SNl mechanism

Substitution nucleophilic unimolecular(SNl) mechanism (Sec tions 4 9 and 8 8) Mechanism for nucleophilic substitution charactenzed by a two step process The first step is rate determining and is the ionization of an alkyl halide to a carbocation and a halide ion... 

The reactant R2 can also be considered to be a solvent molecule. The global kinetics become pseudo first order in Rl. For a SNl mechanism, the bond breaking in R1 can be solvent assisted in the sense that the ionic fluctuation state is stabilized by solvent polarization effects and the probability of having an interconversion via heterolytic decomposition is facilitated by the solvent. This is actually found when external and/or reaction field effects are introduced in the quantum chemical calculation of the energy of such species [2]. The kinetics, however, may depend on the process moving the system from the contact ionic-pair to a solvent-separated ionic pair, but the interconversion step takes place inside the contact ion-pair following the quantum mechanical mechanism described in section 4.1. Solvation then should ensure quantum resonance conditions. 

Rawlins MD, Thomas SNL. Mechanisms of adverse drug reactions. In Davies DM et al., editors. Textbook of adverse drug reactions, 5th ed. Oxford University Press 1998. p. 40-63. 

Problem 14.7 Give (a) Sfg2 and (b) SNl mechanisms for formation of ROR from ROH in cone. H2S04,... 

Problem 14.14 (a) Show how the cleavage of ethers with HI can proceed by an SN2 or an SNl mechanism. (b) Why is HI a better reagent than HBr for this type of reaction (c) Why do reactions with excess HI afford two moles of RI ... 

Illustration of the Snl mechanism. First, in the presence of a polar solvent, the C-X bond breaks, forming the carbocation. This carbocation intermediate is highly reactive. In this case, it reacts with water. Note that the water may attack from either side. 

Two extreme mechanistic possibilities may be considered for such reactions. First, there is the SNl mechanism, in which the complex dissociates, losing the ligand to be replaced, the vacancy in the coordination shell then being taken by the new ligand. This path may be represented as follows ... 

With primary halides, the first step is probably normally SN2, as commonly assumed, although the existing kinetic and stereochemical data do not establish this with certainty. Secondary halides are considerably less reactive and olefins are frequently found among the products, suggestive of greater importance for an SNl mechanism (260). A rather clear-cut example is seen in the exceptional reactivity of benzhydryl and 9-fluorenyl bromide with triethyl phosphite for which Smith and Burger (290) proposed prior formation of a carbonium ion ... 

The relative ease with which triarylmethyl halides enter into the Michaelis-Arbuzov reaction is also suggestive of an SNl mechanism, although a homolytic process has been proposed (22). 

These reactions can be divided into two categories, each leading to a mechanism the SNl mechanism (so called because it leads to a speed of first order) with two steps in the mechanism, such as reaction [2.R4] and steps [2.R4a] and [2.R4b] ... 

With highly reactive alkyl halides, like allylic, benzylic or phenacyl halides, the ZjA-alkylation can be a serious side-reaction. Because of a SNl-like mechanism in those cases, the effect of enolate concentration on the reaction rate is low, and the resulting monoalkylester 5 may be more acidic than the unsubstituted starting material ... 

Prototropic interconversions have been the subject of much detailed study, as they lend themselves particularly well to investigation by deuterium labelling, both in solvent and substrate, and by charting the stereochemical fate of optically active substrates having a chiral centre at the site of proton departure. Possible limiting mechanisms (cf. SNl/SN2) are those (a) in which proton removal and proton acceptance (from the solvent) are separate operations, and a carbanion intermediate is involved, i.e. an intermolecular pathway and (b) in which one and the same proton is transferred intramolecularly ... 

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. 

Another problem with the reaction of phenols with aziridines is the selectivity between O-alkylation vs C-alkylation. A recent report has identified that the use of (ArO)3B selects for C-alkylation <06OL2627>. Most of the examples reported in this paper showed less than 5% of the O-alkylation product. What is interesting about this report is the stereochemistry of the product. While the mechanism is not known, the product is formally an SNl type product. Generally less than 5% was the product of inversion of configuration (the Sn2 product). In addition to the A-tosyl, both the A-Cbz and A-Dpp aziridines gave excellent yields of aziridine-opened product. 

Gas-phase intracomplex substitution in (R)-(- -)-l-arylethanol/CHs OH2 adducts. It is well established that bimolecular Sn2 reactions generally involve predominant inversion of configuration of the reaction center. Unimolecular SnI displacements instead proceed through the intermediacy of free carbocations and, therefore, usually lead to racemates. However, many alleged SnI solvolyses do not give fully racemized products. The enantiomer in excess often, but not always, corresponds to inversion. Furthermore, the stereochemical distribution of products may be highly sensitive to the solvolytic conditions.These observations have led to the concept of competing ° or mixed SNl-SN2 mechanisms. More recently, the existence itself of SnI reactions has been put into question. ... 

Acid hydrolysis of an octahedral metal ion complex is typically a dissociative or SNl-type reaction. In the case of base hydrolysis, reactions tend to display SN2-type reaction mechanisms, although others take place by what is termed an SnI-conjugate base mechanism. The latter involves attack by an electrophile to abstract a proton... 

The obvious solution to this problem is to deposit ZnS at a lower pH when the OH concentration will be lower. However, with thiourea, for example, lowering the pH results in slower hydrolysis of the thiourea and therefore a lower snl-phide concentration (presumably also a reduced decomposition rate if the thiourea-hydroxide complex-decomposition mechanism is effective). This has been circumvented, as described later, by working with alternative sulphiding agents at low values of pH. 

Transition state mimics have generally been synthesized first on an empirical basis tetrahedral analogues if the mechanism involves a tetrahedral intermediate planar analogues if the enzyme catalyses an SNl displacement, as exemplified by the synthesis of DANA (71) for the inhibition of neuraminidase. Recognition that transition state geometry and... 

The SNl-type process occurs mostly when B is a tertiary atom or has one aryl group and at least one other alkyl or aryl group. In other cases, the SN2-type process is more likely. Inversion of configuration (indicating an SN2-type process) has been shown for a neopentyl substrate by the use of the chiral neopentyl-l-d alcohol.18 On the other hand, there is other evidence that neopentyl systems undergo rearrangement by a carbocation (SNl-type) mechanism.19... 

Evidence for the SNl-type mechanism is provided by fluorodehydroxylation of diastereomeric benzylic alcohols both diastercomers give the same mixture of products which implies that bond breaking precedes bond making in precursors that readily form carbenium ions. Evidence for an SN2 displacement is based on the results of fluorodehydroxylation of epimeric a-amino-/ -hydroxypropanoic acids which proceeds with predominant inversion of configuration.40... 

In 95% acetone/water the relative rates of hydrolysis are 0.545 (4-MeO), 0.493 (4-Me) and 1.00 (H), indicating that 4-MeO benzoyl chloride is tending to react partly by an SN1 mechanism. In 95% acetone/water, 2 4 6 trimethyl-benzoyl chloride therefore reacts by an SNl-type mechanism and would not be expected to show an effect with added hydroxide ion. In 80% (v/v) acetone/ ethanol, the reaction is again SN2-type. 

Alkyl chloroformates, R0C(=0)C1, might be expected to hydrolyse rapidly by an SNl-type process, reminiscent of the hydrolysis of alkoxy ethers such as chloromethyl ether. Similarly, carbamates would be expected to react by a similar mechanism because of the possible stabilisation of the acylium ion formed, viz. 

When the mechanism of the reaction is more complex then an analysis of the initial state and transition state must take account of all the individual steps. A reaction which involves more than one step is the base hydrolysis of complexes of Co111, Rh111 and Crm, which are believed to react via the, SNl(cb) mechanism.29 This mechanism involves an initial pre-equilibrium to form the conjugate base, illustrated for [Co(NH3)5C1]2+ in equation (19) ... 

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