Nucleophilic nitrogen

Reagents i, MeaSiCl, EtjN, ZnCl, PhH ii, MeOCH CHjOMe, CCljCO Na iii, MeNH iv, BujSnH 

Reagents i, SnCl2, HCl, THF ii, LiAlH4, Et O iii, KMn04 iv, MeSO CHiNa, DMSO, Mel 

Procedures for the conversion of the readily available nitrile (52) into 4-aza-homoadamantanes, e.g. (53), and alternative procedures, avoiding the use of mercury salts, for the conversion of pinenes into 1-aza-adamantanes are noted. 

Synthesis by Other Cyclization Reactions. Rearrangement of intermediates generated by photolysis of azides has provided an important route from 1-azidoadamantane to aza-homoadamantanes. Now full details have been given 

Pancrazi, I. Kabore, B. Delpech, and Q. Khuong-Huu, Tetrahedron Lett., 1979, 3729. 

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Other interesting regioselective reactions are carried out within the synthesis of nitrofurantoin. Benzaidehyde semicarbazone substitutes chlorine in chloroacetic ester with the most nucleophilic hydrazone nitrogen atom. Transamidation of the ester occurs with the di-protic outer nitrogen atom. Only one nucleophilic nitrogen atom remains in the cyclization product and reacts exclusively with carbonyl compounds. 

This section is organized according to the electrophilic center presented to the nucleophilic nitrogen of the active species. This organization allow s a consistent treatment of the reactivity. However, a small drawback arises when ambident electrophilic centers are considered, and these cases are treated as if the more reactive center were known, which is not always the case. 

The rearrangement of thiophenes to the isomeric pyrroles has proven synthetically useful (Schemes 98a and 98b). In the absence of a suitable internal nucleophilic nitrogen, so-called degenerate ring transformations may occur (Schemes 98c and 98d). 

BMI was also used as a crosslinking agent for poly(iminoethylene). The Michael addition takes place with the nucleophilic nitrogen of the imino group and the double bonds of the electrophilic BMI. The Michael addition of BMI is now adopted as a crosslinking reaction for polymers with amino end groups [2]. 

As shown by Heindel and Corley (1979), ring closure also takes place if the nucleophilic nitrogen is part of a heterocycle, as in the diazotization of 5-amino-3-methyl-2-H-l,2,4-benzothiadiazine-l, 1-dioxide (6.50). In the tricyclic compound 6.51 formed initially, the thiadiazinedioxide ring is opened rapidly in water, forming 1-acetyl-7-aminosulfonyl-l-i/-benzo-l,2,3-triazole (6.52). 

Figure 17.18 The Staudinger ligation reaction uses a modified phosphine derivative containing an electrophilic group that acts as a trap for the nucleophilic nitrogen in the intermediate aza-ylide. The resultant shift yields an amide bond derivative between the phosphine-containing molecule and the azide-containing molecule.

Figure 17.23 A traceless Staudinger ligation process involves the formation of an intermediate aza-ylide with subsequent attack of the nucleophilic nitrogen atom on the neighboring electrophilic group. The formation of an amide bond then occurs concomitant with the loss of the phosphine component, thus forming a zero-length crosslink between the two molecules.

The irradiation of 5-amino-l,2,4-oxadiazoles 60 in the presence of nucleophilic nitrogen sources (primary amines, ammonia or hydrazine) produced l,2,4-triazolin-5-ones 62, a process which proceeds via cleavage of the N-O bond and addition of the nucleophile to form the intermediate 61 (Scheme 3) <1996JOC8397>. 

The reaction of phenylhydrazones with butadiene was carried out by Baker on the basis of the idea that phenylhydrazones have both nucleophilic nitrogen and electrophilic carbon. Products 77-79 were obtained by the reaction of phenylhydrazones with Pd(PPh3)4 (81) ... 

Aryl and alkyl hydroxylations, epoxide formation, oxidative dealkylation of heteroatoms, reduction, dehalogenation, desulfuration, deamination, aryl N-oxygenation, oxidation of sulfur Oxidation of nucleophilic nitrogen and sulfur, oxidative desulfurization Oxidation of aromatic hydrocarbons, phenols, amines, and sulfides oxidative dealkylation, reduction of N-oxides Alcohol oxidation reduction of ketones Oxidative deamination... 

The FAD-containing monooxygenase catalyzes oxidation of nucleophilic nitrogen and sulfur atoms in a diverse array of organic compounds. The enzyme... 

FAD dependent oxidation of nucleophilic nitrogen, sulfur and phosphorus heteroatoms, e.g. conversion of nicotine to nicotine l -iV-oxide, cimetidine to cimetidine S-oxide... 

Figure 11.9 Biuret reaction. The coordination complex formed in alkaline solution between cupric ions and the nucleophilic nitrogen atoms in four molecules of biuret.

Table 19 The incoming nucleophile nitrogen KIEs found for Menshutkin reactions with various amines in several solvents.

Table 23 The secondary a-deuterium and incoming nucleophile nitrogen KIEs found for the Sn2 reactions between p-substituted N,/V-dimethylanilines and methyl iodide in ethanol at 25°C.a...

Table 24 The calculated and experimental incoming nucleophile nitrogen, a-carbon and secondary a-deuterium KIEs for the SN2 Menshutkin reactions between p-substituted iV.jV-dimethylanilines and methyl iodide at 298 K.°...

The anodic oxidation of nitrogen compounds provides an excellent example of how the use of electrochemistry can alter the way in which we view the syntheses of complex organic molecules. Currently, there are two main thrusts to these efforts. First, the oxidation reactions allow for a reversal in the polarity of known functional groups, and therefore molecules with nucleophilic nitrogens can he converted into electrophiles. Second, the oxidation reactions allow for the selective... 

Methyl tricyclo[4.1.0.0 ]heptane-l-carboxylate gives a cation-radical in which the spin density is almost completely localized on C-1 while the positive charge is on C-7. The revealed structural feature of the intermediate cation-radical fairly explains the regioselectivity of N,N-dichlorobenzenesulfonamide addition to the molecular precursor of this cation-radical. In the reaction mentioned, the nucleophilic nitrogen atom of the reactant adds to electrophilic C-7, and the chlorine radical attacks C-1 whose spin population is maximal (Zverev and Vasin 1998, 2000). 

Concerning the mechanism of the rearrangement, it is proposed to involve the addition of the nucleophilic nitrogen of the 1,3-ambident nucleophiles to C-6 (see Section III,A,2,a). This covalent adduct is in equilibrium with the open-chain diamidino compound 83 (R = OCH3, SCH3). Cycliza-tion into 84, followed by a base-catalyzed fragmentation of the nitrogen-carbon bond at N-3 and expulsion of the thiomethyl or methoxy anion, yields the 2-amino-4(5)-phenylpyrimidines (Scheme III.47). 

The first class of amine-based nucleophilic catalysts to give acceptable levels of selectivity in the KR of aryl alkyl. yec-alcohols was a series of planar chiral pyrrole derivatives 13 and 14, initially disclosed by Fu in 1996 [25, 26]. Fu and co-workers had set out to develop a class of robust and tuneable catalysts that could be used for the acylative KR of various classes of. yec-alcohols. Planar-chiral azaferrocenes 13 and 14 seemed to meet their criteria. These catalysts feature of a reasonably nucleophilic nitrogen and constitute 18-electron metal complexes which are highly stable [54-58]. Moreover, by modifying the substitution pattern on the heteroaromatic ring, the steric demand and hence potentially the selectivity of these catalysts could be modulated. 

These structural modifications provided a well-differentiated and highly tuneable chiral environment in the vicinity of the nucleophilic nitrogen as shown by the promising selectivities observed in the KR of 1-phenyl- and 1-naphthylethanol. Indeed,... 

Based on the observation that the majority of secondary amines shown to be effective in iminium ion catalysed transformations were cyclic five-membered nitrogen containing heterocycles, it was postulated that a highly nucleophilic nitrogen was central to catalytic activity [44]. This proposal was reinforced by the discovery that secondary amines with a-heteroatoms (a-effect nucleophiles) provided an effective platform for the acceleration of iminium ion catalysed... 

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