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Amidines are organic compounds with the functional group RC(NR)NR₂, where the R groups can be the same or different. They are the imine derivatives of amides (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 iminoether. Treatment of the resulting compound with ammonia then completes the conversion to the amidine.^[1] Instead of using a Bronsted acid, Lewis acids such as aluminium trichloride promote the direct amination of nitriles,^[2] or, in certain exceptional cases, of amides.^[3] Dimethylformamide acetal reacts with primary amines to give amidines:^[4]

Me₂NC(H)(OMe)₂ + RNH₂ → Me₂NC=NHR + 2 MeOH

Catalysis is likewise not required for direct amination of an imidoyl chloride.^[5]

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.^[6]^[7]

Protonation occurs at the sp²-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^[8] and possesses identical C-N bond lengths.

Applications

Several drug or drug candidates feature amidine substituents. Examples include the antiprotozoal Imidocarb, the insecticide amitraz, the anthelmintic tribendimidine, and xylamidine, an antagonist at the 5HT2A receptor.^[9]

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_nE(=O)OH, where R is a substituent. The −OH group is replaced by an −NH₂ group and the =O group is replaced by =N R, giving amidines the general structure R_nE(=NR)NR₂.^[10]^[11]^[12] 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 cations; which can be represented by the chemical formula [R
₂N−CH=NR
₂]⁺
. Deprotonation of these gives stable carbenes which can be represented by the chemical formula R
₂N−C:−NR
₂.^[13]^[14]

Amidinate salts

Structure of cyclopentadienyl dimethyl zirconium (diisopropyl acetamidinate).^[15]

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.^[16] They are used widely as ligands in organometallic complexes.

References

^ A. W. Dox (1928). "Acetamidine Hydrochloride". Organic Syntheses. 8: 1. doi:10.15227/orgsyn.008.0001.
^ "N-Phenylbenzamidine". Organic Syntheses. 36: 64. 1956. doi:10.15227/orgsyn.036.0064.
^ Taber, Douglass F. (1 Dec 2008). "The Takayama synthesis of (-)-cernuine". Organic Chemistry Highlights.
^ Daniel A. Dickman; Michael Boes; Albert I. Meyers (1989). "(S)-N,N-Dimethyl-N'-(1-tert-Butoxy-3-Methyl-2-Butyl)formamidine". Organic Syntheses. 67: 52. doi:10.15227/orgsyn.067.0052.
^ Arthur C. Hontz, E. C. Wagner (1951). "N,N-Diphenylbenzamidine". Organic Syntheses. 31: 48. doi:10.15227/orgsyn.031.0048.
^ Roche VF. Improving Pharmacy Students’ Understanding and Long-term Retention of Acid-Base Chemistry. American Journal of Pharmaceutical Education. 2007;71(6):122.
^ Clayden; Greeves; Warren (2001). Organic chemistry. Oxford university press. p. 202. ISBN 978-0-19-850346-0.
^ Schrader, Thomas; Hamilton, Andrew D., eds. (2005). Functional synthetic receptors. Wiley-VCH. p. 132. ISBN 3-527-30655-2.
^ Greenhill, John V.; Lue, Ping (1993). 5 Amidines and Guanidines in Medicinal Chemistry. Progress in Medicinal Chemistry. Vol. 30. pp. 203–326. doi:10.1016/S0079-6468(08)70378-3. ISBN 9780444899897. PMID 7905649.
^ IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "amidines". doi:10.1351/goldbook.A00267
^ IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "carboxamidines". doi:10.1351/goldbook.C00851
^ IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "sulfinamidines". doi:10.1351/goldbook.S06107
^ Alder, Roger W.; Blake, Michael E.; Bufali, Simone; Butts, Craig P.; Orpen, A. Guy; Schütz, Jan; Williams, Stuart J. (2001). "Preparation of tetraalkylformamidinium salts and related species as precursors to stable carbenes". Journal of the Chemical Society, Perkin Transactions 1 (14): 1586–1593. doi:10.1039/B104110J.
^ Edward C. Taylor; Wendell A. Ehrhart; M. Kawanisi (1966). "Formamidine Acetate". Organic Syntheses. 46: 39. doi:10.15227/orgsyn.046.0039.
^ Keaton, Richard J.; Jayaratne, Kumudini C.; Henningsen, David A.; Koterwas, Lisa A.; Sita, Lawrence R. (2001). "Dramatic Enhancement of Activities for Living Ziegler−Natta Polymerizations Mediated by "Exposed" Zirconium Acetamidinate Initiators: The Isospecific Living Polymerization of Vinylcyclohexane". Journal of the American Chemical Society. 123 (25): 6197–6198. doi:10.1021/ja0057326. PMID 11414862.
^ Ulrich, Henri (2007). Chemistry and technology of carbodiimides. Chichester, England: John Wiley & Sons. ISBN 9780470065105.

[1] A. W. Dox (1928). "Acetamidine Hydrochloride". Organic Syntheses. 8: 1. doi:10.15227/orgsyn.008.0001.

[2] "N-Phenylbenzamidine". Organic Syntheses. 36: 64. 1956. doi:10.15227/orgsyn.036.0064.

[3] Taber, Douglass F. (1 Dec 2008). "The Takayama synthesis of (-)-cernuine". Organic Chemistry Highlights.

[4] Daniel A. Dickman; Michael Boes; Albert I. Meyers (1989). "(S)-N,N-Dimethyl-N'-(1-tert-Butoxy-3-Methyl-2-Butyl)formamidine". Organic Syntheses. 67: 52. doi:10.15227/orgsyn.067.0052.

[5] Arthur C. Hontz, E. C. Wagner (1951). "N,N-Diphenylbenzamidine". Organic Syntheses. 31: 48. doi:10.15227/orgsyn.031.0048.

[6] Roche VF. Improving Pharmacy Students’ Understanding and Long-term Retention of Acid-Base Chemistry. American Journal of Pharmaceutical Education. 2007;71(6):122.

[7] Clayden; Greeves; Warren (2001). Organic chemistry. Oxford university press. p. 202. ISBN 978-0-19-850346-0.

[8] Schrader, Thomas; Hamilton, Andrew D., eds. (2005). Functional synthetic receptors. Wiley-VCH. p. 132. ISBN 3-527-30655-2.

[9] Greenhill, John V.; Lue, Ping (1993). 5 Amidines and Guanidines in Medicinal Chemistry. Progress in Medicinal Chemistry. Vol. 30. pp. 203–326. doi:10.1016/S0079-6468(08)70378-3. ISBN 9780444899897. PMID 7905649.

[10] IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "amidines". doi:10.1351/goldbook.A00267

[11] IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "carboxamidines". doi:10.1351/goldbook.C00851

[12] IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "sulfinamidines". doi:10.1351/goldbook.S06107

[13] Alder, Roger W.; Blake, Michael E.; Bufali, Simone; Butts, Craig P.; Orpen, A. Guy; Schütz, Jan; Williams, Stuart J. (2001). "Preparation of tetraalkylformamidinium salts and related species as precursors to stable carbenes". Journal of the Chemical Society, Perkin Transactions 1 (14): 1586–1593. doi:10.1039/B104110J.

[14] Edward C. Taylor; Wendell A. Ehrhart; M. Kawanisi (1966). "Formamidine Acetate". Organic Syntheses. 46: 39. doi:10.15227/orgsyn.046.0039.

[15] Keaton, Richard J.; Jayaratne, Kumudini C.; Henningsen, David A.; Koterwas, Lisa A.; Sita, Lawrence R. (2001). "Dramatic Enhancement of Activities for Living Ziegler−Natta Polymerizations Mediated by "Exposed" Zirconium Acetamidinate Initiators: The Isospecific Living Polymerization of Vinylcyclohexane". Journal of the American Chemical Society. 123 (25): 6197–6198. doi:10.1021/ja0057326. PMID 11414862.

[16] Ulrich, Henri (2007). Chemistry and technology of carbodiimides. Chichester, England: John Wiley & Sons. ISBN 9780470065105.

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@@ Line 1: / Line 1: @@
+{{Short description|Organic compounds}}
-'''Amidines''' are a class of [[oxoacid]] [[derivative (chemistry)|derivatives]].
+[[File:Acetamidine Structural Formulae V.1.png|thumb|right|150px|The [[skeletal formula]] of acetamidine (acetimidamide).]]
+'''Amidines''' are [[organic compound]]s 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 [[amide]]s (RC(O)NR<sub>2</sub>). The simplest amidine is formamidine, HC(=NH)NH<sub>2</sub>.
+Examples of amidines include:
-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 [[hydroxyl|−OH group]] is replaced by an [[amine|−NH<sub>2</sub> group]] and the [[Oxo ligand|=O]] group is replaced by =[[nitrogen|N]][[substituent|R]], giving amidines the general structure R<sub>''n''</sub>E(=NR)NR<sub>2</sub>.<ref>{{GoldBookRef|title=amidines|url=http://goldbook.iupac.org/A00267.html}}</ref><ref>{{GoldBookRef|title=carboxamidines|url=http://goldbook.iupac.org/C00851.html}}</ref><ref>{{GoldBookRef|title=sulfinamidines|url=http://goldbook.iupac.org/S06107.html}}</ref>
+* [[1,8-Diazabicycloundec-7-ene|DBU]]
+* [[diminazene]]
+* [[benzamidine]]
+* [[Pentamidine]]
+* Paranyline
-==Carboxamidines==
+==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|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 [[Brønsted–Lowry acid–base theory|Bronsted acid]], [[Lewis acids and bases|Lewis acids]] such as [[Aluminium chloride|aluminium trichloride]] promote the direct [[amination]] of [[nitrile]]s,<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 [[amide]]s.<ref>{{cite journal|journal=Organic Chemistry Highlights|date=1 Dec 2008|first=Douglass&nbsp;F.|last=Taber|title=The Takayama synthesis of (-)-cernuine|url=https://www.organic-chemistry.org/Highlights/2008/01December.shtm}}</ref>  [[Dimethylformamide]] [[acetal]] reacts with primary [[amine]]s 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>
-[[Image:Acetamidine-2D-skeletal.png|thumb|right|150px|The [[skeletal formula]] of acetamidine (acetimidamide)]]
+:Me<sub>2</sub>NC(H)(OMe)<sub>2</sub> + RNH<sub>2</sub> → Me<sub>2</sub>NC=NHR + 2 MeOH
+Catalysis is likewise 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>
+Amidines are also prepared by the addition of [[organolithium reagent]]s to [[diimine]]s, followed by [[protonation]] or [[alkylation]].
-When the parent oxoacid is a [[carboxylic acid]], the resulting amidine is a '''carboxamidine''' or '''carboximidamide''' ([[IUPAC]] name), and has the following general structure:
+==Acid-base chemistry==
-[[Image:Carboxamidine-general-2D-skeletal.png|100px|The general structure of a carboxamidine]]
+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 electron|delocalized]] onto both nitrogen atoms. The resulting [[cation]]ic 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.
-Carboxamidines are frequently referred to simply as amidines, as they are the most commonly encountered type of amidine in [[organic chemistry]].  The simplest amidine is formamidine, HC(=NH)NH<sub>2</sub>.
+[[File:Amidineresonance.png|550px|center]]
-Examples of amidines include:
-*[[1,8-Diazabicycloundec-7-ene|DBU]]
-*[[diminazene]]
-*[[benzamidine]]
-*[[Pentamidine]]
-*[[Paranyline]]
+==Applications==
-The most common way to make primary amidines is by the [[Pinner reaction]]. Reaction of the nitrile with acidic alcohol gives an iminoether; treatment of this with ammonia then completes the conversion to the amidine.
+Several drug or drug candidates feature amidine substituents. Examples include the antiprotozoal [[Imidocarb]], the  insecticide [[amitraz]], the [[anthelmintic]] [[tribendimidine]], and [[xylamidine]], an [[Receptor antagonist|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>
-==Properties==
-Amidines are much more basic than amides and are among the strongest uncharged/unionized<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> bases.<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=202}}</ref>
+Formamidinium (see below) may be reacted with a metal halide to form the light-absorbing [[semiconducting material]] in [[perovskite solar cell]]s. Formamidinium (FA) cations or halides may partially or fully replace [[methylammonium halide]]s in forming perovskite absorber layers in [[Photovoltaic system|photovoltaic devices]].
-Protonation occurs onto the sp² hybridized nitrogen. This occurs because the positive charge can be delocalized onto both nitrogen atoms. The resulting cationic species is known as a '''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.
+==Nomenclature==
-[[Image:Amidineresonance.png|550px|center]]
+Formally, amidines are a class of [[oxoacid]]s. 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 [[hydroxyl|−OH group]] is replaced by an [[amine|−NH<sub>2</sub> group]] and the [[Oxo ligand|=O]] group is replaced by =[[nitrogen|N]][[substituent|R]], 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===
-[[Image:Formamidinium cation.png|right|150px|thumb|general structure of a formamidinium cation]]
+[[Image:Formamidinium cation.png|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&minus;CH{{=}}NR|2|]|+}}. [[Deprotonation]] of these gives [[stable carbene]]s which can be represented by the chemical formula {{chem|R|2|N&minus;C:&minus;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>
+A notable subclass of amidinium ions are the formamidinium [[cation]]s; which can be represented by the chemical formula {{chem|[R|2|N&minus;CH{{=}}NR|2|]|+}}. [[Deprotonation]] of these gives [[stable carbene]]s which can be represented by the chemical formula {{chem|R|2|N&minus;C:&minus;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===
+[[File:CpZrMe2(iPr2amidate)AFIHEC.png|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}}</ref>]]
-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.
+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 chemistry|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==
-*[[Guanidine]]s — a similar group of compounds where the central Carbon is bonded to three Nitrogens.
+* [[Guanidine]]s — a similar group of compounds where the central carbon atom is bonded to three nitrogen atoms.
-*[[Imidazoline]]s contain a cyclic amidine.
+* [[Imidazoline]]s contain a cyclic amidine.
 ==References==
+{{clear}}
 {{Reflist}}
+{{Authority control}}
 [[Category:Amidines| ]]
 [[Category:Functional groups]]
+[[Category:Superbases]]