In organic chemistry, Markovnikov's rule or Markownikoff's rule describes the outcome of some addition reactions. The rule was formulated by Russian chemist Vladimir Markovnikov in 1870. [1] [2] [3]
In organic chemistry, Markovnikov's rule or Markownikoff's rule describes the outcome of some addition reactions. The rule was formulated by Russian chemist Vladimir Markovnikov in 1870. [1] [2] [3]
The rule states that with the addition of a protic acid HX or other polar reagent to an asymmetric alkene, the acid hydrogen (H) or electropositive part gets attached to the carbon with more hydrogen substituents, and the halide (X) group or electronegative part gets attached to the carbon with more alkyl substituents. This is in contrast to Markovnikov's original definition, in which the rule is stated that the X component is added to the carbon with the fewest hydrogen atoms while the hydrogen atom is added to the carbon with the greatest number of hydrogen atoms. [4]
The same is true when an alkene reacts with water in an addition reaction to form an alcohol which involve formation of carbocations. The hydroxyl group (OH) bonds to the carbon that has the greater number of carbon–carbon bonds, while the hydrogen bonds to the carbon on the other end of the double bond, that has more carbon–hydrogen bonds.
The chemical basis for Markovnikov's Rule is the formation of the most stable carbocation during the addition process. The addition of the hydrogen ion to one carbon atom in the alkene creates a positive charge on the other carbon, forming a carbocation intermediate. The more substituted the carbocation, the more stable it is, due to induction and hyperconjugation. The major product of the addition reaction will be the one formed from the more stable intermediate. Therefore, the major product of the addition of HX (where X is some atom more electronegative than H) to an alkene has the hydrogen atom in the less substituted position and X in the more substituted position. But the other less substituted, less stable carbocation will still be formed at some concentration, and will proceed to be the minor product with the opposite, conjugate attachment of X.
Also called Kharasch effect (named after Morris S. Kharasch), these reactions that do not involve a carbocation intermediate may react through other mechanisms that have regioselectivities not dictated by Markovnikov's rule, such as free radical addition. Such reactions are said to be anti-Markovnikov, since the halogen adds to the less substituted carbon, the opposite of a Markovnikov reaction.
The anti-Markovnikov rule can be illustrated using the addition of hydrogen bromide to isobutylene in the presence of benzoyl peroxide or hydrogen peroxide. The reaction of HBr with substituted alkenes was prototypical in the study of free-radical additions. Early chemists discovered that the reason for the variability in the ratio of Markovnikov to anti-Markovnikov reaction products was due to the unexpected presence of free radical ionizing substances such as peroxides. The explanation is that the O-O bond in peroxides is relatively weak. With the aid of light, heat, or sometimes even just acting on its own, the O-O bond can split to form 2 radicals. The radical groups can then interact with HBr to produce a Br radical, which then reacts with the double bond. Since the bromine atom is relatively large, it is more likely to encounter and react with the least substituted carbon since this interaction produces less static interactions between the carbon and the bromine radical. Furthermore, similar to a positive charged species, the radical species is most stable when the unpaired electron is in the more substituted position. The radical intermediate is stabilized by hyperconjugation. In the more substituted position, more carbon-hydrogen bonds are aligned with the radical's electron deficient molecular orbital. This means that there are greater hyperconjugation effects, so that position is more favorable. [5] In this case, the terminal carbon is a reactant that produces a primary addition product instead of a secondary addition product.
A new method of anti-Markovnikov addition has been described by Hamilton and Nicewicz, who utilize aromatic molecules and light energy from a low-energy diode to turn the alkene into a cation radical. [6] [7]
Anti-Markovnikov behaviour extends to more chemical reactions than additions to alkenes. Anti-Markovnikov behaviour is observed in the hydration of phenylacetylene by auric catalysis, which gives acetophenone; although with a special ruthenium catalyst [8] it provides the other regioisomer 2-phenylacetaldehyde: [9]
Anti-Markovnikov behavior can also manifest itself in certain rearrangement reactions. In a titanium(IV) chloride-catalyzed formal nucleophilic substitution at enantiopure 1 in the scheme below, two products are formed – 2a and 2b Due to the two chiral centers in the target molecule, the carbon carrying chlorine and the carbon carrying the methyl and acetoxyethyl group, four different compounds are to be formed: 1R,2R- (drawn as 2b) 1R,2S- 1S,2R- (drawn as 2a) and 1S,2S- . Therefore, both of the depicted structures will exist in a D- and an L-form. : [10]
This product distribution can be rationalized by assuming that loss of the hydroxy group in 1 gives the tertiary carbocation A, which rearranges to the seemingly less stable secondary carbocation B. Chlorine can approach this center from two faces leading to the observed mixture of isomers.
Another notable example of anti-Markovnikov addition is hydroboration.
In organic chemistry, an alkene, or olefin, is a hydrocarbon containing a carbon–carbon double bond. The double bond may be internal or in the terminal position. Terminal alkenes are also known as α-olefins.
Vladimir Vasilyevich Markovnikov, also Markownikoff was a Russian chemist, best known for having developed the Markovnikov's rule, that describes addition reactions of hydrogen halides and alkenes.
The haloalkanes are alkanes containing one or more halogen substituents. They are a subset of the general class of halocarbons, although the distinction is not often made. Haloalkanes are widely used commercially. They are used as flame retardants, fire extinguishants, refrigerants, propellants, solvents, and pharmaceuticals. Subsequent to the widespread use in commerce, many halocarbons have also been shown to be serious pollutants and toxins. For example, the chlorofluorocarbons have been shown to lead to ozone depletion. Methyl bromide is a controversial fumigant. Only haloalkanes that contain chlorine, bromine, and iodine are a threat to the ozone layer, but fluorinated volatile haloalkanes in theory may have activity as greenhouse gases. Methyl iodide, a naturally occurring substance, however, does not have ozone-depleting properties and the United States Environmental Protection Agency has designated the compound a non-ozone layer depleter. For more information, see Halomethane. Haloalkane or alkyl halides are the compounds which have the general formula "RX" where R is an alkyl or substituted alkyl group and X is a halogen.
In organic chemistry, the oxymercuration reaction is an electrophilic addition reaction that transforms an alkene into a neutral alcohol. In oxymercuration, the alkene reacts with mercuric acetate in aqueous solution to yield the addition of an acetoxymercury group and a hydroxy group across the double bond. Carbocations are not formed in this process and thus rearrangements are not observed. The reaction follows Markovnikov's rule and it is an anti addition.
Hydroboration–oxidation reaction is a two-step hydration reaction that converts an alkene into an alcohol. The process results in the syn addition of a hydrogen and a hydroxyl group where the double bond had been. Hydroboration–oxidation is an anti-Markovnikov reaction, with the hydroxyl group attaching to the less-substituted carbon. The reaction thus provides a more stereospecific and complementary regiochemical alternative to other hydration reactions such as acid-catalyzed addition and the oxymercuration–reduction process. The reaction was first reported by Herbert C. Brown in the late 1950s and it was recognized in his receiving the Nobel Prize in Chemistry in 1979.
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.
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.
In organic chemistry, free-radical addition is an addition reaction which involves free radicals. Radical additions are known for a variety of unsaturated substrates, both olefinic or aromatic and with or without heteroatoms.
In organic chemistry, an electrophilic addition reaction is an addition reaction where a chemical compound containing a double or triple bond has a π bond broken, with the formation of two new σ bonds.
A 1,2-rearrangement or 1,2-migration or 1,2-shift or Whitmore 1,2-shift is an organic reaction where a substituent moves from one atom to another atom in a chemical compound. In a 1,2 shift the movement involves two adjacent atoms but moves over larger distances are possible. In the example below the substituent R moves from carbon atom C2 to C3.
A hydrohalogenation reaction is the electrophilic addition of hydrogen halides like hydrogen chloride or hydrogen bromide to alkenes to yield the corresponding haloalkanes.
In organic chemistry, syn- and anti-addition are different ways in which substituent molecules can be added to an alkene or alkyne. The concepts of syn and anti addition are used to characterize the different reactions of organic chemistry by reflecting the stereochemistry of the products in a reaction.
Azobisisobutyronitrile (abbreviated AIBN) is an organic compound with the formula [(CH3)2C(CN)]2N2. This white powder is soluble in alcohols and common organic solvents but is insoluble in water. It is often used as a foamer in plastics and rubber and as a radical initiator.
In organic chemistry, hydroboration refers to the addition of a hydrogen-boron bond to certain double and triple bonds involving carbon. This chemical reaction is useful in the organic synthesis of organic compounds.
In organic chemistry, hyperconjugation refers to the delocalization of electrons with the participation of bonds of primarily σ-character. Usually, hyperconjugation involves the interaction of the electrons in a sigma (σ) orbital with an adjacent unpopulated non-bonding p or antibonding σ* or π* orbitals to give a pair of extended molecular orbitals. However, sometimes, low-lying antibonding σ* orbitals may also interact with filled orbitals of lone pair character (n) in what is termed negative hyperconjugation. Increased electron delocalization associated with hyperconjugation increases the stability of the system. In particular, the new orbital with bonding character is stabilized, resulting in an overall stabilization of the molecule. Only electrons in bonds that are in the β position can have this sort of direct stabilizing effect — donating from a sigma bond on an atom to an orbital in another atom directly attached to it. However, extended versions of hyperconjugation can be important as well. The Baker–Nathan effect, sometimes used synonymously for hyperconjugation, is a specific application of it to certain chemical reactions or types of structures.
In chemistry, a reaction intermediate, or intermediate, is a molecular entity arising within the sequence of a stepwise chemical reaction. It is formed as the reaction product of an elementary step, from the reactants and/or preceding intermediates, but is consumed in a later step. It does not appear in the chemical equation for the overall reaction.
Morris Selig Kharasch was a pioneering organic chemist best known for his work with free radical additions and polymerizations. He defined the peroxide effect, explaining how an anti-Markovnikov orientation could be achieved via free radical addition. Kharasch was born in the Russian Empire in 1895 and immigrated to the United States at the age of 13. In 1919, he completed his Ph.D. in chemistry at the University of Chicago and spent most of his professional career there.
In chemistry, a radical, also known as a free radical, is an atom, molecule, or ion that has at least one unpaired valence electron. With some exceptions, these unpaired electrons make radicals highly chemically reactive. Many radicals spontaneously dimerize. Most organic radicals have short lifetimes.
The vinyl cation is a carbocation with the positive charge on an alkene carbon. Its empirical formula is C
2H+
3. More generally, a vinylic cation is any disubstituted carbon, where the carbon bearing the positive charge is part of a double bond and is sp hybridized. In the chemical literature, substituted vinylic cations are often referred to as vinyl cations, and understood to refer to the broad class rather than the C
2H+
3 variant alone. The vinyl cation is one of the main types of reactive intermediates involving a non-tetrahedrally coordinated carbon atom, and is necessary to explain a wide variety of observed reactivity trends. Vinyl cations are observed as reactive intermediates in solvolysis reactions, as well during electrophilic addition to alkynes, for example, through protonation of an alkyne by a strong acid. As expected from its sp hybridization, the vinyl cation prefers a linear geometry. Compounds related to the vinyl cation include allylic carbocations and benzylic carbocations, as well as aryl carbocations.
The Kharasch–Sosnovsky reaction is a method that involves using a copper or cobalt salt as a catalyst to oxidize olefins at the allylic position, subequently condensing a peroxy ester or a peroxide resulting in the formation of allylic benzoates or alcohols via radical oxidation. This method is noteworthy for being the first allylic functionalization to utilize first-row transition metals and has found numerous applications in chemical and total synthesis. Chiral ligands can be used to render the reaction asymmetric, constructing chiral C–O bonds via C–H bond activation. This is notable as asymmetric addition to allylic groups tends to be difficult due to the transition state being highly symmetric. The reaction is named after Morris S. Kharasch and George Sosnovsky who first reported it in 1958. This method is noteworthy for being the first allylic functionalization to utilize first-row transition metals and has found numerous applications in chemical and total synthesis.