Ammonium phosphoramidate

Phosphoryl triamide, PO(NH2)3, can be made by the direct reaction of liquid ammonia with phosphoryl chloride (7.48), or with triphenyl phosphate (7.64). It forms colourless needles which are very soluble in water, but insoluble in most organic solvents. Prolonged heating results in transformation into polymeric material. Dilute acid hydrolysis or atmospheric moisture will yield mono-ammonium phosphoramidate, while with dilute NaOH, sodium phosphorodiamidate is formed (7.65)... 

The preparation of novel phase transfer catalysts and their application in solving synthetic problems are well documented(l). Compounds such as quaternary ammonium and phosphonium salts, phosphoramides, crown ethers, cryptands, and open-chain polyethers promote a variety of anionic reactions. These include alkylations(2), carbene reactions (3), ylide reactions(4), epoxidations(S), polymerizations(6), reductions(7), oxidations(8), eliminations(9), and displacement reactions(10) to name only a few. The unique activity of a particular catalyst rests in its ability to transport the ion across a phase boundary. This boundary is normally one which separates two immiscible liquids in a biphasic liquid-liquid reaction system. 

In contrast to some related reviews, which use reaction class or electrophiles as organizational elements, this chapter is divided into three main sections according to catalyst class (i) Bronsted acid catalysis by phosphoric acid and phosphoramide derivatives, (ii) N—H hydrogen bond catalysis by organic base and ammonium systems, and (iii) combined acid catalysis including Bronsted-acid-assisted Bronsted acid, Lewis-acid-assisted Bronsted acid, and Lewis-acid-assisted Br0nsted acid systems (Figure 5.1). 

Ammonium hydrogen phosphoramidate (11.4 g., 0.1 mole) is dissolved in 20 ml. of 50% potassium hydroxide solution and warmed to 50-60° for 10 minutes to expel ammonia. The solution is cooled to 5-10°, neutralized to pH 6 (Alkacid test paper) with glacial acetic acid, and treated with 1 1. of ethanol to precipitate the potassium salt which is filtered with suction, washed successively with alcohol and ether, and air-dried. Yield is 8.1 g. (60%). Anal. Calcd. for KHP03NH2 N, 10.37 P, 22.93. Found N, 10.4 P, 22.7. 

Ammonium hydrogen phosphoramidate forms colorless monoclinic crystals that appear to be orthorhombic. The powder x-ray diffraction2 and infrared absorption3 data have been reported. The salt is stable and nonhygroscopic, is moderately soluble in water, and melts at 233-234°. 

Phosphoramidic acid forms colorless, prismatic crystals the x-ray diffraction2 and infrared absorption4 data have been reported. The compound is easily soluble in water, but the aqueous solution hydrolyzes to ammonium dihydrogen phosphate. It is stable in sealed containers, but it converts on heating to an ammonium polyphosphate.5 An unstable monohydrate of phosphoramidic acid has been described.2... 

One of the two hydrogen atoms of phosphoramidates can be temporarily blocked with a trimethylsilyl group. The sodium salt of diethyl V-(trimethylsilyl)phosphoramidate (102) reacted with alkyl bromides in benzene in the presence of 10 mol % of tetra-n-butylammonium bromide to afford, after desilylation, the corresponding V-alkyl derivatives (103) in 79-95% yields for primary alkyl halides. Secondary alkyl halides gave poor results (Scheme 43). The addition of the quaternary ammonium salt is essential to promote the alkylation reaction. Hexamethyldisilazane and its cyclic analogs can also be utilized in the preparation of amines under moderate conditions (Scheme 43). ... 

Phosphorylation. Chambers et al. found the reagent useful for the preparation of nucleoside diphosphoric acids (3, R —adenine, uracil, etc.). A nucleotide (I) is converted into the 5 -phosphoramidate (2) by reaction with ammonia and dicyclo-hexylcarbodiimide (DCC), and the amidate (2) is treated with dioxane diphosphate in o-chlorophenol (3 hrs..0 ). The diphosphoric acid (3) is precipitated with petroleum ether and purified as the ammonium salt. Yields are around 90%, whereas when 8.5% phosphoric add was used yields were in the order of 50-60%. However, anhydrous... 

Cyclic Esters of Phosqphorous Acid.— The cyclic aminophosphite (90), prepared from the corresponding halohydrin and the phosphoramidate (89), slowly forms the novel ammonium salt (91). Both spectroscopic and chemical evidence appear to support the ionic structure over the alternative (92). 

The preparation of (Rp) and (Sp)-N, N, O -tribenzoyladenosine 3, 5 -phosphoranilidates (96) has been greatly improved by treating the cyclic phosphate (97) with oxalyl chloride and a catalytic amount of DMF, rather than the triphenylphosphine-carbon tetrachloride mixture (Appel reaction) used previously, followed by addition of aniline. 5 near-quantitative yield of (97) obtained as a mixture of diastereoisomers is easily separated. The cyclic phosphoramidates (98-100) have also been obtained in improved yield by treating cAMP with a mixture of phosphoryl chloride and trimethyl phosphate (which had previously been pretreated with one-half a molar equivalent of water) at 0°, followed by ammonium carbonate or the appropriate amine. x e (Sp)-diastereoisomers are formed in excess, e.g. for (100) yields of 13 % of the Rp-isomer and 54 % of the Sp-isomer are obtained, and the proportion of Rp-product decreases further if pre-treatment with... 

The potential utility of o-nitrobenzyl as a photocleavable nitrogen protecting group for indoles, benzimidazole and 6-chlorouracil has been evaluated. Simple photolyses of the protected molecules at 300 nm afford good yields of the starting materials. Nitrobenzyl-based phosphoramide mustards (94) with various substituents (R, R, R ) have been developed as potential prodrugs for cancer therapy. UV and P NMR spectroscopy showed that the phosphoramide mustard was quickly liberated upon irradiation with mercury arc lamps. 2-Nitro-benzyl quaternary ammonium derivatives of norbutyrylcholine (A,iV-dimethyla-minoethyl butyrate) have been synthesized and assessed as photolabile inhibitors... 

Phosphoramidic acid is somewhat stronger than phosphorodiamidic acid (Table 5.24). If phosphoramidic acid is heated for several hours at 100°C, it isomerises to a very soluble ammonium polyphosphate, by a process which is probably connected with zwitterion formation (7.59). If carbon dioxide is passed into a solution of Na2P03NH2, the relatively insoluble monosodium salt is obtained, which contains the zwitterion (7.60a). Isoelectronic sulphamic acid (7.60b) also exists as a zwitterion [9]. 

Condensed phosphoramides with linear, cyclic, or cross-linked structures are produced by the reaction of POCI3 with ammonia. The higher molecular weight products are insoluble in water and on fnrther heating are converted to a cross-linked insoluble polymer, phosphorus oxynitride (PON)j (25). Phosphorus oxynitride can be made by prolonged heating of melamine phosphates (26), urea phosphate (26), or ammonium phosphate imder conditions where ammonia is retained (27). Phosphorus oxynitride is an effective flame retardant in those polymers, such as nylon 6, which can be flame retarded by exclusively char-forming condensed-phase means. However, phosphorus oxynitride is ineffective (at least by itself) in those... 

An achiral quaternary ammonium salt such as tetrabutylammonium bromide exerts a synergistic effect on addition of diethylzinc to aldehydes catalysed by a chiral phosphoramide. In the presence of 10mol% tetrabutylammonium bromide, the 0 chiral catalyst can be lowered from 10 to 0.5 mol%, while retaining reactivity and ee. 

The synergistic effect of achiral quaternary ammonium salt on asymmetric additions of diethylzinc to aldehydes catalysed by chiral phosphoramide-Zn(II) complex has been demonstrated. The addition of 10mol% NBU4X can dramatically reduce the loading amount of chiral ligand (up to 0.5 mol%) without loosing the excellent reactivity and enantioselectivity of the asymmetric reaction. 

Tanaka et al. [8] proposed a very elegant strategy based on porphyrins peripherally modified with dibenzol[24]crown-8 and a secondary ammonium ion, able to form rotaxanes. In fact, the interaction of a porphyrin with a phthalocyanine lead to the formation of a stable jt-stacked pseudo-rotaxane after end-capping the ammonium chains by reaction with Staudinger-phosphite in chloroform, followed by metallation with Cu(II). In acidic media, the ammine and phosphoramide groups are protonated generating a tetracationic species that can form ion-pairs with the tetraanionic [Cu-TSPP] species [9]. 

General procedure for the synthesis of a-aminophosphonates using chiral phosphoramidate auxiliaries In a dry vial, under inert gas protection, diethyl H-phosphonate (1.5 mmol) was dissolved in 3 mL of THF. The vial was cooled to —78 °C and into the resulting solution LHMDS (1.5 M in THF, 1.5 mmol) was added dropwise. The reaction solution was stirred at —78 C for 15 minutes, and corresponding chiral A -phosphoryl imine (e.g., 98, 1.00 mmol in 3-mL THF) was added to the reaction mixture at 78 C. The reaction mixture was stirred for another 2 hours before it was quenched by adding saturated ammonium chloride... 

---