Reactions with Nucleophiles giving Substitution Products

D. Reactions with Nucleophiles giving Substitution Products... 

Most of the other silylation-activation-substitution reactions reported in this review are mechanistically related. Several new reactions (such as those discussed in Sections 7.1, 7.2, and 7.4) have been discovered by following these hnes of thinking about activation of functional groups by O-silylation and subsequent or concomitant reaction with nucleophiles giving the expected products and hexamethyldisiloxane 7. It can thus be expected that current and new silylation-activation reactions will be more commonly used in preparative chemistry in the future. 

The products [54] are useful organic intermediates and have a very large scope in reactions (Johnson, 1969). For example, reaction with nucleophiles gives the parent heterocycle and an a-substituted ketone. 

Compounds i and ii (PNP = p-nitrophenyl) undergo reactions with neutral and anionic nucleophiles giving substitution products. The reactions are second order with a first-order dependence on nucleophile, consistent with an S m2 mechanism. However, reasonable Sn-I mechanisms can be written, given that the leaving groups are very good. 

Nucleophilic Substitutions of Benzene Derivatives. Benzene itself does not normally react with nucleophiles such as haUde ions, cyanide, hydroxide, or alkoxides (7). However, aromatic rings containing one or more electron-withdrawing groups, usually halogen, react with nucleophiles to give substitution products. An example of this type of reaction is the industrial conversion of chlorobenzene to phenol with sodium hydroxide at 400°C (8). 

Substitution of an additional nitrogen atom onto the three-carbon side chain also serves to suppress tranquilizing activity at the expense of antispasmodic activity. Reaction of phenothia zine with epichlorohydrin by means of sodium hydride gives the epoxide 121. It should be noted that, even if initial attack in this reaction is on the epoxide, the alkoxide ion that would result from this nucleophilic addition can readily displace the adjacent chlorine to give the observed product. Opening of the oxirane with dimethylamine proceeds at the terminal position to afford the amino alcohol, 122. The amino alcohol is then converted to the halide (123). A displacement reaction with dimethylamine gives aminopromazine (124). ... 

These results show that cyclohexenyl iodonium salt readily gives cyclohexenyl cation under poorly nucleophilic/basic conditions. When a stronger nucleophile like bromide is added to the solution of 3, 1-bromocyclohexene 13 is formed as a main product (eq 5). It is noteworthy here that the rate of the reaction is strongly retarded by the added bromide salt as a nucleophilic reagent (Figure 1), although bromide does react with the substrate to give substitution product 13.6... 

Substituted quinoxalines undergo unusual reactions with nucleophiles. Thus, 2,3-diphenyl-6-nitroquinoxaline (67) with potassium cyanide undergoes substitution in the 5-position, with simultaneous nucleophilic displacement of the 6-nitro group by the methanol solvent to give compound 68 (52%) 5-aminoisoxazolo[4,3-/]quinoxaline (69) is also obtained (35%). The structure of the product 68 was proved by an unambiguous synthesis.85... 

Reductive elimination of A3-iodanes with two carbon ligands often accompanies attack of nucleophiles on the carbon atoms attached to the iodine(III) [Eq. (50)]. The reaction gives substitution products. 

In general, inert SSE s tend to favor coupling reactions between two or more substrate molecules whereas those with nucleophilic or electrophilic properties favor substitution or addition reactions. As an example the anodic oxidation of durene 78 on platinum can be controlled to give substitution product only in a strongly nucleophilic SSE (Eq. (17) ) and coupling product only in a non-nucleo-philic SSE (Eq. (20)). In SSE s of intermediate nucleophilicity, both types of products are formed (Eqs. (18) and (19)). 

Ph3Sn- ions are also reactive nucleophiles for the photoinitiated SRN1 process. This anion gives substitution products in good yields (62-100%) with ArX (X = Cl, Br, 0P(0)(Et0)2) in liquid ammonia [38, 42]. Additionally, the reaction of p-C6H4Cl2 with Ph3Sn- ions gives 75% yield of disubstitution in liquid ammonia [38],... 

Displacement of halides by secondary amines and of sulfonyl groups by alkoxides can also take place. Furoxancarboxylic acids are attacked by base to give acyclic products, but their derivatives can undergo nucleophilic acyl substitutions. Likewise nucleophilic addition reactions can be accomplished for ketofuroxans, although ring cleavage is also commonplace. The generation of new heterocyclic systems by reaction with nucleophiles is dealt with in Section 4.22.3.2.5. 

An acid—base reaction forms a nucleophilic anion that can react with an unhindered alkyl halide— that is, CH3X or RCH2X—in an 5 2 reaction to form a substitution product. This alkylated imide is then hydrolyzed with aqueous base to give a 1° amine and a dicarboxylate. This reaction is similar to the hydrolysis of amides to afford carboxylate anions and amines, as discussed in Section 22.13. The overall result of this two-step sequence is nucleophilic substitution of X by NH2, so the Gabriel synthesis can be used to prepare 1° amines only. 

Since the Lewis acid-promoted reactions of the oxidized products with nucleophiles give the corresponding N-acyl-a-substituted amines efficiently, the present reactions provide a versatile method for selective C-H activation and C-C bond formation at the a-position of amides [138]. Typically, TiCl4-promoted reaction of a-t-butyldioxypyrrolidine 66, which can be obtained by the ruthenium-catalyzed oxidation of l-(methoxycarbonyl)pyrrolidine with f-BuOOH, with a silyl enol ether gave keto amide 67 (81%), while the similar reaction with less reactive 1,3-diene gave a-substituted amide 68 (Eq. 3.80). 

A rationale has been afforded to clarify the difference in reactivity of monoactivated allyl halides which normally give substitution products and diactivated allyl halides which normally afford cyclopropanes upon reaction with nucleophiles It is clear that the extent and the rate of formation of the MIRC product is dependent upon the enolate concentration and the rate constant for ring-closure, k, while the extent and the rate of... 

Electrolysis of carboxylates RCO2 in the presence of olefins (XXVIII) may afford the radical addition products XXX, XXXI, XXXII, and XXXIII. Plausible reaction pathways are illustrated in Eq. (18). The radical R generated by electrodecarboxylation of RCO2 first combines with the olefin (XXVIII) to give the radical intermediates (XXIXa), which may provide the dimers (XXX) or the radical coupling products (XXXI). Further one-electron oxidation of XXIXa may provide cations (XXIXb), which subsequently react with the nucleophiles Nu or liberate to give substituted products (XXXII) or olefins (XXXIII). 

When CH3Li or n-BuLi is used in halogen-metal exchange, a rather electrophilic MeX or n-BuX is obtained as a by-product. The alkyl halide can undergo S 2 substitution with the organolithium compound as nucleophile to give the nucleophilic aromatic substitution product. However, Sn2 reactions of organolithium compounds with alkyl... 

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