Alcohols are molecules with an OH functional group. There are a variety of ways to synthesize alcohols including alkene reactions, SN2 and SN1 reactions, as well as organometallic reagents.
Let's begin with our review of alkene reactions that create alcohols:
Alcohol Synthesis Using Alkene Reactions
1. Acid Catalyzed Hydration Of Alkenes
The reagent is H2O with any catalytic acid such as H2SO4. Examples are: H2O/H2SO4, H3O+
Product:Turn double bond into single and add OH to the MOST substituted carbon from the double bond (Markovnikov rule). Warning: Rearrangements are possible!
The reagent is 1.Hg(OAc)2, H2O 2.NaBH4
Product: Turn double bond into single and add OH to the most substituted carbon from the double bond. The other carbon gets the hydrogen. No Rearrangements!
This reaction is very useful. Both acid catalyzed alkene hydration and oxymercuration give the same product, but the difference is that oxymercuration can not have any rearrangements. Therefore, for synthesis, it might be a better choice for the reagent.
The reagent is 1.BH3, THF 2. H2O2, NaOH or 1.B2H6,diglyme 2.H2O2, NaOH
Product: Turn double bond into single and add OH to the LEAST substituted carbon from the double bond (Anti Markovnikov Rule) and hydrogen on the most substituted carbon from the double bond. OH and H add syn (same side, both are dash or wedge)
Hydroboration is a very useful reaction because it is rare for reactions to go the anti Markovnikov way.
If we notice OH on the less substituted carbon in the product in a synthesis problem, hydroboration most likely led to that product.
4. Syn Hydroxylation
The reagent is 1.OsO4 2.H2O2 OR 1.KMnO4 2. H2O, OH- (cold, dilute)
Product: Turn double bond into single and add two OHs, one on each carbon from the double bond. Stereochemistry: syn (same side, both wedge or both dash).
Alcohol Synthesis Using Organometallic Reagents
The two organometallic reagents are Grignard and Organolithium.
Grignard reagent has a formula of R-MgX where X is Cl, Br or I. Grignard reagent is created from the reaction of alkyl halide with a magnesium metal. The solvent is an ether and most commonly used solvent is diethyl ether.
Alkyl halide used to form Grignard reagent can be primary, secondary, tertiary, vinyl (halogen on a double bond) and aryl (halogen on a benzene ring).
Organolithium reagent has a formula R-Li. It is created by reacting an alkyl halide (vinyl halides and aryl halides can be used as well) with lithium. There are many solvents that are used for this reaction.
Both Grignard and Organolithium reagents react with ketones and aldehydes to product alcohols.
Reactions with ketones produce tertiary alcohols. Reactions with aldehydes product secondary alcohols. Reactions with formaldehyde (CH2O) produce primary alcohols. In the second step, water or H3O+ are used to protonate O- and make it into an alcohol.
Grignard reagent (two equivalents are needed) also reacts with acid chlorides and esters to make tertiary alcohols. Two equivalents of Grignard are needed for these reactions.
Finally, Grignard reagent can also react with epoxides to produce an alcohol. Grignard reagent will attack the epoxide from the least substituted carbon, breaking the bond between carbon and oxygen. In the second step, O- will get protonated with H2O or H3O+.
Alcohol Synthesis Through The Reduction Of Carbonyl Groups
Sodium borohydride (NaBH4) and lithium aluminum hydride (LiAlH4) are the two reducing reagents used to turn carbonyl groups. (=O) into alcohols (OH).
NaBH4 reacts ONLY with ketones, aldehydes and acid chlorides to produce alcohols while LiAlH4 reacts with ketones, aldehydes, acid chlorides, carboxylic acids, acid anhydrides and esters to product alcohols. LiAlH4 is able to react with more molecules because it is a stronger reducing agent.
NaBH4 has a variety of solvents including water, alcohols and ethers. The second step of LiAlH4 reaction is H3O+.
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