Amidines are with the functional group RC(NR)NR2, where the R groups can be the same or different. They are the imine derivatives of (RC(O)NR2). The simplest amidine is formamidine, HC(=NH)NH2.
Examples of amidines include:
Preparation
A common route to primary amidines is the
Pinner reaction. Reaction of the nitrile with alcohol in the presence of acid gives an
Carboximidate. Treatment of the resulting compound with
ammonia then completes the conversion to the amidine.
Instead of using a Bronsted acid, Lewis acids such as aluminium trichloride promote the direct
amination of
,
or, in certain exceptional cases, of
.
Dimethylformamide
acetal reacts with primary
to give amidines:
- Me2NC(H)(OMe)2 + RNH2 → Me2NC=NHR + 2 MeOH
Catalysis is likewise not required for direct amination of an
imidoyl chloride.
Amidines are also prepared by the addition of organolithium reagents to , followed by protonation or alkylation.
Acid-base chemistry
Amidines are much more basic than amides and are among the strongest uncharged/unionized bases.
[Roche VF. Improving Pharmacy Students’ Understanding and Long-term Retention of Acid-Base Chemistry. American Journal of Pharmaceutical Education. 2007;71(6):122.]
Protonation occurs at the sp2-hybridized nitrogen. This occurs because the positive charge can be delocalized onto both nitrogen atoms. The resulting species is known as an amidinium ion
Applications
Several drug or drug candidates feature amidine substituents. Examples include the antiprotozoal
imidocarb, the
insecticide amitraz,
xylamidine, an antagonist at the 5HT2A receptor,
and the
amidantel and
tribendimidine.
Formamidinium (see below) may be reacted with a metal halide to form the light-absorbing semiconducting material in perovskite solar cells. Formamidinium (FA) cations or halides may partially or fully replace methylammonium halides in forming perovskite absorber layers in photovoltaic devices.
Nomenclature
Formally, amidines are a class of
. The oxoacid from which an amidine is derived must be of the form R
nE(=O)OH, where R is a
substituent. The
hydroxyl is replaced by an
amine and the
Oxo ligand group is replaced by =
nitrogensubstituent, giving amidines the general structure R
nE(=NR)NR
2.
When the parent oxoacid is a
carboxylic acid, the resulting amidine is a
carboxamidine or
carboximidamide (
IUPAC name). Carboxamidines are frequently referred to simply as amidines, as they are the most commonly encountered type of amidine in organic chemistry.
Derivatives
Formamidinium cations
A notable subclass of amidinium ions are the formamidinium
; which can be represented by the chemical formula .
Deprotonation of these gives
which can be represented by the chemical formula .
Amidinate salts
An amidinate salt has the general structure M
+RNRCNR
− and can be accessed by reaction of a
carbodiimide with an organometallic compound such as
methyl lithium.
They are used widely as ligands in organometallic complexes.
See also
-
— a similar group of compounds where the central carbon atom is bonded to three nitrogen atoms.
-
contain a cyclic amidine.
