Sodium Cyanide Reacts With 2 Bromobutane In Dimethylsulfoxide

Here's a detailed exploration of the reaction between sodium cyanide and 2-bromobutane in dimethyl sulfoxide (DMSO), covering aspects from reaction mechanisms to practical considerations.

Understanding the Reactants

Sodium cyanide (NaCN) is an inorganic compound with a wide range of applications in various industries. Its chemical formula, NaCN, reveals it as a salt composed of sodium cations (Na+) and cyanide anions (CN-). The cyanide ion is particularly notable due to its ambident nucleophilic nature, meaning it can attack electrophilic centers through either the carbon or nitrogen atom. This characteristic makes sodium cyanide a versatile reagent in organic synthesis.

2-Bromobutane, represented as CH3CHBrCH2CH3, is a secondary alkyl halide. The presence of a bromine atom attached to the second carbon in the butane chain makes it susceptible to nucleophilic substitution reactions. The bromine atom, being a good leaving group, facilitates these reactions. The secondary nature of the carbon bearing the bromine atom has significant implications for the reaction mechanism, influencing whether it proceeds via SN1 or SN2 pathways.

Dimethyl sulfoxide (DMSO) is an organosulfur compound with the formula (CH3)2SO. It is a polar aprotic solvent, meaning it has a high dielectric constant and lacks acidic protons. DMSO is widely used in organic chemistry due to its ability to dissolve a broad range of compounds, including polar and nonpolar substances. Its aprotic nature is crucial because it does not participate in hydrogen bonding with nucleophiles, thereby enhancing their reactivity.

The SN2 Reaction Mechanism

The reaction between sodium cyanide and 2-bromobutane in DMSO primarily follows an SN2 (bimolecular nucleophilic substitution) mechanism. In this process, the cyanide ion (CN-) acts as a nucleophile, attacking the carbon atom bonded to the bromine atom in 2-bromobutane. The reaction occurs in a single step, with the nucleophile attacking from the backside of the carbon-bromine bond, leading to the simultaneous departure of the bromide ion (Br-).

The SN2 mechanism is highly sensitive to steric hindrance. The secondary nature of the carbon atom in 2-bromobutane introduces some steric bulk, which can slow down the reaction rate compared to primary alkyl halides. However, the use of DMSO as a solvent mitigates this effect to some extent.

DMSO's role as a polar aprotic solvent is critical for the SN2 reaction. Unlike protic solvents (e.g., water, ethanol), DMSO does not solvate the cyanide ion through hydrogen bonding. This leaves the cyanide ion "naked" and highly reactive, increasing its nucleophilicity. In protic solvents, the nucleophile would be surrounded by solvent molecules, reducing its ability to attack the electrophilic carbon.

Stereochemistry of the Reaction

The SN2 reaction is stereospecific, meaning it proceeds with inversion of configuration at the chiral center. Since 2-bromobutane is a chiral molecule, the SN2 reaction results in the inversion of the stereocenter at the second carbon atom. If the starting material is a single enantiomer of 2-bromobutane (either R or S), the product will be the corresponding enantiomer of 2-cyanobutane with the opposite configuration.

For example, if (R)-2-bromobutane is used as the starting material, the product will be (S)-2-cyanobutane, and vice versa. This inversion of configuration is a hallmark of the SN2 mechanism and provides strong evidence for its occurrence in this reaction.

Competing Elimination Reactions (E2)

While the SN2 reaction is favored under these conditions, it is essential to consider the possibility of a competing elimination reaction (E2). The E2 reaction involves the removal of a proton from a carbon adjacent to the carbon bearing the leaving group, resulting in the formation of an alkene. In this case, the cyanide ion can act as a base, abstracting a proton from 2-bromobutane and forming but-2-ene.

The likelihood of the E2 reaction depends on several factors, including:

• Base Strength: Cyanide ion is a relatively strong base, which can promote elimination reactions.
• Temperature: Higher temperatures generally favor elimination reactions over substitution reactions due to entropic factors.
• Steric Hindrance: Bulky bases and substrates with significant steric hindrance around the reaction center tend to favor elimination.

In the case of 2-bromobutane, the secondary carbon and the presence of beta-hydrogens make it susceptible to E2 elimination. To minimize the E2 reaction and maximize the yield of the SN2 product, it is crucial to control the reaction conditions. Lower temperatures and the use of a high concentration of the nucleophile (cyanide ion) can help suppress elimination.

Factors Affecting the Reaction Rate

Several factors can influence the rate of the reaction between sodium cyanide and 2-bromobutane in DMSO:

• Concentration of Reactants: The SN2 reaction is bimolecular, meaning the rate of the reaction depends on the concentration of both the nucleophile (cyanide ion) and the substrate (2-bromobutane). Increasing the concentration of either reactant will increase the reaction rate.
• Temperature: Higher temperatures generally increase the reaction rate. However, as mentioned earlier, higher temperatures also favor elimination reactions. Therefore, it is essential to find an optimal temperature that balances the rate of the SN2 reaction with the suppression of the E2 reaction.
• Solvent Effects: DMSO is an ideal solvent for SN2 reactions because it solvates cations effectively while leaving the nucleophile relatively unsolvated. This increases the nucleophilicity of the cyanide ion. The use of protic solvents would significantly decrease the reaction rate.
• Leaving Group Ability: Bromine is a good leaving group, which facilitates the SN2 reaction. Other leaving groups, such as chlorine or iodine, could also be used, but bromine is generally a good compromise between reactivity and cost.
• Steric Hindrance: The secondary nature of 2-bromobutane introduces some steric hindrance, which can slow down the reaction rate compared to primary alkyl halides. However, this effect is mitigated by the use of DMSO and the relatively small size of the cyanide ion.

Experimental Considerations

When performing this reaction in the laboratory, several practical considerations are important:

• Safety: Sodium cyanide is highly toxic and must be handled with extreme care. It is essential to use appropriate personal protective equipment (PPE), including gloves, safety goggles, and a lab coat. The reaction should be carried out in a well-ventilated area or a fume hood to avoid inhalation of toxic fumes.
• Reagent Purity: The purity of the reactants is crucial for obtaining good yields and minimizing side reactions. 2-Bromobutane should be freshly distilled to remove any impurities that could interfere with the reaction. Sodium cyanide should be of high purity and stored in a dry environment to prevent decomposition.
• Reaction Setup: The reaction is typically carried out in a round-bottom flask equipped with a magnetic stirrer and a reflux condenser. The reflux condenser prevents the loss of volatile reactants and solvents during the reaction. The flask should be thoroughly dried before use to avoid unwanted side reactions with water.
• Monitoring the Reaction: The progress of the reaction can be monitored using various techniques, such as thin-layer chromatography (TLC) or gas chromatography (GC). TLC involves spotting samples of the reaction mixture on a silica gel plate and eluting it with a suitable solvent system. The appearance of the product and the disappearance of the starting material can be observed under UV light or by staining the plate with a suitable reagent. GC involves injecting samples of the reaction mixture into a gas chromatograph, which separates the components based on their boiling points. The relative amounts of the starting material and the product can be determined by measuring the peak areas.
• Workup and Purification: After the reaction is complete, the product must be isolated and purified. The workup procedure typically involves the following steps:
  • Quenching the Reaction: The reaction is quenched by adding water to the reaction mixture. This stops the reaction and dissolves any remaining sodium cyanide.
  • Extraction: The product is extracted from the aqueous phase using an organic solvent, such as diethyl ether or ethyl acetate. The organic phase is separated from the aqueous phase using a separatory funnel.
  • Drying: The organic phase is dried over a drying agent, such as anhydrous magnesium sulfate or sodium sulfate. This removes any residual water from the organic phase.
  • Filtration: The drying agent is removed by filtration.
  • Evaporation: The solvent is removed by evaporation using a rotary evaporator. This leaves behind the crude product.
  • Purification: The crude product is purified using techniques such as distillation, recrystallization, or column chromatography. Distillation involves heating the crude product to its boiling point and collecting the vapor, which is then condensed and collected as the purified product. Recrystallization involves dissolving the crude product in a hot solvent and then cooling the solution, which causes the product to crystallize out of the solution. Column chromatography involves passing the crude product through a column packed with a solid adsorbent, which separates the components based on their affinity for the adsorbent.
• Waste Disposal: All waste materials, including unreacted reactants, solvents, and byproducts, must be disposed of properly according to local regulations. Sodium cyanide waste should be treated with a suitable oxidizing agent, such as sodium hypochlorite, to convert it to less toxic compounds before disposal.

Safety Precautions

Working with sodium cyanide requires strict adherence to safety protocols:

• Toxicity: Sodium cyanide is extremely toxic if ingested, inhaled, or absorbed through the skin. It interferes with cellular respiration, leading to rapid oxygen deprivation.
• Handling: Always wear appropriate PPE, including gloves, safety goggles, and a lab coat, when handling sodium cyanide. Use a fume hood to avoid inhalation of toxic fumes.
• Storage: Store sodium cyanide in a tightly sealed container in a cool, dry place away from acids and oxidizing agents.
• First Aid: In case of exposure, immediately seek medical attention. For skin contact, wash the affected area with copious amounts of water. For eye contact, flush the eyes with water for at least 15 minutes. If ingested, do not induce vomiting and seek immediate medical assistance.
• Emergency Procedures: Have a plan in place for dealing with accidental spills or releases of sodium cyanide. This should include the availability of spill control materials and trained personnel to handle the situation.

Alternative Reagents and Methods

While sodium cyanide is a common reagent for introducing the cyano group into organic molecules, there are alternative reagents and methods that can be used in certain situations:

• Potassium Cyanide (KCN): Potassium cyanide is similar to sodium cyanide and can be used interchangeably in many reactions. It is also highly toxic and requires similar safety precautions.
• Trimethylsilyl Cyanide (TMSCN): TMSCN is a less toxic alternative to sodium cyanide. It is a liquid that can be easily handled and used in organic synthesis. However, it is more expensive than sodium cyanide and may require the use of a Lewis acid catalyst to promote the reaction.
• Copper(I) Cyanide (CuCN): Copper(I) cyanide is another alternative reagent for introducing the cyano group. It is less toxic than sodium cyanide but may require higher reaction temperatures and longer reaction times.
• Phase-Transfer Catalysis: Phase-transfer catalysis can be used to improve the reaction rate of SN2 reactions involving ionic reagents such as sodium cyanide. Phase-transfer catalysts are compounds that facilitate the transfer of ions from an aqueous phase to an organic phase, where they can react with organic substrates.

Examples and Applications

The reaction between sodium cyanide and alkyl halides is widely used in organic synthesis for the preparation of nitriles, which are valuable intermediates in the synthesis of various organic compounds. Some examples and applications include:

• Synthesis of Carboxylic Acids: Nitriles can be hydrolyzed to carboxylic acids under acidic or basic conditions. This is a common method for converting alkyl halides to carboxylic acids.
• Synthesis of Amines: Nitriles can be reduced to primary amines using reducing agents such as lithium aluminum hydride or sodium borohydride. This is a useful method for preparing primary amines from alkyl halides.
• Synthesis of Amides: Nitriles can be partially hydrolyzed to amides under mild conditions. This is a useful method for preparing amides from alkyl halides.
• Synthesis of Heterocyclic Compounds: Nitriles are versatile building blocks for the synthesis of various heterocyclic compounds, such as pyridines, pyrimidines, and imidazoles.

Conclusion

The reaction between sodium cyanide and 2-bromobutane in DMSO is a classic example of an SN2 reaction. The reaction is influenced by factors such as the concentration of reactants, temperature, solvent effects, and steric hindrance. Understanding these factors is crucial for optimizing the reaction conditions and maximizing the yield of the desired product. While sodium cyanide is a highly toxic reagent, its use in organic synthesis is widespread due to its effectiveness in introducing the cyano group into organic molecules. By following appropriate safety precautions and understanding the reaction mechanism, chemists can safely and effectively use this reaction to prepare a wide range of organic compounds.