Nitriles

FIELDS OF STUDY: Organic Chemistry

ABSTRACT

The characteristic properties and reactions of nitriles are discussed. Nitriles are linear molecules or substituent groups. They are very useful for the relatively easy formation of complex organic molecular structures from very simple starting materials.

The Nature of Nitriles

A nitrile is an organic compound with at least one cyano functional group (C≡N) in its molecular structure. It is essentially a "disguised" carboxylic acid (of the general form RCOOH, where R− indicates a hydrocarbon derivative), since splitting a nitrile with water, a process known as hydrolysis, yields first the amide RCONH₂ and then the carboxylic acid. Most common nitriles are formed by adding the negatively charged cyanide ion (CN⁻) in an appropriate substitution reaction. Substituting cyanide for a halide, for example, is an easy way to lengthen a target molecule by one carbon atom. The cyanide ion itself and the related compound cyanogen (N≡C−C≡N) are often referred to as a "pseudohalide" and "pseudohalogen," respectively, indicating that the cyanide ion and cyanogen exhibit chemical behaviors similar to those of the halides and halogens. Cyanogen also qualifies as a cyanocarbon, which is a nitrile containing more than one cyano group.

The characteristic feature of a nitrile is the cyano group’s carbon-nitrogen triple bond. The triple bond, like a double bond, is formed by the side-to-side overlap of p orbitals on adjacent atoms. Both the carbon atom and the nitrogen atom have their valence electrons in the 2s and 2p atomic orbitals, and both are able to hybridize their s and p atomic orbitals into sets of energetically equivalent sp, sp², or sp³ orbitals. The sp³ hybrid orbitals are typical of saturated compounds. The term arises because an sp³-hybridized atom can have up to four pairs of electrons filling the four sp³ orbitals, at which point the ability of the orbitals to contain electrons is said to be saturated, meaning that no more electrons can be acquired. When a carbon or nitrogen atom only has enough electrons to fill two orbitals, however, the hybridization involves only the s orbital and one of the three p orbitals, forming two sp hybrid orbitals. The two orbitals are oriented at 180 degrees to each other, in a line with the nucleus of the atom at its center. The other two p orbitals remain unaltered and are perpendicular to each other about the axis of the sp orbitals. The end-to-end overlap of the carbon and nitrogen sp orbitals forms a sigma (σ) bond, or primary covalent chemical bond, between the two atoms, while the side-by-side overlap of the adjacent p orbitals forms two secondary pi (π) bonds parallel to the sigma bond, leaving one sp orbital remaining to form a fourth bond with another atom.

Overall, the nitrile system is linear and extends outward, away from the rest of the molecular structure, forming a site that is highly susceptible to reaction. The carbon-nitrogen triple bond creates an electric dipole because the nitrogen atom is more electronegative than the carbon atom. This, coupled with the electron-rich nature of the triple bond, makes the nitrile functional group a valuable reactive site.

In principle, the series of nitrile compounds is infinite, but it is also restricted to linear compounds. Any addition to the carbon-nitrogen bond destroys its identity as a cyano group. Accordingly, there are no cyclic nitriles in the same sense that there are cyclic hydrocarbons. Rather, a cyano group can only exist in a cyclic compound as a substituent, or side chain.

The most common organic nitrile is acetonitrile (CH₃CN). The reactivity of nitriles is such that they are good solvents in many applications, and acetonitrile is the least toxic of the nitriles, only posing a lethal risk to humans at concentrations of about 2,700 parts per million (ppm) in air and being relatively safe when handled properly. Butyronitrile (C₃H₇CN), in comparison, can be lethal at concentrations of about 250 ppm.

Nomenclature of Nitriles

Nitriles, being similar to carboxylic acids, are commonly named according to the parent acid from which they are formed, as in the case of acetonitrile, the nitrile form of acetic acid. To name the compound systematically, following the rules of the International Union of Pure and Applied Chemistry (IUPAC), the parent hydrocarbon structure is first identified and named as its nitrile. For example, acetonitrile is systemically named "ethanenitrile," indicating that it has a nitrile group attached to an ethane parent molecule. A ring compound in which the cyano group is the principal functional group is called a carbonitrile. When it is not the principal functional group in a compound, the cyano group is named as a substituent group, along with its numerical position in the structure, and listed alphabetically with the other functional groups before the suffix identifying parent structure.

Typically, the carbon atom containing the cyano group is assigned the lowest position number in the molecule, as the group is usually found at the end of a hydrocarbon chain, in which case the number may be omitted from the name. For example, a cyclohexene molecule (a six-membered ring containing one carbon-carbon double bond) with a cyano functional group on the third carbon atom in the ring, counting clockwise from the first carbon in the double bond, would be informally named 3-cyanocyclohexene. To name the same molecule systematically, the cyano carbon atom is assigned the position number 1 and the other carbon atoms are numbered counterclockwise from it, so the double bond begins on the second carbon atom. The molecule would thus have the IUPAC name cyclohex-2-ene-1-carbonitrile, but it could also be called cyclohex-2-enecarbonitrile.

Reactions of Nitriles

Nitriles are reactive compounds that are widely used to form primary amines, carboxylic acids, and their corresponding derivatives. Carboxylic acids are formed by complete hydrolysis of the nitrile in acid. Under mildly acidic conditions, the nitrile becomes protonated (gains a proton, in the form of the hydrogen cation H⁺) and carries the positive charge at its carbon atom, which changes the carbon-nitrogen triple bond to a double bond. The resulting cation is known as the iminium ion (an imine is a group or compound containing a carbon-nitrogen double bond), has the form R₂C=N⁺R₂, and is electronically similar to a protonated carbonyl group (C=O⁺). The positively charged carbon atom becomes the point of attachment for a molecule of water, which then loses one of its hydrogen atoms as another proton. This leaves the molecule as a hydroxy imine, with the hydroxyl group (−OH) bonded to the carbon atom of the imine structure. This is a very unstable arrangement and is prone to intramolecular rearrangement. The hydrogen atom of the hydroxyl group transfers to the nitrogen atom as the electrons from the carbon-nitrogen double bond reorganize to form a carbonyl group (C=O) and an amino group (−NH₂). The resulting product is the corresponding amide.

More vigorous hydrolysis, using a stronger acid medium, hydrolyzes the amide completely to form the carboxylic acid and ammonia (NH₃).

A good reducing agent, such as lithium aluminum hydride (LiAlH₄), can reduce a nitrile directly to the corresponding primary amine. This method is a very useful way of augmenting an existing structure with −CH₂−NH₂. Milder reducing agents, such as boranes, can reduce the nitrile to a corresponding imine. Compared to the iminium ion, the neutral imine is much less susceptible to reaction with water and other nucleophiles (electron-rich species), and since the reduction is carried out in an unreactive anhydrous solvent such as diethyl ether or tetrohydrofuran, it is quite stable. The imine itself can subsequently be used in different reactions to produce other compounds, either as desired final products or as intermediate compounds in a larger synthetic protocol.

Nitriles in which the cyano group is attached directly to a carbon-carbon double bond undergo polymerization reactions very easily. The most well known of these compounds is acrylonitrile, which is commonly used in the plastics industry. In an acrylonitrile molecule, the cyano group is connected by a single bond to a methine group (=CH−), which in turn is carbon-carbon double bonded to a methylene group (=CH₂).The nitrogen atom of the cyano group is sufficiently electron withdrawing that it polarizes the carbon-carbon double bond, making it highly susceptible to polymerization reactions in which the double bond becomes a single bond and numerous acrylonitrile molecules link to each other in a head-to-tail fashion, as below:

Formation of Nitriles

Nitriles are prepared by various methods. One of the most common ways to produce a nitrile is to dehydrate an amide. For example, acetonitrile, the simplest nitrile, is prepared industrially by the dehydration of acetamide (CH₃CONH₂) with thionyl chloride (SOCl₂) or phosphorus pentoxide (P₂O₅), according to the following reaction:

More complex nitriles are synthesized by using a preexisting nitrile group as a cyanide ion. The cyanide ion, as nucleophile, is prone to react with the carbonyl group in acid solution. The components of hydrogen cyanide (HCN) add to the carbonyl group of an aldehyde (RCOH) or a ketone (RCOR') to produce the corresponding hydroxynitrile, or cyanohydrin. Hydroxynitriles are characterized by having a hydroxyl group and a cyano group bonded to the same carbon atom in the hydrocarbon structure. Formation of the hydroxynitrile adds one carbon atom to the basic structure of the molecule and sets the stage for other reactions. Halogenation would then add a halide functional site, dehydration would form an alkene (an unsaturated hydrocarbon with at least one carbon-carbon double bond), reduction with a catalyst would produce a primary amine (RNH₂), and hydrolysis would form the carboxylic acid. A third way to form a nitrile is through a nucleophilic substitution reaction with an alkyl halide, which replaces the halide with the cyano group.

The synthesis of ring-based aryl nitriles is somewhat more difficult and is normally achieved by the formation of a diazonium salt (R−N⁺≡N). In this process, an aryl amine such as phenylamine is converted to the corresponding diazonium salt by reaction with sodium nitrite (NaNO₂) and an acid, such as hydrochloric acid (HCl), at low temperature. The diazonium salt intermediate, being unstable and prone to explode, is never isolated in practice but rather treated with copper cyanide (CuCN) to convert it to the aryl nitrile.

PRINCIPAL TERMS

• cyanocarbon: an organic compound containing multiple cyano groups, which consist of a carbon atom triple bonded to a nitrogen atom.
• dipole: the separation of positive and negative charges within a single molecule due to electron density being relatively high in one part of the molecule and relatively low in another.
• functional group: a specific group of atoms with a characteristic structure and corresponding chemical behavior within a molecule.
• triple bond: a type of chemical bond in which two adjacent atoms are connected by six bonding electrons rather than two.

Bibliography

Acheson, R. M. An Introduction to the Chemistry of Heterocyclic Compounds. 3rd ed. New York: Wiley, 1976. Print.

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, 2013. Web. 16 Apr. 2014.

Morrison, Robert Thornton, and Robert Neilson Boyd. Organic Chemistry. 6th ed. Englewood Cliffs: Prentice, 1992. Print.

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