Nucleophilic Substitution Via SRN1 Mechanism


See: Galli, C.; Gentili, P.; Rappoport, Z. Competition of Mechanisms in Nucleophilic Substitution of Vinyl Halides. An Unequivocal Example of the Vinylic SRN1 Route. J. Org. Chem. 1994, 59, 6786-6795.

Introduction:  The SRN1 reaction was discovered by accident when a strange anomaly in the alkylation of aliphatic nitro compounds by alkyl halides was observed. In 1949 Hass et al. performed a routine alkylation of 2-nitropropane with 4-nitrobenzyl chloride. The product was mainly the C-alkylated compound A Figure 1.1 Further studies of this compound showed that its formation proceeded by a first order mechanism.2 This led the scientific community to believe that a new mechanism was involved in this reaction. This suspicion is based on the following reasoning.

A

Figure 1. Reaction of 4-nitrobenzyl chloride with 2-nitropropane.1
 
 

If an ordinary SN2 route was involved, the reaction would be second order and would proceed with an attack of the strongly nucleophilic oxygen anion of 2-nitropropane on the benzyl carbon. This attack would be accompanied by a displacement of a halogen anion and the formation of the product. This route leads to the formation of the O-alkylated compound B Figure 2.

Figure 2. SN2 mechanism for halogen substitution at the benzyl carbon of 4-nitrobenzyl chloride.

The SN2 mechanism can also proceed with the resonance form that contains a negative charge on the tertiary carbon atom of the 2-nitropropyl anion (Figure 3).2 In this case the nucleophilic carbon will displace the halogen from the benzyl group to give the C-alkylated compound. In an SN2 alkylation the ratio of C-alkylated to O-alkylated products is in favor of the O-alkylated compounds. The proposed reason2 for this is the relatively low steric hindrance present around the oxygen anion in comparison to the secondary carbon anion.

Figure 3. Influence of resonance stabilization on the product of 2-nitropropane alkylation.2
 
 

As stated above, however, in the case of the reaction between 4-nitrobenzyl chloride and 2-nitropropane, the ratio was found to be in favor of the C-alkylated compound, and the kinetics were found to be first order. This apparent contradiction between the expectations for an SN2 route and the results observed led Kerber et al. to propose a first order radical mechanism. They suggested that single electron transfer (SET) to the 4-nitrobenzyl chloride leads to the formation of a radical anion. This radical species then undergoes decomposition to yield a 4-nitrobenzyl radical and a chlorine anion, which is believed to be the rate-determining step of the reaction (Figure 4).4

Figure 4. SRN1 mechanism for the alkylation of 2-nitropropane.3
 
 

The hypothesis of radical involvement was substantiated by the results obtained from running the reaction in the presence of radical scavengers. The presence of compounds such as 1,4-dinitrobenzene strongly decreases the concentration of free radicals. This has led them to be known as "radical scavengers." It was found that when radical scavengers are introduced into the reaction mixture, the alkylation of 2-nitropropane observes second order kinetics and gives the product expected for an SN2 reaction - the O-alkylated compound.2

The SRN1 reaction is a unimolecular (1) radical (R) nucleophilic (N) substitution (S) reaction. The SRN1 reaction can occur via a chain or non-chain mechanism. A chain mechanism is a self-sustaining reaction characterized by the fact that besides products, it leads to the formation of reactive intermediates. These intermediates then react to continue additional processes of the same kind. The chain mechanism is divided into three stages: initiation, propagation, and termination. The SRN1 chain mechanism is initiated by single electron transfer (SET) from a chemical catalyst or an external electron source to the substrate which produces a radical anion (Figure 5, (1)). Examples of such processes include photostimulation (hn), addition of solvated electrons (eg. Nao dissolved in NH3), and electrochemical methods (eg. passing electricity through the system). Propagation occurs when the intermediate reacts with the substrates to produce stable products and regenerate reactive intermediates. These new intermediates react in the same manner as before and thus a repetitive cycle begins. A good example of this general description of radical chain mechanisms is the SRN1 reaction. In it a radical anion is generated, it fragments into the free radical intermediate (R .) and anion leaving group (X -) (Figure 5, (2)). The radical intermediate formation propagates the chain reaction by reacting with the incoming nucleophile (Y -) to yield the radical anion ([RY] -.) (Figure 5, (3)). This radical anion intermediate ([RY] -.) transfers an electron to the initial substrate (RX) to afford the nucleophilic substituted product (RY) (Figure 5, (4)) and another radical anion ([RX] -.) which continues the chain reaction (Figure 5, (2)).5 The four equations seen below can be reduced to the generic substitution equation (Figure 5, (5)). Lastly termination of the chain reaction occurs to end the reaction. Termination may either

Figure 5. SRN1 chain mechanism.5
 
 

occur when all the reactants are consumed, through radical combination or when an inhibitor such as a radical scavenger, O2 or p-dinitrobenzene, is added.2 The SRN1 chain reaction can also be represented by a cyclic mechanism diagram shown in Figure 6.


 
 
 
 
 
 

Figure 6. Cyclic SRN1 chain mechanism.7

Another example of radical reactions is the non-chain radical mechanism. It is defined as a reaction that produces one product molecule per initiation event and is not self-sustaining. Non-chain SRN1 reactions are less frequently encountered than chain SRN1 reactions. A non-chain SRN1 reaction occurs in a solvent cage, a region of space which includes the reacting species surrounded by solvent. Within the cage stepwise substitution occurs and no reactive intermediates are left free in solution to propagate the reaction. The SRN1 non-chain reaction can be represented as shown in Figure 7.5


 
 

Figure 7. Non-chain SRN1 mechanism.5
 
 

The non-chain SRN1 mechanism can be differentiated from the chain mechanism by adding a reaction inhibitor such as a radical scavenger. The chain SRN1 reaction will be inhibited whereas the non-chain SRN1 will proceed normally because it is enclosed in a solvent cage.5 An example of the chain SRN1 reaction is the alkylation of aliphatic nitro compounds by alkyl halides (Figure 4).4 An example of a nitroarylhalide substitution occuring via the non-chain SRN1 reaction is shown in Figure 8.5


 
 

Figure 8. Example of non-chain SRN1 reaction.5

The key intermediate in any SRN1 mechanism is a radical anion species. The propensity of this intermediate to fragment into two pieces, a radical and an anion, will largely dictate the course of an SRN1 reaction. Radical anion fragmentation can best be explained with the help of molecular orbital theory.

For a radical anion to form, a relatively low-lying LUMO must exist to accept a single electron from an outside source and thus become a SOMO. In sp3 systems, this single electron transfer (SET) is usually facilitated by a heteroatom such as a halogen which provides a low-lying s* LUMO for the incoming electron, as can be seen in Figure 9A. The sp2 system is similar, except the system now includes p and p* orbitals. Although many aryl systems have a p* LUMO (Figure 9C), often the s * orbital is lower in energy and is the LUMO instead (Figure 9B). 5 The relative energies of the p * and s * in sp2 systems are primarily

Figure 9. A schematic comparison of sp2 and sp3 systems.14

dependent on two factors: 1) the substituents on the sp2 system and 2) the leaving group bond strength. Conjugated substituents, such as a nitro group, tend to lower the energy of the p* orbital. These substituents do not greatly perturb the energy of the s * orbital associated with the R-X leaving group. However, the energy of the s * orbital is lowered when the leaving group bond is weak, as in the case of the iodine leaving group. Thus, in sp2 radical anions, this SOMO may be either a p* or s * orbital.14

In order for the radical anion [RX] -. to fragment into R . and X - and begin the SRN1 reaction (Figures 5 and 6), the odd electron must first become localized in the s * orbital of the [RX] -.. When the s * is the SOMO, the odd electron density is largely localized in the s bond between the substrate R and leaving group X, quickly promoting bond rupture by decreasing the bond order of the R-X bond.

In the case of stabilized sp2 systems with a p* SOMO, the odd electron must first undergo intramolecular electron transfer into the s * orbital before fragmentation can occur.5 This is possible when the p*- s* energy gap is small because stretching of the R-X bond will lower the s * orbital and raise the s orbital associated with the R-X bond (Figure 10).6 At some point in the R-X bond elongation, the p* and s * orbitals will momentarily become degenerate and the odd electron will


 
 
 
 

Figure 10. Correlation diagram for elongation of the R-X bond.14
 
 

be transferred from the p* to the s * orbital.17 With the odd electron now in the s * orbital, the radical anion is free to fragment. The R-X bond elongation can result from normal vibration and can be assisted by polar solvents which stabilize the anionic leaving group (X -) (Figure 10).13

When the p*- s* energy gap is large, however, normal bond elongation will not cause the p * and s * orbitals to pass each other in energy and no intramolecular electron transfer will occur.2 Without an odd electron in the s * orbital, the radical does not fragment but instead reacts through non-SRN1 pathways, such as by protonation to yield the Birch reduction product.8 Systems with such highly stabilized p * orbitals include m-iodonitrobenzene,5 which has a very low rate of fragmentation, and p-dinitrobenzene, which is in fact used as a radical scavenger.9

The reactivity of radical anions is dependent on their rate of fragmentation. As the fragmentation rate of the radical anion increases, the rate of the SRN1 reaction also increases.17 Specifically, the degree to which the p * orbital is stabilized by the aryl system determines whether fragmentation will occur and, if it will occur, its associated rate.18, 6 The following example in Figure 11 illustrates the affect of p* stability on fragmentation rate.

Figure 11. Comparison of fragmentation rates of phenylacetonitrile with 1-naphthylacetonitrile with molecular orbital rationale.6

Figure 11 compares the fragmentation rate of cyanide from an sp3 position in two different aryl systems, phenylacetonitrile (A) and 1-naphthylacetonitrile (B). As the size and extent of a p system increases, the energy of the system's p* decreases. In the two systems in Figure 11, the p* orbital is the SOMO. The highly conjugated system of B stabilizes the pB* SOMO more than the aromatic system A stabilizes pA*, resulting in a greater energy difference between pB*

and s B* than p A* and s A*. As mentioned earlier, vibrational elongation of the substrate-leaving group bond results in a decrease in the energy of the s * molecular orbital. If the s * is lowered to the energy of the p* orbital, the single electron in the p* orbital can transfer into the s * orbital. When this occurs the substrate-leaving group bond breaks. As the DE between the p* and s * orbitals increases, the probability that the bond will rupture from vibrational elongation decreases. For this reason k-f,A is much greater than kf,B in Figure 11.6 Similar results have been observed for substitution at sp2 positions of aryl systems (Figure 12). Figure 12 displays the different fragmentation rates of bromobenzene and 1-bromonaphthalene. Because the naphthyl system stabilizes the p* orbital more than the phenyl system, bromobenzene fragments two orders of magnitude faster than 1-bromonaphthalene.

Figure 12. Radical anion fragmentation of bromobenzene and 1-bromonaphthalene and the respective fragmentation rates.16
 
 

The reactivity of radical anions has been exploited in organic synthesis. Of particular interest to many synthetic organic chemists is the insensitivity of the SRN1 reaction to steric hindrance. , The reaction of the p-nitrocumyl radical with isopropylnitronate anion in Figure 13 exemplifies the ability of the SRN1 reaction to proceed well with excessive steric hindrance.2

Figure 13. Reaction of p-nitrocumyl with isopropylnitronate anion.2
 
 

The insensitivity of SRN1 reactions to steric hindrance can be easily rationalized (Figure 14). The first step of the mechanism involves unhindered single electron addition to the nitroaromatic group. The subsequent unimolecular elimination is not affected by sterics. The resulting planar radical is readily accessible to nucleophilic attack due to lack of steric hinderence. Finally, the last step involves only another single-electron transfer, a very rapid process insensitive to steric effects (Figure 14). 2
 
 


 
 

 Figure 14. Mechanism demonstrating SRN1 insensitivity to steric hinderance.2
 
 

Not only does the SRN1 reaction provide facile substitution at sterically hindered tertiary carbons, but it also easily displaces leaving groups that would otherwise be considered poor by ordinary SN2 substitution at a tertiary carbon. Figure 15 shows the displacement of an azide anion, a nucleophilic species.2 In addition,


 
 

Figure 15. Azide displacement at a tertiary carbon by SRN1 mechanism.2

although the nitro group is usually considered a poor leaving group, many SRN1 reactions have been reported which proceed with nitro displacement.2 The SRN1 reaction can also be affected by substituents on the substrate. The first example is that a given substituted aryl substrate will show very different reactivity when its substituent occupies either the ortho, meta, or para position. Several studies illustrate the effects of aryl substituents in some SRN1 reactions. Neta and Behar reported the following rate constants for intramolecular electron transfer in radical anions of ortho, meta, and para substituted nitrobenzyl chlorides (Table 1). This data shows a distinct trend: the rate of electron transfer decreases in the order ortho > para > meta.22 When the rate of intramolecular electron transfer from the p* orbital to the s* orbital decreases, the fragmentation rate also decreases. Therefore, fragmentation rate decreases in the following order: ortho > para > meta.1
 
 
 
 

Table 1.Rate Constants for Intramolecular Electron Transfer in the Anion Radicals of Nitrobenzyl Halides a22
Isomer Cl
ortho (1±0.2)E4
para (4±1)E3
meta <5
a First-order rate constants in units of s-1.
 
 

The second example is that SRN1 reactions have been found to occur preferentially when the leaving group is chlorine and less so when it is iodine or bromine. This can be explained if one recognizes that iodine is a better leaving group than chlorine. Therefore, substitution of iodine by an SN2 or SN1 mechanism occurs faster than the competing SRN1 mechanism which requires the initial formation of a radical anion and its decomposition (Figures 1, 2).2

The reactions in Figures 13 and 15 both illustrate the applicability of the SRN1 reaction; however, neither reaction indicates the stereochemistry at the substitution site. TheSRN1 reaction of optically pure p-nitrobenzyl substrates proceeds to yield racemic products.2 Figure 16 shows the radical anion fragmenting into the free radical which assumes a planar sp2 geometry at the site of substitution. Nucleophilic attack can then occur from either the top or the bottom face of the radical, resulting in a racemic mixture of products.2

Figure 16. Stereochemistry of an SRN1 reaction for a p-nitrobenzyl derivative.2
 
 

SRN1 reactions occur frequently in syntheses.20, 21For example, Vanelle et al.23 have demonstrated the formation of 2-isopropylidenemethyl-3-nitroimidazo-[1,2-a]-pyridine, a potential pharmaceutical derivative.23 Figure 17 displays the SRN1 reaction they applied for its synthesis.

Figure 17. Synthesis of 2-isopropylidenemethyl-3-nitroimidazo-[1,2-a]-pyridine through SRN1 mechanism.23
 
 

Most SRN1 reactions involve substrates which have electron withdrawing groups, unactivated aryl substituents, and vinylic halides.2 In 1984, Rossi et al.25 performed the substitution reaction of halocyclopropanes with nucleophiles by the SRN1 mechanism. This is interesting because the reaction cannot occur by either an SN2 reaction or an SN1 reaction unless the leaving group is on a tertiary carbon and upon interaction with a strong base the halocyclopropane will yield the elimination-addition product. Figure 18 shows the photostimulated reaction of 7-bromonorcarane with diphenylphosphide ion.


 
 

 Figure 18. Reaction of 7-bromonorcarane with diphenylphosphide ion.25
 
 

A survey of the current literature does not provide a clear-cut rule that would allow researchers to predict with a fair amount of certainty whether a given compound will undergo an SRN1 reaction or a different type of reaction. An explanation is that many of the requirements for a compound to undergo an SRN1 reaction are also demanded of compounds that undergo other types of substitutions. However, there are certain trends that tend to favor an SRN1 reaction. It has been observed that SRN1 reactions tend to occur in the presence of radical intiators, such as AIBN (2,2'-azobisisobutyronitrile), benzoyl peroxide, or light for example.

The following case study18 illustrates competition between the SRN1 reactions and a,b-elimination and the way this competition is influenced by substituent effects.
 
 

Results: A Case Study

Competition of nucleophilic substitution reactions of vinyl halides was seen when reacting b-bromostyrene, as the substrate, and pinacolone enolate ion, as the nucleophile. Five products were formed (A-E, Figure 19) and the substrate was exhausted after 10 minutes.18

Figure 19. Nucleophilic substitution reactions of pinacolone enolate ion with b-bromostyrene.18
 
 

The reaction products continued to equilibrate for three hours yielding mostly A and B (Table 2).
 
 
 
 

Table 2. Products from Competitive Nucleophilic Substitution Reaction Mechanisms18
Reaction Time Products Yield (%)
(min) A B C D E
10 21 7 42 2 27
180 45 14 9 6 16

 

Another study was performed to test the necessity for a conjugated system in the SRN1 mechanism. The substitution reactions of conjugated triphenylvinyl bromide (F, Figure 20) and unconjugated 1-bromo-2,4,4-trimethyl-2-butene (I, Figure 21) with pinacolone enolate ion were performed to determine if the difference in structure was responsible for the altered mechanism pathways. The substitution reactions of F and I were initiated by photostimulation to give 38-55% and 0% yields, respectively. As predicted, the major product observed from the reaction of I with pinacolone resulted in the hydrodebromination product, J.18


 
 

Figure 20. Conjugated vinylic system undergoes two methods of substitution, SRN1 and hydrogen abstraction.18


 
 

Figure 21. Nonconjugated vinylic system undergoes one method of substitution, hydrogen abstraction.18

Discussion
 
 

The SRN1 products in Figure 19 are A and B, which are separable tautomers. However, it is possible to get to products A and B though an ionic elimination-addition route (Figure 22). The authors differentiate these two routes by the use of radical scavengers.18 When the reaction

Figure 22. Elimination-addition route toward desired product.18
 
 

in Figure 19 was run in the presence of PDNB (p-dinitrobenzene), the yield of products A and B was suppressed to a total of 12 % after 180 min versus the 59 % observed without PDNB. This observation suggested that two different mechanisms, the SRN1 mechanism and the elimination-addition route, are probably involved (Figure 22). The elimination-addition route results from an a,b-elimination to initially form the conjugated alkyne (Figure 22 and Figure 19, E). Other side products C and D result from the coupling of E with the nucleophile and b-bromostyrene, respectively. These side products all stem from the presence of vinylic hydrogens. In analogous systems without vinylic hydrogens, no such byproducts are observed.18

The unwanted side reactions in Figure 19 can be avoided by using substrates that lack vinylic hydrogens. To this end, the authors performed the reactions in Figures 20 and 21. The reaction in Figure 20 uses triphenylvinyl bromide, a conjugated substrate, whereas the reaction in Figure 21 uses 1-bromo-2,4,4-trimethyl-2-butene, an unconjugated substrate. By using these substrates, the authors sought not only to eliminate the side reactions which result from a,b-elimination but also to compare the reactivity of conjugated and unconjugated systems.18

It was observed that both the conjugated substrate (Figure 20) and the unconjugated substrate (Figure 21) form radical anions that fragment to give the planar radical species. However, the unconjugated radical does not yield the substitution product; rather, it abstracts a hydrogen (Figure 21). The conjugated radical, on the other hand, does proceed through the radical chain mechanism to give the SRN1 substitution product G (Figure 20). The disparate reactivities of the two radical species can be explained by the stability of the radical in question. The unconjugated radical is an extremely reactive species, because the radical electron is not stabilized by a conjugated p system. This aggressive radical will abstract a hydrogen from the solvent before it can react through an SRN1 pathway. However, the conjugated radical is delocalized throughout an extensive p system, making it less reactive. This increased stability increases the lifetime of the radical and allows nucleophilic attack by an SRN1 pathway.18

The conjugated substrate also increases the stability of the radical anion formed after nucleophilic attack. The odd electron in this radical anion is initially in the s* orbital but can be easily transferred to the lower energy p* orbital, thus stabilizing the radical anion.18
 
 

Conclusion

SRN1 reactions are used to generate sterically hindered synthetic products. It was shown using molecular orbital considerations that there is a necessary window of stability of the radical intermediates for the SRN1 chain mechanism to take place. Several competing reactions, for example SN2, SN1, and a,b-elimination, can take place concurrently with the SRN1 mechanism. These reactions can be distinguished from the SRN1 mechanism by two methods: kinetics and inhibition using radical scavengers.
 
 

Questions
 
 

1. Based on an SRN1 mechanism, draw out the mechanism of the following reaction. This reaction works by first treating the compound with t-BuOK in DMSO and then initiating the reaction by photostimulation.24 Propose an experiment to support the hypothesis that the reaction proceeds through an SRN1 mechanism. Suggest a possible competing reaction mechanism that might take place and why the experiments you have proposed can differentiate between these mechanisms.


 
 
 
 

Reaction with o-iodoanilide24
 
 
 
 

Answer:
 
 

SRN1 Mechanism:24


 
 

To provide evidence for the SRN1 mechanism, add a radical scavenger to inhibit the reaction and secondly keep the reaction in the dark to prevent photochemical initiation. Possible radical scavengers are p-dinitrobenzene or di-t-butylnitroxide. If the reaction is suppressed by the radical scavengers then the mechanism is most likely proceeding through radical intermediates. Secondly, kinetic studies should show the unimolecular nature of the reaction if first order kinetics are observed. Both possible reaction mechanisms are unimolecular, so the kinetic studies would be used to comfirm the unimolecular nature and the radical scavenger experiment would be used to differentiate between the mechanisms. Thus if the studies implicate a unimolecular radical mechanism, the reaction likely proceeds through an SRN1 mechanism.
 
 
 
 
 
 

Possible competing reaction:

 2. Propose an energy diagram using a molecular orbital representation of the formation of a stable radical anion from an aryl radical and a conjugated nucleophile.14 Explain your diagram.
 
 
 
 

Answer:

The conjugated nucleophile, such as an acetate ion, has both p and p * molecular orbitals (MOs) which combine with a phenyl radical to form a more stable new carbon-carbon s bond and a radical anion intermediate. The intermediate has two p * MOs (LUMOs), one from the phenyl ring and the other from the carbonyl group.14 The carbonyl p * MO is lower than the nucleophile p * MO because it is a system with 2 atoms and 2 electrons whereas the nucleophile has the 4 electron charge spread out to three atoms destabilizing thep* MO.14 There are two orbital crossings and the single electron goes to the p * MO of the carbonyl group to form the radical anion intermediate.14
 
 
 
 
 
 
 
 

References

1Hass, H.B.; Bender, M.L. A Proposed Mechanism of the Alkylation of Benzyl Halides with Nitro Paraffin Salts. J. Am. Chem Soc. 1949, 71, 3482-3485.

2 Kornblum, N. Substitution Reactions Which Proceed via Radical Anion Intermediates. Ang. Chem. Int. Ed., 1975, 14, 734-745.

3 Carey, F.; Sundberg, R. "Advanced Organic Chemistry." Pt. A, 3ed Ed. Plenum Press: New York. pp. 712-718.

4 Kerber, R.C.; Urry, G.W.; Kornblum, N. Radical Anions as Intermediates in Substitution Reactions. The Mechanism of Carbon Alkylation of Nitroparaffin Salts. J. Amer. Chem. Soc. 1965, 87, 4520-4528.

5 Galli, C. Evidence for a Non-Chain SRN1 Reaction Occuring on a Nitroarylhalide. Tetrahedron., 1988, 44, 5205-5208.

6 Rossi, R. A. Phenomenon of Radical Anion Fragmentation in the Course of Aromatic SRN1 Reactions. Acc. Chem. Res., 1982, 15, 164-170.

7 Costentin, C.; Hapiot, P.; Medebielle, M; Saveant, J. "Thermal" SRN1 Reactions: How Do They Work? Novel Evidence that the Driving Force Controls the Transition between Stepwise and Concerted Mechanisms in Dissociatiove Electron Transfers. J. Am. Chem. Soc. 1999, 121, 4451-4460.

8 Fleming, I. "Frontier Orbitals and Organic Chemical Reactions" Wiley-Interscience 1976; pp 199-204.

9 Box, H.C.; Freund, H.G.; Lilga, K.T.; Budzinski, E.E. Magnetic Resonance Studies of the Oxidation and Reduction of Organic Molecules by Ionizing Radiations. J. Phys. Chem. 1970, 74, 40-52.

10 Symons, M.C.R. The Radical Anion [C6F5I]-. J.C.S. Chem. Comm. 1977, 408-409.

11 Mishra, S.P.; Neilson, G.W.; Symons, M.C.R. Unstable Intermediates. Part 146 - Electron Spin Resonance Spectra for Linear BrCN- and Br2CN Radicals in Irradiated Cyanogen Bromide Crystals. J. Chem. Soc., Faraday Trans. II 1974, 70, 1280-1287.

12 Riederer, H.; Huttermann, J. s*-Electron Addition to 5-Halogenouracils in Neutral Glasses. J.C.S. Chem. Comm. 1978, 313-314.

13 Neilson, G.W.; Symons, M.C.R. Unstable Intermediates. Part 116 - Radical Anions of N-Halogenated Amides. J. Chem. Soc., Faraday Trans. II 1972, 68, 1582-1588.

14Rossi, R.A.; Coupling of an Aryl Radical with a Nucleophile and the Reaction Pathway. J. Chem. Educ. 1982, 4, 310-312.

15 Symons, M.C.R.; Electron-Loss and Electron Capture Process in Irradiated Systems. Pure & Appl. Chem. 1981, 53, 223-238.

16 Gores G.J.; Koepped, C.E.; Bartak, D.E.; Electrochemical Formation and Decomposition of Halogenated Acetophenone Anion Radicals. J. Org. Chem. 1979, 44, 380-385.

17 Canadell, E.; Karafilogluo, P.; Salem, L.; Bond Cleavage of the Solvated Methyl Chloride Anion: A Primary Electrochemical Event. J. Am. Chem. Soc. 1980, 102, 855-857.

18Galli, C.; Gentili, P.; Rappaport. Z. Competition of Mechanisms in Nucleophilic Substitution of Vinyl Halides. An Unequivocal example of the Vinylic SRN1 Route. J. Org. Chem. 1994, 59, 6786-6795.

19 Rossi, Roberto A.; Palacios, Sara M. On the SRN1-SRN2 Mechanistic Possibilities. Tetrahedron. 1993, 49, 4485-4494.

20 Beugelmans, R.; Chbani, M.; Soufiaoui, M. First Synthesis of Macrocycles by Quadruple SRN1 Reactions. Tet. Lett. 1996, 37, 1603-1604.

21Norris, Robert K; Randles, David. Regiochemistry of the Association Step in SRN1 Reactions: Kinetically Controlled Coupling of aci-Nitronate Ions and p-Nitrobenzylic Radicals. J. Org. Chem. 1982, 47, 1046-1051.

22 Neta, P.; Behar, D. Intramolecular Electron Transfer in the Anion Radicals of Nitrobenzyl Halides. J. Am. Chem. Soc. 1980, 102, 4798-4902.

23Rossi, R. A.; Santiago, A. N.; Palacios, S. M. Reactions of 7-Bromonorcarane with Nucleophiles by the SRN1 Mechanism. Novel Nucleophilic Substitutions on the Cyclopropane Ring. J. Org. Chem. 1984, 49, 3387-3388.

24 Rossi, R. A.; Santiago, A. N.; Palacios, S. M. Reactions of 7-Bromonorcarane with Nucleophiles by the SRN1 Mechanism. Novel Nucleophilic Substitutions on the Cyclopropane Ring. J. Org. Chem. 1984, 49, 3387-3388.