Grignard Reaction Practice Problems

Grignard reaction with ketones and aldehydes involves the nucleophilic addition of alkyl carbanion to the carbonyl carbon, forming alkoxide, which is then protonated to produce alcohol.

Specific reaction:

Specific mechanism: 

Why does the given reaction generate a racemic mixture of alcohols?

Instead of quenching with an acid, the alkoxide that results from Grignard addition to a carbonyl can be reacted with an alkyl halide to generate an ether. Suggest a mechanism for the given reaction and box the final product(s). 

Strong nucleophiles react with aldehydes via the nucleophilic addition mechanism instead of the addition/elimination mechanism. Why?

The given Grignard reaction proceeds through the nucleophilic addition of an ethyl carbanion to the electrophilic carbon of carbonyl. Explain why the resulting stereoisomers are not equally favored. 

Determine the product(s) that would result from the reaction of (2-methylbutyl)lithium with 7-hydroxyheptan-3-one.

Determine the product of the following Grignard addition to CO ₂.

What will be the product of the following cross-coupling reaction of organocuprates?

Draw the expected product of the ring-opening reaction of the epoxide shown below.

The reaction below is unsuccessful in producing the desired alcohol. Explain why the reaction did not work.

The illustration below is a reaction in which a cuprate is the only organometallic that can produce the desired alcohol. Why can the same reaction not be carried out with a Grignard reagent or an organolithium?

Show how the following compound can be prepared, starting with cyclopentane.

Identify the halo-substituted compound/s that will react with (CH₃CH₂CH₂)₂CuLi to form the product shown below.

Provide the alkyl chloride that will react with (CH₃CH₂)₂CuLi to form the following products.

Provide the alcohol formed in the reaction of (CH₂=CHCH₂)₂CuLi with propylene oxide followed by acidic work-up.

Draw the product of the given reaction sequence.

Draw the structures of X and Y:

A compound with the formula C₅H₁₀Br₂ reacts with NaOH to form an alcohol. The compound also reacts with Mg in ether to form a Grignard reagent. Reacting the Grignard reagent with dilute HCl results in isopentane. Provide possible structure(s) for the compound.

Identify the major product of the given reaction sequences.

Provide the missing reagents:

Which compound/s below can be used to create a Grignard reagent?

Indicate the following compound can be prepared using the given starting material, any necessary inorganic reagents, and any carbon-containing compounds with no more than three carbons.

The Reformatsky reaction can be used for the nucleophilic addition to the carbonyl of a ketone or an aldehyde. The reaction uses an organozinc reagent instead of a Grignard reagent. This organozinc reagent can be produced by the treatment of an α-bromo ester with zinc. The organozinc reagent is less reactive than a Grignard reagent therefore it can not be used for the nucleophilic addition to an ester.

Show how the given compound can be produced using a Reformatsky reaction.

Identify the missing species.

Identify the missing reagents.

Show how the following conversion can be accomplished using any necessary reagents, catalysts, and any other organic compounds with no more than two carbons.

Show how the following conversion can be accomplished using any necessary reagents, catalysts, and any other organic compounds with no more than two carbons.

Show how the following conversion can be accomplished using any necessary reagents, catalysts, and any other organic compounds with no more than two carbons.

Starting with bromocyclopentane, how could the following compound be prepared?

Provide a synthesis to produce the following compound using the given starting material.

Devise a synthetic pathway to produce the following compound using the given starting material.

Identify the missing products.

Provide necessary reagents to carry out the following reaction.

Provide necessary reagents to accomplish the following conversion.

Show how you would accomplish the transformation below. You can use any reagents you need to accomplish the synthesis.

Provide the missing products of each reaction in the following synthesis.

Propose a synthesis to create the following substance using alkyl halides, vinyl halides, and aryl halides that contains no more than six carbon atoms as a starting material.
n-hexane

Propose a synthesis to create the following substance using alkyl halides, vinyl halides, and aryl halides that contains no more than six carbon atoms as a starting material.
trans-hex-2-ene

What is the major product of the reaction shown below?

Synthesize the primary alcohol shown below by reacting an appropriate Grignard reagent with formaldehyde.

Propose two different ways to prepare the secondary alcohol shown below by reacting an appropriate Grignard reagent with an aldehyde.

Synthesize the tertiary alcohol shown below by reacting an appropriate Grignard reagent with a ketone.

Show how you would synthesize the following alcohol by adding Grignard reagent to acid chloride or ester.

Show how you would add Grignard reagent to ethylene oxide to make the following alcohol.
3-methylbutan-1-ol

Determine the identity of the products formed when acetylide ions react with ethylene oxide, followed by a dilute acid workup.

Show how to synthesize 2-cyclohexylethanol by reacting a suitable Grignard reagent with formaldehyde.

Using CD₃MgBr and D₂O as your sources of deuterium, and any non-deuterated starting material, show how to make this deuterium-labeled compound.
CH₃CH₂CH(OD)CD₃

Using CD₃MgBr and D₂O as your sources of deuterium, and any non-deuterated starting material, show how to make this deuterium-labeled compound.
CH₃CH₂C(OH)(CD₃)₂

Using CD₃MgBr and D₂O as your sources of deuterium, and any non-deuterated starting material, show how to make this deuterium-labeled compound.
CH₃CH₂C(OD)(CD₃)₂

A reaction between an excess of a Grignard reagent and a formate ester, followed by a subsequent protonation produce a secondary alcohol with two identical alkyl groups.
Suggest a plausible mechanism for the reaction between an excess of allylmagnesium bromide and methyl formate. Your mechanism should explain the formation of the product.

Determine the identity of products obtained in each of the reactions shown below. Include stereochemistry in your answers.

Determine the identity of products obtained in each of the reactions shown below. If necessary, include a protonation step.
(i) 2,2-dimethyloxirane + ethylmagnesium bromide
(ii) propylene oxide + ethyllithium
(iii) cyclopentyloxirane + tert-butyllithium

Predict the product of the reaction shown below.

Synthesis of carboxylic acids from alkyl halides is accomplished by either converting the alkyl halide to a Grignard reagent followed by addition of carbon dioxide and then dilute aqueous solution of mineral acids, or by reacting the alkyl halide with cyanide ion, followed by subsequent hydrolysis of the resulting nitrile. Determine if either or both of these methods can be used in each of the following reactions, and explain why. Show the reactions you will use.

How would you synthesize the following compound starting from ethyne and any other required substance?

3-methylpent-1-yn-3-ol

How would you synthesize the following compound starting from ethyne and any other required substance?

hepta-1,6-diyne-3,5-diol

How would you synthesize 1-phenylbut-2-yn-1-ol starting from benzaldehyde and any other required reagents?

Determine which products can result from the following reactions involving organometallic reagents:

Can you identify what is wrong with the following Grignard synthesis?

Can you identify what is wrong with the following Grignard synthesis?

Devise a synthetic route for the following conversion:

Devise a synthetic route for the following conversion:

When an unknown compound, A, is treated with chromic acid, it gives a ketone, B. On the other hand, when the same compound A is treated with PBr₃ in a separate reaction, C is formed which is further reacted with Mg in ether to form a Grignard reagent, D. When D and B are mixed, compound E is formed. Hydrolysis of E yields 3,4-diethylhexan-3-ol.

Give the structures of compounds A to E.

Propose a synthetic pathway to synthesize the following compounds starting from cyclopentanol and any necessary reagents and solvents.

For the given synthesis, draw the structures of the missing products A through D.

As an introduction to multistep synthesis, devise the synthesis of 2-butanone from ethanol.

As an introduction to multistep synthesis, devise the synthesis of 2-methylbut-2-ene from propan-2-ol.

Devise an approach for the synthesis of 1-chloro-2-methylcyclohexane. You can start with cyclohexanone, any reagent that contains four carbon atoms or less, and any required reagent or solvent.

Devise a synthetic approach for the following molecule starting with no more than six carbon atoms.

In organic synthesis, a compound can usually be prepared in more than one way. Show how the following molecule can be synthesized using two different ketones.

Show how the following primary alcohol can be synthesized using formaldehyde as one of the reactants.

Show how to utilize Grignard synthesis to prepare hexan-3-ol from butanal as the starting material.

 A reaction between an excess of a Grignard reagent and a formate ester, followed by a subsequent protonation produce a secondary alcohol with two identical alkyl groups.
Utilize the reaction between ethyl formate and Grignard reagents and propose a synthesis plan for each of these compounds.
(a) propan-2-ol
(b) dicylcohexylmethanol
(c) trans,trans-undeca-3,8-dien-6-ol

Determine the identity of the products obtained in each of the reactions shown below (after hydrolysis)

Identify suitable solvents for Grignard reactions from the following list of compounds.
(i) n-heptane
(ii) CH₃CH₂-O-CH₂CH₃
(iii) CHBr₃
(iv) cyclopentane
(v) toluene
(vi) CH₃CH₂OCH₂OCH₂CH₃

For the given synthesis, predict the missing products A through C. Assume that an excess of each reagent is used.

Starting from chlorobenzene and any other reagents you need, show how you would synthesize the following compound.

Styrene

A graduate student was studying nucleophilic addition reactions of ketones. To start with, she added ethyl iodide to a flask containing anhydrous ether and chunks of magnesium metal. The result was an exothermic reaction and the ether in the flask started boiling. After the ether stopped boiling, she added 2-butanone to the flask and the ether started boiling again, indicating another exothermic reaction. After the reaction mixture cooled down, she added dilute acid to the mixture and separated the aqueous and ether layers. She evaporated the ether layer and purified the obtained product. GC-MS analysis of the purified product shows the presence of a major product with a few impurities.
Write the reactions that took place and draw the structure of the major product.

Predict the products obtained in the reaction between cyclopentanone and PhMgBr, followed by workup with mild H₃O⁺.

Draw the structures of the missing compounds A through C in the following synthesis.

Determine the appropriate organocuprate reagent to accomplish each of these substitution reactions.

Determine the major product of these reactions.