SN-reactions

An alternative deseription of these energetic effects has been given by Pross and Shaik. - Again the Sn reaction is used as an example. A valence bond (VB) description is developed by writing linear combinations of a basis set of configurations. These constitute a reasonable set of configurations (compare with Table 5-3) ... 

Table 8-1. Predicted Solvent Effects on Rates of Sn Reactions...

The real world of Sn reactions is not quite as simple as the discussion has so far suggested. The preceding treatment in terms of two clearly distinct mechanisms, SnI and Sn2, implies that all substitution reactions will follow one or the other of these mechanisms. This is an oversimplification. The strength of the dual mechanism hypothesis and its limitations are revealed by these relative rates of solvolysis of alkyl bromides in 80% ethanol methyl bromide, 2.51 ethyl bromide, 1.00 isopropyl bromide, 1.70 /er/-butyl bromide, 8600. Addition of lyate ions increases the rate for the methyl, ethyl, and isopropyl bromides, whereas the tert-butyl bromide solvolysis rate is unchanged. The reaction with lyate ions is overall second-order for methyl and ethyl, first-order for tert-butyl, and first- or second-order for the isopropyl member, depending upon the concentrations. Similar results are found in other solvents. These data show that the methyl and ethyl bromides solvolyze by the Sn2 mechanism, and tert-butyl bromide by the SnI mech-... 

Several proposals have been made to fit the borderline reactions into a well-defined mechanistic scheme. Most of these adopt one of two viewpoints either (1) borderline substrates undergo concurrent SnI and Sn2 processes, with the particular system determining which mechanism, if either, predominates or (2) all Sn reactions are related by essentially the same mechanism, which differs from case to case in the detailed disposition of electrons in the transition state. In this view pure SnI and Sn2 processes are merely the extreme limiting forms of a single mechanism, and the borderline mechanism is a merged process having some features of both. 

The whole concept of direct methylation has recently been critically reviewed and rejected by Gompper as a method to study tautomerism. The difference in the proportions of the two methyl derivatives produced w hen diazomethane is in excess, or the reverse, has now been ascribed to the relative importance of the Sn and Sn reactions of the tautomeric compound with diazomethane. The proportions of N- and 0-methyl derivatives formed by the reaction of cyclic amides with diazomethane has been related to the infrared vC—O frequencies. ... 

The Sn2 mechanism as shown above involves the simultaneous movement of three pairs of electrons. However, Bordwell and co-workers contended that there is no evidence requiring that this bond making and bond breaking be in fact concerted, and that a true Sn2 mechanism is a myth. There is evidence both for and against " this proposal. There is also a review of the Sn reaction. ... 

Leaving the (retro-)aldol addition-initiated threefold anionic domino processes, we are now describing sequences which are initiated by a SN-type transformation. In particular, domino reactions based on SN/1,4-Brook rearrangement/SN reactions are well known. For example, the group of Schaumann obtained functionalized cyclopentanols of type 2-461 by addition of lithiated silyldithioacetals 2-458 to epoxy-homoallyl tosylates 2-459 in 41-75% yield (Scheme 2.106) [248]. 

A SN reaction-based domino route to clerodane diterpenoid tanabalin (2-488) [258] has been described by Watanabe s group (Scheme 2.111) [259]. This natural product is interesting as it exhibits potent insect antifeedant activity against the pink bollworm, Pectinophora gossypiella, a severe pest of the cotton plant The domino sequence towards the substituted trans-decalin 2-487 as the key scaffold is induced by an intermolecular alkylation of the (5-ke toes ter 2-484 with the iodoalkane 2-483 followed by an intramolecular Michael addition/aldol condensation (Robin-... 

The development of synthetic methods for the selective introduction of short-chain perfluoroalkyl groups into organic molecules is of interest in drug development [464]. Fluoromodifications often confer unique properties on a molecule, for example in terms of increased metabolic stability and lipophilicity and, as a consequence, the pharmacokinetic profiles are often improved [465]. Burger and coworkers developed a domino process consisting of a SN reaction combined with a Claisen and a Cope rearrangement which allows the transformation of simple fluorinated compounds into more complex molecules with fluoro atoms [466]. Treatment of furan 2-917 with 2-hydroxymethyl thiophene (2-918) in the presence... 

The reactivity of triflate-substituted pyridopyrrolizines has been investigated. In the presence of a polar aprotic solvent and a nucleophile, these compounds undergo Sn reactions, leading to the a-substituted 3//-3-pyrrolones. This process is thought to involve loss of the trifluoromethanesulfinate ion, formation of an acyliminium ion intermediate, and nucleophilic attack on the latter <1995JOC5382> (Scheme 44). 

The foregoing discussion of micellar charge effects has implicitly assumed that differences in water activity or substrate location in cationic and anionic micelles are not of major importance. If such differences were all important it would be difficult to explain the differences in k+/k for carbonyl addition and SN reactions, because increase of water content in an aqueous-organic solvent speeds all these reactions (Johnson, 1967 Ingold, 1969). As to substrate location, there is very extensive evidence that polar organic molecules bind close to the micelle-water interface in both anionic and cationic micelles, although the more hydrophobic the solute the more time it will spend in the less polar part of the micelle. Substrate hydrophobicity has a marked effect on the overall rate effects in both cationic and anionic micelles, but less so on values of k+/k. It seems impossible to explain all these charge effects in terms of differences in the location of substrates in cationic and anionic micelles. 

For reaction of benzoyl chlorides in water, reactivity follows the electronreleasing ability of p-substituents, and there are striking differences in the micellar effects (Table 7). With electron-withdrawing substituents k+/k > 1, but its value progressively decreases with increasing electron release from a p-substituent. Thus an increase in electron release changes k+/k from values characteristic of a carbonyl addition reaction to values characteristic of SN reactions at saturated carbon. This classification also... 

Bimolecular E2 reactions involving OH " in aqueous solution are speeded by cationic and inhibited by anionic micelles (Minch et al., 1975) whereas spontaneous SN reactions are generally inhibited strongly by cationic micelles and less strongly by anionic micelles it is therefore relatively easy to observe micellar control of product formation. 

The study of S -1 reaction in cyclohexane becomes difficult because of the ease with which the elimination reactions occur at the same time. However it has been shown that SN reaction will be sterically accelerated for an axial substituent, because the formation of carbocation will relieve the steric strain due to 1, 3 interactions which is absent with equatorial substituent. 

Secondary a-deuterium kinetic isotope effects (KIEs) have been widely used to determine the mechanism of SN reactions and to elucidate the structure of their transition states (Shiner, 1970a Westaway, 1987a). Some of the significant studies illustrating these principles are presented in this section. 

SN, reactions of primary stabilized organolithium compounds on polyalkylmethacrylates affords a very versatile synthetic route to model ketonic copolymers substitution is selective and quantitative up to DSm of 0.60,and it is easily monitored by the initial... 

Unsaturated nitriles have been obtained from the SN. reaction of 3-chloroalk-1 -enes [22] using tetra-n-butylammonium iodide as the catalyst. Under the basic reaction conditions, isomerism occurs such that not only is the 1-cyanoalk-2-ene obtained, but also the conjugated 1-cyanoalk-l-ene. Surprisingly, when tetra-n-butylammonium chloride is used, direct SN displacement of the chloro group occurs, followed by isomerization, to give the 3-cyanoalk-2-ene. 

It is noteworthy that, although 4-bromoanisole produces anisic acid in high yield, 4-hydroxybenzoic acid is isolated in only 17% yield from the corresponding reaction of 4-bromophenol. Also, 4-bromoacetophenone, which may react by a normal SN reaction, is readily converted into 4-acetylbenzoic acid, whereas 4-bromonitro-benzene produces 4-nitrobenzoic acid in only 17% yield, together with nitrobenzene (17%). 

A reaction in which an atom, group, or moiety in a molecular entity is replaced by another. See Sn Reactions... 

DISSOCIATION KINETICS SUBSITE MAPPING SUBSTITUENT SUBSTITUTION REACTION Sn REACTIONS... 

A plausible mechanism for the ring expansion (Scheme 65) proceeds via an intermediate zwitterion A, resulting from Michael addition of the tertiary nitrogen to the alkyne. Cleavage of the C(l)-N bond occurs via formation of the six-membered transition state B in which a molecule of alcohol facilitates the Sn reaction. 

For reviews of ion pairs in Sn reactions, see Beletskaya Russ. Chem. Rev. 1975, 44, 1067-1090 Harris Prog. Phys. Org. Chem. 1974, II, 89-173 Raber Harris Schleyer. in Szwarc Ions and Ion Pairs in Organic Reactions, vol. 2 Wiley New York, 1974, pp. 247-374. 

For reviews of Sn reactions at such substrates, see Rao Paknikar Kirtanc Tetrahedron 1983, 39, 2323-2367 Behrens Sharpless Aldrichimica Acta 1983, 16, 67-79 Enikolopiyan Pure Appl. Chem. 1976, 48, 317-328 Fokin Kolomiets Russ. Chem. Rev. 1976, 45, 25-42 Wohl Chimia 1974, 28, 1-5 Kirk Chem. Ind. (London) 1973, 109-116 Buchanan Sable Sel. Org. Transform. 1972, 2, 1-95 Dcrmer Ham Ethylenimine and Other Aziridines Academic Press New York. 1969, pp. 206-273 Akhrem Moiscenkov Dobrynin Russ. Chem. Rev. 1968,37, 448-462 Grittcr. in Patai. Ref. 333. pp. 390-400. 

S Darzen s 1 a-Halo ester XCH — COOR Aldehyde, ketone Epoxidation (Sn reaction) follows... 

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