Nitrogen-substituted compounds

Hydrolysis of phosphoramidic acid (NH2-P03H2) has been studied in the acidity range pH 2-8, in aqueous solution and in some mixed solvents. Reaction appears to occur through the mono-anion, the neutral molecule and through a protonated species (rate equation (1) and Table 13). 

RATE COEFFICIENTS AND PRODUCTS FOR REACTION OF PHOSPHORAMIDIC ACID 

With aqueous methanol, a simple mixture equation (2) 

RATE COEFFICIENTS FOR REACTION OF THE MONO-ANION OF PHOSPHORAMIDIC ACID WITH VARIOUS BASES AT 25 °C  

Other related examples of nucleophilic attack at phosphorus for which some kinetic information is available are reactions of the N-substituted phosphoro-amidates and phosphoradiamidates and of the methyl phosphoroazidate 

---

Although the generation of the corresponding a-nitrogen-substituted compound can be achieved in general in a highly enantioselective manner, a complication can result from the observation that the stereochemical outcome of the reaction with electrophiles (i.e. retention or inversion) depends on the nature of the electrophile and is not always uniform. The chemistry of lithiated carbamates has been reviewed in a comprehensive manner. ... 

In addition since the reaction of 2-oxoethyl - phosphonate with amines showed a preferential formation of an enaminophospho-nate, we used that structure for the production of specifically nitrogen substituted compounds by the following sequence of reactions (11). 

Reaction takes place on nitrogen when the electrophilic center is an sp carbon, particularly if it is charged. Thus Mannich reaction yields the N-substituted compound (71 and 72) (Scheme 34) (54. 157-159). The same reaction is reported with piperidine, o-toluidine. and methylaniline (158). 

Carbon—nitrogen double bonds in imines, hydrazones, oximes, nitrones, azines, and substituted diazomethanes can be cleaved, yielding mainly ketones, aldehydes and/or carboxyHc acids. Ozonation of acetylene gives primarily glyoxal. With substituted compounds, carboxyHc acids and dicarbonyl compounds are obtained for instance, stearoHc acid yields mainly azelaic acid, and a smaH amount of 9,10-diketostearic acid. 

Hydroxypyrroles. Pyrroles with nitrogen-substituted side chains containing hydroxyl groups are best prepared by the Paal-Knorr cyclization. Pyrroles with hydroxyl groups on carbon side chains can be made by reduction of the appropriate carbonyl compound with hydrides, by Grignard synthesis, or by iasertion of ethylene oxide or formaldehyde. For example, pyrrole plus formaldehyde gives 2-hydroxymethylpyrrole [27472-36-2] (24). The hydroxymethylpyrroles do not act as normal primary alcohols because of resonance stabilization of carbonium ions formed by loss of water. 

Diaziridines also show slow nitrogen inversion, and carbon-substituted compounds can be resolved into enantiomers, which typically racemize slowly at room temperature (when Af-substituted with alkyl and/or hydrogen). For example, l-methyl-3-benzyl-3-methyl-diaziridine in tetrachloroethylene showed a half-life at 70 °C of 431 min (69AG(E)212). Preparative resolution has been done both by classical methods, using chiral partners in salts (77DOK(232)108l), and by chromatography on triacetyl cellulose (Section 5.08.2.3.1). 

The rupture of the oxazirane ring at the ON-bond occurring with acid treatment of the alkyl-substituted compounds is probably the result of an electronic shift initiated by the protonated oxygen (arrows as in 21). In principle, a similar rearrangement of the electronic system should also be possible initiated from the nitrogen end (22), Indeed, decomposition products similar to those of the... 

A compound in which the —OH group of an acid is replaced by —NH2 is called an amide. When the —OH is replaced by —NHR, the product is called a nitrogen-substituted amide or, abbreviated, an N-substituted amide. One way to make amides is to react ammonia (or an amine) with an ester ... 

There is considerable multiple character in the carbene carbon-X(Y) bonds. An internal comparison of carbon-X(Y) bond lengths in each of the structures tabulated reveals a substantial shortening of carbene car-bon-X(Y) relative to other carbon-X(Y) bonds in the molecule. Carbene carbon-nitrogen distances are found to be shorter in the mono-N-substituted carbenes than in the bis-N-substituted compounds. 

Since the methoxyl group attached to the carbon adjacent to nitrogen can be readily replaced by various carbon nucleophiles, a-methoxylated carbamates are useful intermediates for the syntheses of nitrogen-containing compounds. The electrochemical oxidation of silyl-substituted carbamates provides a highly regioselective route to these useful compounds. 

Nitrogen compounds are also effective as nucleophiles in the anodic oxidation of silyl-substituted ethers. The electrochemical oxidation in the presence of a carbamate or a sulfonamide in dry THF or dichloromethane results in the selective cleavage of the C-Si bond and the introduction of the nitrogen nucleophile at the carbon (Scheme 21) [55]. Since a-methoxycarbamates are useful intermediates in the synthesis of nitrogen-containing compounds [44], this reaction provides useful access to such compounds. Cyclic silyl-substkuted ethers such as 2-silyltetrahydrofurans are also effective for the introduction of nitrogen nucleophiles. The anodic oxidation in the presence of a carbamate or a... 

A few nitrogen-substituted allenes themselves are known as biologically active compounds [154], For example, the 9-(4 -hydroxy-1, 2 -butadienyl)adenine (268a) was found to inhibit in vitro replication and cytopathic effects of human immunodeficiency viruses HIV-1 and HIV-2 [155], More recently, an increase in the anti-HIV activity in cell cultures using the adenallene phosphotriester derivative 268b was reported (Scheme 8.72) [156]. 

In contrast to the rich chemistry of alkoxy- and aryloxyallenes, synthetic applications of nitrogen-substituted allenes are much less developed. Lithiation at the C-l position followed by addition of electrophiles can also be applied to nitrogen-containing allenes [10]. Some representative examples with dimethyl sulfide and carbonyl compounds are depicted in Scheme 8.73 [147, 157]. a-Hydroxy-substituted (benzotriazo-le) allenes 272 are accessible in a one-pot procedure described by Katritzky and Verin, who generated allenyl anion 271 and trapped it with carbonyl compounds to furnish products 272 [147]. The subsequent cyclization of 272 leading to dihydro-furan derivative 273 was achieved under similar conditions to those already mentioned for oxygen-substituted allenes. 

---