Amidines are

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The ...

s with the

functional group In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the rest ...

RC(NR)NR₂, where the R groups can be the same or different. They are the

imine In organic chemistry, an imine ( or ) is a functional group or organic compound containing a carbon–nitrogen double bond (). The nitrogen atom can be attached to a hydrogen or an organic group (R). The carbon atom has two additional single bo ...

derivatives of

amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it i ...

s (RC(O)NR₂). The simplest amidine is formamidine, HC(=NH)NH₂. Examples of amidines include: *

DBU The decibel (symbol: dB) is a relative unit of measurement equal to one tenth of a bel (B). It expresses the ratio of two values of a Power, root-power, and field quantities, power or root-power quantity on a logarithmic scale. Two signals whose ...

diminazene Diminazene ( INN; also known as diminazen) is an anti-infective medication for animals that is sold under a variety of brand names. It is effective against certain protozoa such as ''Babesia'', ''Trypanosoma'', and '' Cytauxzoon''. The drug may a ...

benzamidine Benzamidine is the organic compound with the formula C6H5C(NH)NH2. It is the simplest aryl amidine. The compound is a white solid that is slightly soluble in water. It is usually handled as the hydrochloride salt, a white, water-soluble solid. ...

* Pentamidine * Paranyline

Preparation

A common route to primary amidines is the

Pinner reaction The Pinner reaction refers to the acid catalysed reaction of a nitrile with an alcohol to form an imino ester salt (alkyl imidate salt); this is sometimes referred to as a Pinner salt. The reaction is named after Adolf Pinner, who first describ ...

. Reaction of the nitrile with alcohol in the presence of acid gives an iminoether. Treatment of the resulting compound with

ammonia Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous was ...

then completes the conversion to the amidine. Instead of using a Bronsted acid,

Lewis acids A Lewis acid (named for the American physical chemist Gilbert N. Lewis) is a chemical species that contains an empty orbital which is capable of accepting an electron pair from a Lewis base to form a Lewis adduct. A Lewis base, then, is any spe ...

such as

aluminium trichloride Aluminium chloride, also known as aluminium trichloride, is an inorganic compound with the formula . It forms hexahydrate with the formula , containing six water molecules of hydration. Both are colourless crystals, but samples are often conta ...

promote the direct amination of nitriles. They are also generated by amination of an

imidoyl chloride Imidoyl chlorides are organic compounds that contain the functional group RC(NR')Cl. A double bond exist between the R'N and the carbon centre. These compounds are analogues of acyl chloride. Imidoyl chlorides tend to be highly reactive and are m ...

. They are also prepared by the addition of

organolithium reagent In organometallic chemistry, organolithium reagents are chemical compounds that contain carbon–lithium (C–Li) bonds. These reagents are important in organic synthesis, and are frequently used to transfer the organic group or the lithium atom ...

s to

diimine Diimines are organic compounds containing two imine (RCH=NR') groups. Common derivatives are 1,2-diketones and 1,3-diimines. These compounds are used as ligands and as precursors to heterocycles. Diimines are prepared by condensation reactions ...

s, followed by

protonation In chemistry, protonation (or hydronation) is the adding of a proton (or hydron, or hydrogen cation), (H+) to an atom, molecule, or ion, forming a conjugate acid. (The complementary process, when a proton is removed from a Brønsted–Lowry acid, ...

alkylation Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effecting ...

Dimethylformamide Dimethylformamide is an organic compound with the formula ( CH3)2NC(O)H. Commonly abbreviated as DMF (although this initialism is sometimes used for dimethylfuran, or dimethyl fumarate), this colourless liquid is miscible with water and the majo ...

acetal In organic chemistry, an acetal is a functional group with the connectivity . Here, the R groups can be organic fragments (a carbon atom, with arbitrary other atoms attached to that) or hydrogen, while the R' groups must be organic fragments n ...

reacts with primary

amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituen ...

s to give amidines: :Me₂NC(H)(OMe)₂ + RNH₂ → Me₂NC=NHR + 2 MeOH

Properties and applications

Amidines are much more basic than amides and are among the strongest uncharged/unionized bases. Protonation occurs at the sp² hybridized nitrogen. This occurs because the positive charge can be

delocalized In chemistry, delocalized electrons are electrons in a molecule, ion or solid metal that are not associated with a single atom or a covalent bond.IUPAC Gold Boo''delocalization''/ref> The term delocalization is general and can have slightly dif ...

onto both nitrogen atoms. The resulting

cation An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...

ic species is known as an amidinium ion and possesses identical C-N bond lengths. Amidineresonance

Several drug or drug candidates feature amidine substituents. Examples include the antiprotozoal

Imidocarb Imidocarb is a urea derivative used in veterinary medicine as an antiprotozoal agent for the treatment of infection with ''Babesia'' (babesiosis Babesiosis or piroplasmosis is a malaria-like parasitic disease caused by infection with a eukary ...

, the insecticide

amitraz Amitraz (development code BTS27419) is a non-systemic acaricide and insecticideCorta, E., Bakkali, A., Berrueta, L. A., Gallo, B., & Vicente, F. (1999). Kinetics and mechanism of amitraz hydrolysis in aqueous media by HPLC and GC-MS. Talanta, 48( ...

, the

anthelmintic Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. They may a ...

tribendimidine Tribendimidine is a broad-spectrum anthelmintic agent developed in China, at the National Institute of Parasitic Diseases in Shanghai. It is a derivative of amidantel.

, and

xylamidine Xylamidine is a drug which acts as an Antagonist (pharmacology), antagonist at the 5-HT2A receptor, 5HT2A Receptor (biochemistry), receptor, and to a lesser extent at the 5HT1A receptor. It does not cross the blood–brain barrier, which makes it ...

, an

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

at the 5HT2A receptor. Formamidinium (see below) may be reacted with a metal halide to form the light-absorbing

semiconducting material A semiconductor is a material which has an electrical conductivity value falling between that of a conductor, such as copper, and an insulator, such as glass. Its resistivity falls as its temperature rises; metals behave in the opposite way. ...

perovskite solar cell A perovskite solar cell (PSC) is a type of solar cell that includes a perovskite-structured compound, most commonly a hybrid organic–inorganic lead or tin halide-based material as the light-harvesting active layer. Perovskite materials, such a ...

s. Formamidinium (FA) cations or halides may partially or fully replace

methylammonium halide Methylammonium halides are organic halides with a formula of , where X is Cl for methylammonium chloride, Br for methylammonium bromide, or I for methylammonium iodide. Generally they are white or light colored powders. Applications These salts ...

s in forming perovskite absorber layers in photovoltaic devices.

Nomenclature

Formally, amidines are a class of

oxoacid An oxyacid, oxoacid, or ternary acid is an acid that contains oxygen. Specifically, it is a compound that contains hydrogen, oxygen, and at least one other element, with at least one hydrogen atom bonded to oxygen that can dissociate to produce ...

s. The oxoacid from which an amidine is derived must be of the form R_''n''E(=O)OH, where R is a

substituent A substituent is one or a group of atoms that replaces (one or more) atoms, thereby becoming a moiety in the resultant (new) molecule. (In organic chemistry and biochemistry, the terms ''substituent'' and ''functional group'', as well as ''side ...

. The −OH group is replaced by an −NH₂ group and the =O group is replaced by = N R, giving amidines the general structure R_''n''E(=NR)NR₂. When the parent oxoacid is a

carboxylic acid In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...

, the resulting amidine is a carboxamidine or carboximidamide (

IUPAC The International Union of Pure and Applied Chemistry (IUPAC ) is an international federation of National Adhering Organizations working for the advancement of the chemical sciences, especially by developing nomenclature and terminology. It is ...

name). Carboxamidines are frequently referred to simply as amidines, as they are the most commonly encountered type of amidine in

organic chemistry Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clayden, J.; ...

Derivatives

Formamidinium cations

A notable subclass of amidinium ions are the formamidinium

s; which can be represented by the chemical formula .

Deprotonation Deprotonation (or dehydronation) is the removal (transfer) of a proton (or hydron, or hydrogen cation), (H+) from a Brønsted–Lowry acid in an acid–base reaction.Henry Jakubowski, Biochemistry Online Chapter 2A3, https://employees.csbsju.ed ...

of these gives stable carbenes which can be represented by the chemical formula .

Amidinate salts

An amidinate salt has the general structure M⁺ NRCNRsup>− and can be accessed by reaction of a

carbodiimide In organic chemistry, a carbodiimide (systematic IUPAC name: methanediimine) is a functional group with the formula RN=C=NR. They are exclusively synthetic. A well known carbodiimide is dicyclohexylcarbodiimide, which is used in peptide synthesi ...

with an

organometallic compound Organometallic chemistry is the study of organometallic compounds, chemical compounds containing at least one chemical bond between a carbon atom of an organic molecule and a metal, including alkali, alkaline earth, and transition metals, and s ...

such as

methyl lithium Methyllithium is the simplest organolithium reagent with the empirical formula CH3Li. This s-block organometallic compound adopts an oligomeric structure both in solution and in the solid state. This highly reactive compound, invariably used in s ...

. They are used widely as ligands in organometallic complexes.

References

{{Reflist Functional groups