Converting Alcohol: Creating Divine Leaving Groups

Alcohols are a crucial component of organic chemistry, but they are poor leaving groups due to their instability after leaving as hydroxide ions (OH-). A good leaving group should be stable after departure, but OH- is not, making it a strong base that is ready to attack. To address this limitation, there are several methods to convert alcohol into a better leaving group. One approach is to treat the alcohol (OH group) with acids like HCl, HBr, or HI, converting it to H2O+, which is an excellent leaving group. Alternatively, the OH group can be activated with sulfonyl chlorides or reacted with TsCl (tosyl chloride) to produce alkyl tosylate (OTs), another effective leaving group. These conversions enhance the reactivity of alcohols, making them more functional in subsequent reactions.

Convert alcohol into an alkyl halide

Alcohols are crucial in organic chemistry, but they are poor leaving groups due to their instability after leaving as hydroxide ions (OH-). To enhance their reactivity, they can be converted into alkyl halides.

There are two major pathways to convert alcohols into better leaving groups. The first option is to convert alcohol into an alkyl halide. The second option is to form a sulfonate ester, which is also a good leaving group.

To convert alcohol into an alkyl halide, the hydroxide of the alcohol is first converted into a better leaving group through the formation of an intermediate. Thionyl chloride creates an intermediate chlorosulfite (-OSOCl2) compound, and phosphorus tribromide makes an intermediate dibromophosphite (-OPBr2) compound. These intermediate compounds can then be eliminated as a leaving group during an SN2 reaction with the corresponding nucleophilic halide ion.

The SN1 mechanism involves protonating the alcohol to form water, which is a much better leaving group than OH-. This is followed by the nucleophilic attack of the halide ion (X-), resulting in the formation of an alkyl halide.

The order of reactivity of alcohols is 3° > 2° > 1° > methyl. The order of reactivity of the hydrogen halides is HI > HBr > HCl (HF is generally unreactive). Tertiary alcohols react reasonably rapidly with HCl, HBr, or HI, but for primary or secondary alcohols, the reaction rates are too slow.

In summary, the conversion of alcohol into an alkyl halide involves transforming the -OH group into a better leaving group, followed by an SN2 attack to obtain the target halide. This can be achieved through various methods, including the use of phosphorus tribromide (PBr3) or thionyl chloride (SOCl2).

React alcohol with HBr or HCl

Alcohols are a crucial functional group in organic chemistry, but they are poor leaving groups due to their instability after leaving as hydroxide ions (OH-). To enhance their reactivity, alcohols can be converted into better leaving groups, such as alkyl halides or sulfonate esters. This is typically done using strong acids like HX (where X can be Br or I).

When reacting alcohol with HBr or HCl, the first step is the protonation of the alcohol to create a good leaving group, H2O. This is followed by a nucleophilic substitution. The reaction pathway can be either SN1 or SN2, depending on the type of alcohol. Tertiary alcohols tend to proceed through an SN1 mechanism, while primary alcohols tend to follow the SN2 pathway.

For example, when reacting with HCl, the halide ion displaces a molecule of water (a good leaving group) from carbon, resulting in the formation of an alkyl halide. Similarly, when reacting with HBr, the bromide ion acts as a nucleophile and attacks the carbon, kicking out the OH group in the form of a neutral water molecule.

It is important to note that the order of reactivity of the hydrogen halides is HI > HBr > HCl, and the order of reactivity of alcohols is 3° > 2° > 1° methyl. Additionally, while strong acidic conditions are often employed, they may not be suitable for organic molecules, and alternative methods, such as using SOCl2 or PBr3, are available.

Convert alcohol to a tosylate

Alcohols are crucial in organic chemistry, but they are poor leaving groups due to their instability after leaving as hydroxide ions (OH-). To enhance their reactivity, alcohols can be converted into better leaving groups.

One way to do this is by converting the hydroxyl group to a tosylate ester, an excellent leaving group. This can be achieved by using para-toluene sulfonyl chloride (Ts-Cl) or methanesulfonyl chloride (Ms-Cl), creating what is termed an organic tosylate or mesylate. The tosylate ester then undergoes subsequent reactions (typically SN1 or SN2) as part of a multiple-step synthesis.

The conversion of an alcohol to a tosylate proceeds with the retention of configuration at the electrophilic carbon. Tosylate groups are excellent leaving groups in nucleophilic substitution reactions due to resonance delocalization of the developing negative charge on the leaving oxygen.

For example, the laboratory synthesis of isopentenyl diphosphate, a 'building block' molecule used by nature for the construction of isoprenoid molecules such as cholesterol and b-carotene, was accomplished by first converting the alcohol into an organic tosylate.

Another way to convert alcohols into better leaving groups is by transforming them into alkyl halides. This can be done using strong acids like HX (where X can be Br or I). The conversion process involves protonating the alcohol to form water, which is a much better leaving group.

Convert alcohol to a mesylate

Alcohols are crucial in organic chemistry, but they are poor leaving groups due to their instability after leaving as hydroxide ions (OH-). The definition of a good leaving group is that it should be stable after departure, but OH- is not. This instability makes alcohols less reactive in many organic reactions that require a good leaving group.

To address this issue, alcohols can be converted into better leaving groups by transforming them into alkyl halides or sulfonate esters. This can be achieved through the use of strong acids like HX (where X can be Br or I). The conversion process involves protonating the alcohol to form water, which is a much better leaving group.

One specific example of converting an alcohol to a mesylate is the formation of mesylates with methanesulfonyl chloride (MeSO2Cl). This reaction typically employs a base (e.g., TEA or pyridine) in a solvent such as DCM, with cooling or at room temperature. Methanesulfonic anhydride conditions are similar but offer the advantage of avoiding the formation of the alkyl chloride side product.

It is important to note that the methyl group of mesylate can be problematic when working with strong bases due to its relatively acidic nature. Additionally, the conversion of OH to OMs/OTs does not always prevent issues with rearrangements and racemization under certain reaction mechanisms.

By converting alcohols into mesylates, we can improve their reactivity and make them more suitable for specific organic reactions that require good leaving groups.

React alcohol with thionyl chloride

Thionyl chloride is a moderately volatile, colourless liquid with a pungent, sickly-sweet odour. It is primarily used as a chlorinating reagent and occasionally as a solvent. It is toxic and reacts violently with water, releasing hydrochloric acid. It is also listed as a controlled substance under the Chemical Weapons Convention as it can be used in the manufacture of chemical weapons.

Thionyl chloride reacts with an excess of anhydrous alcohol to produce anhydrous alcoholic solutions of HCl. The reaction proceeds in several steps. First, a nucleophilic oxygen atom of the alcohol displaces a chloride ion from thionyl chloride to form a protonated alkyl chlorosulfite intermediate. This is followed by deprotonation of this intermediate by a base, yielding an alkyl chlorosulfite. The next step depends on the reaction conditions.

If a base such as pyridine is present, it neutralizes the HCl generated, and an SN2 reaction occurs with inversion of configuration. In this step, the chloride ion attacks the carbon, resulting in cleavage of the C-O bond and the formation of the second pi bond of SO2. The HOSCl breaks down into HCl and sulfur dioxide gas.

Alternatively, in dioxane as a solvent, the substitution reaction occurs with retention of configuration. The alkyl chlorosulfite undergoes heterolytic cleavage of its C—O bond to give a pair of oppositely charged ions: a carbocation and chlorosulfite.

The reaction of thionyl chloride with methanol results in the opening of the furan ring. This reaction also produces anhydrous HCl, which can cleave ethers. Benzyl chloride can be obtained by reacting SOCl2 with benzyl alcohol, but the addition of AlCl3 will result in messy polymerization.

Frequently asked questions