Amines

FIELDS OF STUDY: Organic Chemistry

ABSTRACT

The characteristic properties and reactions of amines are discussed. Essentially unlimited in type, amines are useful compounds in organic synthesis reactions, helping form complex heterocyclic molecular structures from simple starting materials.

The Nature of the Amines

The term "amine" refers to the class of organic compounds that include one or more nitrogen-based functional groups in their molecular structures. The nitrogen atom has five electrons in its valence electron shell, with two electrons in the 2s orbital and three electrons distributed among the three 2p orbitals. In order to minimize electron-electron repulsions between the orbitals, the electrons are able to "hybridize" to form C−N, C=N, and C≡N bonds. Compounds containing the C−N bond are called "amines"; compounds containing the C=N bond are termed "imines"; and compounds containing the −C≡N functional group are termed "nitriles." The amines are divided into four classifications, beginning with the primary amines, which are characterized by the presence of the −NH₂ functional group. Generally, they are represented as R−NH₂ or Ar−NH₂, in which R− and Ar− are generic placeholders indicating an alkyl functional group (derived from a saturated hydrocarbon) and an aryl group (derived from an aromatic ring), respectively. The basic aryl amine is the compound aniline, which consists of a benzene ring with the −NH₂ group in place of one of the hydrogen atoms.

The secondary amines have two substituent groups bonded to the nitrogen atom. Thus, they have the general form R₂−NH, Ar₂−NH, or RAr−NH. Like primary amines, secondary amines are formed when the nitrogen atom is part of the ring structure of the compound. In such heteroatomic compounds, the carbon atoms bonded to the nitrogen atoms are considered to be the alkyl groups of the secondary amine structure. An example of such a compound is pyrrolidine:

Heterocyclic amines are common in nature and include a wide variety of naturally occurring compounds, such as the alkaloids.

The tertiary amines continue the same pattern, having three substituent groups attached to the nitrogen atom. The simplest tertiary amine is trimethylamine, a pungent alkaline compound with a melting point of −117 degrees Celsius (−178.6 degrees Fahrenheit). The simplest triarylamine is triphenylamine, a crystalline solid with melting point of 127 degrees Celsius (260.6 degrees Fahrenheit).

The lone pair of electrons on the nitrogen atom permits the formation of a chemical bond to a fourth alkyl group, which produces a fourth amine group, as quaternary ammonium salts. The reaction of trimethylamine with chloromethane, for example, produces the ionic compound tetramethylammonium chloride, according to the equation

Tetraalkylammonium salts are common additives in soap and shampoo formulations.

The lone pair of electrons on the nitrogen atom affords some special reactivity to amines. Because the p orbital holds its two electrons, there is less stability to be gained from hybridizing. When the nitrogen atom is bonded to a C=C bond, the orbital retains all or most of its p orbital character. In alkyl amines, the nitrogen atom adopts a tetrahedral arrangement, but in aryl amines, the geometry about the nitrogen atom is essentially a plane.

Nomenclature of Amines

Amines are named systemically according to the identity of the parent hydrocarbon from which they have been formed. The hydrocarbon structure is named for the number of carbon atoms on the longest unbranched chain in the molecular structure; the positions of substituent groups, or side chains, are identified accordingly. The formal name sequence begins with methane, ethane, propane, and butane as common names, and then progresses through names based on the number of carbon atoms: pentane, hexane, heptane, octane, nonane, decane, and so on. For alkene and alkyne compounds (unsaturated hydrocarbons), the corresponding -ene or -yne ending of the name is used. After the base chain has been determined, the positions of the substituents are assigned according to the lowest position numbers in the structure. The position number is inserted into the name of the primary chain immediately before the name of the substituent. Thus, a seven-carbon chain with two amino groups bonded to the second and third carbon atoms would thus be named 2,3-diaminoheptane and not 5,6-diaminoheptane. Using the standard International Union of Pure and Applied Chemistry (IUPAC) format, the substituent groups are named in alphabetical order in the formal name of the compound, which usually puts the amino substituents first.

Several "informal" names exist for many of the amines, and it is common practice to name a primary amine compound as a substituted amine rather than as an amino-substituted hydrocarbon. For example, 1-aminocycloheptane would typically be referred to as cycloheptylamine. Indeed, many common names for amines have been adopted as the proper IUPAC base name for derivative compounds.

Organic structures are typically represented by line drawings that depict the angles between the carbon atoms in such a way that every angle vertex and line end represents a single carbon atom. Such line drawings allow chemists to communicate a large amount of chemical information in a small space. This is a convenient representation that makes the nature and identity of the side chains readily apparent. These "stick drawings" use the elemental symbol of any atom other than carbon and hydrogen in its proper location in the molecular structure. The compound 2,8-diamino-nona-cis-3-trans-6-diene, for example, is more readily comprehended when depicted as

than as

For amines in which the nitrogen atom of the amino group bears alkyl or aryl substituents, an N- is placed before the name of the substituent. For example, a hexane bearing on the third carbon atom of an amino group that has a methyl and an ethyl substituent would be named 3-(N-ethyl, N-methyl)aminohexane.

Cyclic amines are named in a similar manner. The basic name reflects the number of carbon atoms in the largest ring structure in the molecule. The first position in the ring structure corresponds to either the carbon atom with the first substituent or the first carbon atom of a C=C or other definitive functional group; other substituents are assigned so as to attain the lowest set of position numbers.

Formation of Amines

Simple amines are formed by the reaction of an alkyl halide with ammonia. Ammonia (NH₃) is produced commercially by the Haber-Bosch process—the high-temperature, high-pressure reaction of nitrogen gas and hydrogen gas—according to the equation

N₂ + 3H₂ → 2NH₃

As the result of the reaction, ammonia displaces the halogen atom as halide ion, assisted by the elimination of a proton, to form the ammonium salt. Neutralization of the HX product releases the free amine. Aryl amines are normally produced by reducing the corresponding nitro- compound. Nitroarenes are prepared by the reaction of nitric acid (HNO₃) on an appropriate aryl compound, followed by reduction, using hydrogen (H₂) and a catalyst, to convert the −NO₂ (nitro) group to the amino group (−NH₂). Amines can also be prepared by reacting an ammonia or a primary amine with an appropriate aldehyde (R−CHO) or ketone (R−CO−R') compound, followed by reduction with H₂. In the initial reaction, the nitrogen atom adds to the carbonyl group (C=O) as a nucleophile (electron donor). A proton shifts from the nitrogen atom to the oxygen atom of the carbonyl group, and a molecule of water is subsequently eliminated to form an imine. Reduction of the imine produces the corresponding primary or secondary amine.

The reduction of nitriles can also produce primary amines. Reaction of the −C≡N bond with two molar equivalents of H₂ reduces the nitrile to the corresponding primary amine. When this type of reduction is too powerful, however, a variety of other reducing agents are available. More selectivity in the site of reduction and gentler conditions are the hallmark of reagents such as lithium aluminum hydride and sodium borohydride.

Reactions of Amines

Amines are reactive compounds widely used to form amides. An amine reacts with an acid chloride to produce the corresponding amide, in which the acyl functional group (−RCO) of the acid chloride substitutes for one of the hydrogen atoms on the nitrogen atom of the amine. For example, acetyl chloride reacts with methylamine to produce N-methylacetamide. Similarly, benzoyl chloride (the acid chloride of benzoic acid) can react with diethylamine to produce N,N-diethylbenzamide. Reaction with alkyl halides occurs in the same way. For the reaction to be effective, at least one replaceable hydrogen atom must be on the amine nitrogen atom. A similar reaction occurs with acid anhydrides (which contain two acyl groups bonded to a single oxygen atom), as in the reaction between ammonia and acetic anhydride that produces acetamide and ammonium acetate:

Reaction of a diamine with two equivalents of an acid chloride or an alkyl halide forms the corresponding diamide. However, if the two acid chlorides are in the same molecule, the reaction becomes a polymerization reaction. This is the means by which the series of nylon polymer formulations was discovered, and it remains the major means of their production. From that beginning, a large number of polyamides, including Kevlar, have been developed.

One of the more generally useful reactions of amines is their ability to add to a carbonyl group as a nucleophile. Under the proper conditions, the reaction can be used to convert an ester (R−COO−R') into an amide. More commonly, the reaction is used to form an imine as an intermediate stage in an overall synthesis plan. Once formed, the imine can be easily converted into a variety of other compounds.

PRINCIPAL TERMS

• functional group: a specific group of atoms with a characteristic structure and corresponding chemical behavior within a molecule.
• hydrogen bond: a weak type of chemical bond formed by the attraction of a hydrogen atom to an electronegative atom—an atom with a strong tendency to attract electrons—in the same or another molecule.
• primary: describes an organic compound in which one of the hydrogen atoms bonded to a central atom is replaced by another atom or group of atoms, called a substituent.
• secondary: describes an organic compound in which two of the hydrogen atoms bonded to a central atom are replaced by other atoms or groups of atoms, called substituents.
• tertiary: describes an organic compound in which three of the hydrogen atoms bonded to a central atom are replaced by other atoms or groups of atoms, called substituents.

Bibliography

Hendrickson, James B., Donald J. Cram, and George S. Hammond. Organic Chemistry. 3rd ed. New York: McGraw, 1970. Print.

Jones, Mark M., et al. Chemistry and Society. 5th ed. Philadelphia: Saunders Coll., 1987. Print.

Lide, David R., ed. CRC Handbook of Chemistry and Physics. 94th ed. Taylor and Francis Group, 2013. Web. 7 Apr. 2014.

Miessler, Gary L., Paul J. Fischer, and Donald A. Tarr. Inorganic Chemistry. 5th ed. Boston: Pearson, 2014. Print.

Morrison, Robert Thornton, and Robert Neilson Boyd. Organic Chemistry. 7th ed. Englewood Cliffs: Prentice, 2003. Print.

Myers, Richard. The Basics of Chemistry. Westport: Greenwood, 2003. Print.

Powell, P., and P. L. Timms. The Chemistry of the Non-Metals. London: Chapman, 1974. Print.

Wuts, Peter G. M., and Theodora W. Greene. Greene’s Protective Groups in Organic Synthesis. 4th ed. Hoboken: Wiley, 2007. Print.