Basic Organic Chemistry: What is a Lactam?

Compounds are chemicals formed by combining two or more different atoms, the basic building blocks of matter. Organic compounds contain carbon, frequently bonded to itself, whether in chains, rings, or some other geometric structure. There are so many organic compounds, they must be categorized according to "functional groups." Functional groups are specialized structures within a compound that may contain a special atom, such as nitrogen, sulfur, phosphorous, etc. One kind of compound categorized according to functional group is the amide. An amide is the result of the reaction of an organic acid group with a nitrogen-containing amine group. A lactam is a special type of amide. Although in itself, not among the most important of compounds, it is useful in the formation of what are called heterocyclic rings.

Inorganic and Organic Compounds

Simple examples of inorganic compounds include NaCl, MgSO₄, NH₃, and H₃PO₄. These compounds are, respectively, salt, magnesium sulfate, ammonia, and phosphoric acid. In order the number of different kinds of atoms in each are two, three, two, and three. The compound with the greatest number of atoms in this list is H₃PO₄, with three hydrogen atoms, one phosphorous atom, and four oxygen atoms, or eight atoms complete.

Two examples of organic compounds are CH₃CH₂CH₂-OH and C₆H₆-or propyl alcohol and benzene. These two compounds contain carbon atoms bonded to one another. Ethyl alcohol contains two carbons bonded to each other, while for benzene the carbon atoms form a 6-membered ring (See the diagram associated with this article).

Functional Groups

Functional groups are atomic combinations or structures (including double and triple bonds) that are generally more reactive or of greater interest than the overall structure. Examples of functional groups include (along with many others),

-NH₂ (amino)
-COOH (carboxylic acid)
-SH (mercaptan)
-C=C- (alkene)
-OH (hydroxyl)
-C=O (carbonyl).

Of these, amides and lactams are combinations of the first two-amino and carboxylic acid.

Amides

An amide may be produced by combining a carboxylic acid with an amino group. In addition to amide formation, a molecule of water is related. For example, ethyl amine reacts with acetic acid to form ethyl acetamide and water.

CH₃CH₂-NH₂ + HOOC-CH₃ → CH₃CH₂-NH-OC-CH₃ + HOH

Notice that, in this instance, two short-chain compounds react to form a longer-chain compound.¹ The result is called an amide.

Lactams - Cyclic Amides

With some modification, a reaction may be carried out that generates a ring structure containing a similar linkage. Consider the result if two functional groups are a distance apart on the same molecule and react together. Consider, for instance, 4-aminobutyric acid, H₂N-CH₂CH₂CH₂-COOH. If reacted utilizing the proper conditions,²

H₂N-CH₂CH₂CH₂-COOH → 5-member ring + HOH (see associated image).

The amino group at one end reacts with the carboxylic acid group at the other, closing the molecule to form the ring. The ring structure is called a lactam. The type of lactam is designated by using a Greek letter prefix that indicating the number of carbons in the ring, not counting the carbonyl group. For instance, if there are two such carbons, the prefix is beta (the 2nd letter of the alphabet)-if there are four, the prefix is delta, and so on. The ring formed in the above reaction is a gamma-lactam. It's name is based on the number of carbon atoms in the skeleton-in this instance, butyrolactam. There are other ways of naming the structure, one of which is 2-pyrollidinone.

Reducing the Carbonyl in Lactam to CH2

The carbonyl of a lactam can be reduced to produce a heterocyclic ring. "Heterocyclic" refers to the presence of a non-carbon atom in the ring. It is thus easy to produce a four member ring containing a nitrogen atom, or a five member ring, a six member ring, and so on. Such rings often occur in very important organic compounds related to living things. There are heterocyclic rings in the active ingredients of a plethora of medications. There are a variety of methodologies for reducing the carbonyl. To visualize the end result, again refer to the image associated with this article.

¹ Although it isn't obvious as drawn, the carbon-containing chain formed actually consists of six atoms, C-C-C-N-C-C. The oxygen is actually attached to the next-to-last carbon by a double-bond off to the side.
² Utilizing different conditions can produce a polymeric product. The amino group of one molecule would react with the carboxylic acid of a different molecule, and so on.

References and Resources:

"The Amide Linkage: Structural Significance in Chemistry, Biochemistry, Materials Science," by Arthur Greenberg, et. al., 2002.

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