Question

Outline all steps in the synthesis of propyne from each of the following compounds, using any needed organic or inorganic reagents. (a) 1,2 -dibromopropane (e) n-propyl alcohol (b) propylene (f) 1,1 -dichloropropane (c) isopropy1 bromide (g) acetylene (d) propane (h) \(1,1,2,2\) -tetrabromopropane

Short answer

(a) 1,2-dibromopropane: Perform an elimination reaction using excess alcoholic KOH to form propyne. \(CH_3CHBrCH_2Br + 2\ KOH \rightarrow CH_3C\equiv CH + 2KBr + 2H_2O\) (e) n-propyl alcohol: Oxidize with PCC to form propanal, then perform a Corey-Fuchs reaction using CBr_4, PPh_3, and t-BuLi to form propyne. (b) propylene: Perform a hydroboration-oxidation reaction using 9-BBN, H_2O_2, and NaOH to form propanal, then perform a Corey-Fuchs reaction using CBr_4, PPh_3, and t-BuLi to form propyne. (f) 1,1-dichloropropane: Perform a Grignard reaction with Mg, HCHO, and H_3O^+ to form n-propyl alcohol, then follow steps (e) to complete the synthesis. (c) isopropyl bromide: Perform a Grignard reaction with Mg, CO_2, and H_3O^+ to form propionic acid, perform a Hofmann rearrangement with Br_2, NaOH, and H_3O^+ to form n-propyl alcohol, then follow steps (e) to complete the synthesis. (g) acetylene: Perform an alkylation reaction with propyl bromide and NaNH_2 to form propyne. \(HC\equiv CH + CH_3CH_2CH_2Br + NaNH_2 \rightarrow CH_3C\equiv CH\) (d) propane: Synthesis of propyne from propane is not possible using simple organic chemistry transformations. (h) 1,1,2,2-tetrabromopropane: Perform two elimination reactions using excess alcoholic KOH to form propyne. \(CHBr_2CHBr_2 + 4\ KOH \rightarrow CH_3C\equiv CH + 4KBr + 4H_2O\)

Step-by-step solution

Elimination of Dibromide

Use excess alcoholic KOH as the reagent to perform an elimination reaction on 1,2-dibromopropane to form propyne. The overall reaction is: \[CH_3CHBrCH_2Br + 2\ KOH \rightarrow CH_3C\equiv CH + 2KBr + 2H_2O\] (e) n-propyl alcohol

Oxidation

Perform an oxidation reaction using PCC (Pyridinium Chlorochromate) as the reagent to convert n-propyl alcohol to propanal. The overall reaction is: \[CH_3CH_2CH_2OH + PCC \rightarrow CH_3CH_2CHO + H_2O\]

Corey-Fuchs Reaction

Perform a Corey-Fuchs reaction using CBr_4 and PPh_3 followed by t-BuLi to convert propanal to propyne. The overall reaction is: \[CH_3CH_2CHO \xrightarrow{CBr_4, PPh_3} CH_3CBrCH_2CBr \xrightarrow{t-BuLi} CH_3C\equiv CH\] (b) propylene

Hydroboration-Oxidation

Perform a hydroboration-oxidation reaction on propylene using 9-BBN followed by H_2O_2 and NaOH to form propanal. The overall reaction is: \[CH_3CH \equiv CH_2 + 9-BBN \xrightarrow{H_2O_2, NaOH} CH_3CH_2CHO\]

Corey-Fuchs Reaction

Perform a Corey-Fuchs reaction using CBr_4 and PPh_3 followed by t-BuLi to convert propanal to propyne. The overall reaction is: \[CH_3CH_2CHO \xrightarrow{CBr_4, PPh_3} CH_3CBrCH_2CBr \xrightarrow{t-BuLi} CH_3C\equiv CH\] (f) 1,1-dichloropropane

Grignard Reaction

Perform a Grignard reaction using excess Mg to form a Grignard reagent followed by a reaction with formaldehyde (HCHO) and H_3O^+ to convert 1,1-dichloropropane to n-propyl alcohol. The overall reaction is: \[CH_3CHCl_2 + 2Mg \xrightarrow{HCHO, H_3O^+} CH_3CH_2CH_2OH\] Then, follow the steps (e) to complete the synthesis. (c) isopropyl bromide

Grignard Reaction

Perform a Grignard reaction using Mg to form a Grignard reagent. Perform the reaction with CO_2 and H_3O^+ to convert isopropyl bromide to propionic acid. The overall reaction is: \[CH_3CH(Br)CH_3 + Mg \xrightarrow{CO_2, H_3O^+} CH_3CH_2COOH\]

Hofmann Rearrangement

Perform a Hofmann rearrangement using Br_2 and NaOH followed by H_3O^+ to convert propionic acid to n-propyl alcohol. The overall reaction is: \[CH_3CH_2COOH \xrightarrow{Br_2, NaOH, H_3O^+} CH_3CH_2CH_2OH\] Then, follow the steps (e) to complete the synthesis. (g) acetylene

Alkylation

Perform an alkylation reaction using propyl bromide (CH_3CH_2CH_2Br) and NaNH_2 to convert acetylene to propyne. The overall reaction is: \[HC\equiv CH + CH_3CH_2CH_2Br + NaNH_2 \rightarrow CH_3C\equiv CH\] (d) propane Synthesis of propyne from propane is not possible using simple organic chemistry transformations. (h) 1,1,2,2-tetrabromopropane

Elimination of Dibromide

Use excess alcoholic KOH as the reagent to perform two elimination reactions on 1,1,2,2-tetrabromopropane to form propyne. The overall reaction is: \[CHBr_2CHBr_2 + 4\ KOH \rightarrow CH_3C\equiv CH + 4KBr + 4H_2O\]

Key concepts

Elimination Reaction

The elimination reaction is a crucial process in organic chemistry. It involves the removal of atoms or groups from a molecule, resulting in a new, often unsaturated, compound. In the context of synthesizing propyne, the elimination reaction is used to remove halogen atoms from dihalogenated compounds like 1,2-dibromopropane and 1,1,2,2-tetrabromopropane to form the triple-bonded alkyne, propyne.

During an elimination reaction, a reagent like alcoholic KOH is used. KOH serves as a strong base that extracts hydrogen atoms adjacent to the halogen in the molecule. As these hydrogen atoms are abstracted, the halogen atoms leave as halide ions, resulting in the formation of a carbon-carbon double or triple bond.

• This reaction typically occurs in a two-step mechanism, with the base deprotonating the molecule and the leaving group departing.
• Factors like temperature and the nature of the substrate influence the course of the reaction.

Alcoholic KOH is preferred because it favors elimination over substitution by promoting the formation of unsaturation, such as double or triple bonds.

Oxidation Reaction

Oxidation reactions play a vital role in transforming alcohols into aldehydes or ketones, thus adjusting the functional group as needed for further synthesis. In the synthesis of propyne, oxidation is used to convert n-propyl alcohol into propanal.

The oxidizing agent, PCC (Pyridinium Chlorochromate), is particularly useful for converting primary alcohols into aldehydes without over-oxidizing them into carboxylic acids. The reaction proceeds with selective removal of hydrogen (dehydrogenation) from the alcohol.

• PCC is a mild oxidizing agent that offers precision control over the oxidation process, ensuring no further alteration of propanal into carboxylic acids.
• The reaction is carried out under anhydrous conditions to prevent further oxidation to acids.

Understanding oxidation is essential because it sets the stage for subsequent reactions in multi-step synthesis pathways.

Hydroboration-Oxidation

Hydroboration-oxidation is a two-step synthetic method used to transform alkenes into alcohols. It is a stereospecific reaction that adds water across a double bond in an anti-Markovnikov fashion. In the context of synthesizing propyne, this method converts propylene into propanal.

Initially, hydroboration involves the addition of borane derivatives, like 9-BBN, across the carbon-carbon double bond. This step proceeds without rearrangement, conserving the configuration of the starting material.
The oxidation step follows, where peroxide (H₂O₂) in a basic medium (like NaOH) replaces the boron with a hydroxyl group, thus yielding an alcohol.

• The attraction of hydroboration-oxidation lies in its ability to add water in an orderly and predictable manner without rearrangement, unlike many other addition reactions.
• It's an efficient way to advance the structure of a compound without introducing unwanted changes.

This reaction sequence showcases the balance of organic synthesis in converting simple alkenes into more complex functional groups with precision.

Grignard Reaction

The Grignard reaction is a cornerstone of carbon-carbon bond formation in organic chemistry. It involves the formation of a Grignard reagent, an organomagnesium compound, from an alkyl or aryl halide reacting with magnesium. This reagent is highly reactive and can act as a nucleophile to attack various electrophilic centers, converting them into alcohols or other functional groups.

In synthesizing propyne, the Grignard reaction helps convert 1,1-dichloropropane into n-propyl alcohol. This is achieved by first forming the Grignard reagent from 1,1-dichloropropane, which then reacts with formaldehyde (as an electrophile) followed by acid workup to produce the alcohol.

• Grignard reactions require strict anhydrous conditions as water can deactivate the Grignard reagent by converting it back to its starting materials.
• These reactions are valuable for forming carbon-carbon bonds, allowing the assembly of complex carbon skeletons from basic ones.

Once the alcohol is formed, it can be further transformed through oxidation reactions and other steps to synthesize the target molecule, illustrating the utility of the Grignard reaction in multi-step organic syntheses.