were also reported. In these compounds, the electronic influence of the carbo-rane on the phosphonate group is low. Their synthesis starts from the Grignaid reagent (l-bromomagnesiomethyl)-ort/io-carborane and diethyl chlorophosphite (Scheme 2.3). Transformation into phosphonates 3 and 4 as well as into phosphonothioate 5 was achieved in the same manner as reported for the above-mentioned carborane derivatives. 

Butynediol allowed to react with 2 moles of diethyl chlorophosphite whereby rearrangement starts at room temp, and is accompanied by spontaneous heating, the product isolated by distillation in vacuo 2,3-bis(diethylphos-phono)-1,3-butadiene. Y 50-60%. F. e. s. A. N. Pudovik and I. M. Aladzheva, 33, 708 (1963) G. A. 59, 2852h f. rearrangement s. 33, 707 G. A. 59, 2851f. 

Quinoxalin-2(17f)-ones of different stmcture react with methyl isocyanides under the action of bases to form imidazo[ 1,5-a]quinoxaline derivatives (Hansen and Waetjen 1989a, b, c, 1990, 1991 Jacobsen et al. 1996a, b, 1999 Mickelson et al. 1996 Nispen et al. 1980 Waetjen 1987 TenBrink et al. 1992, 1993, 1994, 1996 Wang et al. 2012). The reaction is usually carried out in the presence of diethyl chlorophosphite at low temperatures. The in situ formed diethyl quinox-alinylphosphonate (see below) readily reacts with substituted methyl isocyanides, and 1,3-dipolar cycloaddition thereby leads to annulation of the imidazole ring. By this method, quinoxalinones 45a, b have been convened into imidazo[l,5-fl] quinoxalines 46a-h with different substituents in the 3-posilion (Scheme 4.23) (Hansen and Waetjen 1989a, 1990). 

Scheme 4.23 Synthesis of imidazofl, 5-a]quinoxalines from quinoxalin-2(17f)-ones when exposed to methyl isocyanides in the presence of diethyl chlorophosphite...

A method of synthesis of imidazoquinoxalin-4-ones that affords these heterocyclic systems with different substiments in the 3-, 5-, 6- and 7-positions has been well developed (Waetjen 1987 Wae en and Hansen 1988, 1990, 1991 Hansen and Wae en 1989b, c Jacobsen et al. 1996a TenBrink et al. 1993). The method is based on the reaction of quinoxaline-2,3-dione derivatives 53 with diethyl chlorophosphite leading to diethyl quinoxaUnyl phosphates 54. The latter, without isolation, are introduced into the reaction with substimted methyl isocyanides in the presence of a base leading to products 55 (Scheme 4.27). 

The Michaelis-Arbusov and the Michaelis-Becker reactions are the methods of choice to access aliphatic phosphonates. Aromatic phosphonates are inaccessible in this way. They can be readily prepared by condensation of a (het)aryllithium with triethyl phosphite or diethyl chlorophosphite. Anilines or (thio)phenols can be orr/io-phosphorylated with particular ease by docking first the dialkoxyphosphoryl entity at the heteroatom before treating the 0,0-dialkyl... 

Synthesis of allenylphosphonate 191 Diethyl chlorophosphite (0.68 g, 4.3 mmol) in 20mL of CH2CI2 was added dropwise to a stirred solution of pyridine (0.35 g, 4.4 mmol) and mestranol 190 (979 mg, 3.15 mmol) in 40 mL of dichloromethane under nitrogen at 0°C. The resulting mixture was stirred for 18 hours at room temperature washed successively with 1N HCl, saturated aqueous sodium hicarhonate and hrine dried over sodium sulfate and evaporated, leaving 1.20 g (1.35 theoretical yield) of the crude allenic ester 191. The crude product was subjected to column chromatography (silica gel, eluted with EtOAc/henzene 4 1, (v/v) and recrystallized from methylene chloride-methylcyclohexane (yield, 767 mg, 56.8%). 

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