Reactivity of the Nitrogen

In order to study the reactivity of the nitrogen atom in saccharidic OZT moieties Rollin and co-workers13,55 explored some standard reactions IV-acylation, IV-sulfonylation, IV-vinylsulfonylation by Michael addition, reductive elimination, conjugated addition and cycloaddition. 

Due to the low reactivity of the nitrogen, incorporation of the pyroglutamic acid into endo-positions by stepwise chain elongation is difficult (see reft49 and refs cited therein). It may be achieved using suitably protected aminoacyl-pyroglutamic acid derivatives as dipeptide synthons. These are accessible in satisfactory yields, e.g. by acylation of pGlu-OBzl with N-protected amino acid pentafluorophenyl esters in the presence of NaH or LiHMDS. 49 ... 

A unique feature of phosphaadamantane is the reactivity of the nitrogen with alkylating agents such that ammonium salts are formed preferentially to phosphonium salts. The synthesis of the methylammonium salt of PTA as well as the phosphine oxide, 0=PTA, are described below. The latter is achieved by the reaction of PTA with 30% H202. This harsh reagent is necessary because of the resistance of PTA, as well as its nitrogen analog, hexamethylenetetraamine, to mild oxidants. 

The influence of substituents, including aza, on reactivity of the nitrogen atom in such systems have been considered in detail1 6,7,47 102,188 189 and may be correlated with Dewar—Grisdale calculations [Eq. (2)],6 33-190-192 or dual-substituent parameter [Eqs. (3) and (4)].6,7,47,188-190 Thus, analysis6 of pXa s (HzO, 25°) of substituted quinolinium and isoquinolinium cations according to Eq. (20) gave the results shown in Table V, where they are compared with those for substituted naphthoic acids (aq. EtOH, 25°). 

It should be clear that the reactivity of amines normally involves some process in which a bond is made to the unshared electron pair on nitrogen. Therefore any reaction of an amine that reduces the reactivity of this electron pair should reduce the reactivity of the nitrogen atom. The simplest way to do this would be to convert the amine to an ammonium salt with an acid. Protonation amounts to protection of the amine function ... 

In contrast with the above discussion, a radical itself (rather than a radical acceptor) can be activated by complexation with a Lewis acid. The aminyl radical cycliza-tion shown in Eq. (304) is a slow process and yields of the cyclic product are often low. It is, however, known that a Brpnsted acid promotes this cyclization [676], and by analogy the reaction proved to be promoted by the addition of a Lewis acid, which should coordinate with the nitrogen atom to increase the reactivity of the nitrogen radical. The effect of a series of titanium salts, Ti(0-i-Pr) CL , at a concentration of 0.025 M, is shown in Eq. (304). It is apparent that use of Ti(0-i-Pr)Cl3 resulted in significantly improved yield. 

A low reactivity of the nitrogen in the 2-position is noticeable, as pointed out in ref. [236] (failure to acylate with Fmoc-Gly) and ref [230] (derivatiza-tion with alkylating reagents such as a-bromomethyl acetate achieved no vahdation of the reaction with a wide series of substrates). 

Recent advances in the Staudinger reaction of tertiary phosphines with azido compounds have been reviewed.The reaction of the alkynylphosphine (88) with phenylazide yields the unstable intermediate (89), which in the presence of protic substances undergoes nucleophilic addition to the triple bond. The reactivity of the nitrogen-silicon bond of the phosphinimine derived from triphenylphosphine and trimethylsilylazide has been exploited in reactions with chloroformyl reagents to generate new functionalised phosphinimines, e.g., (90). ... 

An interesting observation was reported by Deady who advocated a lone-pair cooperativity in the N-alkylation of some N,N -bridged 2,2 -bii-midazoles. The second order rate constants of alkylation are in the order 525 > 524 > 523. Bridging has a considerable effect on the reactivity of the nitrogen atom (81AJC2569). Such a quantitative study would be interesting on other ortho-orthc/-Mnked azaheterocycles. 

The diazonium ions formed from aminoazoles are relatively strong acids. The pa s values of five di-, tri- and tetrazolediazonium ions are reported to be between 3 and 4, i.e. about 10 units lower (more acidic) than those of the respective unsubstituted heterocycles (Vilarrasa and coworkers ). Therefore, deprotonation of the diazonium ion is easy and, depending on reaction conditions, yields either the diazonium salt or its conjugate base, i.e. the diazo compound. The electrophilic reactivity of the nitrogen atom in the diazo group of the base is lower than the reactivity of the diazonio group of the cation. ... 

The higher reactivity of the nitrogen compounds in the mixture indicates that they occupy the majority of the catal5dic centers and hinder the reaction of the sulfur compounds by blocking the adsorption sites. 

The nucleophilic reactivity of the nitrogen atoms in thioureas towards carbonyl compounds has been further exemplified by some recently described addition and addition-elimination reactions of thioureas with aldehydes. The same reactivity also played an important part in recent syntheses of heterocyclic compounds containing the thioureido-grouping. ... 

To solve the first challenge, the structure of the carbamate was tuned to optimal reactivity of the nitrogen-centered radical. Ultimately, a trifluoroethyl carbamate 7 proved to affect the desired intra-molecular C—H functionalization most productively. Investigations into the second challenge established that silver carbonate ensured the carbamate cyclized through the carbonyl oxygen atom, rather than the carbamate nitrogen atom. 

It is well known that the attempts to transform laudanosoline (199, 200) or iV-norlaudanosoline (201) into aporphine bases by oxidation have failed instead compounds with a dibenzopyrrocoline structure (CXXXIX) were obtained. Franck and Schlingloff (202) found that if the reactivity of the nitrogen atom is eliminated by quaternization, then the mild oxidation of laudanosoline methiodide (CXL) with ferric chloride in aqueous solution affords in 60% yield the aporphine base... 

Nitrogen monoxide, NO (nitrogen oxidation number -i-2), is one of the most reactive of the nitrogen oxides. It is an odd-electron molecule and is therefore paramagnetic it has a bond order of 2. ... 

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