Substitution reactions SRN1 mechanism

The base may deprotonate either C3 or C4. Deprotonation of C3 makes it nucleophilic. We need to form a new bond from C3 to C8 via substitution. The mechanism of this aromatic substitution reaction could be addition-elimination or Sr I. The requirement of light strongly suggests SRN1. See Chap. 2, section C.2, for the details of drawing an SRN1 reaction mechanism. 

Just as in phenyl halides, the halogen can be replaced by hydrogen, by a metal, or be coupled. Two of the four mechanisms of such nucleophilic substitutions are also familiar from benzene chemistry via arynes and by the SRN1 mechanism. However, of the two further mechanisms of nucleophilic replacement, the ANRORC is unique to heterocycles, and SAE reactions occur only with strongly activated benzenoid systems. 

Unactivated aryl halides also undergo nucleophilic displacement via electron transfer in the initial step the so-called SRN1 mechanism. It is now clear that in the case of heteroaromatic compounds, nucleophilic substitution by the Srn process often competes with the addition-elimination pathway. The SRN reactions are radical chain processes, and are usually photochemically promoted. For example, ketone (895) is formed by the SRN1 pathway from 2-chloroquinoxaline (894) (82JOC1036). 

Thus, ketone enolates easily substitute chlorine in position 2 of the electrophilic nucleus of pyrazine (1,4-diazabenzene), and even in the dark the reaction proceeds via the SRN1 mechanism (Carver, Komin, et al. 1981). It might be expected that the introduction of the second chlorine in the ortho position to another nitrogen in the electrophilic nucleus of pyrazine promotes the ion radical pathway even more effectively. However, 2,6-... 

Scheme 10.29 Srn1 mechanism for reactions between nucleophiles and a-substituted nitroalkanes.

Barolo, S.M., Lukach, A.E. and Rossi, R.A. (2003) Syntheses of 2-substituted indoles and fused indoles by photostimulated reactions of o-iodoanilines with carbanions by the SRN1 mechanism. Journal of Organic Chemistry, 68, 2807—2811. 

Halothiophenes undergo photostimulated reaction with acetone enolate ion to form substitution products (76H(5j377). This is believed to occur by the radical-chain SRN1 mechanism. The propagation steps are as follows ... 

Electron-catalyzed (or electron-stimulated) processes constitute a relatively new class of reactions of great potential synthetic interest (Zelenin and Khidekel, 1970 Linck, 1971). Foremost among these ranks the SRN1 mechanism, which is an electron-initiated radical-chain mechanism of nucleophilic substitution (21-24 X- = halide ion) (for reviews, see Kornblum, 1975 Bunnett, 1978, 1982). The initiation step (21) can be performed photochemically, electrochemically, or by adding alkali metal (Pinson and Saveant, 1978 Amatore et al., 1979 van Tilborg et al., 1977, 1978 Saveant, 1980). 

No arylation was observed when 1,1-enediamines 8 reacted with 2,4-dinitrohalo-benzenes 147 under neutral conditions. However, the a-anion of 8, prepared with sodium hydride in DMF, can displace a halide ion from 147 to afford C-arylated products 148. Excellent yield was obtained with 2,4-dinitrofluorobenzene (equation 56)131. It has been demonstrated that the reaction proceeds via the radical nucleophilic substitution (SRN1) mechanism. 

The best known PET bond cleavage reaction involves the substitution of aryl halides by the S l mechanism. This mechanism was first recognized by Bunnett and Rossi in 1970 [55]. The SRN1 mechanism [56,57] requires one-electron reduction of an aryl halide to initiate the substitution reaction. The anion-radical undergoes... 

Substitution by the SN2 mechanism and -elimination by the E2 and Elcb mechanisms are not the only reactions that can occur at C(sp3)-X. Substitution can also occur at C(sp3)-X by the SRN1 mechanism, the elimination-addition mechanism, a one-electron transfer mechanism, and metal insertion and halogen-metal exchange reactions. An alkyl halide can also undergo a-elimination to give a carbene. 

Determine and draw the mechanism (SN2, SRN1, addition-elimination, or elimination-addition) of each of the following substitution reactions. Some reactions might reasonably proceed by more than one mechanism in these cases,... 

The same high preference for trans addition is found in substitution reactions of nitro-sugars that proceed through the SRN1 mechanism with intermediate formation of a nitrofuranosyl radical51. These are trapped by carbon nucleophiles that are formed from other nitro compounds by deprotonation. 

Apparently, an electron-transfer reaction is occurring. This reaction can therefore be used as a model for the first step of the SRN1 mechanism. This competition between nucleophilic substitution and electron transfer is a subject of general interest. 

Substitution reactions by anions at carbon are also known to occur by initial electron transfer. The mechanism of such transformations was first characterized by Russell and Danen (14) and Kornblum et al. (15), and Bunnett (16) significantly developed its applications and named it the SRN1 reaction an... 

Intramolecular nucleophilic substitution by the anions of o-haloanilides is another viable oxindole synthesis. This is a special example of the category Ic process described in Section 3.06.2.3. The reaction is photo-stimulated and the mechanism is believed to be of the electron-transfer type SRN1 rather than a classical addition-elimination mechanism. The reaction is effective when R = H if 2 equivalents of the base are used to generate the dianion (equation 202) (80JA3646). 

The mechanism of the reaction depicted in Scheme 4-6 differs from the SN1 or SN2 mechanism in that it involves the stage of one-electron oxidation reduction. The impetus of this stage may be the easy detachment of the bromine anion followed by the formation of the fluorenyl radical. The latter is unsaturated at position 9, near three benzene rings that stabilize the radical center. The radical formed is intercepted by the phenylthio anion. That leads to the anion radical of the substitution product. Further electron exchange produces the substrate anion radical and the final product in its neutral state. The reaction takes place and consists of radical (R) nucleophilic (N) monomolecular (1) substitution (S), with the combined symbol of SRN1. Reactions of SrnI type may have both branch-chain and nonchain character. 

A large number of radical reactions proceed by redox mechanisms. These all require electron transfer (ET), often termed single electron transfer (SET), between two species and electrochemical methods are very useful to determine details of the reactions (see Chapter 6). We shall consider two examples here - reduction with samarium di-iodide (Sml2) and SRN1 (substitution, radical-nucleophilic, unimolecular) reactions. The SET steps can proceed by inner-sphere or outer-sphere mechanisms as defined in Marcus theory [19,20]. 

Substitutions by the SRn 1 mechanism (substitution, radical-nucleophilic, unimolecular) are a well-studied group of reactions which involve SET steps and radical anion intermediates (see Scheme 10.4). They have been elucidated for a range of precursors which include aryl, vinyl and bridgehead halides (i.e. halides which cannot undergo SN1 or SN2 mechanisms), and substituted nitro compounds. Studies of aryl halide reactions are discussed in Chapter 2. The methods used to determine the mechanisms of these reactions include inhibition and trapping studies, ESR spectroscopy, variation of the functional group and nucleophile reactivity coupled with product analysis, and the effect of solvent. We exemplify SRN1 mechanistic studies with the reactions of o -substituted nitroalkanes (Scheme 10.29) [23,24]. 

The SRN1 process has proven to be a versatile mechanism for replacing a suitable leaving group by a nucleophile at the ipso position. This reaction affords substitution in nonactivated aromatic (ArX) compounds, with an extensive variety of nucleophiles ( u ) derived from carbon, nitrogen, and oxygen to form new C—C bonds, and from tin, phosphorus, arsenic, antimony, sulfur, selenium, and tellurium to afford new C-heteroatom bonds. 

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