{{Short description|Organic compounds}} [[File:Acetamidine Structural Formulae V.1.png|thumb|right|150px|The structural formula of acetamidine (acetimidamide).]] '''Amidines''' are organic compounds with the functional group RC(NR)NR<sub>2</sub>, where the R groups can be the same or different. They are the imine derivatives of amides (RC(O)NR<sub>2</sub>). The simplest amidine is formamidine, HC(=NH)NH<sub>2</sub>.
Examples of amidines include: * DBU * diminazene * benzamidine * Pentamidine * Paranyline
==Preparation== A common route to primary amidines is the Pinner reaction. Reaction of the nitrile with alcohol in the presence of acid gives an iminoether. Treatment of the resulting compound with ammonia then completes the conversion to the amidine.<ref>{{cite journal|doi=10.15227/orgsyn.008.0001|title=Acetamidine Hydrochloride|journal=Organic Syntheses|year=1928|volume=8|pages=1|author=A. W. Dox}}</ref> Instead of using a Bronsted acid, Lewis acids such as aluminium trichloride promote the direct amination of nitriles,<ref>{{cite journal|doi=10.15227/orgsyn.036.0064|title=''N''-Phenylbenzamidine|journal=Organic Syntheses|year=1956|volume=36|pages=64}}</ref> or, in certain exceptional cases, of amides.<ref>{{cite journal|journal=Organic Chemistry Highlights|date=1 Dec 2008|first=Douglass F.|last=Taber|title=The Takayama synthesis of (-)-cernuine|url=https://www.organic-chemistry.org/Highlights/2008/01December.shtm}}</ref>
Catalysis is not required for direct amination of an imidoyl chloride.<ref>{{cite journal|doi=10.15227/orgsyn.031.0048|title=N,N-Diphenylbenzamidine|journal=Organic Syntheses|year=1951|volume=31|pages=48|author=Arthur C. Hontz, E. C. Wagner}}</ref> Likewise, dimethylformamide acetal reacts with primary amines to give amidines:<ref>{{cite journal|doi=10.15227/orgsyn.067.0052|title=(S)-N,N-Dimethyl-N'-(1-tert-Butoxy-3-Methyl-2-Butyl)formamidine|journal=Organic Syntheses|year=1989|volume=67|pages=52|author1=Daniel A. Dickman |author2=Michael Boes |author3=Albert I. Meyers}}</ref> :Me<sub>2</sub>NC(H)(OMe)<sub>2</sub> + RNH<sub>2</sub> → Me<sub>2</sub>NC=NHR + 2 MeOH Monoformamides react with isocyanates to give formamidines and carbon dioxide, presumably via rearrangement of the imide.<ref name=ChemRev>{{cite journal|doi=10.1021/cr60261a005|title=The chemistry of formic acid and its simple derivatives|first=Harry W.|last=Gibson|orig-date=January 27, 1969|journal=Chemical Reviews|p=691}}</ref>
Amidines are also prepared by the addition of organolithium reagents to diimines, followed by protonation or alkylation.
==Acid-base chemistry== Amidines are much more basic than amides and are among the strongest uncharged/unionized bases.<ref>Roche VF. Improving Pharmacy Students’ Understanding and Long-term Retention of Acid-Base Chemistry. American Journal of Pharmaceutical Education. 2007;71(6):122.</ref><ref>{{cite book |title=Organic chemistry |last1=Clayden |last2=Greeves |last3=Warren |year=2001 |publisher=Oxford university press |isbn=978-0-19-850346-0 |page=[https://archive.org/details/organicchemistry00clay_0/page/202 202] |url-access=registration |url=https://archive.org/details/organicchemistry00clay_0/page/202}}</ref>
Protonation occurs at the sp<sup>2</sup>-hybridized nitrogen. This occurs because the positive charge can be delocalized onto both nitrogen atoms. The resulting cationic species is known as an '''amidinium''' ion<ref>{{cite book|title=Functional synthetic receptors|editor-first=Thomas|editor-last=Schrader|editor2-first=Andrew D.|editor2-last=Hamilton|publisher=Wiley-VCH|year=2005|isbn=3-527-30655-2|pages=132}}</ref> and possesses identical C-N bond lengths.
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==Applications==
Several drug or drug candidates feature amidine substituents. Examples include the antiprotozoal imidocarb, the insecticide amitraz, xylamidine, an antagonist at the 5HT2A receptor,<ref>{{cite book|doi=10.1016/S0079-6468(08)70378-3|title=5 Amidines and Guanidines in Medicinal Chemistry|series=Progress in Medicinal Chemistry|year=1993|last1=Greenhill|first1=John V.|last2=Lue|first2=Ping|volume=30|pages=203–326|pmid=7905649|isbn=9780444899897}}</ref> and the anthelmintics 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 oxoacids. The oxoacid from which an amidine is derived must be of the form R<sub>''n''</sub>E(=O)OH, where R is a substituent. The −OH group is replaced by an −NH<sub>2</sub> group and the =O group is replaced by =NR, giving amidines the general structure R<sub>''n''</sub>E(=NR)NR<sub>2</sub>.<ref>{{GoldBookRef|title=amidines|file=A00267}}</ref><ref>{{GoldBookRef|title=carboxamidines|file=C00851}}</ref><ref>{{GoldBookRef|title=sulfinamidines|file=S06107}}</ref> 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=== left|upright=0.75|thumb|general structure of a formamidinium cation
A notable subclass of amidinium ions are the formamidinium cations; which can be represented by the chemical formula {{chem|[R|2|N−CH{{=}}NR|2|]|+}}. Deprotonation of these gives stable carbenes which can be represented by the chemical formula {{chem|R|2|N−C:−NR|2}}.<ref>{{cite journal|last1=Alder|first1=Roger W.|last2=Blake|first2=Michael E.|last3=Bufali|first3=Simone|last4=Butts|first4=Craig P.|last5=Orpen|first5=A. Guy|last6=Schütz|first6=Jan|last7=Williams|first7=Stuart J.|title=Preparation of tetraalkylformamidinium salts and related species as precursors to stable carbenes|journal=Journal of the Chemical Society, Perkin Transactions 1|date=2001|issue=14|pages=1586–1593|doi=10.1039/B104110J}}</ref><ref>{{cite journal|doi=10.15227/orgsyn.046.0039|author1=Edward C. Taylor |author2=Wendell A. Ehrhart |author3=M. Kawanisi |title=Formamidine Acetate|journal=Organic Syntheses|year=1966|volume=46|pages=39}}</ref>
===Amidinate salts=== thumb|Structure of cyclopentadienyl dimethyl zirconium (diisopropyl acetamidinate).<ref>{{cite journal|doi=10.1021/ja0057326|title= Dramatic Enhancement of Activities for Living Ziegler−Natta Polymerizations Mediated by "Exposed" Zirconium Acetamidinate Initiators: The Isospecific Living Polymerization of Vinylcyclohexane|year=2001|last1=Keaton|first1=Richard J.|last2=Jayaratne|first2=Kumudini C.|last3=Henningsen|first3=David A.|last4=Koterwas|first4=Lisa A.|last5=Sita|first5=Lawrence R.|journal=Journal of the American Chemical Society|volume=123|issue=25|pages=6197–6198|pmid=11414862|bibcode= 2001JAChS.123.6197K}}</ref> {{main|Amidinate organometallic complexes}} An amidinate salt has the general structure M<sup>+</sup>[RNRCNR]<sup>−</sup> and can be accessed by reaction of a carbodiimide with an organometallic compound such as methyl lithium.<ref>{{cite book|last1=Ulrich|first1=Henri|title=Chemistry and technology of carbodiimides|date=2007|publisher=John Wiley & Sons|location=Chichester, England|isbn=9780470065105}}</ref> They are used widely as ligands in organometallic complexes.
==See also== * Guanidines — a similar group of compounds where the central carbon atom is bonded to three nitrogen atoms. * Imidazolines contain a cyclic amidine.
==References== {{clear}} {{Reflist}}
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Category:Amidines Category:Functional groups Category:Superbases