Heteroatom Displacement

NaNHTs For carbon nucleophiles, see page 236, Section 8, 

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Many nucleophiles we haven t mentioned can be used in these reactions. In every case a nucleophilic heteroatom displaces a leaving group from a compound derived from an alcohol. 

Subsequent work by Ruwet and co-workers proposed something similar to the proposal 1 mechanism, albeit they did not think that the phenolate ester rearranged via a Fries reaction. Ruwet and co-workers studied the heteroatom displacement of the phenol oxygen with S and Se. They suggested that the first step could be esterification followed by nucleophilic attack of the phenol on the more electrophilic carbon of the ketone moiety. Ruwet and co-workers prepared the phenolate 22a-c from the diketene and the corresponding phenols la-c. Treatment of la-c (X = O, S or Se) and diketene 21 with PPA (polyphosphoric acid) did indeed provide the chromone 23a-c in about 40% yield.This was the first reported use of PPA for this transformation. 

Structural parameters in aromatic five-membered rings are shown in Table 2. All the C—H distances are near 107.5 pm, close to the C—H link in ethylene. With heteroatoms at adjacent ring positions, the C—H groups are displaced from the bisector of the ring angles toward the adjacent heteroatom (74PMH(6)53). 

Electrophiles, such as C—Hal functions, contained in side chains may be well positioned for interaction with ring heteroatoms. Thus, Af-t-butyl-2-tosyloxymethylaziridine in ethanol displaces tosylate ion from the side chain, and nucleophilic opening of the resulting azabicyclobutanonium ion by solvent gives 3-hydroxy- and 3-ethoxy-azetidine (Section 5.09.2.3.2). 

Formation of One Bond between Carbon and a Heteroatom S.03,2.2.1 Displacement reactions... 

Displacement reactions involving a heteroatom and a carbon atom are very common in the synthesis of heterocyclics of many sizes. Most often, the heteroatom functions as a... 

CENTRAL RING CONTAINING ONE HETEROATOM Reaction of 2-bromobenzoic acid (1) with chloroSulfonic acid proceeds to afford the sulfonyl chloride 2 treatment with dimethylamine leads to the corresponding sulfonamide (3). Condensation of bromoacid 3 with the anion from thiophenol in the presence of copper powder results in displacement of halogen by sulfur... 

Allylic nitro groups are readily displaced by nucleophiles via an SNl-type mechanism. Thus, nitro groups with heteroatoms at the OC- or P-positions (for example, a- or P-nitrosulfides) are expected to be cleaved in a similar way. In fact, the nitro group in a-nitrosulfides is replaced by nucleophiles in the presence of a Lewis acid31 or acetic acid.32 The nitro groups in the reaction of Eqs. 7.27 and 7.28 are cleanly replaced by CN, allyl, or PhS group on treatment with MejSiY (Y = CN, allyl) in the presence of SnCl4 or simple treatment with PhSH in AcOH. 

Halide displacement from the carbene ligands of Ru, Os, and Ir halocarbene complexes by N-, O-, and S-based nucleophiles frequently leads to the formation of new heteroatom-substituted carbene complexes. This important class of reactivity will be discussed in more detail in Section V,D, but it is appropriate here to illustrate the scope of this method with several examples ... 

The second salient feature of heterocycles is the marked activation at positions a- and y- to the heteroatom. For N-containing heterocycles, the presence of the N-atom polarizes the aromatic ring, thereby activating the a and y positions, making them more prone to nucleophilic attack. The order of SNAr displacement of heteroaryl halides with EtO is [14] ... 

A review of the reaction of nitroalkanes RNO2 with carbon and heteroatom nucleophiles X to yield RX has appeared438. The nucleophilic displacement of a nitro group in benzylic and tertiary nitroalkanes by a thiophenyl group is exemplified in equation 130439. 

In contrast with aliphatic nucleophilic substitution, nucleophilic displacement reactions on aromatic rings are relatively slow and require activation at the point of attack by electron-withdrawing substituents or heteroatoms, in the case of heteroaromatic systems. With non-activated aromatic systems, the reaction generally involves an elimination-addition mechanism. The addition of phase-transfer catalysts generally enhances the rate of these reactions. 

Another traditional method used for polymer support characterization is elemental analysis. Its use as an accurate quantitative technique for monitoring solid-phase reactions has also been demonstrated [146]. Microanalysis can be extremely valuable if a solid-phase reaction results in the loss or introduction of a heteroatom (usually N, S, P or halogen). In addition, this method can be used for determination of the loading level of a functional group (e. g. usually calculated directly from the observed microanalytical data). For example, in many cases, the displacement of chloride from Merrifield resin has been used as a guide to determine the yield of the solid-phase reaction. 

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