SN1 reaction

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The SN1 reaction is a substitution reaction in organic chemistry, the name of which refers to the Hughes-Ingold symbol of the mechanism. "SN" stands for "nucleophilic substitution", and the "1" says that the rate-determining step is unimolecular. [1] [2] Thus, the rate equation is often shown as having first-order dependence on the substrate and zero-order dependence on the nucleophile. This relationship holds for situations where the amount of nucleophile is much greater than that of the intermediate. Instead, the rate equation may be more accurately described using steady-state kinetics. The reaction involves a carbocation intermediate and is commonly seen in reactions of secondary or tertiary alkyl halides under strongly basic conditions or, under strongly acidic conditions, with secondary or tertiary alcohols. With primary and secondary alkyl halides, the alternative SN2 reaction occurs. In inorganic chemistry, the SN1 reaction is often known as the dissociative substitution . This dissociation pathway is well-described by the cis effect. A reaction mechanism was first proposed by Christopher Ingold et al. in 1940. [3] This reaction does not depend much on the strength of the nucleophile, unlike the SN2 mechanism. This type of mechanism involves two steps. The first step is the ionization of alkyl halide in the presence of aqueous acetone or ethyl alcohol. This step provides a carbocation as an intermediate.

Contents

In the first step of SN1 mechanism, a carbocation is formed which is planar and hence attack of nucleophile (second step) may occur from either side to give a racemic product, but actually complete racemization does not take place. This is because the nucleophilic species attacks the carbocation even before the departing halides ion has moved sufficiently away from the carbocation. The negatively charged halide ion shields the carbocation from being attacked on the front side, and backside attack, which leads to inversion of configuration, is preferred. Thus the actual product no doubt consists of a mixture of enantiomers but the enantiomers with inverted configuration would predominate and complete racemization does not occurs.

Mechanism

An example of a reaction taking place with an SN1 reaction mechanism is the hydrolysis of tert-butyl bromide forming tert-butanol:

ReakcjaSn1hydrolizabromkutertbutylowego.svg

This SN1 reaction takes place in three steps:

Sn1pierwszyetapreakcjipowstaniekarbokationu.svg
Recombination of carbocation with nucleophile Nucleophilic attack of oxonium ion.gif
Recombination of carbocation with nucleophile
NS1 reaction part2 recombination carbocation nucleophile.svg

NS1 reaction part3 proton transfer forming alcohol.svg

Rate law

Although the rate law of the SN1 reaction is often regarded as being first order in alkyl halide and zero order in nucleophile, this is a simplification that holds true only under certain conditions. While it, too, is an approximation, the rate law derived from the steady state approximation (SSA) provides more insight into the kinetic behavior of the SN1 reaction. Consider the following reaction scheme for the mechanism shown above:

SN1-steady-state-approximation.png

Though a relatively stable tertiary carbocation, tert-butyl cation is a high-energy species that is present only at very low concentration and cannot be directly observed under normal conditions. Thus, the SSA can be applied to this species:

Under normal synthetic conditions, the entering nucleophile is more nucleophilic than the leaving group and is present in excess. Moreover, kinetic experiments are often conducted under initial rate conditions (5 to 10% conversion) and without the addition of bromide, so [Br–] is negligible. For these reasons, k–1[Br–] ≪ k2[H2O] often holds. Under these conditions, the SSA rate law reduces to

rate = d[tBuOH]/dt = k1k2[tBuBr][H2O]/(k2[H2O]) = k1[tBuBr],

the simple first-order rate law described in introductory textbooks. Under these conditions, the concentration of the nucleophile does not affect the rate of the reaction, and changing the nucleophile (e.g. from H2O to MeOH) does not affect the reaction rate, though the product is, of course, different. In this regime, the first step (ionization of the alkyl bromide) is slow, rate-determining, and irreversible, while the second step (nucleophilic addition) is fast and kinetically invisible.

However, under certain conditions, non-first-order reaction kinetics can be observed. In particular, when a large concentration of bromide is present while the concentration of water is limited, the reverse of the first step becomes important kinetically. As the SSA rate law indicates, under these conditions there is a fractional (between zeroth and first order) dependence on [H2O], while there is a negative fractional order dependence on [Br–]. Thus, SN1 reactions are often observed to slow down when an exogenous source of the leaving group (in this case, bromide) is added to the reaction mixture. This is known as the common ion effect and the observation of this effect is evidence for an SN1 mechanism (although the absence of a common ion effect does not rule it out). [5] [6]

Scope

The SN1 mechanism tends to dominate when the central carbon atom is surrounded by bulky groups because such groups sterically hinder the SN2 reaction. Additionally, bulky substituents on the central carbon increase the rate of carbocation formation because of the relief of steric strain that occurs. The resultant carbocation is also stabilized by both inductive stabilization and hyperconjugation from attached alkyl groups. The Hammond–Leffler postulate suggests that this, too, will increase the rate of carbocation formation. The SN1 mechanism therefore dominates in reactions at tertiary alkyl centers.

An example of a reaction proceeding in a SN1 fashion is the synthesis of 2,5-dichloro-2,5-dimethylhexane from the corresponding diol with concentrated hydrochloric acid: [7]

SN1reactionWagner2009.svg

As the alpha and beta substitutions increase with respect to leaving groups, the reaction is diverted from SN2 to SN1.

Stereochemistry

The carbocation intermediate formed in the reaction's rate determining step (RDS) is an sp2 hybridized carbon with trigonal planar molecular geometry. This allows two different ways for the nucleophilic attack, one on either side of the planar molecule. If neither approach is favored, then these two ways occur equally, yielding a racemic mixture of enantiomers if the reaction takes place at a stereocenter. [8] This is illustrated below in the SN1 reaction of S-3-chloro-3-methylhexane with an iodide ion, which yields a racemic mixture of 3-iodo-3-methylhexane:

A typical SN1 reaction, showing how racemisation occurs SN1Stereochemistry.png
A typical SN1 reaction, showing how racemisation occurs

However, an excess of one stereoisomer can be observed, as the leaving group can remain in proximity to the carbocation intermediate for a short time and block nucleophilic attack. This stands in contrast to the SN2 mechanism, which is a stereospecific mechanism where stereochemistry is always inverted as the nucleophile comes in from the rear side of the leaving group.

Side reactions

Two common side reactions are elimination reactions and carbocation rearrangement. If the reaction is performed under warm or hot conditions (which favor an increase in entropy), E1 elimination is likely to predominate, leading to formation of an alkene. At lower temperatures, SN1 and E1 reactions are competitive reactions and it becomes difficult to favor one over the other. Even if the reaction is performed cold, some alkene may be formed. If an attempt is made to perform an SN1 reaction using a strongly basic nucleophile such as hydroxide or methoxide ion, the alkene will again be formed, this time via an E2 elimination. This will be especially true if the reaction is heated. Finally, if the carbocation intermediate can rearrange to a more stable carbocation, it will give a product derived from the more stable carbocation rather than the simple substitution product.

Solvent effects

Since the SN1 reaction involves formation of an unstable carbocation intermediate in the rate-determining step (RDS), anything that can facilitate this process will speed up the reaction. The normal solvents of choice are both polar (to stabilize ionic intermediates in general) and protic solvents (to solvate the leaving group in particular). Typical polar protic solvents include water and alcohols, which will also act as nucleophiles, and the process is known as solvolysis.

The Y scale correlates solvolysis reaction rates of any solvent (k) with that of a standard solvent (80% v/v ethanol/water) (k0) through

with m a reactant constant (m = 1 for tert-butyl chloride) and Y a solvent parameter. [9] For example, 100% ethanol gives Y = −2.3, 50% ethanol in water Y = +1.65 and 15% concentration Y = +3.2. [10]

See also

Related Research Articles

In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they are Lewis bases.

A nucleophilic substitution is a class of chemical reactions in which an electron-rich chemical species replaces a functional group within another electron-deficient molecule. The molecule that contains the electrophile and the leaving functional group is called the substrate.

Elimination reaction Reaction where 2 substituents are removed from a molecule in a 1 or 2 step mechanism

An elimination reaction is a type of organic reaction in which two substituents are removed from a molecule in either a one- or two-step mechanism. The one-step mechanism is known as the E2 reaction, and the two-step mechanism is known as the E1 reaction. The numbers refer not to the number of steps in the mechanism, but rather to the kinetics of the reaction: E2 is bimolecular (second-order) while E1 is unimolecular (first-order). In cases where the molecule is able to stabilize an anion but possesses a poor leaving group, a third type of reaction, E1CB, exists. Finally, the pyrolysis of xanthate and acetate esters proceed through an "internal" elimination mechanism, the Ei mechanism.

Leaving group

In chemistry, a leaving group is defined by the IUPAC as an atom or group of atoms that detaches from the main or residual part of a substrate during a reaction or elementary step of a reaction. However, in common usage, the term is often limited to a fragment that departs with a pair of electrons in heterolytic bond cleavage. In this usage, a leaving group is a less formal but more commonly used synonym of the term nucleofuge. In this context, leaving groups are generally anions or neutral species, departing from a neutral or cationic substrates, respectively, though in rare cases, cations leaving from a dicationic substrate are also known. A species' ability to serve as a leaving group depends on its ability to stabilize the additional electron density that results from bond heterolysis. Common anionic leaving groups are halides such as Cl−, Br−, and I−, and sulfonate esters such as tosylate (TsO−), while water (H2O), alcohols (HOR), and amines (R3N) are common neutral leaving groups.

Carbocation Ion with a positively charged carbon atom

A carbocation is an ion with a positively charged carbon atom. Among the simplest examples are the methenium CH+
3, methanium CH+
5 and vinyl C
2H+
3 cations. Occasionally, carbocations that bear more than one positively charged carbon atom are also encountered.

S<sub>N</sub>2 reaction Substitution reaction where bonds are broken and formed simultaneously

The SN2 reaction is a type of reaction mechanism that is common in organic chemistry. In this mechanism, one bond is broken and one bond is formed synchronously, i.e., in one step. SN2 is a kind of nucleophilic substitution reaction mechanism, the name referring to the Hughes-Ingold symbol of the mechanism. Since two reacting species are involved in the slow (rate-determining) step, this leads to the term substitution nucleophilic (bi-molecular) or SN2; the other major kind is SN1. Many other more specialized mechanisms describe substitution reactions.

In chemistry, an electrophile is a chemical species that forms bonds with nucleophiles by accepting an electron pair. Because electrophiles accept electrons, they are Lewis acids. Most electrophiles are positively charged, have an atom that carries a partial positive charge, or have an atom that does not have an octet of electrons.

A substitution reaction is a chemical reaction during which one functional group in a chemical compound is replaced by another functional group. Substitution reactions are of prime importance in organic chemistry. Substitution reactions in organic chemistry are classified either as electrophilic or nucleophilic depending upon the reagent involved, whether a reactive intermediate involved in the reaction is a carbocation, a carbanion or a free radical, and whether the substrate is aliphatic or aromatic. Detailed understanding of a reaction type helps to predict the product outcome in a reaction. It also is helpful for optimizing a reaction with regard to variables such as temperature and choice of solvent.

In chemical kinetics, the overall rate of a reaction is often approximately determined by the slowest step, known as the rate-determining step or rate-limiting step. For a given reaction mechanism, the prediction of the corresponding rate equation is often simplified by using this approximation of the rate-determining step.

Appel reaction

The Appel reaction is an organic reaction that converts an alcohol into an alkyl chloride using triphenylphosphine and carbon tetrachloride. The use of carbon tetrabromide or bromine as a halide source will yield alkyl bromides, whereas using carbon tetraiodide, methyl iodide or iodine gives alkyl iodides. The reaction is credited to and named after Rolf Appel, it had however been described earlier. The use of this reaction is becoming less common, due to carbon tetrachloride being restricted under the Montreal protocol.

Solvolysis is a type of nucleophilic substitution (SN1/SN2) or elimination where the nucleophile is a solvent molecule. Characteristic of SN1 reactions, solvolysis of a chiral reactant affords the racemate. Sometimes however, the stereochemical course is complicated by intimate ion pairs, whereby the leaving anion remains close to the carbocation, effectively shielding it from an attack by the nucleophile. Particularly fast reactions can occur by neighbour group participation, with nonclassical ions as intermediates or transition states.

In chemistry the intimate ion pair concept introduced by Saul Winstein describes the interactions between a cation, anion and surrounding solvent molecules. In ordinary aqueous solutions of inorganic salts an ion is completely solvated and shielded from the counterion. In less polar solvents two ions can still be connected to some extent. In a tight or intimate or contact ion pair there are no solvent molecules between the two ions. When solvation increases, ionic bonding decreases and a loose or solvent-shared ion pair results. The ion pair concept explains stereochemistry in solvolysis.

S<sub>N</sub>i

SNi or Substitution Nucleophilic intramolecular stands for a specific but not often encountered nucleophilic aliphatic substitution reaction mechanism. The name was introduced by Cowdrey et al. in 1937 to label nucleophilic reactions which occur with retention of configuration, but later was employed to describe various reactions that proceed with similar mechanism.

In organic chemistry, neighbouring group participation has been defined by the International Union of Pure and Applied Chemistry (IUPAC) as the interaction of a reaction centre with a lone pair of electrons in an atom or the electrons present in a pi bond contained within the parent molecule but not conjugated with the reaction centre. When NGP is in operation it is normal for the reaction rate to be increased. It is also possible for the stereochemistry of the reaction to be abnormal when compared with a normal reaction. While it is possible for neighbouring groups to influence many reactions in organic chemistry this page is limited to neighbouring group effects seen with carbocations and SN2 reactions.

Grignard reagent Organometallic compounds used in organic synthesis

A Grignard reagent or Grignard compound is a chemical compound with the generic formula R−Mg−X, where X is a halogen and R is an organic group, normally an alkyl or aryl. Two typical examples are methylmagnesium chloride Cl−Mg−CH3 and phenylmagnesium bromide (C6H5)−Mg−Br. They are a subclass of the organomagnesium compounds.

In physical organic chemistry, the Grunwald–Winstein equation is a linear free energy relationship between relative rate constants and the ionizing power of various solvent systems, describing the effect of solvent as nucleophile on different substrates. The equation, which was developed by Ernest Grunwald and Saul Winstein in 1948, could be written

In chemistry, solvent effects are the influence of a solvent on chemical reactivity or molecular associations. Solvents can have an effect on solubility, stability and reaction rates and choosing the appropriate solvent allows for thermodynamic and kinetic control over a chemical reaction.

Living cationic polymerization is a living polymerization technique involving cationic propagating species. It enables the synthesis of very well defined polymers and of polymers with unusual architecture such as star polymers and block copolymers and living cationic polymerization is therefore as such of commercial and academic interest.

2-Chlorobutane Chemical compound

2-Chlorobutane is a compound with formula C4H9Cl. It is also called sec-butyl chloride. It is a colorless, volatile liquid at room temperature that is not miscible in water.

Ether cleavage refers to chemical substitution reactions that lead to the cleavage of ethers. Due to the high chemical stability of ethers, the cleavage of the C-O bond is uncommon in the absence of specialized reagents or under extreme conditions.

References

  1. ↑ L. G. Wade, Jr., Organic Chemistry, 6th ed., Pearson/Prentice Hall, Upper Saddle River, New Jersey, USA, 2005
  2. ↑ March, J. (1992). Advanced Organic Chemistry (4th ed.). New York: Wiley. ISBN   0-471-60180-2.
  3. ↑ Bateman LC, Church MG, Hughes ED, Ingold CK, Taher NA (1940). "188. Mechanism of substitution at a saturated carbon atom. Part XXIII. A kinetic demonstration of the unimolecular solvolysis of alkyl halides. (Section E) a general discussion". Journal of the Chemical Society (Resumed): 979. doi:10.1039/JR9400000979.
  4. ↑ Peters, K. S. (2007). "Nature of Dynamic Processes Associated with the SN1 Reaction Mechanism". Chem. Rev. 107 (3): 859–873. doi:10.1021/cr068021k. PMID   17319730.
  5. ↑ Anslyn, Eric V., 1960- (2006). Modern physical organic chemistry. Dougherty, Dennis A., 1952-. Mill Valley, California: University Science Books. pp. 638–639. ISBN   1-891389-31-9. OCLC   55600610.{{cite book}}: CS1 maint: multiple names: authors list (link)
  6. ↑ Lowry, Thomas H. (1987). Mechanism and theory in organic chemistry. Richardson, Kathleen Schueller. (3rd ed.). New York: Harper & Row. pp. 330–331. ISBN   0-06-044084-8. OCLC   14214254.
  7. ↑ Wagner, Carl E.; Marshall, Pamela A. (2010). "Synthesis of 2,5-Dichloro-2,5-dimethylhexane by an SN1 Reaction". J. Chem. Educ. 87 (1): 81–83. Bibcode:2010JChEd..87...81W. doi:10.1021/ed8000057.
  8. ↑ Sorrell, Thomas N. "Organic Chemistry, 2nd Edition" University Science Books, 2006
  9. ↑ Ernest Grunwald & S. Winstein (1948). "The Correlation of Solvolysis Rates". J. Am. Chem. Soc. 70 (2): 846. doi:10.1021/ja01182a117.
  10. ↑ Arnold H. Fainberg & S. Winstein (1956). "Correlation of Solvolysis Rates. III.1 t-Butyl Chloride in a Wide Range of Solvent Mixtures". J. Am. Chem. Soc. 78 (12): 2770. doi:10.1021/ja01593a033.
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