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Amide Practical Group | ChemTalk

Core Ideas

Amides are a typical and helpful natural practical group consisting of a carbon, oxygen, and nitrogen atom. On this article, the construction, atomic properties, synthesis, reactions, and position in peptide bonding of the amide practical group are explored.

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What’s the Amide Practical Group?

Amides are an natural practical group that encompass a carbon, oxygen, and nitrogen atoms. Amide practical teams have a particular structure of atoms, the place the nitrogen bonds to the carbonyl carbon. Primarily based on the variety of non-hydrogen teams hooked up to the nitrogen atom, amides are both categorized as main, secondary, tertiary, and even quaternary.

Different Types of Amides: Primary; Secondary; Tertiary, Quaternary
Determine 1: Major Amide (Left); Secondary Amide (Middle Left); Tertiary Amide (Middle Proper); Quaternary Amide (Proper

Observe that the quaternary amine carries a optimistic formal cost, making it helpful to kind ionic bonds with an anion.

Amides are most structurally just like carboxylic acids, which have a second oxygen instead of the nitrogen. Amides are additionally just like amines, which encompass  solely a nitrogen atom bonded to no less than one carbon atom.

Carboxylic Acids (Left) and Amines (Center), Compared to Amides (Right)
Determine 2: Carboxylic Acid (Left), Amines (Middle), Amides (Proper)

Amides usually have a C-N bond size of 132 to 134 picometers, shorter than an amine C-N bond. This discrepancy is attributable to the partial delocalization of the carbonyl pi bond to the C-N bond to kind an imine.

Isomerization of Amides
Determine 3: Isomerization of Amides

When writing out a molecule linearly, amides are written as CON. Nevertheless, IUPAC has very particular nomenclature for naming amides. When naming a molecule with an amide practical group, the chain numbering begins at carbonyl carbon and counts away following normal IUPAC chain naming procedures. It is best to title any substituents hooked up to the N molecule with the N- prefix. Following IUPAC nomenclature, one ought to title the remainder of the carbon chain appropriately. Lastly, the molecule ought to finish with the suffix -amide. For example this, examples of two molecules containing an amide practical group are proven beneath.

Naming of Amides: Butanamide (Left); N-chloro-5-methoxy-N,2-dimethylhexanamide
Determine 4: Amide Naming

Examples of Molecules with an Amide Practical Group

Amides are a key natural practical group and kind essential items of each artificial and pure molecules. Amides are essentially the most plentiful practical group in medicinal molecules, proteins, and plastics attributable to their versatility as a ‘linker’ to attach two or extra moieties.

Polymers typically comprise amides for this connective capability. One of the crucial widespread plastics, nylon, is replete with secondary amides, combining versatile carbon teams in between giving nylon its versatile attribute. Alternatively, Kevlar, one of many strongest artificial supplies, additionally accommodates many amides. Exploiting the hydrogen bonding capability of amides (and a few intelligent spacing) creates inflexible forces between polymer chains that give Kevlar its power. The beneath molecules are Nylon (high) and Kevlar (backside).

Amide Containing Polymers: Nylon (top), Kevlar (bottom)
Determine 5: The polymer construction of nylon (high) with the construction of Kevlar (backside) with hydrogen bonds proven. Observe the numerous amides connecting the repeating models of every polymer.

Ubiquitously present in medicinal molecules, amides can hydrogen bond with amino acids within the protein goal, guaranteeing a powerful and potent bond with the protein. In biologics, amides are ubiquitous in peptide (protein) medicine as they kind the spine of small proteins. This shall be explored within the Amides in Proteins paragraph.

Properties of the Amide Practical Group

The amide group is fairly polar because of the excessive electronegativities of the oxygen and the nitrogen. This normally makes small molecules containing amides soluble in polar solvents, together with water. The amide group has a polar floor space of 29 sq. angstroms, which is lower than the comparable carboxylic acid practical group however greater than the amine group. The flexibility of main and secondary amides to donate and settle for hydrogen bonds with water additionally contributes to their solubility.

Amides have a pKa of roughly 16, which means that they don’t wish to readily donate a hydrogen molecule. This results in a lot much less acidic habits than a carboxylic acid (pKa of 4-5) however extra acidic than the amine practical group, which usually acts as a base. This reasonable acidity makes them best candidates for ionized drug molecules, that are usually extra soluble that their non-ionized counterparts.

Amides are simply detectable with spectroscopic strategies because of the presence of two properly understood practical teams. The carbonyl group is definitely detectable in IR spectra at roughly 1650 cm-1and the amine is detectable at 3300-3500 cm-1. Hydrogen atoms hooked up to the nitrogen atom in a main or secondary amide exhibit a chemical shift in NMR research from 5.5 to eight.5 ppm.

Synthesis of Amides

Amides are produced via two major households of artificial routes. The synthesis of amides entails the response of a carboxylic acid and an amine (main) in an natural solvent resembling DCM. These two reactants want a coupling agent (resembling DCC or HATU) to mix immediately within the lab, via a course of often known as peptide bonding. Additionally, an acyl chloride (ready via the response of the carboxylic acid and thionyl chloride) can react with an amine to kind an amide. This course of is an instance of nucleophillic acyl substitution.

Artificial Peptide Bonding with DCC as a coupling agent
Determine 6: Synthetic Peptide Bonding: A carboxylic acid and an amide are immediately reacted with a coupling reagent in primary circumstances. The archetypal solvent for this response is dichloromethane (DCM).  
Nucleophilic Acyl Substitution Synthesis of Amides
Determine 7: Nucleophilic Acyl Substitution: The carboxylic acid is first transformed to an acyl chloride utilizing thionyl chloride, which is then reacted with a main or secondary amine to afford the specified amide.

The earlier household of reactions works properly for big molecules or molecules with fragile practical teams. Nevertheless, chemists usually favor a less expensive, faster, and extra environment friendly response for smaller and fewer fragile reactants. By reacting a carboxylic acid immediately with an amide to kind a carboxylate and ammonium salt, one can obtain these targets. In a ultimate step, amides condense from the ionic combination upon heating.

Amide Synthesis via Ammonium Salt
Determine 8: Amide Manufacturing Through an Ammonium Salt.   

Reactions Involving Amides

Amides are very versatile practical teams and might endure many various reactions. One widespread ambition of chemists is to transform main amides into main amines. Luckily, there are two reactions to attain this. The primary is an ordinary discount of the amide to kind the amine utilizing a lowering agent resembling lithium aluminum hydride.

Direct Reduction of Amides to Amines
Determine 9: Direct Discount of an Amide to Produce an Amine

Exploiting a intelligent response, one also can convert an amide to an amine with one fewer carbon atom. Referred to as the Hoffman rearrangement, this response converts the amide to an isocyanate utilizing aqueous bromine and sodium hydroxide. Hydrolyzing the isocyanate affords the amine with one fewer carbon atom.

Hoffman Rearrangement: Amides are converted to an isocyanate which is hydrolyzed into an amine with one less carbon atom.
Determine 10: Hoffman Rearrangement

Amides two carbon atoms earlier than an fragrant moiety can endure a really distinctive and helpful response. These kinds of amides are capable of react with themselves to kind a brand new ring on the molecule (often known as an imine heterocycle). This mechanism, often known as the Bischler-Napieralski response may be very helpful in synthesizing medicinal molecules, which frequently have rings of this kind.

Bischler-Napieralski Reaction
Determine 11: Bischler-Napieralski Response

Amides in Proteins

Amides are essential to life, the truth is, you’ve gotten about 1022 amides within your physique proper now. It’s because amides kind a essential spine to proteins, the equipment of our cells. In our physique, these amides present versatile help to the molecules that perform duties inside our cells. Throughout translation, a ribosome brings a carboxylic acid of an amino acid sufficiently near an amine on the following amino acid reacting to construct up a protein like a sequence.  

Amides As the Backbone of Proteins: 3D structure (top), 2D Structure (Bottom)
Determine 12: Amides Kind the Spine of All Proteins Between Amino Acids


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