PAPER No. 05: TITLE: ORGANIC CHEMISTRY-II MODULE No. 12: TITLE: S N 1 Reactions

Transcription

1 Subject hemistry Paper o and Title Module o and Title Module Tag 05, ORGAI EMISTRY-II 12, S 1 Reactions E_P5_M12 EMISTRY PAPER o. 05: TITLE: ORGAI EMISTRY-II

2 TABLE OF OTETS 1. Learning Outcomes 2. Introduction 3. S 1 Reaction 3.1 Kinetics of S 1 Reactions 3.2 Stereochemical Factors of S 1 Reaction 3.3 Factors Influencing S 1 Reaction Solvent ucleophile Substrate Leaving group 3.4 Rearrangement reaction in S 1 reaction 4. Examples of S 1 Reactions 5. Summary EMISTRY PAPER o. 05: TITLE: ORGAI EMISTRY-II

3 1. Learning Outcomes After studying this module, you shall be able to Know about S 1 reaction. Learn how S 1 reaction works. Identify key aspects of S 1 reaction. Evaluate mechanism and factors affecting S 1 reaction. 2. Introduction Ingold and ughes coined the term S 1 (subsitution nucleophile and unimolecular) which depends on only substrate concentration. ucleophilic 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 (u), u attacks the carbocation intermediate. 3. S 1 Reaction ucleophilic substitution reactions that follow first order kinetics are known as S 1 reactions. The rate of first order reaction depends only upon the concentration of the substrate. These reactions can be completed in following manner: 1. -X bond undergoes heterolysis in the first step (dissociation), 2. The positively charged carbon that is produced in the first step is called a carbocation and is of major importance in S 1 reactions, 3. In the second step, nucleophile (u) forms bonds to the carbon of carbocation (heterogenesis). The mechanism of these reactions as follows: EMISTRY PAPER o. 05: TITLE: ORGAI EMISTRY-II

4 3.1 Kinetics of S 1 Reactions The S 1 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 EMISTRY PAPER o. 05: TITLE: ORGAI EMISTRY-II

5 Energy Profile of S 1 reaction The S 1 reactions are sometimes referred to solvolysis reactions. 3.2 Stereochemical Features of S 1 Reaction: When a reaction is proceeding by S1 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 EMISTRY PAPER o. 05: TITLE: ORGAI EMISTRY-II

6 For example, (R)-1-hloro-1-phenylbutane undergoes solvolysis in water lead to optically inactive product enantiomeric alcohols. Ph 2 l Slow Ph 2 Fast Ph 2 O + Ph O 2 (R) O (R) (S) 3.3 Factors Influencing S 1 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 -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 S 1 reactions because some of them can react with the carbocation intermediate and lead to unwanted product. Thus, polar protic solvents are preferred in S 1 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. EMISTRY PAPER o. 05: TITLE: ORGAI EMISTRY-II

7 Sometimes in an S 1 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 S 1 reactions the faster the rate. Table Solvent Dielectric onstant Relative rate Acetic acid 6 1 thanol 33 4 Water The example given here illustrates this concept. 2 O 3 O Relative rate Relative rate ucleophile: ucleophiles involved in the S 1 mechanism are mostly weak and neutral molecules (viz. 2 O, RO). The strength of the nucleophile does not affect the reaction rate of S 1 because; the nucleophile is involved in the rate-determining step. owever, 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 ( 3 ) 3 l reacting in water and formic acid where the water and formic acid are competing nucleophiles, you will get two different products: ( 3 ) 3 O and ( 3 ) 3 OO. The relative yields of these products depend on the concentrations and relative reactivities of the nucleophiles. EMISTRY PAPER o. 05: TITLE: ORGAI EMISTRY-II

8 OO 2 O O O l O 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 S 1 reaction occurs faster. In general, the S 1 reaction is favored in the order is Benzylic > Allylic > 3 > 2 > 1 >> +. Substrates wherein the leaving group (LG) is on a 3 carbon will lead to a reaction in the presence of a good nucleophile (u). 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, 3 o > 2 o > 1 o > X. Thus, we can say the electronic factor is more important than the steric factor. The E act for the carbocation intermediate will be highest for X (1 o ), while least for the 3 o. The molecules in which carbon next to the site of substitution contains a double bond, the S 1 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 2 o and 3 o carbocation intermediates. Thus, second reaction will lead to 3 o product through stable 3 o 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: + + Unreactive forms EMISTRY PAPER o. 05: TITLE: ORGAI EMISTRY-II

9 3.4.4 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). S 1 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 -leaving group bond faster. Examples of LG: (Good.) - OMs, - OTos, Triflate ion, 3 > 2 O I -, - > l - > F - ( - O, - 2 ) (.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. alides 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 - > - > l - > 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. ao O (Faster), 3 ao O Slower 4. Examples of S 1 Reactions 1. omination: S 1 chanism for Reaction of Alcohols with : 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: leavage of the -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. O Fast O Slow - 2 O Fast 2. Rearrangement reactions in S 1 reactions: arbocation intermediates, once formed rearrangements can potentially occur which include S 1 reactions, E1 elimination and electrophilic addition to double bonds. Some examples are as follows which involve either hydride shift or alkyl shift. EMISTRY PAPER o. 05: TITLE: ORGAI EMISTRY-II

10 a) 3 O O 3 b) O c) 2 O O d) u + R R R u + R u EMISTRY PAPER o. 05: TITLE: ORGAI EMISTRY-II

11 4. Summary S 1 stands for substitution nucleophilic unimolecular. It is a two step process and involves initial ionization to form a carbocation intermediate followed by nucleophilic attack leading to product. The S 1 process exhibits first order kinetics and solely dependent on the concentration of the reactant The rate of the overall reaction is dependent on several factors including the structure of the substrate solvent leaving group and others. Stereochemcially reactions proceeding via S1 are usually attended with racemization of the product. The intermediate carbocation tends to be planar (sp 2 hybridisation ) EMISTRY PAPER o. 05: TITLE: ORGAI EMISTRY-II