Examples of Carbon Carbon Bond Formation Reactions

In a chemical synthesis lab, we often encounter carbon carbon bond formation reactions during the organic synthesis process. There are many kinds of such reactions. This article mainly discusses common reactions that form a carbon-carbon bond. According to the different reaction substrates, this type of reaction can be divided into adding carbon atoms from aromatic rings and extending carbon chain from linear alkanes; according to the different reaction products, this type of reaction can be divided into reaction generating carboxylic acid or ester, reaction generating aldehyde group, and reaction generating a cyano group, etc. Common reagents for this type of reaction are CO2, CO, DMF-DMA, cyanide, formaldehyde or paraformaldehyde, nitromethane, diazomethane, etc. 

Carbon carbon forming reactions — example 1. carbonization reaction

1.1 Carbonization with CO2

Use a strong base to remove the halogen on the aromatic ring, and then react with CO2 to generate aryl formic acid. E.g:Carbonization with CO2

The approximate course of the reaction is: i-PrMgBr first reacts with aromatic halogenated compounds to generate aryl format reagent, and then the aryl format reagent reacts with CO2.

process of Carbonization with CO2

1.2 Carbonization with CO

Similar Buchwald reaction can occur when the aromatic halides react with CO under palladium catalysis, and this reaction generates formate. E.g:Carbonization with CO

The general mechanism of this reaction is as follows:

mechanism of carbonization with CO

Carbon carbon forming reactions — example 2. formylation reaction on aromatic ring

2.1 Strong base, DMF method

Use a strong base to remove the halogen on the aromatic ring, and then react with DMF to form an aldehyde group. This reaction requires low temperature, anhydrous, and oxygen-free operation. E.g:

Strong base, DMF method

2.2 Vilsmeier-Haack reaction

Using DMF and POCl3 to make aromatic ring formylation reaction. E.g:

Vilsmeier-Haack reaction

2.3 Reimer-Tiemann reaction

This reaction is only suitable for adding the aldehyde group to the phenolic hydroxyl group. E.g:Reimer-Tiemann reaction

Three commonly used formylation methods are introduced above. They are also carbon carbon bond reactions. These three methods are adapted to the formylation of substrates with different substituents, and appropriate methods should be selected according to the different substrates.

Carbon carbon forming reactions — example 3. reaction with cyanide

The reaction of linear halides with cyanide is a common method for synthesizing primary amines with one carbon chain. E.g:reaction with cyanide

Aromatic halides can also react with cyanide, and the resulting arylacetonitrile can be hydrolyzed to acid or reduced to amine. E.g:reaction with cyanide,

Carbon carbon forming reactions — example 4. Henry reaction

Henry reaction is also an example of carbon carbon bond reactions. In the presence of a trace amount of alkali, the α-active methylene groups of primary or secondary nitroalkanes can react with aldehydes and generates a reaction similar to aldol condensation to form nitroalcohol compounds, which are then dehydrated to form double bonds. This reaction can also synthesize primary amines that extend a carbon chain. E.g:Henry reaction

Carbon carbon forming reactions — example 5. reactions involving DMF-DMA or HC(OEt)3

After the nucleophile reacts with DMF-DMA or HC(OEt)3, the N,N-dimethyl or methoxy group connected to the double bond is generated, which is a good leaving group and is widely used to make aromatic heterocycles. E.g:reactions involving DMF-DMA or HC(OEt)3

Carbon carbon forming reactions — example 6. reaction with formaldehyde or paraformaldehyde

The reaction of nucleophiles with formaldehyde or paraformaldehyde is a common method for synthesizing primary alcohols that extend a carbon chain. E.g:reaction with formaldehyde or paraformaldehyde

Carbon carbon forming reactions — example7. reactions involving HCOOMe or dimethyl carbonate

Compounds containing α-active methylene groups can react to generate similar ClaisenCondensation with methyl formate or dimethyl carbonate, and the resulting products can be used to construct aromatic heterocycles. E.g:reactions involving HCOOMe or dimethyl carbonate

Carbon carbon forming reactions — example 8. arndt-eistert synthesis (Wolff Rearrangement)

For companies that offer custom synthesis services, this reaction is a commonly-seen one. It is a kind of carboxylic acid homologation reaction, and it is a very useful synthetic method to increase the carbon chain of carboxylic acid. The carboxylic acid is first converted to acid chloride, and then reacts with diazomethane to form diazoketones, which are rearranged under the action of appropriate reagents and catalysts, and lose nitrogen to form ketenes (this step is called Wolff Rearrangement). The reaction of ketene with water, alcohol, ammonia or amines can obtain a carboxylic acid or its derivative with one more methylene group than the original carboxylic acid. E.g:arndt-eistert synthesis (Wolff Rearrangement)