The Best Ways To Add Alcohol To Your Shopping List

The addition of water across a double bond to make an alcohol is known as hydration. To make the alcohol on the least-substituted carbon, you can use hydroboration. This involves adding borane (BH3) in a tetrahydrofuran solvent (THF) to the alkene, followed by the addition of hydrogen peroxide (H2O2) and sodium hydroxide (NaOH). The borane adds to the least substituted side of the double bond to form the alkyl borane. Alternatively, you can break the alkene with chlorine gas, adding Cl to both sides of the alkene, and then add -OH to Sn2 the Cl.

Oxymercuration-demercuration

The first step of the mechanism involves the addition of mercuric acetate (Hg(OAc)2) to the alkene, forming a three-membered ring intermediate called a mercurinium ion. This is achieved by the pi electrons forming a bond to mercury while the lone pair on the mercury simultaneously bonds to the other vinyl carbon. The mercurium ion forms in conjunction with the loss of an acetate ion.

In the second step, a water molecule reacts with the most substituted carbon of the mercurinium ion, opening the ring and forming a mercurial alcohol. This is followed by a proton transfer to a solvent water molecule to neutralize the addition product.

The third step is the reduction of the organomercury intermediate with sodium borohydride (NaBH4) under basic conditions. This step replaces the mercuric portion with hydrogen, resulting in the formation of the Markovnikov product with the OH group attached to the most substituted carbon.

To form the alcohol on the least-substituted carbon (the anti-Markovnikov product), a different reaction pathway is required, such as hydroboration. In this reaction, borane (BH3) is added to the least substituted side of the double bond in a tetrahydrofuran solvent (THF). This is followed by the addition of hydrogen peroxide (H2O2) and sodium hydroxide (NaOH) to substitute a hydroxyl group (OH) for the boryl unit, forming the anti-Markovnikov alcohol.

Hydroboration

In the first step of hydroboration, the addition of borane to the alkene is initiated, and it proceeds as a concerted reaction as bond breaking and bond formation occur simultaneously. The C-C pi bond is broken, and a C-H bond and a C-B bond are formed. The borane acts as a Lewis acid by accepting two electrons in its empty p orbital from an alkene that is electron-rich. This allows boron to have an electron octet.

The second step involves oxidation, where an oxidant such as hydrogen peroxide (H2O2) is added, usually in the presence of a base such as NaOH or KOH. A rearrangement then occurs, where the C-B bond is broken and a new C-O bond is formed, resulting in the formation of an alcohol. This oxidation step replaces the C-B bond with a C-OH bond, leading to the final product of an alcohol.

The hydroboration-oxidation reaction is stereospecific and regioselective. It proceeds in an anti-Markovnikov manner, where the hydrogen adds to the most substituted carbon, and the boron attaches to the least substituted carbon in the alkene double bond. This regioselectivity is useful in the synthesis of bulky boranes that can enhance regioselectivity.

The hydroboration reaction is widely practiced as the resulting alkylboranes are susceptible to many reactions, such as oxidation to produce alcohols. It is an excellent way to produce alcohols in a stereospecific and anti-Markovnikov fashion.

Cyclic transition state

A cyclic transition state is a type of elimination reaction where two vicinal substituents on an alkane framework leave simultaneously to form an alkene. This is known as a syn elimination or pericyclic syn elimination. Unlike regular eliminations, this reaction is thermally activated and does not require additional reagents. The reaction mechanism is commonly observed in pyrolysis.

Compounds that undergo elimination through cyclic transition states upon heating, with no other reagents present, are designated as Ei reactions. Depending on the compound, elimination can take place through a four, five, or six-membered transition state. For example, β-hydroxy phenyl sulfoxides undergo thermal elimination through a 5-membered cyclic transition state, yielding β-keto esters and methyl ketones.

In the context of adding an alcohol on the least substituted side, the Ei mechanism is relevant. This mechanism involves the formation of a selenophosphonium salt that reacts with the alcohol to create an oxaphosphonium salt. The subsequent displacement of tributylphosphine oxide by the aryl selenium anion leads to the formation of the alkyl aryl selenide species. Treatment of the selenide with excess hydrogen peroxide results in the formation of the selenoxide, which eliminates the β-hydrogen through a 5-member cyclic transition state, ultimately yielding an alkene.

Furthermore, the Cope elimination, which is an example of the Ei mechanism, is also worth mentioning. In this process, a tertiary amine oxide is oxidized using m-chloroperoxybenzoic acid (mCPBA) and subjected to high temperatures. This results in the thermal syn elimination of the β-hydrogen and amine oxide through a cyclic transition state, yielding an alkene and a hydroxylamine.

Markovnikov product

In 1870, Russian chemist Vladimir Markovnikov formulated Markovnikov's rule, also known as Markownikoff's rule. This rule describes the outcome of some addition reactions in organic chemistry. Specifically, it predicts the regiochemistry of the reaction when a protic acid (usually denoted by HX) is added to an unsymmetrically substituted alkene.

Markovnikov's rule states that the halide part of the protic acid attaches itself to the carbon with the most hydrogen substituents, while the hydrogen component attaches itself to the carbon with the least hydrogen substituents. This rule is based on the formation of the most stable carbocation during the addition reaction. The more substituted the carbocation, the more stable it is due to induction and hyperconjugation.

However, it's important to note that Markovnikov's rule does not apply in the presence of peroxide and symmetrical alkenes. In these cases, the negative half of the reagent will attach to the carbon atom with more hydrogen atoms, which is known as the peroxide effect. Additionally, some reactions that do not involve carbocation intermediates may exhibit regioselectivities not dictated by Markovnikov's rule, such as free radical addition reactions. These reactions are referred to as anti-Markovnikov reactions.

The synthesis of branched "Markovnikov" alcohols is crucial in various chemical industries. One method to prepare these alcohols involves the catalytic reduction of substituted epoxides under mild conditions. This approach offers excellent chemoselectivity and turnover efficiencies, making it a highly attractive method for alcohol synthesis.

Anti-Markovnikov product

The Anti-Markovnikov rule describes the regiochemistry where the substituent is bonded to a less substituted carbon, rather than the more substituted carbon. This is in contrast to the more common carbon cation formation, which tends to favour the more substituted carbon. This is because a carbon radical is more stable when it is at a more substituted carbon due to induction and hyperconjugation.

The rule was formulated by Russian chemist Vladimir Markovnikov in 1870. Markovnikov's rule states that when a protic acid or other polar reagent is added to an asymmetric alkene, the acid hydrogen (H) or electropositive part attaches to the carbon with more hydrogen substituents, while the halide (X) group or electronegative part attaches to the carbon with more alkyl substituents.

Anti-Markovnikov behaviour can be observed in certain rearrangement reactions, such as in the hydration of phenylacetylene by auric catalysis, which gives acetophenone. It can also be illustrated using the addition of hydrogen bromide to isobutylene in the presence of benzoyl peroxide or hydrogen peroxide.

A new method of producing anti-Markovnikov products has been developed by Prof. Tobias Ritter and his team at the Max-Planck-Institut für Kohlenforschung. Their method uses ordinary hydrochloric acid added to alkenes with the aid of a catalyst and light, without the need for other substances stoichiometrically. This methodology provides new insights into the chemical behaviour of molecules and expands the "toolbox" for chemical synthesis.

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