13. Alcohols and Carbonyl Compounds

Which of the following solvents are reasonable choices for a Grignard reaction? Justify your choices. [Hint: Carbonyls are good electrophiles.]

A student, when solving the following 'predict-the-product' question, made a common mistake by writing the answer shown here. Explain why this reaction would not work as written.

Dimerization is a side reaction that occurs during the preparation of a Grignard reagent. Propose a mechanism that accounts for the formation of the dimer.

List three different sets of reagents (each set consisting of a carbonyl compound and a Grignard reagent) that could be used to prepare each of the following tertiary alcohols:

a.

A student added an equivalent of 3,4-epoxy-4-methylcyclohexanol to a solution of methylmagnesium bromide in diethyl ether, and then added dilute hydrochloric acid. He expected that the product would be 1,2-dimethyl-1,4-cyclohexanediol. He did not get any of the expected product. What product did he get?

List three different sets of reagents (each set consisting of a carbonyl compound and a Grignard reagent) that could be used to prepare each of the following tertiary alcohols:

b.

Addition of 1-bromobut-2-ene to magnesium metal in dry ether results in formation of a Grignard reagent. Addition of water to this Grignard reagent gives a mixture of but-1-ene and but-2-ene (cis and trans). When the Grignard reagent is made using 3-bromobut-1-ene, addition of water produces exactly the same mixture of products in the same ratios. Explain this curious result

Propose a mechanism for the reaction of acetyl chloride with phenylmagnesium bromide to give 1,1-diphenylethanol.

Two of the methods for converting alkyl halides to carboxylic acids are covered in Sections 20-8B and 20-8C. One is formation of a Grignard reagent followed by addition of carbon dioxide and then dilute acid. The other is substitution by cyanide ion, followed by hydrolysis of the resulting nitrile. For each of the following conversions, decide whether either or both of these methods would work, and explain why. Show the reactions you would use.

(e)

(f)

Grignard reagents react slowly with oxetane to produce primary alcohols. Propose a mechanism for this reaction, and suggest why oxetane reacts with Grignard reagents even though most ethers do not.

Draw the organic products you would expect to isolate from the following reactions (after hydrolysis).

(f)

(g)

Show how you would use Grignard syntheses to prepare the following alcohol from the indicated starting material and any other necessary reagents.

(g) cyclopentylphenylmethanol from benzaldehyde (Ph–CHO)

Show how to make these deuterium-labeled compounds, using CD₃MgBr and D₂O as your sources of deuterium, and any non-deuterated starting materials you wish.

c. CD₃CH₂CH₂OH

Often, compounds can be synthesized by more than one method. Show how this 3° alcohol can be made from the following:

(c) an ester

Show how you would synthesize the following primary alcohol by adding an appropriate Grignard reagent to formaldehyde.

(c)