SN1 REACTIONS Introduction Ingold and Hughes coined the term SN1 (subsitution nucleophile and unimolecular) which depends on only substrate concentration. Nucleophilic substitution reaction occurs when the substrate and nucleophile react together in a two-step process, where the first step involves leaving group (LG),it leaves first and leads to a carbocation intermediate, while the second step involves the nucleophile (Nu), Nu attacks the carbocation intermediate. SN1 Reaction Nucleophilic substitution reactions that follow first order kinetics are known as SN1 reactions. The rate of first order reaction depends only upon the concentration of the substrate. These reactions can be completed in following manner: Kinetics of SN1 Reactions The SN1 reaction is initiated by the dissociation of the leaving group and formation of the carbocation intermediate in the first step. After formation of the carbocation intermediate, the nucleophile takes part in the second step. Increasing or decreasing the concentration of the nucleophile has no measurable effect on the rate. The nucleophile is not involved in the initial step of rate-determination, thus the concentration does not affect the overall reaction rate. This reaction follows first order kinetics. The reaction is first order with respect to alkyl halide while zero order with respect to the nucleophile. Rate = k [Substrate] The energy profile diagram is shown in fig.1 Energy Profile of SN1 reaction The SN1 reactions are sometimes referred to solvolysis reactions. Stereochemical Features of SN1 Reaction: When a reaction is proceeding by SN1 mechanism , then inversion and retention of congiguration will occur , the amount of each depending on vatious factors. In case the substrate is optically active , the carbonium ion is flat (trigonal hybridisation ) and hence attack by the nucleophilic reagent can take place equally on either side. This means that equal amounts of (+) and (-) forms of the product will be produced. The result is racemisation. As mentioned earlier , this is broad generalisation and the composition of product(enantiomers) is depended on several experimental conditions. A possible explanation is that the departing group shields the side carbon atom at which it was attached so that the incoming nucleophile more easily approached from the other side For example, (R)-1-Chloro-1-phenylbutane undergoes solvolysis in water lead to optically inactive product enantiomeric alcohols. Factors Influencing SN1 Reaction Solvent: The rate of the reaction can be affected by the energy level of the reagents. Solvation of the carbocation allows the carbocation to be surrounded by more electron density, making the positive charge more stable (see below). The solvent can be protic or aprotic, but it must be polar solvent. Polar protic solvents have a H-atom attached to an electronegative atom so the hydrogen is highly polarized. Polar aprotic solvents have a dipole moment, but their hydrogen is not highly polarized. Polar aprotic solvents are not used in SN1 reactions because some of them can react with the carbocation intermediate and lead to unwanted product. Thus, polar protic solvents are preferred in SN1 reaction which helps to speed up the rate of reaction due to large dipole moment of the solvent which helps to stabilize the transition state. The highly positive and highly negative parts interact with the substrate to lower the energy of the transition state. Since the carbocation is unstable, anything that can stabilize this even a little will speed up the reaction. Sometimes in an SN1 reaction the solvent acts as the nucleophile known as solvolysis reaction. The polarity and the ability of the solvent to stabilize the intermediate carbocation, is very important as shown by the relative rate data for the solvolysis (in table). The dielectric constant of a solvent provides a measure of the solvent's polarity. A dielectric constant below 15 is usually considered non-polar. Thus, higher the dielectric constant more polar will be substance and in the case of SN1 reactions the faster the rate. Table Solvent Dielectric Constant Relative rate Acetic acid 6 1 Methanol 33 4 Water 78 150000 The example given here illustrates this concept. Nucleophile: Nucleophiles involved in the SN1 mechanism are mostly weak and neutral molecules (viz. H2O, ROH). The strength of the nucleophile does not affect the reaction rate of SN1 because; the nucleophile is involved in the rate- determining step. However, if you have more than one nucleophile competing to bond to the carbocation, the strengths and concentrations of those nucleophiles affect the distribution of products. For example, if you have (CH3)3CCl reacting in water and formic acid where the water and formic acid are competing nucleophiles, you will get two different products: (CH3)3COH and (CH3)3COCOH. The relative yields of these products depend on the concentrations and relative reactivities of the nucleophiles. Substrate: The hyperconjugation and the inductive effect allow alkyl groups to stabilize carbocations. The more stable carbocation intermediate has a lower activation barrier, so the SN1 reaction occurs faster. In general, the SN1 reaction is favored in the order is Benzylic > Allylic > 3° > 2° > 1° >> Me+. Substrates wherein the leaving group (LG) is on a 3° carbon will lead to a reaction in the presence of a good nucleophile (Nu). Since, 1° carbocations are highly energetically unfavorable, as a rule of thumb they generally do not form. The rate for hydrolysis of alkyl halide is in the order of halides, 3o > 2o > 1o > MeX. Thus, we can say the electronic factor is more important than the steric factor. The Eact for the carbocation intermediate will be highest for MeX (1o), while least for the 3o. The molecules in which carbon next to the site of substitution contains a double bond, the SN1 reaction is possible. The reason is that the positive charge on the carbocation can be delocalized among multiple possible resonance structures (resonance and delocalization) making the carbocation dramatically stable. This effect can occur when the carbon atom of interest is next to one double bond (allylic) or a benzene ring (benzylic). In allylic case the delocalization of the positive charge, the nucleophile can attack at multiple sites while this effect is absent in the benzylic system due to the need to preserve aromaticity. For example, the allylic carbocation can form two different resonance structure, both are available for reaction (see below). In the first example we end up with similar carbocation intermediate but we have different situation in the second example where we have 2o and 3o carbocation intermediates. Thus, second reaction will lead to 3o product through stable 3o carbocation intermediate. Delocalization and resonance If there is a benzylic carbocation, it is also resonance stabilized but only the carbocation on the benzylic position is reactive (retains the aromatic ring) as follows: Leaving Group: The leaving group is almost always expelled with a full negative charge. The best leaving groups are those that can best stabilize an anion (i.e. a weak base). SN1 reaction speeds up with a good leaving group. This is because the leaving group is involved in the rate-determining step. A good leaving group wants to leave so it breaks the C-leaving group bond faster. Examples of LG: - - - - - - - - (Good…….) OMs, OTos, Triflate ion, NH3 > H2O ≈ I , Br > Cl > F ( OH, NH2) (…….poor) As you go from left to right on the periodic table, electron donating ability decreases and thus ability to be a good leaving group increases. Halides are an example of a good leaving group whose leaving-group ability increases as you go down the column. Other examples of good leaving group viz. methyl sulfate ion and other sulfonate ions. - - - - (Good)….. I > Br > Cl > F …..(poor) For example: The two reactions below is the same reaction done with two different leaving groups. One is significantly faster than the other. This is because the better leaving group leaves faster and thus the reaction can proceed faster. 1. Examples of SN1 Reactions Bromination: SN1 Mechanism for Reaction of Alcohols with HBr: Step i: Acid/base Reaction: Protonation of the alcoholic oxygen to make it a better leaving group. This step is fast and reversible. The lone pairs on the oxygen make it a Lewis base. Step ii: Rate determining step: Cleavage of the C-O bond allows the loss of the leaving group, a neutral water molecule, to give a carbocation intermediate. Step iii: Attack of the nucleophilic bromide ion on the electrophilic carbocation creates the alkyl bromide. Rearrangement reactions in SN1 reactions: Carbocation intermediates, once formed rearrangements can potentially occur which include SN1 reactions, E1 elimination and electrophilic addition to double bonds. Some examples are as follows which involve either hydride shift or alkyl shift. .