Diazomethane Synthesis and Applications (Arndt-Eistert Homologation)

Professor Dave Explains
27 Jan 202105:58
EducationalLearning
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TLDRThis tutorial delves into the synthesis and applications of diazomethane, a highly reactive compound used in organic chemistry. It is synthesized from N-methyl-N-nitrosotoluenesulfonamide using sodium hydroxide in ether, resulting in a zwitterionic form that is unstable and should be used immediately. Diazomethane's applications include converting carboxylic acids into methyl esters and phenols into methyl ethers, as well as the Arndt-Eistert homologation for extending carboxylic acid chains by one carbon atom. The process involves nucleophilic attack, Wolff rearrangement, and ketene formation, offering a valuable synthetic technique for creating carboxylic acids of varying chain lengths.

Takeaways
  • ๐Ÿงช Diazomethane is commonly synthesized from N-methyl-N-nitrosotoluenesulfonamide using sodium hydroxide in ether.
  • ๐Ÿ” The synthesis involves a mechanism where hydroxide ions attack the sulfur atom and protonate the intermediates, leading to the formation of diazomethane.
  • โš ๏ธ Diazomethane is highly explosive and should only be handled by trained chemists.
  • ๐Ÿ”‘ Diazomethane is used to convert carboxylic acids into methyl esters via a simple protonation and substitution reaction.
  • ๐ŸŒŸ The resonance structure of diazomethane allows for its carbanion to be protonated, facilitating the SN2 reaction with carboxylate anions.
  • ๐Ÿƒ Diazomethane can also methylate phenols due to their relative acidity and resonance stabilization of the conjugate base.
  • ๐Ÿšซ Normal alcohols are not acidic enough to protonate diazomethane under normal conditions.
  • ๐ŸŒž Alcohols can be methylated by diazomethane under specific light irradiation conditions, which will be discussed in later tutorials.
  • ๐Ÿ”„ Diazomethane is crucial for the Arndt-Eistert homologation, a method to extend the carbon chain of carboxylic acids by one atom.
  • ๐Ÿ”ฌ The Arndt-Eistert process involves the conversion of carboxylic acids to acid chlorides and subsequent reaction with diazomethane to form an alpha diazoketone.
  • ๐Ÿ”„ The Wolff rearrangement, a 1,2-shift, occurs during the homologation process, converting the intermediate into a more stable ketene.
  • ๐Ÿ› ๏ธ Homologation can be repeated to synthesize carboxylic acids of any desired chain length, making it a valuable synthetic technique.
Q & A

  • What is a common method for carbene formation mentioned in the script?

    -A common method for carbene formation is through the decomposition of diazomethane.

  • What compound is used to synthesize diazomethane as described in the script?

    -Diazomethane can be synthesized from N-methyl-N-nitrosotoluenesulfonamide.

  • What is the role of sodium hydroxide in the synthesis of diazomethane?

    -Sodium hydroxide in ether is used to treat the starting compound, facilitating the reaction mechanism that leads to the formation of diazomethane.

  • Why is diazomethane co-distilled with ether after its formation?

    -Diazomethane is co-distilled with ether to facilitate its use directly, as it is quite explosive and should not be stored.

  • What is the primary reason diazomethane is titrated with a carboxylic acid immediately after synthesis?

    -Diazomethane is titrated with a carboxylic acid to stabilize it due to its explosive nature and to use it directly in reactions.

  • How can diazomethane be used to convert carboxylic acids into methyl esters?

    -Diazomethane can be protonated by the carboxylic acid to form a diazonium cation, which then undergoes an SN2 reaction with the carboxylate anion to form a methyl ester and release molecular nitrogen.

  • Why is diazomethane effective for methylating phenols but not normal alcohols?

    -Phenols can be methylated by diazomethane due to their relative acidity and resonance stabilization of the conjugate base, while normal alcohols lack sufficient acidity to protonate diazomethane.

  • What is the photochemical process that allows for the methylation of normal alcohols using diazomethane?

    -The photochemical process involves irradiating the mixture of diazomethane and alcohol with light of a particular wavelength, which facilitates the methylation reaction.

  • What is the Arndt-Eistert homologation, and how does it involve diazomethane?

    -The Arndt-Eistert homologation is a reaction that allows for the insertion of a carbon atom between the carboxyl carbon and the adjacent carbon of a carboxylic acid, effectively lengthening the carbon chain by one. Diazomethane plays a key role in this reaction after the carboxylic acid is converted into an acid chloride.

  • What is the intermediate formed when diazomethane reacts with an acid chloride, and what is its significance?

    -The intermediate formed is an alpha diazoketone, which upon heating, loses nitrogen gas to form an acyl carbene. This intermediate is significant as it leads to the formation of a ketene through a Wolff rearrangement.

  • What is the final product of the Arndt-Eistert homologation reaction, and how is it obtained?

    -The final product is a carboxylic acid with one more carbon than the original. It is obtained through the hydrolysis of the ketene formed after the Wolff rearrangement, where water performs a nucleophilic attack.

  • Why is the Arndt-Eistert homologation considered valuable in synthetic chemistry?

    -The Arndt-Eistert homologation is valuable because it allows for the repeated extension of the carbon chain of a carboxylic acid to any desired length, providing a versatile synthetic technique.

Outlines
00:00
๐Ÿงช Synthesis and Applications of Diazomethane

This paragraph discusses the synthesis of diazomethane from N-methyl-N-nitrosotoluenesulfonamide using sodium hydroxide in ether, detailing the mechanism of its formation through a series of reactions involving hydroxide ions and nitrogen atoms. The paragraph also highlights the explosive nature of diazomethane and the necessity for trained chemists to handle it. Applications include converting carboxylic acids into methyl esters, methylating phenols, and the homologation of carboxylic acids by one carbon atom through the Arndt-Eistert homologation process, which involves the insertion of a carbon atom between the carboxyl carbon and the adjacent carbon, leading to a longer carbon chain. The paragraph concludes with the Wolff rearrangement, which results in the formation of a ketene and ultimately a carboxylic acid with an extended chain.

05:01
๐Ÿ”ฌ Repeatability of Diazomethane Homologation

The second paragraph emphasizes the versatility of the homologation reaction using diazomethane. It explains that once the initial homologation is completed, the process can be repeated multiple times to synthesize carboxylic acids of varying chain lengths. This feature makes diazomethane a valuable tool in synthetic chemistry, allowing for the creation of a wide range of carboxylic acid derivatives tailored to specific needs.

Mindmap
Keywords
๐Ÿ’กCarbenes
Carbenes are highly reactive intermediates in organic chemistry with a carbon atom bearing two fewer electrons than its group valency, typically represented with a singlet or triplet state. In the video, carbenes are discussed as the focus of previous tutorials, and their formation through the decomposition of diazomethane is highlighted as a common method, which is central to the theme of the video.
๐Ÿ’กDiazomethane
Diazomethane is an organic compound with the formula CH2N2, known for its use as a methylating agent and as a precursor to carbenes. The video script details its synthesis and applications, emphasizing its role in organic synthesis and its reactivity, which makes it a key compound in the discussed chemical reactions.
๐Ÿ’กN-methyl-N-nitrosotoluenesulfonamide
This compound serves as the starting material for the synthesis of diazomethane. It is a specific chemical precursor that undergoes a reaction with sodium hydroxide in ether to form diazomethane, as described in the script. Understanding this term is crucial for grasping the synthesis process of diazomethane.
๐Ÿ’กSodium Hydroxide
Sodium hydroxide, commonly known as lye or caustic soda, is a strong base used in various chemical reactions. In the context of the video, it is used to treat N-methyl-N-nitrosotoluenesulfonamide, initiating the synthesis of diazomethane by attacking the sulfur atom.
๐Ÿ’กEther
Ether, specifically diethyl ether in this context, is an organic solvent used in the synthesis of diazomethane. It is mentioned in the script as the medium in which the reaction with sodium hydroxide takes place, and also for co-distilling the zwitterionic form of diazomethane.
๐Ÿ’กZwitterionic Form
A zwitterion is a molecule that contains both a positive and a negative charge within its structure. In the script, the zwitterionic form of diazomethane is discussed as an intermediate in its synthesis, highlighting the step-by-step mechanism of its formation.
๐Ÿ’กExplosive
The term 'explosive' in the script refers to the hazardous nature of diazomethane, which is why it is used directly after synthesis rather than being stored. This characteristic is important for understanding the safety precautions required when handling this compound.
๐Ÿ’กCarboxylic Acids
Carboxylic acids are organic compounds containing the carboxyl functional group (-COOH). The script discusses their conversion into methyl esters using diazomethane, illustrating a key application of diazomethane in organic chemistry.
๐Ÿ’กMethyl Esters
Methyl esters are esters formed from the reaction of a carboxylic acid and methanol. The video explains how diazomethane can be used to convert carboxylic acids into methyl esters, which is an important synthetic technique in organic chemistry.
๐Ÿ’กPhenols
Phenols are a class of chemical compounds consisting of a hydroxyl group (-OH) bonded directly to a benzene ring. The script mentions that phenols can also be methylated using diazomethane due to their relative acidity, which is an application of the compound's reactivity.
๐Ÿ’กArndt-Eistert Homologation
Arndt-Eistert homologation is a chemical reaction that involves the insertion of a carbon atom between the carboxyl carbon and the adjacent carbon of a carboxylic acid, effectively lengthening the carbon chain by one. The script describes this as a significant application of diazomethane, named after the chemists who discovered the reaction.
๐Ÿ’กWolff Rearrangement
The Wolff rearrangement is a type of 1,2-shift in organic chemistry that converts an alpha diazoketone into a ketene. The script explains this rearrangement as part of the Arndt-Eistert homologation process, showcasing a key step in the synthesis of longer-chain carboxylic acids.
Highlights

Diazomethane is commonly synthesized for carbene formation.

Synthesis involves decomposition of N-methyl-N-nitrosotoluenesulfonamide with sodium hydroxide in ether.

Mechanism involves hydroxide ion attacking sulfur, proton transfer, and nitrogen pushing lone pair to form zwitterionic diazomethane.

Diazomethane is co-distilled in ether and titrated with carboxylic acid before use due to its explosive nature.

Diazomethane converts carboxylic acids into methyl esters, avoiding typical acid catalysis.

Resonance structure of diazomethane allows carbanion protonation by carboxylic acid, forming diazonium cation.

Diazonium cation undergoes SN2 reaction with carboxylate anion, yielding methyl ester and nitrogen gas.

Phenols can also be methylated by diazomethane due to their relative acidity and resonance stabilization.

Normal alcohols are not acidic enough for methylation with diazomethane without photochemical assistance.

Diazomethane can homologate carboxylic acids by inserting a carbon atom, a reaction known as Arndt-Eistert homologation.

Homologation involves conversion of carboxylic acid to acid chloride and nucleophilic attack by diazomethane.

Triethylamine acts as a proton sponge in the formation of alpha diazoketone.

Heating alpha diazoketone leads to loss of nitrogen gas and formation of acyl carbene.

Acyl carbene undergoes Wolff rearrangement, forming a more stable ketene.

Hydrolysis of ketene results in the carboxylic acid with an extended carbon chain.

Arndt-Eistert homologation can be repeated to synthesize carboxylic acids of any desired chain length.

Diazomethane provides a valuable synthetic technique for organic chemistry.

Transcripts

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Related Tags
DiazomethaneCarbeneArndt-EistertHomologationOrganic ChemistryMethyl EsterPhenol MethylationCarboxylic AcidsChemical SynthesisWolff RearrangementSynthetic Techniques