Draw The Product Of The Reaction Shown Between Propanoyl Chloride

Propanoyl chloride, a reactive acyl chloride, undergoes a variety of reactions due to its electrophilic carbonyl carbon. Understanding these reactions is fundamental to organic chemistry, especially in the synthesis of various organic compounds. This article aims to explore the reactions of propanoyl chloride, detailing the mechanisms and products formed when it interacts with different nucleophiles.

Reactions of Propanoyl Chloride: An Overview

Propanoyl chloride, with the molecular formula CH3CH2COCl, is an acyl chloride derived from propanoic acid. The presence of the highly electronegative chlorine atom bonded to the carbonyl carbon makes it a potent electrophile. Consequently, propanoyl chloride reacts readily with nucleophiles in nucleophilic acyl substitution reactions. Key reactions include:

• Hydrolysis: Reaction with water.
• Alcoholysis: Reaction with alcohols.
• Aminolysis: Reaction with amines.
• Friedel-Crafts Acylation: Reaction with aromatic compounds.
• Grignard Reaction: Reaction with Grignard reagents.

Hydrolysis: Reaction with Water

The reaction of propanoyl chloride with water is a classic example of nucleophilic acyl substitution. The water molecule acts as the nucleophile, attacking the electrophilic carbonyl carbon.

Mechanism:

1. Nucleophilic Attack: The oxygen atom of water attacks the carbonyl carbon of propanoyl chloride. This forms a tetrahedral intermediate.
2. Proton Transfer: A proton is transferred from the oxygen atom of the water molecule to the chlorine atom.
3. Elimination: The carbon-chlorine bond breaks, and the chloride ion departs. Simultaneously, the carbonyl group reforms, expelling a proton.
4. Product Formation: Propanoic acid (CH3CH2COOH) and hydrochloric acid (HCl) are formed.

Overall Reaction:

CH3CH2COCl + H2O → CH3CH2COOH + HCl

The reaction is typically exothermic and proceeds rapidly at room temperature. The formation of hydrochloric acid as a byproduct necessitates the use of a base to neutralize the acid, preventing it from catalyzing the reverse reaction or causing other unwanted side reactions.

Alcoholysis: Reaction with Alcohols

Propanoyl chloride reacts with alcohols to form esters. This reaction, known as esterification, is another significant application of acyl chlorides in organic synthesis.

Mechanism:

1. Nucleophilic Attack: The oxygen atom of the alcohol attacks the carbonyl carbon of propanoyl chloride, forming a tetrahedral intermediate.
2. Proton Transfer: A proton is transferred from the oxygen atom of the alcohol to the chlorine atom.
3. Elimination: The carbon-chlorine bond breaks, and the chloride ion departs. Simultaneously, the carbonyl group reforms, expelling a proton.
4. Product Formation: An ester and hydrochloric acid are formed.

Example: Reaction with Ethanol

CH3CH2COCl + CH3CH2OH → CH3CH2COOCH2CH3 + HCl

In this specific example, propanoyl chloride reacts with ethanol to form ethyl propanoate, an ester with a fruity odor. The reaction is often carried out in the presence of a base, such as pyridine or triethylamine, to neutralize the hydrochloric acid formed.

Aminolysis: Reaction with Amines

Amines react with propanoyl chloride to form amides. This reaction is widely used in the synthesis of peptides and other complex organic molecules containing amide linkages.

Mechanism:

1. Nucleophilic Attack: The nitrogen atom of the amine attacks the carbonyl carbon of propanoyl chloride, forming a tetrahedral intermediate.
2. Proton Transfer: A proton is transferred from the nitrogen atom of the amine to the chlorine atom.
3. Elimination: The carbon-chlorine bond breaks, and the chloride ion departs. Simultaneously, the carbonyl group reforms, expelling a proton.
4. Product Formation: An amide and hydrochloric acid are formed.

Example: Reaction with Ammonia

CH3CH2COCl + 2 NH3 → CH3CH2CONH2 + NH4Cl

In this reaction, propanoyl chloride reacts with ammonia to form propanamide. Note that two equivalents of ammonia are used; one to form the amide and the other to neutralize the hydrochloric acid, forming ammonium chloride.

Reaction with Primary Amines

CH3CH2COCl + 2 RNH2 → CH3CH2CONHR + RNH3Cl

With a primary amine (RNH2), propanoyl chloride forms an N-substituted propanamide.

Reaction with Secondary Amines

CH3CH2COCl + 2 R2NH → CH3CH2CONR2 + R2NH2Cl

Similarly, with a secondary amine (R2NH), an N,N-disubstituted propanamide is formed.

Friedel-Crafts Acylation: Reaction with Aromatic Compounds

Propanoyl chloride can be used in Friedel-Crafts acylation reactions to introduce a propanoyl group onto an aromatic ring. This reaction requires a Lewis acid catalyst, such as aluminum chloride (AlCl3).

Mechanism:

1. Formation of Acylium Ion: The Lewis acid catalyst (AlCl3) coordinates with the chlorine atom of propanoyl chloride, forming an acylium ion (CH3CH2CO+). This acylium ion is a strong electrophile.
2. Electrophilic Attack: The acylium ion attacks the aromatic ring, forming a sigma complex.
3. Deprotonation: A proton is removed from the aromatic ring, restoring aromaticity and forming the acylated product.
4. Product Formation: A propanoyl-substituted aromatic compound and hydrochloric acid are formed.

Example: Reaction with Benzene

CH3CH2COCl + Benzene --(AlCl3)--> CH3CH2COC6H5 + HCl

In this reaction, propanoyl chloride reacts with benzene in the presence of aluminum chloride to form propanophenone.

Grignard Reaction: Reaction with Grignard Reagents

Grignard reagents are powerful nucleophiles that react with propanoyl chloride to form ketones or tertiary alcohols, depending on the reaction conditions and stoichiometry.

Reaction to form Ketones

When propanoyl chloride reacts with one equivalent of a Grignard reagent, it initially forms a ketone. However, ketones are also reactive towards Grignard reagents, leading to further reaction. To isolate the ketone, the reaction must be carefully controlled, often at low temperatures.

Mechanism (Ketone Formation):

1. Nucleophilic Attack: The carbanion of the Grignard reagent attacks the carbonyl carbon of propanoyl chloride, forming a tetrahedral intermediate.
2. Elimination: The carbon-chlorine bond breaks, and the chloride ion departs. Simultaneously, the carbonyl group reforms, forming a ketone.

Example:

CH3CH2COCl + RMgX → CH3CH2COR + MgXCl

Reaction to form Tertiary Alcohols

If excess Grignard reagent is used, the initially formed ketone reacts further to form a tertiary alcohol.

Mechanism (Tertiary Alcohol Formation):

1. Ketone Formation: As described above, the initial reaction with one equivalent of Grignard reagent forms a ketone.
2. Further Nucleophilic Attack: The carbanion of a second equivalent of the Grignard reagent attacks the carbonyl carbon of the ketone, forming a tetrahedral alkoxide intermediate.
3. Protonation: Addition of acid (H3O+) protonates the alkoxide, forming a tertiary alcohol.

Example:

CH3CH2COCl + 2 RMgX + H3O+ → CH3CH2C(R)2OH + MgXCl

In this reaction, propanoyl chloride reacts with two equivalents of a Grignard reagent, followed by protonation, to form a tertiary alcohol.

Reaction with Ammonia: A Detailed Exploration

Ammonia (NH3) reacts with propanoyl chloride (CH3CH2COCl) through a nucleophilic acyl substitution mechanism. In this reaction, the nitrogen atom of ammonia acts as a nucleophile, attacking the carbonyl carbon of propanoyl chloride. This leads to the formation of propanamide (CH3CH2CONH2) and ammonium chloride (NH4Cl). Let's delve into the detailed mechanism and stoichiometry of this reaction.

Mechanism of the Reaction

1. Nucleophilic Attack:

   • The nitrogen atom in ammonia (NH3) has a lone pair of electrons, making it nucleophilic.
   • The carbonyl carbon in propanoyl chloride (CH3CH2COCl) is electrophilic due to the electron-withdrawing effect of the chlorine atom and the oxygen atom in the carbonyl group.
   • The nitrogen atom of ammonia attacks the carbonyl carbon, forming a tetrahedral intermediate.

2. Formation of Tetrahedral Intermediate:

   • The nucleophilic attack results in the formation of a tetrahedral intermediate with the following structure:

             O
             ||
        CH3CH2-C-Cl
                |
                NH3^+
     

   • In this intermediate, the nitrogen atom is now positively charged because it is bonded to three hydrogen atoms and the carbonyl carbon.

3. Proton Transfer:

   • A proton is transferred from the nitrogen atom to a neighboring atom (in this case, another ammonia molecule can act as a base). This step neutralizes the positive charge on the nitrogen atom.
   • The proton transfer can be represented as follows:

             O
             ||
        CH3CH2-C-Cl
                |
                NH2
     

4. Elimination of Chloride Ion:

   • The carbon-chlorine bond breaks, and the chloride ion (Cl-) is eliminated from the tetrahedral intermediate.
   • This elimination step reforms the carbonyl double bond (C=O).
   • The reaction proceeds as follows:

             O
             ||
        CH3CH2-C
                |
                NH2
             O
             ||
     CH3CH2-C-NH2 + Cl-
     

5. Formation of Propanamide and Ammonium Chloride:

   • The elimination of the chloride ion leads to the formation of propanamide (CH3CH2CONH2).
   • The chloride ion (Cl-) then reacts with another molecule of ammonia (NH3) to form ammonium chloride (NH4Cl). This neutralizes the hydrochloric acid that would otherwise be formed.

     NH3 + Cl- → NH4Cl
     

Overall Reaction

The overall reaction between propanoyl chloride and ammonia can be represented as:

CH3CH2COCl + 2 NH3 → CH3CH2CONH2 + NH4Cl

• Propanoyl Chloride (CH3CH2COCl): The acyl chloride that undergoes nucleophilic attack.
• Ammonia (NH3): Acts as the nucleophile and also as a base to neutralize the HCl byproduct.
• Propanamide (CH3CH2CONH2): The amide product.
• Ammonium Chloride (NH4Cl): The salt formed from the reaction of HCl with ammonia.

Stoichiometry

• One molecule of propanoyl chloride reacts with two molecules of ammonia.
• One molecule of ammonia acts as the nucleophile, while the second molecule acts as a base to neutralize the hydrochloric acid formed during the reaction, yielding ammonium chloride.

Reaction Conditions

• Temperature: The reaction is typically carried out at low temperatures to control the reaction rate and prevent side reactions.
• Solvent: The reaction can be performed in a solvent such as diethyl ether or dichloromethane to dissolve the reactants and facilitate mixing.
• Excess Ammonia: It is common to use excess ammonia to ensure complete conversion of propanoyl chloride to propanamide and to effectively neutralize the HCl byproduct.

Significance

The reaction of propanoyl chloride with ammonia is significant for several reasons:

• Amide Synthesis: It provides a straightforward method for synthesizing propanamide, which is a precursor in the synthesis of various organic compounds.
• Laboratory Use: It is a common reaction in organic chemistry labs for demonstrating nucleophilic acyl substitution reactions.
• Industrial Applications: Amides are important compounds in pharmaceuticals, polymers, and other industrial applications, making this reaction relevant in industrial chemistry.

Safety Considerations

When working with propanoyl chloride, several safety precautions must be observed:

• Corrosive: Propanoyl chloride is corrosive and can cause severe burns upon contact with skin or eyes.
• Moisture-Sensitive: It reacts violently with water, releasing hydrochloric acid.
• Toxic: Inhalation of propanoyl chloride vapors can be harmful.

Safety Measures:

• Personal Protective Equipment (PPE): Always wear appropriate PPE, including gloves, safety goggles, and a lab coat.
• Fume Hood: Conduct reactions involving propanoyl chloride in a well-ventilated fume hood to avoid inhalation of vapors.
• Proper Handling: Handle propanoyl chloride with care to avoid spills and contact with moisture.
• Neutralization: Have a plan for neutralizing any spills with a suitable base, such as sodium bicarbonate.

Conclusion

Propanoyl chloride is a versatile reagent in organic synthesis due to its high reactivity towards nucleophiles. Its reactions with water, alcohols, amines, aromatic compounds (via Friedel-Crafts acylation), and Grignard reagents provide routes to a wide variety of organic compounds, including carboxylic acids, esters, amides, ketones, and tertiary alcohols. Understanding the mechanisms and conditions of these reactions is essential for any chemist working in organic synthesis. Always remember to handle propanoyl chloride with appropriate safety precautions due to its corrosive and reactive nature.