Question

Write structures for the products of the following reactions involving Grignard reagents. Show the structures of both the intermediate substances and the substances obtained after hydrolysis with dilute acid. Unless otherwise specified, assume that sufficient Grignard reagent is used to cause those reactions to go to completion which occur readily at room temperatures. (a) \(\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{MgBr}+\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{CHO}\) (b) \(\mathrm{CH}_{3} \mathrm{MgI}+\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{CO}_{2} \mathrm{C}_{2} \mathrm{H}_{5}\) (c) \(\left(\mathrm{CH}_{3}\right)_{3} \mathrm{CMgCl}+\mathrm{CO}_{2}\) (d) \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{MgBr}+\mathrm{ClCO}_{2} \mathrm{C}_{2} \mathrm{H}_{5}\) (e) \(\mathrm{CH}_{3} \mathrm{Mg} 1+\mathrm{CH}_{3} \mathrm{COCH}_{2} \mathrm{CH}_{2} \mathrm{CO}_{2} \mathrm{C}_{2} \mathrm{H}_{5}\) \((1\) mole \()\) \((1\) mole \()\) 0

Short answer

(a) Diphenylmethanol: \(\mathrm{C}_{6} \mathrm{H}_{5}-\mathrm{CH}(\mathrm{OH})(\mathrm{C}_{6} \mathrm{H}_{5})\) (b) 2-butanone: \(\mathrm{CH}_{3}\mathrm{CH}_{2}\mathrm{C}(\mathrm{O})(\mathrm{CH}_{3})\) (c) tert-butyl carboxylic acid: \(\left(\mathrm{CH}_{3}\right)_{3}\mathrm{C}-\mathrm{C}(\mathrm{O})(\mathrm{OH})\) (d) ethyl propanoate: \(\mathrm{CH}_{3}\mathrm{CH}_{2}\mathrm{C}(\mathrm{O})(\mathrm{O} \mathrm{C}_{2} \mathrm{H}_{5})\) (e) Please provide a valid Grignard reagent for this reaction.

Step-by-step solution

Identify the reactive sites

The Grignard reagent \(\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{MgBr}\) has a reactive site at the carbon bonded to the magnesium atom (phenyl anion). The aldehyde $\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{CHO}$ has a carbonyl group that can react with the Grignard reagent.

Nucleophilic attack

The phenyl anion in the Grignard reagent acts as a strong nucleophile and attacks the electrophilic carbonyl carbon in $\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{CHO}\(, forming a new C-C bond. This process generates a negatively charged alkoxide intermediate (\)\mathrm{C}_{6} \mathrm{H}_{5}-\mathrm{C}(\mathrm{OH})(\mathrm{C}_{6} \mathrm{H}_{5})$).

Hydrolysis with dilute acid

Upon treatment with a dilute acid, the intermediate formed in step 2 is converted to an alcohol. The alkoxide intermediate obtains a hydrogen from the acid, resulting in the final product, diphenylmethanol (\(\mathrm{C}_{6} \mathrm{H}_{5}-\mathrm{CH}(\mathrm{OH})(\mathrm{C}_{6} \mathrm{H}_{5})\)). The other reactions can be similarly broken down into steps: (b) Reaction of \(\mathrm{CH}_{3} \mathrm{MgI}\) with $\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{CO}_{2} \mathrm{C}_{2} \mathrm{H}_{5}$:

Identify the reactive sites

The Grignard reagent \(\mathrm{CH}_{3} \mathrm{MgI}\) has a reactive site at the carbon bonded to the magnesium atom (methyl anion). The ester $\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{CO}_{2} \mathrm{C}_{2} \mathrm{H}_{5}$ has a carbonyl group that can react with the Grignard reagent.

Nucleophilic attack

The methyl anion in the Grignard reagent acts as a strong nucleophile and attacks the electrophilic carbonyl carbon in $\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{CO}_{2} \mathrm{C}_{2} \mathrm{H}_{5}\(, forming a new C-C bond and causing the leaving of the ethoxy group. The resulting intermediate is a ketone, \)\mathrm{CH}_{3}\mathrm{CH}_{2}\mathrm{C}(\mathrm{O})(\mathrm{CH}_{3})$.

Hydrolysis with dilute acid

Since Grignard reagents do not react with ketones under mild conditions, hydrolysis with a dilute acid does not affect the ketone, and the final product remains \(\mathrm{CH}_{3}\mathrm{CH}_{2}\mathrm{C}(\mathrm{O})(\mathrm{CH}_{3})\), also known as 2-butanone. (c) Reaction of \(\left(\mathrm{CH}_{3}\right)_{3} \mathrm{CMgCl}\) with \(\mathrm{CO}_{2}\):

Identify the reactive sites

The Grignard reagent \(\left(\mathrm{CH}_{3}\right)_{3} \mathrm{CMgCl}\) has a reactive site at the carbon bonded to the magnesium atom (tert-butyl anion). The carbon dioxide (\(\mathrm{CO}_{2}\)) has a carbonyl group that can react with the Grignard reagent.

Nucleophilic attack

The tert-butyl anion in the Grignard reagent acts as a strong nucleophile and attacks the electrophilic carbonyl carbon in \(\mathrm{CO}_{2}\), forming a new C-C bond. The intermediate formed has a carboxyl group, i.e., \(\left(\mathrm{CH}_{3}\right)_{3}\mathrm{C}-\mathrm{C}(\mathrm{O})(\mathrm{O}^{-})\).

Hydrolysis with dilute acid

Upon treatment with a dilute acid, the carboxylate group of the intermediate formed in step 2 is protonated, forming the final product, tert-butyl carboxylic acid (\(\left(\mathrm{CH}_{3}\right)_{3}\mathrm{C}-\mathrm{C}(\mathrm{O})(\mathrm{OH})\)). (d) Reaction of \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{MgBr}\) with $\mathrm{ClCO}_{2} \mathrm{C}_{2} \mathrm{H}_{5}$:

Identify the reactive sites

The Grignard reagent \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{MgBr}\) has a reactive site at the carbon bonded to the magnesium atom (ethyl anion). The acid chloride $\mathrm{ClCO}_{2} \mathrm{C}_{2} \mathrm{H}_{5}$ has a carbonyl group that can react with the Grignard reagent.

Nucleophilic attack

The ethyl anion in the Grignard reagent acts as a strong nucleophile and attacks the electrophilic carbonyl carbon in $\mathrm{ClCO}_{2} \mathrm{C}_{2} \mathrm{H}_{5}\(, forming a new C-C bond and causing the leaving of the chloride group. The resulting intermediate is an ester, \)\mathrm{CH}_{3}\mathrm{CH}_{2}\mathrm{C}(\mathrm{O})(\mathrm{O} \mathrm{C}_{2} \mathrm{H}_{5})$.

Hydrolysis with dilute acid

Hydrolysis with a dilute acid does not affect the ester, and the final product remains \(\mathrm{CH}_{3}\mathrm{CH}_{2}\mathrm{C}(\mathrm{O})(\mathrm{O} \mathrm{C}_{2} \mathrm{H}_{5})\), also known as ethyl propanoate. (e) Reaction of \(\mathrm{CH}_{3} \mathrm{Mg} 1\) with $\mathrm{CH}_{3} \mathrm{COCH}_{2} \mathrm{CH}_{2} \mathrm{CO}_{2} \mathrm{C}_{2} \mathrm{H}_{5}$:

Identify the reactive sites

There must be an understanding error, as \(\mathrm{CH}_{3} \mathrm{Mg}1\) is not an existing Grignard reagent. Please provide a valid Grignard reagent for this reaction.

Key concepts

Nucleophilic Attack

When discussing Grignard reagents, the concept of nucleophilic attack is vital to understanding their reactivity. Grignard reagents, such as phenylmagnesium bromide, have a highly nucleophilic carbon atom bonded to the magnesium. This nucleophilic carbon is known as the carbanion, which we'll explore further in the following section.

In a nucleophilic attack, the Grignard reagent's carbanion targets an electrophilic carbon, typically from a carbonyl group. Carbonyl carbons are excellent targets due to their polar nature, with a slight positive charge on the carbon that attracts the negative carbanion. For instance, when phenylmagnesium bromide reacts with benzaldehyde (\(\mathrm{C_6H_5CHO} \), the nucleophile attacks the carbonyl carbon, forming a new carbon-carbon bond. This crucial step sets the stage for subsequent transformations, leading to the formation of intermediates, such as alkoxides, which are precursors to alcohols after hydrolysis.

Carbanion

The term 'carbanion' is used to describe the negatively charged carbon species in a Grignard reagent. Each Grignard reagent is defined by a carbon atom bonded to magnesium (\(\mathrm{Mg} \) that effectively carries this negative charge. This unique feature makes carbanions exceptionally good nucleophiles.

Carbanions stand out due to their ability to easily form new carbon-carbon bonds. This is a key characteristic in organic synthesis, allowing for the transformation of simple molecules into more complex structures. For example, when the methyl carbanion in \(\mathrm{CH_3MgI} \), reacts with esters, the weaker base of the carbanion displaces the leaving group, such as the ethoxy group in esters, creating a more complex molecule. This specific property of Grignard reagents to act as carbanions highlights their critical role in developing a vast array of organic compounds.

Alcohol Formation

Alcohol formation through the use of Grignard reagents is a classic example of their utility in organic chemistry. Once a nucleophilic attack occurs forming an alkoxide intermediate, a simple hydrolysis step converts it into an alcohol.

During alcohol formation, the alkoxide — a negatively charged oxygen species — needs to be neutralized. This is achieved through a hydrolysis reaction, typically using a dilute acid to introduce a proton to the alkoxide, yielding a stable alcohol. For instance, phenylmagnesium bromide, when reacted with benzaldehyde, yields an alkoxide intermediate that becomes diphenylmethanol upon hydrolysis. The ability of Grignard reagents to transform carbonyl compounds into alcohols exemplifies their versatility and power in synthesizing complex organic molecules efficiently.

Hydrolysis Reaction

Hydrolysis reactions play an essential role in the completion of processes initiated by Grignard reagents. This follows their initial reaction, where the nucleophilic carbanion attacks an electrophilic site to form an intermediate. The term 'hydrolysis' refers to the reaction of these intermediates with water, often accelerated by an acidic or basic medium, resulting in a new compound.

In the case of Grignard reactions, hydrolysis typically involves the addition of an acid like HCl or H2SO4. The acid donates a proton, neutralizing the charged intermediate and leading to the formation of an alcohol as the final product. For example, after a Grignard reagent transforms a carbonyl group into an alkoxide, hydrolysis yields the corresponding alcohol. This conversion highlights the step-wise progression of chemical changes Grignard reagents reliably undergo during synthesis processes.