Diethyl H-phosphonate

By transesterification Diethyl H-phosphonate (27.6 g, 0.2 mol) and 1,2- or 1,3-glycol (0.2 mol) were placed in a round-bottom flask connected to a Claisen head fitted with a downward condenser and a receiver for vacuum distillation. The resulting solution was heated to 130 C at 120-160 mm pressure under nitrogen. Ethanol evolution ceased after about 3 h of heating at the above temperature. The remaining crude product was fractionated at 2-3 mm. The cyclic hydrogen phosphonates were obtained as very viscous, colorless liquids. 

In the NMR spectrum of the methylammonium salt of the monomethyl ester of H-phosphonic add, the phosphorus signal appears at 4.55 ppm as a doublet of quartets with V(P,H) = 600 Hz indicating phosphonate structure. Kers et al. [23] confirm that in the reaction mixture of diethyl H-phosphonate and pyridine or pyridine with 2 equiv. of tertiary base (TEA), there were no signals that could be assigned to Iriethyl phosphite. The results obtained show that the basic activation in these reactions involves at the first step formation of the monoalkyl H-phosphonate anion [(R0)P(0)(H)0] , which further plays the key role in interactions where the phosphorus atom acts as a nucleophile. 

Diethyl H-phosphonate reacts with ethyl hypochloride to give triethyl phosphate [73],... 

Diethyl H-phosphonate is oxidized by permanganate to the corresponding phosphates [74]. The process is pH-dependent and becomes more rapid at higher pH. Monoethyl H-phosphonate is also formed as a product of the subsequent oxidation of the initially obtained diethyl phosphate. 

Trifluoromethanesulfonic acid catalyzes the reaction of phenyl diazomethane with dimethyl H-phosphonate. Diazoacetate and diethyl H-phosphonate react less effectively under similar conditions [76]. 

The reaction of diethyl H-phosphonate with aziridines is reported to proceed without ringopening under Atherton-Todd conditions [97]. 

The phosphoramide undergoes a facile isomerization on heating to give the corresponding phosphate. Amidophosphate obtained by reacting diethyl H-phosphonate in the presence of chloroform and triethylamine does not undergo such isomerization. 

Diethyl H-phosphonate has been added to acrylonitrile in the presence of RONa [146]. 

The Pudovik addition of diethyl H-phosphonate to nitrosubstituted aUcenes of the type Ph2C=CRN02 in DMSO or excess diethyl H-phosphonate yields the aziridine I (R = H, Me, Ph), formed presumably via the azirine II [150, 151],... 

Surface-mediated solid phase reactions are of growing interest [195] because of their ease of set-up and work, mild reaction conditions, rate of the reaction, selectivity, high yields, lack of solvent, and the low cost of the reactions compared to their homogeneous counterparts. Kaboudin et al. have described a method for synthesis of diethyl 1-hydroxyarylmethylphosphonates from aldehydes and diethyl H-phosphonate on a magnesia surface without a solvent [196] (see Appendix). The important features of this... 

Reaction of the 2 -keto nucleoside [214] with diethyl H-phosphonate at -78 °C in the presence of lithium bis(trimethylsily)amide gave the desired 2 -hydroxyl-2 -phospho-nonucleosides as a single diasteieomer in 80% yield [215] (see Appendix). 

Reaction of diethyl H-phosphonate with the 3 -keto derivatives of uridine [216], adenosine [217], and 2 -deoxythymidine [218] furnished in high yield the desired 3 -hydroxy-3 -phosphononucleosides. 

Stoichiometric reactions of diethyl benzoylphosphonate with a variety of amines gave amides 1 as the main products along with diethyl H-phosphonate 2 and a-(phosphoryl-oxy)benzyl phosphonates 3 [235]. The use of hindered diethyl benzoylphosphonate resulted in high yield of amides in the case of primary amines and poorer yields of amides in the case of the reaction with a hindered amine such as diethylamine. 

Carbamoyl phosphonate derivatives of methacrylic acid and ot-methyl styrene were synthesized by reacting dimethyl and diethyl H-phosphonate with the corresponding... 

Dimethyl and diethyl H-phosphonates were used as alkylating agents of polyurethanes... 

The NMR chemical shifts are very sensitive with respect to changes in the electron density at a given carbon atom and provide useful information about differences in the structures of the salts I and II. Thus, the signal of the ot-carbon atom in the sodium salt of monoethyl H-phosphonate (type I) is shifted 2.3 ppm downfield (Table 3.5) with respect to the same signal in diethyl H-phosphonate, which indicates a deaease in its electron density. In contrast, the signal of the ot-carbon atom in the triethyl methylammonium salt of monomethyl H-phosphonate (type n) is shifted 2.1 ppm upfield with respect to dimethyl H-phosphonate as a result of an increased electron density, due to the negative charge delocalization. 

To a solntion of diethyl H-phosphonate (Immol) in anhydrous THE (1 mL) at -78 C, lithium bis(trimethylsily)amide (2 equiv, 1.0 M) in THE under a nitrogen atmosphere was added dropwise via a syringe. After 10-15 min, a solution of keto nucleoside (1 mmol) in... 

MgO (2 g) was added to a stirred mixture of diethyl H-phosphonate (0.02 mol) and aldehyde (0.02 mol) at room temperature. After 2 h, the mixture was washed by dichloromethane (4 x 50 mL) and dried with CaCl2 evaporation of the solvent gave the crnde product. The product was crystallized from CH2CI2 n-hexane (1 2) or distilled under rednced pressure. 

A novel route has been developed for the preparation of a series of diethyl 1-aminoaryl-methylphosphonates. The route involves facile reaction among aromatic aldehydes, diethyl H-phosphonate, and hexamethyldisilazane on the surface of alumina [16],... 

Thus, the aromatic aldehyde 1 is treated with hexamethyldisilazane 2 in the presence of diethyl H-phosphonate 3 on the snrface of acidic alnmina. The prodncts are benzylidene derivatives of 1-aminoarylmethylphosphonate 4. The removal of the benzylidene gronp by treatment of 4 with p-tolnenesnlfonic acid monohydrate in ether and the snbseqnent neutralization of the ammoninm salts 5 with ammonia resulted in 1-aminoaryhnethylphos-phonate 6. A simple set-up, low consumption of solvents, fast reaction rates, mild reaction conditions, good yields, and selectivity of the reaction make this method very attractive. 

Lanthanide triflates were found to be efficient catalysts in the one-pot reaction of aldehydes, amines, and diethyl H-phosphonate to afford a-aminophosphonates in good to excellent yield under mild conditions [20],... 

Aminoethylphosphonic acid (a-alanine analogue) was synthesized reacting acetaldehyde, diethyl H-phosphonate, and ammonia. 

The rather low yields of the aminophosphonic acids can be fairly substantially improved over those reported by Kabachnik and Medved if anhydrons ammonia and the aldehyde are premixed in alcohol solution. Using this procedure, a few amino-substituted phosphonic acids are prepared a-aminobenzylphosphonic acid (benzaldehyde, dibutyl H-phosphonate, solution of dry ammonia in absolute ethyl alcohol) a-amino-propylphosphonic acid propionaldehyde, diethyl H-phosphonate, and a solntion of dry ammonia in absolute ethyl alcohol) p-methoxybenzyl-a-aminophosphonic acid (p-hydroxybenzaldehyde, diethyl H-phosphonate, and solution of dry ammonia in absolute ethyl alcohol). 

The best method for synthesis of various pyridine aminophosphonates is a thermal addition of diethyl phosphonate to pyridine aldimines. Pyridine aldehydes react easily with aliphatic or aromatic amines in toluene solution to form corresponding aldimines (Schiff bases). The obtained imines were reacted in situ with diethyl H-phosphonate to give aminophosphonate diethyl esters [24],... 

The first synthesis of an optically active a-aminophosphonic acid was reported by Gilmore and McBride [25], Diastereoselective addition of diethyl H-phosphonate to imine, derived from enantiomerically pure a-methylbenzylamine, furnished a-aminobenzylphos-phonic acid enantiomers. 

Subsequently, a large number of methods have been developed for the preparation of optically active a-aminophosphonates nucleophilic addition of lithium dibenzyl phosphonate to the spironitrone [26] Lewis add-catalyzed addition of diethyl H-phosphonate to A -galactosyUmine [27] addition of lithium diethyl phosphonate to chiral chelating imines [28]. 

Two aminophosphonic groups have been introduced in the upper rim [32] of the calix[4]arenes, reacting amino-containing calix[4]arenes with diethyl H-phosphonate and a carbonyl compound. 

The addition of diethyl H-phosphonate to symmetrical diimines proceeds stereospecifi-caUy with the predominant formation of one of the two possible diastereomeric forms [50], The addition of diethyl H-phosphonate to the diimines should generate, owing to the... 

The addition of diethyl H-phosphonate to 3,4-dihydroisoquinoline yielded 1,2,3,4,-tetrahydroiosquinoline-l-phosphonic acid [55b],... 

Anthracene-derived tnsfaminophosphonate), l,3-bis[Af-methyl(diethoxyphosphynyl)-l-(9-anthryl)diaminobenzene was synthesized through the addition of diethyl H-phosphonate to the bis-imine, AA -di(9-anthrylidene)-l,3-phenylenediamine 1 [59]. The analysis of the NMR spectra of reaction products revealed that the addition of diethyl H-phosphonate to... 

Trisubstituted-hexahydro-s-triazines reacted with 3 equivalents of diethyl H-phosphonates at 100 °C for 6 h to afford aminomethyldiethylphosphonate [76]. 

Here, we will discuss a few widely utilized methods. The most important method for the preparation of Al-(phosphonomethyl) glycine is from glycine, formaldehyde, tertiary base, and diethyl H-phosphonate in alcoholic solution (see Appendix) [84]. 

Phosphonylmethylaminocyclopentane-l-carboxylic acid 1 was obtained in a good yield of 86% by reacting aminocyclopentane-l-carboxylic acid, cycloleuicin, paraformaldehyde, and diethyl H-phosphonate [92],... 

Diphenyhnethylamine was reacted with formalin to give 2,4,6-tris(benzydryl)hexahy-dro-l,3,5-triazine 1. Addition of diethyl H-phosphonate to 1 gave diethyl N-(diphenyl-methyl)methylphosphonate 2. The oxidation of 2 furnished the imine 3, which was... 

It was found that in the case of diphosphonylation reactions with cyclic aliphatic oximes, diethyl H-phosphonate is the better phosphorus reagent All bisphosphonates thus obtained show diagnostic triplets (/ === 140 Hz) at 57.8-63.6 ppm due to carbons bearing gem-diphosphonate groups in their C H] NMR spectra. 

The reaction between diethyl H-phosphonate and a-chloroketone in the presence of KF resulted in the formation of diethyl-l,2-epoxy-2-propylphosphonate [255],... 

An alternative procedure for the preparation of dialkyl-1,2-epoxyalkylphosphonates includes reaction of diethyl H-phosphonate in methanol with ot-tosyloxy ketones in the presence of DBU (l,8-diazobicyclo[5.4.0]undec-7-ene) [256]. 

---