Nitriles

 

Nitriles

Suffix:    -nitrile or -onitrile

Prefix:    cyano-

Nitriles contain a carbon - nitrogen triple bond (R-CºN or R-CN). They are indirectly related to amides (by the loss of H₂O from a primary amide), and react chemically similar to carboxylic acids and their derivatives.  It should be noted that H-CºN is not truly a nitrile and is named hydrogen cyanide.

When a nitrile group is the highest priority functional group present in the molecule, it is named as an alkanenitrile (alkenenitrile, alkynenitrile, ...). Since the -CºN must occur at the end of a chain of carbon atoms, the carbon of the nitrile will be carbon 1 in the numbering scheme. Other functional groups are located by this numbering scheme. Since the nitrile group is always at carbon number 1, there is no need to indicate its' location.

Examples naming simple nitriles:

Compound Name	Line Drawing
ethanenitrile
propanenitrile
butanenitrile
2-methylpropanenitrile
cyclobutyronitrile *
pentanedinitrile **

* note: the -yl is changed to a -yro.
** note: numbers are not needed as the nitriles must be at the ends of the chain.

Examples naming more complex nitriles:

Compound Name	Line Drawing
4,4-dimethylpentanenitrile
2,4-pentadienenitrile
4-amino-3-hydroxy-2-methylhexanenitrile
4-chloro-2-cyclohexenenitrile

2-mercapto-4-oxo-6-heptynenitrile

Nitriles as Substituents:

In more complex molecules with higher priority functional groups the nitrile group is named as a cyano-substituent. It is located by numbering the longest chain of carbons (according to the higher priority functional group) and locating the carbon atom to which the -CN group is attached by this numbering scheme.  

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Compounds with the general structure are called "nitriles" or "cyanides" generically and may be named substitutively in a manner closely related to that for acids and other related compounds. Acyclic mono- and dinitriles in which  may be considered to have replaced the group(s) of an acid named by an "-oic acid" or "-dioic acid" suffix are named by adding the suffix "-nitrile" or "-dinitrile" to the name of the hydrocarbon from which the acid name was derived.

Nitriles in which  may be considered to have replaced  of an acid with a retained trivial name are named by changing the "-ic acid", or "-oic acid" ending of the name of the acid to "-onitrile".

Nitriles in which  may be considered to have replaced the group(s) of an acid named by a "-carboxylic acid" suffix are named by replacing that suffix with "carbonitrile".

Functional class names for nitriles of the general structure are formed by citing the prefix name for the group R followed by the class name "cyanide" as a separate word. Compounds with a general structure such as  and may be named similarly.

When a group is present that has priority for citation as the principal characteristic group or when all  groups cannot be expressed as the principal characteristic group, groups are described by the prefix "cyano-".

Cyanide-related compounds. Compounds containing a group X listed in the first column of are named by methods analogous to those described for halides; the functional class names given in the second column of the Table are used in place of "halide" or the prefixes given in the third column of the Table in place of "halo-".

Nitrile oxides. Compounds with the general structure have the generic name "nitrile oxides". In specific cases, the class name "oxide" is added as a separate word after a nitrile name, but not a cyanide name.

 

Introduction to nitrile hydrolysis

The hydrolysis of nitriles to amides and carboxylic acids are very important transformations in organic chemistry.Many industrial examples are known, such as the hydrolysis of amino nitriles to amino acids, acrylonitrile to acrylamide and acetone cyanohydrin to the corresponding amide, en route to methyl methacrylate. Only using specific conditions, it is possible to stop the hydrolysis at the amide stage. Frequently used methods for nitrile hydrolysis to amides use strong acid (96% H₂SO₄) or base (50% KOH /t-BuOH). However, in general, selective hydrolysis of nitriles to amides is troublesome and yields are reasonable at best due to two reasons:

(1) It is difficult to stop the hydrolysis at the amide stage and further hydrolysis to the carboxylic acid often takes place, as the rate constant of amide hydrolysis is usually larger than that for nitrile hydrolysis, especially under dilute acidic or basic conditions. However, in concentrated acid or base the relationship is reversed.

 (2) Since the nitrile group is not very reactive, harsh conditions using strong acids or bases at high temperatures are generally required, which precludes the presence of acid or base sensitive functional groups.

In addition to strong base or acid, enzymes and transition metal catalysts are also used to convert a variety of nitriles to amides. With enzymes, asymmetric hydrolysis or dynamic kinetic resolution of nitriles is possible. Below these three different are reviewed.

Nitrile Hydrolysis under Basic Conditions

Nitrile Hydrolysis under Acid Conditions

Description: Addition of water and acid to a nitrile leads to formation of a carboxylic acid.

Notes:

• This reaction is referred to as “acidic hydrolysis”.
• The reaction is generally used with water as solvent, so an excess of water is present. The acid used is often written as “H3O(+)”

Examples:

Notes: Note that example 4 is a cyanohydrin, so this produces an “alpha hydroxy carboxylic acid”

Mechanism:

Protonation of the nitrile nitrogen by acid (Step 1, arrows A and B) makes the nitrile carbon a better electrophile. Attack at the carbon by water (Step 2, arrows C and D) followed by proton transfer (Step 3, arrows E and F) gives a species that is in resonance with a protonated amide (arrows G and H). Addition of water to the protonated amide (Step 4, arrows I and J) followed by proton transfer (Step 5, arrows K and L) result in formation of NH3(+) which is an excellent leaving group. Expulsion of NH3 through 1,2-addition (Step 6, arrows M and N) followed by deprotonation (Step 7, arrows O and P) give the carboxylic acid.