Review of Nitriles: Videos & Practice Problems

Nitriles are an important functional group in organic chemistry, characterized by the presence of a cyano group (-C≡N). There are three primary methods for synthesizing nitriles, each involving different chemical reactions.

The first method is through an SN2 reaction, where an alkyl halide (denoted as RX) reacts with a nucleophile, specifically the cyanide ion (CN^-). This reaction results in the substitution of the halide with the cyano group, forming the nitrile.

The second method involves the formation of cyanohydrins. In this process, the cyanide ion acts as a nucleophile and adds to either an aldehyde or a ketone. This nucleophilic addition leads to the creation of a cyanohydrin, which can subsequently be converted into a nitrile.

Lastly, nitriles can be synthesized through amide dehydration. This method involves the reaction of an amide with a dehydrating agent. Common dehydrating agents include diphosphorus pentoxide (P₂O₅) and thionyl chloride (SOCl₂). The dehydration process removes water from the amide, resulting in the formation of a nitrile.

Understanding these synthesis methods is crucial for effectively working with nitriles in various chemical applications.

In the synthesis of nitriles, one effective method involves the use of SN2 reactions, where the cyanide ion acts as a nucleophile to displace halides, such as bromine. In this process, the carbon atom bonded to the electronegative bromine exhibits a partial positive charge, while the bromine carries a partial negative charge. This polarization facilitates the nucleophilic attack by the cyanide ion.

During the SN2 reaction, the cyanide ion approaches the carbon atom, resulting in the displacement of the bromine atom. A key characteristic of SN2 reactions is the inversion of configuration at the carbon center. For instance, if the bromine was initially represented with a wedged bond, the incoming cyanide ion will convert this to a dashed bond upon substitution. Consequently, the reaction transforms an alkyl bromide into a nitrile, with the bromide ion released as a byproduct.

This method provides a straightforward approach to synthesizing nitriles from alkyl halides, highlighting the utility of SN2 reactions in organic chemistry.

In this example, we are tasked with selecting the best synthetic route to transform an alkyl bromide into a nitrile, while also adding an additional carbon atom to the structure. The initial compound contains a branching group with two carbons, and the final product retains these two carbons while incorporating a new carbon and a nitrile group. The methyl group remains unchanged throughout the process.

Considering the options provided, option A involves using sodium cyanide in DMSO, which could facilitate an SN2 reaction. However, this method does not introduce the necessary additional carbon, making it an unsuitable choice. Option C suggests using sodium amide, a strong base that would likely lead to an E2 elimination reaction, resulting in an alkene. Since the desired product is not an alkene, this option is also eliminated.

This leaves us with options B and D, both of which start with magnesium in ether to create a Grignard reagent from the alkyl halide. The Grignard reagent then reacts with formaldehyde, leading to the formation of a primary alcohol. This step adds a -CH2OH group to the structure. The key difference between options B and D lies in the subsequent steps.

In option D, thionyl chloride is used to convert the -OH group into a -Cl group. While thionyl chloride is effective for this transformation, it works best with secondary or tertiary alcohols. Since we are dealing with a primary alcohol, this method is not the most efficient, making option D less favorable.

Conversely, option B employs KCN after the conversion to the -CH2Cl group. The cyanide ion (CN^-) performs an SN2 reaction, displacing the chloride and resulting in the desired nitrile product with the additional carbon. Thus, option B is the most efficient synthetic route to achieve the transformation from the alkyl bromide to the final nitrile product.

A nitrile can be synthesized through the formation of cyanohydrins, which occurs when an aldehyde or ketone undergoes nucleophilic addition with a cyanide ion. In this process, the ketone features a carbonyl group where the oxygen is partially negative and the carbon is partially positive. The cyanide ion, which is ionic and consists of a potassium ion (K⁺) and a cyanide ion (CN^-), acts as a nucleophile. When the cyanide ion approaches the carbonyl carbon, it breaks the double bond between the carbon and oxygen, resulting in the attachment of the cyanide to the carbonyl carbon and the formation of a negatively charged oxygen.

To stabilize this intermediate, a protonation step occurs, typically facilitated by a proton donor such as H₃O⁺. This results in the formation of a hydroxyl group (–OH) alongside the cyanide group (–CN). Importantly, the carbon that was originally part of the carbonyl group now becomes a chiral center, as it is bonded to four different groups: the hydroxyl group, the cyanide group, and the two remaining groups from the original ketone. Due to this chirality, the stereochemistry of the hydroxyl and cyanide groups can vary, necessitating the use of wavy lines in structural representations to indicate that either group could be in a wedged or dashed configuration.

In summary, the formation of cyanohydrins through the nucleophilic addition of cyanide to aldehydes or ketones is a significant method for synthesizing nitriles, highlighting the importance of understanding chirality and stereochemistry in organic reactions.

In organic synthesis, transforming compounds through a series of reactions requires careful selection of reagents. In this example, we start with an alkene and aim to convert it into an alcohol. Since the alkene carbons are identical, we can utilize various methods for this transformation. One effective approach is hydroboration-oxidation, which involves the use of borane (BH₃) in tetrahydrofuran (THF) followed by hydrogen peroxide (H₂O₂) and hydroxide ion (OH^-). This method allows for the conversion of the alkene to the corresponding alcohol.

Next, we need to oxidize the secondary alcohol to a ketone. This can be achieved through oxidation, and since we are dealing with a secondary alcohol, we can choose between weak or strong oxidizing agents. In this case, we opt for strong oxidation using potassium dichromate (K₂Cr₂O₇) in the presence of sulfuric acid (H₂SO₄). This step successfully converts the secondary alcohol into a ketone.

Finally, we need to transform the ketone into a more complex structure that includes a nitrile (cyanide) group and an ether. The carbonyl carbon of the ketone is electrophilic, making it susceptible to nucleophilic attack. We introduce potassium cyanide (KCN) to facilitate this reaction, where the cyanide ion (CN^-) attacks the carbonyl carbon, resulting in the formation of a cyanohydrin. At this stage, the oxygen becomes negatively charged.

To convert the cyanohydrin into the desired ether, we need to replace the hydroxyl group with a methoxy group (OCH₃). This can be accomplished by introducing a methyl halide, such as methyl iodide (CH₃I), which acts as a good leaving group. The negatively charged oxygen can perform a nucleophilic attack on the methyl carbon, leading to the displacement of iodine (I^-) and forming the ether.

In summary, the reagents required for this synthesis are: for the first step, BH₃ in THF followed by H₂O₂ and OH^-; for the second step, K₂Cr₂O₇ with H₂SO₄; and for the final step, KCN followed by CH₃I. These reagents effectively guide the transformation from the initial alkene to the final product with the desired functional groups.

Amide dehydration is a significant reaction in organic chemistry that allows for the conversion of primary amides into nitriles. This transformation is facilitated by dehydrating agents such as diphosphorus pentoxide (P₂O₅) or thionyl chloride (SOCl₂). The process involves the removal of water from the primary amide, specifically the loss of one oxygen atom and two hydrogen atoms from the nitrogen atom.

During this reaction, the structure of the primary amide is altered. The carbonyl carbon, which is initially part of the amide, remains while forming a triple bond with the nitrogen atom. This is crucial because carbon typically forms four bonds, while nitrogen forms three. By losing the oxygen and hydrogen, both elements can achieve their ideal bonding configurations: carbon completes its four bonds through the formation of a triple bond with nitrogen, which retains a lone pair of electrons.

In summary, the dehydration of primary amides using diphosphorus pentoxide or thionyl chloride effectively produces nitriles, showcasing the importance of understanding molecular bonding and the role of dehydrating agents in organic synthesis.

In this transformation, we start with methylbenzene (toluene) and aim to produce a nitrile group. The methyl group is an ortho/para director, while the nitrile group acts as a meta director. This means that the nitrile groups cannot be ortho or para to each other. To achieve the desired product, we first need to block the para position of the toluene by performing sulfonation using SO₃ and H₂SO₄. This introduces a sulfonic acid group at the para position, effectively blocking it for subsequent reactions.

Next, we perform nitration using a mixture of nitric acid and sulfuric acid. The presence of the methyl group, being an activating ortho/para director, ensures that the nitrile group is added ortho to the methyl group. After this step, we have both the methyl and nitrile groups in the desired positions, but we need to remove the sulfonic acid group. This is accomplished through desulfonation using H₃O⁺, which eliminates the sulfonic acid group.

To convert the methyl group into a nitrile, we perform side chain oxidation with potassium permanganate. The benzylic carbon, which is directly attached to the benzene ring, will be oxidized to a carboxylic acid, provided it has at least one hydrogen atom. Following this, we react the carboxylic acid with ammonia (NH₃) to form a primary amide. Finally, we can convert the primary amide into a nitrile using diphosphorus pentoxide, which facilitates the dehydration process, resulting in the formation of the desired nitrile group.

Among the options provided, the correct sequence of reactions is outlined in option D. Other options fail due to incorrect positioning of the groups or the introduction of additional carbons that do not align with the desired product structure. Thus, the stepwise approach in option D effectively leads to the successful synthesis of the target nitrile compound.

Nitriles, which are organic compounds containing the cyano group (-C≡N), exhibit several important reactions that are analogous to those of other carboxylic acid derivatives. Understanding these reactions is crucial for applications in organic synthesis.

Firstly, nitriles undergo hydrolysis, a reaction where water is used to break down the nitrile into a carboxylic acid. This transformation can be represented by the equation:

$$ R-C≡N + H_2O \rightarrow R-COOH $$

In this equation, R represents a hydrocarbon chain or group, and the product is a carboxylic acid.

Secondly, nitriles can be subjected to reduction, which can occur through catalytic methods or using hydride reagents. This process converts nitriles into primary amines. The general reaction can be expressed as:

$$ R-C≡N + 2[H] \rightarrow R-CH_2NH_2 $$

Here, [H] denotes the reducing agent, and the product is a primary amine.

Lastly, nitriles can react with Grignard reagents to form ketones. This reaction highlights the versatility of nitriles in synthetic chemistry. The reaction can be illustrated as follows:

$$ R-C≡N + R'MgX \rightarrow R-C(=O)R' + MgX $$

In this case, R' represents the alkyl or aryl group from the Grignard reagent, and the product is a ketone.

In summary, the three primary reactions of nitriles include hydrolysis to carboxylic acids, reduction to primary amines, and conversion to ketones via Grignard reagents. Mastery of these reactions is essential for effective manipulation of nitriles in organic synthesis.

In the study of nitriles, hydrolysis is a key reaction that transforms nitriles into carboxylic acids or carboxylate anions, depending on the conditions used. During acidic hydrolysis, nitriles react with hydronium ions (H₃O⁺), resulting in the formation of a carboxylic acid and a positively charged amine, specifically ammonium (NH₄⁺). This process highlights the conversion of the nitrile functional group (–C≡N) into a more stable carboxylic acid functional group (–COOH).

Conversely, in basic hydrolysis, the reaction involves hydroxide ions (OH^–) instead of hydronium ions. This reaction leads to the formation of a carboxylate anion (RCOO^–) or carboxylate salts, along with the generation of a neutral amine, typically ammonia (NH₃). Thus, hydrolysis serves as a crucial method for converting nitriles into either carboxylic acids or carboxylate derivatives, depending on whether an acidic or basic environment is utilized.

In this transformation process, we start with a reactant and aim to convert it into a product that features a carboxylic acid. The initial step involves catalytic halogenation, specifically bromination, which is preferred over chlorination due to its controllability. The reaction utilizes bromine (Br₂) in the presence of hydrogen bromide (HBr), targeting the replacement of a tertiary hydrogen with a bromine atom. This step results in the formation of a brominated intermediate where the halogen is attached to the alpha carbon.

Next, we proceed with an elimination reaction, which can be guided by either Zaitsev's or Hoffman's rule. In this case, since the carboxylic acid is added to the terminal carbon, we want to eliminate from the less substituted beta carbon. Hoffman's rule is applicable here, which necessitates the use of a bulky base for deprotonation. Among the options, tert-butoxide (a bulky base) is chosen, as it effectively removes a hydrogen from the less substituted beta carbon, leading to the formation of a double bond and the expulsion of bromine.

Following this, we introduce HBr in the presence of hydrogen peroxide. This step involves hydrohalogenation, where the presence of peroxide causes the reaction to follow anti-Markovnikov's rule, resulting in bromine attaching to the less substituted alkene carbon. The product from this step is then subjected to an SN₂ reaction with potassium cyanide (KCN) in DMSO solvent, where the cyanide ion attacks the carbon, displacing the bromine and forming a nitrile.

Finally, we perform acidic hydrolysis using water (H₂O) and an acid (H⁺), which converts the nitrile into the desired carboxylic acid. This comprehensive sequence of reactions illustrates the effective use of specific reagents to achieve the transformation from the initial reactant to the final product, confirming that option C is the optimal choice for this synthetic pathway.

Nitriles can be effectively converted into primary amines through reduction processes. This transformation can be achieved using strong reducing agents such as lithium aluminum hydride (LiAlH₄) or through catalytic hydrogenation using hydrogen gas (H₂) over a metal catalyst, typically palladium (Pd).

In the reduction of nitriles, the carbon-nitrogen triple bond is converted into a single bond. Specifically, the carbon atom gains two hydrogen atoms, resulting in a methylene group (–CH₂), while the nitrogen atom also gains two hydrogen atoms, forming an amine group (–NH₂). This process can be summarized by the following reaction:

\[\text{R-C} \equiv \text{N} + 2 \text{H} \rightarrow \text{R-CH}_2\text{NH}_2\]

Thus, the reduction of nitriles is a crucial reaction in organic chemistry, allowing for the synthesis of primary amines from nitriles through either strong reduction or catalytic hydrogenation methods.

In organic synthesis, transforming benzene into a compound with both a bromine atom and an amine group involves a series of strategic reactions. Starting with benzene, the first step typically involves bromination, which introduces a bromine atom to the aromatic ring. Bromine acts as an ortho/para director, meaning that subsequent substituents will preferentially attach to the ortho or para positions relative to the bromine.

Next, to introduce a nitro group (–NO₂), one can perform nitration. However, if the nitro group is added after bromination, it would typically go to the meta position due to the influence of the bromine. To achieve the desired ortho relationship between the bromine and the nitro group, sulfonation can be employed first. This process introduces a sulfonic acid group (–SO₃H) at the para position, effectively blocking it and allowing the nitro group to be added ortho to the bromine.

After sulfonation, the next step is to perform nitration, where the nitro group is added to the ortho position. Following this, desulfonation can be achieved using H₃O⁺, which removes the sulfonic acid group, leaving the bromine and nitro groups on the benzene ring.

To convert the nitro group into an amine group (–NH₂), reduction is necessary. This can be accomplished using tin (Sn) in hydrochloric acid (HCl), which reduces the nitro group to an amine. The next step involves generating a diazonium salt from the amine using sodium nitrite (NaNO₂) and HCl. This diazonium salt can then be transformed into a nitrile group (–CN) using copper(I) cyanide (CuCN), a process known as the Sandmeyer reaction.

Finally, the nitrile group can be reduced to a primary amine using lithium aluminum hydride (LiAlH₄). This series of reactions effectively transforms benzene into the desired product with both a bromine and an amine group. The optimal set of reagents for this synthesis is option B, which includes the necessary steps to achieve the final compound.

In the conversion of nitriles to ketones, the reaction involves the use of Grignard reagents followed by hydrolysis. Initially, a nitrile group is present, characterized by a carbon-nitrogen triple bond. Due to nitrogen's higher electronegativity, it carries a partial negative charge, while the carbon atom is partially positive.

When a Grignard reagent is introduced, it reacts with the nitrile. The bond between carbon and nitrogen breaks, allowing the carbon from the Grignard reagent to bond with the nitrile carbon. This process results in the formation of an intermediate where the nitrogen atom, now with two lone pairs and two bonds, carries a negative charge. The magnesium bromide (MgBr) from the Grignard reagent remains positively charged, creating a complex that includes a carbon-nitrogen double bond, indicative of an imine functional group.

To complete the transformation, the next step involves acidic hydrolysis. This process effectively removes the nitrogen atom from the intermediate, replacing it with an oxygen atom. The final product of this reaction is a ketone, demonstrating a successful conversion from a nitrile through the strategic use of a Grignard reagent followed by hydrolysis.

To synthesize benzophenone from benzene, incorporating a nitrile reaction, we can follow a multi-step process. The target molecule, benzophenone, consists of two benzene rings connected by a carbonyl group. The synthesis begins with the nitration of benzene to introduce a nitro group.

First, we perform a nitration reaction using a mixture of nitric acid and sulfuric acid. This step adds a nitro group (–NO₂) to the benzene ring, resulting in nitrobenzene. The next step involves reducing the nitro group to an amino group (–NH₂) using tin (Sn) in hydrochloric acid (HCl). This reduction transforms nitrobenzene into aniline.

Subsequently, we convert the amino group into a diazonium salt by treating aniline with sodium nitrite (NaNO₂) in hydrochloric acid. The diazonium salt can then undergo a Sandmeyer reaction, where it reacts with copper(I) cyanide (CuCN) to form a nitrile group (–C≡N), yielding benzonitrile.

Now that we have the nitrile, the next step is to convert this nitrile into a ketone. This transformation can be achieved by reacting benzonitrile with a Grignard reagent, which is typically an organomagnesium compound. The Grignard reagent adds to the carbon of the nitrile, forming an intermediate that is then hydrolyzed with water (H₂O) or an acid (H₃O⁺). This hydrolysis step introduces the carbonyl group, resulting in the formation of benzophenone.

In summary, the synthesis of benzophenone from benzene through a nitrile reaction involves the following key steps: nitration to form nitrobenzene, reduction to aniline, diazotization to create a diazonium salt, Sandmeyer reaction to introduce the nitrile, and finally, conversion of the nitrile to a ketone using a Grignard reagent followed by hydrolysis. This method effectively demonstrates the versatility of organic synthesis pathways.