Markownikoff s rule

A considerable amount of hydrobromic acid is consumed in the manufacture of inorganic bromides, as well as in the synthesis of alkyl bromides from alcohols. The acid can also be used to hydrobrominate olefins (qv). The addition can take place by an ionic mechanism, usually in a polar solvent, according to Markownikoff s rule to yield a secondary alkyl bromide. Under the influence of a free-radical catalyst, in aprotic, nonpolar solvents, dry hydrogen bromide reacts with an a-olefin to produce a primary alkyl bromide as the predominant product. Primary alkyl bromides are useful in synthesizing other compounds and are 40—60 times as reactive as the corresponding chlorides (6). 

Reaction of the natural rubber hydrocarbon with hydrochloric acid yields rubber hydrochloride. The hydrogen chloride adds on according to Markownikoff s rule (that the halogen atom attaches itself to the carbon atom with the least number of hydrogen atoms). 

As will be indicated when the mechanism is discussed in more detail, discrete carbocations may not be formed in all cases. An unsymmetrical alkene will nevertheless follow Markownikoff s rule, because the partial positive charge that develops will be located preferentially at the carbon that is better able to accommodate the electron deficiency, that is, the more substituted one. 

This mechanism explains the observed formation of the more highly substituted alcohol from unsymmetrical alkenes (Markownikoff s rule). A number of other points must be considered in order to provide a more complete picture of the mechanism. Is the protonation step reversible Is there a discrete carbocation intermediate, or does the nucleophile become involved before proton transfer is complete Can other reactions of the carbocation, such as rearrangement, compete with capture by water ... 

The regioselectivity of the second step is consistent with MarkownikofF s rule because a halogen atom can stabilize a carbocation by resonance. 

With unsymmetrical alkenes, Markownikoff s rule is applied. On addition of H-X, the hydrogen atom adds to the carbon atom which already has the more hydrogen atoms directly bonded to it. Applying the rule results in 2-bromopropane as the major product below. 

On the other hand, the fact that the methyl resonances appear as sharp singlets at 1.53 ppm for the hydrochlorinated product and at 1.69 ppm for the hydrobrominated product indicates the exclusiveness of Markownikoff s rule for the addition of either hydrogen halide to the repeating units of 1,4-polyisoprene. 

The term regioselective is used to describe addition reactions that proceed selectively in one direction with unsymmetrical alkenes.1 Markownikoff s rule describes a specific case of regioselectivity that is based on the stabilizing effect that alkyl and aryl substituents have on carbocations. 

Addition of a proton occurs to give the more substituted carbocation and addition is regioselective, in accord with Markownikoff s rule. A more detailed discussion of the reaction mechanism is given in Section 6.2 of Part A. The reaction is occasionally applied to the synthesis of tertiary alcohols ... 

Trifhioroacetic acid is a sufficiently strong acid to react with alkenes under relatively mild conditions.11 The addition is regioselective in the direction predicted by Markownikoff s rule. 

The elimination is promoted by oxidation of the addition product to the selenoxide by t-butyl hydroperoxide. The regioselectivity in this reaction is such that the hydroxyl group becomes bound at the more substituted end of the carbon-carbon double bond. The origin of this regioselectivity is that the addition step follows Markownikoff s rule, with PhSe+ acting as the electrophile. The elimination step specifically proceeds away from the oxygen functionality. 

Calculation of the proton affinities of the carbon atoms of the doubly-bonded pairs in propylene and isobutylene has shown that the proton affinity of the end carbon atom is greater in each case (Evans and Pol-anyi, 14). This means that the proton will add to the double bond at the CH2 more readily than at the CHCH3 or C(CH3)2. Hence, if the addition of HX to a double bond proceeds by way of initial addition of a proton, the hydrogen atom will become attached to the carbon atom holding the greater number of hydrogen atoms. Markownikoff s rule has thus been interpreted in terms of proton affinities which in turn are calculated from bond strengths and ionization potentials. 

The radical chain mechanism for the abnormal addition of thiols and hydrogen sulfide (contrary to MarkOwnikofF s rule) is of great practical... 

Exercise 10-13 Explain how Markownikoff s rule for orientation in electrophilic additions can be accounted for in terms of the modern view of how these reactions occur, using the reaction of HCI with 1-methyicyclohexene as an example. 

We can extend Markownikoff s rule to cover additions of substances of the general type X—Y to unsymmetrically substituted alkenes when a clear-cut decision is possible as to whether X or Y is the more electrophilic atom of X—Y. If the polarization of the X—Y bond is such that X is positive, 6 X—Y 0, then X will be expected to add as X to the alkene to form the more stable carbocation. This step will determine the direction of addition. For example, if we know that the O-Br bond of HOBr is polarized as 60 6 ... 

Vaughan et al. (103) studied the photobromination of ethylene, propylene, 1-butene, isobutene, and vinyl chloride in the gas phase and found in every case where a distinction could be made that the product was almost entirely the so-called abnormal addition product in terms of the Markownikoff s rule. However, the more recent work of Skell et al. (95) shows that 2-bromo-w-propyl radical may rearrange very rapidly to 1-bromo-isopropyl radical. In view of this the observed exclusive terminal addition of Br atoms in the case of propylene could be in part due to rapid rearrangement. 

Spectroscopic data of a-silylketones and the chemical behaviour of vinylsilanes (addition reactions opposite to Markownikoff s rule) are in agreement with this (p- -d) . model. 

Mercaptans add to olefins according to Markownikoff s rule in the presence of sulfur or sulfuric acid. The mode of addition is reversed by peroxides. The yields of sulfides are generally in the range of 60-90%. Somewhat lower yields (50-60%) are obtained by the addition of mercaptans to vinyl chloride and allyl alcohol. Conjugated olefinic aldehydes, ketones, esters, and cyanides add mercaptans and thiophenols in excellent yield. In certain cases the unsaturated compound may be converted directly to a symmetrical sulfide by addition of hydrogen sulfide (cf. method 388). 

Aqueous solutions of bisulfites react with olefins in the presence of oxygen or certain oxidizing agents. Addition of the bisulfite takes place by a free-radical mechanism contrary to Markownikoff s rule. The yields of sulfonates are usually low (12-62%). Styrene gives mainly 2-hydroxy-2-phenylethanesulfonic acid. Bisulfite has also been added to the double bonds in allyl and cinnamyl alcohols. /3-Sulfocarboxylic acids are prepared in this way from a,/3-olefinic acids. /3,/3-Disulfopropionic acid is made in 80% yield by the addition of two molecules of bisulfite to... 

The direction of addition of the B-H bond to atrisubstituted double bond seems to be determined by the addition of the more electronegative hydrogen atom to the more highly substituted carbon atom of the double bond. Thus, with the B H bond assumed to be polarised in the sense B " —the process may be considered in terms of the electronic arguments summarised in the modern interpretation of Markownikoff s rule for ionic additions to double bonds [15]. The outcome of the hydroboration/oxidation sequence corresponds to an "anti-Markownikoff hydration of the double bond, which has many synthetic applications. If steric factors are also important, these of course operate in the same sense, generally favouring attachment of boron to the less-hindered secondary carbon atom. 

Uasymmetrical reagents add to olefins in such a way that the more negative fragment appears on the carbon atom carrying the smaller number of hydrogen atoms. (Markownikoff s rule,) In terms of hyperconjugation theory, this is the more positive atom (see p. 32). 

Markownikoff s rule can be inverted by groups that have a high affinity for electrons, such as NO2. It is also inverted in additions... 

It is clear from the above data that the addition of HBr to the alkenes containing terminal double bonds results in the formation of primary bromides whenever peroxides are present in the reaction mixture. Secondary and tertiary bromides are formed during the normal addition in the presence of antioxidants in accordance with Markownikoff s rule. In general, the yields of the alkyl halides are high and the formation of the specific product is almost quantitative. 

The effect of conjugation of a C=C with a C=0 or C=N bond would be to permit the formation of addition products that would not be expected from Markownikoff s rule, as is evidenced by the following reactions ... 

The addition takes place according to Markownikoff s rule. The addition of carbo lic acida to the double bonds of isobutylene and trimethyl-ethylene gives tertiary esters. A true equilibrium independent of sulfuric acid concentrations is established in the exothermic reaction. The addition does not go well with ethylene, but goes well with many of the higher alkenes, particularly with some of the terpenes. To avoid the polymerizing effects of sulfuric acid, various other catalysts, such as sulfonic acids, triethylamine, hydrofluoric acid, boron trifluoride, and cuprous chloride have been used. The addition may take place at room temperature or higher and is aided by pressure. The vapors of the acid and hydrocarbon may be passed over catalysts, such as activated carbon, heteropoly acids, or metal phosphates. ... 

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