Halogen substitution, nucleophilic

Construction of isolated or benzannulated five-membered rings of NHPs can be accomplished by means of various condensation or cycloaddition reactions all of which involve interaction of an electrophilic Pj and a nucleophilic C2N2 building block. Salts containing 1,3,2-diazaphospholide anions or 1,3,2-diazaphospholenium cations can be directly accessed by some of these reactions but the products are in most cases neutral 1,3,2-diazaphospholes or NHP. A particularly concerted effort has been directed toward the synthesis of P-halogen-substituted NHP which are capable of undergoing further reactions via halide displacement or halide abstraction and serve thus as entry points for the preparation of a wide variety of neutral and cationic NHP derivatives. 1,3,2-Diazaphospholide anions are normally accessed by deprotonation of suitable iV-H-substituted precursors. 

The transformation of 1,2,4-thiadiazoles bearing a reactive substituent such as amino or halogen group in the 5-position is the most useful method for the synthesis of 5-substituted 1,2,4-thiadiazole derivatives. The latter compounds can be reacted with nucleophiles to afford a wide range of derivatives this is not the case for 3-halogen-substituted compounds. 

In these reaetions, the most reliable mechanism is considered to involve the initial metal-coordination at the nitrogen atom of the pyridine ring and the subsequent attack of an alkyl or aryl anion at the most probable cationic sites on the ring, namely, the 2- and/or 4-position of the ring. If a 2-halogen substituted pyridine is used, the nucleophilic anion attacks the 6-position. Thus, the addition is a more prefered reaction than the ipso-substitution as shown in reaction (29). The substitution of amide or phenyl-... 

Alkyl and aryl derivatives of poly(dichlorophosphazene) are not efficiently synthesized by nucleophilic reaction of LXXXIV with metal alkyls or aryls. The halogen substitution reaction occurs but is accompanied by polymer chain cleavage. Use of poly(difluorophosphazene) or introduction of aryl and alkyl groups at the monomer stage offer some improvement, but neither method is fully satisfactory. The best route to alkyl and aryl derivatives is polymerization of A-(trimethylsilyl)-/).P-dialkyl-.P-halophosphoranimines at moderate temperatures (25-60°C) in the presence of a Lewis acid [Allcock et al., 1996, 2000, 2001a,b Neilson and Wisian-Neilson, 1988]. The reaction proceeds as a cationic chain polymerization ... 

Nucleophilic displacement reactions of some halogen-substituted phenylcyclobutenes [159-161]. 

Reed s group reported the X-ray structures of trialkyl-silicenium ions R3ST6 complexed to low-nucleophilic hexahalo carborane anions90,91. The authors varied systematically both the alkyl substituents R (R = Me, Et, z -Pr and t-Buj and the halogen substitution of the XgCBnlL (X = Cl, Br, I) counterions. The degree of silicenium ion character in the... 

In the context of mechanistic studies, the electrochemical behavior and reactions with nucleophiles of 4-chloro-2,6-diphenylpyrylium and 4-chloro(bromo)flavylium have been studied <1999CHE653>. The proposed mechanism for nucleophilic substitution in halogen-substituted pyrylium and flavylium salts passes through formation of a charge-transfer complex that is converted into an ion-radical pair by simple electron transfer. Heterocyclic cleavage of the C-halogen bond occurs at the stage of the radical or the adduct from the reaction of the pyrylium salt and the nucleophile. In this study, an amine nucleophile was used however, the data are likely relevant for other types of nucleophiles as well (Scheme 5). 

Two types of mechanisms have been proposed for the reactions of carbanions with per-haloalkanes, one ionic and the other a single electron transfer (SET). The ionic mechanism, also termed X-philic 630 or positive halogen substitution (S X)631, is a direct attack of the nucleophile on a positive halogen (equation 80) ... 

Nucleophilic halogen substitution in solutions of halobenzenes containing aliphatic amines has been used by Norseyev and coworkers24-27 to produce astatobenzene and its substituted derivatives. 

The initial stage of this reaction involves a nucleophilic halogen substitution followed by intermolecular redox cyclization of ort/zo-nitrohydrazobcnzcncs [642], Instead of halogen the substrate can contain another group (N02, OAlk) [643-645], It has been shown that in ethanol the aforementioned reaction proceeds with the formation of 2//-benzotriazole nitro derivatives, whereas in acetic acid their IV-oxides are formed and, when boiled in ethanol, turn into the final products (Scheme 2.123) [637, 638, 646],... 

Although aryl halides are generally inert to nucleophilic substitution, aryl halides that also contain a nitro group ortho or para to the halogen undergo nucleophilic aromatic substitution, as shown in the following example. 

Under this heading it is convenient to discuss not only reactions of the amide ion, NHJ, but also some reactions of ammonia and halogen-substituted ammonia with hypochlorous acid, hydroxide ion and with other nucleophiles. 

The cyano group in position 4 of quinazolines behaves like a halogen towards nucleophilic reagents and can be displaced by a hydroxide anion, alkoxides, amines, hydrazines, and various carbon nucleophiles, o.g. ketones, a-keto esters, dialkyl malonates, nitroalkanes, Gri-gnard reagents, and enamines, to give 4-substituted quinazolines 1. The cyano group of quin-azoline-2-carbonitriles is less reactive for nucleophilic substitution but its displacement has not been intensively studied. Alkaline or acid hydrolysis of quinazoline-4-carbonitriles affords quinazolin-4(3// )-oncs. ... 

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