Amine

Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines, trimethylamine, and aniline; see Category:Amines for a list of amines. Inorganic derivatives of ammonia are also called amines, such as chloramine (NClH₂).

Compounds with the nitrogen atom attached to a carbonyl of the structure R-C(=O)NR'R'' are called amides and have different chemical properties from amines.‌

Classes of amines

 Aliphatic amines

Primary amines arise when one of three hydrogen atoms in ammonia is replaced by an alkyl. Important primary alkyl amines include methylamine, ethanolamine (2-aminoethanol), and the buffering agent tris. Secondary amines have two alkyl substituents bound to N together with one hydrogen. Important representatives include dimethylamine and methylethanolamine. In tertiary amines, all three hydrogen atoms are replaced by organic substituents. Examples include trimethylamine, a distinctively fishy smell. Cyclic amines are either secondary or tertiary amines. Examples of cyclic amines include the 3-member ring aziridine and the six-membered ring piperidine. N-methylpiperidine is a cyclic tertiary amine. It is also possible to have four alkyl substituents on the nitrogen. These compounds are not amines but are called quaternary ammonium cations, have a charged nitrogen center, and necessarily come with an anion.

 Aromatic amines

Main article: Aromatic amine

Aromatic amines have the nitrogen atom connected to an aromatic ring as in anilines. The aromatic ring decreases the alkalinity of the amine, depending on its substituents. The presence of an amine group strongly increases the reactivity of the aromatic ring, due to an electron-donating effect.

Naming conventions

Amines are named in several ways. Typically, the compound is given the prefix "amino-" or the suffix: "-amine." The prefix "N-" shows substitution on the nitrogen atom. An organic compound with multiple amino groups is called a diamine, triamine, tetraamine and so forth.

Systematic names for some common amines:

Lower amines are named with the suffix -amine. methylamine

Higher amines have the prefix amino as a functional group. 2-aminopentane (or sometimes: pent-2-yl-amine or pentan-2-amine)

Synthesis

 Alkylation

The most industrially significant amines are prepared from ammonia by alkylation with alcohols:

ROH + NH₃ → RNH₂ + H₂O

These reactions require catalysts, specialized apparatus, and additional purification measures since the selectivity can be problematic. The same amines can be prepared by treatment of Haloalkanes with ammonia and amines:

RX + 2 R'NH₂ → RR'NH + [RR'NH₂]X

Such reactions, which are most useful for alkyl iodides and bromides, are rarely employed because the degree of alkylation is difficult to control.

 Reductive routes

Via the process of hydrogenation, nitriles are reduced to amines using hydrogen in the presence of a nickel catalyst. Reactions are sensitive acidic or alkaline conditions, which can cause hydrolysis of -CN group. LiAlH₄ is more commonly employed for the reduction of nitriles on the laboratory scale. Similarly, LiAlH₄ reduces amides to amines. Many amines are produced from aldehydes and ketones via reductive amination, which can either proceed catalytically or stoichiometrically.

Aniline (C₆H₅NH₂) and its derivatives are prepared by reduction of the nitroaromatics. In industry, hydrogen is the preferred reductant, whereas in the laboratory, tin and iron are often employed.

 Specialized methods

Many laboratory methods exist for the preparation of amines, many of these methods being rather specialized.

Reaction name	Substrate	Comment
Gabriel synthesis	organohalide	reagent: potassium phthalimide
Staudinger reduction	Azide	This reaction also takes place with a reducing agent such as lithium aluminium hydride.
Schmidt reaction	carboxylic acid
Aza-Baylis–Hillman reaction	imine	Synthesis of allylic amines
Hofmann degradation	amide	This reaction is valid for preparation of primary amines only. Gives good yields of primary amines uncontaminated with other amines.
Hofmann elimination	Quaternary ammonium salt	upon treatment with strong base
Amide reduction	amides
Nitrile reduction	nitriles
Reduction of nitro compounds	nitro compounds	can be accomplished with elemental zinc, tin or iron with an acid.
Amine alkylation	haloalkane
Delepine reaction	organohalide	reagent hexamine
Buchwald-Hartwig reaction	aryl halide	specific for aryl amines
Menshutkin reaction	tertiary amine	reaction product a quaternary ammonium cation
hydroamination	alkenes and alkynes
Hofmann-Löffler reaction	haloamine

 

Amide

Amide Definition

In chemistry, the term amide has several meanings. It may refer to a particular inorganic anion, it may refer to a functional group found in organic compounds, or to compounds that contain this functional group.

Overview

The amide anion is the conjugate base of ammonia, NH2-. It is an extremely strong base, due to the extreme weakness of ammonia as a Bronsted acid.

Amides are the members of a group of chemical compounds containing nitrogen. Specifically, an amide is a derivative of a carboxylic acid in which the hydroxyl group has been replaced by an amine or ammonia.

Compounds in which a hydrogen atom on nitrogen from ammonia or an amine is replaced by a metal cation are also known as amides or azanides. The amide functional group is:

Synthesis and breakdown

Amides are commonly formed from the reaction of a carboxylic acids with an amine:

This is the reaction that forms peptide bonds between amino acids. These amides can participate in hydrogen bonding as hydrogen bond acceptors and donors, but do not ionize in aqueous solution, whereas their parent acids and amines are almost completely ionized in solution at neutral pH.

Amide formation plays a role in the synthesis of some condensation polymers, such as nylon. Their breakdown is possible via amide hydrolysis.

Amide linkages

An amide linkage is kinetically stable to hydrolysis. Amide linkages in a biochemical context are called peptide linkages. Amide linkages constitute a defining molecular feature of proteins, the secondary structure of which is due in part to the hydrogen bonding abilities of amides.

Derivatives

Sulfonamides are analogs of amides in which the atom double bonded to oxygen is sulfur rather than carbon.

Naming

• Example: CH3CONH2 is named acetamide or ethanamide
• Other examples: propan-1-amide, N,N-dimethylpropanamide

Properties

 Basicity

Compared to amines, amides are very weak bases. While the conjugate acid of an amine has a pKa of about 9.5, the conjugate acid of an amide has a pKa around -0.5. Therefore amides don't have as clearly noticeable acid-base properties in water. This lack of basicity is explained by the electron-withdrawing nature of the carbonyl group where the lone pair of electrons on the nitrogen is delocalized by resonance. On the other hand, amides are much stronger bases than carboxylic acids, esters, aldehydes, and ketones (conjugated acid pKa between -6 and -10). It is estimated in silico that acetamide is represented by resonance structure A for 62% and by B for 28%.Resonance is largely prevented in the very strained quinuclidone.

Because of the greater electronegativity of oxygen, the carbonyl (C=O) is a stronger dipole than the N-C dipole. The presence of a C=O dipole and, to a lesser extent a N-C dipole, allows amides to act as H-bond acceptors. In primary and secondary amides, the presence of N-H dipoles allows amides to function as H-bond donors as well. Thus amides can participate in hydrogen bonding with water and other protic solvents; the oxygen atom can accept hydrogen bonds from water and the N-H hydrogen atoms can donate H-bonds. As a result of interactions such as these, the water solubility of amides is greater than that of corresponding hydrocarbons.

The proton of a primary or secondary amide does not dissociate readily under normal conditions; its pK_a is usually well above 15. Conversely, under extremely acidic conditions, the carbonyl oxygen can become protonated with a pK_a of roughly –1.

 Solubility

The solubilities of amides and esters are roughly comparable. Typically amides are less soluble than comparable amines and carboxylic acids since these compounds can both donate and accept hydrogen bonds. Tertiary amides, with the important exception of N,N-dimethylformamide, exhibit low solubility in water.

 Characterization

The presence of the functional group is generally easily established, at least in small molecules. They are the most common non-basic functional group. They can be distinguished from nitro and cyano groups by their IR spectra. Amides exhibit a moderately intense ν_CO band near 1650 cm⁻¹. By ¹H NMR spectroscopy, CONHR signals occur at low fields. In X-ray crystallography, the C(O)N center together with the three immediately adjacent atoms characteristically define a plane.

Amide synthesis

Amides are commonly formed via reactions of a carboxylic acid with an amine. Many methods are known for driving the unfavorable equilibrium to the right:

RCO₂H + R'R"NH RC(O)NR'R" + H₂O

For the most part, these reactions involve "activating" the carboxylic acid and the best known method, the Schotten-Baumann reaction, which involves conversion of the acid to the acid chlorides:

Reaction name	Substrate	Details
Beckmann rearrangement	cyclic ketone	reagent: hydroxylamine and acid
Schmidt reaction	ketones	reagent: hydrazoic acid
nitrile hydrolysis	nitrile	reagent: water; acid catalyst
Willgerodt-Kindler reaction	aryl alkyl ketones	sulfur and morpholine
Passerini reaction	carboxylic acid, ketone or aldehyde
Ugi reaction	isocyanide, carboxylic acid, ketone, primary amine
Bodroux reaction[4][5]	carboxylic acid, Grignard reagent with an aniline derivative ArNHR'
Chapman rearrangement[6][7]	aryl imino ether	for N,N-diaryl amides. The reaction mechanism is based on a nucleophilic aromatic substitution.[8]
Leuckart amide synthesis [9]	isocyanate	Reaction of arene with isocyanate catalysed by aluminium trichloride, formation of aromatic amide.

 Other methods

The seemingly simple direct reaction between an alcohol and an amine to an amide was not tried until 2007 when a special ruthenium-based catalyst was reported to be effective in a so-called dehydrogenative acylation:

The generation of hydrogen gas compensates for unfavorable thermodynamics. The reaction is believed to proceed by one dehydrogenation of the alcohol to the aldehyde followed by formation of a hemiaminal and the after a second dehydrogenation to the amide. Elimination of water in the hemiaminal to the imine is not observed.