Diethyl phosphite, reactions

Huorinated etiolates are generally difficult to form. Ishihara and coworkers used fluorovinyl phosphates, which can be prepared from a-fluoro ketones and sodium diethyl phosphite. Reaction of these fluorinated enol phosphates with a reagent prepared from lithium aluminum hydride (LiAIH4> and cop-per(II) bromide, zinc(II) chloride, tin(II) chloride or bromine afforded the enolate (Scheme 34).The reaction of the enol phosphate with the reagents mentioned above suggests that the metal cation of the enolate is an aluminum species, though its actual structure is not known at present. 

This reaction also takes place with halogenides of dibasic acids. Thus adipoyl chloride and diethyl phosphite are reacted at 90°C for 8 h yielding adipyl-diphosphonic acid diethyl ester, according to Eq. (41). 

The following reaction sequence was used to obtain methyl hydroxymethanediphosphonic acid. This compound is widely used as a water hardness sequestering agent and detergent builder. Triethyl chloride was reacted with acetyl chloride to give diethylacetylphosphonate, followed by a conversion with diethyl phosphite and sodium. After completion of this reaction the substance was hydrolyzed with HC1 to yield hydroxymethanediphosphonic acid, [93,94], as shown in Eqs. (49)-(51) ... 

In a similar reaction of ketene with diethyl phosphite in the presence of boron fluoride etherate as catalyst, diethyl 1-acetoxyvinylphosphonate is formed [113] see Eq. (69) ... 

Another method for the preparation of hydroxyalkanephosphonic acids is the conversion of aldehydes with dialkyl phosphites in the presence of triethylamine or sodium methylate leading directly to the corresponding a-hydroxyalkane-phosphonates. This reaction is reversible, leading to the starting materials aldehyde and diethyl phosphite again [143,146]. 

These results contrasted sharply with those obtained with a HHT that was relatively unstable to the reaction conditions. For example, the commercially available HHT of glycinonitrile 28 gave a very poor yield (6%) of coupled glyphosate product with diethyl phosphite because the reaction must be run with acid-catalysis at much lower temperatures (27,38). Somewhat higher yields were observed when 28 was used directly under the modified, acidic Mannich conditions to provide iV-phosphonomethylglycinonitrile 29, which was hydrolyzed direedy to GLYNa3 (39). 

Another AMPA-derived procedure took advantage of the neat reaction between the N-carbamoyl-HHT 59 and diethyl phosphite catalyzed by boron trifluoride etherate to generate the AMPA carbamate 60. Subsequent alkylation with ethyl bromoacetate and base produced the glyphosate triester carbamate 61, which was hydrolyzed to GLYH3 (59). 

The herbicide activity ascribed to the 1,2,4-oxadiazole derivative 67 (60) has prompted the search for other biologically active derivatives. This example was prepared from the corresponding 5-chloromethyl-1,2,4-oxadiazole 63 via conversion to the HHT 65 through the aminomethyl analog 64. Reaction of the HHT 65 with diethyl phosphite under neat conditions produced the desired diethyl ester intermediate 66, which was hydrolyzed to 67. 

The rigid, planar pyridine analog 111 was isolated in low yield by first hydrolyzing the known (67) pyridine diethyl phosphonate 109 to the corresponding free acid 110 followed by permanganate oxidation (2). An alternative synthesis of 111 has recently been reported (68). Alkylation of pyridine-2-carboxylate -oxide with dimethylsulfate and subsequent reaction with the sodium salt of diethyl phosphite gave the triester 112, which was readily converted to 111. 

Japanese workers have prepared diethyl phosphite in 43% yield from the reaction of white phosphorus with ethanol and oxygen. 

Metal-catalyzed asymmetric addition of dialkyl phosphites to aldehydes (Pudovik reaction) has been extensively developed since the initial reports in 1993 by Shibuya. Scheme 5-25 illustrates the use of TiCh to promote diastereoselective addition of diethyl phosphite to an a-amino aldehyde. 

SRNl substitution include ketone enolates,183 ester enolates,184 amide enolates,185 2,4-pentanedione dianion,186 pentadienyl and indenyl carbanions,187 phenolates,188 diethyl phosphite anion,189 phosphides,190 and thiolates.191 The reactions are frequently initiated by light, which promotes the initiating electron transfer. As for other radical chain processes, the reaction is sensitive to substances that can intercept the propagation intermediates. 

Schrader prepared the ester (38) in 60% yield by reaction of sodium p-nitrophenate with diethyl chlorophosphate, using xylene as solvent for the reaction. He made it, but in lower yields, from p-nitrophenol and diethyl chlorophosphate, using, respectively, pyridine and sodium cyanide as acceptors for hydrogen chloride. Schrader also prepared it in 96% yield by nitrating diethyl phenyl phosphate at 0° C. or below. Under the conditions he used, Schrader claims that the nitro group is directed to the para position. No yield is given for the diethyl phenyl phosphate, which he presumably made from sodium phenate and diethyl chlorophosphate. Diethyl chlorophosphate may be prepared in high yield (30) from diethyl phosphite and chlorine. 

The broad use of A -carbonyldiimidazole (CDI) for the synthesis of amide and peptide linkages became a routine method only in the early sixties. JV-Protected amino acids were treated at room temperature with an equimolar amount of CDI to give imidazolides. Anhydrous tetrahydrofuran, dimethoxyethane, dichloromethane, pyridine, dimethylfor-mamide, and diethyl phosphite were utilized as solvents. In the second step the esters of amino acids, their hydrochlorides, or sodium salts were added to yield the peptide after several minutes or hours of reaction time. 

Preparation of diethyl isobutyrylphosphonate — Reaction of a trialkyl phosphite with a carboxylic acid chloride... 

Preparation of diethyl phenylphosphonate — Reaction of an aryl halide with a dialkyl phosphite in the presence of a Pd(0) catalyst and a tertiary amine... 

Reaction of the conjugate base of diethyl phosphite with 3-car-boxyethyl-substituted 2,5-halomethylfurans provided interesting products as alternatives to the normally anticipated Michaelis-Becker substitution-type products.452 Rather than simple substitution, overall reduction of the halomethyl linkage(s) to methyl(s) were observed with a Michael-type addition of phosphorus to the 4-position of the ring. 

Kilbardin, A.M., Gazizov, T.K., and Pudovik, A.N., Reactions of diethyl tri-methylsilyl phosphite and of acetyl diethyl phosphite with fluorinated ketones,. Gen. Chem. U.S.S.R., 45,1947,1975. 

Butyllithium (23% in hexane) (63 ml, 0.15 mol) was added dropwise to diethyl phosphite (25 g, 0.18 mol) at -20 to -30°C over a period of 2 h. To the resulting mixture was added A/-methoxy pyridinium meth-osulfate in dimethyl phosphite (40 ml) over a period of 1 h at -15°C. The reaction mixture was stirred at room temperature overnight, and water (100 ml) was then added. The mixture was extracted with chloroform (3 x 75 ml), and the combined organic extracts were separated into neutral and basic fractions by extraction (4 N HC1), bas-ification, and reextraction with chloroform. The basic portion was distilled yielding diethyl pyridine-2-phosphonate (22.9 g, 67%) of boiling point (bp) 105-112°C/0.08 torr. 

In order to synthesize biologically relevant phosphonylimidazole 73, bromoimidazole 72 was derived from radical-initiated bromination of methyl l-p-methoxybenzyl-2-thiomethyl-5-imidazolylcarboxylate (71) [56]. The thiomethyl group served to block the C(2) position, which would otherwise undergo preferential halogenation under these conditions. As expected, a variety of Arbusov-Michaelis reaction conditions failed even under forcing conditions. On the other hand, Pd-catalyzed phosphorylation of 72 with diethyl phosphite led to methyl-4-diethylphosphonyl-l-p-methoxybenzyl-2-thiomethyl-5-imidazolylcarboxylate (73). After further manipulations, the desired phosphonic acid-linked aminoimidazoles, which resembled intermediates formed during purine biosynthesis, were accessed. 

This type of reaction was originally carried out with ethyl iodide1 and has been extended to other alkyl halides,2 halogeno-carboxylic esters3 and to substituted arsine halides.4 Incidentally when p-toluene sulphonyl chloride and naphthalene-2-sulphonyl chloride were allowed to react with sodium diethyl phosphite, the corresponding disulphones were obtained in small yield.5... 

A 1 M or 2 M solution of sodium ethylate in ethanol was added dropwise at 60°C to a 1 1 mixture of acetamidomethylenemalonate (1568) and diethyl phosphite, while the temperature of the reaction mixture was raised to 100°C. At this temperature, the reaction mixture was stirred for 1.0-1.5 hr [76RC661 88JCS(P1)61]. If the mixture was hydrolyzed with boiling concentrated hydrochloric acid overnight, 3-amino-3-phosphonopropionic acid (1572) was obtained in 75% yield (76RC661). When the cooled reaction mixture was treated with diethyl ether, then again boiled and filtered, and... 

Attack on Unsaturated Carbon. The annual addition of phosphites to every variety of activated double bond continues. These include nitro-alkenes,9 a/S-unsaturated carboxylic acid derivatives,10 maleimides,11 fulvenes,12 and pyridinium salts.13 The reaction of diethyl phosphite with keten 0,N-, S,N, and Al,AT-acetals has been used to prepare the enamine phosphonates (19).14... 

Diethyl dl-1 -aminobenzylphosphonate has been prepared by a Mannich reaction of diethyl phosphite, benzaldehyde, and ammonia, resolved as its D-mandelate salt, and hydrolysed to give (+)-l-aminobenzylphosphonic acid.27 While the tetraethyl-diamide (33) reacts with benzaldehyde to give the expected phosphonic diamide (34), the corresponding tetramethyl-diamide reacts, with migration of the dimethyl-amino-group, to give (35).28... 

Diethyl phosphate esters of the sterically congested phenols of calixarenes have been prepared in acceptable yields (>55%) and used in the preparation of meta-cyclophanes [8]. The corresponding reaction using diethyl phosphite, with triethylamine in place of the quaternary ammonium catalyst, results in only partial phosphorylation of the hydroxyl groups. 

Aryl radical additions to anions are generally very fast, with many reactions occurring at or near the diffusion limit. For example, competition studies involving mixtures of nucleophiles competing for the phenyl radical showed that the relative reactivities were within a factor of 10, suggesting encounter control,and absolute rate constants for additions of cyanophenyl and 1-naphthyl radicals to thiophenox-ide, diethyl phosphite anion, and the enolate of acetone are within an order of magnitude of the diffusional rate constant. ... 

The light-induced addition elimination reaction of diethyl phosphite to both 1,3,3,4,4-penta-fluorocyclobutene and l-chloro-3,3,4,4-tetrafluorocyclobutene afforded a mixture of diethyl 3,3,4,4-letrafluorocyclobutene-l-phosphonate (11) and tetraethyl 3,3,4,4-tetrafluorocyclobutane-1,2-diphosphonate (12). The postulated mechanism of addition involves phosphonyl radical attack at the cyclobutene moiety.17... 

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